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Sample records for rats small intestine

  1. Histomorphometric changes of small intestine in pregnant rat.

    PubMed

    Sabet Sarvestani, Fatemeh; Rahmanifar, Farhad; Tamadon, Amin

    2015-01-01

    Food intake of rats increases during pregnancy. This requires changes in the structure of the small intestine to absorb additional food. The aim of the present study was to investigate the morphological changes in the layers of small intestine in rats during pregnancy. Duodenum, jejunum and ileum of 18 pregnant Sprague-Dawley rats (day 7, 14 and 21 of pregnancy) were collected. Villous height and width and thickness of lamina propria, tunica muscularis entirely and separately (circular and longitudinal layers) were measured on transverse sections. During pregnancy increasing villi length and muscular layer thickness was observed in duodenum. Furthermore, along with the progress of gestation greatest histomorphometric change in small intestine was observed in the jejunum. The reduction in the ileum histomorphologic indices was observed during pregnancy. In conclusion, increase in histomorphologic indices of duodenum and jejunum supplies more capacity of duodenum to digest food intake during pregnancy and decrease in these indices in ileum controls the absorption of excess produced amino acids and glucose by hyperphagia.

  2. 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

  3. Small intestinal transit of spherical particles in the active rat

    SciTech Connect

    Beall, P.T.; Sutton, S.C.; LeRoy-Wayne, S.

    1986-03-05

    Reproducible measurements of small intestine transit for spherical particles of 0.5 ..mu.. to 1 mm diameter, have been accomplished in the conscious rat. A short cannula of polyethylene is surgically implanted into the duodenum and exists through the abdominal wall. After recovery, a bolus of saline containing colored or isotopically labeled particulate material and an internal standard of NaCr/sup 51/O/sub 4/ is introduced with a modified pipette tip that snugly fills the cannula to prevent back flow. The rats eat and drink during the transit period and are maintained on a reversed light cycle so that transit is measured during their physically active period. Glass microspheres of 1mm, 500 ..mu.., and 50 ..mu.. were followed at 30 min, 1 hr, and 2 hr intervals by opening the intestine and photographing 1 cm segments along its length. Polymer beads of 500 ..mu.., 125 ..mu.., and 70 ..mu.. were labeled with /sup 125/I and located by freezing the exteriorized intestine and counting 1 cm segments in a gamma counter. Movement of the fluid bolus as detected by NaCr/sup 51/O/sub 4/ was reproducible with the fluid front moving through 59%, 73%, and 81% of the length at 30 min, 1 hr, and 2 hr. One millimeter to 125 ..mu.. glass and polymer beads moved with the fluid bolus. Evidence for separation of the fluid phase and particles under approx. 100 ..mu.. is accumulating. It is hypothesized that small particles under a critical size may become lodged in the mucus lining of the intestinal wall.

  4. Radioprotective potential of histamine on rat small intestine and uterus.

    PubMed

    Carabajal, E; Massari, N; Croci, M; Martinel Lamas, D J; Prestifilippo, J P; Bergoc, R M; Rivera, E S; Medina, V A

    2012-12-18

    The aim of this study was to improve knowledge about histamine radioprotective potential investigating its effect on reducing ionising radiation-induced injury and genotoxic damage on the rat small intestine and uterus. Forty 10-week-old male and 40 female Sprague-Dawley rats were divided into 4 groups. Histamine and histamine-5Gy groups received a daily subcutaneous histamine injection (0.1 mg/kg) starting 24 h before irradiation. Histamine-5Gy and untreated-5Gy groups were irradiated with a dose of whole-body Cesium-137 irradiation. Three days after irradiation animals were sacrificed and tissues were removed, fixed, and stained with haematoxylin and eosin, and histological characteristics were evaluated. Proliferation, apoptosis and oxidative DNA markers were studied by immunohistochemistry, while micronucleus assay was performed to evaluate chromosomal damage. Histamine treatment reduced radiation-induced mucosal atrophy, oedema and vascular damage produced by ionising radiation, increasing the number of crypts per circumference (239 ± 12 vs 160 ± 10; P<0.01). This effect was associated with a reduction of radiation-induced intestinal crypts apoptosis. Additionally, histamine decreased the frequency of micronuclei formation and also significantly attenuated 8-OHdG immunoreactivity, a marker of DNA oxidative damage. Furthermore, radiation induced flattening of the endometrial surface, depletion of deep glands and reduced mitosis, effects that were completely blocked by histamine treatment. The expression of a proliferation marker in uterine luminal and glandular cells was markedly stimulated in histamine treated and irradiated rats. The obtained evidences indicate that histamine is a potential candidate as a safe radioprotective agent that might increase the therapeutic index of radiotherapy for intra-abdominal and pelvic cancers. However, its efficacy needs to be carefully investigated in prospective clinical trials.

  5. Goblet cells and intestinal Alkaline phosphatase expression (IAP) during the development of the rat small intestine.

    PubMed

    Gomes, José Rosa; Ayub, Laís Costa; Dos Reis, Camila Audrey; Machado, Miriam Joice; da Silva, Jéssica; Omar, Nádia Fayez; de Miranda Soares, Maria Albertina

    2017-01-01

    This study aimed to evaluate the temporal and spacial distribution of the mucins produced by goblet cells and intestinal alkaline phosphatase (IAP) expression during the development of the small intestine of the rat. Intestines were removed from rats on the 15th, 17th and 18th days of intratuterine life (i.u.) and on the 3rd, 10th, 17th and 25th days after birth (a.b.). Intestines were processed for routine histological procedures and sections were submitted to histochemistry using PAS to stain neutral glycoproteins and Alcian blue for acidic glycoproteins, as well as immunohistochemistry to detect IAP. In rats, glycoprotein production was seen to begin in the intestinal epithelium cell at around the 17th day of i.u. life; however, this production was not accompanied by morphological indications of the presence of goblet cells. By the 18th i.u. day, the villus epithelium was undergoing differentiation and the first goblet cells could be identified from this time. At around the 10th day a.b., both compartments of the small intestine were detected; i.e. the villi and the crypts. At this timepoint, goblet cells were present in the villi, and also in the upper regions of the crypts. On the 3rd, 10th 17th and 25th days a.b., the presence of the goblet cells increased and presented regional differences in the sections evaluated. IAP was not detected during i.u. life, but was weakly detected in the cells of the villi from the 3rd day a.b., along the entire extension of the villi. On the 10th day, IAP was detected at the tip of the villi, while on the 25th day, it was detected along the extension of the villi, but with a weaker intensity. In conclusion, a temporal and spacial distribution of goblet cells and IAP activity occurs during the development of the small intestine, suggesting a possible regulatory control in accordance with the suckling and weaning phases of food intake in the rat's life.

  6. Intestinal mast cells and eosinophils in relation to Strongyloides ratti adult expulsion from the small and large intestines of rats.

    PubMed

    Shintoku, Y; Kadosaka, T; Kimura, E; Takagi, H; Kondo, S; Itoh, M

    2013-04-01

    Mucosal mast cells (MMC) play a crucial role in the expulsion of Strongyloides ratti adults from the small intestine of mice. We reported the large intestinal parasitism of S. ratti in rats, and there has been no report on MMC in the large intestine of the natural host. We studied kinetics of MMC, together with eosinophils, in the upper and lower small intestines, caecum and colon of infected rats. Two distinct phases of mastocytosis were revealed: one in the upper small intestine triggered by stimulation of 'ordinary' adults, and the other in the colon stimulated by 'immune-resistant' adults that started parasitizing the colon around 19 days post-infection. In all 4 intestinal sites, the MMC peaks were observed 5-7 days after the number of adult worms became the maximum and the height of MMC peaks appeared to be dependent on the number of parasitic adults, suggesting an important role played by worms themselves in the MMC buildup.

  7. Ghrelin in small intestine, its contribution to regulation of food intake and body weight in cross-intestinal parabiotic rats.

    PubMed

    Noguchi, Hitoshi; Masaki, Takayuki; Kakuma, Tetsuya; Nakazato, Masamitsu; Yoshimatsu, Hironobu

    2011-01-01

    Ghrelin has been shown to be associated with feeding behavior in humans and rodents. It has been suggested that ghrelin may play a role behind the effect of bariatric surgery. Inbred rats were made into parabiotic pairs so that they shared a single abdominal cavity. A further operation is performed later in which the small intestines are transected and re-connected so that one rat continually lost nutrition to its partner. Changes in food intake and body weight were recorded. Seven weeks later, content of ghrelin in the plasma, stomach and upper intestines were measured in the paired rats. Rats which lost nutrients to its counterpart (Loss rats) ingested significantly more food than sham control rats (p<0.001). Rats which gained nutrient (Gain rats) ingested less than controls (p<0.001). There was no significant difference in body weight, blood glucose, insulin, free fatty acids and triglycerides between the paired rats. There was significantly higher levels of ghrelin in the plasma (p<0.008) and the intestine of the Loss rats (p<0.02). There were no difference in ghrelin in the stomach between parabiotic rats and sham operated controls. The ghrelin content of the plasma and intestines were significantly higher in the Loss rats, which ate more, and normal in the Gain rats, which ate less than controls. Because no remarkable changes in the ghrelin content were observed in the stomach, difference in the quality of the chime may affect the local synthesis and release of ghrelin.

  8. Histopathological changes in small and large intestines during hymenolepidosis in rats.

    PubMed

    Kosik-Bogacka, Danuta I; Kolasa, Agnieszka

    2012-01-01

    The tapeworm Hymenolepis diminuta is a chronic parasite living in the small intestine of rats, mice and humans. The aim of this study was to determine histopathological changes in the rat intestine during experimental hymenolepidosis. Our results showed that in rats infected with H. diminuta slight changes occurred in the length of the villus and crypts in different parts of the digestive tract. The changes were most distinct in the duodenum and jejunum on the 16 days post H. diminuta infection.

  9. 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.

  10. Transfer of propionate by rat small intestine in vitro

    PubMed Central

    Barry, R. J. C.; Jackson, M. J.; Smyth, D. H.

    1966-01-01

    1. The transfer of propionate by sacs of rat everted intestine has been investigated in relation to a number of physico-chemical factors which affect movement of weak electrolytes. 2. Neither the observed movement nor the distribution of propionate can be accounted for by the theory of non-ionic diffusion or by modifications of it, such as the microclimate hypothesis or partial permeability to ions. 3. It is not possible to account for the observed propionate movement by the electrical potential across the gut or by solvent drag. 4. The most satisfactory explanation for the observations is a transfer process in the gut for volatile fatty acids, and some features of this are discussed. PMID:5937409

  11. Plasma catecholamines and postoperative gastric emptying and small intestinal propulsion in the rat.

    PubMed

    Dubois, A; Henry, D P; Kopin, I J

    1975-03-01

    The role of adrenal medullary discharge of catecholamines on inhibition of gastric emptying and small intestinal propulsion after laparotomy was examined in rats. The rate of movement of a 51Cr-labeled liquid test meal, which had been introduced by gastric intubation, out of the stomach and through the small intestine, was retarded 12 hr after laparotomy. Adrenal demedullation produced a striking decrease in plasma catecholamines and abolished surgically induced elevation of the catecholamines, but had no significant effect on gastric emptying or intestinal propulsion in rats subjected to laparotomy or in the unoperated control animals. Thus circulating catecholamines play little if any role in controlling normal gastroinestinal motility or in the postoperative decrease in rate of gastric emptying and small intestinal motility.

  12. Intestinal absorption of berberine and 8-hydroxy dihydroberberine and their effects on sugar absorption in rat small intestine.

    PubMed

    Wei, Shi-chao; Dong, Su; Xu, Li-jun; Zhang, Chen-yu

    2014-04-01

    The intestinal absorption of berberine (Ber) and its structural modified compound 8-hydroxy dihydroberberine (Hdber) was compared, and their effects on the intestinal absorption of sugar by perfusion experiment were investigated in order to reveal the mechanism of low dose and high activity of Hdber in the treatment of hyperglycemia. The absorption of Hdber and Ber in rat small intestine was measured by in situ perfusion. High performance liquid chromatography (HPLC) was used to determine the concentrations of Hdber and Ber. In situ perfusion method was also used to study the effects of Hdber and Ber on sugar intestinal absorption. Glucose oxidase method and UV spectrophotometry were applied to examine the concentrations of glucose and sucrose in the perfusion fluid. The results showed that the absorption rate of Ber in the small intestine was lower than 10%, but that of Hdber was larger than 70%. Both Hdber and Ber inhibited the absorption of glucose and sucrose at the doses of 10 and 20 μg/mL. However, Hdber presented stronger activity than Ber (P<0.01). It is suggested that Hdber is absorbed easily in rat small intestine and that its inhibitory effect on the absorption of sugar is better than Ber.

  13. Blood flow, O2 extraction and O2 consumption along the rat small intestine.

    PubMed

    Stevenson, N R; Weiss, H R

    1988-05-01

    Differences in O2 delivery and consumption along the fed and fasted small intestine are described. Total wall blood flow was determined in sequential segments of small intestine from 5 to 6-month-old male, anesthetized Fischer 344 rats either 75-80 min before or after feeding, using radioactive microspheres. Oxygen saturation in submucosal arterioles and venules (50-60 micron diam) was determined throughout the intestine, using a microspectrophotometric technique. Venous O2 saturations showed considerable heterogeneity in all regions, and ranged from 0 to 77%. Arterial-venous O2 content differences (CaO2-CvO2) did not change along the fasted rat intestine, and averaged 8.2 ml O2/100 ml blood. However, CaO2-CvO2 followed a small proximal to distal gradient (proximal greater than distal) in the fed rats. Larger proximal to distal gradients (proximal greater than distal) occurred in both blood flow and O2 consumption in both groups. Feeding did not change intestinal average CaO2-CvO2. However, feeding induced a 53% increase in average O2 consumption, with the greatest increase (130%) occurring in the middle third of the intestine. Feeding induced a 42% increase in average blood flow, with the greatest increase (70%) occurring in the distal third of the intestine. The increased O2 used by the fed intestine was primarily provided by the increased blood flow. The O2 consumption gradient is assumed to reflect differences in mucosal mass along the intestine and/or differences in metabolic activity.

  14. 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

  15. 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...

  16. [Somatic pain sensitivity under indometacin induced gastric and small intestinal injury in rats].

    PubMed

    Iarushkina, N I; Bagaeva, T R; Filaretova, L P

    2014-01-01

    The aim was to study the effect of indometacin (IM) induced gastrointestinal injury on somatic pain sensitivity in awake rats. IM was administered at the ulcerogenic dose (35 mg/kg, s. c.) to fasted (24 h) and fed rats. Somatic pain sensitivity was evaluated using a tail flick test. Latency time was measured under conditions of the formation of gastric erosion (1 - 4 h after IM injection) as well as small intestinal injury (24, 48 and 72 h after IM injection). IM administration caused the gastric erosion formation only in fasted rats (4 h after the administration) and the small intestinal injury in both fasted and fed rats (24, 48, 72 h after the administration). Indomethacin-caused gastric and small intestinal injury resulted in an increase in tail flick latency. We did not observe any changes in tail flick latency in IM-treated rats without significant gastrointestinal injury. The gastrointestinal injury was accompanied by signs of chronic stress: long-lasting increase in corticosterone blood level, adrenal hypertrophy, thymus involution, and loss of body weight. Thus, the IM-induced gastrointestinal injury formation resulted in somatic pain inhibition in awake rats.

  17. Protective effect of vitamin E against ethanol-induced small intestine damage in rats.

    PubMed

    Shirpoor, Alireza; Barmaki, Hanieh; Khadem Ansari, Mohamadhasan; Lkhanizadeh, BehrouzI; Barmaki, Haleh

    2016-03-01

    The role of oxidative stress and inflammatory reaction has been reported in various ethanol-induced complications. The purpose of this study was to evaluate the effect of ethanol-induced structural alteration, oxidative stress, and inflammatory reaction on the small intestine of rats, and plausible protective effect of vitamin E to determine whether it inhibits the abnormality induced by ethanol in the small intestine. Twenty-four male wistar rats were divided into three groups, namely: Control, ethanol, and vitamin E treated ethanol groups. After six weeks of treatment, the small intestine length, villus height, crypt depth and muscular layer thickness, oxidative stress, and inflammatory parameters showed significant changes in the ethanol treated group compared to the control group. Vitamin E consumption along with ethanol ameliorated structural alteration of the small intestine and reduced the elevated amount of oxidative stress and inflammatory markers such as protein carbonyl, OX-LDL, IL-6, Hcy, and TNF-α. Furthermore, their total antioxidant capacity was increased significantly compared to that of the ethanol group. These findings indicate that ethanol induces the small intestine abnormality by oxidative and inflammatory stress, and that these effects can be alleviated by using vitamin E as an antioxidant and anti-inflammatory molecule.

  18. 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

  19. Immunohistochemical characterization of cellular proliferation in small intestinal hyperplasia of rats with hepatic Strobilocercus fasciolaris infection.

    PubMed

    Lagapa, J T; Oku, Y; Kamiya, M

    2008-07-01

    Rats infected with the larvae of Taenia taeniaeformis harbour the intermediate stage of the parasite Strobilocercus fasciolaris within the liver. Affected animals also develop gastric and intestinal hyperplasia. The pathogenesis of the gastric hyperplasia has been extensively investigated, but few studies have addressed the nature of the intestinal changes. This study characterizes the proliferation of small intestinal epithelial cells by immunohistochemical labelling for proliferating cell nuclear antigen (PCNA) and bromodeoxyuridine (BrdU) uptake. At 6 weeks post-infection (wpi) there was an increase in villous length but crypt depth was normal. At 9 wpi there was evidence of epithelial hyperplasia, increased villous length and crypt depth, and expansion of zones of epithelial proliferation. Immunohistochemical labelling indicated that an increase in the number of proliferating cells produced a greater number of progeny cells. Intestinal hyperplasia during experimental infection with T. taeniaeformis larvae is likely to be related to the associated gastropathy, although the mechanisms underlying both changes remain undefined.

  20. Effects of nimesulide on the small intestine mucositis induced by methotrexate in rats.

    PubMed

    Arslan, Aynur; Ozcicek, Adalet; Suleyman, Bahadir; Coban, Taha Abdulkadir; Cimen, Ferda Keskin; Nalkiran, Hatice Sevim; Kuzucu, Mehmet; Altuner, Durdu; Cetin, Nihal; Suleyman, Halis

    2016-11-01

    Intestinal mucositis is one of the major problems in the patients receiving cancer treatment. Nimesulide is a drug with antioxidant, antiinflammatory and antiulcer features. We aimed to investigate the effect of nimesulide on the small intestine mucositis induced by methotrexate (MTX) in rats. Experimental animals were divided into the control group, MTX group (MTXG) and nimesulide+MTX administered group (NMTXG) with eight rats per group. The control and MTXG groups were given distilled water by gavage and the NMTXG was given nimesulide 100 mg/kg orally. After one hour, the NMTXG and MTXG rat groups were administered oral MTX 5 mg/kg. This procedure was repeated once a day for 15 days and the rats were sacrificed. The duodenum and jejunum of each rat was removed for the assessment of biochemical markers and histopathological evaluation. Malondialdehyde (MDA) and myeloperoxidase (MPO) levels were significantly higher in the duodenal and jejunal tissues of the animals which received MTX, compared to the control and NMTXG (P<0.001). Also, the levels of total glutathione (tGSH), glutathione reductase (GSHRd), glutathione peroxidase (GSHPx), catalase (CAT) and superoxide dismutase (SOD) were significantly lower in the MTXG (P<0.001) compared to other groups. MTX led to villus and crypt epithelial damage and inflammation containing marked PMNL and eosinophils in the intestinal tissues histopathologically. Whereas, there was only mild irregularities in the villus structures of the NMTXG. Nimesulide protected the small intestines against damage by MTX. Intestinal mucositis caused by MTX may be preventable by co-administered nimesulide.

  1. Effects of nimesulide on the small intestine mucositis induced by methotrexate in rats

    PubMed Central

    Arslan, Aynur; Ozcicek, Adalet; Suleyman, Bahadir; Coban, Taha Abdulkadir; Cimen, Ferda Keskin; Nalkiran, Hatice Sevim; Kuzucu, Mehmet; Altuner, Durdu; Cetin, Nihal; Suleyman, Halis

    2016-01-01

    Intestinal mucositis is one of the major problems in the patients receiving cancer treatment. Nimesulide is a drug with antioxidant, antiinflammatory and antiulcer features. We aimed to investigate the effect of nimesulide on the small intestine mucositis induced by methotrexate (MTX) in rats. Experimental animals were divided into the control group, MTX group (MTXG) and nimesulide+MTX administered group (NMTXG) with eight rats per group. The control and MTXG groups were given distilled water by gavage and the NMTXG was given nimesulide 100 mg/kg orally. After one hour, the NMTXG and MTXG rat groups were administered oral MTX 5 mg/kg. This procedure was repeated once a day for 15 days and the rats were sacrificed. The duodenum and jejunum of each rat was removed for the assessment of biochemical markers and histopathological evaluation. Malondialdehyde (MDA) and myeloperoxidase (MPO) levels were significantly higher in the duodenal and jejunal tissues of the animals which received MTX, compared to the control and NMTXG (P<0.001). Also, the levels of total glutathione (tGSH), glutathione reductase (GSHRd), glutathione peroxidase (GSHPx), catalase (CAT) and superoxide dismutase (SOD) were significantly lower in the MTXG (P<0.001) compared to other groups. MTX led to villus and crypt epithelial damage and inflammation containing marked PMNL and eosinophils in the intestinal tissues histopathologically. Whereas, there was only mild irregularities in the villus structures of the NMTXG. Nimesulide protected the small intestines against damage by MTX. Intestinal mucositis caused by MTX may be preventable by co-administered nimesulide. PMID:27333839

  2. 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.

  3. 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

  4. Subcellular localization of enterokinase (enteropeptidase EC 3.4.21.9) in rat small intestine.

    PubMed

    Lebenthal, E; Morrissey, G W

    1977-04-27

    The subcellular localization of enterokinase is controversial. In this study, enterokinase was extracted from a soluble fraction and a brush border fraction of rat small intestine by differential centrifugation. The soluble fraction contained 41% of the initial enterokinase activity while the brush border fraction contained only 4.6% of the initial activity. In contrast, alkaline phosphatase monitored as a brush border marker, yielded 26.3% in the brush border fraction and only 6% in the soluble fraction. Further separation of the soluble fraction on a Sepharose 4B column revealed three peaks of enterokinase activity. One small peak (3%) of a bound enzyme (Mr, 2 - 10(6)) and two larger peaks of free enzyme (Mr, 3 - 10(5) and 9 -10). In contrast, alkaline phosphatase major fraction was in a high molecular weight peak of bound enzyme. When the brush border fraction was chromatographed only a single peak of bound enterokinase and alkaline phosphatase were found. In the lower part of the small intestine, no brush border-bound enterokinase was found, while the peak of alkaline phosphatase was the same as in the upper intestine. These data suggest that enterokinase activity in the rat intestine is mainly in a free form localized in the mucin and soluble fraction and to a negligible extent in the brush border.

  5. [The x-ray microanalysis of the mucosa of the rat small intestine].

    PubMed

    Pogorelov, A G; Matys, Iu V

    1990-01-01

    A rat small intestine mucosa is shown to accumulate significant amount of potassium and chloride. There was found a correlation between the content of these chemical elements and glycoprotein compartmentalization in goblet cell secret, brush border of enterocytes and a mucus layer. In this connection a role of mucus glycoproteins in membrane digestion is discussed. For preparation of samples the cryotechniques of electron microscopy are used.

  6. 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.

  7. Small intestinal morphometric and biomechanical changes during physiological growth in rats.

    PubMed

    Lu, Xiao; Zhao, Jingbo; Gregersen, Hans

    2005-03-01

    Changes in small intestinal geometry, residual strain and stress-strain properties during physiological growth were studied in rats ranging from 1 to 32 weeks of age. Small intestinal mass and dimensions increased many-fold with age, e.g. the weight per unit length increased five-fold with age and the wall cross-sectional area increased four-fold. The opening angle of duodenum obtained at zero-stress state was approximately 220 degrees and 290 degrees during the first and second week after birth and decreased to 170 degrees at other ages (p < 0.005). The opening angle of ileum ranged between 120 degrees and 150 degrees . The residual strain of duodenum at the mucosal surface did not vary with age (p > 0.05) whereas the residual strain of ileum at the mucosal surface decreased with age (p < 0.001). The circumferential and longitudinal stress-strain curves fitted well to a mono-exponential function. At a given circumferential stress, the corresponding strain values increased during the first 8 weeks of age (p < 0.05) where after no further change was observed. Hence, the small intestine became more compliant during early life. At a given longitudinal stress, the corresponding strains of ileum and duodenum became larger during the first 2-4 weeks of age (p < 0.05) where after no further change was observed. The small intestine was stiffer in longitudinal direction compared to the circumferential direction. In conclusion, pronounced morphometric and biomechanical changes were observed in the rat small intestine during physiological growth. Such data may prove useful in the understanding of the functional changes of the digestive tract during early life.

  8. [Responses of peptide hydrolases of the small and large intestines in rats on the administration of antibiotics].

    PubMed

    Borshchëv, Iu Iu; Gromova, L V; Ermolenko, E I; Grefner, N M; Borshchëva, I Iu; Gruzdkov, A A

    2012-06-01

    Effects of antibiotics on the structure and functional state of the intestine are not clear. We investigated some structural parameters of the small and large intestine, and activities of two intestinal peptide hydrolases in rats after administration of ampicillin and metronidazole during 3 and 5 days. After 3 days of antibiotic administration a decrease in the weight of mucosa in the small intestine, accompanied with a reduction in the villous height and width in this part of the intestine, and in the weight ofmucosa in the colon occured. At the same time the number of goblet cells in the small intestinal epithelium was increased. Specific activities of aminopeptidase M, and glycyl-L-leucine dipeptidase (micromol/min per g) in the mucosa of the small intestine were increased, and the total activities (micromol/min calculated per a part of the intestine) of the same enzymes did not change. The administration of antibiotics for 5 days resulted in increase of specific activity ofaminopeptidase M in the mucosa of the proximal part of the small intestine. In the chyme of the small intestine and colon, activities of the same enzymes (micromol/min calculated per a part of the intestine) were increased on the third and fifth days of the antibiotic administration. Thus, the application ofampicillin and metronidazole within 3-5 days causes a disturbance of the structural and functional parameters in the small and large intestines, which is most pronounced on the third day of the drug administration.

  9. Membrane potentials of epithelial cells in rat small intestine

    PubMed Central

    Barry, R. J. C.; Eggenton, Jacqueline

    1972-01-01

    1. Stripped sacs of rat jejunum in which the outer muscle layers had been removed were found to maintain substantial transport and electrical activities. 2. Mucosal and serosal membrane potentials of epithelial cells of normal and stripped everted sacs of rat jejunum were recorded in vitro together with the transmural potential difference. 3. The cell interior was negative relative to both serosal and mucosal fluids, the transmural potential being the sum of the two membrane potentials. 4. Changes in the transmural potentials in the presence of actively transferred hexoses and amino acids were entirely due to variations in the serosal potential, the mucosal potential being unchanged. 5. Serosal and transmural potential increases on the addition of galactose were consistent with Michaelis—Menten kinetics, giving apparent Km values of 14·9 and 14·1 mM respectively. 6. Phlorrhizin, ouabain, 2,4-dinitrophenol and sodium fluoroacetate inhibited serosal potential changes in the presence of galactose. 7. Osmotic potentials resulting from transmural osmotic gradients originated from the serosal layers of the tissue. 8. The results are consistent with the concept of a serosally located, electrogenic sodium pump which is stimulated by actively transferred hexoses and amino acids. The sodium-dependent entry mechanism at the mucosal membrane is non-electrogenic. ImagesPlate 1 PMID:4646578

  10. Ingestion of potato starch containing esterified phosphorus increases alkaline phosphatase activity in the small intestine in rats.

    PubMed

    Mineo, Hitoshi; Morikawa, Nao; Ohmi, Sayako; Ishida, Kyo; Machida, Ayaka; Kanazawa, Takumi; Chiji, Hideyuki; Fukushima, Michihiro; Noda, Takahiro

    2010-05-01

    Alkaline phosphatase (ALP) hydrolyzes a variety of monophosphate esters and plays an important role in phosphorus (P) metabolism. Several nutrients in food have been reported to affect intestinal ALP activity in animal models. Previous reports indicated that high levels of P or phosphate in diets decreased intestinal ALP activity in rats. Because potato starch contains considerable amounts of esterified P, unlike other starch-derived plants, we hypothesized that the feeding of potato starch would decrease ALP activity in the intestinal tract. Male Sprague-Dawley rats (7 weeks old) were fed 3 different types of diet containing 60% corn starch or 1 of 2 types of potato starch with different esterified P content for 1 or 5 weeks. Body weight and food intake of each rat were measured every day throughout the experimental periods. At the end of the feeding periods, the small intestine was removed to determine ALP activity in the mucosal tissues. Significant differences were observed in ALP activity in the small intestine between the 2 feeding periods, among the 4 segments of the small intestine, and among the 3 diet groups. Significant positive linear correlations between the amount of P derived from the starch and mucosal ALP activity were obtained in the jejunum and jejunoileum in rats after feeding for 5 weeks. We concluded, contrary to our hypotheses, that the ingestion of potato starch adaptively increases ALP activity in the upper part of the small intestine of growing rats in an esterified P content-dependent manner.

  11. Exacerbation of nonsteroidal anti-inflammatory drug-induced small intestinal lesions by antisecretory drugs in rats: the role of intestinal motility.

    PubMed

    Satoh, Hiroshi; Amagase, Kikuko; Takeuchi, Koji

    2012-11-01

    Antisecretory drugs such as histamine H2-receptor antagonists (H2-RAs) and proton pump inhibitors (PPIs) are commonly used for the treatment of gastric and duodenal ulcers induced by nonsteroidal anti-inflammatory drugs (NSAIDs). However, the effects of these drugs on NSAID-induced small intestinal ulcers are not fully understood. The effects of H2-RAs and PPIs on NSAID-induced gastrointestinal lesions and small intestinal motility were examined in rats. Male Wistar rats (180-220 g) were used. Indomethacin (10 mg/kg) was administered orally in fasted or fed rats, and gastrointestinal lesions were examined 24 h after indomethacin administration. Intestinal motility was measured by using a balloon method under urethane anesthesia. Indomethacin produced multiple lesions in the gastric corpus in fasted rats and in the small intestine in fed rats: 1) H2-RAs (cimetidine, ranitidine, and famotidine) and PPIs (omeprazole, lansoprazole, and rabeprazole) markedly inhibited the formation of gastric lesions. 2) The drugs, except for lansoprazole, increased intestinal lesions. 3) H2-RAs augmented the increase in intestinal motility caused by indomethacin, and the effects of H2-RAs on motility and intestinal lesions were markedly inhibited by atropine. 4) Lansoprazole inhibited the formation of intestinal lesions, and the effect was prevented by both pharmacological ablation of capsaicin-sensitive sensory neurons and pretreatment with N-nitro-l-arginine methyl ester, a selective inhibitor of nitric-oxide synthesis. The results suggest that: 1) inhibition of acid secretion by antisecretory drugs may exacerbate NSAID-induced intestinal lesions, 2) H2-RAs further aggravate lesions by increasing intestinal motility via the activation of cholinergic pathways, and 3) lansoprazole protects the intestinal mucosa against NSAID-related ulcerative stimuli.

  12. 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.

  13. Transesterification of a series of 12 parabens by liver and small-intestinal microsomes of rats and humans.

    PubMed

    Fujino, Chieri; Watanabe, Yoko; Uramaru, Naoto; Kitamura, Shigeyuki

    2014-02-01

    Hydrolytic transformation of parabens (4-hydroxybenzoic acid esters; used as antibacterial agents) to 4-hydroxybenzoic acid and alcohols by tissue microsomes is well-known both in vitro and in vivo. Here, we investigated transesterification reactions of parabens catalyzed by rat and human microsomes, using a series of 12 parabens with C1-C12 alcohol side chains. Transesterification of parabens by rat liver and small-intestinal microsomes occurred in the presence of alcohols in the microsomal incubation mixture. Among the 12 parabens, propylparaben was most effectively transesterified by rat liver microsomes with methanol or ethanol, followed by butylparaben. Relatively low activity was observed with longer-side-chain parabens. In contrast, small-intestinal microsomes exhibited higher activity towards moderately long side-chain parabens, and showed the highest activity toward octylparaben. When parabens were incubated with liver or small-intestinal microsomes in the presence of C1-C12 alcohols, ethanol and decanol were most effectively transferred to parabens by rat liver microsomes and small-intestinal microsomes, respectively. Human liver and small-intestinal microsomes also exhibited significant transesterification activities with different substrate specificities, like rat microsomes. Carboxylesterase isoforms, CES1b and CES1c, and CES2, exhibited significant transesterification activity toward parabens, and showed similar substrate specificity to human liver and small-intestinal microsomes, respectively.

  14. Effects of titanium dioxide nanoparticles on small intestinal mucosa in rats.

    PubMed

    Onishchenko, G E; Erokhina, M V; Abramchuk, S S; Shaitan, K V; Raspopov, R V; Smirnova, V V; Vasilevskaya, L S; Gmoshinski, I V; Kirpichnikov, M P; Tutelyan, V A

    2012-12-01

    Penetration of titanium dioxide nanoparticles into enterocytes after their administration into isolated loop of rat small intestine was shown in vivo by transmission electron microscopy. Using electron diffraction, titanium dioxide nanoparticles were identified in the apical regions of the cells under plasma membranes and in deeper parts of the cytoplasm as solitary objects or small aggregations. Water dispersions of nanoparticles (3-h exposure to high concentrations) caused no appreciable morphological changes in enterocyte ultrastructure. A 28-day subacute intragastric administration of water dispersion of nanoparticles to rats led to titanium accumulation in the liver, their level was significantly higher than in the control group, which was shown by mass spectrometry with inductive-bound plasma. These data indicated the possibility of penetration of titanium dioxide nanoparticles through the gastrointestinal barrier under near-physiological conditions.

  15. Small Intestine Disorders

    MedlinePlus

    Your small intestine is the longest part of your digestive system - about twenty feet long! It connects your stomach to ... many times to fit inside your abdomen. Your small intestine does most of the digesting of the foods ...

  16. Small intestine (image)

    MedlinePlus

    The small intestine is the portion of the digestive system most responsible for absorption of nutrients from food into the ... the duodenum. This short first portion of the small intestine is followed by the jejunum and the ileum. ...

  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. The effects of age on mucosal morphology and epithelial cell production in rat small intestine.

    PubMed Central

    Clarke, R M

    1977-01-01

    Six groups of male Wistar rats were used, with mean weights of 29, 63, 97, 161, 249 and 399 g. Pieces of small intestine from three sites were examined after staining in bulk with the Feulgen reaction. Crypt/villus ratio (the number of crypts per villus) rose with age at all three sites, Villus height and crypt depth were measured on microdissected specimens. Villi in the proximal intestine were always taller than those distally. Proximal villi increased in height in successively older rats, except in the oldest group. Villi at the two distal sites tended to be tall in the youngest group of rats, but suffered a temporary reduction in height in the next two age groups. Crypt depth increased markedly within the first three age groups, and more slowly thereafter. Colchicine-metaphase accumulation rate was estimated from counts on microdissected intact crypts. The rate was low in the youngest group (8 cells/crypt/hour) but about 30 cells/crypt/hour in all other groups. After the changes during the early phase of rapid growth, no marked changes were seen during later life. The significance of these findings is discussed. PMID:885792

  19. GABA-related actions in isolated in vitro preparations of the rat small intestine.

    PubMed

    Krantis, A; Harding, R K

    1987-09-11

    Longitudinal organ bath preparations of the rat duodenum, jejunum and ileum were tested for their responsiveness to GABA-receptor agonists. The GABAA-receptor agonists, GABA and 3APS, induced non-adrenergic, non-cholinergic relaxations and/or contractions, although the magnitude and type of response varied depending upon the region tested. All regions relaxed to applied GABA or 3APS, however the jejunum and ileum also responded with cholinergic contractions. These relaxant and contractile actions were neurogenic and sensitive to blockade by the GABA antagonists bicuculline or picrotoxinin, and desensitization to either agonist. The GABAB-receptor agonist baclofen, caused a reduction in electrically evoked cholinergic contractions. These inhibitory actions of baclofen were insensitive to bicuculline or picrotoxinin. Taken together, these results show that GABA-ergic actions in the rat small intestine are mediated by two pharmacologically distinct neural receptor populations, the GABAA and GABAB sites, the distribution and sensitivity of which differ along the length of the small intestine.

  20. Glutamine supplementation and deprivation: effect on artificially reared rat small intestinal morphology.

    PubMed

    Potsic, Bradley; Holliday, Nicolette; Lewis, Pat; Samuelson, Donald; DeMarco, Vincent; Neu, Josef

    2002-09-01

    The mechanisms of how glutamine benefits critically ill patients have not been established. The purpose of this study was to determine the effects of dietary and endogenously produced glutamine on small intestinal morphology using light and transmission electron microscopy in artificially reared rat pups. It was hypothesized that deprivation of dietary glutamine leads to intestinal disease that is exacerbated by inhibition of glutamine synthetase by methionine sulfoximine (MS). Rat pups were placed into five different test groups: The first was a reference group that was reared by their mother. The other four groups were reared artificially and received a 10% Travasol amino acid solution at 5 g/kg per day, which does not contain glutamine, added to a mixture containing carbohydrates, lipids, and vitamins. This dose was chosen because it represents an approximation of the amount of glutamine these rats would be receiving in a normal rat diet (approximately 40 g/kg per day total protein, 10 to 15% of which is glutamine + glutamate). The glutamine was manipulated by adding glutamine (Q) or MS or both. The four groups were as follows: MS-Q-, MS-Q+, MS+Q-, and MS+Q+. Light microscopy revealed the greatest blunting of villus height in the ileum of rats from the MS+Q- group when compared with the MS-Q+ group (123 +/- 48.9 micro m versus 207 +/- 36 microm, p < 0.05). The other two groups exhibited intermediate villus heights, but all were shorter than the villi from the mother-reared animals. The number of villi per unit length of bowel was also lowest in the animals that were treated with MS and not provided with dietary glutamine. Transmission electron microscopy demonstrated breakdown of the epithelial junctions in the glutamine-deprived and glutamine synthetase-inhibited intestines. Glutamine-deprived animals also displayed sloughing of microvilli, decreased actin cores, and degeneration of the terminal web. In summary, these studies support the hypothesis that

  1. A rat decellularized small bowel scaffold that preserves villus-crypt architecture for intestinal regeneration

    PubMed Central

    Totonelli, Giorgia; Maghsoudlou, Panagiotis; Garriboli, Massimo; Riegler, Johannes; Orlando, Giuseppe; Burns, Alan J.; Sebire, Neil J.; Smith, Virpi V.; Fishman, Jonathan M.; Ghionzoli, Marco; Turmaine, Mark; Birchall, Martin A.; Atala, Anthony; Soker, Shay; Lythgoe, Mark F.; Seifalian, Alexander; Pierro, Agostino; Eaton, Simon; De Coppi, Paolo

    2012-01-01

    Management of intestinal failure remains a clinical challenge and total parenteral nutrition, intestinal elongation and/or transplantation are partial solutions. In this study, using a detergent-enzymatic treatment (DET), we optimize in rats a new protocol that creates a natural intestinal scaffold, as a base for developing functional intestinal tissue. After 1 cycle of DET, histological examination and SEM and TEM analyses showed removal of cellular elements with preservation of the native architecture and connective tissue components. Maintenance of biomechanical, adhesion and angiogenic properties were also demonstrated strengthen the idea that matrices obtained using DET may represent a valid support for intestinal regeneration. PMID:22305104

  2. The mesenterially perfused rat small intestine: A versatile approach for pharmacological testings.

    PubMed

    Schreiber, Dominik; Klotz, Markus; Laures, Kerstin; Clasohm, Jasmin; Bischof, Michael; Schäfer, Karl-Herbert

    2014-05-01

    Pharmaceutical compounds enter the body via several major natural gateways; i.e. the lung, the skin and the gastrointestinal tract. Drug application during surgical operations can lead to severe impairment of gastrointestinal motility, which can contribute to a paralytic ileus. Here we investigated an ex vivo perfused small intestine model that allows us to ascertain the influence of pharmaceuticals upon the gut. Corresponding segments from the proximal jejunum of adult rats were used. Their mesenteric arteries and veins were cannulated and the jejunal segment excised. The individual segments were placed in a custom designed perfusion chamber and perfusion performed through the intestinal lumen as well as the mesenteric superior artery. Three test drugs, which are commonly used in anesthesiology; i.e. pentobarbital, propofol and ketamine were administered via the blood vessels. Their effects upon gastrointestinal motility patterns were evaluated by optical measurements. Longitudinal and pendular movements were distinguishable and separately analyzed. Pharmacological effects of the individual substances could be investigated. Propofol (50-200 μg/ml) was found to decrease intestinal motility, especially longitudinal movements in a dose dependent manner. Pentobarbital decreased intestinal motility only at high concentrations, above 2.5 mg/ml. A dose of 2.5 mg/ml lead to an increase in longitudinal- and pendular movements in comparison to control, while ketamine (2.5-10 mg/ml) did not alter intestinal motility at all. Histological examination of the perfused segments revealed only minor changes in tissue morphology after perfusion. The perfusion approach shown here allows for the identification of compounds which interfere with gut motility in a highly sophisticated way. It is suitable for characterization of drug and dose specific changes in motility patterns and can be used in drug development and preclinical studies.

  3. Dexamethasone damages the rat stomach but not small intestine during inhibition of COX-1.

    PubMed

    Yokota, Aya; Taniguchi, Masaki; Takahira, Yuka; Tanaka, Akiko; Takeuchi, Koji

    2007-06-01

    We previously reported that inhibition of both COX-1 and COX-2 is required for the gastrointestinal ulcerogenic properties of nonsteroidal anti-inflammatory drugs (NSAIDs). Inhibition of COX-1 up-regulates COX-2 expression, and the prostaglandins (PGs) produced by COX-2 help to maintain the mucosal integrity during inhibition of COX-1. In the present study we investigated whether dexamethasone damages rat gastrointestinal mucosa during inhibition of COX-1 and further developed the idea that COX-2 expression is a key event in the ulcerogenic actions of NSAIDs. Dexamethasone was given p.o. in the absence or presence of SC-560 (a selective COX-1 inhibitor), and the stomach or intestine was examined 8 or 24 hr later, respectively. Neither dexamethasone nor SC-560 alone damaged the gastrointestinal mucosa. In the presence of SC-560, however, dexamethasone damaged the stomach but not small intestine. SC-560 decreased PGE(2) levels in both tissues, with a gradual recovery accompanying the up-regulation of COX-2 expression, and both the recovery of PGE(2) levels and the expression of COX-2 were inhibited by dexamethasone. In the animals treated with SC-560, iNOS expression was up-regulated in the intestinal but not the gastric mucosa, and this response was also inhibited by dexamethasone. These results suggest a risk from steroid therapy in the stomach when COX-2 expression is up-regulated. Dexamethasone does not provoke damage in the intestine, despite inhibiting the up-regulation of COX-2 expression under conditions of PG deficiency; at least one of the reasons is that this agent prevents the expression of iNOS, a major factor in the pathogenesis of intestinal lesions.

  4. Expression and effects of metabotropic CRF1 and CRF2 receptors in rat small intestine.

    PubMed

    Porcher, Christophe; Juhem, Aurélie; Peinnequin, André; Sinniger, Valérie; Bonaz, Bruno

    2005-05-01

    Corticotropin-releasing factor (CRF)-like peptides mediate their effects via two receptor subtypes, CRF1 and CRF2; these receptors have functional implication in the motility of the stomach and colon in rats. We evaluated expression and functions of CRF1 and CRF2 receptors in the rat small intestine (i.e., duodenum and ileum). CRF(1-2)-like immunoreactivity (CRF(1-2)-LI) was localized in fibers and neurons of the myenteric and submucosal ganglia. CRF(1-2)-LI was found in nerve fibers of the longitudinal and circular muscle layers, in the mucosa, and in mucosal cells. Quantitative RT-PCR showed a stronger expression of CRF2 than CRF1 in the ileum, whereas CRF1 expression was higher than CRF2 expression in the duodenum. Functional studies showed that CRF-like peptides increased duodenal phasic contractions and reduced ileal contractions. CRF1 antagonists (CP-154,526 and SSR125543Q) blocked CRF-like peptide-induced activation of duodenal motility but did not block CRF-like peptide-induced inhibition of ileal motility. In contrast, a CRF2 inhibitor (astressin2-B) blocked the effects of CRF-like peptides on ileal muscle contractions but did not influence CRF-like peptide-induced activation of duodenal motility. These results demonstrate the presence of CRF(1-2) in the intestine and demonstrate that, in vitro, CRF-like peptides stimulate the contractile activity of the duodenum through CRF1 receptor while inhibiting phasic contractions of the ileum through CRF2 receptor. These results strongly suggest that CRF-like peptides play a major role in the regulatory mechanisms that underlie the neural control of small intestinal motility through CRF receptors.

  5. Polyamidoamine dendrimers as novel potential absorption enhancers for improving the small intestinal absorption of poorly absorbable drugs in rats.

    PubMed

    Lin, Yulian; Fujimori, Takeo; Kawaguchi, Naoko; Tsujimoto, Yuiko; Nishimi, Mariko; Dong, Zhengqi; Katsumi, Hidemasa; Sakane, Toshiyasu; Yamamoto, Akira

    2011-01-05

    Effects of polyamidoamine (PAMAM) dendrimers on the intestinal absorption of poorly absorbable drugs were examined by an in situ closed loop method in rats. 5(6)-Carboxyfluorescein (CF), fluorescein isothiocyanate-dextrans (FDs) with various molecular weights, calcitonin and insulin were used as model drugs of poorly absorbable drugs. The absorption of CF, FD4 and calcitonin from the rat small intestine was significantly enhanced in the presence of PAMAM dendrimers. The absorption-enhancing effects of PAMAM dendrimers for improving the small intestinal absorption of CF were concentration and generation dependent and a maximal absorption-enhancing effect was observed in the presence of 0.5% (w/v) G2 PAMAM dendrimer. However, G2 PAMAM dendrimer had almost no absorption-enhancing effect on the small intestinal absorption of macromolecular drugs including FD10 and insulin. Overall, the absorption-enhancing effects of G2 PAMAM dendrimer in the small intestine decreased as the molecular weights of drug increased. However, G2 PAMAM dendrimer did not enhance the intestinal absorption of these drugs with different molecular weights in the large intestine. Furthermore, we evaluated the intestinal membrane damage with or without G2 PAMAM dendrimer. G2 PAMAM dendrimer (0.5% (w/v)) significantly increased the activities of lactate dehydrogenase (LDH) and the amounts of protein released from the intestinal membranes, but the activities and amounts of these toxic markers were less than those in the presence of 3% Triton X-100 used as a positive control. Moreover, G2 PAMAM dendrimer at concentrations of 0.05% (w/v) and 0.1% (w/v) did not increase the activities and amounts of these toxic markers. These findings suggested that PAMAM dendrimers at lower concentrations might be potential and safe absorption enhancers for improving absorption of poorly absorbable drugs from the small intestine.

  6. Digestion and assimilation features of dietary DAG in the rat small intestine.

    PubMed

    Kondo, Hidehiko; Hase, Tadashi; Murase, Takatoshi; Tokimitsu, Ichiro

    2003-01-01

    Several recent studies have demonstrated that dietary DAG oil rich in 1,3-species suppresses the postprandial increase of serum TAG level and decreases body fat accumulation, compared with TAG oil. To clarify the mechanisms underlying the beneficial effects of DAG, we investigated the metabolic features of DAG in the small intestine with regard to the digestion pathway in the lumen and the TAG-synthesis pathway in the mucosa. When intraduodenally infused as an emulsion, TAG was digested to 1,2-DAG, 2-MAG, and FFA, whereas 1,3-DAG was digested to 1(3)-MAG and FFA. When assessed by the incorporation of [1-14C]linoleic acid in lipids, the mucosal TAG-synthesis was significantly reduced by DAG infusion compared with TAG infusion. However, the mucosal 1,3-DAG synthesis was remarkably increased in the DAG-infused rats. The total amount of mucosal 1,3-DAG was also increased (4.5-fold) after DAG infusion compared with that after TAG infusion. Next, we examined the synthesis pathway of 1,3-DAG. In cultures of the everted intestinal sacs, 1,3-DAG production required the presence of 1-MAG, suggesting that the 1,3-DAG synthesis was due to acylation of 1(3)-MAG in the DAG-infused rats. Furthermore, measurements of DAG acyltransferase activity indicated that 1,3-DAG was little utilized in TAG synthesis. These findings suggest that features of 1,3-DAG digestion and assimilation in the intestine may be responsible for the reduction of the postprandial serum TAG level by dietary DAG.

  7. 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.

  8. Regulation of metallothionein gene expression and cellular zinc accumulation in a rat small intestinal cell line

    SciTech Connect

    Carlson, J.M.; Cousins, R.J. )

    1991-03-15

    The effects of extracellular zinc concentration on metallothionein gene expression and cellular zinc accumulation were studied in IRD-98 cells. This is a non-transformed clonal line established by Negrel, et al. from fetal rat small intestine which possess characteristics of small bowel epithelial cells. Cells were maintained in DMEM and grown to confluent monolayers. The response to media zinc concentrations over the range of 5-150 {mu}mol/L was assessed. After 24 h in culture, cell zinc and metallothionein protein concentrations were significantly increased in cells provided higher levels of media zinc. Subsequent time course experiments showed that cells exposed to higher zinc levels had significant elevations in both metallothionein mRNA, peaking at 24 h, and metallothionein protein increasing through 48 h. Furthermore, cell zinc concentrations were significantly increased. At 48 h of culture, greater than 50% of the additional cellular zinc accumulated could be attributed to elevated metallothionein protein levels. These cells represent a zinc-responsive model to examine the mechanism of zinc uptake and transcellular transport by intestinal cells and the regulatory factors involved.

  9. 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.

  10. 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.

  11. 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

  12. Influence of high-calorie (cafeteria) diets on the population of Paneth cells in the small intestine of the rat.

    PubMed

    Becerril, Adriana; Castillo-Robles, Guadalupe; González-Hernández, Margarita; Villanueva, Iván

    2005-01-01

    A high-calorie (cafeteria) diet is known to cause changes in the intestinal morphology and functioning that seem to be related to calorie overfeeding. Among the cell lineages found in the small intestine epithelium, the Paneth cell (PC) population is known to be influenced by factors related mainly to the intestinal microbiota. The role of PCs in the intestinal cell concert remains unclear, because experimental evidence suggests PC involvement in local processes other than protection against pathogens. Participation of PC in digestive mechanisms has been proposed on this basis. We have analyzed the effect of high-carbohydrate (HC) and high-fat (HF) cafeteria diets on the PC population in the small intestine of the adult rat. For 8 weeks, both HC and HF diets caused a gain in body weight, but whereas the HC-fed rats showed reduced counts of intestinal crypts per 5-mum section, the HF-fed group showed the opposite. In control rats, the number of crypts per section showed a slight tendency to decrease along the duodenum - ileum axis, whereas the number of PCs per crypt was increased towards the ileum. As a result, the number of PCs per section (calculated from these data) remained constant along the three segments of the intestine. The hypercaloric diets did not modify the general tendencies seen in the crypt and PC counts, but reduced the number of PCs per section in the duodenum by 50%. HC-fed, but not HF-fed, rats showed a similar reduction in jejunum also. These changes do not correlate particularly with any of the predictable effects of diet composition, so that a multifactorial control of PC density is proposed.

  13. Structural and Functional Analysis of the Small Intestine in Rats After Six-Month-Long Exposure to Multiwalled Carbon Nanotubes.

    PubMed

    Belyaeva, N N; Sycheva, L P; Savostikova, O N

    2016-10-01

    Structural and functional analysis of the small intestinal villi in outbred rats was performed after treatment with multiwalled carbon nanotube suspension in comparison with the effects of fine charcoal suspension. Chronic (6 months) exposure to nanotubes in a concentration of 0.2 mg/liter and, particularly, 0.5 mg/liter induced significant changes in the small intestine manifested in a decrease in the number of villi without changes in the brush border integrity, increase in the number of destructed villi, and appearance of villi with apical necrosis. These abnormalities were not observed after treatment for a shorter period of time (2 months).

  14. Effect of prostaglandin E/sub 2/ on the small intestine of indomethacin-treated rats

    SciTech Connect

    Romain, N.; Dandrifosse, G.; Forget, P.; Lepoint, A.

    1987-09-07

    In the present study, the protective effect of PGE/sub 2/ on intestinal damage in indomethacin-treated adult rats was investigated. Ileal integrity was evaluated making use of different biochemical and histological parameters : activities of sucrase, maltase and diamine oxidase; concentrations of DNA, putrescine, spermidine and spermine; incorporation of /sup 3/H-thymidine into DNA; mitotic index and mucosal thickness. Results expressed per g of mucosal weight, showed that : - maltase and diamine oxidase activities as well as DNA, spermidine and spermine concentrations decreased markedly in indomethacin-treated rats when compared to control rats; - the decrease of maltase activity as well as DNA, spermidine and spermine concentration was less pronounced in PGE/sub 2/-treated rats when compared to indomethacin-treated rats; - /sup 3/H-thymidine incorporation into DNA and mitotic index values showed no significant variation in the course of different treatments; - mucosal thickness increased strongly, the PGE/sub 2/-protected rats. The authors suggest that PGE/sub 2/ could protect the rat's intestinal mucosa against the effects of indomethacin through a trophic action on intestinal villi. 15 references, 3 tables.

  15. Reconstruction of abdominal wall musculofascial defects with small intestinal submucosa scaffolds seeded with tenocytes in rats.

    PubMed

    Song, Zhicheng; Peng, Zhiyou; Liu, Zhengni; Yang, Jianjun; Tang, Rui; Gu, Yan

    2013-07-01

    The repair of abdominal wall defects following surgery remains a difficult challenge. Although multiple methods have been described to restore the integrity of the abdominal wall, there is no clear consensus on the ideal material for reconstruction. This study explored the feasibility of in vivo reconstruction of a rat model of an abdominal wall defect with a composite scaffold of tenocytes and porcine small intestinal submucosa (SIS). In the current study, we created a 2×1.5 cm abdominal wall defect in the anterolateral abdominal wall of Sprague-Dawley rats, which were assigned into three groups: the cell-SIS construct group, the cell-free SIS scaffold group, and the abdominal wall defect group. Tenocytes were obtained from the tendons of rat limbs. After isolation and expansion, cells (2×10(7)/mL) were seeded onto the three-layer SIS scaffolds and cultured in vitro for 5 days. Cell-SIS constructs or cell-free constructs were implanted to repair the abdominal wall defects. The results showed that the tenocytes could grow on the SIS scaffold and secreted corresponding matrices. In addition, both scaffolds could repair the abdominal wall defects with no hernia recurrence. In comparison to the cell-free SIS scaffold, the composite scaffold exhibited increased vascular regeneration and mechanical strength. Furthermore, following increased time in vivo, the mechanical strength of the composite scaffold became stronger. The results indicate that the composite scaffold can provide increased mechanical strength that may be suitable for repairing abdominal wall defects.

  16. Glycoprotein biosynthesis in small intestine

    PubMed Central

    Kim, Young S.; Perdomo, Jose

    1972-01-01

    Rat small intestinal mucosa was examined for ability to produce mucins with human blood group A, B, and H activity. Blood group activity of the mucins was compared to antigenic activity of red blood cells in individual rats and the enzymatic basis for differences was investigated. Red cells in all the rats examined contained human blood group A and B antigens. All rats synthesized intestinal mucins having B and H antigenic activity but 57% failed to produce mucins with blood group A activity (A-); the remaining 43% (A+) produced A substance. The activities of five glycosyltransferases including α(1→2) fucosyltransferase, the determinant of human secretor status, were measured in the intestine of A+ and A- rats. Four enzymes were the same in both groups, while the fifth, N-acetylgalactosaminyltransferase, was present only in A+ rats. The specificity of this latter enzyme, as found in the rat, appeared similar to that in humans, since it catalyzed addition of N-acetyl-D-galactosamine only to acceptors which had the H determinant structure. In the presence of the enzyme, A- mucin could be converted to A+ mucin; this was shown both by hemagglutination inhibition and immunoprecipitin studies of the products of incubation of A- mucin with UDP-N-acetyl-D-galactosamine and the enzyme. These studies indicate that the difference between A+ and A- rats is due to the apparent absence of N-acetylgalactosaminyltransferase in the intestinal mucosa of A- rats. These rats may provide experimental models for studies on the effect of ABO and secretor status on susceptibility to ulceration and carcinogenesis. Images PMID:4112001

  17. Evidence for regulatory control of iron uptake from ferric maltol across the small intestine of the rat.

    PubMed Central

    Barrand, M. A.; Callingham, B. A.

    1991-01-01

    1. 59Fe absorption from the novel iron compound, ferric maltol, was studied in rats pretreated twice daily for two weeks with non-radioactive ferric maltol in oral doses containing 7 mg elemental iron. Tissue accumulation of 59Fe 2 h after administration of radioactive ferric maltol into the stomach was significantly lower in iron pretreated animals than in saline-treated controls. 2. 59Fe uptake from ferric maltol into isolated fragments of ileum and of duodenum was of similar magnitude in control animals but in iron-treated animals, duodenal uptake was significantly lower than that of the ileum. 3. Absorption of 59Fe was also investigated in anaesthetized rats after intestinal perfusion with saline (controls) or with 5 mM chenodeoxycholate to render the intestines more permeable. 4. Changes in permeability of the small intestine were monitored by estimating the amount of [14C]-mannitol absorbed and fluid secreted with reference to the non-absorbable [3H]-inulin in the perfusate effluents. 5. Despite the increased permeability of the intestines after bile salt treatment, there was little difference from control in the tissue accumulation of 59Fe from ferric maltol 2 h after intraduodenal administration. However 59Fe absorption from ferrous sulphate was significantly increased after bile salt treatment. 6. Gel filtration profiles of plasma made 5 and 60 min after intraduodenal administration of [59Fe]-ferric [3H]-maltol demonstrated that metal and ligand do not enter the circulation as the complex even when intestinal permeability is increased. 7. Uptake of 59Fe was investigated in isolated fragments of rat small intestine after saline or bile salt perfusion. Although 59Fe uptake from ferric maltol was somewhat greater in the bile salt-treated intestinal fragments, saturable kinetics were still observed.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 1 Figure 4 PMID:2015422

  18. 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.

  19. Effect of vitamin A deficiency on permeability of the small intestinal mucosa for macromolecules in adult rats

    SciTech Connect

    Gmoshinskii, I.V.; Khvylya, S.I.; Kon', I.Ya.

    1987-07-01

    The authors study the effect of experimental vitamin A deficiency on absorption of macromolecules of hen's ovalbumin in the intestine. An electron-microscopic study of permeability of small intestine enterocytes for particles of colloidal lanthanum hydroxide La(OH)/sub 3/ was carried out at the same time. The concentration of unsplit hen's ovalbumin in the blood of the rats used in the experiment was determined by competitive radioimmunoassay. Samples of serum were incubated with indicator doses of /sup 125/I-OA. Radioactivity of the precipitates was measured.

  20. 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

  1. 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.

  2. Effect of fiber length of carbon nanotubes on the absorption of erythropoietin from rat small intestine.

    PubMed

    Ito, Yukako; Venkatesan, Natarajan; Hirako, Noriko; Sugioka, Nobuyuki; Takada, Kanji

    2007-06-07

    Erythropoietin (EPO) loaded carbon nanotubes (CNTs) with surfactant as an absorption enhancer were prepared for the oral delivery of EPO using two types of CNTs, long and short fiber length CNTs, and the effect of CNT fiber length on the absorption efficiency of EPO was studied. After Labrasol, PEG-8 caprylic/capric glycerides, as absorption enhancer was adsorbed into long fiber CNTs of which mean fiber length was 20-80 microm, as a carrier, EPO and casein as protease inhibitor and Explotab (sodium starch glycolate) as a disintegrating agent, were mixed. The resulting solid preparation was administered into the rat jejunum and serum EPO levels were measured by ELISA. The dose of EPO, CNTs, casein and Explotab were 100 IU/kg, 5mg/kg, 25mg/kg and 2.5mg/kg, respectively. Serum EPO level reached to C(max), 69.0+/-3.9 mIU/ml, at 3.5+/-0.1h and AUC was 175.7+/-13.8 mIU h/ml. These values were approximately half of that obtained with short fiber length CNTs of which C(max) was 143.1+/-15.2 mIU/ml and AUC was 256.3+/-9.7 mIU h/ml. When amphoteric surfactant, Lipomin LA, sodium beta-alkylaminopropionic acid, was used to accelerate the disaggregation of long fiber length CNTs, C(max) was 36.0+/-4.9 and AUC was 96.9+/-11.9, which showed less bioavailability (BA) of EPO. These results suggest that the short fiber length CNTs deliver more both EPO and absorption enhancer to the absorptive cells of the rat small intestine and the aggregation of CNTs is not the critical factor for the oral delivery of EPO.

  3. Existence of serotonin and neuropeptides-immunoreactive endocrine cells in the small and large intestines of the mole-rats (Spalax leucodon).

    PubMed

    Yaman, M; Bayrakdar, A; Tarakçı, B G

    2012-08-01

    The present study was conducted to clarify the regional distribution and relative frequency of endocrine cells secreting serotonin, substance P (SP), cholecystokinin-8 (CCK-8), vasoactive intestinal polypeptide (VIP) and neurotensin in the small and large intestine of the mole-rats (Spalax leucodon), by specific immunohistochemical methods. In the small and large intestine of mole-rats (Spalax leucodon), serotonin, SP and VIP were identified with various frequencies, but CCK-8 and neurotensin were not observed. Most of the IR cells in the small and large intestine were located in the intestinal crypt and epithelium however, they were more frequency in the intestinal crypt. Serotonin-IR cells were detected throughout the whole intestinal tract, predominantly in the duodenum and colon. SP-IR cells were demonstrated throughout the whole intestinal tract except for the ileum and rectum with highest frequencies in the cecum. VIP-IR cells were found in all parts of the small intestine except for the large intestine. In conclusion, the general distribution patterns and relative frequency of intestinal endocrine cells of the mole-rats (Spalax leucodon) was similar to those of some rodent species. However, some species-dependent unique distributions and frequencies characteristics of endocrine cells were also observed in the present study.

  4. 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

  5. Emu oil expedites small intestinal repair following 5-fluorouracil-induced mucositis in rats.

    PubMed

    Mashtoub, Suzanne; Tran, Cuong D; Howarth, Gordon S

    2013-11-01

    Mucositis resulting from cancer chemotherapy is characterized by intestinal inflammation and ulceration. Previously, emu oil (EO) improved intestinal architecture (Br J Nutr, 2010) in a rat model of chemotherapy-induced mucositis. We investigated EO for its further potential to promote intestinal repair in this mucositis model. Female Dark Agouti rats (n = 8/group) were gavaged with water, olive oil (OO) or EO once daily (1 mL), injected with 5-fluorouracil (5-FU) or saline on day 5 and euthanized on day 8, 9, 10 or 11. Intestinal villus height (VH) and crypt depth (CD), neutral mucin-secreting goblet cell (GC) count, myeloperoxidase (MPO) activity and selected cytokines were quantified; P < 0.05 was considered significant. In 5-FU-injected rats, only EO administration significantly increased VH in the ileum (day 8), jejunum and jejunum-ileum junction (days 8 and 9) compared to 5-FU controls (P < 0.05). GC count was significantly reduced by 5-FU (jejunum: days 8 and 9; ileum: day 8; P < 0.05) and EO increased ileal GC on days 10 and 11 compared to 5-FU controls. MPO activity was significantly increased in jejunum (days 8 and 9) and ileum (day 8) following 5-FU injection, compared to normal controls (P < 0.05). Both EO and OO significantly reduced jejunal MPO on days 8 and 9; however, only EO decreased ileal MPO on day 8. Cytokine levels were not significantly affected by either oil or 5-FU administration at the day 8 time point. Promotion of repair from injury could represent a new mechanism of action for EO, suggesting potential as an adjunct to conventional treatment approaches for cancer management.

  6. Folate-binding protein and the absorption of folic acid in the small intestine of the suckling rat

    SciTech Connect

    Mason, J.B.; Selhub, J.

    1988-09-01

    The folate in milk is largely bound to high-affinity folate-binding protein (FBP). With an in vivo intestinal loop technique, we examined the absorption of folic acid bound to FBP (FA-FBP) in the small intestine of the suckling rat. In contrast to unbound folic acid (FA), FA-FBP is absorbed more avidly in the ileum than in the jejunum (p less than 0.025) and its absorption is not inhibited by 1 mmol sulfasalazine/L. Folate-binding activities in the mucosa of the proximal (duodenum and jejunum combined) and distal (ileum) small intestine were also examined and found to be 0.32 and 1.31 pmol/mg protein, respectively (p less than 0.001). A 6-h fast produced a 42% decrease in folate-binding activity in the distal small intestine (p less than 0.01) but did not change activity in the proximal portion. Collectively, these observations suggest that FA-FBP is absorbed by a mechanism that is distinct from that responsible for the absorption of FA and that absorption does not require prior dissociation of the vitamin-binding protein complex.

  7. 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

    2013-11-05

    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.

  8. 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.

  9. Myoelectrical activity of small intestine in rats with experimental Parkinson's disease.

    PubMed

    Banach, Tomasz; Zurowski, Daniel; Kania, Dariusz; Thor, Piotr J

    2005-01-01

    Gastrointestinal (GI) motility is governed by enteric nervous system being under surveillance of central and autonomic representation. In Parkinson's disease (PD) GI dysmotility has been attributed in part to peripheral action of neurotoxines. We evaluated the effect of chronic salsolinol administration on intestinal myoelectrical activity (IMA) during fasting and in response to gastric distension (GD) in rats. Fasting IMA recordings didn't reveal differences in frequency of migrating myoelectrical complexes (MMC) (p = 0.06) and dominant frequency (DF) of slow waves (p = 0.1) between salsolinol and saline group. However in response to gastrointestinal stimulation with GD in the salsolinol group DF of IMA remained unchanged whereas in the controls increased (p = 0.04). The results suggest the direct effect of salsolinol on gastro-duodenal reflexes in PD rats.

  10. A carrier-mediated transport for folate in basolateral membrane vesicles of rat small intestine.

    PubMed Central

    Said, H M; Redha, R

    1987-01-01

    The mechanism of exit of folate from the enterocyte, i.e. transport across the basolateral membrane, is not known. In this study we examined, using basolateral membrane vesicles, the transport of folic acid across the basolateral membrane of rat intestine. Uptake of folic acid by these vesicles represents transport of the substrate into the intravesicular compartment and not binding to the membrane surface. The rate of folic acid transport was linear for the first 1 min of incubation but decreased thereafter, reaching equilibrium after 5 min of incubation. The transport of folic acid was: (1) saturable as a function of concentration with an apparent Km of 0.6 +/- 0.17 microM and Vmax. of 1.01 +/- 0.11 pmol/30 s per mg of protein; (2) inhibited in a competitive manner by the structural analogues 5-methyltetrahydrofolate and methotrexate (Ki = 2 and 1.4 microM, respectively); (4) electroneutral; (5) Na+-independent; (6) sensitive to the effect of the anion exchange inhibitor 4,4'-di-isothiocyanatostilbene-2,2'-disulphonic acid (DIDS). These data indicate the existence of a carrier-mediated transport system for folic acid in rat intestinal basolateral membrane and demonstrate that the transport process is electroneutral, Na+-independent and sensitive to the effect of anion exchange inhibition. PMID:3689340

  11. [Effect of gaseous hypoxic mixture GHM-10 on the intestinal death of Wistar rats and Na+,K+-ATPase activity of the plasma membrane of the small intestine mucosa after irradiation].

    PubMed

    Strelkov, R B; Dvoretskiĭ, A I; Kucherenko, N G

    1986-01-01

    It was shown that gas hypoxic mixture containing O2 (10%) and N2 (90%) significantly decreases "intestinal" death of Wistar rats on the 5th day following irradiation and normalizes Na+,K+-ATPase activity of the small intestine mucosa plasma membranes.

  12. 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.

  13. 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 ...

  14. 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.

  15. In vitro influence of spices and spice-active principles on digestive enzymes of rat pancreas and small intestine.

    PubMed

    Ramakrishna Rao, R; Platel, Kalpana; Srinivasan, K

    2003-12-01

    In vitro influence of 14 individual spices (curcumin, capsaicin, piperine, garlic, onion, ginger, mint, coriander, cumin, ajowan, fennel, fenugreek, mustard, and asafoetida) on the activities of digestive enzymes of rat pancreas and small intestine was examined by including them in the reaction mixture at two different concentrations. A majority of spices enhanced the activity of pancreatic lipase and amylase when they are directly in contact with the enzyme. It is inferred that this positive influence on the activity of enzymes may have a supplementary role in the overall digestive stimulant action of spices, besides causing an enhancement of the titres of digestive enzymes in pancreatic tissue.

  16. Small-intestinal manifestations of dextran sulfate sodium consumption in rats and assessment of the effects of Lactobacillus fermentum BR11.

    PubMed

    Geier, Mark S; Smith, Cassie L; Butler, Ross N; Howarth, Gordon S

    2009-06-01

    The dextran sulfate sodium (DSS) colitis model has been utilized to screen for novel therapeutics for ulcerative colitis. Evidence suggests the small intestine may also be affected by DSS. We characterized the effects of DSS on the small intestine and assessed the potential for Lactobacillus fermentum BR11 to modify or normalize DSS-induced changes. Rats were allocated to three groups, Water + Vehicle, DSS + Vehicle, and DSS + L. fermentum BR11. BR11 was administered twice daily for 14 days. DSS (2%) was provided from days 7 to 14. Small-intestinal tissue was analyzed for sucrase activity, histology, and crypt cell proliferation. Increased ileum crypt depth and cell proliferation was observed in DSS-treated rats compared to controls (P < 0.05). BR11 normalized these parameters. While DSS predominantly induces colonic damage, minor morphological alterations were also detected in the distal small intestine. L. fermentum BR11 normalized these features.

  17. Intracellular hydrolysis of short chain glycerides by rat small intestine in vitro and transfer of glycerol

    PubMed Central

    Howard, J.; Jackson, M. J.; Smyth, D. H.

    1970-01-01

    1. When triacetin, tripropionin and tributyrin are incubated with sacs of rat everted intestine, they enter the epithelial cells and are completely hydrolysed to free fatty acids and glycerol. 2. The distribution between the mucosal and serosal fluids of the glycerol released is very different from that of the fatty acid. Although both hydrolytic products are accumulated in the serosal fluid, a much higher fraction of the fatty acid appears in this compartment. 3. When glycerol is initially present in the mucosal fluid there is no evidence of its movement against a concentration gradient. 4. The results confirm the existence of a transport mechanism for fatty acids released intracellularly but do not require the hypothesis of a special mechanism for glycerol transfer. PMID:5500736

  18. Handling of glycerides of acetic acid by rat small intestine in vitro

    PubMed Central

    Barry, R. J. C.; Jackson, M. J.; Smyth, D. H.

    1966-01-01

    1. When mono-, di- and triacetins are incubated with sacs of rat everted intestine, they enter the epithelial cells and are hydrolysed to free glycerol and acetic acid. 2. The rate-limiting step in the process is the entry of glyceride into the epithelial cell. 3. The three acetins enter the epithelial cell at the same rate, and the mechanism of this remains unknown. 4. The acetate released appears in higher concentrations on the serosal side, and the relation of this to the mechanism for transfer of volatile fatty acids is discussed. 5. It is not necessary to postulate a special mechanism for entry of volatile fatty acids into the cell. PMID:5950558

  19. Effects of 4-nitrophenol on expression of the ER-α and AhR signaling pathway-associated genes in the small intestine of rats.

    PubMed

    Tang, Juan; Song, Meiyan; Watanabe, Gen; Nagaoka, Kentaro; Rui, Xiaoli; Li, ChunMei

    2016-09-01

    4-Nitrophenol (PNP) is a persistent organic pollutant that was proven to be an environmental endocrine disruptor. The aim of this study was to evaluate the role of the estrogen receptor-α (ER-α) and aryl hydrocarbon receptor (AhR) signaling pathway in regulating the damage response to PNP in the small intestine of rats. Wistar-Imamichi male rats (21 d) were randomly divided into two groups: the control group and PNP group. Each group had three processes that were gavaged with PNP or vehicle daily: single dose (1 d), repeated dose (3 consecutive days) (3 d), and repeated dose with recovery (3 consecutive days and 3 recovery days) (6 d). The weight of the body, the related viscera, and small intestine were examined. Histological parameters of the small intestine and the quantity of mucus proteins secreted by small goblet cells were determined using HE staining and PAS staining. The mRNA expression of AhR, ER-α, CYP1A1, and GST was measured by real-time qPCR. In addition, we also analyzed the AhR, ER-α, and CYP1A1 expression in the small intestine by immunohistochemical staining. The small intestines histologically changed in the PNP-treated rat and the expression of AhR, CYP1A1, and GST was increased. While ER-α was significantly decreased in the small intestine, simultaneously, when rats were exposed to a longer PNP treatment, the damages disappeared. Our results demonstrate that PNP has an effect on the expression of AhR signaling pathway genes, AhR, CYP1A1, and GST, and ER-α in the rat small intestine.

  20. Effect of antibiotics on the 5-hydroxytryptamine content of the small intestine and other organs in rats and mice

    PubMed Central

    Sullivan, T. J.

    1961-01-01

    Rats and mice were given antibiotics orally and by subcutaneous injection and the effects on tissue levels of 5-hydroxytryptamine and intestinal bacteria were studied. In mice it was found that antibiotics which caused a large reduction in the bacterial flora of the intestine when given orally also caused a significant increase in intestinal 5-hydroxytryptamine. In rats, neomycin caused a reduction in the urinary excretion of 5-hydroxyindoleacetic acid. In both rats and mice, many antibiotics caused a significant reduction in the weight of the spleen. PMID:19108146

  1. The dynamic structure of a flat small intestinal mucosa studied on the explanted rat jejunum.

    PubMed

    Loehry, C A; Grace, R

    1974-04-01

    Small pieces of jejunum with an intact blood supply were explanted to the anterior abdominal wall in rats. Six weeks after explantation the mucosa appeared totally flat in many areas, both histologically and under the dissecting microscope. The structure of the flattened mucosa was shown to be identical to that in coeliac disease with hypertrophied intervillous ridges. A dynamic study with tritium-labelled thymidine demonstrated a considerably increased turnover in the flat mucosa with some disorganization of cell production and migration.

  2. The Intestinal Transport of Bovine Milk Exosomes Is Mediated by Endocytosis in Human Colon Carcinoma Caco-2 Cells and Rat Small Intestinal IEC-6 Cells123

    PubMed Central

    Wolf, Tovah; Baier, Scott R; Zempleni, Janos

    2015-01-01

    Background: MicroRNAs play essential roles in gene regulation. A substantial fraction of microRNAs in tissues and body fluids is encapsulated in exosomes, thereby conferring protection against degradation and a pathway for intestinal transport. MicroRNAs in cow milk are bioavailable in humans. Objective: This research assessed the transport mechanism of bovine milk exosomes, and therefore microRNAs, in human and rodent intestinal cells. Methods: The intestinal transport of bovine milk exosomes and microRNAs was assessed using fluorophore-labeled bovine milk exosomes in human colon carcinoma Caco-2 cells and rat small intestinal IEC-6 cells. Transport kinetics and mechanisms were characterized using dose-response studies, inhibitors of vesicle transport, carbohydrate competitors, proteolysis of surface proteins on cells and exosomes, and transepithelial transport in transwell plates. Results: Exosome transport exhibited saturation kinetics at 37°C [Michaelis constant (Km) = 55.5 ± 48.6 μg exosomal protein/200 μL of media; maximal transport rate = 0.083 ± 0.057 ng of exosomal protein · 81,750 cells−1 · h−1] and decreased by 64% when transport was measured at 4°C, consistent with carrier-mediated transport in Caco-2 cells. Exosome uptake decreased by 61–85% under the following conditions compared with controls in Caco-2 cells: removal of exosome and cell surface proteins by proteinase K, inhibition of endocytosis and vesicle trafficking by synthetic inhibitors, and inhibition of glycoprotein binding by carbohydrate competitors. When milk exosomes, at a concentration of 5 times the Km, were added to the upper chamber in transwell plates, Caco-2 cells accumulated miR-29b and miR-200c in the lower chamber, and reverse transport was minor. Transport characteristics were similar in IEC-6 cells and Caco-2 cells, except that substrate affinity and transporter capacity were lower and higher, respectively. Conclusion: The uptake of bovine milk exosomes is

  3. Anti-fatigue effect of ginsenoside Rb1 on postoperative fatigue syndrome induced by major small intestinal resection in rat.

    PubMed

    Tan, Shanjun; Zhou, Feng; Li, Ning; Dong, Qiantong; Zhang, Xiaodong; Ye, Xingzhao; Guo, Jian; Chen, Bicheng; Yu, Zhen

    2013-01-01

    Ginsenoside Rb1 (GRb1), one of the principle active ingredients of Panax ginseng, exerts multiple pharmacological activities to fight fatigue. In the present study, we investigate the anti-fatigue effect of GRb1 on postoperative fatigue syndrome (POFS) in a rat model induced by major small intestinal resection. GRb1 (10 mg/kg) was administrated intraperitoneally once daily for 1, 3, 7, and 10 d from the operation day. Anti-fatigue effect was assessed by grasping test and biochemical parameters in blood or skeletal muscle were determined by autoanalyzer or commercially available kits. Transmission electron microscope was applied to observe the ultra microstructure of skeletal muscles. The results revealed that GRb1 significantly enhanced rat maximum grip strength with POFS. Similarly, negative alterations in biochemical parameters (lactic acid, hepatic glycogen, muscle glycogen and malondialdehyde) of POFS rats were improved by GRb1. In addition, GRb1 also increased the activity of lactate dehydrogenase and superoxide dismutase in POFS. No significant differences of levels of blood urea nitrogen and ultra microstructure of skeletal muscles were found between the POFS and GRb1 treatment rats. The potent anti-fatigue effect of GRb1 on POFS might be achieved through improvement of energy metabolism and suppression of skeletal muscle oxidative stress.

  4. Digestion and absorption of sugars and sugar substitutes in rat small intestine.

    PubMed

    Tsuji, Y; Yamada, K; Hosoya, N; Moriuchi, S

    1986-02-01

    The bioavailability of newly developed sugar substitutes was observed by measuring the transmural potential difference (delta PD) evoked by Na+-dependent active transport of glucose, which is supposed to be produced by the hydrolysis of sugar substitutes. delta PD was measured using everted intestinal sac prepared from jejunum of adult rats and compared with the digestibility of sugar substitutes in the mucosal homogenate of everted sac. delta PDs evoked by glucose, maltose or maltosylfructose had almost the same levels, however, the delta PD evoked by sucrose was a little lower. delta PDs evoked by maltitol or palatinose were low, and delta PDs evoked by fructo-oligosaccharides were negligible. The hydrolyzing activities of these sugars and sugar substitutes by the mucosal homogenate were correlated with the delta PDs. A significant positive correlation was observed between delta PDmax of various sugars and sugar substitutes and the Vmax of their corresponding hydrolyzing activities. Also, a significant positive correlation was observed between Kt and Km values of these sugars. These results suggest that the absorption of sugar substitutes is dependent on digestibility by membrane digestive enzymes.

  5. Strongyloides ratti: transplantation of adults recovered from the small intestine at different days after infection into the colon of naive and infection-primed Wistar rats, and the effect of antioxidant treatment on large intestinal parasitism.

    PubMed

    Shintoku, Y; Takagi, H; Kadosaka, T; Nagaoka, F; Kondo, S; Itoh, M; Honda, S; Kimura, E

    2011-07-01

    Strongyloides ratti (Nagoya strain) is unique in that a portion of adults parasitizing the small intestine withstands 'worm expulsion', which starts at around day 8 post-infection (p.i.) by host immunity, and establishes in the large intestine after day 19 p.i. To investigate the mechanism, adults obtained from the small intestine at day 7 or 19 p.i. were transplanted into the colon of infection-primed immune rats. Adults obtained at day 7 p.i. were rejected quickly, whereas those obtained at day 19 p.i. could establish infection. Moreover, the body length and the number of intrauterine eggs increased in the large intestine. In a separate experiment, large intestinal parasitism was abolished by the treatment of host rats with an anti-oxidant, butylated hydroxyanisole. These results indicate that small intestinal adults between days 7 and 19 p.i. acquired the ability to parasitize the large intestine of immune rats, and that free radicals produced by the host may have played a significant role in the process.

  6. Effects of the pyrones, maltol and ethyl maltol, on iron absorption from the rat small intestine.

    PubMed

    Barrand, M A; Callingham, B A; Hider, R C

    1987-03-01

    The pyrones, 3-hydroxy-2-methyl-4-pyrone (maltol) and 3-hydroxy-2-ethyl-4-pyrone (ethyl maltol) chelate iron with a high affinity and selectivity. The resulting 1:3 (metal-ligand) complexes, being neutral, are able to partition readily across cell membranes and thus may facilitate iron transport across the intestinal wall. Absorption of radioactive iron (59Fe) in the presence of these pyrones was investigated in male rats 1, 2, 4 and 6 h after intraduodenal administration of a 7 micrograms dose and compared with that of 59Fe given as the sulphate, gluconate, fumarate or complexed to EDTA. Total body absorption and distribution were calculated from the 59Fe content of various tissue samples. With all the iron preparations used, blood levels of 59Fe were highest 1 h after injection whilst the 59Fe content at the major site of deposition, i.e. the bone marrow, increased up to 6 h. No 59Fe was found in the urine. Total body absorption of 59Fe was significantly higher from the pyrones than from the other four preparations. Over the dose range 0.7-700 micrograms, the proportion of 59Fe absorbed from both iron maltol and iron sulphate decreased with increasing dose. Enhanced 59Fe uptake from maltol was evident at 0.7-70 micrograms but not at 700 micrograms suggesting that use of these pyrones will not result in iron overload. Absorption of 59Fe given into the stomach was slower in onset but was sustained longer presumably via a steady delivery of iron to the duodenum from the gastric reservoir.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. Digestion-Resistant Dextrin Derivatives Are Moderately Digested in the Small Intestine and Contribute More to Energy Production Than Predicted from Large-Bowel Fermentation in Rats.

    PubMed

    Kondo, Takashi; Handa, Kei; Genda, Tomomi; Hino, Shingo; Hamaguchi, Norihisa; Morita, Tatsuya

    2017-03-01

    Background: Digestion-resistant dextrin derivatives (DRDDs), including resistant maltodextrin (RM), polydextrose, and resistant glucan (RG), have been developed as low-energy foods. However, data on the resistance of DRDDs to small-intestinal digestion are scarce.Objective: We sought to determine the site and extent of DRDD breakdown in the rat intestine and to predict its energy contributions.Methods: In vitro small-intestinal resistance of DRDDs was evaluated by the AOAC method for dietary fiber measurement and by artificial digestion with the use of pancreatic α-amylase and brush-boarder membrane vesicles. In vivo small-intestinal resistance of DRDDs was determined from the feces of male ileorectostomized Sprague-Dawley rats fed a control diet or a diet containing one of the DRDDs at 50 g/kg for 9 d (period 1) and then for 10 d (period 2), during which they received 1 g neomycin/L in their drinking water. Separately, male Sprague-Dawley rats were fed the same diets for 4 wk, and the whole-gut recoveries of DRDDs were determined from feces at days 8-10.Results: Small-intestinal resistances determined in vitro by artificial digestion (RM: 70%; polydextrose: 67%; RG: 69%) were lower than those measured by the AOAC method (RM: 92%; polydextrose: 80%; RG: 82%). In the ileorectostomized rats, fecal dry-matter excretions were consistently greater in the DRDDs than in the control. The small-intestinal resistances of the DRDDs were 68%, 58%, and 62% in period 1 and 66%, 61%, and 67% during period 2 for RM, polydextrose, and RG, respectively. The resistances did not differ among the DRDDs at either time. In the normal rats, food intakes and body weight gains did not differ among the groups. The whole-gut recovery of RM (13%) was lower than that of polydextrose (33%) and RG (29%), which did not differ.Conclusions: DRDDs were more digestible in the rat small intestine than the AOAC method. The energy contribution from small-intestine digestibility, not just large

  8. 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.

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

    PubMed

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

    2013-02-15

    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.

  10. 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. PMID:27746864

  11. 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]. PMID:27635197

  12. Amino acid and peptide absorption after proximal small intestinal resection in the rat.

    PubMed Central

    Garrido, A B; Freeman, H J; Chung, Y C; Kim, Y S

    1979-01-01

    In experimental animals with massive proximal intestinal resection, in vivo ileal absorption of an amino acid mixture containing L-leucine and glycine as well as two different dipeptides, L-leucyl-glycine and glycyl-L-leucine, were compared. Both amino acid and dipeptide absorption were markedly enhanced in the ileal segments. However, the absorption rates from the two perfused dipeptides differed. L-leucine absorption from L-leucyl-glycine was much greater than from glycyl-L-leucine. Brush border amino-peptidase activities after resection were also increased but dissociation between absorption and hydrolytic activity occurred. This study indicates that certain dipeptides are handled differently by adapting ileal segments. Furthermore, the changes observed probably reflect mucosal cellular hyperplasia occurring in association with intestinal adaptation. PMID:428822

  13. 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

  14. Vascular, but not luminal, activation of FFAR1 (GPR40) stimulates GLP-1 secretion from isolated perfused rat small intestine

    PubMed Central

    Christensen, Louise W; Kuhre, Rune E; Janus, Charlotte; Svendsen, Berit; Holst, Jens J

    2015-01-01

    Glucagon-like peptide 1 (GLP-1) plays a central role in modern treatment of type 2 diabetes (T2DM) in the form of GLP-1 enhancers and GLP-1 mimetics. An alternative treatment strategy is to stimulate endogenous GLP-1 secretion from enteroendocrine L cells using a targeted approach. The G-protein-coupled receptor, FFAR1 (previously GPR40), expressed on L cells and activated by long-chain fatty acids (LCFAs) is a potential target. A link between FFAR1 activation and GLP-1 secretion has been demonstrated in cellular models and small-molecule FFAR1 agonists have been developed. In this study, we examined the effect of FFAR1 activation on GLP-1 secretion using isolated, perfused small intestines from rats, a physiologically relevant model allowing distinction between direct and indirect effects of FFAR1 activation. The endogenous FFAR1 ligand, linoleic acid (LA), and four synthetic FFAR1 agonists (TAK-875, AMG 837, AM-1638, and AM-5262) were administered through intraluminal and intra-arterial routes, respectively, and dynamic changes in GLP-1 secretion were evaluated. Vascular administration of 10 μmol/L TAK-875, 10 μmol/L AMG 837, 1 μmol/L and 0.1 μmol/L AM-1638, 1 μmol/L AM-6252, and 1 mmol/L LA, all significantly increased GLP-1 secretion compared to basal levels (P < 0.05), whereas luminal administration of LA and FFAR1 agonists was ineffective. Thus, both natural and small-molecule agonists of the FFAR1 receptor appear to require absorption prior to stimulating GLP-1 secretion, indicating that therapies based on activation of nutrient sensing may be more complex than hitherto expected. PMID:26381015

  15. 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.

  16. Effect of a cocoa diet on the small intestine and gut-associated lymphoid tissue composition in an oral sensitization model in rats.

    PubMed

    Camps-Bossacoma, Mariona; Pérez-Cano, Francisco J; Franch, Àngels; Untersmayr, Eva; Castell, Margarida

    2017-04-01

    Previous studies have attributed to the cocoa powder the capacity to attenuate the immune response in a rat oral sensitization model. To gain a better understanding of cocoa-induced mechanisms at small intestinal level, 3-week-old female Lewis rats were fed either a standard diet or a diet containing 10% cocoa for 4 weeks with or without concomitant oral sensitization with ovalbumin (OVA). Thereafter, we evaluated the lymphocyte composition of the Peyer's patches (PPL), small intestine epithelium (IEL) and lamina propria (LPL). Likewise, gene expression of several immune molecules was quantified in the small intestine. Moreover, histological samples were used to evaluate the proportion of goblet cells, IgA+ cells and granzyme+cells as well. In cocoa-fed animals, we identified a five-time reduction in the percentage of IgA+ cells in intestinal tissue together with a decreased proportion of TLR4+ IEL. Analyzing the lymphocyte composition, almost a double proportion of TCRγδ+cells and an increase of NK cell percentage in PPL and IEL were found. In addition, a rise in CD25+, CD103+ and CD62L- cell proportions was observed in CD4+ PPL from cocoa-fed animals, along with a decrease in gene expression of CD11b, CD11c and IL-10. These results suggest that changes in PPL and IEL composition and in the gene expression induced by the cocoa diet could be involved, among other mechanisms, on its tolerogenic effect.

  17. 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

  18. Antioxidant activity of a novel extract from bamboo grass (AHSS) against ischemia-reperfusion injury in rat small intestine.

    PubMed

    Kurokawa, Toshimitsu; Itagaki, Shirou; Yamaji, Toshihiko; Nakata, Chie; Noda, Toshihiro; Hirano, Takeshi; Iseki, Ken

    2006-11-01

    Production of free radical species in cells and body tissues is known to cause many pathological disorders. Therefore, free radical scavengers play an important role in the prevention of various human diseases. Bamboo grass, Sasa senanensis, is a native Japanese plant. Sasa has been used for medicine in Japan for many centuries. In this study, we investigated the antioxidative activity of Absolutely Hemicellulose Senanensis (AHSS), a novel extract from Sasa. In the first part of this study, we found that AHSS has antioxidant activities by the assay using superoxide anion-2-methyl-6-methoxyphenylethynylimidazopyrazynone (MPEC) reaction kit. We then confirmed its antioxidative activity using a rat ischemia and subsequent reperfusion (I/R) injury model. Breakdown of the intestinal wall caused by intestinal I/R was attenuated by pretreatment with AHSS. Moreover, AHSS inhibited the production of lipid peroxide by intestinal I/R. AHSS could be an important source of ingredients for use in functional foods and other applications.

  19. Prevention by lansoprazole, a proton pump inhibitor, of indomethacin -induced small intestinal ulceration in rats through induction of heme oxygenase-1.

    PubMed

    Yoda, Y; Amagase, K; Kato, S; Tokioka, S; Murano, M; Kakimoto, K; Nishio, H; Umegaki, E; Takeuchi, K; Higuchi, K

    2010-06-01

    The effect of lansoprazole, a proton pump inhibitor (PPI), on indomethacin-induced small intestinal ulceration was examined in rats, particularly in relation to heme oxygenase (HO)-1. The animals were administered indomethacin (10 mg/kg, p.o.) and killed 24 h later. Lansoprazole (30-100 mg/kg, p.o.) and omeprazole (30-100 mg/kg, p.o.) were given 30 min before the administration of indomethacin, while tin-protoporphyrin IX (SnPP: 30 mg/kg, i.v.), an inhibitor of HO-1, was injected 10 min before indomethacin or lansoprazole. Indomethacin produced hemorrhagic lesions in the small intestine, accompanied with an increase of mucosal invasion of enterobacteria, inducible nitric oxide synthase (iNOS) expression, and myeloperoxidase (MPO) activity in the mucosa. Pretreatment with lansoprazole dose- dependently reduced the severity of the indomethacin-induced intestinal lesions, with suppression of the increased MPO activity, while omeprazole had no effect. Pretreatment with SnPP significantly exacerbated these intestinal lesions and almost totally abolished the protective effect of lansoprazole. The up-regulation of iNOS mRNA expression following indomethacin was suppressed by lansoprazole in a SnPP-inhibitable manner, although the enhanced enterobacterial invasion remained unaffected. The amount of HO-1 protein in the intestinal mucosa was significantly increased by lansoprazole but not by omeprazole. Prior administration of carbon monoxide (CO)-releasing molecule-2 (CORM-2; 10 mg/kg, i.p.) significantly reduced the severity of these lesions and the enhancement of mucosal iNOS mRNA expression induced in the small intestine by indomethacin. These results suggest that lansoprazole prevents indomethacin-induced small intestinal ulceration, and this effect is associated with inhibition of iNOS expression, through up-regulation of HO-1/CO production in the mucosa.

  20. 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.

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

    SciTech Connect

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

    1986-11-01

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

  2. Small intestinal physiology and pathophysiology.

    PubMed

    Sarna, S K; Otterson, M F

    1989-06-01

    The small intestine, like the rest of the gastrointestinal tract, is an intelligent organ. It generates a wide variety of motor patterns to meet motility requirements in different situations. Its basic motor function after a meal is to mix the chyme with exocrine and intestinal secretions, agitate its contents to uniformly and evenly expose them to the mucosal surface, and to propel them distally at a rate that allows optimal absorption of food components, and reabsorption of bile. Most of these functions are performed by individual phasic contractions. In humans, the phasic contractions are largely disorganized in time and space. These contractions may cause mixing and agitation of luminal contents with slow distal propulsion. Occasionally, an individual contraction of large amplitude and long duration migrates over several centimeters and may rapidly propel the contents over this distance. In general, the spatial and temporal relationships of individual phasic contractions become less organized distally, resulting in a slower propulsion rate in the distal small intestine than in the proximal small intestine. The migrating clustered contractions generated after a meal may also be propulsive, but because of their unpredictable and irregular occurrence, their precise role in postprandial propulsion is incompletely understood. Rapidly migrating contractions may occur when the electrical control activity is obliterated by pharmacologic agents or during parasitic infections. Their effects on motility are not known yet. Between meals, when digestion is complete, the small intestine generates migrating motor complexes that help keep the small intestine clean by dislodging debris from the villi and dumping them into the colon. This may prevent decay of these materials in the small intestine and limit their contribution to bacterial overgrowth. Giant migrating contractions may perform a similar function in the distal small intestine as well as return any refluxed fecal

  3. What Happens After Treatment for Small Intestine Adenocarcinoma?

    MedlinePlus

    ... After Treatment What Happens After Treatment for Small Intestine Adenocarcinoma? For some people with small intestine cancer, ... Small Intestine Adenocarcinoma Stops Working More In Small Intestine Cancer About Small Intestine Cancer Causes, Risk Factors, ...

  4. 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

  5. Effects of intraluminal hydrostatic pressure on L-methionine absorption in the obstructed small intestine of the rat

    SciTech Connect

    Enochsson, L.; Nylander, G.

    1986-03-01

    The effects of elevated intraluminal hydrostatic pressure on the active absorption of the amino acid selenium 75 L-methionine has been analyzed in the normal and obstructed small intestine. An intestinal loop of defined position and length was included in a recircling perfusion system from which the elimination rate of the radiolabeled amino acid was measured. Preset pressure levels within the system were maintained by a servo-controlled unit, which added or subtracted volume to keep the pressure constant. The rate of amino acid elimination increased when the nonobstructed loop was subjected to a pressure of 10 cm H2O but decreased when exposed to 20cm H2O. Using a loop of intestine subjected to 48 hours of obstruction, amino acid elimination was greatly retarded compared with that of the nonobstructed loop. By increasing the intraluminal pressure to 10 and 20 cm H2O, the elimination rate increased, equalling that of the nonobstructed gut. The results suggest that intestinal obstruction per se decreases active absorption secondary to impaired intestinal viability. Moderately increased intraluminal pressure adds a driving force to L-methionine absorption, the mechanism of which is obscure.

  6. Inhibitory effect of aluminium on calcium absorption in small intestine of rats with different thyroid hormone status.

    PubMed

    Orihuela, Daniel

    2009-11-01

    To analyse the influence of thyroid status on the effect of aluminium (Al) upon intestinal calcium (Ca) absorption, adult male Wistar rats with experimentally altered thyroid hormones circulating levels, were orally treated (o.g.) with 0 (control), or 50 mg elemental Al (as chloride)/kg body weight (b.w.) per day, for a 14 d period. Hyper- and hypo-thyroid conditions were respectively achieved by means of administration of either sodium levothyroxine (50 microg/kg b.w. per day, o.g.) or methimazole, a thyroxine synthesis inhibitor (1mg/kg b.w. per day, o.g.). In duodenum-jejunum segments, in vitro mucosa-to-serosa (45)Ca flux (JCa(ms)) and kinetics of (45)Ca uptake in isolated enterocytes, were determined. In serum, concentrations of thyroxine (T4) and triiodothyronine (T3) were measured by chemiluminescent enzyme immunoassay. Unlike non-Al-treated rats, JCa(ms) of Al-exposed rats decreased as serum levels of T4 and T3 increased, showing a significant inverse correlation in both cases (T4: r(2)=0.414, P=0.024; T3: r(2)=0.443, P=0.018). Enterocytes isolated from rats treated with Al plus thyroxine showed a reduction of both maximum Ca uptake (4.86+/-0.44 vs. 6.85+/-1.04 nmol Ca/mg protein, P<0.05) and K(m) (0.84+/-0.18 vs. 1.05+/-0.36 mM, P<0.05) when compared to control. The observed variability in the Al effect on Ca transport with thyroid status of rats could be reflecting a negative interaction of Al with thyroid hormone action mechanisms on intestinal Ca absorption, which would take place mainly at Ca entry into enterocyte from lumen.

  7. Differentiation of epithelial cells to M cells in response to bacterial colonization on the follicle-associated epithelium of Peyer's patch in rat small intestine.

    PubMed

    Chin, Keigi; Onishi, Sachiko; Yuji, Midori; Inamoto, Tetsurou; Qi, Wang-Mei; Warita, Katsuhiko; Yokoyama, Toshifumi; Hoshi, Nobuhiko; Kitagawa, Hiroshi

    2006-10-01

    To clarify the relationship between M cells and intestinal microflora, histoplanimetrical investigation into the bacterial colonization and the differentiation to M cells was carried out in rat Peyer's patch under physiological conditions. The follicle-associated epithelium (FAE), except for the narrow area of apical region, was closely covered with both neighboring intestinal villi and a thick mucous layer, the latter of which also filled the intervillous spaces as well as the space between the FAE and the neighboring intestinal villi. Indigenous bacteria adhered almost constantly to the narrow areas of apical regions of both intestinal villi and the FAE. Bacterial colonies were occasionally located on the basal to middle region of FAE, where M cells also appeared, forming large pockets. When bacterial colonies were located on the basal to middle region of FAE, bacteria with the same morphological characteristics also proliferated in the intervillous spaces neighboring the Peyer's patch. In cases with no bacterial colonies on the basal to middle region of FAE, however, M cells were rare in the FAE. Histoplanimetrical analysis showed the similar distribution pattern of bacterial colonies on the FAE and M cells in the FAE. M cells ultrastructurally engulfed indigenous bacteria, which were then transported to the pockets. These results suggest that indigenous bacterial colonization on the FAE stimulates the differentiation of M cells in the FAE under physiological conditions. The uptake of bacteria by M cells might contribute the regulation of the development of indigenous bacterial colonies in the small intestine.

  8. Experimental colonic carcinogenesis: changes in faecal bile acids after promotion of intestinal tumours by small bowel resection in the rat.

    PubMed Central

    Savage, A P; Sian, M S; Matthews, J L; Bloom, S R; Cooke, T

    1988-01-01

    Small bowel resection promotes the development of colonic tumours in azoxymethane treated rats. As high faecal bile acid concentrations are associated with colonic cancer and may be altered by resection, we have studied changes in faecal bile acid concentrations during promotion of colonic carcinogenesis by increasing small bowel resection. Twenty rats in each group underwent either jejunal transection or 20%, 50%, or 80% proximal small bowel resection. Tumours were induced with azoxymethane 10 mg/kg by 12 weekly subcutaneous injections, and faecal bile acid concentrations were measured at six and 16 weeks. Colonic tumour number rose from 0.6 per rat in the transection group to 1.6 per rat in the 50% resection group (p less than 0.01) but were not significantly different to transection values at 0.8 per rat in the 80% resection group. Total daily faecal bile acid excretion and bile acid concentrations fell with increasing resection from 14.2 (1.6) mg/rat/day and 5.8 (0.7) mg/g dry faeces respectively in the transection group to 6.5 (0.5) mg/rat/day and 2.9 (0.2) mg/g respectively in the 80% resection group (p less than 0.001). The greatest reduction was seen in the concentration of deoxycholic acid which has been particularly associated with the aetiology of colonic cancer. The promotion of colonic tumours following small bowel resection in carcinogen treated rats is unlikely to be mediated by changes in faecal bile acid concentration or composition. PMID:3371718

  9. Short term effects of indomethacin on rat small intestinal permeability. Role of eicosanoids and platelet activating factor.

    PubMed Central

    Mion, F; Cuber, J C; Minaire, Y; Chayvialle, J A

    1994-01-01

    Short term effects of indomethacin on intestinal permeability were studied on a model of rat isolated vascularly perfused terminal ileum. The objectives of this study were (a) to assess the effects of indomethacin on intestinal permeability and histology; (b) to assess the effects of prostaglandins, leukotrienes, and platelet activating factor (PAF) on the same parameters; (c) to evaluate the role of these inflammation mediators on indomethacin induced permeability modifications. Intravascular administration of 1.25 and 2.5 mM indomethacin induced a significant increase of 51Cr-EDTA transfer rate. Histological analysis showed only mucosal oedema. Pretreatment with 16,16 dimethyl-prostaglandin E2 did not reverse these changes. Intravascular administration of PAF, leukotrienes B4 and D4 provoked a significant rise in 51Cr-EDTA transfer rate and intraluminal protein leakage, with an intense vascocongestion of the mucosal capillaries. These changes were completely prevented by perfusion of the respective specific antagonists (BN52021 for PAF, LY255,583 for leukotriene B4 and MK571 for leukotriene D4). None of these three antagonists, however, or MK886, a selective 5'-lipo-oxygenase inhibitor, could reverse the indomethacin induced permeability changes. Indomethacin induced increased intestinal permeability at these high concentrations does not seem to be a result of changed prostanoid or PAF metabolism. Alternative mechanisms of the initial damage of non-steroid anti-inflammatory drugs should be sought. Images Figure 2 Figure 3 Figure 5 PMID:8174986

  10. Antiinflammatory effects of soluble complement receptor type 1 promote rapid recovery of ischemia/reperfusion injury in rat small intestine.

    PubMed

    Eror, A T; Stojadinovic, A; Starnes, B W; Makrides, S C; Tsokos, G C; Shea-Donohue, T

    1999-02-01

    We examined the effect of soluble complement receptor type 1 (sCR1) on mucosal injury and inflammation in a rat model of ischemia/reperfusion. Groups of vehicle- and sCR1-treated rats underwent 30 min of mesenteric ischemia followed by 60 or 120 min of reperfusion. When compared to vehicle-treated rats, treatment with sCR1 (12 mg/kg) prior to 120 min of reperfusion significantly reduced mucosal injury, neutrophil infiltration, leukotriene B4 production, and restored villus height to control levels. The protective effect of sCR1 evident at 120 min of reperfusion was not observed at 60 min of reperfusion despite rapid inactivation of complement. These data suggest that complement inhibition minimized mucosal disruption by facilitating mucosal restitution or interrupting the inflammatory process. Delayed administration of sCR1 for 30 or 60 min into the reperfusion period progressively reduced the protection. sCR1-mediated rapid recovery of rat intestine after ischemia/reperfusion underscores the fundamental role of complement activation in neutrophil-mediated tissue injury.

  11. The effects of cyclooxygenase inhibitors on the gastric emptying and small intestine transit in the male rats following traumatic brain injury

    PubMed Central

    Keshavarzi, Zakieh; Khaksari, Mohammad; Shahrokhi, Nader

    2014-01-01

    Objective(s): This study was carried out to investigate the effects of COX-2 selective inhibitor (Celecoxib) or non-selective COX inhibitor (Ibuprofen) on gastrointestinal motility. Materials and Methods: The rats were randomly divided into five groups including: intact, sham, traumatic brain injury (TBI) group (intact rats under TBI), Celecoxib group (10 mg/kg), Ibuprofen group (10 mg/kg). Rats of the treatment groups received gavages at 1 hr before the TBI induction. The TBI was moderate and diffused using the Marmarou method. The gastric emptying and small intestine transit were measured by phenol red method. Results: The gastric emptying didn’t change following TBI induction compared to intact group. The consumption of ibuprofen or celecoxib didn’t have any effect on gastric emptying compared to sham group. TBI induction didn’t have any effect on the intestinal transit. Also, there was no significant difference between ibuprofen or celecoxib consumption vs. sham group (P>0.05). Conclusion: The COX-2 selective inhibitor (celecoxib) or non-selective COX inhibitor (ibuprofen) have no effects on gastric or small bowel transit. Further work is necessary to investigate the effects of non-selective COX inhibitors and their impact on gastrointestinal motility disorders. PMID:25140201

  12. Schlafen 3 changes during rat intestinal maturation

    PubMed Central

    Walsh, Mary F.; Hermann, Rebecca; Sun, Kelian; Basson, Marc D.

    2015-01-01

    BACKGROUND Understanding gut development may illuminate the adaptive response to massive small-bowel resection and facilitate enteral nutrition. We reported that Schlafen-3 (Slfn3) mediates differentiation in vitro in rat intestinal epithelial. We hypothesized that Slfn3 is involved in intestinal development in vivo. METHODS We removed fetal intestines, liver, and lungs on day 20 of gestation, at birth, and on postnatal days 1 and 5. Expression of Slfn3, markers of intestinal differentiation, and Slfn5, to address specificity, were determined by quantitative reverse-transcription polymerase chain reaction. RESULTS Villin expression increased on days 1 and 5 (8.7 ± .6 and 5.4 ± .4, respectively; P < .01). Intestinal Slfn3 expression was increased substantially after birth (2.1- ± .5-fold) and on days 1 and 5 (P < .02). Slfn3 was higher after birth in liver and lung but decreased sharply thereafter. Slfn5 expression was mostly unchanged. CONCLUSIONS The data suggest that the developmental/maturation effects we observed correlate with Slfn3 but not Slfn5 and are more relevant to the intestines. A better understanding of how Slfn3 promotes intestinal differentiation could help promote intestinal maturation, improving outcomes in children or adults with short-gut syndrome. PMID:22906252

  13. The Ingestion of Proteins and Colloidal Materials by Columnar Absorptive Cells of the Small Intestine in Suckling Rats and Mice

    PubMed Central

    Clark, Sam L.

    1959-01-01

    Proteins and colloidal materials, administered orally to suckling rats and mice, were ingested by columnar absorptive cells of the jejunum and ileum, but not of the duodenum. Bovine gamma globulin and ovalbumin were identified in the apical cytoplasm by staining with fluorescent antibody; trypan blue, Evans blue, saccharated iron oxide, and colloidal gold were detected intracellularly by their color, specific staining, and appearance in the electron microscope. Each substance was segregated in membrane-enclosed vacuoles, apparently part of a system of potentially interconnecting vacuoles and tubules in the apical cytoplasm which is continuous in places with the apical cell membrane. We postulate that ingestion of foreign materials was accomplished by pinocytosis, that is, by invagination of the apical cell membrane to form vacuoles containing material from the intestinal lumen. Approximately 18 days after birth columnar absorptive cells lost the ability to ingest proteins and colloids, and no longer contained large vacuoles and numerous tubules. At this age rats and mice lose the ability to absorb antibodies from the intestine in an immunologically intact form, and we conclude that cellular ingestion is part of the mechanism of absorption of intact proteins in suckling animals. Particulate fat apparently is absorbed in both newborn and adult animals by micropinocytosis. Thus adult animals may not have lost the capacity for pinocytosis, but rather have become selective as to what substances provoke it. Cortisone acetate, administered subcutaneously to rats 8 to 10 days old alters the columnar absorptive cells within 72 hours so that they resemble the cells in adult animals and no longer ingest proteins. PMID:13630932

  14. What Should You Ask Your Doctor About Small Intestine Adenocarcinoma?

    MedlinePlus

    ... What Should You Ask Your Doctor About Small Intestine Adenocarcinoma? It’s important to have honest, open discussions ... Doctor About Small Intestine Adenocarcinoma? More In Small Intestine Cancer About Small Intestine Cancer Causes, Risk Factors, ...

  15. Correction of enhanced Na(+)-H+ exchange of rat small intestinal brush-border membranes in streptozotocin-induced diabetes by insulin or 1,25-dihydroxycholecalciferol

    SciTech Connect

    Dudeja, P.K.; Wali, R.K.; Klitzke, A.; Sitrin, M.D.; Brasitus, T.A. )

    1991-05-01

    Diabetes was induced in rats by administration of a single i.p. injection of streptozotocin (50 mg/kg body wt). After 7 d, diabetic rats were further treated with insulin or 1,25-dihydroxycholecalciferol (1,25(OH)2D3) for an additional 5-7 d. Control, diabetic, diabetic + insulin, and diabetic + 1,25(OH)2D3 rats were then killed, their proximal small intestines were removed, and villus-tip epithelial cells were isolated and used to prepare brush-border membrane vesicles. Preparations from each of these groups were then analyzed and compared with respect to their amiloride-sensitive, electroneutral Na(+)-H+ exchange activity, using {sup 22}Na uptake as well as acridine orange techniques. The results of these experiments demonstrated that (a) H+ gradient-dependent {sup 22}Na uptake as well as Na+ gradient-dependent transmembrane H+ fluxes were significantly increased in diabetic vesicles compared to their control counterparts, (b) kinetic studies demonstrated that this enhanced {sup 22}Na uptake in diabetes was a result of increased maximal velocity (Vmax) of this exchanger with no change in apparent affinity (Km) for Na+, (c) serum levels of 1,25(OH)2D3 were significantly lower in diabetic animals compared with their control counterparts; and (d) insulin or 1,25(OH)2D3 treatment restored the Vmax alterations to control values, without any significant changes in Km, concomitant with significantly increasing the serum levels of 1,25(OH)2D3 in diabetic animals. These results indicate that Na(+)-H+ activity is significantly increased in proximal small intestinal luminal membranes of streptozotocin-induced diabetic rats. Moreover, alterations in the serum levels of 1,25(OH)2D3 may, at least in part, explain this enhanced antiporter activity and its correction by insulin.

  16. The metallohormone cadmium modulates AhR-associated gene expression in the small intestine of rats similar to ethinyl-estradiol.

    PubMed

    Kluxen, Felix M; Diel, Patrick; Höfer, Nicola; Becker, Eugenia; Degen, Gisela H

    2013-04-01

    Cadmium (Cd) affects the expression of estrogen receptor (ER) and aryl hydrocarbon receptor (AhR)-associated genes in rat uterus and elicits estrogen-like activity in vitro. The small intestine is highly exposed to dietary Cd which may mimic or antagonize estrogen action in this tissue. We investigated the effects of Cd and 17-alpha-ethinylestradiol (EE₂) on AhR-associated gene expression after oral exposure of ovariectomized female Wistar rats, and metallothionein (Mt1a) expression as a typical metal-response marker. Mt1a in the small intestine was strongly induced by co-treatment with CdCl₂ at 2 mg/kg b.wt (Cd 2) and 0.1 mg/kg b.wt EE2 than by the single compound (3-day gavage). The Cd 2-induced down-regulation of Cyp1a1, Gsta2, and Nqo1 mRNA was not antagonized by pure anti-estrogen (2.5 mg/kg b.wt ZK191703 s.c., ZK). Interestingly, the EE₂-induced down-regulation of Cyp1a1, Gsta2, and Nqo1 mRNA was antagonized by Cd 2 in vivo and in colon cancer cell lines (HT-29 and CaCo-2, treated 5 days with Cd 1 µM and/or E₂ 0.01 µM) with low or no ER-beta expression. Dose dependency was studied after Cd exposure with drinking water (5 and 50 ppm CdCl₂ equivalent to 0.4 and 4 mg/kg b.wt; Cd 0.4, Cd 4) for 28 days and EE₂ as reference. Intestinal Mt1a expression was dose dependently induced, while AhR target genes were down-regulated by Cd 0.4 similar to EE₂ and more pronounced than by Cd 4. We propose that Cd modulates intestinal AhR-associated gene expression similar to estrogens, but (contrary to its effects in uterus) via ER-independent and/or ER-beta-mediated mechanisms. Our new data suggest interference of Cd with estrogen and AhR signaling in the small intestine.

  17. 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

  18. Sodium/proton antiport in brush-border-membrane vesicles isolated from rat small intestine and kidney.

    PubMed

    Murer, H; Hopfer, U; Kinne, R

    1976-03-15

    Studies on proton and Na+ transport by isolated intestinal and renal brush-border-membrane vesicles were carried out to test for the presence of an Na+/H+-exchange system. Proton transport was evaluated as proton transfer from the intravesicular space to the incubation medium by monitoring pH changes in the membrane suspension induced by sudden addition of cations. Na+ transport was determined as Na+ uptake into the vesicles by filtration technique. A sudden addition of sodium salts (but not choline) to the membrane suspension provokes an acidification of the incubation medium which is abolished by the addition of 0.5% Triton X-100. Pretreatment of the membranes with Triton X-100 prevents the acidification. The acidification is also not observed if the [K+] and proton conductance of the membranes have been increased by the simultaneous addition of valinomycin and carbonyl cyanide p-trifluoromethoxyphenylhydrazone to the K+-rich incubation medium. Either valinomycin or carbonyl cyanide p-trifluoromethoxyphenylhydrazone when added alone do not alter the response of the membranes to the addition of Na+. Na+ uptake by brush-border microvilli is enhanced in the presence of a proton gradient directed from the intravesicular space to the incubation medium. Under these conditions a transient accumulation of Na+ inside the vesicles is observed. It is concluded that intestinal and renal brush-border membranes contain a NA+/H+ antiport system which catalyses an electroneutral exchange of Na+ against protons and consequently can produce a proton gradient in the presence of a concentration difference for Na+. This system might be involved in the active proton secretion of the small intestine and the proximal tubule of the kidney.

  19. Evaluation of a canine small intestinal submucosal xenograft and polypropylene mesh as bioscaffolds in an abdominal full-thickness resection model of growing rats

    PubMed Central

    Lee, A-Jin; Lee, Sung-Ho; Chung, Wook-Hun; Kim, Dae-Hyun; Chung, Dai-Jung; Do, Sun Hee

    2013-01-01

    We evaluated the biological scaffold properties of canine small intestinal submucosa (SIS) compared to a those of polypropylene mesh in growing rats with full-thickness abdominal defects. SIS is used to repair musculoskeletal tissue while promoting cell migration and supporting tissue regeneration. Polypropylene mesh is a non-resorbable synthetic material that can endure mechanical tension. Canine SIS was obtained from donor German shepherds, and its porous collagen fiber structure was identified using scanning electron microscopy (SEM). A 2.50-cm2 section of canine SIS (SIS group) or mesh (mesh group) was implanted in Sprague-Dawley rats. At 1, 2, 4, 12, and 24 weeks after surgery, the implants were histopathologically examined and tensile load was tested. One month after surgery, CD68+ macrophage numbers in the SIS group were increased, but the number of CD8+ T cells in this group declined more rapidly than that in rats treated with the mesh. In the SIS group, few adhesions and well-developed autologous abdominal muscle infiltration into the SIS collagen fibers were observed. No significant differences in the tensile load test results were found between the SIS and mesh groups at 24 weeks. Canine SIS may therefore be a suitable replacement for artificial biological scaffolds in small animals. PMID:23628657

  20. Intraoperative scintigraphy for active small intestinal bleeding

    SciTech Connect

    Biener, A.; Palestro, C.; Lewis, B.S.; Katz, L.B. )

    1990-11-01

    Localizing active sites of bleeding within the small intestine remains a difficult task. Endoscopic, angiographic or scintigraphic studies may point to the small intestine as the site of blood loss, but at operation, without a palpable lesion, the exact site of bleeding remains elusive. Patients are managed at laparotomy with intraoperative endoscopy, angiography, multiple enterotomies, blind resections, or placement of an enterostomy. We describe two patients in whom intraoperative scintigraphy accurately identified active sites of bleeding in the small intestine when other modalities failed. Intraoperative scintigraphy is rapid, easy to perform and is an effective means of identifying active sites of bleeding within the small intestine.

  1. Efficacy of royal jelly on methotrexate-induced systemic oxidative stress and damage to small intestine in rats.

    PubMed

    Kaynar, Leylagül; Cetin, Aysun; Hacioglu, Sibel K; Eser, Barış; Koçyigit, İsmail; Canöz, Özlem; Tasdemir, Arzu; Karadag, Canan; Kurnaz, Fatih; Saraymen, Recep; Silici, Sibel

    2012-01-01

    The aim of this present study is to investigate the mucositis caused by methotrexate (MTX), as well as whether the application of royal jelly (RJ) has a protective effect on oxidative stress. This present study included six groups each consisted of 12 Wistar rats. Distilled water (po: peroral) was given to the 1st group as placebo for 10 days and MTX (20 mg/kg, intraperitoneal: ip) on the 7th day. The 2nd group received RJ (50mg/kg, po) for 10 days and normal saline (NS) instead of MTX. RJ (50mg/kg) was given to the 3rd group for 10 days and MTX on the 7th day. The 4th group received RJ (100 mg/kg, po) for 10 days and NS was given intraperitoneally. RJ (100mg/kg) was given to the 5th group for 10 days and a single dose of MTX. Distilled water was given to the 6th (control) group for 10 days and intraperitoneal NS on the 7th day. Malondialdehyde (MDA), glutathione peroxidase and superoxide dismutase were analyzed in blood samples on the 11th day. Morphological and histopathological changes were examined in the intestinal tissue samples. Villus length and mucosal thickness, as well as the villus length/crypt ratio, were significantly decreased with MTX administration, and the semi-quantitative histological evaluation (SQHE) score was measured high (p<0.001). In addition, a decrease in the antioxidant parameters and an increase in the MDA levels were identified. The villus length and SQHE were significantly different in the groups receiving RJ (p<0.001) as compared to the MTX group. Although RJ addition had no effect on the decreased mucosal thickness and villus/crypt ratio in MTX groups, it caused an improvement in the antioxidant levels and a remarkable decrease in MDA levels. Adding RJ has a decreasing effect on the MTX-induced intestinal damage and it has a suppressive effect on MTX-induced oxidative stress by means of increasing antioxidant enzyme activity and decreasing lipid peroxidation.

  2. 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.

  3. Calcium and glucose uptake in rat small intestinal brush-border membrane vesicles. Modulation by exogenous hypercortisolism and 1,25-dihydroxyvitamin D-3.

    PubMed

    Braun, H J; Birkenhäger, J C; De Jonge, H R

    1984-07-11

    The effect of exogenous hypercortisolism and 1,25-dihydroxyvitamin D-3 on small-intestinal calcium and glucose transport in the rat was studied at the level of brush-border membrane vesicles generated from isolated villous cells by a freeze-thaw procedure. At 5 X 10(-5) M extravesicular calcium, initial uptake rates in vesicles prepared from triamcinolone-treated adult rats were decreased by 30% after 5 days. Since calcium ionophore A23187 virtually abolished the difference in calcium uptake, triamcinolone appeared to affect calcium channel density or activity rather than intravesicular binding capacity. Kinetic analysis showed that a decrease in Vmax of a saturable calcium transport system could entirely account for the diminished rate of vesicular calcium uptake. Calcium transport rates could be partially restored by in vivo administration of 1,25-dihydroxyvitamin D-3 at a dosage which did not affect vesicular calcium uptake in control animals. Conversely, sodium-driven glucose accumulation in brush-border vesicles from triamcinolone-treated rats was stimulated by 50-70% after 36 h and appeared insensitive to vitamin D. A specific triamcinolone action on the glucose carrier itself rather than on the driving force of the sodium gradient was indicated by (i) a similar stimulation of glucose transport under equilibrium exchange conditions and (ii) an opposite effect of triamcinolone on sodium-driven alanine transport. The triamcinolone-induced changes in calcium and glucose uptake were not accompanied by a gross alteration of membrane integrity in vitro or by major alterations in vesicular protein composition, intravesicular glucose space and sucrase or alkaline phosphatase activity. The modification of vesicular transport properties is discussed in relation to the vitamin D-antagonized inhibition of intestinal calcium uptake and the stimulation of glucose absorption in response to supraphysiologic amounts of glucocorticoids observed in intact epithelium.

  4. Small intestinal goblet cell proliferation induced by ingestion of soluble and insoluble dietary fiber is characterized by an increase in sialylated mucins in rats.

    PubMed

    Hino, Shingo; Takemura, Naoki; Sonoyama, Kei; Morita, Akio; Kawagishi, Hirokazu; Aoe, Seiichiro; Morita, Tatsuya

    2012-08-01

    The study aimed to examine the effects of insoluble and soluble fibers on mucin sialylation and sulfation in the small intestine. First, diets containing soluble [konjac mannan (KM), psyllium, or guar gum; 50 g/kg) or insoluble (polystyrene foam, wheat bran, or cornhusk; 80 g/kg) fiber were fed to rats for 13 d. The fiber-fed groups had more goblet cells in the ileum than the fiber-free control group. High-iron diamine/alcian blue staining showed more sialylated mucin-producing cells in the fiber-fed groups than in the control, whereas sulfated mucin-producing cells were fewer (insoluble fibers) or unchanged (soluble fibers). Second, feeding KM (50 g/kg) and beet fiber (BF) (80 g/kg) diets for 7 d yielded a higher ileum Siat4C expression than the control, but Gal3ST2 and Gal3ST4 expression was comparable. Luminal mucin content correlated with sialic acid (r = 0.96; P < 0.001) or sulfate (r = 0.62; P < 0.01), but the slope of the sialic acid-derived equation was greater than that of the sulfate-derived equation, indicating a preferred increase in sialylated mucins. Third, rats were fed the control diet for 10 d while receiving antibiotic treatment. Analysis of the luminal mucin showed that sialylated mucins were more vulnerable to bacterial degradation than sulfated mucins. Finally, a study of bromo-deoxyuridine incorporation in rats fed a BF diet indicated that goblet cell proliferation accompanied by increased sialylated mucin appeared to be related to accelerated ileal epithelial cell migration. We conclude that intestinal goblet cell responses to insoluble and soluble fibers are characterized by increases in sialylated mucin production.

  5. Protection of radiation-induced damage to the hematopoietic system, small intestine and salivary glands in rats by JNJ7777120 compound, a histamine H4 ligand.

    PubMed

    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.

  6. Synthetic Small Intestinal Scaffolds for Improved Studies of Intestinal Differentiation

    PubMed Central

    Costello, Cait M.; Hongpeng, Jia; Shaffiey, Shahab; Yu, Jiajie; Jain, Nina K.; Hackam, David

    2014-01-01

    In vitro intestinal models can provide new insights into small intestinal function, including cellular growth and proliferation mechanisms, drug absorption capabilities, and host-microbial interactions. These models are typically formed with cells cultured on 2D scaffolds or transwell inserts, but it is widely understood that epithelial cells cultured in 3D environments exhibit different phenotypes that are more reflective of native tissue. Our focus was to develop a porous, synthetic 3D tissue scaffold with villous features that could support the culture of epithelial cell types to mimic the natural microenvironment of the small intestine. We demonstrated that our scaffold could support the co-culture of Caco-2 cells with a mucus-producing cell line, HT29-MTX, as well as small intestinal crypts from mice for extended periods. By recreating the surface topography with accurately sized intestinal villi, we enable cellular differentiation along the villous axis in a similar manner to native intestines. In addition, we show that the biochemical microenvironments of the intestine can be further simulated via a combination of apical and basolateral feeding of intestinal cell types cultured on the 3D models. PMID:24390638

  7. 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

  8. Mast-cell-releasing tryptase triggers acute lung injury induced by small intestinal ischemia-reperfusion by activating PAR-2 in rats.

    PubMed

    Gan, Xiaoliang; Liu, Dezhao; Huang, Pinjie; Gao, Wanling; Chen, Xinzhi; Hei, Ziqing

    2012-06-01

    Mast cell has been demonstrated to be involved in the small intestinal ischemia-reperfusion (IIR) injury, however, the precise role of tryptase released from mast cell on acute lung injury(ALI) induced by IIR remains to be elucidated, our study aimed to observe the roles of tryptase on ALI triggered by IIR and its underlying mechanism. Adult SD rats were randomized into sham-operated group, sole IIR group in which rats were subjected to 75 min superior mesenteric artery occlusion followed by 4 h reperfusion, or IIR being respectively treated with cromolyn sodium, protamine, and compound 48/80. The above agents were, respectively, administrated intravenously 5 min before reperfusion. At the end of experiment, lung tissue was obtained for assays for protein expressions of tryptase and mast cell protease 7 (MCP7) and protease-activated receptor 2 (PAR-2). Pulmonary mast cell number and levels of IL-8 were quantified. Lung histologic injury scores and lung water content were measured. IIR resulted in lung injury evidenced as significant increases in lung histological scores and lung water contents, accompanied with concomitant increases of expressions of tryptase and MCP7, and elevations in PAR-2 expressions and IL-8 levels in lungs. Stabilizing mast cell with cromolyn sodium and inhibiting tryptase with protamine significantly reduced IIR-mediated ALI and the above biochemical changes while activating mast cell with compound 48/80 further aggravated IIR-mediated ALI and the increases of above parameters. Tryptase released from mast cells mediates ALI induced by intestinal ischemia-reperfusion by activating PAR-2 to produce IL-8.

  9. Biotin absorption by distal rat intestine

    SciTech Connect

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

    1987-12-01

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

  10. Hymenolepis diminuta: analysis of the expression of Toll-like receptor genes (TLR2 and TLR4) in the small and large intestines of rats. Part II.

    PubMed

    Kosik-Bogacka, D I; Wojtkowiak-Giera, A; Kolasa, A; Czernomysy-Furowicz, D; Lanocha, N; Wandurska-Nowak, E; Salamatin, R; Jagodzinski, P P

    2013-10-01

    Toll-like receptors in the gastrointestinal tract can influence intestinal homeostasis and play a role in the repair and restitution of intestinal epithelium following tissue damage. In our previous study a statistically significant increase in the level of TLR4 and TLR2 gene expression was observed in rats in early stages of hymenolepidosis. Moreover, the immunopositive cell number and the intensity of immunohistochemical staining (indicating the presence of TLRs within intestinal epithelial cells) increased over the infection period. In this paper, we determined changes in the expression of TLR2 and TLR4 and the number of anaerobic intestinal commensal bacteria in Hymenolepis diminuta infected rats. In the isolated jejunum of infected rats at 16 days post infection (dpi), the expression of TLR4 and TLR2 was significantly higher than uninfected rats. In the colon, a statistically significantly increased expression of TLR2 was observed from 16 to 40 dpi, and TLR4 from 16 to 60 dpi. The jejunum and colon of infected rats contained Gram-negative bacteria (Escherichia coli), Gram-positive bacteria (Enterococcus, Streptococcus, Staphylococcus, Bacillus, Lactobacillus) and Candida. The total number of intestinal bacteria was higher in H. diminuta infected rats, but the observed microbiota had only minor effects on the expression of TLR2 and TLR4. Toll-like receptors play a role in maintaining epithelial barrier function in response to enteric pathogens and parasites. In our study, the alteration of TLR2 and TLR4 expression in the infected rats indicates the potential role of the innate immune system in the pathomechanism of this infection.

  11. Update on small intestinal stem cells.

    PubMed

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

    2013-08-07

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

  12. Small intestine dysfunction in Parkinson's disease.

    PubMed

    Dutkiewicz, Justyna; Szlufik, Stanisław; Nieciecki, Michał; Charzyńska, Ingeborga; Królicki, Leszek; Smektała, Piotr; Friedman, Andrzej

    2015-12-01

    The aim of this study was to assess the small bowel transit time in patients with Parkinson's disease (PD). Ten patients with PD with no gastrointestinal complaints and ten healthy control subjects were investigated using single photon emission computed tomography fused with computed tomography after swallowing of a specially prepared capsule containing technetium 99m, which allowed visualization of the passage in the intestines. Preliminary results show that the small intestine passage in PD patients was prolonged compared to controls.

  13. Basic fibroblast growth factor suppresses radiation-induced apoptosis and TP53 pathway in rat small intestine.

    PubMed

    Matsuu-Matsuyama, Mutsumi; Nakashima, Masahiro; Shichijo, Kazuko; Okaichi, Kumio; Nakayama, Toshiyuki; Sekine, Ichiro

    2010-07-01

    The effect of basic fibroblast growth factor (bFGF) was studied in radiation-induced apoptosis in rat jejunal crypt cells. Six-week-old male Wistar rats were administered 4 mg/kg bFGF intraperitoneally 25 h before receiving 8 Gy whole-body X rays. The jejunum was removed for analysis from time 0 to 120 h after irradiation. Villus length in control rats declined steadily until 72 h, while in bFGF-treated rats the villi were longer than in the controls until 48 h. Crypt lengths were similar to villi. bFGF treatment increased Ki-67-positive cells in the jejunal crypt at 0, 24 and 48 h. The treatment with bFGF reduced the number of apoptotic cells per jejunal crypt to 23% and 10% of the control values at 3 and 6 h, respectively, and increased numbers of mitotic cells significantly at 48 and 72 h. bFGF decreased the levels of TP53, CDKN1A, Puma and Cleaved caspase 3 at 3 h as detected by Western blot analyses. Our results suggest that bFGF protected against acute radiation-induced injury by suppressing the crypt apoptotic cells including the stem cells and promoted crypt cell proliferation. The inhibition of apoptosis thus might be related to suppression of the TP53 pathway.

  14. 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

  15. 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

  16. 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.

  17. Food proteins and gut mucosal barrier. IV. Effects of acute and chronic ethanol administration on handling and uptake of bovine serum albumin by rat small intestine

    SciTech Connect

    Stern, M.; Carter, E.A.; Walker, W.A.

    1986-11-01

    The effects of ethanol exposure on small intestinal handling and uptake of radiolabeled bovine serum albumin were investigated using everted gut sacs. There was less breakdown of BSA after acute ethanol administration in vitro and after acute and chronic in vivo exposure. Thus, the vascular compartment of the small intestine was confronted with more complete and potentially more antigenic material after ethanol. Changes in BSA binding and uptake after acute exposure were shown to be reversible after 4-6 hr. In all groups, there was more BSA binding when the small intestine was exposed to ethanol. This difference was most pronounced after chronic exposure. In the same group, uptake of BSA was correlated with binding and significantly increased. Combined effects of ethanol on the gut mucosal barrier may account for changes in food antigen handling and uptake.

  18. The effects of age on the overall population and on subpopulations of myenteric neurons in the rat small intestine

    PubMed Central

    JOHNSON, R. J. R.; SCHEMANN, M.; SANTER, R. M.; COWEN, T.

    1998-01-01

    Previous studies on ageing animal and human subjects have demonstrated a significant overall decline in neuronal numbers in the myenteric plexus of the enteric nervous system (ENS). Our study aimed to confirm this observation by counting myenteric neurons stained with the panneuronal markers PGP 9.5 and NADH-diaphorase. We also wished to examine the possibility that particular subpopulations of neurons are vulnerable. Therefore, we have immunostained and counted a number of nerve cell groups within the myenteric plexus of old and young Sprague Dawley rats using markers which reflect some of the neuronal phenotypes present, including ChAT and VIP. The number of neurons demonstrating NADH-diaphorase activity was significantly reduced (P<0.05) by approximately 15% in old rats. However, the number of neurons stained for PGP 9.5 immunohistochemistry was not reduced and demonstrated larger numbers of neurons than the NADH-diaphorase method. None of the other neuronal markers studied showed any significant reductions with age. In contrast to previous work, this study has gathered little evidence for extensive cell loss in the myenteric plexus of the aged rat, either in overall populations, or in any of the principal functional groups of neurons. PMID:9723975

  19. [The ratio between the initial stages of assimilation of intact and hydrolyzed dipeptides in rat small intestine].

    PubMed

    Metel'skiĭ, S T

    2013-04-01

    Absorption of amino acids and dipeptides in the intestine may be coupled with sodium or proton, respectively. In both cases, when these nutrients are added to the mucosal solution (solution bathing the mucosa) through the epithelial layer should flow additional electric current. which is the most convenient to register by the short-circuit current method (SCC). It was shown that at pH 8.5, we can observe more efficient dipeptide transport (SCC response amplitudes on dipeptides have greater amplitude then SCC responses to equimolar mixture of the corresponding amino acid). In contrast, at pH 5.5 we observe the reverse situation - the SCC responses to mixture of amino acids are more then SCC responses to dipeptides. Increased with pH sodium dependent component of the stimulating effect of easily hydrolysable dipeptides is due to the membrane digestion. Sodium independent effect of dipeptides assimilation decreasing with pH caused by, apparently, functioning of proton-dependent transporter PepT1 for oligopeptides in the apical membrane of enterocytes. We believe that sequential "conditioning" of the stomach contents in the ever-increasing pH while its moving along the gastrointestinal tract (from stomach to colon) enables optimal use of both the mechanism of absorption of oligodipeptides, which is accompanied by a more complete digestion of oligodipeptides.

  20. 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.

  1. Characteristics of β-galactosidase in the mucosa of the small intestine of infant rats. Physicochemical properties

    PubMed Central

    Kraml, Jiří; Koldovský, Otakar; Heringová, Aleša; Jirsová, Věra; Kácl, Karel; Ledvina, Miloš; Pelichová, Hana

    1969-01-01

    1. The characteristics of acid and neutral β-galactosidases isolated chromatographically from homogenates of the mucosa of the jejunum and ileum of suckling rats were studied. 2. The minimal molecular weight of the acid β-galactosidase, as estimated by gel filtration on Sephadex G-200, was in the range 83000–105000, whereas for the neutral β-galactosidase the estimated molecular weight was in the range 360000–510000. 3. The acid and neutral β-galactosidases were inhibited competitively by galactono-(1→4)-lactone, with respective Ki values of 0·15mm and 1·1mm. Only the acid β-galactosidase was inhibited competitively by sodium galactonate (Ki 0·17mm). 4. Heat inactivation of both β-galactosidases occurred according to first-order kinetics. The neutral enzyme was more labile, but bovine serum albumin protected acid enzyme only. 5. Urea treatment inactivated both β-galactosidases, the neutral β-galactosidase being more sensitive than the acid β-galactosidase. 6. No differences were found between preparations from the jejunum and ileum. PMID:5820646

  2. Grape seed extract protects IEC-6 cells from chemotherapy-induced cytotoxicity and improves parameters of small intestinal mucositis in rats with experimentally-induced mucositis.

    PubMed

    Cheah, Ker Y; Howarth, Gordon S; Yazbeck, Roger; Wright, Tessa H; Whitford, Eleanor J; Payne, Caroline; Butler, Ross N; Bastian, Susan E P

    2009-02-01

    Mucositis is a common side-effect of high-dose chemotherapy regimens. Grape seed extract (GSE) represents a rich source of proanthocyanidins with the potential to decrease oxidative damage and inflammation within the gastrointestinal tract. We evaluated GSE for its capacity to decrease the severity of chemotherapy-induced mucositis in vitro and in vivo. In vitro: GSE was administered to IEC-6 intestinal epithelial cells prior to damage induced by 5-Fluorouracil (5-FU). Cell viability was determined by neutral red assay. In vivo: Female Dark Agouti rats (130-180 g) were gavaged with 1 ml GSE (400 mg/kg) daily (day 3-11) and received 5-FU (150 mg/kg) by intraperitoneal (i.p.) injection on day nine to induce mucositis. Rats were sacrificed at day 12 and intestinal tissues collected for myeloperoxidase and sucrase activity assays and histological analyses. Statistical analysis was performed by one-way ANOVA. GSE prevented the decrease in IEC-6 cell viability induced by 5-FU (p < 0.01). Compared with 5-FU controls, GSE significantly reduced myeloperoxidase activity by 86% and 27% in the proximal jejunum (p < 0.001) and distal ileum (p < 0.05) respectively; decreased qualitative histological scores of damage (p < 0.05) in the proximal jejunum; increased villus height in the proximal jejunum (17%; p < 0.05) and distal ileum (50%; p < 0.01), and attenuated the 5-FU-induced reduction of mucosal thickness by 16% in the jejunum (p < 0.05) and 45% in the ileum (p < 0.01). GSE partially protected IEC-6 cells from 5-FU-induced cytotoxicity and ameliorated intestinal damage induced by 5-FU in rats. GSE may represent a promising prophylactic adjunct to conventional chemotherapy for preventing intestinal mucositis.

  3. 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

  4. Localization of binding sites for concanavalin A, Ricinus communis I and Helix pomatia lectin in the Golgi apparatus of rat small intestinal absorptive cells.

    PubMed

    Pavelka, M; Ellinger, A

    1985-09-01

    Binding sites for concanvalin A (Con A), Ricinus communis I agglutinin (RCA I), and Helix pomatia lectin (HPA) were localized in the Golgi apparatus of rat small intestinal absorptive cells. A preembedment technique, a modification of the one originally used by Bernhard and Avrameas (Exp Cell Res 64:232, 1971), was employed, with horse-radish peroxidase being used for cytochemical visualization. Incubations were performed on 10 microns thick cryosections of duodenal segments that were fixed in a mixture of 4% formaldehyde and 0.5% glutaraldehyde; fixation was preceded by a 2-min rinse in 0.1 M sodium cacodylate and followed by storage in the same buffer for up to 7 days. Incubation with Con A, which binds preferably to alpha-D-mannose and alpha-D-glucose residues, caused intense reaction of the dilated cisternae of the cis Golgi side; staining was variable in intermediate and trans cisternae. RCA I, recognizing beta-D-galactose residues, could only be demonstrated in intermediate cisternae. Reaction for HPA, which indicates alpha-N-acetyl-D-galactosamine residues, stained intensely 1 to 2 cisternae of the cis Golgi side, as well as being localized in the peripheral regions of the cisternae of the intermediate compartment of the stacks. Deposits of reaction product covered the luminal surface of the cisternal membranes, but usually left the lumen itself, as well as lipid particles, devoid of reaction. The differences in Con A, RCA I, and HPA reactivity between cis, intermediate, and trans cisternae suggest compositional and structural differences of the carbohydrates in the respective compartments; they may reflect conversion processes that are known to occur in the oligosaccharide side chains of glycoconjugates at the Golgi complex level.

  5. Rat small-intestinal β-galactosidases. Studies on the fractionation of `acid' β-galactosidase with isoelectric focusing, gel filtration and ion-exchange chromatography

    PubMed Central

    Asp, Nils-Georg

    1970-01-01

    1. Different forms of the rat small-intestinal `acid' β-galactosidase were separated by using the isoelectric-focusing technique. The isoelectric points of the different forms were at pH4.2, 4.6, 5.4, 6.1 and approx. 8. 2. The two forms of `acid' β-galactosidase isoelectric at pH4.2 and 4.6 were completely excluded from the Sephadex G-200 gel, whereas the form isoelectric at pH8 had Kav. 0.4. The concentration and pH of the elution buffer influenced the distribution of enzyme activity between different forms. Thus, under certain conditions of ionic strength and pH, the enzyme seems to form high-molecular-weight aggregates with low isoelectric points. These may be homopolymeric aggregates or the result of binding of enzyme to, for example, membrane fragments. The forms isoelectric at pH5.4 and 6.1 are probably aggregates of intermediate size. 3. During ion-exchange chromatography at pH6.0 one fraction of `acid' β-galactosidase was not retained on the column and was isoelectric at pH8 and another fraction was eluted when the buffer concentration in the eluate had increased to about 50mm. The main part of enzyme eluted in this second fraction was also isoelectric at pH8, indicating that the elution of this fraction is not a simple ion-exchange procedure but probably also involves a splitting of high-molecular-weight aggregates, originally retained because of their low isoelectric points. The enzyme subunits have a higher isoelectric point, and are therefore no longer bound to the ion-exchange resin. PMID:5420050

  6. Small intestinal ganglioneuromatosis in a dog.

    PubMed

    Paris, J K; McCandlish, I A P; Schwarz, T; Simpson, J W; Smith, S H

    2013-05-01

    A 9-year-old female neutered collie-cross dog was presented with a 2-month history of persistent diarrhoea, weight loss and intermittent vomiting. Abdominal ultrasonography revealed one loop of jejunum with a markedly thickened and multifocally hyperechoic wall, without loss of wall layering. Laparotomies were performed for biopsy and resection of affected intestine. Histopathological examination revealed small intestinal ganglioneuromatosis (GN). The dog recovered well from surgery and the diarrhoea resolved. Eleven months later the dog has gained weight and remains asymptomatic. This is the first report of small intestinal GN affecting a mature dog, in which pathology was localized to the mucosal lamina propria and surgical treatment resulted in a successful outcome.

  7. Effect of cortisone on the developmental pattern of the neutral and the acid β-galactosidases of the small intestine of the rat

    PubMed Central

    Koldovský, Otakar; Sunshine, Philip

    1970-01-01

    1. The developmental pattern and effect of cortisone on acid β-galactosidase and neutral β-galactosidase were studied in postnatal rats by a recently proposed method for their independent determination. 2. After birth the acid β-galactosidase activity increases in the ileum, whereas it decreases slightly in the jejunum. On day 16 after birth the activity in the ileum decreases and in 20-day-old rats activity in both parts of the intestine decreases to adult values. In suckling animals the activity in the ileum exceeds the jejunal activity severalfold and in adult animals the activity in the jejunum is slightly higher than that in the ileum. 3. Neutral β-galactosidase activity is high after birth and decreases in both jejunum and ileum after day 20 after birth. In 12–20-day-old rats activity in both parts is essentially the same, but in adult animals jejunal activity exceeds ileal activity four-to five-fold. 4. Cortisone (0.5, 2.0 or 5.0mg/100g body wt. daily for 4 days) does not influence the activity of either enzyme in 60-day-old rats. Acid β-galactosidase activity is decreased after cortisone treatment in 8-, 12-, 16-and 18-day-old rats, with sensitivity to cortisone increasing with the approach of weaning. No effect of cortisone on acid β-galactosidase is seen in 8-day-old rats. Neutral β-galactosidase activity is increased in the ileum of 8-, 12-, 16- and 18-day old rats, but only in the jejunum of 8-and 12-day-old rats. PMID:5419744

  8. Structural and mechanical architecture of the intestinal villi and crypts in the rat intestine: integrative reevaluation from ultrastructural analysis.

    PubMed

    Hosoyamada, Yasue; Sakai, Tatsuo

    2005-08-01

    The ultrastructure of the rat intestinal interstitium was analyzed from the viewpoint of mechanical dynamics to stabilize the intestinal villi, crypts and mucosal folds. In the rat, the small intestine lacks circular folds, but the large intestine possesses spiral folds. The intestinal villi, the largest in the duodenum, decreased in size in the jejunum and ileum successively, and were absent in the large intestine. The intestinal interstitium consisted of lamina propria mucosae (LPM) and tela submucosa (TSM) separated by muscularis mucosae (MM), the LPM was subdivided into an upper part within the villi and a lower part among the crypts in the small intestine. The light microscopic density of interstitium in the intestinal wall was lowest in the upper LPM, moderately dense in the lower LPM and highest in the TSM, and that among the intestinal region was highest in the duodenum and decreased successively in the jejunum and ileum. In the large intestine, the TSM bulged to form spiral folds with very low density. The intestinal epithelium in the villi possessed wide intercellular spaces and that in the crypts had closed intercellular spaces. At electron microscopic level, the upper and lower LPM contained subepithelial supportive meshwork that consisted of collagen fibrils and myofibroblast processes. The lower LPM and TSM contained conspicuous bundles of collagen fibrils and, in addition, TSM contained minor populations of scattered collagen fibrils near the smooth muscle layer (SML). The diameter of collagen fibrils was the largest in the bundles of TSM, and decreased from the duodenum through the jejunum and ileum to the large intestine. On the basis of these observations, we hypothesize that the intestinal villi are mechanically stabilized by the balance between the expansive interstitial pressure and inward pull by the subepithelial supportive meshwork. This hypothesis explains the hitherto neglected fact that the intestinal epithelium possesses wide

  9. Characteristics of iron(III) uptake by isolated fragments of rat small intestine in the presence of the hydroxypyrones, maltol and ethyl maltol.

    PubMed

    Levey, J A; Barrand, M A; Callingham, B A; Hider, R C

    1988-05-15

    Accumulation of radioactive iron (59Fe) into isolated fragments of rat small intestine in the presence of two hydroxypyrones, maltol and ethyl maltol, was compared with that in the presence of another chelator of iron(III), nitrilotriacetic acid (NTA). The characteristics of uptake were similar with all three ligands. Between 10(-6) and 10(-4) M, iron uptake showed saturable kinetics. The uptake was partially inhibited by metabolic inhibitors. Above 10(-4) M a non-saturable uptake, unaffected by metabolic inhibitors became evident in the presence of the pyrones. The distribution of 59Fe after uptake was determined by gel filtration. At low iron concentrations (10(-6) M), 35-40% of absorbed iron was associated with proteins of molecular weights similar to those of ferritin and transferrin. At high concentrations (10(-3) M), the majority of 59Fe was found in a low molecular weight fraction. At each concentration, a small amount of 59Fe was bound to a membrane fraction. 5% Polyethylene glycol, which reduces glycocalyx viscosity enhanced uptake at low iron concentrations (10(-6) M) but did not affect the non-saturable diffusion seen at higher concentrations (10(-3) M). The iron(II) chelator, bathophenanthroline sulphonate (10(-3) M), decreased uptake at low iron concentrations but did not affect the non-saturable uptake. It is suggested that conversion of iron(III) to iron(II) may take place at the mucosal cell surface before uptake via the saturable system. Apparent Km values for iron uptake via the saturable system were higher in the presence of maltol and ethyl maltol than in the presence of NTA, presumably since the iron binds more avidly to the hydroxypyrones and so is less readily donated. Excess ligand, either pyrone or NTA, reduced the rate at which 59Fe was donated to the uptake system. The Vmax value for uptake from the pyrones was greater than from NTA. It is concluded that maltol, ethyl maltol and NTA can hold iron(III) in solution and donate it to an

  10. Teaching intestinal transplantation in the rat for medical student.

    PubMed

    Galvão, Flávio Henrique Ferreira; Bacchella, Telesforo; Cerqueira Machado, Marcel

    2007-01-01

    Technical difficulties hamper the widespread use of intestinal transplantation in rats. We evaluated the feasibility in training this microsurgical model for medical students. Thirty eight students were assessed. After information about intestinal transplantation in rats, they spontaneously agreed to be trained for this procedure. The course consisted of 4-h weekly lessons during 4-month period. The teaching process includes assessment in four phases: I) conception of intestinal transplantation and rat anatomy; II) basic microsurgery training; III) donor operation; IV) donor/recipient operation. Wistar rats were used as donors and recipients in one-step small bowel transplantation. All students (100%) reached phase II, seven students (18.42%) reached phase III and two students (5.26%) reached phase IV. Decreased interest about the theme, lack of time and patience, frustration and/or inability were all reasons given by the student that may have contributed to the low rate of success. Medical students achieved a low rate of completion for training in rat intestinal transplantation microsurgical procedures.

  11. Enhanced small intestinal absorption of beta-lactam antibiotics in rats in the presence of monodesmosides isolated from pericarps of Sapindus mukurossi (Enmei-hi).

    PubMed

    Yata, N; Sugihara, N; Yamajo, R; Murakami, T; Higashi, Y; Kimata, H; Nakayama, K; Kuzuki, T; Tanaka, O

    1986-02-01

    Monodesmoside, saponin A, B and C, isolated from pericarps of Sapindus mukurossi (Enmei-hi) have been shown to promote absorption of poorly absorbed beta-lactam antibiotics by the small intestine using an in situ loop method. Monodesmosides were solubilized with ginseng crude saponin extract, a mixture of bisdesmosides, saponin X, Y1 and Y2 which were isolated also from Sapindus mukurossi. These solubilizing agents were demonstrated not to influence the absorption promoting effect of monodesmosides. Among the monodesmosides, saponin B showed the greatest effect. No influence of osmolarity of the administered solution on the absorption promoting action was observed. The promoting functions of the three monodesmosides for the small intestinal absorption of antibiotics were suppressed by Ca2+ ion coexisting in the administered solution.

  12. 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.

  13. 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.

  14. Iron absorption by small intestine of chickens.

    PubMed

    Sáiz, M P; Martí, M T; Mitjavila, M T; Planas, J

    1993-01-01

    Iron (Fe) absorption by three segments (duodenum, jejunum, and ileum) of the small intestine of chickens was studied by a perfusion technique in vivo in closed circuit using 59Fe Cl3 and was related to the histological characteristics of each segment. The serosal transfers of Fe for the duodenum and jejunum were the same (14%/cm), but significantly different (p < 0.05) from those of the ileum (9%/cm), which may be explained by the morphological and histological properties of the gut of chickens. However, the presence of Fe in blood and in liver was significantly lower after perfusion of the jejunum and ileum than after perfusion of the duodenum. It is concluded that chickens show an early adaptation of small intestine to Fe absorption in response to the considerable loss of Fe suffered during the laying process.

  15. Glucagon effects on the human small intestine.

    PubMed

    Patel, G K; Whalen, G E; Soergel, K H; Wu, W C; Meade, R C

    1979-07-01

    In healthy volunteers, the effects of intravenously administered glucagon on small intestinal function was investigated. Bolus doses resulting in plasma glucagon concentrations of greater than 800 pg/ml (5 min after injection) abolished jejunal contractions for 4.4 +/- 0.4 (SEM) min after a latency period of 49 +/- 4 sec. During continuous intravenous glucagon infusion, jejunal dilatation and increase in mean transit time (MTT) occurred at plasma levels greater than 720 pg/ml, while inhibition of water and electrolyte absorption was observed only with plasma glucagon concentrations of 1760 +/- 114 pg/ml. Under these conditions, the propulsion of fasting intestinal contents was slowed without change in flow rate. The observed effects cannot be attributed to the simultaneously occurring rise in plasma insulin and glucose concentrations. Short-term increases in circulating glucagon concentration inhibit intestinal tone, contractions, and propulsion with only a minor effect on water and electrolyte absorption limited to a narrow concentration range of plasma glucagon. Neither effect occurs at glucagon levels likely to occur under physiologic concentrations. The latency period preceding the abolition of jejunal contractions suggests that glucagon does not act directly on intestinal smooth muscle cells.

  16. Species differences in in vitro and in vivo small intestinal metabolism of CYP3A substrates.

    PubMed

    Komura, Hiroshi; Iwaki, Masahiro

    2008-05-01

    Intestinal first-pass metabolism has a great impact on the bioavailability of CYP3A substrates in humans, and the in vivo impact has quantitatively been evaluated using CYP3A inhibitors or inducers. In vitro and in vivo preclinical investigations for intestinal metabolism are essential in clarifying pharmacokinetic behavior in animal species and predicting the effect of intestinal metabolism in the human. In this review, we will discuss species differences in intestinal CYP3A enzymes, and CYP3A-mdediated intestinal elimination. Identical CYP3A4 enzyme is expressed in human intestine and liver, but different CYP3A enzymes in both tissues of the mouse and rat are found, that is, respective intestinal enzyme is considered as cyp3a13 and CYP3A62. There is little information on CYP3A enzymes in the monkey and dog intestine, unlike the liver. In vitro metabolic activities of midazolam and nisoldipine are higher in the human and monkey than in the rat. In vivo assessment of cyclosporine, midazolam, nifedipine, tacrolimus, and verapamil has been reported in various species (monkey, rat, mouse, and/or dog) including the human. For midazolam, the monkey shows significant in vivo intestinal metabolism, as evidenced in the human. The monkey might be an appropriate animal model for evaluating small intestinal first-pass metabolism of CYP3A substrates.

  17. Dietary regulation of rat intestinal cholecystokinin gene expression.

    PubMed Central

    Liddle, R A; Carter, J D; McDonald, A R

    1988-01-01

    Cholecystokinin (CCK) is a gastrointestinal hormone produced by discrete endocrine cells in the upper small intestine and released after ingestion of a meal. The present study was designed to determine if enhanced CCK secretion is associated with increases in intestinal CCK mRNA levels. Rats, prepared with indwelling intraduodenal cannulae, were first fed an elemental diet that did not stimulate CCK release. Next, as a means of stimulating CCK secretion, soybean trypsin inhibitor was perfused for up to 24 h. Trypsin inhibitor administration increased plasma CCK levels from 0.9 +/- 0.1 to approximately 5 pmol/liter. RNA was prepared from the proximal small intestine at various times after trypsin inhibitor perfusion and mRNA levels analyzed by hybridization with a CCK cDNA probe. After 12 and 24 h of trypsin inhibitor treatment there were three- and fourfold increases, respectively, in CCK mRNA levels. In comparison, there was no change in beta-actin mRNA levels. To determine if regulation of CCK mRNA was at the level of CCK gene transcription, labeled transcripts from nuclear run-on incubations were hybridized to immobilized CCK cDNA. In trypsin inhibitor-treated rats, a two- to threefold increase in transcriptional activity was observed, whereas beta-actin gene transcription levels were unaltered. These studies indicate that stimulation of CCK secretion is associated with an increase in intestinal CCK mRNA content resulting from an increase in CCK gene transcription. Images PMID:2454954

  18. 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...

  19. 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...

  20. Improved purification of rat intestinal lactase.

    PubMed

    Nsi-Emvo, E; Launay, J F; Raul, F

    1986-02-01

    A rapid and improved method to obtain purified lactase from rat intestine is described. The purification procedure involved only two chromatographic steps. The degree of purification was far above (500 fold) the values reached with classical methods. Rabbit antisera raised to the purified lactase were characterized using conventional immunological techniques. The specificity of the lactase antibodies was confirmed by the lack of interference on maltase, aminopeptidase and alkaline phosphatase activities measured after papain extraction of the membrane proteins.

  1. Expression and Function of Intestinal Hexose Transporters after Small Intestinal Denervation

    PubMed Central

    Iqbal, Corey W.; Fatima, Javairiah; Duenes, Judith; Houghton, Scott G.; Kasparek, Michael S.; Sarr, Michael G.

    2009-01-01

    Background The role of neural regulation in expression and function of intestinal hexose transporters is unknown. Aim To determine the role of intestinal innervation in gene expression and function of the membrane hexose transporters, SGLT1, GLUT2, and GLUT5 in the enterocyte. Hypothesis Denervation of the small intestine decreases expression of hexose transporters leading to decreased glucose absorption. Methods Six groups of Lewis rats were studied (n=6 each): control, 1 wk after sham laparotomy, 1 and 8 wk after syngeneic (no immune rejection) orthotopic small bowel transplantation (SBT) (SBT1, SBT8) to induce complete extrinsic denervation, and 1 and 8 wk after selective disruption of intrinsic neural continuity to jejunoileum by gut transection and reanastomosis (T/A1, T/A8). All tissue was harvested between 8AM and 10AM. In duodenum, jejunum, and ileum, mucosal mRNA levels were quantitated by real time PCR, protein by Western blotting, and transporter-mediated glucose absorption using the everted sleeve technique. Results Across the six groups, relative gene expression of hexose transporter mRNA and protein levels were unchanged and no difference in transporter-mediated glucose uptake was evident in any region. Glucose transporter affinity (Km) and functional transporter levels (Vmax) calculated for duodenum and jejunum showed no difference between the six groups. Conclusion Baseline regulation of hexose transporter function is not mediated tonically by intrinsic or extrinsic neural continuity to the jejunoileum. PMID:19541015

  2. Misoprostol in the intestinal lumen protects against radiation injury of the mucosa of the small bowel

    SciTech Connect

    Delaney, J.P.; Bonsack, M.E.; Felemovicius, I. )

    1994-03-01

    Systemically administered misoprostol, a PGE analog, has been shown to be an intestinal radioprotector. The purpose of this study was to determine if administration of misoprostol into the intestinal lumen can also reduce the severity of acute radiation enteritis. The rat small bowel was operatively exteriorized and segmented by means of suture ties. The remainder of the intestine and the rat were shielded in a lead box. Misoprostol was introduced into the lumen in various doses. After 30 min exposure to misoprostol, the isolated, exteriorized, segmented bowel was subjected to 11 Gy X irradiation. Five days later the animals were sacrificed and the intestines harvested for evaluation. Surviving crypt numbers per circumference and mucosal height were the criteria used for quantification of damage. Mucosa exposed to misoprostol at the time of radiation delivery showed significantly increased crypt numbers and mucosal height compared to adjacent saline-filled intestine. 24 refs., 2 figs., 2 tabs.

  3. Intestinal folate binding protein (FBP) and folate absorption in the suckling rat

    SciTech Connect

    Mason, J.B.; Selhub, J.

    1986-03-01

    The folate in milk is bound to high affinity FBPs but it is unknown whether this binding affects intestinal transport of milk folate in the suckling rat. The authors examined the FBP activity of segments of the GI tract in fed and fasting states. Under fed conditions, the FBP activity in the mucosa of the stomach and proximal small intestine were similar (0.28 and 0.32 pMole folic acid binding/mg protein, N.S.). Both demonstrated less activity than the mucosa of the distal small intestine (1.31 pMole/mg protein, P < .001). A 6 hr fast produced no change in the FBP activity in the stomach or proximal small intestine but resulted in a 42% decrease in the distal small intestine (p < .01). Intestinal transport of unbound and FB-bound H/sup 3/pteryolmonoglutamate (H/sup 3/PGA) was examined in suckling rats by the intestinal loop model. Unbound H/sup 3/PGA demonstrated greater lumenal disappearance in the proximal segment of the small intestine compared to the distal segment (79% vs. 56%, P < .001) whereas the bound H/sup 3/PGA demonstrated greater lumenal disappearance in the distal segment (36% vs. 21%, p < .005). That porton of FBP activity in the distal small intestine that disappears with fasting may represent FBP absorbed from the lumen of the intestine. The FBP-bound folate in milk appears to be absorbed in the suckling rat by a mechanism that favors the distal small intestine and is different from the mechanism responsible for absorption of the unbound folate.

  4. Differential gene expression in liver and small intestine from lactating rats compared to age-matched virgin controls detects increased mRNA of cholesterol biosynthetic genes

    PubMed Central

    2011-01-01

    Background Lactation increases energy demands four- to five-fold, leading to a two- to three-fold increase in food consumption, requiring a proportional adjustment in the ability of the lactating dam to absorb nutrients and to synthesize critical biomolecules, such as cholesterol, to meet the dietary needs of both the offspring and the dam. The size and hydrophobicity of the bile acid pool increases during lactation, implying an increased absorption and disposition of lipids, sterols, nutrients, and xenobiotics. In order to investigate changes at the transcriptomics level, we utilized an exon array and calculated expression levels to investigate changes in gene expression in the liver, duodenum, jejunum, and ileum of lactating dams when compared against age-matched virgin controls. Results A two-way mixed models ANOVA was applied to detect differentially expressed genes. Significance calls were defined as a p < 0.05 for the overall physiologic state effect (lactation vs. control), and a within tissue pairwise comparison of p < 0.01. The proportion of false positives, an estimate of the ratio of false positives in the list of differentially expressed genes, was calculated for each tissue. The number of differentially expressed genes was 420 in the liver, 337 in the duodenum, 402 in the jejunum, and 523 in the ileum. The list of differentially expressed genes was in turn analyzed by Ingenuity Pathways Analysis (IPA) to detect biological pathways that were overrepresented. In all tissues, sterol regulatory element binding protein (Srebp)-regulated genes involved in cholesterol synthesis showed increased mRNA expression, with the fewest changes detected in the jejunum. We detected increased Scap mRNA in the liver only, suggesting an explanation for the difference in response to lactation between the liver and small intestine. Expression of Cyp7a1, which catalyzes the rate limiting step in the bile acid biosynthetic pathway, was also significantly increased in liver. In

  5. STUDIES ON SMALL INTESTINAL CRYPT EPITHELIUM

    PubMed Central

    Trier, Jerry S.

    1963-01-01

    Small intestinal crypt epithelium obtained from normal fasting humans by peroral biopsy of the mucosa was studied with the electron microscope. Paneth cells were identified at the base of the crypts by their elaborate highly organized endoplasmic reticulum, large secretory granules, and small lysosome-like dense bodies within the cytoplasm. Undifferentiated cells were characterized by smaller cytoplasmic membrane-bounded granules which were presumed to be secretory in nature, a less elaborate endoplasmic reticulum, many unattached ribosomes and, in some cells, the presence of glycogen. Some undifferentiated cells at the base of the crypts contained lobulated nuclei and striking paranuclear accumulations of mitochondria. Membrane-bounded cytoplasmic fragments, probably originating from undifferentiated and Paneth cells, were frequently apparent within crypt lumina. Of the goblet cells, some were seen actively secreting mucus. In these, apical mucus appeared to exude into the crypt lumen between gaps in the microvilli. The membrane formerly surrounding the apical mucus appeared to fuse with and become part of the plasma membrane of the cell, suggesting a merocrine secretory mechanism. Enterochromaffin cells were identified by their location between the basal regions of other crypt cells and by their unique intracytoplasmic granules. PMID:14064112

  6. Analysis of Small Intestinal Microbiome in Children with Autism

    DTIC Science & Technology

    2013-01-01

    AD_________________ Award Number: W81XWH-10-1-0477 TITLE: Analysis of Small Intestinal Microbiome ...of Small Intestinal Microbiome in Children with Autism 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-10-1-0477 5c. PROGRAM ELEMENT NUMBER 6...will be requested to complete this project. 15. SUBJECT TERMS- Autism, duodenal microbiome , DNA extraction, PCR, sequencing 16. SECURITY

  7. Oral exposure to the organophosphorus insecticide, Monocrotophos induces intestinal dysfunction in rats.

    PubMed

    Vismaya; Rajini, P S

    2014-09-01

    There is limited experimental evidence to imply the role of organophosphorus insecticides on intestinal dysfunctions. Residues of Monocrotophos (MCP), above maximum residue limits (MRL), have been reported in fruits and vegetables from various parts of India. Hence, in this study, we investigated the potential of MCP to induce intestinal dysfunction in rats. MCP was administered orally to rats at sublethal doses (0.45, 0.9 and 1.8 mg/kgb.w/d) for 30 days. MCP at the highest dose significantly increased the unit weight of the small intestine. MCP increased the activities of intestinal brush border disaccharidases, intestinal alkaline phosphatase, glycyl-glycine dipeptidase, and Na(+)/K(+)-ATPase while it decreased cholesterol: phospholipid ratio. Histology and scanning electron microscopy of small intestine of MCP treated rats revealed disruption in terms of congestion, increased length of villi, goblet cell hyperplasia, infiltration of inflammatory cells and necrotic villi tip. Further, the intestinal transit rate was found to be increased in MCP treated rats. Collectively, our findings provide evidence that repeated oral intake of MCP has the propensity to alter small intestinal structure and functions, which might lead to intestinal dysfunctions and abnormal nutrient uptake and thereby affect the human health. Although we have employed doses, which are higher than those likely to be encountered as residues, we speculate that further studies should be performed to determine whether MCP residues in foods in the long-term will interfere with the digestive capacity of the small intestine and thus exert adverse effects on the health of human.

  8. Role of dietary fiber in formation and prevention of small intestinal ulcers induced by nonsteroidal anti-inflammatory drug.

    PubMed

    Satoh, Hiroshi

    2010-01-01

    Recent advances in endoscopic techniques such as capsule endoscopy have revealed that nonsteroidal anti-inflammatory drugs (NSAIDs) often cause ulcers in the small intestine in humans, but there are few effective agents for treatment of small intestinal ulcers. Although the pathogenesis of NSAID-induced intestinal ulcer has been widely studied, dietary factors have seldom been considered. In the present review, the role of dietary fiber (DF) in the formation of NSAID-induced intestinal ulcers is discussed. In previous studies, small intestinal lesions were not observed when NSAIDs were administered to fasted rats, dogs, and cats, but were observed in conventionally-fed animals, suggesting the importance of feeding in the formation of intestinal lesions induced by NSAIDs. However, in animals fed diets containing low or no DF, indomethacin (IND) did not produce lesions in the small intestine, but did produce lesions in animals fed diets supplemented with insoluble dietary fiber (IDF, cellulose). The results suggest that IDF in the diet plays an important role in the formation of NSAID-induced intestinal lesions. On the other hand, addition of soluble dietary fibers (SDFs) such as pectin or mucin to regular diet markedly decreased NSAID-induced intestinal lesions. Thus, IDF and SDF have opposing effects on IND-induced intestinal lesions, i.e., IDF is harmful while SDF is protective. SDFs potentially represent a novel and safe means for protecting the small intestine against NSAID-induced intestinal lesions.

  9. Influence of the Gut Microflora and of Biliary Constituents on Morphological Changes in the Small Intestine in Obstructive Jaundice

    PubMed Central

    Quraishy, M. Saeed; Chescoe, Dawn; Mullervy, Jenny; Coates, Marie; Hinton, Richard H.

    1996-01-01

    Increased amounts of intestinal endotoxin are absorbed in obstructive jaundice. The precise mechanism is not known but the increased absorption may arise from alterations in the luminal contents, in the intestinal flora, in the gut wall or in interactions between all three. To examine the effects of the intestinal flora we have compared the morphological changes in the small intestine in obstructive jaundice in germ free and conventional rats while the effects of bile constituents have been examined by addition of bile constituents to the diet of bile duct ligated rats. Changes in the intestine were examined, histologically, by enzyme histochemistry, and by transmission and scanning electron microscopy. The results showed no differences in response between germ free and conventional rats. Feeding of diets containing bile salts exacerbated the lesion. Feeding of diets containing cholesterol, however, reduced the degree of intestinal changes produced by cholestasis and completely antagonised the increase in damage caused by feeding of bile salts. PMID:9187547

  10. 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

  11. 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).

  12. Gastrin attenuates ischemia-reperfusion-induced intestinal injury in rats

    PubMed Central

    Liu, Zhihao; Luo, Yongli; Cheng, Yunjiu; Zou, Dezhi; Zeng, Aihong; Yang, Chunhua

    2016-01-01

    Intestinal ischemia-reperfusion (I/R) injury is a devastating complication when the blood supply is reflowed in ischemic organs. Gastrin has critical function in regulating acid secretion, proliferation, and differentiation in the gastric mucosa. We aimed to determine whether gastrin has an effect on intestinal I/R damage. Intestinal I/R injury was induced by 60-min occlusion of the superior mesenteric artery followed by 60-min reperfusion, and the rats were induced to be hypergastrinemic by pretreated with omeprazole or directly injected with gastrin. Some hypergastrinemic rats were injected with cholecystokinin-2 (CCK-2) receptor antagonist prior to I/R operation. After the animal surgery, the intestine was collected for histological analysis. Isolated intestinal epithelial cells or crypts were harvested for RNA and protein analysis. CCK-2 receptor expression, intestinal mucosal damage, cell apoptosis, and apoptotic protein caspase-3 activity were measured. We found that high gastrin in serum significantly reduced intestinal hemorrhage, alleviated extensive epithelial disruption, decreased disintegration of lamina propria, downregulated myeloperoxidase activity, tumor necrosis factor-α, and caspase-3 activity, and lead to low mortality in response to I/R injury. On the contrary, CCK-2 receptor antagonist L365260 could markedly impair intestinal protection by gastrin on intestinal I/R. Severe edema of mucosal villi with severe intestinal crypt injury and numerous intestinal villi disintegrated were observed again in the hypergastrinemic rats with L365260. The survival in the hypergastrinemic rats after intestinal I/R injury was shortened by L365260. Finally, gastrin could remarkably upregulated intestinal CCK-2 receptor expression. Our data suggest that gastrin by omeprazole remarkably attenuated I/R induced intestinal injury by enhancing CCK-2 receptor expression and gastrin could be a potential mitigator for intestinal I/R damage in the clinical setting. PMID

  13. 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

  14. 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.

  15. 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

  16. Distinct human stem cell populations in small and large intestine.

    PubMed

    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.

  17. 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

  18. The transit of dosage forms through the small intestine.

    PubMed

    Yuen, Kah-Hay

    2010-08-16

    The human small intestine, with its enormous absorptive surface area, is invariably the principal site of drug absorption. Hence, the residence time of a dosage form in this part of the gut can have a great influence on the absorption of the contained drug. Various methods have been employed to monitor the gastrointestinal transit of pharmaceutical dosage forms, but the use of gamma-scintigraphy has superceded all the other methods. However, careful consideration of the time interval for image acquisition and proper analysis of the scintigraphic data are important for obtaining reliable results. Most studies reported the mean small intestinal transit time of various dosage forms to be about 3-4h, being closely similar to that of food and water. The value does not appear to be influenced by their physical state nor the presence of food, but the timing of food intake following administration of the dosage forms can influence the small intestinal transit time. While the mean small intestinal transit time is quite consistent among dosage forms and studies, individual values can vary widely. There are differing opinions regarding the effect of density and size of dosage forms on their small intestinal transit properties. Some common excipients employed in pharmaceutical formulations can affect the small intestinal transit and drug absorption. There is currently a lack of studies regarding the effects of excipients, as well as the timing of food intake on the small intestinal transit of dosage forms and drug absorption.

  19. How Is Small Intestine Adenocarcinoma Diagnosed?

    MedlinePlus

    ... the intestine a foot at a time. An advantage of this over capsule endoscopy is that the ... Life Events College Relay For Life Donate a Car Ways to Give Memorial Giving Planned Giving Leadership ...

  20. INTESTINAL TRIGLYCERIDE ABSORPTION IN THE RAT

    PubMed Central

    Cardell, Robert R.; Badenhausen, Susan; Porter, Keith R.

    1967-01-01

    This report provides information on the morphology of fat absorption in rat intestinal epithelial cells. Three types of experiments were performed: (a) intubation of corn oil into fasted rats, (b) injection of physiological fatty-chyme prepared from fat-fed donor rats into ligated segments of jejunum of fasted animals, and (c) administration of electron-opaque particles in corn oil and markers given concurrently with the fat. These results support the hypothesis that fat is absorbed by selective diffusion of monoglycerides and fatty acids from micelles rather than by pinocytosis of unhydrolized triglycerides. Evidence is presented that the pits between the microvilli, previously believed to function in the transport of fat, are not involved in this process. Instead they appear to contribute their contents to lysosomes in the apical cytoplasm. Arguments are offered that the monoglycerides and fatty acids diffuse from the micelle while the latter is associated with the microvillous membrane of the absorptive cell. These micellar components penetrate the plasma membrane and diffuse into the cytoplasmic matrix where they encounter the SER. Triglyceride synthesis occurs in the SER and results in the deposition of fat droplets within its lumina. The synthesis of triglycerides and their sequestration into the SER establishes an inward diffusion gradient of monoglycerides and fatty acids. PMID:6033529

  1. Adipose triglyceride lipase is a TG hydrolase of the small intestine and regulates intestinal PPARα signaling.

    PubMed

    Obrowsky, Sascha; Chandak, Prakash G; Patankar, Jay V; Povoden, Silvia; Schlager, Stefanie; Kershaw, Erin E; Bogner-Strauss, Juliane G; Hoefler, Gerald; Levak-Frank, Sanja; Kratky, Dagmar

    2013-02-01

    Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme mediating triglyceride (TG) hydrolysis. The lack of ATGL results in TG accumulation in multiple tissues, underscoring the critical role of ATGL in maintaining lipid homeostasis. Recent evidence suggests that ATGL affects TG metabolism via activation of peroxisome proliferator-activated receptor α (PPARα). To investigate specific effects of intestinal ATGL on lipid metabolism we generated mice lacking ATGL exclusively in the intestine (ATGLiKO). We found decreased TG hydrolase activity and increased intracellular TG content in ATGLiKO small intestines. Intragastric administration of [(3)H]trioleate resulted in the accumulation of radioactive TG in the intestine, whereas absorption into the systemic circulation was unchanged. Intraperitoneally injected [(3)H]oleate also accumulated within TG in ATGLiKO intestines, indicating that ATGL mobilizes fatty acids from the systemic circulation absorbed by the basolateral side from the blood. Down-regulation of PPARα target genes suggested modulation of cholesterol absorption by intestinal ATGL. Accordingly, ATGL deficiency in the intestine resulted in delayed cholesterol absorption. Importantly, this study provides evidence that ATGL has no impact on intestinal TG absorption but hydrolyzes TGs taken up from the intestinal lumen and systemic circulation. Our data support the role of ATGL in modulating PPARα-dependent processes also in the small intestine.

  2. 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.

  3. Effects of phorbol esters on fluid transport and blood flow in the small intestine

    SciTech Connect

    Sjoeqvist, A.; Henderson, L.S.; Fondacaro, J.D.

    1986-07-01

    Studies were designed to examine the effects of phorbol esters on intestinal fluid transport and blood flow in the anesthetized cat and enteropooling in the conscious rat. Intraluminal administration of phorbol ester into a segment of isolated small bowel produced a copious intestinal secretion and a concomitant mesenteric hyperemia in the cat. Net fluid movement in the intestine was converted from absorption in the control state to secretion following phorbol ester administration. Intravenous atropine reduced the phorbol ester-induced secretion by 56%; clonidine abolished the remaining secretory response. In the rat, intragastric administration of phorbol ester produced enteropooling comparable to that of other potent intestinal secretagogues. Since phorbol esters are known to activate protein kinase C, these suggest that activation of protein kinase C in the small intestine may lead to a full secretory response. The evidence suggests that this secretion is accompanied by a metabolic hyperemia. These results suggest that protein kinase C plays an important role in the regulation of intestinal fluid transport.

  4. Chromium absorption in the vascularly perfused rat intestine

    SciTech Connect

    Dowling, H.J.; Offenbacher, E.G.; Pi-Sunyer, F.X.

    1986-03-01

    The mechanism of chromium (Cr) absorption by the rat small intestine was investigated using a double perfusion technique wherein the luman of the small intestine and the vasculature supplying it were separately perfused. The intestinal perfusate (IP) was a nutrient-rich tissue culture medium (TCM) with added inorganic Cr and /sup 51/Cr. The vascular perfusate (VP) was a Krebs-Ringer bicarbonate solution (KRB) containing 4.7% dextran, 0.1% glucose and 5% human serum. Cr absorption was calculated by the amount of /sup 51/Cr detected in the VP. To determine the transport mechanism for Cr, its absorption into the VP was measured at various Cr concentrations of the IP ranging from 10-400 ppb CrCl/sub 3/. The amount of Cr absorbed into the blood rose linearly with the intestinal Cr concentration suggesting a process of simple diffusion. Manipulations of the VP and IP constituents were made to investigate their effects on Cr absorption. When serum was omitted from the VP, Cr adsorption was suppressed, suggesting that serum component(s) are necessary for optimal Cr absorption. When either of 2 plasma transport proteins (apo-transferrin, albumin) were added to the serum-free VP at physiological levels, Cr absorption returned to, but did not exceed, control levels. When the TCM was replaced with a KRB solution; Cr absorption was suppressed indicating that there are nutrient(s) of the TCM which facilitate Cr absorption. Further suppression occurred when a Cr concentration gradient opposing Cr absorption was created (IP at 100 ppb Cr, VP at 400 ppb Cr).

  5. Mucositis and non-invasive markers of small intestinal function.

    PubMed

    Tooley, Katie L; Howarth, Gordon S; Butler, Ross N

    2009-05-01

    Mucositis is a common and debilitating side effect of chemotherapy that manifests due to the inability of chemotherapy agents to discriminate between normal and neoplastic cells. This results in ulcerating lesions lining the gastrointestinal tract. Moreover, the development of efficacious treatments for small intestinal mucositis has been hindered as the pathobiology of mucositis is still not fully understood. The small intestine is an extensive organ which is largely inaccessible by conventional means. Non-invasive biomarkers such as small intestinal permeability, H(2) breath tests, serum citrulline tests and the (13)C-sucrose breath test (SBT) have emerged as potential markers of small intestinal function. The SBT is emerging as the more appropriate biomarker to assess chemotherapy-induced mucositis in cancer patients and animal models, where it measures the decrease in sucrase activity associated with villus blunting and crypt disruption. The SBT has been successfully applied to detect mucositis induced by different classes of chemotherapy agents and has been used successfully to monitor small intestinal function with a range of candidate anti-mucositis treatments. We propose the SBT a superior biomarker of small intestinal function that could be successfully applied in clinical practice for monitoring the development of mucositis in cancer patients undergoing chemotherapy.

  6. Colonization by lactobacilli of piglet small intestinal mucus.

    PubMed

    Rojas, M; Conway, P L

    1996-11-01

    The colonization potential of lactobacilli was investigated using small intestinal mucus extracts from 35-d-old pigs. Mucus-secreting tissue from the small intestine of piglets was gently rinsed to remove contents and then shaken in buffer to release mucus from the surface. Numbers of lactobacilli in different portions of the small intestine of 35-d-old pigs were enumerated. Also, mucus isolated from the small intestine of pigs was investigated for its capacity to support the growth of lactobacilli. Results indicated that Lactobacillus spp. inhabit the mucus layer of the small intestine and can grow and adhere to ileal mucus. From adhesion studies of Lactobacillus fermentum 104R to mucus analysed by Scatchard plot, it is suggested that an associating system showing positive cooperativity is involved. Proteinaceous compounds(s) involved in the adhesion to mucus were detected in the spent culture fluid from the growth of strain 104R. Studies are continuing in order to identify and characterize the adhesion-promoting protein(s). From the data, it is proposed that lactobacilli colonize the mucus layer of the small intestine of pigs.

  7. Normal and abnormal electrical propagation in the small intestine.

    PubMed

    Lammers, W J E P

    2015-02-01

    As in other muscular organs, small intestinal motility is determined to a large degree by the electrical activities that occur in the smooth muscle layers of the small intestine. In recent decades, the interstitial cells of Cajal, located in the myenteric plexus, have been shown to be responsible for the generation and propagation of the electrical impulse: the slow wave. It was also known that the slow waves as such do not cause contraction, but that the action potentials ('spikes') that are generated by the slow waves are responsible for the contractions. Recording from large number of extracellular electrodes simultaneously is one method to determine origin and pattern of propagation of these electrical signals. This review reports the characteristics of slow wave propagation through the intestinal tube, the occurrence of propagation blocks along its length, which explains the well-known decrease in frequency, and the specific propagation pattern of the spikes that follow the slow waves. But the value of high-resolution mapping is highest in discovering and analysing mechanisms of arrhythmias in the gut. Most recently, circus movements (also called 're-entries') have been described in the small intestine in several species. Moreover, several types of re-entries have now been described, some similar to what may occur in the heart, such as functional re-entries, but others more unique to the small intestine, such as circumferential re-entry. These findings seem to suggest the possibilities of hitherto unknown pathologies that may be present in the small intestine.

  8. 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.

  9. Medicinal foodstuffs. X. Structures of new triterpene glycosides, gymnemosides-c, -d, -e, and -f, from the leaves of Gymnema sylvestre R. Br.: influence of gymnema glycosides on glucose uptake in rat small intestinal fragments.

    PubMed

    Yoshikawa, M; Murakami, T; Matsuda, H

    1997-12-01

    Following the characterization of gymnemosides-a and -b, new triterpene glycosides, gymnemosides-c, -d, -e, and -f, were isolated from the leaves of Gymnema (G.) sylvestre R. BR. Their chemical structures were elucidated on the basis of chemical and physicochemical evidence as follows: 21-O-benzoyl-28-O-acetylgymnemagenin 3-O-beta-D-glucopyranosiduronic acid (gymnemoside-c), 23-O-[beta-D-xylopyranosyl (1-->6)-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranosyl] gymnestrogenin (gymnemoside-d), 23-O-[beta-D-xylopyranosyl (1-->6)-beta-D-glucopyranosyl (1-->6)-beta-D- glucopyranosyl]-28-O-[beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranosyl] 23-hydroxylongispinogenin (gymnemoside-e), 23-O-[beta-D-xylopyranosyl (1-->6)-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranosyl]-28-O-[beta-O-glucopyranosyl (1-->6)-beta-D-glucopyranosyl] 3 beta,16 beta,23,28-tetrahydroxyolean-18-ene (gymnemoside-f). The inhibitory effects of gymnemosides-c, -d, -e, and -f and principal triterpene glycosides from G. sylvestre on glucose uptake in rat small intestinal fragments were examined, and gymnemic acids II, III, and IV, gymnemasaponin V, and gymnemoside-f were found to exhibit the inhibitory activity.

  10. 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

  11. 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

    2015-10-12

    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.

  12. 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.

  13. Hymenolepis diminuta: analysis of the expression of Toll-like receptor genes and protein (TLR3 and TLR9) in the small and large intestines of rats.

    PubMed

    Kosik-Bogacka, Danuta I; Wojtkowiak-Giera, Agnieszka; Kolasa, Agnieszka; Baranowska-Bosiacka, Irena; Lanocha, Natalia; Wandurska-Nowak, Elzbieta; Izabela, Gutowska; Salamatin, Ruslan; Jagodzinski, Paweł P

    2014-10-01

    Toll-like receptors (TLRs) play a fundamental role in the rapid activation of innate immune responses to a variety of pathogen-associated molecular patterns (PAMPs). In a previous study we observed an increase in the level of expression of TLR2 and TLR4 mRNA in the jejunum and colon during experimental hymenolepidosis in rats. In this study, we performed a quantitative real-time polymerase chain reaction (qRT-PCR), Western blot analysis and immunohistochemical staining of TLR3 and TLR9 receptors during experimental hymenolepidosis in rats. The levels of mRNA and protein expression of TLR3 and TLR9 in the jejunum had increased at 16 days post Hymenolepis diminuta infection (dpi) in the case of TLR3 and at 16 and 25 dpi in the case of TLR9. In the colon the expression of TLR3 and TLR9 had increased at 16, 25 and 40 dpi. The results of the immunohistochemical reactions showed that H. diminuta infected rats (16, 25, 40 and 60 dpi) exhibited changes in TLR3 and TLR9 localization and intensity in the epithelial cells of the jejunum and colon. The changes in the level of TLR3 and TLR9 expression may confirm involvement of the innate immune system in the pathomechanism of hymenolepidosis.

  14. 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

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

    PubMed

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

    2015-01-01

    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.

  16. Intestinal absorption of biotin in the rat

    SciTech Connect

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

    1986-07-01

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

  17. Intestinal anisakiasis as a rare cause of small bowel obstruction.

    PubMed

    Kojima, Gotaro; Usuki, Shinichiro; Mizokami, Ken; Tanabe, Marianne; Machi, Junji

    2013-09-01

    Anisakiasis, a parasitic infection by larvae of the nematode Anisakis found in raw or undercooked saltwater fish, mostly involves stomach but rarely small intestine. We report a rare case of a 61-year-old man who presented with abdominal pain and developed small bowel obstruction caused by intestinal anisakiasis. Abdominal computed tomography revealed segmental edema of the intestinal wall with proximal dilatation. The patient underwent urgent laparotomy because strangulated small bowel obstruction was suspected. A localized portion of the intestine around jejunoileal junction was found to be erythematous, edematous, and hardened, which was resected. The resected specimen showed a linear whitish worm, Anisakis simplex, penetrating into the intestinal mucosa. It is often clinically challenging to consider intestinal anisakiasis in the differential diagnosis because of its nonspecific abdominal symptoms and findings. Although gastrointestinal anisakiasis is still rare in the United States, the incidence is expected to rise given the growing popularity of Japanese cuisine such as sushi or sashimi. Anisakiasis should be considered as one of the differential diagnoses in patients with nonspecific abdominal symptoms after consumption of raw or undercooked fish.

  18. Characteristics of Small Intestinal Diseases on Single-Balloon Enteroscopy

    PubMed Central

    Tao, Zhang; Liu, G.X.; Cai, L.; Yu, H.; Min, X.J.; Gan, H.T.; Yang, K.; SQ, Li; Yan, J.; Chen, L.; Tan, Q.H.; Wu, J.C.; Huang, X.L.

    2015-01-01

    Abstract The small intestine has been considered inaccessible for a long term. The development of single-balloon endoscopy has greatly improved the diagnosis and treatment possibilities for small intestinal diseases. In this study, we aimed to explore the demographic characteristics and small intestinal diseases of patients who underwent single-balloon enteroscopy between 2009 and 2014 at our endoscopy center. We determined the enteroscopic findings for each small intestinal disease and the most susceptible age groups. In total, 186 patients were included in the study. Their mean age was 45.87 ± 15.77 years. Patients who underwent single-balloon enteroscopy were found to have neoplasms (most common age group: 14–45 years, most common lesion location: jejunum), lymphoma (46–59 and 60–74 years, ileum), protuberant lesions (45–59 years, jejunum), inflammation (14–45 and 46–59 years, ileum), benign ulcers (14–45 years, jejunum), diverticulum (14–45 years, ileum), vascular malformations (60–74 years, jejunum), polyps (14–45 years, jejunum), Crohn's disease (14–45 years, jejunum), hookworm infection (14–45 years, jejunum), lipid pigmentation (14–45 and 46–59 years, jejunum), undetermined bleeding (46–59 years, ileum), or undetermined stenosis (31 years, duodenum). Each small intestinal disease had distinct enteroscopic findings. PMID:26496270

  19. 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.

  20. Pancreatic digestive enzyme blockade in the small intestine prevents insulin resistance in hemorrhagic shock.

    PubMed

    DeLano, Frank A; Schmid-Schönbein, Geert W

    2014-01-01

    Hemorrhagic shock is associated with metabolic defects, including hyperglycemia and insulin resistance, but the mechanisms are unknown. We recently demonstrated that reduction of the extracellular domain of the insulin receptor by degrading proteases may lead to a reduced ability to maintain normal plasma glucose values. In shock, transfer of digestive enzymes from the lumen of the intestine into the systemic circulation after breakdown of the intestinal mucosal barrier causes inflammation and organ dysfunction. Suppression of the digestive enzymes in the lumen of the intestine with protease inhibitors is effective in reducing the level of the inflammatory reactions. To determine the degree to which blockade of digestive enzymes affects insulin resistance in shock, rats were exposed to acute hemorrhagic shock (mean arterial pressure of 30 mmHg for 2 h) at which time all shed blood volume was returned. Digestive proteases in the intestine were blocked with a serine protease inhibitor (tranexamic acid in polyethylene glycol and physiological electrolyte solution), and the density of the insulin receptor was measured with immunohistochemistry in the mesentery microcirculation. The untreated rat without enzyme blockade had significantly attenuated levels of insulin receptor density as compared with control and treated rats. Blockade of the digestive proteases after 60 min of hypotension in the lumen of the small intestine led to a lesser decrease in insulin receptor density compared with controls without protease blockade. Glucose tolerance test indicates a significant increase in plasma glucose levels 2 h after hemorrhagic shock, which are reduced to control values in the presence of protease inhibition in the lumen of the intestine. The transient reduction of the plasma glucose levels after an insulin bolus is significantly attenuated after shock but is restored when digestive enzymes in the lumen of the intestine are blocked. These results suggest that in

  1. Viability of the vascularly perfused, recirculating rat intestine and intestine-liver preparations

    SciTech Connect

    Hirayama, H.; Xu, X.; Pang, K.S. )

    1989-08-01

    Function and stability of vascularly perfused, recirculating in situ rat intestine (I) and intestine-liver (IL) preparations were evaluated in fasted and nonfasted rats because these techniques may be readily applied in drug metabolism studies. The rat intestine was perfused with blood medium (7.5 ml/min) via the superior mesenteric artery, with the venous outflow draining into the portal vein, which, together with hepatic arterial flow (2.5 ml/min), constituted the total blood flow (10 ml/min) to the liver. Maintenance of intestinal membrane integrity was observed. Rapid ({sup 14}C)glucose absorption against a concentration gradient and a lack of ({sup 3}H)-polyethylene glycol 4000 (PEG 4000, less than 4%) and Evans blue absorption by the recirculating I and IL preparations resulted after bolus injections of these markers into the pyloric end of the duodenum. Other indexes that revealed stable intestinal and liver functions were the following: preservation of reservoir perfusate volume, constancy in perfusion pressure, bile flow, and hemoglobin concentrations, evidence of intestinal glucose utilization and liver glucose production, and a lack of significant leakage of serum glutamic oxalic transaminase. The intestine and liver consumed oxygen at relatively constant rates, but the consumption rates for the fasted tissues (I or L) were significantly higher than those for nonfasted tissues. These results indicate that the vascularly perfused I and IL preparations were maintained in a viable and stable state for a 2-h perfusion period.

  2. Remodeling Intestinal Flora with Sleeve Gastrectomy in Diabetic Rats

    PubMed Central

    Huang, Xiaofei; Weng, Pan; Zhang, Huixin; Lu, Yingli

    2014-01-01

    Objective. As a complicated symbiotic system, intestinal flora is reported closely related to the development of type 2 diabetes recently. Sleeve gastrectomy is one of the approaches of bariatric surgery and could improve blood glucose control in type 2 diabetes patients. This study was to explore the relationship between remodeled intestinal flora and glucose metabolism in diabetic rats. Methods. 20 male diabetic rats were operated; 10 of them underwent sleeve gastrectomy, and 10 of them underwent sham operation. Meanwhile 10 male normal rats underwent sleeve gastrectomy as control. The animals' weight and FBG had been measured. The composition changes of intestinal flora were detected by 16S rDNA sequence analysis. Results. In diabetic rats, weight and fasting blood glucose decreased significantly after sleeve gastrectomy. However, there was no significant change for weight and blood glucose in normal rats after operation. The intestinal flora of diabetic rats reduced in the proportion of Firmicutes and increased in the proportion of Bacteroidetes after sleeve gastrectomy. Conclusion. The change of dominant microorganisms in intestinal flora might play an important role in the glucose metabolism. PMID:25165722

  3. Cryptosporidium, chronic diarrhoea and the proximal small intestinal mucosa.

    PubMed Central

    Phillips, A D; Thomas, A G; Walker-Smith, J A

    1992-01-01

    The association between Cryptosporidium, chronic diarrhoea and a proximal small intestinal mucosal enteropathy was reviewed over a six and a half year period. One hundred and twenty three children with cryptosporidiosis and no clinical evidence of immune deficiency were identified. 50% of children excreting only Cryptosporidium had chronic diarrhoea. Most cases (63%) of chronic diarrhoea occurred in the first two years of life. A mild to moderate enteropathy was present in all nine children undergoing a small intestinal biopsy and seven showed the presence of Cryptosporidium adhering to villous epithelium. All patients eventually recovered spontaneously. Cryptosporidium is a cause of chronic diarrhoea and a proximal small intestinal mucosal enteropathy in children without immune deficiency. Screening for the parasite should be part of the investigative procedures in children with chronic diarrhoea. Images Figure 4 PMID:1398230

  4. Diagnosis and management of small intestinal bacterial overgrowth.

    PubMed

    Bohm, Matthew; Siwiec, Robert M; Wo, John M

    2013-06-01

    Small intestinal bacterial overgrowth (SIBO) can result from failure of the gastric acid barrier, failure of small intestinal motility, anatomic alterations, or impairment of systemic and local immunity. The current accepted criteria for the diagnosis of SIBO is the presence of coliform bacteria isolated from the proximal jejunum with >10(5) colony-forming units/mL. A major concern with luminal aspiration is that it is only one random sampling of the small intestine and may not always be representative of the underlying microbiota. A new approach to examine the underlying microbiota uses rapid molecular sequencing, but its clinical utilization is still under active investigation. Clinical manifestations of SIBO are variable and include bloating, flatulence, abdominal distention, abdominal pain, and diarrhea. Severe cases may present with nutrition deficiencies due to malabsorption of micro- and macronutrients. The current management strategies for SIBO center on identifying and correcting underlying causes, addressing nutrition deficiencies, and judicious utilization of antibiotics to treat symptomatic SIBO.

  5. Heterogeneity across the murine small and large intestine.

    PubMed

    Bowcutt, Rowann; Forman, Ruth; Glymenaki, Maria; Carding, Simon Richard; Else, Kathryn Jane; Cruickshank, Sheena Margaret

    2014-11-07

    The small and large intestine of the gastrointestinal tract (GIT) have evolved to have discrete functions with distinct anatomies and immune cell composition. The importance of these differences is underlined when considering that different pathogens have uniquely adapted to live in each region of the gut. Furthermore, different regions of the GIT are also associated with differences in susceptibility to diseases such as cancer and chronic inflammation. The large and small intestine, given their anatomical and functional differences, should be seen as two separate immunological sites. However, this distinction is often ignored with findings from one area of the GIT being inappropriately extrapolated to the other. Focussing largely on the murine small and large intestine, this review addresses the literature relating to the immunology and biology of the two sites, drawing comparisons between them and clarifying similarities and differences. We also highlight the gaps in our understanding and where further research is needed.

  6. Developmental morphology of the small intestine of African ostrich chicks.

    PubMed

    Wang, J X; Peng, K M

    2008-12-01

    The objective of this study was to investigate the morphological development of the small intestine of African ostrich chicks and to examine the changes in the number of goblet cells therein by observing the gross anatomy and performing histochemistry and morphometry. The BW; length, height, and width of the villi; muscle thickness; depth of the crypts; and number of goblet cells in the intestinal villi and crypts were measured on neonatal d 1, 45, 90, and 334. Our results revealed that the weights of the duodenum, jejunum, and ileum (relative to the BW) peaked on d 90, 45, and 45, respectively, and tended to decline thereafter. The villus height and width and muscle thickness in the small intestine were positively correlated with the age of the birds. The ratio of the villus height to the crypt depth differed among the segments of the small intestine and at the different time points. The number of goblet cells in the intestinal villi and crypts increased rapidly up to postnatal d 45 and then decreased rapidly between d 45 and 90. The number of goblet cells in the villi was greatest in the jejunum on d 1 and in the ileum on d 45, whereas that in the crypt was greatest in the ileum on d 1 and 90 and in the duodenum on d 45. These results suggest that the small intestine develops gradually from postnatal d 1 to 90 and that the period up to postnatal d 45 is marked by significant developmental changes in the parameters reflective of the digestive capacity, such as the weight, length, and surface area of the intestine and the number of goblet cells. Therefore, in reared African ostrich chicks, feed management should be enhanced between postnatal d 1 and 45.

  7. 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

  8. 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.

  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. Ischemic postconditioning provides protection against ischemia-reperfusion injury in intestines of rats.

    PubMed

    Chu, Weiwei; Li, Sheng; Wang, Shanwei; Yan, Aili; Nie, Lei

    2015-01-01

    In the present study, we investigated the protective role of ischemic postconditioning (IPOST) against intestine ischemia-reperfusion (I/R) injury in rats. Male Sprague-Dawley rats were divided into sham-operation group (S), I/R group (I/R), ischemic preconditioning group (IPC), ischemic postconditioning group (IPOST). After reperfusion, small intestines were resected for histopathologic evaluations. To evaluate DNA fragmentation, resolving agarose gel electrophoresis was performed. To measure cellular apoptotic rates in intestine tissues, we performed TUNEL staining. To examine lipid peroxidation, production of superoxide radicals and tissue neutrophil infiltration, we tested the content of malondialdehyde and activities of superoxidase dismutase and myeloperoxidase in intestine tissues, respectively. Under light microscope, intestinal mucosal impairment in IPOST and IPC groups was found milder than that in I/R group (P < 0.05). The number of apoptosis cells in I/R group was significantly higher than that in IPOST and IPC groups (P < 0.05). The content of malondialdehyde and activity of myeloperoxidase were significantly reduced in IPOST group and IPC group compared with I/R group, but the activity of superoxidase dismutase in IPOST group and IPC group was enhanced compared with I/R group (P < 0.05). These results suggest that IPOST results in protection against intestine I/R injury, which may be related to reduced production of reactive oxygen species, enhanced activities of antioxidant systems and inhibited apoptosis of intestinal mucosal cells.

  11. Nonlinear intestinal absorption kinetics of cefuroxime axetil in rats.

    PubMed Central

    Ruiz-Balaguer, N; Nacher, A; Casabo, V G; Merino, M

    1997-01-01

    Cefuroxime is commercially available for parenteral administration as a sodium salt and for oral administration as cefuroxime axetil, the 1-(acetoxy)ethyl ester of the drug. Cefuroxime axetil is a prodrug of cefuroxime and has little, if any, antibacterial activity until hydrolyzed in vivo to cefuroxime. In this study, the absorption of cefuroxime axetil in the small intestines of anesthetized rats was investigated in situ, by perfusion at four concentrations (11.8, 5, 118 and 200 microM). Oral absorption of cefuroxime axetil can apparently be described as a specialized transport mechanism which obeys Michaelis-Menten kinetics. Parameters characterizing absorption of prodrug in free solution were obtained: maximum rate of absorption (Vmax) = 289.08 +/- 46.26 microM h-1, and Km = 162.77 +/- 31.17 microM. Cefuroxime axetil transport was significantly reduced in the presence of the enzymatic inhibitor sodium azide. On the other hand, the prodrug was metabolized in the gut wall through contact with membrane-bound enzymes in the brush border membrane before absorption occurred. This process reduces the prodrug fraction directly available for absorption. From a bioavailability point of view, therefore, the effects mentioned above can explain the variable and poor bioavailability following oral administration of cefuroxime axetil. Thus, future strategies in oral cefuroxime axetil absorption should focus on increasing the stability of the prodrug in the intestine by modifying the prodrug structure and/or targeting the compound to the absorption site. PMID:9021205

  12. Role of intestinal cytochrome p450 enzymes in diclofenac-induced toxicity in the small intestine.

    PubMed

    Zhu, Yi; Zhang, Qing-Yu

    2012-11-01

    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.

  13. Diacylglycerol acyltransferase-1 inhibition enhances intestinal fatty acid oxidation and reduces energy intake in rats.

    PubMed

    Schober, Gudrun; Arnold, Myrtha; Birtles, Susan; Buckett, Linda K; Pacheco-López, Gustavo; Turnbull, Andrew V; Langhans, Wolfgang; Mansouri, Abdelhak

    2013-05-01

    Acyl CoA:diacylglycerol acyltransferase-1 (DGAT-1) catalyzes the final step in triacylglycerol (TAG) synthesis and is highly expressed in the small intestine. Because DGAT-1 knockout mice are resistant to diet-induced obesity, we investigated the acute effects of intragastric (IG) infusion of a small molecule diacylglycerol acyltransferase-1 inhibitor (DGAT-1i) on eating, circulating fat metabolites, indirect calorimetry, and hepatic and intestinal expression of key fat catabolism enzymes in male rats adapted to an 8 h feeding-16 h deprivation schedule. Also, the DGAT-1i effect on fatty acid oxidation (FAO) was investigated in enterocyte cell culture models. IG DGAT-1i infusions reduced energy intake compared with vehicle in high-fat diet (HFD)-fed rats, but scarcely in chow-fed rats. IG DGAT-1i also blunted the postprandial increase in serum TAG and increased β-hydroxybutyrate levels only in HFD-fed rats, in which it lowered the respiratory quotient and increased intestinal, but not hepatic, protein levels of Complex III of the mitochondrial respiratory chain and of mitochondrial hydroxymethylglutaryl-CoA synthase. Finally, the DGAT-1i enhanced FAO in CaCo2 (EC50 = 0.3494) and HuTu80 (EC50 = 0.00762) cells. Thus, pharmacological DGAT-1 inhibition leads to an increase in intestinal FAO and ketogenesis when dietary fat is available. This may contribute to the observed eating-inhibitory effect.

  14. The protective effect of N-acetylcysteine against acrylamide toxicity in liver and small and large intestine tissues.

    PubMed

    Altinoz, E; Turkoz, Y; Vardi, N

    2015-01-01

    The aim of this study was to investigate the protective effects of N-acetylcysteine against acrylamide toxicity in liver and small and large intestine tissues in rats.The rats were divided into four groups. Acrylamide administration increased MDA levels in all tissues significantly (p < 0.05). But acrylamide+NAC administration decreased MDA levels significantly as compared to the acrylamide group, and lowered it to a level close to the control group values (p < 0.05). GSH levels in liver and small intestine tissues reduced significantly in the acrylamide group (p < 0.05). But acrylamide+NAC administration increased GSH levels significantly in all tissues. Whereas GST activity decreased significantly in the acrylamide group in liver and small intestine tissues as compared to the other groups (p < 0.05), the GST activity increased significantly in the acrylamide+NAC group in all tissues as compared to the acrylamide group (p < 0.05). Liver histopathology showed that the liver epithelial cells were damaged significantly in the acrylamide group. Small intestine histopathology showed that the intestinal villous epithelial cells were damaged significantly in the acrylamide group.Our results indicate that a high level of acrylamide causes oxidative damage in liver and small and large intestine tissues, while N-acetylcysteine administration in a pharmacological dose shows to have an antioxidant effect in preventing this damage (Tab. 2, Fig. 2, Ref. 66).

  15. Transfer across mucosal epithelium, tissue content and metabolic fate of 125I-(ipodate-sodium) on isolated everted segments of rat small intestine.

    PubMed

    Komp, B; Forth, W

    1980-04-01

    1. Transfer and tissue content of 125I-radioactivity was measured after administration of 125I-(ipodate-sodium) to everted rat jejunal segments. 2. After having administered 10(-5) M 125I-(ipodate-sodium) on both sides of the everted sacs the S/M ratio of the concentration of 125I-radioactivity was 1.5 in jejunal segments and 2.3 in ileal segments. The tissue content was nearly equal for both segments. According to the apparent partition coefficient for ipodate-sodium at pH 7, the 125I-radioactivity is accumulated in the tissue about 10-fold. 3. Lowering of the temperature of the incubation medium from 37 degrees C to 15 degrees C prevents the building up of a concentration gradient between the serosal and the mucosal side on either jejunal and ileal segments whereas the tissue content of 125I-radioactivity was nearly unchanged. 4. With increasing concentrations (1.6--10(-6)--9.6-10(-4) M) of 125I-(ipodate-sodium) administered on the mucosal side the transfer and the tissue content of 125I-radioactivity were decreased. This appears to be a toxic effect since in jejunal segments also the S/M ratio for the concentration of glucose decreases. 5. The analysis of the 125I-radioactivity in the serosal fluid of jejunal segments showed that the bulk of the 125I-radioactivity was present in the aqueous phase and only 33% as the unchanged ipodate-sodium in the organic phase. 10% of the 125I-radioactivity must be attributed to inorganic iodine. The concentration of 125I-(ipodate-sodium) administered in the mucosal fluid only was 3.2-10(-6) M. At lower temperature (7 degrees C) the bulk of the 125I-radioactivity in the serosal fluid was found in the organic phase, i.e. as unchanged ipodate-sodium. 6. After the incubation of the aqueous phase with beta-glucuronidase or NaOH about 97% of the 125I-radioactivity could be extracted into the organic phase. This means that the bulk of the 125I-radioactivity in the aqueous phase is present as a conjugate, e.g. ester glucuronide of the

  16. Edaravone ameliorates the adverse effects of valproic acid toxicity in small intestine.

    PubMed

    Oktay, S; Alev, B; Tunali, S; Emekli-Alturfan, E; Tunali-Akbay, T; Koc-Ozturk, L; Yanardag, R; Yarat, A

    2015-06-01

    Valproic acid (VPA) is a drug used for the treatment of epilepsy, bipolar psychiatric disorders, and migraine. Previous studies have reported an increased generation of reactive oxygen species and oxidative stress in the toxic mechanism of VPA. Edaravone, a free radical scavenger for clinical use, can quench free radical reaction by trapping a variety of free radical species. In this study, effect of edaravone on some small intestine biochemical parameters in VPA-induced toxicity was investigated. Thirty seven Sprague Dawley female rats were randomly divided into four groups. The groups include control group, edaravone (30 mg(-1) kg(-1) day(-1)) given group, VPA (0.5 g(-1) kg(-1) day(-1)) given group, VPA + edaravone (in same dose) given group. Edaravone and VPA were given intraperitoneally for 7 days. Biochemical parameters such as malondialdehyde, as an index of lipid peroxidation(LPO), sialic acid (SA), glutathione levels and glutathione peroxidase, glutathione-S-transferase, superoxide dismutase, catalase, myeloperoxidase, alkaline phosphatase (ALP), and tissue factor (TF) activities were determined in small intestine samples by colorimetric methods. Decreased small intestine antioxidant enzyme activities, increased LPO and SA levels, and increased activities of ALP and TF were detected in the VPA group. Based on our results edaravone may be suggested to reverse the oxidative stress and inflammation due to VPA-induced small intestine toxicity.

  17. 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.

  18. Small intestinal model for electrically propelled capsule endoscopy

    PubMed Central

    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

  19. Giant primary angiosarcoma of the small intestine showing severe sepsis.

    PubMed

    Takahashi, Mizuna; Ohara, Masanori; Kimura, Noriko; Domen, Hiromitsu; Yamabuki, Takumi; Komuro, Kazuteru; Tsuchikawa, Takahiro; Hirano, Satoshi; Iwashiro, Nozomu

    2014-11-21

    Primary malignant tumors of the small intestine are rare, comprising less than 2% of all gastrointestinal tumors. An 85-year-old woman was admitted with fever of 40 °C and marked abdominal distension. Her medical history was unremarkable, but blood examination showed elevated inflammatory markers. Abdominal computed tomography showed a giant tumor with central necrosis, extending from the epigastrium to the pelvic cavity. Giant gastrointestinal stromal tumor of the small intestine communicating with the gastrointestinal tract or with superimposed infection was suspected. Because no improvement occurred in response to antibiotics, surgery was performed. Laparotomy revealed giant hemorrhagic tumor adherent to the small intestine and occupying the peritoneal cavity. The giant tumor was a solid tumor weighing 3490 g, measuring 24 cm × 17.5 cm × 18 cm and showing marked necrosis. Histologically, the tumor comprised spindle-shaped cells with anaplastic large nuclei. Immunohistochemical studies showed tumor cells positive for vimentin, CD31, and factor VIII-related antigen, but negative for c-kit and CD34. Angiosarcoma was diagnosed. Although no postoperative complications occurred, the patient experienced enlargement of multiple metastatic tumors in the abdominal cavity and died 42 d postoperatively. The prognosis of small intestinal angiosarcoma is very poor, even after volume-reducing palliative surgery.

  20. Spontaneous free perforation of the small intestine in adults

    PubMed Central

    Freeman, Hugh James

    2014-01-01

    Spontaneous free perforation of the small intestine is uncommon, especially if there is no prior history of visceral trauma. However, free, even recurrent, perforation may complicate a defined and established clinical disorder, such as Crohn’s disease. In addition, free perforation may be the initial clinical presentation of an occult intestinal disorder, such as a lymphoma complicating celiac disease, causing diffuse peritonitis and an acute abdomen. Initial diagnosis of the precise cause may be difficult, but now has been aided by computerized tomographic imaging. The site of perforation may be helpful in defining a cause (e.g., ileal perforation in Crohn’s disease, jejunal perforation in celiac disease, complicated by lymphoma or collagenous sprue). Urgent surgical intervention, however, is usually required for precise diagnosis and treatment. During evaluation, an expanding list of other possible causes should be considered, even after surgery, as subsequent management may be affected. Free perforation may not only complicate an established intestinal disorder, but also a new acute process (e.g., caused by different infectious agents) or a longstanding and unrecognized disorder (e.g., congenital, metabolic and vascular causes). Moreover, new endoscopic therapeutic and medical therapies, including use of emerging novel biological agents, have been complicated by intestinal perforation. Recent studies also support the hypothesis that perforation of the small intestine may be genetically-based with different mutations causing altered connective tissue structure, synthesis and repair. PMID:25110427

  1. Acute ethanol administration inhibits Toll-like receptor 4 signaling pathway in rat intestinal epithelia.

    PubMed

    Zhou, Chao; Zhao, Ji; Li, Jing; Wang, Haiying; Tang, Chengwei

    2013-05-01

    Excess alcohol intake, as in binge drinking, increases susceptibility to microbial pathogens. Alcohol impairs macrophage function by suppression of the Toll-like receptor 4 (TLR4) pathway. This study investigated the effects of acute ethanol intake on the TLR4 pathway in rat intestinal epithelia, which usually encounters luminal antigens at first and participates in the development of intestinal immunity. Twenty Wistar rats were randomly assigned to an ethanol group given ethanol as a 25% (v/v) solution in water at 7.5 g/kg, or a control group given saline, by oral gavage daily for 3 days. The epithelial histology and ultrastructure, the intestinal microflora, peripheral and portal venous plasma lipopolysaccharide (LPS) levels, and somatostatin (SST) levels in the peripheral plasma and small intestine were evaluated. Somatostatin receptor 2 (SSTR2), TLR4, TANK binding kinase-1 (TBK1), activated nuclear factor-κB (NF-κB), interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) in the intestinal mucosa were assayed. LPS responsiveness with or without SST pretreatment was assayed in vitro by quantification of TLR4, TBK1, activated NF-κB, IFN-γ and TNF-α in isolated intestinal epithelia. Mucosal damage was observed in the ethanol group by light and electron microscopy. Escherichia coli cultures were unchanged in rat intestine of the ethanol group compared with controls, but lactobacilli cultures were reduced (p < 0.05). LPS levels increased in peripheral and portal venous plasma (p < 0.05), but mucosal TLR4, TBK1, nuclear NF-κB, IFN-γ and TNF-α were unchanged in the ethanol group. LPS treatment in vitro up-regulated the level of TLR4, TBK1 and nuclear NF-κB as well as the production of IFN-γ and TNF-α in isolated intestinal epithelia in the control (p < 0.05), but not the ethanol group. The stimulatory effects of LPS on intestinal epithelia isolated from the control group were significantly inhibited by SST pretreatment (p < 0.05). The

  2. Functional disorders of the small intestine.

    PubMed

    Kellow, J E; Bennett, E

    1996-10-01

    Sensorimotor disturbances of the small bowel are implicated increasingly in the pathogenesis of the functional gastrointestinal disorders. In irritable bowel syndrome (IBS), alterations in both interdigestive and postprandial motility have been described, for example, the specific peristaltic contractions that are normally present in the ileum appear to occur more frequently and to be associated with abdominal pain in some patients. The latter finding is likely to be related to the selective mechanoreceptor hypersensitivity that has been demonstrated in the small bowel of IBS patients. The level of this afferent dysfunction has, however, not been established; some evidence suggests that personality traits, which predispose to a more severe and prolonged sympathetic response to stressors, may hasten the development of such sensorimotor disturbances.

  3. Cancer of the small intestine in patients with Crohn's disease.

    PubMed

    Higashi, Daijiro; Futami, Kitaro; Kojima, Daibo; Futatsuki, Ryo; Ishibashi, Yukiko; Maekawa, Takafumi; Yano, Yutaka; Takatsu, Noritaka; Hirai, Fumihito; Matsui, Toshiyuki; Iwashita, Akinori

    2013-07-01

    Due to an increase in the number of long-term cases of Crohn's disease, the risk of combined cancer in these patients has been assessed in numerous articles. Most of these reports have involved patients with cancer of the large intestine, while cases of cancer of the small intestine combined with Crohn's disease are very rare. We experienced two cases of cancer of the small intestine combined with Crohn's disease. In both cases, the patients had suffered from Crohn's disease for over 10 years and a second operation was performed after a long period without treatment following the first operation, which had achieved a favorable outcome. In both cases of combined cancer, the patients experienced ileus; however, it was difficult to discern this from ileus due to the presence of Crohn's disease. Therefore, making a definitive diagnosis of combined cancer was not possible before surgery, and the definitive diagnosis was obtained based on an intraoperative pathological diagnosis. It is thought that tumor markers transition in a manner parallel to the progression of cancer, providing a clue for cancer diagnosis. In patients with Crohn's disease, there is a pressing need to establish a method for diagnosing cancer of the small intestine at an early stage.

  4. 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

  5. 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

  6. Breath hydrogen concentration and small intestinal malabsorption in calves.

    PubMed

    Holland, R E; Herdt, T H; Refsal, K R

    1986-09-01

    Breath hydrogen concentrations were measured to assess intestinal carbohydrate malabsorption in preruminating calves. Oral administration of 1.25 g of lactulose (a nonabsorbable carbohydrate)/kg to calves produced breath hydrogen concentrations significantly (P less than 0.001) higher than values determined after calves were fed milk and before the treatment was given. This indicates that, in the calf, fermentation of nonabsorbed carbohydrates results in increased breath hydrogen values. To induce small intestinal malabsorption, chloramphenicol was administered orally at 50 mg/kg, 2 times a day, to 5 calves for 3 days. Before therapy was started, each calf was fitted with a duodenal cannula to facilitate collection of intestinal mucosal biopsy samples during treatment. Chloramphenicol therapy significantly (P less than 0.001) increased breath hydrogen concentrations from those values measured after calves were fed milk alone. Concurrently, chloramphenicol administration significantly decreased intestinal villous length (P less than 0.001) and D-xylose absorption (P less than 0.05), compared with those values before treatment was given. These results demonstrate that decreased intestinal absorptive capacity is associated with an increase in breath hydrogen concentrations and that breath hydrogen may be useful in evaluating malabsorption in calves with naturally occurring enteric disease.

  7. 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.

  8. Digestion modeling in the small intestine: impact of dietary fiber.

    PubMed

    Taghipoor, M; Barles, G; Georgelin, C; Licois, J R; Lescoat, P

    2014-12-01

    In this work, the modeling of the digestion in the small intestine is developed by investigating specifically the effects of dietary fiber. As our previous model, this new version takes into account the three main phenomena of digestion: transit of the bolus, degradation of feedstuffs and absorption through the intestinal wall. However the two main physiochemical characteristics of dietary fiber, namely viscosity and water holding capacity, lead us to substantially modify our initial model by emphasizing the role of water and its intricated dynamics with dry matter in the bolus. Various numerical simulations given by this new model are qualitatively in agreement with the positive effect of insoluble dietary fiber on the velocity of bolus and on its degradation all along the small intestine. These simulations reproduce the negative effect of soluble dietary fiber on digestion as it has been experimentally observed. Although, this model is generic and contains a large number of parameters but, to the best of our knowledge, it is among the first qualitative dynamical models of fiber influence on intestinal digestion.

  9. Caffeine Induction of Sulfotransferases in Rat Liver and Intestine

    PubMed Central

    Zhou, Tianyan; Chen, Yue; Huang, Chaoqun; Chen, Guangping

    2011-01-01

    Sulfotransferases (SULTs) are important phase II drug-metabolizing enzymes. SULTs regulation by hormones and other endogenous molecules is relatively well understood, while xenobiotic induction of SULTs is not well studied. Caffeine is one of the most widely consumed psychoactive substances. However, SULTs regulation by caffeine has not been reported. In this report, male and female rats were treated with different oral doses of caffeine (2, 10, 50 mg/kg/day) for 7 days. Western blot and real-time RT-PCR were used to investigate the changes of SULT protein and mRNA expression following the caffeine treatment. Caffeine induced both rat aryl sulfotransferase (rSULT1A1, AST-IV) and rat hydroxysteroid sulfotransferase (rSULT2A1, STa) in the liver and intestine of female rats in a dose-dependent manner. Caffeine induction of rSULT1A1 and rSULT2A1 in the female rat intestine was much stronger than that in the liver. Although caffeine induced rSULT1A1 significantly in the male rat liver, it did not significantly induce rSULT2A1. In male rat intestine, caffeine significantly induced rSULT2A1. The different SULTs induction patterns in male and female rats suggest that the regulation of rat SULTs by caffeine may be affected by different hormone secretion patterns and levels. Our results suggest that consumption of caffeine can induce drug metabolizing SULTs in drug detoxification tissues. PMID:21721019

  10. Cloning of the rat ecotropic retroviral receptor and studies of its expression in intestinal tissues

    SciTech Connect

    Puppi, M.; Henning, S.J.

    1995-05-01

    A long-term goal of our laboratory is to establish a rat model to study the feasibility of using the intestinal tract as a site for somatic gene therapy. As a step toward that goal, the current study reports the cloning of the rat ecotropic retroviral receptor (EcoR) cDNA and the study of various aspects of its expression in the intestinal cDNA library with mouse EcoR cDNA. A clone of approximately 7 kb, designated MP10, was obtained. Partial sequencing of MP10 from the 5{prime} end revealed a level of similarity of 92% compared with mouse EcoR. The presence of a 5{prime} untranslated region and a 3{prime} poly(A)tract, together with the overall size of the cDNA, suggest that is very close to being a full-length cDNA for this large transcript. Northern blots with MP10 showed an RNA of approximately 7.9 kb present along the entire length of the small intestine and somewhat less abundant in the colon. Developmental studies showed high levels of EcoR in fetal rat intestine, a decline in the early postnatal period, then a gradual rise to adulthood. Caco-2 cells were used to assess the expression of EcoR in proliferating compared with differentiated intestinal epithelial cells. EcoR mRNA was found to be very much more abundant in nondifferentiated cells and declined to low levels as the cells underwent spontaneous differentiation. These patterns of EcoR expression indicate that ecotropic retroviruses should be suitable vectors with which to attempt gene transfer into the intestinal epithelium. In addition, since the endogenous role of EcoR is as the y{sup +} cationic amino acid transporter, these data have significance for understanding patterns of amino acid transport in the intestinal epithelium. 37 refs., 4 figs.

  11. Ultrasonographic examination of the small intestine, large intestine and greater omentum in 30 Saanen goats.

    PubMed

    Braun, U; Steininger, K; Tschuor, A; Hässig, M

    2011-09-01

    The small and large intestine of 30 healthy Saanen goats were examined ultrasonographically using a 5.0 MHz-linear transducer. The goats were examined on the right side, from the eighth rib to the caudal aspect of the flank. The small and large intestine could be easily differentiated. The descending duodenum could be imaged in 19 goats, and the jejunum and ileum seen in all goats. The jejunum and ileum were most often seen in cross-section and rarely in longitudinal section in the ventral region of the right flank. The intestinal contents were usually homogenously echoic, and active motility was observed in all the goats. The diameter of the small intestine was 0.8-2.7 cm (1.6 [0.33] cm). The spiral ansa of the colon was imaged in all the goats, and in 21 the caecum was also seen. Both these sections of large intestine were most commonly seen in the dorsal region of the right flank. The spiral ansa of the colon was easily identified by its spiral arrangement of centripetal and centrifugal gyri, which had a garland-like appearance. Because of intraluminal gas, only the wall of the colon closest to the transducer could be imaged. The diameter of the spiral colon ranged from 0.8 to 2.0 cm (1.1 [0.24] cm). Usually only the wall of the caecum closest to the transducer could be imaged and it appeared as a thick, echoic, slightly undulating line. The greater omentum could be seen in all the goats.

  12. 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.

  13. 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

  14. Small intestinal mucosal abnormalities in post-perinatal deaths.

    PubMed Central

    Variend, S; Sunderland, R

    1984-01-01

    Examination of small intestinal mucosa from cases of post-perinatal death in Sheffield between September 1980 and September 1981 showed mucosal changes before death in 18 of 78 cases (20%). There was no significant difference in prevalence between explained and unexplained deaths, nor was there any positive association with viral isolation from the small intestine. The lesion was much more common in males than females and showed a strong association with bottle feeding--no infant wholly breast fed showed an enteropathy. There was a low incidence of symptoms referrable to the gastrointestinal tract among affected infants, and no appreciable evidence of failure to thrive, as reflected by the postmortem body weight, was present. Mucosal changes of the small intestine in cases of sudden infant death syndrome have previously been reported and attributed to heatstroke. Although the finding of similar lesions in infants who died explicably does not appear to support this view, overheating is difficult to exclude as most of the explained deaths with a mucosal lesion occurred at home. Images PMID:6699191

  15. 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.

  16. Histochemical features of the Muscovy duck small intestine during development.

    PubMed

    Ding, Bao An; Pirone, Andrea; Lenzi, Carla; Xiaoming, Nie; Baglini, Alessandro; Romboli, Isabella

    2011-06-01

    We demonstrated for the first time the distribution and morphology of argyrophil and of goblet cells in the mucosa of the small intestine of the Muscovy duck during development using the Grimelius silver staining and alcian blue/periodic acid-Schiff (AB/PAS) staining technique. The argyrophil cells distribution was variable over the length of the small intestine from embryonic day 24 (24E) to post-hatching day 13 (13d). In the villi most argyrophil cells belonged to the open-type, while in the crypts they belonged to the closed-type. In the duodenum the density of argyrophil cells was highest at hatching, while in the jejunum and in the ileum the highest density value was at hatching and 13d. AB/PAS-positive goblet cells appeared on the villi and crypts of the duodenum and jejunum at 30E, and in the ileum at hatching. The density of AB/PAS-positive cells was the highest in the three segments at hatching. The AB-positive cells, compared with the PAS-positive cells, predominated in villi and crypts of the three segments, moreover the rate of AB-positive cells to PAS-positive cells significantly decreased from 30E to 9d. An increase in argyrophil and goblet cells number during the later incubation and at hatching, could indicate the small intestine in that period is being prepared to face a new diet.

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

    PubMed

    Lu, Hui; Zhu, Bing

    2014-11-01

    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.

  18. The Effect of Infliximab on Intestinal Anastomosis Healing in Rats.

    PubMed

    Karaköse, Oktay; Eken, Hüseyin; Ulusoy, Ali Naki; Topgül, Hüseyin Koray; Bilgin, Mehmet; Yürüker, Saim Savaş; Gülbahar, Mustafa Yavuz

    Intestinal anastomosis healing is a complex physiological process in which many local and systemic factors play a role. One of the significant cytokines in this process is TNF-α. Infliximab is a chimeric monoclonal antibody which binds to TNF-α with high affinity. Although this agent is used in ulcerative colitis and Crohn's disease, intestinal surgery may be required in these patients. In this study it was aimed to determine whether or not there was any negative effect of preoperative single dose infliximab treatment on intestinal anastomosis healing. Two groups of 10 rats were formed. One of these groups was administered with a single dose of infliximab 8 mg/kg as a 20-minute intravenous infusion from the femoral vein. Four days after the infusion, a full layer incision was made to the colon and anastomosis was applied to all the rats. At 7 days after anastomosis, the subjects were sacrificed. The anastomosis segment was removed and the bursting pressure was measured. Tissue samples were taken from this segment for hydroxyproline concentration and histopathological examination. A blood sample was taken to measure TNF-α values. No statistically significant difference was determined between the groups in terms of bursting pressure, tissue hydroxyproline concentration or histopathological scoring. A single dose of 8 mg/kg infliximab administered 4 days preoperatively was not found to have any negative effect on intestinal anastomosis healing in rats.

  19. Rat intestinal mast cell amines are released during nitric oxide synthase inhibition in vitro

    PubMed Central

    Northover, B. J.

    1996-01-01

    Inhibition of nitric oxide synthase increases microvascular permeability in rat small intestinal villi. To determine the mechanism(s) whereby this occurs we have perfused the vasculature of rat isolated small intestines with a gelatin-containing physiological salt solution. Inclusion of N-nitro-L-argintne methyl ester (L-NAME, 100 μM) or indomethacin (1 μM) in the perfusate increased leakage of injected colloidal carbon into microvessel walls. Pre-treatment with sodium nitroprusside (10 μM) significantly reduced the effects of both L-NAME and indomethacin, whereas carbacyclin (1 μM) only reduced the effects of indomethacin. PD151242 (1 μM) showed some antagonism towards the effects of L-NAME, but nordihydroguaiaretic acid (3 μM) was inactive. Pre-tment with cyproheptadine (10 μM) reduced the effects of both L-NAME and indomethacin, and also significantly reduced background (control) colloidal carbon leakage. Small intestines from polymixin B-treated rats showed significantly reduced colloidal carbon leakage in response to L-NAME. This suggests that the leakage-enhancing effects of both L-NAME and indomethacin in this preparation may be mediated by mast cell-derived amines. PMID:18475694

  20. 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.

  1. 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

  2. Cloning of the rat ecotropic retroviral receptor and studies of its expression in intestinal tissues.

    PubMed

    Puppi, M; Henning, S J

    1995-05-01

    A long-term goal of our laboratory is to establish a rat model to study the feasibility of using the intestinal tract as a site for somatic gene therapy. As a step toward that goal, the current study reports the cloning of the rat ecotropic retroviral receptor (EcoR) cDNA and the study of various aspects of its expression in the intestinal tissues. The cDNA for rat EcoR was cloned by screening a size-selected rat intestinal cDNA library with mouse EcoR cDNA. A clone of approximately 7 kb, designated MP10, was obtained. Partial sequencing of MP10 from the 5' end revealed a level of similarity of 92% compared with mouse EcoR. The presence of a 5' untranslated region and a 3' poly(A) tract, together with the overall size of the cDNA, suggest that is very close to being a full-length cDNA for this large transcript. Northern blots with MP10 showed an RNA of approximately 7.9 kb present along the entire length of the small intestine and somewhat less abundant in the colon. Developmental studies showed high levels of EcoR in fetal rat intestine, a decline in the early postnatal period, then a gradual rise to adulthood. Caco-2 cells were used to assess the expression of EcoR in proliferating compared with differentiated intestinal epithelial cells. EcoR mRNA was found to be very much more abundant in nondifferentiated cells and declined to low levels as the cells underwent spontaneous differentiation. These patterns of EcoR expression indicate that ecotropic retroviruses should be suitable vectors with which to attempt gene transfer into the intestinal epithelium. In addition, since the endogenous role of EcoR is as the y+ cationic amino acid transporter, these data have significance for understanding patterns of amino acid transport in the intestinal epithelium.

  3. 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.

  4. Inhibitory effect and mechanism of acarbose combined with gymnemic acid on maltose absorption in rat intestine

    PubMed Central

    Luo, Hong; Wang, Le Feng; Imoto, Toshiaki; Hiji, Yasutake

    2001-01-01

    AIM: To compare the combinative and individual effect of acarbose and gymnemic acid (GA) on maltose absorption and hydrolysis in small intestine to determine whether nutrient control in diabetic care can be improved by combination of them. METHODS: The absorption and hydrolysis of maltose were studied by cyclic perfusion of intestinal loops in situ and motility of the intestine was recorded with the intestinal ring in vitro using Wistar rats. RESULTS: The total inhibitory rate of maltose absorption was improved by the combination of GA (0.1 g/L-1.0 g/L) and acarbose (0.1 mmol/L-2.0 mmol/L) throughout their effective duration (P < 0.05, U test of Mann-Whitney), although the improvement only could be seen at a low dosage during the first hour. With the combination, inhibitory duration of acarbose on maltose absorption was prolonged to 3 h and the inhibitory effect onset of GA was fastened to 15 min. GA suppressed the intestinal mobility with a good correlation (r = 0.98) to the inhibitory effect of GA on maltose absorption and the inhibitory effect of 2 mmol/L (high dose) acarbose on maltose hydrolysis was dual modulated by 1 g/L GA in vivo indicating that the combined effects involved the functional alteration of intestinal barriers. CONCLUSION: There are augmented effects of acarbose and GA, which involve pre-cellular and paracellular barriers. Diabetic care can be improved by employing the combination. PMID:11819725

  5. Dab2, megalin, cubilin and amnionless receptor complex might mediate intestinal endocytosis in the suckling rat.

    PubMed

    Vázquez-Carretero, María D; Palomo, Marta; García-Miranda, Pablo; Sánchez-Aguayo, Inmaculada; Peral, María J; Calonge, María L; Ilundain, Anunciación A

    2014-03-01

    We previously proposed that Dab2 participates in the endocytosis of milk macromolecules in rat small intestine. Here we investigate the receptors that may mediate this endocytosis by studying the effects of age and diet on megalin, VLDLR, and ApoER2 expression, and that of age on the expression of cubilin and amnionless. Of megalin, VLDLR and ApoER2, only the megalin expression pattern resembles that of Dab2 previously reported. Thus the mRNA and protein levels of megalin and Dab2 are high in the intestine of the suckling rat, down-regulated by age and up-regulated by milk diet, mainly in the ileum. Neither age nor diet affect ApoER2 mRNA levels. The effect of age on VLDLR mRNA levels depends on the epithelial cell tested but they are down-regulated by milk diet. In the suckling rat, the intestinal expressions of both cubilin and amnionless are similar to that of megalin and megalin, cubilin, amnionless and Dab2 co-localize at the microvilli and in the apical endocytic apparatus. Co-localization of Dab2 with ApoER2 and VLDLR at the microvilli and in the apical endocytic apparatus is also observed. This is the first report showing intestinal co-localization of: megalin/cubilin/amnionless/Dab2, VLDLR/Dab2 and ApoER2/Dab2. We conclude that the megalin/cubilin/amnionless/Dab2 complex/es participate in intestinal processes, mainly during the lactation period and that Dab2 may act as an adaptor in intestinal processes mediated by ApoER2 and VLDLR.

  6. Mucosal projections of enteric neurons in the porcine small intestine.

    PubMed

    Hens, J; Schrödl, F; Brehmer, A; Adriaensen, D; Neuhuber, W; Scheuermann, D W; Schemann, M; Timmermans, J P

    2000-06-05

    In the present study, a combination of immunohistochemistry and retrograde 1,1;-didodecyl-3,3,3;,3;-tetramethylindocarbocyanine perchlorate (DiI) tracing was used to unravel the morphology, distribution, and neurochemical coding of submucous and myenteric neurons with axonal projections to the mucosa of the porcine small intestine. The majority of traced neurons was located in the inner submucous plexus (ISP; 78%), whereas the remaining part was distributed between the outer submucous plexus (OSP; 10%) and myenteric plexus (MP; 12%). Among these traced neurons, some distinct neuronal populations could be distinguished according to their morphologic and neurochemical properties. In the ISP, several types of traced neurons were detected: 1) morphologic type II neurons expressing choline acetyltransferase (ChAT) immunoreactivity, calcitonin gene-related peptide (CGRP) immunoreactivity, and substance P (SP) immunoreactivity; 2) ChAT/SP-immunoreactive (-IR) small neurons; 3) vasoactive intestinal polypeptide (VIP) -IR small neurons; and 4) multidendritic ChAT/somatostatin (SOM) -IR neurons. The traced neuronal populations of the OSP and MP were similar to each other. In both plexuses, the following DiI-labelled neurons were found: 1) ChAT/CGRP/(SP)-IR type II neurons; 2) multidendritic ChAT/SP-IR neurons; and 3) multidendritic ChAT/SOM-IR neurons. Comparison of the present findings with previously obtained data concerning the mucosal innervation pattern of the intestine of small mammals, revealed significant species differences with respect to the morphologic and neurochemical features of the involved enteric neuronal classes. Although not identical, a closer resemblance between pig and human enteric nervous system seems to be at hand, as far as the anatomic organization and the presence of neurochemically identified neuronal subtypes within the enteric nervous system are concerned.

  7. 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

  8. Diagnosis of intestinal ischemia in the rat using magnetic resonance imaging.

    PubMed

    Park, A; Towner, R A; Langer, J C

    1993-01-01

    Noninvasive diagnosis of persistent ischemia after intestinal revascularization has remained an elusive goal. Because magnetic resonance imaging (MRI) can detect changes in tissue water, we studied its efficacy in differentiating ischemic from perfused intestine in an animal model. Six-week-old rats were subjected to (1) 30-min superior mesenteric artery (SMA) occlusion and reperfusion, (2) permanent SMA ligation, or (3) sham operation, and were then imaged for 90 min using a small-animal MRI scanner with T1 weighting (TR = 1000 msec, TE = 25 msec). In an additional group of rats, the experiment was repeated using a new contrast technique consisting of oral ferrite to decrease luminal signal and intravenous gadolinium to increase bowel wall signal. Mean abdominal intensity over the scanning period was calculated for each animal (n = 5 rats per experimental group). Definition of individual bowel loops was subjectively improved in animals scanned with intravenous and oral contrast. Mean abdominal intensity was significantly lower in ligated vs sham rats (43.90 +/- 8 vs 59.63 +/- 6 and 46.19 +/- 6 vs 54.26 +/- 6, with and without contrast, respectively). There was no significant difference in intensity between reperfused and sham animals. MRI differentiated persistently ischemic bowel from viable bowel in this model, both with and without the use of contrast. These data suggest that MRI may have a potential role in the noninvasive diagnosis of persistent intestinal ischemia.

  9. 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.

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

    PubMed

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

    2016-04-04

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

  11. 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.

  12. 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.

  13. 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

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

    PubMed Central

    Liu, Dengqun; Wang, Fengchao; Zou, Zhongmin; Dong, Shiwu; Wang, Junping; Ran, Xinze; Li, Chunxue; Shi, Chunmeng; Su, Yongping

    2010-01-01

    Interstitial cells of Cajal (ICCs) in gastrointestinal tract are specialized cells serving as pacemaker cells. The origin of ICCs is currently not fully characterized. In this work, we aimed to study whether bone marrow-derived cells (BMDCs) could contribute to the origin of ICCs in the muscular plexus of small intestine using GFP-C57BL/6 chimeric mice.Engraftment of BMDCs in the intestine was investigated for GFP expression. GFP positive bone marrow mononuclear cells reached a proportion of 95.65% ± 3.72% at different times in chimerism. Donor-derived cells distributed widely in all the layers of the gastrointestinal tract. There were GFP positive BMDCs in the myenteric plexus, which resembled characteristics of ICCs, including myenteric location, c-Kit positive staining, and ramified morphology. Donor-derived ICCs in the myenteric plexus contributed to a percentage ranging 9.25% ± 4.9% of all the ICCs in the myenteric plexus. In conclusion, here we described that donor-derived BMDCs might differentiate into gastrointestinal ICCs after radiation injury, which provided an alternative source for the origin of the ICCs in the muscular plexus of adult intestine. These results further identified the plasticity of BMDCs and indicated therapeutic implications of BMDCs for the gastrointestinal dysmotility caused by ICCs disorders. PMID:20396598

  15. Postprandial increase of oleoylethanolamide mobilization in small intestine of the Burmese python (Python molurus).

    PubMed

    Astarita, Giuseppe; Rourke, Bryan C; Andersen, Johnnie B; Fu, Jin; Kim, Janet H; Bennett, Albert F; Hicks, James W; Piomelli, Daniele

    2006-05-01

    Oleoylethanolamide (OEA) is an endogenous lipid mediator that inhibits feeding in rats and mice by activating the nuclear receptor peroxisome proliferator-activated receptor-alpha (PPAR-alpha). In rodents, intestinal OEA levels increase about threefold upon refeeding, a response that may contribute to the induction of between-meal satiety. Here, we examined whether feeding-induced OEA mobilization also occurs in Burmese pythons (Python molurus), a species of ambush-hunting snakes that consume huge meals after months of fasting and undergo massive feeding-dependent changes in gastrointestinal hormonal release and gut morphology. Using liquid chromatography/mass spectrometry (LC/MS), we measured OEA levels in the gastrointestinal tract of fasted (28 days) and fed (48 h after feeding) pythons. We observed a nearly 300-fold increase in OEA levels in the small intestine of fed compared with fasted animals (322 +/- 121 vs. 1 +/- 1 pmol/mg protein, n = 3-4). In situ OEA biosynthesis was suggested by the concomitant increase of N-acyl phosphatidylethanolamine species that serve as potential biosynthetic precursors for OEA. Furthermore, we observed a concomitant increase in saturated, mono- and diunsaturated, but not polyunsaturated fatty-acid ethanolamides (FAE) in the small intestine of fed pythons. The identification of OEA and other FAEs in the gastrointestinal tract of Python molurus suggests that this class of lipid messengers may be widespread among vertebrate groups and may represent an evolutionarily ancient means of regulating energy intake.

  16. Investigations on the estrogenic activity of the metallohormone cadmium in the rat intestine.

    PubMed

    Höfer, Nicola; Diel, Patrick; Wittsiepe, Jürgen; Wilhelm, Michael; Kluxen, Felix M; Degen, Gisela H

    2010-07-01

    Cadmium (Cd), a toxic heavy metal and an important environmental pollutant, is now also regarded as potential endocrine disruptor. Its estrogenic effects have been examined so far just in classical target tissues, e.g. uterus, and mostly upon intraperitoneal (i.p.) injection of CdCl(2). Yet, estrogen receptors are also expressed in the gut, and food is the main source of cadmium intake in the general population. Therefore, possible estrogenic effects were now investigated in the intestine of ovariectomized Wistar rats after oral short- and long-term administration of CdCl(2) (0.05-4 mg/kg bw on 3 days by gavage and 0.4-9 mg/kg bw for 4 weeks in drinking water) or upon i.p. injection (0.00005-2 mg CdCl(2)/kg bw), and compared to steroid estrogen (estradiol or ethinylestradiol) treated groups. Analysis of Cd in kidneys and small intestine by atomic absorption spectrometry showed dose-dependent increases in tissue levels with rather high Cd concentrations in the gut, both after oral and i.p. administration. Expression of metallothionein (MT1a), a typical metal response parameter, was clearly induced in kidney and small intestine of several CdCl(2) treated groups, but also notably increased by steroid estrogens. Levels of estrogen-regulated genes, i.e. pS2/TFF1, vitamin D receptor (VDR), and estrogen receptor alpha and beta (ER alpha/beta) were studied as parameters of hormonal activity: The intestinal mRNA expression of pS2/TFF1 was significantly decreased in the estrogen reference groups, but also after single i.p. injection and oral long-term administration of CdCl(2). In contrast, the mRNA and protein expression of the VDR were unaffected by long-term administration of Cd via drinking water. We detected expression of ERbeta, but not ERalpha in the small intestine of OVX rats. ERbeta mRNA and protein expression were significantly down-regulated by Cd, similar to the ethinylestradiol reference group. The mRNA expression and immunostaining of proliferating cell

  17. 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.

  18. Gastric emptying and intestinal absorption of ingested water and saline by hypovolemic rats.

    PubMed

    Stricker, Edward M; Bykowski, Michael R; Hossler, Carrie A Smith; Curtis, Kathleen S; Smith, James C

    2009-12-07

    Recent experiments showed that in a one-bottle test conducted 16h after sc injection of polyethylene glycol (PEG) solution, hypovolemic rats consumed water or 0.30 M NaCl in an initial drinking episode but did not empty the ingested fluid from the stomach or absorb it from the small intestine very rapidly, certainly not as rapidly as when 0.15M NaCl was consumed (Smith et al., Am J Physiol 292: R2089-R2099, 2007). The present experiments examined the patterns of water and 0.30 M NaCl ingestion and the movement of consumed fluid through the gastrointestinal tract when PEG-treated rats were given a two-bottle delayed-access test. We found that both fluids always were consumed in the first drinking episode, that the fluid mixture ingested was equivalent to 0.10-0.15M NaCl, and that gastric emptying rate and net fluid absorption from the small intestine usually were much faster than when PEG-treated rats drank either water or hypertonic saline alone. Thus, ingestion of water and 0.30 M NaCl by hypovolemic rats in the same episode adaptively facilitated the movement into the circulation of a near-isotonic fluid that is ideal for restoring plasma volume deficits.

  19. Laparoscopic Herniorrhaphy with Porcine Small Intestinal Submucosa: A Preliminary Study

    PubMed Central

    2002-01-01

    Introduction: Using mesh or a synthetic prosthesis during the laparoscopic repair of inguinal hernias has been demonstrated to be safe and effective. A new material, porcine small intestinal submucosa (SIS mesh), has been successfully used in canine and rodent animal models with excellent results. This mesh is degradable and resorbable with a marked decrease in the possibility of becoming infected. However, the amount of fibroblast ingrowth is equal to that with polypropylene mesh. Methods: A comparison was made between this new SIS mesh to repair 15 inguinal hernias in 12 patients and polypropylene mesh used in 12 similar patients. A preperitoneal approach with balloon dissection was used in all patients. Results: Demographics were similar in both groups. The results were excellent and compared equally. Complications (seroma, discomfort) were minimal in both groups and were similar. Conclusions: Porcine small intestinal submucosa, SIS mesh, can be used for laparoscopic repair of inguinal hernias. Long-term follow-up will be necessary to confirm these preliminary results. PMID:12166756

  20. [Coordination of the myoelectrical activity of the large and small intestine].

    PubMed

    Lychkova, A E

    2012-01-01

    Coordination of the myoelectrical activity of the large and small intestine was studied. Pacemaker cells of intestine are predominantly located at the proximal divisions of large and small intestine and have an increased spontaneous slow-wave activity, which ensures the distribution of excitation in smooth muscle underlying intestines. Due to the ileocecal coordination by sequential motor activity of small and large intestine is provided. The distal direction gradient of slow waves frequency reduction was established. Pacemaker cells possess certain structural specificity and is specialized in the spontaneous bioelectric activity.

  1. [Rat intestinal absorption trait of peimine and peiminine in Thunberg fritillary bulb extract].

    PubMed

    Guan, Zhi-Yu; Zhang, Li-Hua; Chen, Li-Hua; Zhu, Wei-Feng; Liu, Hong-Ning

    2013-12-01

    To study the in situ intestinal absorption kinetics and compatibility influence of peimine and peiminine in rats, the absorption of peimine and peiminine in small intestine (duodenum, jejunum and ileum) and colon of rats was investigated using in situ single-pass perfusion method and the drug content was measured by HPLC-ELSD. Perfusion rate, pH, concentration of drug, gender and bile duct ligation can significantly affect the absorption of peimine and peiminine, the Ka, and Papp values in the condition of pH 6.8 and pH 7.4 had significant difference (P<0.01), as drug concentration irlcreased, the absorption parameters of peimine and peiminine decreased, Ka and Papp between low concentrations and middle concentrations was significant difference (P<0.01). Verapamil can not affect Ka and Papp of peimine and peiminine which are in the extract (P> 0.05). Bitter almonds and licorice can significantly reduce the absorption of peimine and peiminine with the usual dose (P<0.01), extracted separately and together had no significant difference on Ka and Papp (P> 0.05). Experimental results show that the absorption features of peimine and peiminine are basically the same, both of them could be absorbed at all segments of the intestine in rats and had no special absorption window, and with significant differences between male and female individuals. The absorption of peimine and peiminine complies with the active transport and facilitated diffusion in the general intestinal segments. Bitter almond and licorice can reduce the intestinal absorption rate ofpeimine and peiminine.

  2. 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.

  3. 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.

  4. Intestinal transport of sugars and amino acids in diabetic rats

    PubMed Central

    Olsen, Ward A.; Rosenberg, Irwin H.

    1970-01-01

    The specificity and mechanism of altered intestinal transport of diabetic rats was studied with an everted ring technique. Increased intracellular accumulation of amino acids, as well as galactose and 3-O-methylglucose, was demonstrated in diabetes. The greater accumulation by diabetic intestine could not be attributed to a direct effect of the agent used to induce diabetes or to an alteration in food consumption. Although the changes were related to the severity of diabetes and could be reversed with treatment with insulin, they could not be modified by addition of insulin in vitro. The changes could not be induced in control intestine either with hyperglycemia from glucose infusion or preincubation with glucose in vitro. Although the higher concentration gradients of amino acids, galactose, and 3-O-methylglucose could result from increased energy utilization by diabetic intestine, an alteration of cell membrane function, as well, is suggested by the demonstration with kinetic studies of increased influx with an increase in Vmax. PMID:5409812

  5. 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.

  6. 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.

  7. 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.

  8. [An improved single-layer suture in the surgery of small and large intestines].

    PubMed

    Kapustin, B B; Sysoev, S V

    2010-01-01

    The methods and results of using single-layer interrupted intestinal suture in operations on the small and large intestines are presented. Using the suture decreases the number of complications associated with this technique, improves the direct results of operations and reduces postoperative lethality both in urgent and planned surgery. The proposed intestinal suture is thought to be justified in connecting similar and dissimilar parts of the intestinal tube in the variants of longitudinal, transversal, terminal, lateral and termino-lateral interintestinal anastomoses.

  9. 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

  10. [Characterization of the microflora of the small intestine (author's transl)].

    PubMed

    Bernhardt, H; Knoke, M

    1980-03-01

    Normal and abnormal microflora of the upper small intestine was studied in 356 patients. Low counts are characteristic of normal microbial colonization (eubiosis), changes in quality and/or quantity are pathological (dysbiosis). The latter status is described as overgrowth syndrome. We found some types of dysbiosis. Prevalent was type Dys1 with the highest counts and the greatest variety of bacteria and yeasts. In contrast to this, type Dys2 showed higher germ counts of only one genus like coliforms (Dys2 Coli), streptococci (Dys2 Str.), lactobacilli (Dys2 L.) or yeasts (Dys2 Y.). In dysbiosis, we frequently saw bifidobacterium and bacteroides. Simultaneous sampling from stomach, duodenum, and jejunum indicated different modes of colonization of these parts (oral or fecal type).

  11. [Effect of chronic intake of dietary fiber complex on the intestinal structure and function in hypercholesterolemic rats].

    PubMed

    Ma, Zhengwei; Zhang, Xizhong

    2003-07-01

    To investigate the long-term effect of dietary fiber complex (DFC) on intestinal structure and function in hypercholesterolemic rats, 60 healthy SD rats were feed with food rich in lipids and hypercholesterolemic animal models were established. The animals were randomly divided into 5 groups. Rats were fed DFC at levels of 4%, 16%, or 64% for three month in the experimental groups. Wheat fiber was used in the hypercholesterolemic control (HC) group and rats feeding on normal food were used as normal control (NC). Morphology of the small intestine, reticum and caecum were observed by light and electron microscope examination. Intestinal function was measured physically. The results showed that (1) compared with NC group, fecal weight was significantly raised in DFC group of higher level (group D and E, P < 0.05); (2) the weights of small intestine wall in D and E group were significantly higher than those of NC and HC group and weights of caecum wall in E group were significantly higher than those of NC and HC group (P < 0.05); (3) widen villi and thickened muscle layer of small intestine were observed in DFC group of higher level. No demonstrable changes in reticulum morphology in any group of animals were found under the observation of light microscope (4) microvilla becoming short and/or absent, mitochondria swelling, impairment of the integrity of the cristae were commonly observed in DFC groups. Conclusions Long-term intake of DFC composed mainly of Hippophae rhamnoides L, Bran, oat bran and guar gum at higher levels might induce some morphological changes of intestine and caecum. Therefore, DFC might be used at low level as an effective cholesterol-lowering agent.

  12. 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.

  13. 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.

  14. Genetics and epigenetics in small intestinal neuroendocrine tumours.

    PubMed

    Stålberg, P; Westin, G; Thirlwell, C

    2016-12-01

    Neuroendocrine tumour of the small intestine (SI-NET), formerly known as midgut carcinoid tumour, is the most common small intestinal malignancy. The incidence is rising, with recent reports of 0.67 per 100 000 in the USA and 1.12 per 100 000 in Sweden. SI-NETs often present a challenge in terms of diagnosis and treatment, as patients often have widespread disease and are beyond cure by surgery. Somatostatin analogues provide the mainstay of medical treatment to control hormonal excess and increase the time to progression. Despite overall favourable prognosis (5-year overall survival of 65%), there is a need to find markers to identify both patients with worse outcome and new targets for therapy. Loss on chromosome 18 has been reported in 60-90% of SI-NETs, but mutated genes on this chromosome have failed detection. Recently, a putative tumour suppressor role has been suggested for TCEB3C occurring at 18q21 (encoding elongin A3), which may undergo epigenetic repression. CDKN1B has recently been revealed as the only recurrently mutated gene in SI-NETs but, with a frequency as low as 8%, its role as a driver in SI-NET development may be questioned. Integrated genomewide analysis including exome and whole-genome sequencing, gene expression, DNA methylation and copy number analysis has identified three novel molecular subtypes of SI-NET with differing clinical outcome. DNA methylation analysis has demonstrated that SI-NETs have significant epigenetic dysregulation in 70-80% of tumours. In this review, we focus on understanding of the genetic, epigenetic and molecular events that lead to development and progression of SI-NETs.

  15. 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).

  16. 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.

  17. 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

  18. Diacylglycerol acyltransferase-1 inhibition enhances intestinal fatty acid oxidation and reduces energy intake in rats[S

    PubMed Central

    Schober, Gudrun; Arnold, Myrtha; Birtles, Susan; Buckett, Linda K.; Pacheco-López, Gustavo; Turnbull, Andrew V.; Langhans, Wolfgang; Mansouri, Abdelhak

    2013-01-01

    Acyl CoA:diacylglycerol acyltransferase-1 (DGAT-1) catalyzes the final step in triacylglycerol (TAG) synthesis and is highly expressed in the small intestine. Because DGAT-1 knockout mice are resistant to diet-induced obesity, we investigated the acute effects of intragastric (IG) infusion of a small molecule diacylglycerol acyltransferase-1 inhibitor (DGAT-1i) on eating, circulating fat metabolites, indirect calorimetry, and hepatic and intestinal expression of key fat catabolism enzymes in male rats adapted to an 8 h feeding-16 h deprivation schedule. Also, the DGAT-1i effect on fatty acid oxidation (FAO) was investigated in enterocyte cell culture models. IG DGAT-1i infusions reduced energy intake compared with vehicle in high-fat diet (HFD)-fed rats, but scarcely in chow-fed rats. IG DGAT-1i also blunted the postprandial increase in serum TAG and increased β-hydroxybutyrate levels only in HFD-fed rats, in which it lowered the respiratory quotient and increased intestinal, but not hepatic, protein levels of Complex III of the mitochondrial respiratory chain and of mitochondrial hydroxymethylglutaryl-CoA synthase. Finally, the DGAT-1i enhanced FAO in CaCo2 (EC50 = 0.3494) and HuTu80 (EC50 = 0.00762) cells. Thus, pharmacological DGAT-1 inhibition leads to an increase in intestinal FAO and ketogenesis when dietary fat is available. This may contribute to the observed eating-inhibitory effect. PMID:23449193

  19. 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.

  20. Rat enterohepatic circulation and intestinal distribution of enterally infused thyroid hormones

    SciTech Connect

    DiStefano, J.J. III; Sternlicht, M.; Harris, D.R.

    1988-11-01

    The enterohepatic circulation (recycling), intestinal (gut) distribution, metabolism, and excretion of enterally infused thyroid hormones were studied in the intact rat under approximately normal physiological steady state conditions. Rats with 7-day osmotic minipumps implanted ip received constant intraduodenal infusions to steady state of very small trace doses of either 125I-labeled T3 (T3*) or T4 (T4*). Enterohepatic and other pathways remained open to normal function, and in particular, there was no biliary diversion or ligation. Complete feces and urine were collected daily, to assess daily distributions of radioactivity and establishment of the steady state, which occurred by day 3. On day 7, rats were anesthetized, blood was sampled, whole intestine and minipumps were removed, and the gut was separated into six segments. Fecal samples and the contents of each gut section were homogenized, ethanol extracted, evaporated, and reconstituted in NaOH for quantitative aqueous chromatography along with infusate, urine, and plasma samples, on Sephadex G-25 columns. No T3* or T4* was found in urine, but feces contained 39% of the T3* infused and 36% of the T4* infused in steady state. Statistically significant amounts of both T3* and T4* in systemic plasma on day 7 clearly indicated absorption of the hormones from the intestine, distinctly demonstrating an enterohepatic circulation of T3 and T4 under experimental conditions closely approximating the physiological steady state. This also establishes the intestine (with its contents) as an exchangeable hormone pool, physiologically internal to the system regulating thyroid hormones and their distribution. Gut contents contained 52 times more T3* and 4.34 times more T4* than corresponding plasma pools in steady state.

  1. 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

  2. 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

  3. Berberine Attenuates Intestinal Mucosal Barrier Dysfunction in Type 2 Diabetic Rats.

    PubMed

    Gong, Jing; Hu, Meilin; Huang, Zhaoyi; Fang, Ke; Wang, Dingkun; Chen, Qingjie; Li, Jingbin; Yang, Desen; Zou, Xin; Xu, Lijun; Wang, Kaifu; Dong, Hui; Lu, Fuer

    2017-01-01

    Background: Intestinal mucosal barrier dysfunction plays an important role in the development of diabetes mellitus (DM). Berberine (BBR), a kind of isoquinoline alkaloid, is widely known to be effective for both DM and diarrhea. Here, we explored whether the anti-diabetic effect of BBR was related to the intestine mucosal barrier. Methods and Results: The rat model of T2DM was established by high glucose and fat diet feeding and intravenous injection of streptozocin. Then, those diabetic rats were treated with BBR at different concentrations for 9 weeks. The results showed, in addition to hyperglycemia and hyperlipidemia, diabetic rats were also characterized by proinflammatory intestinal changes, altered gut-derived hormones, and 2.77-fold increase in intestinal permeability. However, the treatment with BBR significantly reversed the above changes in diabetic rats, presenting as the improvement of the high glucose and triglyceride levels, the relief of the inflammatory changes of intestinal immune system, and the attenuation of the intestinal barrier damage. BBR treatment at a high concentration also decreased the intestinal permeability by 27.5% in diabetic rats. Furthermore, BBR regulated the expressions of the molecules involved in TLR4/MyD88/NF-κB signaling pathways in intestinal tissue of diabetic rats. Conclusion: The hypoglycemic effects of BBR might be related to the improvement in gut-derived hormones and the attenuation of intestinal mucosal mechanic and immune barrier damages.

  4. Berberine Attenuates Intestinal Mucosal Barrier Dysfunction in Type 2 Diabetic Rats

    PubMed Central

    Gong, Jing; Hu, Meilin; Huang, Zhaoyi; Fang, Ke; Wang, Dingkun; Chen, Qingjie; Li, Jingbin; Yang, Desen; Zou, Xin; Xu, Lijun; Wang, Kaifu; Dong, Hui; Lu, Fuer

    2017-01-01

    Background: Intestinal mucosal barrier dysfunction plays an important role in the development of diabetes mellitus (DM). Berberine (BBR), a kind of isoquinoline alkaloid, is widely known to be effective for both DM and diarrhea. Here, we explored whether the anti-diabetic effect of BBR was related to the intestine mucosal barrier. Methods and Results: The rat model of T2DM was established by high glucose and fat diet feeding and intravenous injection of streptozocin. Then, those diabetic rats were treated with BBR at different concentrations for 9 weeks. The results showed, in addition to hyperglycemia and hyperlipidemia, diabetic rats were also characterized by proinflammatory intestinal changes, altered gut-derived hormones, and 2.77-fold increase in intestinal permeability. However, the treatment with BBR significantly reversed the above changes in diabetic rats, presenting as the improvement of the high glucose and triglyceride levels, the relief of the inflammatory changes of intestinal immune system, and the attenuation of the intestinal barrier damage. BBR treatment at a high concentration also decreased the intestinal permeability by 27.5% in diabetic rats. Furthermore, BBR regulated the expressions of the molecules involved in TLR4/MyD88/NF-κB signaling pathways in intestinal tissue of diabetic rats. Conclusion: The hypoglycemic effects of BBR might be related to the improvement in gut-derived hormones and the attenuation of intestinal mucosal mechanic and immune barrier damages. PMID:28217099

  5. Xanthine dehydrogenase to xanthine oxidase conversion in ischemic rat intestine

    SciTech Connect

    McKelvey, T.G.; Engerson, T.D.; Elmore, C.R.; Jones, H.P. )

    1990-02-26

    The ischemic conversion of the NADH-producing xanthine dehydrogenase (XDH) to an oxidase form, that produces both superoxide radical and hydrogen peroxide, has been proposed as an important step in initiating oxygen radical-mediated ischemia-reperfusion injury. It has also been reported that two forms of converted oxidase are produced in ischemic rat liver; a reversible xanthine oxidase produced through sulfhydryl oxidation, that can be reconverted to XDH by incubation with 10mM dithiothreitol (Dtt) at 37{degrees}C, and a Dtt-irreversible oxidase produced via proteolysis. The authors report that increased oxidase in the ischemic rat intestine results from significant increases in both the Dtt-reversible and Dtt-irreversible forms of xanthine oxidase. Total oxidase activity (Irreversible + Dtt-reversible) was 19% of the total enzyme activity (XDH + XO) in control ileum and distal jejunum, increased to 26% after 1 hour of ischemia at 37{degrees}C, and significantly to 36% after 1.5 hours. After 3 hours 73% of the activity was in the oxidase form. Irreversible oxidase comprised 15% of the total activity in control intestine, significantly increased to 25% after 2 hours, and further to 42% after 3 hours. Dtt-reversible oxidase was 3% of the total activity in controls, increased to 13% after 1.5 hours, and significantly to 29% after 2 hours.

  6. 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.

  7. The Mesenteric Lymph Duct Cannulated Rat Model: Application to the Assessment of Intestinal Lymphatic Drug Transport

    PubMed Central

    Trevaskis, Natalie L.; Hu, Luojuan; Caliph, Suzanne M.; Han, Sifei; Porter, Christopher J.H.

    2015-01-01

    The intestinal lymphatic system plays key roles in fluid transport, lipid absorption and immune function. Lymph flows directly from the small intestine via a series of lymphatic vessels and nodes that converge at the superior mesenteric lymph duct. Cannulation of the mesenteric lymph duct thus enables the collection of mesenteric lymph flowing from the intestine. Mesenteric lymph consists of a cellular fraction of immune cells (99% lymphocytes), aqueous fraction (fluid, peptides and proteins such as cytokines and gut hormones) and lipoprotein fraction (lipids, lipophilic molecules and apo-proteins). The mesenteric lymph duct cannulation model can therefore be used to measure the concentration and rate of transport of a range of factors from the intestine via the lymphatic system. Changes to these factors in response to different challenges (e.g., diets, antigens, drugs) and in disease (e.g., inflammatory bowel disease, HIV, diabetes) can also be determined. An area of expanding interest is the role of lymphatic transport in the absorption of orally administered lipophilic drugs and prodrugs that associate with intestinal lipid absorption pathways. Here we describe, in detail, a mesenteric lymph duct cannulated rat model which enables evaluation of the rate and extent of lipid and drug transport via the lymphatic system for several hours following intestinal delivery. The method is easily adaptable to the measurement of other parameters in lymph. We provide detailed descriptions of the difficulties that may be encountered when establishing this complex surgical method, as well as representative data from failed and successful experiments to provide instruction on how to confirm experimental success and interpret the data obtained. PMID:25866901

  8. 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.

  9. Enzymatic biodegradation of hydrogels for protein delivery targeted to the small intestine.

    PubMed

    Knipe, Jennifer M; Chen, Frances; Peppas, Nicholas A

    2015-03-09

    Multiresponsive poly(methacrylic acid-co-N-vinylpyrrolidone) hydrogels were synthesized with biodegradable oligopeptide crosslinks. The oligopeptide crosslinks were incorporated using EDC-NHS zero-length links between the carboxylic acid groups of the polymer and free primary amines on the peptide. The reaction of the peptide was confirmed by primary amine assay and IR spectroscopy. The microgels exhibited pH-responsive swelling as well as enzyme-catalyzed degradation targeted by trypsin present in the small intestine, as demonstrated upon incubation with gastrointestinal fluids from rats. Relative turbidity was used to evaluate enzyme-catalyzed degradation as a function of time, and initial trypsin concentration controlled both the degradation mechanism as well as the extent of degradation. Trypsin activity was effectively extinguished by incubation at 70 °C, and both the microgels and degradation products posed no cytotoxic effect toward two different cell lines. The microgels demonstrated pH-dependent loading of the protein insulin for oral delivery to the small intestine.

  10. 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.

  11. A model for calcium permeation into small intestine.

    PubMed

    Dolinska, Barbara; Mikulska, Agnieszka; Caban, Artur; Ostrozka-Cieslik, Aneta; Ryszka, Florian

    2011-09-01

    An in vitro model was used to simulate the intestinal permeation of calcium ions depending on the type of salt (carbonate, fumarate, citrate, or gluconate), its concentration (1.0, 2.5, 5.0, or 10 mM/l), and pH (1.3, 4.2, 6.2, or 7.5). To simulate the conditions for calcium permeation in a patient in a fasting state, the solutions were placed in contact with segments of small intestine of pig: stomach, duodenum, jejunum, and ileum. The percent permeation, its rate, and half-time were measured in each case. In all cases, the maximum permeation was seen at 1 mM concentration, depending on pH: 100% for carbonate at pH 1.3; 82% for fumarate, pH 6.2; 79.5% for citrate at pH 4.2, and 81% for gluconate at pH 7.4. The maximum rate of permeation (% h(-1)) was also observed at 1 mM: 2.16 for carbonate at pH 1.3, 0.29 for fumarate at pH 6.2, 0.26 for citrate at pH 4.2, and 0.28 for gluconate at pH 7.4. The shortest half-time permeation (t (1/2), h) for 1 mM solutions depended also on pH (in parentheses): carbonate 0.3 (1.3), fumarate 2.4 (6.2), citrate 2.6 (4.2), and gluconate 2.5 (7.4). The results suggest that calcium carbonate and citrate can be recommended to patients with normal gastric acidity and hyperacidity while fumarate and gluconate to patients with hypoacidity.

  12. Subacute stress and chronic stress interact to decrease intestinal barrier function in rats.

    PubMed

    Lauffer, Adriana; Vanuytsel, Tim; Vanormelingen, Christophe; Vanheel, Hanne; Salim Rasoel, Shadea; Tóth, Joran; Tack, Jan; Fornari, Fernando; Farré, Ricard

    2016-01-01

    Psychological stress increases intestinal permeability, potentially leading to low-grade inflammation and symptoms in functional gastrointestinal disorders. We assessed the effect of subacute, chronic and combined stress on intestinal barrier function and mast cell density. Male Wistar rats were allocated to four experimental groups (n = 8/group): 1/sham; 2/subacute stress (isolation and limited movement for 24 h); 3/chronic crowding stress for 14 days and 4/combined subacute and chronic stress. Jejunum and colon were collected to measure: transepithelial electrical resistance (TEER; a measure of epithelial barrier function); gene expression of tight junction molecules; mast cell density. Plasma corticosterone concentration was increased in all three stress conditions versus sham, with highest concentrations in the combined stress condition. TEER in the jejunum was decreased in all stress conditions, but was significantly lower in the combined stress condition than in the other groups. TEER in the jejunum correlated negatively with corticosterone concentration. Increased expression of claudin 1, 5 and 8, occludin and zonula occludens 1 mRNAs was detected after subacute stress in the jejunum. In contrast, colonic TEER was decreased only after combined stress, and the expression of tight junction molecules was unaltered. Increased mast cell density was observed in the chronic and combined stress condition in the colon only. In conclusion, our data show that chronic stress sensitizes the gastrointestinal tract to the effects of subacute stress on intestinal barrier function; different underlying cellular and molecular alterations are indicated in the small intestine versus the colon.

  13. 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

  14. 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

  15. Regulation of GLUT5 gene expression in rat intestinal mucosa: regional distribution, circadian rhythm, perinatal development and effect of diabetes.

    PubMed Central

    Castelló, A; Gumá, A; Sevilla, L; Furriols, M; Testar, X; Palacín, M; Zorzano, A

    1995-01-01

    1. GLUT5 gene expression was studied in small intestine under a variety of conditions characterized by altered intestinal absorption of monosaccharides. 2. RNA-blotting studies showed that GLUT5 mRNA was abundantly expressed in rat and rabbit intestine and kidney, but it was not detected in heart or brown adipose tissue. GLUT5 mRNA levels were higher in the upper segments of the small intestine (duodenum and proximal jejunum) than in the lower segments (distal jejunum and ileum). 3. The intestinal expression of GLUT5 mRNA in rat proximal jejunum showed circadian rhythm. A 12-fold increase in GLUT5 mRNA levels was detected at the end of the light cycle and at the beginning of the dark cycle when compared with the early light period. In keeping with this, GLUT5 protein content in brush-border membranes was also increased at the beginning of the dark cycle compared with that in the light period. 4. In streptozotocin-induced diabetes an 80% increase in GLUT5 mRNA levels in mucosa from the proximal jejunum was detected under conditions in which enhanced intestinal absorption of monosaccharides has been reported. 5. The intestinal expression of GLUT5 mRNA showed regulation during perinatal development. Levels of GLUT5 mRNA were low during fetal life, increased progressively during the postnatal period and reached levels comparable with the adult state after weaning. Weaning on to a high-fat diet partially prevented the induction of GLUT5 gene expression. 6. Our results indicate that GLUT5 gene expression is tightly regulated in small intestine. Regulation involves maximal expression in the upper part of the small intestine, circadian rhythm, developmental regulation dependent on the fat and carbohydrate content in the diet at weaning and enhanced expression in streptozotocin-induced diabetes. Furthermore, changes observed in intestinal GLUT5 expression correlate with reported alterations in intestinal absorption of fructose. This suggests a regulatory role for GLUT5 in

  16. Alanyl-glutamine dipeptide-supplemented parenteral nutrition improves intestinal metabolism and prevents increased permeability in rats.

    PubMed Central

    Haque, S M; Chen, K; Usui, N; Iiboshi, Y; Okuyama, H; Masunari, A; Cui, L; Nezu, R; Takagi, Y; Okada, A

    1996-01-01

    OBJECTIVE: The authors determined the effects of alanyl-glutamine-supplemented total parenteral nutrition (TPN) on mucosal metabolism, integrity, and permeability of the small intestine in rats. METHODS: Male Sprague-Dawley rats were randomized to receive TPN supplemented with a conventional amino acids mixture (STD group) or the same solution supplemented with alanyl-glutamine; both solutions were isocaloric and isonitrogenous. On the seventh day of TPN, D-xylose and fluorescein isothiocyanate (FITC)-dextran were administered orally. One hour later, superior mesenteric vein (SMV) D-xylose and plasma FITC-dextran concentration were measured. Intestinal blood flow and calculated intestinal substrates flux were measured with ultrasonic transit time flowmetery. RESULTS: Plasma FITC-dextran increased significantly in the STD group. Intestinal blood flow and SMV D-xylose concentration did not differ between the groups. Mucosa weight, villus height, mucosal wall thickness, mucosal protein, and DNA and RNA content in jejunal mucosa were significantly increased in the alanyl-glutamine group. Jejunal mucosal glutaminase activity and net intestinal uptake of glutamine (glutamine flux) were significantly higher in the alanyl-glutamine group as compared with the STD group. CONCLUSION: Addition of alanyl-glutamine dipeptide to the TPN solution improves intestinal glutamine metabolism and prevents mucosal atrophy and deterioration of permeability. PMID:8604914

  17. The influence of cooked kidney beans (Phaseolus vulgaris) on intestinal cell turnover and faecal nitrogen excretion in the rat.

    PubMed

    Fairweather-Tait, S J; Gee, J M; Johnson, I T

    1983-05-01

    Male Wistar rats were fed on semi-synthetic diets containing cooked white kidney beans (Phaseolus vulgaris) or equivalent levels of protein and carbohydrate. No change was observed in over-all nitrogen balance in animals fed on the bean diet, but there was a two- to three-fold increase in their faecal excretion, compared with control rats. This was compensated by a decrease in urinary-N excretion. Homogenized small intestinal mucosa, prepared from bean-fed animals, showed a 28% increase in protein content compared with control material. Measurements of 3H-labelled thymidine turnover indicated that mucosal cell exfoliation was increased by approximately 35% in the small intestines of bean-fed rats compared with controls. It is concluded that though a diet rich in cooked P. vulgaris leads to some increase in mucosal cell turnover in the small intestine of rats, the consequent increase in mucosal protein loss could not account for the increased faecal-N excretion seen in these animals.

  18. Cat eye syndrome associated with aganglionosis of the small and large intestine.

    PubMed

    Ward, J; Sierra, I A; D'Croz, E

    1989-10-01

    A newborn male infant is presented with the characteristic phenotype of the cat eye syndrome and a small supernumerary chromosome shorter than a 22. He also had complete absence of parasympathetic ganglion cells throughout the small and large intestine.

  19. A Novel Model of P-Glycoprotein Inhibitor Screening Using Human Small Intestinal Organoids.

    PubMed

    Zhao, Junfang; Zeng, Zhiyang; Sun, Jialiang; Zhang, Yuanjin; Li, Dali; Zhang, Xueli; Liu, Mingyao; Wang, Xin

    2017-03-01

    P-glycoprotein (P-gp), an important efflux transporter in intestine, regulates the bioavailability of orally taken drugs. To develop an in vitro model that preferably mimics the physiological microenvironment of human intestine, we employed the three-dimensionally (3D) cultured organoids from human normal small intestinal epithelium. It was observed that the intestinal crypts could efficiently form cystic organoid structure with the extension of culture time. Furthermore, the physiological expression of ABCB1 was detected at both mRNA and protein levels in cultured organoids. Rhodamine 123 (Rh123), a typical substrate of P-gp, was actively transported across 3D organoids and accumulated in the luminal space. This transport process was also inhibited by verapamil and mitotane. In summary, the above-mentioned model based on human small intestinal 3D organoids is suitable to imitate the small intestinal epithelium and could be used as a novel in vitro model especially for P-gp inhibitor screening.

  20. Failure of d-psicose absorbed in the small intestine to metabolize into energy and its low large intestinal fermentability in humans.

    PubMed

    Iida, Tetsuo; Hayashi, Noriko; Yamada, Takako; Yoshikawa, Yuko; Miyazato, Shoko; Kishimoto, Yuka; Okuma, Kazuhiro; Tokuda, Masaaki; Izumori, Ken

    2010-02-01

    Experiments with rats have produced data on the metabolism and energy value of d-psicose; however, no such data have been obtained in humans. The authors assessed the availability of d-psicose absorbed in the small intestine by measuring carbohydrate energy expenditure (CEE) by indirect calorimetry. They measured the urinary excretion rate by quantifying d-psicose in urine for 48 hours. To examine d-psicose fermentation in the large intestine, the authors measured breath hydrogen gas and fermentability using 35 strains of intestinal bacteria. Six healthy subjects participated in the CEE test, and 14 participated in breath hydrogen gas and urine tests. d-Psicose fermentation subsequent to an 8-week adaptation period was also assessed by measuring hydrogen gas in 8 subjects. d-Psicose absorbed in the small intestine was not metabolized into energy, unlike glucose, because CEE did not increase within 3 hours of d-psicose ingestion (0.35 g/kg body weight [BW]). The accumulated d-psicose urinary excretion rates were around 70% for 0.34, 0.17, and 0.08 g/kg BW of ingested d-psicose. Low d-psicose fermentability was observed in intestinal bacteria and breath hydrogen gas tests, in which fructooligosaccharide (0.34, 0.17, and 0.08 g/kg BW) was used as a positive control because its available energy is known to be 8.4 kJ/g. Based on the results of the plot of breath hydrogen concentration vs calories ingested, the energy value of d-psicose was expected to be less than 1.6 kJ/g. Incremental d-psicose fermentability subsequent to an adaptation period was not observed.

  1. P-glycoprotein (P-gp)-mediated efflux limits intestinal absorption of the Hsp90 inhibitor SNX-2112 in rats.

    PubMed

    Liu, Hongming; Sun, Hua; Wu, Zhufeng; Zhang, Xingwang; Wu, Baojian

    2014-08-01

    1. The promising anticancer agent SNX-2112 (a novel Hsp90 inhibitor) is poorly bioavailable after oral administration. Here, we aim to determine the role of P-glycoprotein (P-gp) in the intestinal absorption of SNX-2112. 2. We found that SNX-2112 significantly stimulated P-gp ATPase activity in in vitro ATPase assay with a small EC50 (the half-maximal effective concentration) value of 0.32 µM. 3. In the single-pass perfused rat intestine model, absorption of SNX-2112 was not favored in the small intestine with a [Formula: see text] (the wall permeability) value of 0.38-0.64. By contrast, the compound was well absorbed in the colon with a [Formula: see text] value of 1.19. The P-gp inhibitors cyclosporine and elacridar (i.e. GF120918A) markedly enhanced SNX-2112 absorption in all four intestinal segments (i.e. duodenum, jejunum, ileum and colon) and the fold change ranged from 3.1 to 14.1. Pharmacokinetic study revealed that cyclosporine increased the systemic exposure of SNX-2112 by a 2.5-fold after oral administration. 4. This is the first report that P-gp-mediated efflux is a limiting factor for intestinal absorption of SNX-2112 in rats.

  2. The preventive effects of dexmedetomidine against intestinal ischemia-reperfusion injury in Wistar rats

    PubMed Central

    Zhang, Xue-kang; Zhou, Xiao-ping; Zhang, Qin; Zhu, Feng

    2015-01-01

    Objective(s): Intestinal ischemia-reperfusion is a major problem, which may lead to multiorgan failure and death. The aim of this study was to evaluate the protective effects of dexmedetomidine on cell proliferation, antioxidant system, cell death, and structural integrity in intestinal injury induced by ischemia-reperfusion in rats. Materials and Methods: Animals were randomized into three groups: group A, sham-operated or control; group B, intestinal ischemia/reperfusion (IR); and group C, intestinal IR pretreated with 50 μg of dexmedetomidine. Intestine tissue was collected from all rats 30 min after desufflation, and fresh frozen for histological and biochemical evaluation. Results: The intestinal tissue of group B rats showed a significant decrease in the antioxidant enzyme activities. However, these enzyme activities were improved by the administration of dexmedetomidine. Inhibiting the protein expression of MCP7, PAR2, P-JAK, P-STAT1, and P-STAT3 proved the protective effect of dexmedetomidine. The immunohistochemical staining revealed its protective effect by maintaining the normal structural integrity, less caspase-3 immuno reactivity, and increased cell proliferation count in the intestinal tissues. Conclusions: Intraperitoneal injection of dexmedetomidine significantly protected intestine IR injury in rats by inhibiting the inflammatory response, intestinal epithelial apoptosis, and maintaining structural integrity of intestinal cells. PMID:26221485

  3. 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.

  4. Morphometric characteristics of the small and large intestines of Mus musculus during postnatal development.

    PubMed

    Wołczuk, K; Wilczyńska, B; Jaroszewska, M; Kobak, J

    2011-11-01

    The objective of this study was to investigate the size of the small and large intestine in postnatal development of Mus musculus mice. The gut was obtained from 2-, 4-, 6-, and 12-week-old animals. The morphometric analysis was performed at microscopic level. Measurements and calculations included dimensions of villi (height, diameter) and their number per 1 mm(2) surface area in the proximal, middle, and distal section of the small intestine, as well as the length and surface area (external and internal) of the small and large intestines. To find the allometric relationship between the size of the small and large intestines and body mass, reduced major axis regression was applied. The length and surface area of both intestinal segments gradually increased with age. The increase in the internal surface area of the small intestine was the result of lengthening of the intestine and increasing diameter of the villi in its proximal and middle sections. No increase in villus height during the studied period was detected. A marked increase in the size of the intestinal segments was observed between the 2(nd) and 4(th) weeks of life, when the length doubled and the surface area tripled in size. Allometric analysis revealed that the increase in length and internal surface area of the small and large intestines was more rapid than the body mass increase during the weaning period, while it was not different from isometry after the weaning. In conclusion, the greatest changes in the structure and size of the small and large intestines of mice occurred in the weaning period. During this period these two segments of intestine grew faster than the rest of the body and reached adult proportions.

  5. Absorption enhancing effects of chitosan oligomers on the intestinal absorption of low molecular weight heparin in rats.

    PubMed

    Zhang, Hailong; Mi, Jie; Huo, Yayu; Huang, Xiaoyan; Xing, Jianfeng; Yamamoto, Akira; Gao, Yang

    2014-05-15

    Absorption enhancing effects of chitosan oligomers with different type and varying concentration on the intestinal absorption of low molecular weight heparin (LMWH) were examined by an in situ closed loop method in different intestinal sections of rats. Chitosan hexamer with the optimal concentration of 0.5% (w/v) showed the highest absorption enhancing ability both in the small intestine and large intestine. The membrane toxicities of chitosan oligomers were evaluated by morphological observation and determining the biological markers including amount of protein and activity of lactate dehydrogenase (LDH) released from intestinal epithelium cells. There was no obvious change both in levels of protein and LDH and morphology in the intestinal membrane between control and various chitosan oligomers groups, suggesting that chitosan oligomers did not induce any significant membrane damage to the intestinal epithelium. In addition, zeta potentials became less negative and amount of free LMWH gradually decreased when various chitosan oligomers were added to LMWH solution, revealing that electrostatic interaction between positively charged chitosan oligomers and negative LMWH was included in the absorption enhancing mechanism of chitosan oligomers. In conclusion, chitosan oligomers, especially chitosan hexamer, are safe and efficient absorption enhancers and can be used promisingly to improve oral absorption of LMWH.

  6. Heavy ion induced changes in small intestinal parameters

    NASA Astrophysics Data System (ADS)

    Carr, K. E.; McCullough, J. S.; Brennan, P.; Hayes, T. L.; Ainsworth, E. J.; Nelson, A. C.

    1994-10-01

    The effects on 17 different structural parameters of mouse small intestine three days after treatment with three types of heavy ion (neon, iron and niobium) are compared, the first two being of particular relevance to space flight. The data for niobium are given in full, showing that changes after niobium ion treatment are not standard and are concentrated in the epithelial compartment, with few of the parameters having a response which is dose dependent. When comparisons are made for the three types of heavy ion, the damage is greatest after neon ion irradiation, implying that the additional non-epithelial damage produced as LET rises from X rays through neutrons to neon ions is not necessarily maintained as LET continues to rise. Further understanding is therefore needed of the balance between changes affecting the vascular and absorptive components of the organ. Variation from group to group is also important, as is variation of strain or gastrointestinal status. All such factors are important in the understanding of changes in multicellular organs after exposure to heavy ion radiation.

  7. Protective role of adiponectin in a rat model of intestinal ischemia reperfusion injury

    PubMed Central

    Liu, Xu-Hui; Yang, Yue-Wu; Dai, Hai-Tao; Cai, Song-Wang; Chen, Rui-Han; Ye, Zhi-Qiang

    2015-01-01

    AIM: To determine the potential protective role of adiponectin in intestinal ischemia reperfusion (I/R) injury. METHODS: A rat model of intestinal I/R injury was established. The serum level of adiponectin in rats with intestinal I/R injury was determined by enzyme-linked immunosorbent assay (ELISA). The serum levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were also measured by ELISA. Apoptosis of intestinal cells was detected using the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. The production of malondialdehyde (MDA) and superoxide dismutase (SOD) and villous injury scores were also measured. RESULTS: Adiponectin was downregulated in the serum of rats with intestinal I/R injury compared with sham rats. No significant changes in the expression of adiponectin receptor 1 and adiponectin receptor 2 were found between sham and I/R rats. Pre-treatment with recombinant adiponectin attenuated intestinal I/R injury. The production of pro-inflammatory cytokines, including IL-6, IL-1β, and TNF-α, in rats with intestinal I/R injury was reduced by adiponectin pre-treatment. The production of MDA was inhibited, and the release of SOD was restored by adiponectin pre-treatment in rats with intestinal I/R injury. Adiponectin pre-treatment also inhibited cell apoptosis in these rats. Treatment with the AMP-activated protein kinase (AMPK) signaling pathway inhibitor, compound C, or the heme oxygenase 1 (HO-1) inhibitor, Snpp, attenuated the protective effects of adiponectin against intestinal I/R injury. CONCLUSION: Adiponectin exhibits protective effects against intestinal I/R injury, which may involve the AMPK/HO-1 pathway. PMID:26715807

  8. 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.

  9. The Virtual Intestine: in-silico modeling of small intestinal electrophysiology and motility and the applications

    PubMed Central

    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 co-regulated 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 multi-scale research challenges in interdisciplinary gastrointestinal sciences. PMID:26562482

  10. Survival After Total Body Irradiation: Effects of Irradiation of Exteriorized Small Intestine

    DTIC Science & Technology

    1993-01-01

    exteriorized small intestine H . M. Vriesendorp 1, R. M. Vigneulle’, G. Kitto ’, T. Pelky t, P. Taylor ’-* and J . Smith ’Armed Forces Radiobiologv...P., Fiedner, T. M. and Archambeau, J . 0. Mare- Schultheiss, T. E. and Jardine, J . H . Acute and late radiation malian Radiation Lethality, a...acute intestinal 4 Dowling, R. H . Update on intestinal adaptation. Triangle radiation syndrome through shielding. Am. J . Physiol. 185, Sandoz J . Med

  11. Beneficial influence of dietary spices on the ultrastructure and fluidity of the intestinal brush border in rats.

    PubMed

    Prakash, Usha N S; Srinivasan, Krishnapura

    2010-07-01

    The beneficial influence of three common spices was examined in experimental rats on: (i) the membrane fluidity of intestinal brush-border membranes (BBM), (ii) the activity of intestinal membrane-bound enzymes, and (iii) ultrastructural alterations in the intestinal epithelium. Groups of male Wistar rats were maintained on dietary black pepper (0.5 %), red pepper (3.0 %), ginger (0.05 %) and spice bioactive compounds piperine (0.02 %) and capsaicin (0.01 %) for 8 weeks. A membrane fluidity study using an apolar fluorescent probe showed increased BBM fluidity in all the spice-fed animals. This was corroborated by a decreased cholesterol:phospholipid ratio in the jejunal and ileal regions of the intestine. These dietary spices stimulated the activities of BBM enzymes (glycyl-glycine dipeptidase, leucine amino peptidase and gamma-glutamyl transpeptidase) in the jejunal mucosa, suggesting a modulation in membrane dynamics due to the apolar spice bioactive compounds interacting with surrounding lipids and hydrophobic portions in the protein vicinity, which may decrease the tendency of membrane lipids to act as steric constraints to enzyme proteins and thus modify enzyme conformation. Scanning electronic microscopy of the intestinal villi in these spice treatments revealed alterations in the ultrastructure, especially an increase in microvilli length and perimeter which would mean a beneficial increase in the absorptive surface of the small intestine, providing for an increased bioavailability of micronutrients. Thus, dietary spices (black pepper, red pepper and ginger) were evidenced to induce alterations in BBM fluidity and passive permeability property, associated with the induction of an increased microvilli length and perimeter, resulting in an increased absorptive surface of the small intestine.

  12. Isolation of high density lipoproteins from rat intestinal epithelial cells.

    PubMed Central

    Magun, A M; Brasitus, T A; Glickman, R M

    1985-01-01

    Previous studies have defined forms of high density lipoproteins (HDL) in rat mesenteric lymph, suggesting that they have a secretory origin. This study describes the isolation and characterization of intestinal intracellular HDL. Two preparations were made as follows: (a) Rat enterocytes were isolated and a Golgi organelle fraction was prepared. (b) Cell homogenates were subjected to nitrogen cavitation and a cytoplasmic fraction was prepared. Lipoproteins were isolated from both preparations by sequential ultracentrifugation. When the HDL fraction (1.07-1.21 g/ml) was subjected to isopyknic density gradient ultracentrifugation, a peak of apoproteins A-I and B (apoA-I and apoB, respectively) was found at a density of 1.11-1.14 g/ml. Electron microscopy of the fraction showed spherical particles ranging in size from 6 to 13 nm. Immunoelectrophoresis revealed a precipitin arc in the alpha region against apoA-I which extended into the pre-beta region where a precipitin arc against apoB was also seen. ApoB antisera depleted the pre-beta particles whereas the alpha migrating particles remained. Lipid analysis of the whole HDL fraction revealed phospholipid, cholesteryl ester, and triglyceride as the major lipids. [3H]leucine was then administered into the duodenum and a radiolabeled intracellular HDL fraction was isolated. The newly synthesized apoproteins of the HDL fraction, as determined by gel electrophoresis, were apoB, apoA-I, and apolipoprotein A-IV (ApoA-IV). Immunoprecipitation of the apoB particles revealed apoA-I and apoA-IV in the supernatant. These data demonstrate that there are at least two intracellular intestinal forms of HDL particles, one of which contains apoB. The other particle contains apoA-I and apoA-IV, has alpha mobility, is spherical, and resembles a particle found in the lymph. Images PMID:3965504

  13. Consequences of Mrp2 deficiency for diclofenac toxicity in the rat intestine ex vivo.

    PubMed

    Niu, Xiaoyu; de Graaf, Inge A M; van de Vegte, Dennis; Langelaar-Makkinje, Miriam; Sekine, Shuichi; Groothuis, Geny M M

    2015-02-01

    The non-steroidal anti-inflammatory drug diclofenac (DCF) has a high prevalence of intestinal side effects in humans and rats. It has been reported that Mrp2 transporter deficient rats (Mrp2) are more resistant to DCF induced intestinal toxicity. This was explained in vivo by impaired Mrp2-dependent biliary transport of DCF-acylglucuronide (DAG), leading to decreased intestinal exposure to DAG and DCF. However, it is not known to what extent adaptive changes in the Mrp2 intestine itself influence its sensitivity to DCF toxicity without the influence of liver metabolites. To investigate this, DCF toxicity and disposition were studied ex vivo by precision-cut intestinal slices and Ussing chamber using intestines from wild type(WT) and Mrp2 rats. The results show that adaptive changes due to Mrp2 deficiency concerning Mrp2, Mrp3 and BCRP gene expression, GSH content and DAG formation were different between liver and intestine. Furthermore, Mrp2 intestine was intrinsically more resistant to DCF toxicity than its WT counterpart ex vivo. This can at least partly be explained by a reduced DCF uptake by the Mrp2 intestine, but isnot related to the other adaptive changes in the intestine. The extrapolation of this data to humans with MRP2 deficiency is uncertain due to species differences in activity and regulation of transporters.

  14. 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.

  15. Role of parotid amylase in starch digestion in the gastro-intestinal tracts of diabetic rats.

    PubMed

    Kurahashi, M; Inomata, K

    1989-09-01

    In order for the role of parotid amylase in starch digestion in the gastro-intestinal tracts of diabetic rats to be clarified, this study investigated the effect of parotid-duct ligation on both amylase secretion from the parotid glands and pancreas into the gastro-intestinal tract and on starch digestion in the gastro-intestinal contents during feedings. In both diabetic rats and control rats, parotid-duct ligation reduced amylase activity in both the parotid glands during fasting and in the gastric contents after feeding. The amylase activity in the intestinal contents after feeding was reduced by parotid-duct ligation in the diabetic rats. Starch digestion in the gastro-intestinal tract after feeding was reduced by parotid-duct ligation in the diabetic rats. The results suggest that most of the amylase activity in the gastric contents and a large part of the amylase activity in the intestinal contents are derived from the parotid glands, and that parotid amylase plays an important role in starch digestion in the gastro-intestinal tracts of diabetic rats.

  16. Diffuse lymphoplasmacytic infiltration of the small intestine with damage to nerve plexus. A cause of intestinal pseudo-obstruction.

    PubMed

    Arista-Nasr, J; González-Romo, M; Keirns, C; Larriva-Sahd, J

    1993-08-01

    We describe the clinicopathologic characteristics of three patients with chronic intestinal pseudo-obstruction and malabsorption. The patients were young women (average age, 25 years) who presented with abdominal pain, nausea, vomiting, diarrhea, and weight loss that led to extreme inanition and death in two patients despite multiple treatment schemes. The evolution of the process averaged 8 years. No case manifested evidence of malignant lymphoproliferative progression. Histologically, a diffuse lymphoplasmacytic infiltrate that affected all the layers of the intestinal wall was observed in full-thickness biopsy specimens. The proliferating lymphocytes were small and mixed with mature plasma cells that proved to be polyclonal on immunohistochemical analysis. An outstanding finding in all three cases was extensive damage to submucosal and myenteric nerve plexus associated with a lymphoid infiltrate. Quantification of the myenteric plexus by using immunohistochemical and morphometric techniques also revealed a marked reduction in their number. We concluded that diffuse lymphoplasmacytic infiltration of the small intestine associated with damage to the intestinal nerve plexus constitutes a specific disorder that is different from other diseases that produce intestinal pseudo-obstruction.

  17. 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.

  18. Occurrence of small intestinal volvulus in a terrier puppy-a case report

    PubMed Central

    Golshahi, Hannaneh; Tavasoly, Abbas; Namjoo, Abdolrasol; Bahmani, Mahmoud

    2014-01-01

    Volvulus is the torsion of an organ around its root. In dogs, volvulus of the stomach is well known, but volvulus of the small intestine is rare. A dead 3-month-old female terrier puppy was presented for postmortem examination. According to owner statements, the puppy was depressed, lethargic and had abdominal pain, abdominal distension, severe diarrhea and vomiting a few hours before death. With gross and histopathologic studies, the death of this puppy was indorsed to small intestinal volvulus, subsequent infarction, peritonitis and likely acute toxaemia and/or septicaemia. The present case is going to be the first recorded case of small intestinal volvulus in dog in Iran.

  19. Melatonin Immunoreactivity in Malignant Small Intestinal Neuroendocrine Tumours

    PubMed Central

    Söderquist, Fanny; Janson, Eva Tiensuu; Rasmusson, Annica J.; Ali, Abir; Stridsberg, Mats; Cunningham, Janet L.

    2016-01-01

    Background/Aims Small intestinal neuroendocrine tumours (SI-NETs) are derived from enterochromaffin cells. After demonstrating melatonin in enterochromaffin cells, we hypothesized that SI-NETs may express and secrete melatonin, which may have an impact on clinical factors and treatment response. Methods Tumour tissue from 26 patients with SI-NETs, representing paired sections of primary tumour and metastasis, were immunohistochemically stained for melatonin and its receptors, MT1 and MT2. Plasma melatonin and immunoreactivity (IR) for melatonin, MT1 and MT2 in tumour cells were compared to other tumour markers and clinical parameters. Melatonin was measured at two time points in fasting morning plasma from 43 patients with SI-NETs. Results Melatonin IR was found in all SI-NETS. Melatonin IR intensity in primary tumours correlated inversely to proliferation index (p = 0.022) and patients reported less diarrhoea when melatonin IR was high (p = 0.012). MT1 IR was low or absent in tumours. MT2 expression was medium to high in primary tumours and generally reduced in metastases (p = 0.007). Plasma-melatonin ranged from 4.5 to 220.0 pg/L. Higher levels were associated with nausea at both time points (p = 0.027 and p = 0.006) and flush at the second sampling. In cases with disease stabilization or remission (n = 34), circulating melatonin levels were reduced in the second sample (p = 0.038). Conclusion Immunoreactive melatonin is present in SI-NETs. Circulating levels of melatonin in patients with SI-NETs are reduced after treatment. Our results are congruent with recent understanding of melatonin’s endocrine and paracrine functions and SI-NETs may provide a model for further studies of melatonin function. PMID:27736994

  20. Parameterization of small intestinal water volume using PBPK modeling.

    PubMed

    Maharaj, Anil; Fotaki, Nikoletta; Edginton, Andrea

    2015-01-25

    To facilitate accurate predictions of oral drug disposition, mechanistic absorption models require optimal parameterization. Furthermore, parameters should maintain a biological basis to establish confidence in model predictions. This study will serve to calculate an optimal parameter value for small intestinal water volume (SIWV) using a model-based approach. To evaluate physiologic fidelity, derived volume estimates will be compared to experimentally-based SIWV determinations. A compartmental absorption and transit (CAT) model, created in Matlab-Simulink®, was integrated with a whole-body PBPK model, developed in PK-SIM 5.2®, to provide predictions of systemic drug disposition. SIWV within the CAT model was varied between 52.5mL and 420mL. Simulations incorporating specific SIWV values were compared to pharmacokinetic data from compounds exhibiting solubility induced non-proportional changes in absorption using absolute average fold-error. Correspondingly, data pertaining to oral administration of acyclovir and chlorothiazide were utilized to derive estimates of SIWV. At 400mg, a SIWV of 116mL provided the best estimates of acyclovir plasma concentrations. A similar SIWV was found to best depict the urinary excretion pattern of chlorothiazide at a dose of 100mg. In comparison, experimentally-based estimates of SIWV within adults denote a central tendency between 86 and 167mL. The derived SIWV (116mL) represents the optimal parameter value within the context of the developed CAT model. This result demonstrates the biological basis of the widely utilized CAT model as in vivo SIWV determinations correspond with model-based estimates.

  1. Laser acupuncture causes thermal changes in small intestine meridian pathway.

    PubMed

    de Souza, Regina Célia; Pansini, Mario; Arruda, Gisele; Valente, Caroline; Brioschi, Marcos Leal

    2016-11-01

    The acupuncture meridians represent the flow of corporal energy which contains the acupuncture points. Laser acupuncture is a form of acupuncture stimulation by the use of laser. Thermographic images represent the propagation of heat in micro-environmental systems. The objective of this study was to investigate the use of thermographic images to document the changes on the small intestine meridian (S.I.M.) when submitted to laser acupuncture. Another important issue regards to the analysis of the flow direction if it is upward when stimulated by acupuncture points. For the execution of this work, a laser acupuncture pen was used in points of the meridian in the S.I.M. Two healthy male volunteers were selected (18 and 60 years old, respectively), and doses of 576,92 J/cm(2) with low-power infrared laser equipment with a wavelength of 780 nm in the SI.3 and SI.19 points were applied. An infrared thermal camera was used to measure the temperature of the S.I.M. during the 6 min laser acupuncture pen stimulus. When the laser acupuncture of both volunteers was conducted in the SI.3 point, it presented hyper-radiation of the hemi face in the same side, far from the application site. When this was applied in the SI.19 point, hyper-radiation in the same point and temperature lowering at the end of the meridian were observed. The laser energy caused thermal changes along the path of the S.I.M., distal, and proximal at the same time, proving the existence of the S.I.M.

  2. Effects of exposure to cigarette smoke on intestinal propulsion in rats.

    PubMed

    Furuno, K; Okazaki, M; Eto, K; Kawasaki, H; Gomita, Y

    1995-08-01

    The effects of acute exposure to cigarette smoke and systemic administration of nicotine on intestinal propulsion were investigated in rats. The propulsive activity was measured as migration of charcoal powder in the intestine. This activity was suppressed by acute exposure (10 min) to cigarette smoke and by nicotine (0.5 mg/kg x 2, s.c.) administration. This intestinal suppression was more marked in the rats given nicotine than in those exposed to cigarette smoke, whereas the plasma concentrations of nicotine in both rats were similar. These results suggest that acute exposure to cigarette smoke and nicotine administration delay gastric emptying and/or suppress intestinal propulsion, and that some components other than nicotine contained in cigarette smoke may attenuate the suppression of intestinal propulsion induced by nicotine.

  3. Scintigraphic determination of small intestinal transit time: Comparison with the hydrogen breath technique

    SciTech Connect

    Caride, V.J.; Prokop, E.K.; Troncale, F.J.; Buddoura, W.; Winchenbach, K.; McCallum, R.W.

    1984-04-01

    The hydrogen breath test was used as a standard against which a scintigraphic method for determination of small intestinal transit time was evaluated and compared. A total of 19 male volunteers ranging in age from 23 to 28 yr participated in the study. The subjects ingested an isosmotic lactulose solution containing /sup 99m/technetium-diethylenetriaminepentaacetic acid (Sn) and then remained supine under a large field of view gamma-camera that interfaced with a computer system. Data were visually analyzed and then quantified to determine gastric emptying and small intestinal transit time. The small intestinal transit time ranged from 31 to 139 min with the scintigraphic method and 30 to 190 min with the hydrogen breath test (r . 0.77). The mean small intestinal transit time for 20 individual determinations with the scintigraphic method, 73.0 +/- 6.5 min (mean +/- SEM), was similar to the results from the hydrogen breath test technique, 75.1 +/- 8.3 min. Thirteen volunteers underwent two studies with the scintigraphic method separated by intervals ranging from 2 days to 8 wk. Individual variations in small intestinal transit time were significantly correlated with individual variations in gastric emptying (p less than 0.05). We conclude that the scintigraphic method allows accurate determination of gastrocecal time and is a noninvasive technique which may be a useful clinical test for small intestinal transit time as well as for providing information on the pathophysiology and pharmacology of intestinal motility.

  4. Cattle Bile Aggravates Diclofenac Sodium-Induced Small Intestinal Injury in Mice

    PubMed Central

    Ishikawa, Hironori; Watanabe, Shiro

    2011-01-01

    Cattle bile (CB) has long been used in Japan as an ingredient of digestive medicines. Bile acids are major chemical constituents of CB, and CB ingestion is assumed to affect small intestinal injury induced by nonsteroidal anti-inflammatory drugs (NSAIDs). Mice were fed a diet supplemented with or without CB for 7 days and treated with diclofenac sodium (DIF) to induce small intestinal injury. Lesion formation was enhanced, and PGE2 content and COX expression levels were elevated in the small intestine of DIF-treated mice fed the CB diet compared with those fed the control diet. The administration of a reconstituted mixture of bile acids found in CB enhanced lesion formation in DIF-treated mice. CB administration elevated the contents of CB-derived bile acids in the small intestine, some of which exhibited a high cytotoxicity to cultured intestinal epithelial cells. These results suggest that the elevated levels of CB-derived cytotoxic bile acids in the small intestine contribute to the aggravation of DIF-induced small intestinal injury. The use of CB may be limited during the therapy of inflammatory diseases with NSAIDs. PMID:21584236

  5. Obscure Gastrointestinal Bleeding Due to a Small Intestinal Gastrointestinal Stromal Tumor in a Young Adult

    PubMed Central

    Yamamoto, Mami; Yamamoto, Kentaroh; Taketomi, Hirotaka; Yamamoto, Fumio; Yamamoto, Hiroshi

    2016-01-01

    The source of most cases of gastrointestinal bleeding is the upper gastrointestinal tract. Since bleeding from the small intestine is very rare and difficult to diagnose, time is required to identify the source. Among small intestine bleeds, vascular abnormalities account for 70–80%, followed by small intestine tumors that account for 5–10%. The reported peak age of the onset of small intestinal tumors is about 50 years. Furthermore, rare small bowel tumors account for only 1–2% of all gastrointestinal tumors. We describe a 29-year-old man who presented with obscure anemia due to gastrointestinal bleeding and underwent laparotomy. Surgical findings revealed a well-circumscribed lesion measuring 45 × 40 mm in the jejunum that initially appeared similar to diverticulosis with an abscess. However, the postoperative pathological diagnosis was a gastrointestinal stromal tumor with extramural growth. PMID:27920659

  6. 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

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

    PubMed

    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.

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

    PubMed

    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 14C-triolein marker remained proportional to the load up to 2,359 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 14C-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.

  9. Reentrant cannulation of the small intestine in sheep: cannula and surgical method.

    PubMed

    Ivan, M; Johnston, D W

    1981-04-01

    The function, design and production of a reentrant cannula for the small intestine of sheep and the corresponding surgical procedure are described. The cannula is molded in one piece from polyvinylchloride plastisol. It consists of a curved intestinal tube joined to a stem with an external elliptical ring on the distal end and a perforated flange that encircles the stem above the intestinal tube. A circular perspex valve with two curved channels was made to fit into the interior of the cannula, making it capable of either a "maintenance" or a "collection" function. The cannula was inserted into the proximal duodenum and(or) terminal ileum of sheep via a 5-cm incision on the antimesenteric side of the intestine. The intestine was attached to the cannula by a Dacron straight arterial graft. This reentrant cannulation method does not require an intestinal transection and a mesenteric incision under the transection. Therefore, little damage was done to the blood and nervous system.

  10. Adult stem cells in the small intestine are intrinsically programmed with their location-specific function.

    PubMed

    Middendorp, Sabine; Schneeberger, Kerstin; Wiegerinck, Caroline L; Mokry, Michal; Akkerman, Ronald D L; van Wijngaarden, Simone; Clevers, Hans; Nieuwenhuis, Edward E S

    2014-05-01

    Differentiation and specialization of epithelial cells in the small intestine are regulated in two ways. First, there is differentiation along the crypt-villus axis of the intestinal stem cells into absorptive enterocytes, Paneth, goblet, tuft, enteroendocrine, or M cells, which is mainly regulated by WNT. Second, there is specialization along the cephalocaudal axis with different absorptive and digestive functions in duodenum, jejunum, and ileum that is controlled by several transcription factors such as GATA4. However, so far it is unknown whether location-specific functional properties are intrinsically programmed within stem cells or if continuous signaling from mesenchymal cells is necessary to maintain the location-specific identity of the small intestine. Using the pure epithelial organoid technique, we show that region-specific gene expression profiles are conserved throughout long-term cultures of both mouse and human intestinal stem cells and correlated with differential Gata4 expression. Furthermore, the human organoid culture system demonstrates that Gata4-regulated gene expression is only allowed in absence of WNT signaling. These data show that location-specific function is intrinsically programmed in the adult stem cells of the small intestine and that their differentiation fate is independent of location-specific extracellular signals. In light of the potential future clinical application of small intestine-derived organoids, our data imply that it is important to generate GATA4-positive and GATA4-negative cultures to regenerate all essential functions of the small intestine.

  11. Establishment and evaluation of an experimental rat model for high-altitude intestinal barrier injury

    PubMed Central

    Luo, Han; Zhou, Dai-Jun; Chen, Zhang; Zhou, Qi-Quan; Wu, Kui; Tian, Kun; Li, Zhi-Wei; Xiao, Zhen-Liang

    2017-01-01

    In the present study an experimental high-altitude intestinal barrier injury rat model was established by simulating an acute hypoxia environment, to provide an experimental basis to assess the pathogenesis, prevention and treatment of altitude sickness. A total of 70 healthy male Sprague-Dawley rats were divided into two groups: Control group (group C) and a high-altitude hypoxia group (group H). Following 2 days adaptation, the rats in group H were exposed to a simulated 4,000-m, high-altitude hypoxia environment for 3 days to establish the experimental model. To evaluate the model, bacterial translocation, serum lipopolysaccharide level, pathomorphology, ultrastructure and protein expression in rats were assessed. The results indicate that, compared with group C, the rate of bacterial translocation and the apoptotic index of intestinal epithelial cells were significantly higher in group H (P<0.01). Using a light microscope it was determined that the intestinal mucosa was thinner in group H, there were fewer epithelial cells present and the morphology was irregular. Observations with an electron microscope indicated that the intestinal epithelial cells in group H were injured, the spaces among intestinal villi were wider, the tight junctions among cells were open and lanthanum nitrate granules (from the fixing solution) had diffused into the intestinal mesenchyme. The expression of the tight junction protein occludin was also decreased in group H. Therefore, the methods applied in the present study enabled the establishment of a stable, high-altitude intestinal barrier injury model in rats. PMID:28352318

  12. 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

  13. 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.

  14. E-NPP3 controls plasmacytoid dendritic cell numbers in the small intestine

    PubMed Central

    Kinoshita, Makoto; Fujimoto, Kosuke; Okumura, Ryu; Umemoto, Eiji; Kurashima, Yosuke; Kiyono, Hiroshi; Kayama, Hisako; Takeda, Kiyoshi

    2017-01-01

    Extracellular adenosine 5’-triphosphate (ATP) performs multiple functions including activation and induction of apoptosis of many cell types. The ATP-hydrolyzing ectoenzyme ecto-nucleotide pyrophosphatase/phosphodiesterase 3 (E-NPP3) regulates ATP-dependent chronic allergic responses by mast cells and basophils. However, E-NPP3 is also highly expressed on epithelial cells of the small intestine. In this study, we showed that E-NPP3 controls plasmacytoid dendritic cell (pDC) numbers in the intestine through regulation of intestinal extracellular ATP. In Enpp3-/- mice, ATP concentrations were increased in the intestinal lumen. pDC numbers were remarkably decreased in the small intestinal lamina propria and Peyer’s patches. Intestinal pDCs of Enpp3-/- mice showed enhanced cell death as characterized by increases in annexin V binding and expression of cleaved caspase-3. pDCs were highly sensitive to ATP-induced cell death compared with conventional DCs. ATP-induced cell death was abrogated in P2rx7-/- pDCs. Accordingly, the number of intestinal pDCs was restored in Enpp3-/- P2rx7-/- mice. These findings demonstrate that E-NPP3 regulates ATP concentration and thereby prevents the decrease of pDCs in the small intestine. PMID:28225814

  15. [Gastro-intestinal neuroectodermal tumor (GNET): A case report of a small intestine tumor with hepatic metastases].

    PubMed

    Kervarrec, Thibault; Lecointre, Claire; Kerdraon, Rémy; Bens, Guido; Piquard, Arnaud; Michenet, Patrick

    2015-12-01

    The gastro-intestinal neuroectodermal tumor (GNET) is a rare sarcoma of the digestive tract, which was recently recognised. The knowledge of the morphological, immunohistochemical and molecular diagnostic criteria is necessary to not mistake it for the metastasis of a melanoma or for another sarcoma of the digestive tract as the gastro-intestinal clear cells sarcoma or the malignant peripheral nervous system tumor (MPNST). We report the case of a 41-year-old patient with a GNET of the small intestine with hepatic metastasis. The histological examination showed a diffuse proliferation of epithelioid cells, which only express PS100. The presence EWSR1-ATF1 gene fusions with any melanocytic differentiation leads to the diagnosis of GNET.

  16. Clinical outcome in patients with small-intestinal non-Hodgkin lymphoma.

    PubMed

    Kako, Shinichi; Oshima, Kumi; Sato, Miki; Terasako, Kiriko; Okuda, Shinya; Nakasone, Hideki; Yamazaki, Rie; Tanaka, Yukie; Tanihara, Aki; Kawamura, Yutaka; Kiyosaki, Hirokazu; Higuchi, Takakazu; Nishida, Junji; Konishi, Fumio; Kanda, Yoshinobu

    2009-10-01

    The clinical features and outcome of small intestinal lymphoma remain unclear. We retrospectively analyzed 23 patients who had non-Hodgkin lymphoma with a small intestinal lesion. With a median follow-up of 37 months, the 5-year overall survival and failure-free survival (FFS) were 64% and 60%, respectively. In a univariate analysis, a worse performance status at the start of treatment and the occurrence of abdominal symptoms or perforation during treatment were associated with poor survival. Perforation often resulted in a dismal prognosis in patients with uncontrollable lymphoma, but not in patients with lymphoma in remission. The role of surgery in small intestinal lymphoma remains equivocal. In the current study, surgery before other therapies favorably influenced FFS, and all patients who underwent complete resection of the small intestinal lesion had extremely favorable results. Further studies are warranted to establish optimal therapeutic strategies.

  17. Effect of wood creosote and loperamide on propulsive motility of mouse colon and small intestine.

    PubMed

    Ogata, N; Ataka, K; Morino, H; Shibata, T

    1999-10-01

    To elucidate a mechanism of the antidiarrheal activity of wood creosote, its effect on the propulsive motility of mouse colon and small intestine was studied using a charcoal meal test and a colonic bead expulsion test. The effect was compared with that of loperamide. At an ordinary therapeutic dose, wood creosote inhibited the propulsive motility of colon, but not of small intestine. On the other hand, loperamide inhibited the propulsive motility of small intestine, but not of colon. The results indicate that at least a part of the antidiarrheal activity of wood creosote and loperamide is attributable to their antikinetic effect predominantly on colon of the former and predominantly on small intestine of the latter.

  18. 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.

  19. Effect of Indomethacin on Intestinal Tumors Induced in Rats by the Acetate Derivative of Dimethylnitrosamine

    NASA Astrophysics Data System (ADS)

    Pollard, Morris; Luckert, Phyllis H.

    1981-10-01

    Over the course of 20 weeks, Sprague-Dawley rats developed intestinal tumors in response to an intraperitoneal injection of the acetate derivative of dimethylnitrosamine. The same agent did not induce tumors in Lobund-Wistar rats. The number of tumors was significantly smaller in rats given drinking water containing indomethacin (beginning 14 days after the injections) than in control rats given drug-free water.

  20. Small Intestine Inflammation in Roquin-Mutant and Roquin-Deficient Mice

    PubMed Central

    Schaefer, Jeremy S.; Montufar-Solis, Dina; Nakra, Niyati; Vigneswaran, Nadarajah; Klein, John R.

    2013-01-01

    Roquin, an E3 ubiquitin ligase that localizes to cytosolic RNA granules, is involved in regulating mRNA stability and translation. Mice that have a M199R mutation in the Roquin protein (referred to as sanroque or Roquinsan/san mice) develop autoimmune pathologies, although the extent to which these occur in the intestinal mucosa has not been determined. Here, we demonstrate that Roquinsan/san mice reproducibly develop intestinal inflammation in the small intestine but not the colon. Similarly, mice generated in our laboratory in which the Roquin gene was disrupted by insertion of a gene trap cassette (Roquingt/gt mice) had small intestinal inflammation that mimicked that of Roquinsan/san mice. MLN cells in Roquinsan/san mice consisted of activated proliferating T cells, and had increased numbers of CD44hi CD62Llo KLRG1+ short-lived effector cells. Proportionally more small intestinal intraepithelial lymphocytes in Roquinsan/san mice expressed the ICOS T cell activation marker. Of particular interest, small intestinal lamina propria lymphocytes in Roquinsan/san mice consisted of a high proportion of Gr-1+ T cells that included IL-17A+ cells and CD8+ IFN-γ+ cells. Extensive cytokine dysregulation resulting in both over-expression and under-expression of chemotactic cytokines occurred in the ileum of Roquinsan/san mice, the region most prone to the development of inflammation. These findings demonstrate that chronic inflammation ensues in the intestine following Roquin alteration either as a consequence of protein mutation or gene disruption, and they have implications for understanding how small intestinal inflammation is perpetuated in Crohn's disease (CD). Due to the paucity of animal models of CD-like pathophysiology in the small intestine, and because the primary gene/protein defects of the Roquin animal systems used here are well-defined, it will be possible to further elucidate the underlying genetic and molecular mechanisms that drive the disease process

  1. Investigation of coco-glucoside as a novel intestinal permeation enhancer in rat models.

    PubMed

    Aguirre, Tanira A S; Rosa, Mónica; Guterres, Sílvia S; Pohlmann, Adriana R; Coulter, Ivan; Brayden, David J

    2014-11-01

    Due to instability in the GI tract and low intestinal permeability, peptides invariably have oral bioavailabilities below 1% and this has prevented the development of oral formulations. A mild plant-derived naturalalkyl polyglycoside (APG), coco-glucoside (CG), was studied for its capacity to enable rat intestinal permeation of the paracellular sugar marker, fluorescein isothiocyanate-dextran 4000 (FD4), across isolated rat jejunal and colonic mucosae mounted in Ussing chambers, as well as the polypeptide, salmon calcitonin (sCT) following intra-intestinal instillations in rats. 0.1% (w/v) CG enabled a 2.9-fold increase in the apparent permeability coefficient (Papp) of FD4 over the basal Papp across colonic mucosae, but it was without effect in jejunal mucosae. In situ intestinal instillations revealed that although sCT was absorbed across rat colonic loops to a greater extent than jejunal, CG still improved sCT absolute bioavailability(F) from both segments. Histopathology of rat intestinal mucosae following exposure to CG indicated only minor perturbation with adequate maintenance of secretory function. High content analysis(HCA) on Caco-2 showed that acute and chronic exposure to a range of concentrations of CG did not cause sub-lethal damage at concentrations at which it was effective as an enhancer. Overall, CG increased bioavailability of sCT across rat jejunal and colonic loops without indication of tissue damage. Thus, CG has potential as a safe and effective intestinal enhancer for oral delivery of proteins and peptides.

  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.

  3. Preoperative diagnosis of cavernous hemangioma presenting with melena using wireless capsule endoscopy of the small intestine

    PubMed Central

    Akazawa, Yu; Hiramatsu, Katsushi; Nosaka, Takuto; Saito, Yasushi; Ozaki, Yoshihiko; Takahashi, Kazuto; Naito, Tatsushi; Ofuji, Kazuya; Matsuda, Hidetaka; Ohtani, Masahiro; Nemoto, Tomoyuki; Suto, Hiroyuki; Yamaguchi, Akio; Imamura, Yoshiaki; Nakamoto, Yasunari

    2016-01-01

    Background and study aims: Primary neoplasms of the small intestine are relatively rare in all age groups, accounting for about 5 % of all gastrointestinal tumors 1. Cavernous hemangiomas of the small intestine are also rare, can cause gastrointestinal bleeding, and are extremely difficult to diagnose preoperatively 2. We present a patient who presented with melena and iron deficiency anemia, for whom wireless capsule endoscopy and single-balloon enteroscopy facilitated the diagnosis of cavernous hemangioma. PMID:27004239

  4. Fluorescence polarization studies of rat intestinal microvillus membranes.

    PubMed Central

    Schachter, D; Shinitzky, M

    1977-01-01

    Rat intestinal microvillus membranes and lipid extracts prepared from them have been studied by fluorescence polarization with three lipid-soluble fluorophores: diphenylhexatriene, retinol, and anthroyl-stearate. The degree of fluorescence polarization of diphenylhexatriene, which provides an index of the "microviscosity" of the lipid regions of the membrane, is exceptionally high in microvillus membranes, the highest yet reported in normal biological membranes. Both the membrane proteins and lipids were found to contribute to the high values. With each of the three probes the polarization values are higher in ileal microvillus membranes as compared to membranes from proximal intestinal segments. Temperature-dependence studies of the fluorescence polarization of diphenylhexatriene and anthroylstearate demonstrate a phase transition in microvillus membranes and in liposomes prepared from their lipid extracts at approximately 26+/-2 degrees C. Ambient pH influences markedly the diphenylhexatriene fluorescence polarization in microvillus membranes but has little effect on that of human erythrocyte ghost membranes. The "microviscosity" of jejunal microvillus membranes is maximal at pH 6.5-7.0 and decreases as much as 50% at pH 3.0, an effect which depends largely upon the membrane proteins. Addition of calcium ions to suspensions of microvillus membranes increases the fluorescence polarization of retinol and anthroyl-stearate, but not that of diphenyl-hexatriene. This confirms the localization of the last compound to the hydrophobic interior of the membrane, relatively distant from the hydrophilic head groups of the polar lipids. Microvillus membrane proteins solubilized with Triton X-100 give relatively high fluorescence polarization and intensity values with retinol, suggesting the presence of binding proteins which could play a role in the normal absorptive mechanism for the vitamin. PMID:14174

  5. Imaging diagnosis--muscular hypertrophy of the small intestine and pseudodiverticula in a horse.

    PubMed

    Navas De Solís, Cristobal; Biscoe, Elisabeth W; Lund, Caleb M; Labbe, Karyn; Muñoz, Juan; Farnsworth, Kelly

    2015-01-01

    A 14-year-old Thoroughbred gelding was presented for chronic colic and weight loss. Transcutaneous and transrectal abdominal ultrasonography revealed distended, thickened small intestine with primary thickening of the muscularis and a focally more thickened loop with an echoic structure crossing the wall from the mucosa to the serosa. Visualization of diffuse thickening of the muscularis (muscular hypertrophy of the small intestine) and a focal lesion (pseudodiverticulum) helped clinicians make informed decisions. This case illustrates the importance of transabdominal and transrectal ultrasonography in horses with chronic colic and the relevance of considering the abnormalities in layering pattern of the intestinal wall.

  6. Effect of honey consumption on intestinal motility in male albino rats.

    PubMed

    Alagwu, E A; Egwurugwu, J N; Nneli, R O; Oguike, F; Osim, E E

    2013-12-20

    This study investigated the effects of honey on intestinal motility and transit using twenty (20) male albino rats of Wistar strain weighing 210-220g. The rats were randomly grouped into control and honey-fed (test) groups of ten (10) rats each. The control group was fed on normal rat chow ( Pfizer Company, Nigeria ) and water while the test group was fed on rat feed, water and honey ( 1 ml of honey to every 10 ml initial drinking water daily) for twenty two (22) weeks after which the rats were starved over night before the experiment and sacrificed by stunning. Laparatomy was immediately performed, proximal and distal portions of the intestine identified, cut and put in aerated tyrode solution. Cut sections of the ileum (2-3cm) were mounted on organ bath instrument for motility experiment with varying concentrations of acetylcholine and carbachol. Contractions were recorded as well as the intestinal transit in each group and lengths of intestine with total mean values calculated. Results obtained showed that honey significantly decreased (p<0.01 ) intestinal transit in the test group (21.15±0.75 ) compared with the control group ( 35.96±1.15); decreased intestinal motility in the test group compared with the control and caused significant percentage reduction of intestinal motility with varied concentrations of acetylcholine and carbachol in the test group ( Ach-75.00±0.75%; Carbachol-79.00±0.28%) compared with the control group (Ach-62.00±0.39%; Carbachol-51.00±0.39%). In conclusion, unprocessed Nigerian honey decreased intestinal transit, caused intestinal smooth muscle inhibition and motility and reduced sensitivity of gastrointestinal tract to cholinergic agents.

  7. 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.

  8. Dunnione ameliorates cisplatin-induced small intestinal damage by modulating NAD(+) metabolism.

    PubMed

    Pandit, Arpana; Kim, Hyung-Jin; Oh, Gi-Su; Shen, AiHua; Lee, Su-Bin; Khadka, Dipendra; Lee, SeungHoon; Shim, Hyeok; Yang, Sei-Hoon; Cho, Eun-Young; Kwon, Kang-Beom; Kwak, Tae Hwan; Choe, Seong-Kyu; Park, Raekil; So, Hong-Seob

    2015-11-27

    Although cisplatin is a widely used anticancer drug for the treatment of a variety of tumors, its use is critically limited because of adverse effects such as ototoxicity, nephrotoxicity, neuropathy, and gastrointestinal damage. Cisplatin treatment increases oxidative stress biomarkers in the small intestine, which may induce apoptosis of epithelial cells and thereby elicit damage to the small intestine. Nicotinamide adenine dinucleotide (NAD(+)) is a cofactor for various enzymes associated with cellular homeostasis. In the present study, we demonstrated that the hyper-activation of poly(ADP-ribose) polymerase-1 (PARP-1) is closely associated with the depletion of NAD(+) in the small intestine after cisplatin treatment, which results in downregulation of sirtuin1 (SIRT1) activity. Furthermore, a decrease in SIRT1 activity was found to play an important role in cisplatin-mediated small intestinal damage through nuclear factor (NF)-κB p65 activation, facilitated by its acetylation increase. However, use of dunnione as a strong substrate for the NADH:quinone oxidoreductase 1 (NQO1) enzyme led to an increase in intracellular NAD(+) levels and prevented the cisplatin-induced small intestinal damage correlating with the modulation of PARP-1, SIRT1, and NF-κB. These results suggest that direct modulation of cellular NAD(+) levels by pharmacological NQO1 substrates could be a promising therapeutic approach for protecting against cisplatin-induced small intestinal damage.

  9. Intestinal absorption of calcium from calcium ascorbate in rats.

    PubMed

    Tsugawa, N; Yamabe, T; Takeuchi, A; Kamao, M; Nakagawa, K; Nishijima, K; Okano, T

    1999-01-01

    The intestinal absorption of calcium (Ca) from Ca ascorbate (Ca-AsA) was investigated in normal rats. Each animal was perorally administered either 5mg (low dose) or 10mg (high dose) of Ca in 1ml of distilled water as Ca-AsA, Ca carbonate (CaCO3), or Ca chloride (CaCl2), which were intrinsically labeled with 45Ca using 45CaCl2. The amount of radioactivity in plasma was measured periodically up to 34h after dosing, and pharmacokinetic parameters were calculated from the radioactivity in plasma. The time taken to reach the maximum 45Ca level (Tmax) did not differ among the three groups. The area under the plasma 45Ca level/time curve (AUCinfinity) value for the Ca-AsA group was significantly higher than those for the CaCO3 and the CaCl2 groups. The radioactivity at Tmax (Cmax) for the Ca-AsA group was significantly higher than those for the CaCO3 and the CaCl2 groups for the low dose, and comparable with or significantly higher than those for the CaCl2 and CaCO3 groups for the high dose. Similar results were observed for whole-body 45Ca retention. Radioactivity in the femur 34h after dosing was the highest in the Ca-AsA group and the lowest in the CaCO3 group. The rank order of solubility in water, the first fluid (pH 1.2, JP-1) of JPXIII disintegration medium, acetate buffer solution (pH 4.0), triethanolamine-malate buffer solution (pH 7.0) and ammonium chloride buffer solution (pH 10.0) at 37 degrees C was CaCl2 > Ca-AsA > CaCO3. In contrast, the rank order of the solubility in the second fluid (pH 6.8, JP-2) of JPXIII disintegration medium at 37 degrees C was Ca-AsA > CaCl2 > CaCO3. These results indicate that the absorbability of Ca from Ca-AsA is almost comparable with, or higher than, that from CaCl2 and significantly higher than that from CaCO3 because of its high degree of solubility in the intestine. Therefore, Ca-AsA would be useful as a Ca supplement with relatively high absorption from intestine.

  10. Prevalence of intestinal and blood parasites among wild rats in Kuala Lumpur, Malaysia.

    PubMed

    Siti Shafiyyah, C O; Jamaiah, I; Rohela, M; Lau, Y L; Siti Aminah, F

    2012-12-01

    A survey was undertaken to investigate the prevalence of intestinal and blood parasites among wild rats in urban area of Kuala Lumpur, Malaysia. A total of 137 stool and blood samples were collected from wild rats from Sentul and Chow Kit areas. Five species of rats were captured and supplied by Kuala Lumpur City Hall. The most common was Rattus rattus diardii (Malayan Black rat), 67%, followed by Rattus norvegicus (Norway rat), 10%, Rattus argentiventer (rice-field rat), 10%, Rattus tiomanicus (Malaysian field rat), 9% and Rattus exulans (Polynesian rat), 4%. Rattus rattus diardii is commonly known to live in human environment and they are normally identified as pests to human community. More male rats were captured (61%) compared to female (39%). Out of 137 samples, 81.8% samples were positive with intestinal parasites, with 86.2% from Sentul area and 78.5% from Chow Kit area. Six different parasites were detected. The most common intestinal helminth parasite detected was Nippostrongylus brasiliensis (80.3%), followed by Hymenolepis nana (23.4%), Capillaria hepatica (13.9%) and Hymenolepis diminuta (2.9%). Intestinal protozoan detected was Entamoeba histolytica/E. dispar (8.8%). Trypanosoma lewisi (1.5%) was the only blood parasite detected.

  11. 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

  12. An in vivo model of human small intestine using pluripotent stem cells.

    PubMed

    Watson, Carey L; Mahe, Maxime M; Múnera, Jorge; Howell, Jonathan C; Sundaram, Nambirajan; Poling, Holly M; Schweitzer, Jamie I; Vallance, Jefferson E; Mayhew, Christopher N; Sun, Ying; Grabowski, Gregory; Finkbeiner, Stacy R; Spence, Jason R; Shroyer, Noah F; Wells, James M; Helmrath, Michael A

    2014-11-01

    Differentiation of human pluripotent stem cells (hPSCs) into organ-specific subtypes offers an exciting avenue for the study of embryonic development and disease processes, for pharmacologic studies and as a potential resource for therapeutic transplant. To date, limited in vivo models exist for human intestine, all of which are dependent upon primary epithelial cultures or digested tissue from surgical biopsies that include mesenchymal cells transplanted on biodegradable scaffolds. Here, we generated human intestinal organoids (HIOs) produced in vitro from human embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) that can engraft in vivo. These HIOs form mature human intestinal epithelium with intestinal stem cells contributing to the crypt-villus architecture and a laminated human mesenchyme, both supported by mouse vasculature ingrowth. In vivo transplantation resulted in marked expansion and maturation of the epithelium and mesenchyme, as demonstrated by differentiated intestinal cell lineages (enterocytes, goblet cells, Paneth cells, tuft cells and enteroendocrine cells), presence of functional brush-border enzymes (lactase, sucrase-isomaltase and dipeptidyl peptidase 4) and visible subepithelial and smooth muscle layers when compared with HIOs in vitro. Transplanted intestinal tissues demonstrated digestive functions as shown by permeability and peptide uptake studies. Furthermore, transplanted HIO-derived tissue was responsive to systemic signals from the host mouse following ileocecal resection, suggesting a role for circulating factors in the intestinal adaptive response. This model of the human small intestine may pave the way for studies of intestinal physiology, disease and translational studies.

  13. 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.

  14. 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

  15. Carrier-mediated intestinal absorption of valacyclovir, the L-valyl ester prodrug of acyclovir: 1. Interactions with peptides, organic anions and organic cations in rats.

    PubMed

    Sinko, P J; Balimane, P V

    1998-05-01

    The mechanism of intestinal transport of valacyclovir (VACV), the L-valyl ester prodrug of acyclovir, was investigated in rats using an in situ intestinal perfusion technique. VACV demonstrates an oral bioavailability that is three to five time greater than acyclovir, concentration dependent, and saturable in humans. Homogenate and perfused buffer stability results demonstrated that VACV was increasingly unstable with increasing pH. VACV was converted to ACV in a concentration dependent manner during a single pass through the intestinal segment. Perfusions were performed at 37 degrees C, pH 6.5, and under iso-osmotic conditions (290 +/- 10 mOsm L-1). Intestinal outlet concentrations were corrected for VACV that was converted to ACV during the perfusion. The effective dimensionless intestinal permeability (P*e) of VACV was concentration dependent, saturable (intrinsic Km = 1.2 +/- 0.7 mM), and significantly reduced (p < 0.05) in the presence of peptide analogues (amoxicillin, ampicillin, cefadroxil, and cephradine), by the organic anion, p-amino hippuric acid and by the organic cation quinine. VACV transport was not inhibited by classical nucleoside competitive substrates or inhibitors or by valine. These results suggest that H(+)-oligopeptide, H(+)-organic cation, and organic anion transporters are involved in the small intestinal uptake of VACV. The permeability of VACV in the colon was very low, indicating that VACV is predominantly absorbed from the small intestine. VACV P*e was not altered in the presence of glucose-induced convective fluid flow, suggesting that carrier-mediated, transcellular uptake is the predominant absorption pathway of VACV in rat small intestine. Based on these results, the oral bioavailability of VACV appears to be significantly influenced by the preabsorptive conversion of VACV to the poorly absorbed ACV, by the involvement of multiple transporters in VACV small-intestinal uptake, and by the low permeability of VACV in the colon.

  16. Expression of TLR2 and TLR4 in murine small intestine during postnatal development.

    PubMed

    Inoue, Ryo; Yajima, Takaji; Tsukahara, Takamitsu

    2017-02-01

    The important role played by the gut microbiota in host immunity is mediated, in part, through toll-like receptors (TLRs). We evaluated the postnatal changes in expression of TLR2 and TLR4 in the murine small intestine and assessed how expression is influenced by gut microbiota. The expression of TLR2 and TLR4 in the murine small intestine was highly dynamic during development. The changes were especially profound during the suckling period, with the maximal mRNA levels detected in the mid-suckling period. Immunohistochemical and flow-cytometric analyses indicated that the changes in TLR2 and TLR4 expression involve primarily epithelial cells. The germ-free mice showed minor changes in TLR2/TLR4 mRNA and TLR2 protein during the suckling period. This study demonstrated that the postnatal expression of TLR2 and TLR4 in small intestinal epithelial cells is dynamic and depends on the presence of commensal intestinal microbiota.

  17. 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

  18. 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.

  19. 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.

  20. Oral administration of protease inhibits enterotoxigenic Escherichia coli receptor activity in piglet small intestine.

    PubMed Central

    Mynott, T L; Luke, R K; Chandler, D S

    1996-01-01

    The virulence of enterotoxigenic Escherichia coli (ETEC) is attributed to their ability to adhere via fimbrial adhesins to specific receptors located on the intestinal mucosa. A novel approach to preventing ETEC induced diarrhoea would be to prevent attachment of ETEC to intestine by proteolytically modifying the receptor attachment sites. This study aimed to examine the effect of bromelain, a proteolytic extract obtained from pineapple stems, on ETEC receptor activity in porcine small intestine. Bromelain was administered orally to piglets and K88+ ETEC attachment to small intestine was measured at 50 cm intervals using an enzyme immunoassay. K88+ ETEC attachment to intestinal sections that were not treated with bromelain varied appreciably between sampling sites. Variability in receptor activity along the intestinal surface is though to be caused by the localised effects of endogenous proteases. Oral administration of exogenous protease inhibited K88+ ETEC attachment to pig small intestine in a dose dependent manner (p < 0.05). Attachment of K88+ ETEC was negligible after treatment, resembling the levels of attachment of K88 to piglets of the genetically determined non-adhesive phenotype, which are resistant to K88+ ETEC infection. Serum biochemical analysis and histopathological examination of treated piglets showed no adverse effects of the bromelain treatment. It is concluded that administration of bromelain can inhibit ETEC receptor activity in vivo and may therefore be useful for prevention of K88+ ETEC induced diarrhoea. PMID:8566855

  1. Eosinophilic venulitis in the small intestines in a mouse model of late asthma.

    PubMed

    Bui, Linh Kan; Hayashi, Toshiharu; Nakashima, Tomomi; Horii, Yoichiro

    2011-10-01

    The allergen-unchallenged enteric lesions in late allergic asthma are largely unknown. To clarify this point, BALB/c mice were sensitized by ovalbumin (OVA)/aluminum adjuvant intraperitoneally two times (on days 0 and 10) and then challenged with OVA intranasally on day 14 (asthma group). Four days after the challenge, small intestinal lesions were examined. By this treatment, diarrhea was not observed in the asthma group. Compared to the controls with or without OVA sensitization and/or OVA challenge, the asthma group developed eosinophilic venulitis without an increase in mucosal mast cells in small intestines, whereas intestinal epithelial cells were relatively intact. A few numbers of interleukin (IL)-4(+) and IL-5(+) lymphoid cells were recognized in intestines in the asthma group, but not in the controls. Expression of vascular cell adhesion molecule-1 on venular endothelium and eotaxin-2(+) eosinophils, but not epithelial cells, in intestines were detected in the asthma group, but not in the controls. Total IgE, OVA-specific IgE and eotaxin, and IL-5, but not interferon-γ, were produced systemically in the asthma group compared to the controls. The present study suggests that eosinophilic venulitis without mast cells in the intestine may be induced by the systemic, but not by local, helper T 2-type responses. In addition, eosinophilic venulitis in small intestines may be subclinical enteric lesions.

  2. Influence of microcystin-LR on the activity of membrane enzymes in rat intestinal mucosa.

    PubMed

    Moreno, I M; Mate, A; Repetto, G; Vázquez, C M; Cameán, A M

    2003-12-01

    The objective of the present study was to evaluate the effects of microcystin-LR (MCLR) on the activity of membrane enzymes from intestinal mucosa. In addition, serum chemistry and peroxidative status of both serum and intestinal homogenate were evaluated after treatment with MCLR. Wistar rats were treated with intraperitoneal injection of either 100 microg pure MCLR/Kg body weight or saline solution. A significant increase in liver weight and altered serum enzyme activities were found in MCLR-treated rats, indicating damage to the liver in these rats, as previously suggested. A higher specific activity of sucrase (1.5-fold) was observed after the administration of MCLR, whereas other intestinal apical membrane enzymes, such as lactase, maltase and alkaline phosphatase were not modified by the treatment. The specific activities of acid phosphatase and succinate dehydrogenase, markers for lysosomal and mitochondrial membranes, respectively, were also increased (32% and 60%, respectively) in treated rats. The analysis of lipid peroxidation showed that the peroxidative status was increased in both serum and intestinal mucosa from MCLR-treated rats, reflecting an excess production of oxygen free radicals induced by this cyanobacterial toxin. In conclusion, this study shows that acute exposure to MCLR affects the intestinal physiology by modifying the intestinal peroxidation status as well as the activity of membrane enzymes.

  3. Morphometrics of the avian small intestine compared with that of nonflying mammals: a phylogenetic approach.

    PubMed

    Lavin, Shana R; Karasov, William H; Ives, Anthony R; Middleton, Kevin M; Garland, Theodore

    2008-01-01

    Flying animals may experience a selective constraint on gut volume because the energetic cost of flight increases and maneuverability decreases with greater digesta load. The small intestine is the primary site of absorption of most nutrients (e.g., carbohydrates, proteins, fat) in both birds and mammals. Therefore, we used a phylogenetically informed approach to compare small intestine morphometric measurements of birds with those of nonflying mammals and to test for effects of diet within each clade. We also compared the fit of nonphylogenetic and phylogenetic models to test for phylogenetic signal after accounting for effects of body mass, clade, and/or diet. We provide a new MATLAB program (Regressionv2.m) that facilitates a flexible model-fitting approach in comparative studies. As compared with nonflying mammals, birds had 51% less nominal small intestine surface area (area of a smooth bore tube) and 32% less volume. For animals <365 g in body mass, birds also had significantly shorter small intestines (20%-33% shorter, depending on body mass). Diet was also a significant factor explaining variation in small intestine nominal surface area of both birds and nonflying mammals, small intestine mass of mammals, and small intestine volume of both birds and nonflying mammals. On the basis of the phylogenetic trees used in our analyses, small intestine length and nominal surface area exhibited statistically significant phylogenetic signal in birds but not in mammals. Thus, for birds, related species tended to be similar in small intestine length and nominal surface area, even after accounting for relations with body mass and diet. A reduced small intestine in birds may decrease the capacity for breakdown and active absorption of nutrients. Birds do not seem to compensate for reduced digestive and absorptive capacity via a longer gut retention time of food, but we found some evidence that birds have an increased mucosal surface area via a greater villus area

  4. Intestinal barrier function in response to abundant or depleted mucosal glutathione in Salmonella-infected rats

    PubMed Central

    van Ampting, Marleen TJ; Schonewille, Arjan J; Vink, Carolien; Brummer, Robert Jan M; Meer, Roelof van der; Bovee-Oudenhoven, Ingeborg MJ

    2009-01-01

    Background Glutathione, the main antioxidant of intestinal epithelial cells, is suggested to play an important role in gut barrier function and prevention of inflammation-related oxidative damage as induced by acute bacterial infection. Most studies on intestinal glutathione focus on oxidative stress reduction without considering functional disease outcome. Our aim was to determine whether depletion or maintenance of intestinal glutathione changes susceptibility of rats to Salmonella infection and associated inflammation. Rats were fed a control diet or the same diet supplemented with buthionine sulfoximine (BSO; glutathione depletion) or cystine (glutathione maintenance). Inert chromium ethylenediamine-tetraacetic acid (CrEDTA) was added to the diets to quantify intestinal permeability. At day 4 after oral gavage with Salmonella enteritidis (or saline for non-infected controls), Salmonella translocation was determined by culturing extra-intestinal organs. Liver and ileal mucosa were collected for analyses of glutathione, inflammation markers and oxidative damage. Faeces was collected to quantify diarrhoea. Results Glutathione depletion aggravated ileal inflammation after infection as indicated by increased levels of mucosal myeloperoxidase and interleukin-1β. Remarkably, intestinal permeability and Salmonella translocation were not increased. Cystine supplementation maintained glutathione in the intestinal mucosa but inflammation and oxidative damage were not diminished. Nevertheless, cystine reduced intestinal permeability and Salmonella translocation. Conclusion Despite increased infection-induced mucosal inflammation upon glutathione depletion, this tripeptide does not play a role in intestinal permeability, bacterial translocation and diarrhoea. On the other hand, cystine enhances gut barrier function by a mechanism unlikely to be related to glutathione. PMID:19374741

  5. 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

    2015-10-26

    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.

  6. 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

  7. 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.

  8. 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.

  9. Phosphate transport by rat intestinal basolateral-membrane vesicles.

    PubMed Central

    Ghishan, F K; Kikuchi, K; Arab, N

    1987-01-01

    The characteristics of phosphate transport across intestinal basolateral membranes of the rat were determined by using enriched preparations in which uphill Na+-dependent D-glucose transport could not be demonstrated, but ATP-dependent Ca2+ transport was present. Phosphate transport was saturable, Na+-dependent and exhibited Michaelis-Menten kinetics. Vmax. was 51.1 +/- 4.2 pmol/10 s per mg of protein and Km was 14 +/- 3.9 microM. The transport process was electroneutral. Tracer-exchange experiments and counter-transport studies confirmed the presence of a Na+-Pi carrier at the basolateral membrane. The presence of inside-positive membrane potential did not enhance phosphate uptake, indicating that the Na+ effect is secondary to the presence of the Na+-Pi carrier rather than an induction of positive membrane potential. The stoichiometry of this carrier at pH 7.4 was 2 Na+:1 phosphate, as shown by direct studies utilizing the static-head method. These studies are the first to determine the presence of a phosphate carrier at the basolateral membrane. PMID:3663094

  10. 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.

  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.

  12. The effects of probiotic, prebiotic and synbiotic diets containing Bacillus coagulans and inulin on rat intestinal microbiota

    PubMed Central

    Abhari, Kh; Shekarforoush, S. S; Sajedianfard, J; Hosseinzadeh, S; Nazifi, S

    2015-01-01

    An in vivo experiment was conducted to study the effects of probiotic Bacillus coagulans spores, with and without prebiotic, inulin, on gastrointestinal (GI) microbiota of healthy rats and its potentiality to survive in the GI tract. Forty-eight male Wistar rats were randomly divided into four groups (n=12) and fed as follows: standard diet (control), standard diet supplied with 5% w/w long chain inulin (prebiotic), standard diet with 109/day spores of B. coagulans by orogastric gavage (probiotic), and standard diet with 5% w/w long chain inulin and 109 spores/day of B. coagulans by orogastric gavage (synbiotic). Rats were fed the diets for 30 days. At day 10, 20 and 30 of experiment, 24 h post administration, four rats from each group were randomly selected and after faecal collection were sacrificed. Small intestine, cecum, and colon were excised from each rat and used for microbial analysis. Administration of synbiotic and probiotic diets led to a significant (P<0.05) increment in lactic acid bacteria (LAB), total aerobic and total anaerobic population compared the prebiotic and control diets. A significant decrease in Enterobacteriaceae counts of various segments of GI tract (except small intestine) in synbiotic, probiotic and prebiotic fed groups were also seen. The obvious decline in spores count through passing GI tract and high surviving spore counts in faecal samples showed that spores are not a normal resident of GI microbiota and affect intestinal microbiota by temporary proliferation. In conclusion, the present study clearly showed probiotic B. coagulans was efficient in beneficially modulating GI microbiota and considering transitional characteristics of B. coagulans, daily consumption of probiotic products is necessary for any long-term effect. PMID:27175187

  13. The effects of probiotic, prebiotic and synbiotic diets containing Bacillus coagulans and inulin on rat intestinal microbiota.

    PubMed

    Abhari, Kh; Shekarforoush, S S; Sajedianfard, J; Hosseinzadeh, S; Nazifi, S

    2015-01-01

    An in vivo experiment was conducted to study the effects of probiotic Bacillus coagulans spores, with and without prebiotic, inulin, on gastrointestinal (GI) microbiota of healthy rats and its potentiality to survive in the GI tract. Forty-eight male Wistar rats were randomly divided into four groups (n=12) and fed as follows: standard diet (control), standard diet supplied with 5% w/w long chain inulin (prebiotic), standard diet with 10(9)/day spores of B. coagulans by orogastric gavage (probiotic), and standard diet with 5% w/w long chain inulin and 10(9) spores/day of B. coagulans by orogastric gavage (synbiotic). Rats were fed the diets for 30 days. At day 10, 20 and 30 of experiment, 24 h post administration, four rats from each group were randomly selected and after faecal collection were sacrificed. Small intestine, cecum, and colon were excised from each rat and used for microbial analysis. Administration of synbiotic and probiotic diets led to a significant (P<0.05) increment in lactic acid bacteria (LAB), total aerobic and total anaerobic population compared the prebiotic and control diets. A significant decrease in Enterobacteriaceae counts of various segments of GI tract (except small intestine) in synbiotic, probiotic and prebiotic fed groups were also seen. The obvious decline in spores count through passing GI tract and high surviving spore counts in faecal samples showed that spores are not a normal resident of GI microbiota and affect intestinal microbiota by temporary proliferation. In conclusion, the present study clearly showed probiotic B. coagulans was efficient in beneficially modulating GI microbiota and considering transitional characteristics of B. coagulans, daily consumption of probiotic products is necessary for any long-term effect.

  14. Differences in intraepithelial lymphocytes in the proximal, middle, distal parts of small intestine, cecum, and colon of mice.

    PubMed

    Suzuki, Hodaka

    2009-01-01

    We have previously reported the regional differences in the intraepithelial lymphocytes (IELs) present in the small intestine of mice. In this study, we further investigated these differences on the basis of our previous findings and studied the entire intestine, including the cecum and colon. Most of the significant differences in phenotypic compositions were found between the small and large intestines, although some differences were found among the different parts of the small and large intestines. In particular, the composition of the subsets in alphabeta T cells and gammadelta T cells clearly differed between the small and large intestines. For example, in alphabeta T cells, the percentages of double negative (DN) and CD8alphaalpha(+) cells were higher in the large intestine, that of CD8alphabeta(+) cells was higher in the small intestine, and those of CD4(+) and CD4(+) CD8alphaalpha(+) double positive (DP) cells were higher in the distal part of the small intestine. In gammadelta T cells, the percentage of CD8alphaalpha(+) cells was higher in the small intestine and that of DN cells was higher in the large intestine. These results indicate that the differences between IELs in the small and large intestines are discontinuous.

  15. [Comparative studies on the enzymatic absorption of protein hydrolysates in the small intestine of the rat. 3. The absorption trypsins thermatatic and trypsin-thermatatic hydrolysates of a fava bean protein isolate compared to an equimolar mixture of free amino acids].

    PubMed

    Proll, J; Friedrich, M; Noack, J; Noack, R

    1985-01-01

    Tryptic, thermitatic, and tryptic-thermitatic Faba bean protein hydrolyzates as well as their equimolar mixture of amino acids were perfused through proximal and distal parts of the intestine (10 cm length) of non-narcotized rats. The total amino-acid concentration of the perfused solution was 50 mM. The absorption of nitrogen and total amino acids from the tryptic and tryptic-thermitatic hydrolyzates was lower than that from the amino-acid mixture, the absorption from the thermitatic hydrolyzate was in accordance with that from the amino-acid mixture. The absorption pattern of the amino acids which preferably undergo a peptidic absorption is similar with the three hydrolyzates: in the proximal intestinal part this concerns glutamic acid and serine, in the distal intestinal part--methionine, alanine, glycin, and serine. The absorption pattern of the amino acids is different between the three hydrolyzates and the amino-acid mixture. Between the absorption pattern of the amino acids from the three hydrolyzates little differences were evident only in the proximal intestinal part. The coefficients of variation of the tryptic-thermitatic hydrolyzates are in accordance with those of the amino-acid mixture, whereas that of the thermitatic hydrolyzates is significantly lower. In the distal intestinal part all supplied forms are more rapidly absorbed than in the proximal part of the intestine.

  16. Effect of experimental diabetes and insulin replacement on intestinal metabolism and excretion of 4-nitrophenol in rats.

    PubMed

    Fischer, Emil; Almási, Attila; Bojcsev, Sztojan; Fischer, Tamás; Kovács, Noémi Piroska; Perjési, Pál

    2015-06-01

    Luminal appearance of 4-nitrophenol (PNP) metabolites (4-nitrophenol-β-glucuronide (PNP-G) and 4-nitrophenol-sulfate (PNP-S)) and activity of the related metabolic enzymes have been investigated in control and experimental diabetic rats. Experimental diabetes was induced by administration of streptozotocin (65 mg/kg i.v.). PNP (500 μmol/L) was luminally perfused in the small intestine and the metabolites were determined in the perfusion solution. Effect of insulin replacement was also investigated in the diabetic rats. It was found that experimental diabetes increased the luminal appearance of PNP-G, which could be completely compensated by rapid-acting insulin administration (1 U/kg i.v.). Activities of the enzymes involved in PNP-G production (UDP-glucuronyltransferase and β-glucuronidase) were also elevated; however, these changes were only partially compensated by insulin. Luminal appearance of PNP-S was not significantly changed by administration of streptozotocin and insulin. Activities of the enzymes of PNP-S production (sulfotransferases and arylsulfatases) did not change in the diabetic rats. The results indicate that experimental diabetes can provoke changes in intestinal drug metabolism. It increased intestinal glucuronidation of PNP but did not influence sulfate conjugation. No direct correlation was found between the changes of metabolic enzyme activities and the luminal appearance of the metabolites.

  17. Simvastatin nanoparticles attenuated intestinal ischemia/reperfusion injury by downregulating BMP4/COX-2 pathway in rats

    PubMed Central

    Tong, Fei; Dong, Bo; Chai, Rongkui; Tong, Ke; Wang, Yini; Chen, Shipiao; Zhou, Xinmei; Liu, Daojun

    2017-01-01

    The purpose of the research was to explore the therapeutic action of simvastatin-loaded poly(ethylene glycol)-b-poly(gamma-benzyl l-glutamate) (PEG-b-PBLG50) on intestinal ischemia/reperfusion injury (II/RI) through downregulating bone morphogenetic protein 4 (BMP4)/cyclooxygenase-2 (COX-2) pathway as compared to free simvastatin (Sim). Sprague Dawley rats were preconditioned with 20 mg/kg Sim or simvastatin/PEG-b-PBLG50 (Sim/P) compounds, and then subjected to 45 min of ischemia and 1 h of reperfusion. The blood and small intestines were collected, serum levels of interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-α, and nitric oxide (NO) were checked, and the dry/wet intestine ratios, superoxide dismutase activity, myeloperoxidase content, reactive oxygen species, endothelial nitric oxide synthase, protein 47 kDa phagocyte oxidase (p47phox), BMP4, COX-2, and p38 mitogen-activated protein kinase (p38MAPK) expressions were measured in intestinal tissues. Both Sim and Sim/P pretreatment reduced intestinal oxidative damnification, restricted inflammatory harm, and downregulated the BMP4 and COX-2 expressions as compared to II/RI groups, while Sim/P remarkably improved this effect.

  18. The Disposition of Oxymatrine in the Vascularly Perfused Rat Intestine-Liver Preparation and Its Metabolism in Rat Liver Microsomes.

    PubMed

    Huang, Li Hua; Zhong, Yun Ming; Xiong, Xiao Hong; Cen, Mei Feng; Cheng, Xuan Ge; Wang, Gui Xiang; Chen, Ji Sheng; Wang, Su Jun

    2016-02-01

    The study was aimed to investigate the absorption and metabolism of oxymatrine (OMT) which contributed to its poor bioavailability. Determinations of OMT absorption and metabolism in rats were evaluated using techniques of the in situ perfused rat intestine-liver preparation and recirculated intestine preparation. Furthermore, chemical inhibition experiments in rat liver microsomes were used to determine the principal cytochrome P450 (CYP) isoforms involved in OMT metabolism. In the intestine-liver preparation, the steady state liver extraction ratio (0.753 ± 0.054) of OMT was 33 times higher than that for the intestine (0.023 ± 0.002). The portal vein mainly consisted of OMT, and was devoid of the metabolite matrine, whereas both OMT and matrine were detected in hepatic vein. With the intestine preparation, the extent of OMT absorption at the end of 120 min of perfusion was 4.79 ± 0.352%. The first-order rate constant for OMT absorption was 0.05 ± 0.003 min(-1). The inhibitor of CYP3A2 had strong inhibitory effect on OMT metabolism in a concentration-dependent manner, and value was reduced to 29.73% of control. The 2 perfusion techniques indicated that poor bioavailability of OMT in rats is due mostly to poor absorption and higher hepatic elimination and CYP3A2 appears to contribute to OMT metabolism in rat liver.

  19. 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

  20. Irritable Bowel Syndrome and the Small Intestinal Microflora. What Do We Know?

    PubMed

    Moraru, Ioana G; Moraru, A G; Dumitraşcu, D L

    2015-01-01

    Irritable bowel syndrome, one of the most common functional gastro intestinal disorders all over the world is considered to have a multi factorial pathogenesis. Recently more and more studies are focusing on the changes that take place in the microbiota of patients with irritable bowel syndrome, underlining the bacterial role in this pathogenesis. As a consequence, bacterial overgrowth, along with intestinal dysmotility, altered brain-gut axis and genetic factors are considered part of this pathophysiology. This report intends to summarize the actual knowledge on irritable bowel syndrome and small intestinal bacterial overgrowth syndrome, from details on the epidemiology, clinical manifestation, pathophysiology, diagnosis, treatment to details on the relationship between these two syndromes.

  1. Effect of syngeneic thymocytes on proliferation of the small intestinal epithelium in mice

    SciTech Connect

    Shmakov, A.N.; Aparovich, G.G.; Trufakin, V.A.

    1986-12-01

    This paper describes the study of the action of syngeneic thymocytes on proliferation of the epithelium of the mouse small intestine. The mice were injected with /sup 3/H-thymidine in the experiments. Under the experimental conditions presented here, syngeneic thymocytes can reduce the number of DNA-synthesizing cells in the intestinal epithelium, causing narrowing of the zone of proliferation and enlargement of the zone of differentiation of the enterocytes.

  2. 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 ...

  3. Effect of clarification techniques and rat intestinal extract incubation on phenolic composition and antioxidant activity of black currant juice.

    PubMed

    Pinelo, Manuel; Landbo, Anne-Katrine R; Vikbjerg, Anders F; Meyer, Anne S

    2006-09-06

    This study examined the phenolic composition and the antioxidant potencies of black currant juices that had been experimentally clarified with acidic proteases and pectinases to retain the phenolics and which had been subjected to rat intestinal mucosa extract incubation to mimic gut cell mediated biotransformation of phenolics. When compared at equimolar levels of 2.5 microM gallic acid equivalents, the black currant juice samples prolonged the induction time of human low-density lipoprotein oxidation in vitro by 2.6-3.6 times, and the order of antioxidant potency of differently clarified black currant juices was centrifuged juice > gelatin silica sol clarified juice > enzymatically clarified juice approximately raw juice. No immediate relationship between the, almost similar, phenolic profiles of the juice samples and their relative antioxidant activities could be established. Incubation of juices with a rat small intestine cell extract for 19 h promoted significant decreases in the contents of the anthocyanin 3-O-beta-glucosides (cyanidin 3-O-beta-glucoside and delphinidin 3-O-beta-glucoside), but did not affect the anthocyanin 3-O-beta-rutinosides (cyanidin 3-O-beta-rutinoside and delphinidin 3-O-beta-rutinoside) of the black currant juice. Black currant juice samples subjected to such intestinal cell extract incubation had approximately 30% decreased antioxidant capacity. Incubation of juices with the rat small intestine cell extracts at neutral pH appeared to decrease the levels of delphinidin glucosides more than the levels of cyanidin glucosides. The results provide an explanation for the predominant detection of anthocyanin rutinosides, and not anthocyanin glucosides, in plasma and urine in in vivo studies and provide important clues to better understand the complex mechanisms affecting dietary phenols in the gut.

  4. 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.

  5. 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

  6. Effects of orlistat and its relationship with nitric oxide in the small intestinal mucosa.

    PubMed

    Caner, Metin; Dogruman, Husniye; Taşkin, Elif; Kandil, Asli; Demirci, Cihan

    2005-12-31

    Nitric oxide (NO) is known to be a messenger molecule that plays an important role in physiological and pathological conditions. It is synthesized by an enzyme called nitric oxide synthase (NOS). Inducible NOS (iNOS), one of the three isomers of NOS, has both protective and toxic properties. In this study, the role of NO has been evaluated by gastrointestinal symptoms induced by orlistat which is used in obesity treatment. Orlistat was given to Wistar rats with and without iNOS inhibition. The effects of orlistat and inhibition of NOS were studied. Glucose, urea, alanine transaminase (ALT), and gamma glutamil transpeptidase (GGT) were descreased after short- and long- term orlistat applications. Dexamethasone increased level of these enzymes. Cholesterol and triglyceride were increased in all experimental groups than the controls. This increment was more severe in animals received orlistat and dexamethasone together. Small intestinal tissue also were researched histologically and NADPH-diaphorase (NADPH-d) histochemistrically. Orlistat caused histological damages in brush border membranes, connective tissues of villi, and lymphocyte migration also increased. Dexamethasone treatment prevented these damages partially while orlistat increased the NOS distribution in the tissue sections. Dexamethasone, which is an iNOS inhibitor, decreased NADPH-d histochemistry. There was a similiar NOS distribution both in the control and orlistat+dexamethasone group. Hence, we concluded that long- term trials with orlistat and similar drugs are needed.

  7. Protein transport across the small intestine in food allergy.

    PubMed

    Reitsma, Marit; Westerhout, Joost; Wichers, Harry J; Wortelboer, Heleen M; Verhoeckx, Kitty C M

    2014-01-01

    In view of the imminent deficiency of protein sources for human consumption in the near future, new protein sources need to be identified. However, safety issues such as the risk of allergenicity are often a bottleneck, due to the absence of predictive, validated and accepted methods for risk assessment. The current strategy to assess the allergenic potential of proteins focuses mainly on homology, stability and cross-reactivity, although other factors such as intestinal transport might be of added value too. In this review, we present an overview of the knowledge of protein transport across the intestinal wall and the methods currently being used to measure this. A literature study reveals that protein transport in sensitised persons occurs para-cellularly with the involvement of mast cells, and trans-cellularly via enterocytes, while in non-sensitised persons micro-fold cells and enterocytes are considered most important. However, there is a lack of comparable systematic studies on transport of allergenic proteins. Knowledge of the multiple protein transport pathways and which model system can be useful to study these processes may be of added value in the risk assessment of food allergenicity.

  8. 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.

  9. Influence of mesenchymal stem cells on stomach tissue engineering using small intestinal submucosa.

    PubMed

    Nakatsu, Hiroki; Ueno, Tomio; Oga, Atsunori; Nakao, Mitsuhiro; Nishimura, Taku; Kobayashi, Sei; Oka, Masaaki

    2015-03-01

    Small intestinal submucosa (SIS) is a biodegradable collagen-rich matrix containing functional growth factors. We have previously reported encouraging outcomes for regeneration of an artificial defect in the rodent stomach using SIS grafts, although the muscular layer was diminutive. In this study, we investigated the feasibility of SIS in conjunction with mesenchymal stem cells (MSCs) for regeneration of the gastrointestinal tract. MSCs from the bone marrow of green fluorescence protein (GFP)-transgenic Sprague-Dawley (SD) rats were isolated and expanded ex vivo. A 1 cm whole-layer stomach defect in SD rats was repaired using: a plain SIS graft without MSCs (group 1, control); a plain SIS graft followed by intravenous injection of MSCs (group 2); a SIS graft co-cultured with MSCs (group 3); or a SIS sandwich containing an MSC sheet (group 4). Pharmacological, electrophysiological and immunohistochemical examination was performed to evaluate the regenerated stomach tissue. Contractility in response to a muscarinic receptor agonist, a nitric oxide precursor or electrical field stimulation was observed in all groups. SIS grafts seeded with MSCs (groups 3 and 4) appeared to support improved regeneration compared with SIS grafts not seeded with MSCs (groups 1 and 2), by enabling the development of well-structured smooth muscle layers of significantly increased length. GFP expression was detected in the regenerated interstitial tissue, with fibroblast-like cells in the seeded-SIS groups. SIS potently induced pharmacological and electrophysiological regeneration of the digestive tract, and seeded MSCs provided an enriched environment that supported tissue regeneration by the SIS graft in the engineered stomach.

  10. Rotavirus Infection Is Not Associated with Small Intestinal Fluid Secretion in the Adult Mouse▿

    PubMed Central

    Kordasti, Shirin; Istrate, Claudia; Banasaz, Mahanez; Rottenberg, Martin; Sjövall, Henrik; Lundgren, Ove; Svensson, Lennart

    2006-01-01

    In contrast to humans, adult but not infant small animals are resistant to rotavirus diarrhea. The pathophysiological mechanism behind this age-restricted diarrhea is currently unresolved, and this question was investigated by studying the secretory state of the small intestines of adult mice infected with rotavirus. Immunohistochemistry and histological examinations revealed that rotavirus (strain EDIM) infects all parts of the small intestines of adult mice, with significant numbers of infected cells in the ilea at 2 and 4 days postinfection. Furthermore, quantitative PCR revealed that 100-fold more viral RNA was produced in the ilea than in the jejuna or duodena of adult mice. In vitro perfusion experiments of the small intestine did not reveal any significant changes in net fluid secretion among mice infected for 3 days or 4 days or in those that were noninfected (37 ± 9 μl · h−1 · cm−1, 22 ± 13 μl · h−1 · cm−1, and 33 ± 6 μl · h−1 · cm−1, respectively) or in transmucosal potential difference (4.0 ± 0.3 mV versus 3.9 ± 0.4 mV), a marker for active chloride secretion, between control and rotavirus-infected mice. In vivo experiments also did not show any differences in potential difference between uninfected and infected small intestines. Furthermore, no significant differences in weight between infected and uninfected small intestines were found, nor were any differences in fecal output observed between infected and control mice. Altogether, these data suggest that rotavirus infection is not sufficient to stimulate chloride and water secretion from the small intestines of adult mice. PMID:16943290

  11. 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

  12. 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.

  13. Origin and propagation of individual slow waves along the intact feline small intestine.

    PubMed

    Lammers, Wim J E P; Stephen, Betty

    2008-03-01

    The pattern of propagation of slow waves in the small intestine is not clear. Specifically, it is not known whether propagation is determined by a single dominant ICC-MP (Interstitial cells of Cajal located in the Myenteric Plexus) pacemaker unit or whether there are multiple active pacemakers. To determine this pattern of propagation, waveforms were recorded simultaneously from 240 electrodes distributed along the whole length of the intact isolated feline small intestine. After the experiments, the propagation patterns of successive individual slow waves were analysed. In the intact small intestine, there was only a single slow wave pacemaker unit active, and this was located at or 6-10 cm from the pyloric junction. From this site, slow waves propagated in the aboral direction at gradually decreasing velocities. The majority of slow waves (73%) reached the ileocaecal junction while the remaining waves were blocked. Ligation of the intestine at one to four locations led to: (a) decrease in the distal frequencies; (b) disappearance of distal propagation blocks; (c) increase in velocities; (d) emergence of multiple and unstable pacemaker sites; and (e) propagation from these sites in the aboral and oral directions. In conclusion, in the quiescent feline small intestine a single pacemaker unit dominates the organ, with occasional propagation blocks of the slow waves, thereby producing the well-known frequency gradient.

  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. Absorption and intestinal metabolism of SDZ-RAD and rapamycin in rats.

    PubMed

    Crowe, A; Bruelisauer, A; Duerr, L; Guntz, P; Lemaire, M

    1999-05-01

    The new immunosuppressive agent, SDZ-RAD, and its analog rapamycin were examined for intestinal absorption, metabolism, and bioavailability in Wistar rats. Intestinal first-pass metabolism studies from rat jejunum showed that at 0.5 mg of SDZ-RAD/kg rat, 50% of the parent compound was metabolized in the intestinal mucosa, and this decreased to around 30% when SDZ-RAD was increased to 5.0 mg/kg rat. Results for rapamycin at the low dose were similar to those for SDZ-RAD, but at the higher dose only 1 to 14% of the total rapamycin absorbed was metabolized by the intestine. After i.v. administration of 1 mg/kg SDZ-RAD or rapamycin, the area under the concentration curve (AUC) for rapamycin was twice that of SDZ-RAD, resulting in a systemic clearance of 6.2 ml/min and 3.0 ml/min for SDZ-RAD and rapamycin, respectively. However, the AUC for oral absorption was similar for the two compounds: 140 and 172 ng*h/ml for SDZ-RAD and rapamycin, respectively. Because blood clearance was faster for SDZ-RAD after i.v. administration, the absolute oral bioavailability for SDZ-RAD was 16% compared with 10% for rapamycin. Overall, the data suggest that intestinal first pass is a major site of metabolism for SDZ-RAD and rapamycin and that intestinal absorption of SDZ-RAD was much faster than that of rapamycin. This allowed it to counteract the combined actions of faster systemic clearance and increased intestinal metabolism, resulting in comparable absolute exposure when given orally. Also, the coadministration of cyclosporin A with SDZ-RAD was shown to dramatically increase blood AUCs for SDZ-RAD, probably through saturating intestinal metabolism mechanisms.

  16. Diamine oxidase as a marker of intestinal mucosal injury and the effect of soluble dietary fiber on gastrointestinal tract toxicity after intravenous 5-fluorouracil treatment in rats.

    PubMed

    Fukudome, Ian; Kobayashi, Michiya; Dabanaka, Ken; Maeda, Hiromichi; Okamoto, Ken; Okabayashi, Takehiro; Baba, Ryoko; Kumagai, Nana; Oba, Koji; Fujita, Mamoru; Hanazaki, Kazuhiro

    2014-06-01

    The level of plasma diamine oxidase (DAO) activity is associated with the maturation and integrity of small intestinal mucosa. This study in rats investigated whether a decreased level of plasma DAO could reflect the severity of mucosal injury due to intravenous 5-fluorouracil (5-FU) treatment. The beneficial effect of soluble dietary fiber (SDF) on preventing diarrhea after 5-FU treatment was also examined. To induce diarrhea, 5-FU (50 mg/kg/day for four days) was administered via the tail vein with or without SDF supplementation. After 5-FU treatment, the majority of rats developed moderate to severe diarrhea, and levels of plasma DAO activity significantly decreased compared to those of control group (P < 0.05). Scanning electron microscopy revealed disarrangement of the small intestinal villi. Contrarily, the rats supplemented with SDF had diarrhea less frequently (50.0 vs. 91.7 %, P = 0.025) on day five, and DAO activity levels were significantly higher than in those rats administered 5-FU alone (8.25 ± 5.34 vs. 5.50 ± 4.32, P = 0.023). In conclusion, plasma DAO activity decreases in response to severe intestinal mucosal injury after 5-FU treatment, and SDF supplementation might be a practical and useful treatment for reducing the intestinal toxicity of 5-FU.

  17. Type 2 Diabetes Mellitus Is Associated with More Serious Small Intestinal Mucosal Injuries

    PubMed Central

    Xie, Wen-Rui; Chen, Mei-Hui; He, Xing-Xiang

    2016-01-01

    Background Clinical and experimental research has revealed that diabetes mellitus (DM) is characterized by intestinal hypomotility, gut microbial dysbiosis, increased gut permeability, microcirculation disorders, circulatory changes, and dysfunction of intestinal stem cells, which may be linked to inflammation of intestinal mucosa. However, the relationship between type 2 DM (T2DM) and macroscopic small intestinal mucosal injuries is still unclear. Therefore, we retrospectively studied capsule endoscopy data to determine the relationship between T2DM and small intestinal mucosal injuries. Materials and Methods We compared the records of 38 T2DM patients with those of 152 non-DM patients for small intestinal mucosal injuries. Different types of mucosal injuries and Lewis scores were compared between T2DM and non-DM patients. The relationships between patients with or without different types of diabetic complications and the Lewis score was assessed. Moreover, the relationships between insulin resistance and Lewis score, between HbA1c and Lewis score, were also both assessed. Results The prevalence of a villous edema in subjects with T2DM was significantly higher than in those without DM (P < 0.001), but incidence of ulcers was not different (P = 1.000). With T2DM, the Lewis score was also significantly higher (P = 0.002). In addition, subjects with diabetic nephropathy showed significantly higher Lewis scores than patients without diabetic nephropathy (P = 0.033). In Pearson’s correlation tests, the homeostasis model assessment of insulin resistance (HOMA-IR) value was correlated positively with the Lewis score (γ = 0.175, P = 0.015), but no statistical correlation was found between HbA1c level and Lewis score (γ = 0.039, P = 0.697). Conclusions Subjects with T2DM, especially those with diabetic nephropathy, have higher Lewis scores and more serious small intestinal mucosal lesions. PMID:27598308

  18. Effects of early feeding and exogenous putrescine on growth and small intestinal development in posthatch ducks.

    PubMed

    Peng, P; Xu, J; Chen, W; Tangara, M; Qi, Z L; Peng, J

    2010-02-01

    1. Effects of early feeding with a diet containing added putrescine on duck intestinal development and growth performance were examined by a 2 x 2 factorial arrangement with two different feeding times (6 and 48 h) and two levels of putrescine (0 and 025%). 2. A significant main effect of early feeding on increasing body weight (BW) was observed from hatch to 35 d, whereas dietary putrescine had no significant effect on BW. 3. In the first week posthatch, enhanced small intestinal weight and intestinal density (weight of intestinal tissue/unit length of intestine), increased villus length and reduced crypt depth were observed in the early feeding group, while no effect was observed when putrescine was added to the diet. 4. Maltase and sucrase activity and protein/DNA ratio in jejunum were increased by early feeding in the first week, while decreased by putrescine supplementation. 5. In conclusion, early feeding methods have great potential for small intestine development and thereafter enhanced the growth performance of ducks, but dietary putrescine used during this period should be used cautiously to avoid toxicity.

  19. Diagnostic algorithm to differentiate lymphoma from inflammation in feline small intestinal biopsy samples.

    PubMed

    Kiupel, M; Smedley, R C; Pfent, C; Xie, Y; Xue, Y; Wise, A G; DeVaul, J M; Maes, R K

    2011-01-01

    Differentiating between inflammatory bowel disease (IBD) and small intestinal lymphoma in cats is often difficult, especially when only endoscopic biopsy specimens are available for evaluation. However, a correct diagnosis is imperative for proper treatment and prognosis. A retrospective study was performed using surgical and endoscopic intestinal biopsy specimens from 63 cats with a history of chronic diarrhea or vomiting or weight loss. A diagnosis of lymphoma or inflammation was based on microscopic examination of hematoxylin and eosin (HE)-stained sections alone, HE-stained sections plus results of immunohistochemical labeling (IHC) for CD3e and CD79a, and HE staining, immunophenotyping, and polymerase chain reaction (PCR) results for B and/or T cell clonality. In addition, various histomorphologic parameters were evaluated for significant differences between lymphoma and IBD using Fisher's exact test. The sensitivity and specificity of each parameter in the diagnosis of lymphoma were also determined. Results of Bayesian statistical analysis demonstrated that combining histologic evaluation of small intestinal biopsy specimens with immunophenotyping and analysis of clonality of lymphoid infiltrates results in more accurate differentiation of neoplastic versus inflammatory lymphocytes. Important histologic features that differentiated intestinal lymphoma from IBD included lymphoid infiltration of the intestinal wall beyond the mucosa, epitheliotropism (especially intraepithelial nests and plaques), heterogeneity, and nuclear size of lymphocytes. Based on the results of this study, a stepwise diagnostic algorithm that first uses histologic assessment, followed by immunophenotyping and then PCR to determine clonality of the lymphocytes, was developed to more accurately differentiate between intestinal lymphoma and IBD.

  20. 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 recombinant IL-1β. Indomethacin-induced small intestinal damage was reduced by 77%, as determined by the lesion index in NLRP3−/− mice, and colchicine treatment failed to inhibit small intestinal damage in NLRP3−/− mice. These results demonstrate that colchicine prevents NSAID-induced small intestinal injury by inhibiting activation of the NLRP3 inflammasome. PMID:27585971

  1. A Rare Type of Primary Internal Hernia Causing Small Intestinal Obstruction

    PubMed Central

    Mohapatra, Vandana; Rath, Pratap Kumar

    2016-01-01

    Primary internal hernias are extremely rare in adults. They are an important cause of small intestinal obstruction and lead to high morbidity and mortality if left untreated. Clinical presentation of internal hernia is nonspecific. Imaging has been of limited utility in cases of acute intestinal obstruction; moreover, interpretation of imaging features is operator dependant. Thus, internal hernias are usually detected at laparotomy and preoperative diagnosis in an emergency setting is either difficult or most of the time not suspected. We report herein a case of a 45-year-old male who presented with acute intestinal obstruction which was attributed later to a very rare type of internal hernia on exploratory laparotomy. A loop of ileum was found to enter the retroperitoneum through a hernia gate which was located lateral to the sigmoid colon in the left paracolic gutter. The segment of intestine was reduced and the hernial defect was closed. Our finding represents an extremely rare variant of retroperitoneal hernias. PMID:27999703

  2. 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

  3. Effect of carbachol on intestinal mucosal blood flow, activity of Na+-K+-ATPase, expression of aquaporin-1, and intestinal absorption rate during enteral resuscitation of burn shock in rats.

    PubMed

    Bao, Chengmei; Hu, Sen; Zhou, Guoyong; Tian, Yijun; Wu, Yan; Sheng, Zhiyong

    2010-01-01

    We investigated the effect of carbachol (CAR, a cholinergic agent) on intestinal mucosal blood flow (IMBF), activity of Na-K-ATPase, expression of aquaporin (AQP)-1, and intestinal absorption rate during enteral resuscitation of a 35%TBSA scald in rats with a glucose electrolyte solution (GES). One hundred male Wistar rats were randomly divided into five groups: sham scald (N group); scald without fluid resuscitation (S group); scald resuscitated with enteral GES alone (GES group); scald resuscitated with enteral CAR alone (CAR group); and scald resuscitated with enteral CAR plus GES (GES/CAR group). The rats were inflicted 35%TBSA third degree of scald injury on the back with boiling water (100 degrees C, 15 seconds) in all groups, except the sham scald group. A catheter was inserted into the proximal duodenum (5 cm distal to pylorus) and distal ileum (5 cm proximal to cecum), of each rats through laparotomy, thus a segment of intestine was virtually isolated to form a loop for inlet and outlet of introduced fluid. In N, GES, and GES/CAR groups, fluids were introduced 30 minutes after scald injury. The speed of fluid infusion was 4 ml/kg/1%TBSA for 4 hours. CAR (60 microg/kg) was injected into the intestinal lumen at 30-minute after injury in CAR and GES/CAR groups. At 2 and 4 hours after scald, intestinal absorption rate of water and Na, and IMBF were determined, respectively. Then, animals were killed, and specimens of intestinal tissue were obtained for the determination of the activity of Na-K-ATPase, hematoxylin-eosin coloring, and expression of AQP-1. The intestinal absorption rate was reduced markedly in GES group compared with sham scald group at 2 and 4 hours after scald, and absorption rate of small intestine in GES/CAR was significantly higher than that in GES group (P < .05). It was also found that there was significant decrease in IMBF, activity of Na-K-ATPase, and expression of AQP-1 in scald group compared with the sham group. However, in GES

  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.

  5. A comparative study on the metabolism of Epimedium koreanum Nakai-prenylated flavonoids in rats by an intestinal enzyme (lactase phlorizin hydrolase) and intestinal flora.

    PubMed

    Zhou, Jing; Chen, Yan; Wang, Ying; Gao, Xia; Qu, Ding; Liu, Congyan

    2013-12-24

    The aim of this study was to compare the significance of the intestinal hydrolysis of prenylated flavonoids in Herba Epimedii by an intestinal enzyme and flora. Flavonoids were incubated at 37 °C with rat intestinal enzyme and intestinal flora. HPLC-UV was used to calculate the metabolic rates of the parent drug in the incubation and LC/MS/MS was used to determine the chemical structures of metabolites generated by different flavonoid glycosides. Rates of flavonoid metabolism by rat intestinal enzyme were quicker than those of intestinal flora. The sequence of intestinal flora metabolic rates was icariin>epimedin B>epimedin A>epimedin C>baohuoside I, whereas the order of intestinal enzyme metabolic rates was icariin>epimedin A>epimedin C>epimedin B>baohuoside I. Meanwhile, the LC/MS/MS graphs showed that icariin produced three products, epimedin A/B/C had four and baohuoside I yielded one product in incubations of both intestinal enzyme and flora, which were more than the results of HPLC-UV due to the fact LC/MS/MS has lower detectability and higher sensitivity. Moreover, the outcomes indicated that the rate of metabolization of flavonoids by intestinal enzyme were faster than those of intestinal flora, which was consistent with the HPLC-UV results. In conclusion, the metabolic pathways of the same components by intestinal flora and enzyme were the same. What's more, an intestinal enzyme such as lactase phlorizin hydrolase exhibited a more significant metabolic role in prenylated flavonoids of Herba Epimedi compared with intestinal flora.

  6. 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.

  7. An in vivo model of human small intestine using pluripotent stem cells

    PubMed Central

    Watson, Carey L; Mahe, Maxime M; Múnera, Jorge; Howell, Jonathan C; Sundaram, Nambirajan; Poling, Holly M; Schweitzer, Jamie I; Vallance, Jefferson E; Mayhew, Christopher N; Sun, Ying; Grabowski, Gregory; Finkbeiner, Stacy R; Spence, Jason R; Shroyer, Noah F; Wells, James M; Helmrath, Michael A

    2015-01-01

    Differentiation of human pluripotent stem cells (hPSCs) into organ-specific subtypes offers an exciting avenue for the study of embryonic development and disease processes, for pharmacologic studies and as a potential resource for therapeutic transplant1,2. To date, limited in vivo models exist for human intestine, all of which are dependent upon primary epithelial cultures or digested tissue from surgical biopsies that include mesenchymal cells transplanted on biodegradable scaffolds3,4. Here, we generated human intestinal organoids (HIOs) produced in vitro from human embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs)5,6 that can engraft in vivo. These HIOs form mature human intestinal epithelium with intestinal stem cells contributing to the cryptvillus architecture and a laminated human mesenchyme, both supported by mouse vasculature ingrowth. In vivo transplantation resulted in marked expansion and maturation of the epithelium and mesenchyme, as demonstrated by differentiated intestinal cell lineages (enterocytes, goblet cells, Paneth cells, tuft cells and enteroendocrine cells), presence of functional brush-border enzymes (lactase, sucrase-isomaltase and dipeptidyl peptidase 4) and visible subepithelial and smooth muscle layers when compared with HIOs in vitro. Transplanted intestinal tissues demonstrated digestive functions as shown by permeability and peptide uptake studies. Furthermore, transplanted HIO-derived tissue was responsive to systemic signals from the host mouse following ileocecal resection, suggesting a role for circulating factors in the intestinal adaptive response7–9. This model of the human small intestine may pave the way for studies of intestinal physiology, disease and translational studies. PMID:25326803

  8. From Intestinal Permeability to Dysmotility: The Biobreeding Rat as a Model for Functional Gastrointestinal Disorders

    PubMed Central

    Vanheel, Hanne; Masaoka, Tatsuhiro; Salim Rasoel, Shadea; Tóth, Joran; Houben, Els; Verbeke, Kristin; De Hertogh, Gert; Berghe, Pieter Vanden; Tack, Jan; Farré, Ricard

    2014-01-01

    Background Impaired intestinal barrier function, low-grade inflammation and altered neuronal control are reported in functional gastrointestinal disorders. However, the sequence of and causal relation between these events is unclear, necessitating a spontaneous animal model. The aim of this study was to describe the natural history of intestinal permeability, mucosal and neuromuscular inflammation and nitrergic motor neuron function during the lifetime of the BioBreeding (BB) rat. Methods Normoglycemic BB-diabetes prone (DP) and control rats were sacrificed at different ages and jejunum was harvested to characterize intestinal permeability, inflammation and neuromuscular function. Results Both structural and functional evidence of increased intestinal permeability was found in young BB-DP rats from the age of 50 days. In older animals, starting in the mucosa from 70 days and in half of the animals also in the muscularis propria from 110 days, an inflammatory reaction, characterized by an influx of polymorphonuclear cells and higher myeloperoxidase activity, was observed. Finally, in animals older than 110 days, coinciding with a myenteric ganglionitis, a loss of nitrergic neurons and motor function was demonstrated. Conclusion In the BB-rat, mucosal inflammatory cell infiltration is preceded by intestinal barrier dysfunction and followed by myenteric ganglionitis and loss of nitrergic function. This sequence supports a primary role for impaired barrier function and provides an insightful model for the pathogenesis of functional gastrointestinal disorders. PMID:25354336

  9. Phloroglucinol Protects Small Intestines of Mice from Ionizing Radiation by Regulating Apoptosis-Related Molecules

    PubMed Central

    Ha, Danbee; Bing, So Jin; Cho, Jinhee; Ahn, Ginnae; Kim, Dae Seung; Al-Amin, Mohammad; Park, Suk Jae

    2013-01-01

    Phloroglucinol (PG) is a phenolic compound isolated from Ecklonia cava, a brown algae abundant on Jeju island, Korea. Previous reports have suggested that PG exerts antioxidative and cytoprotective effects against oxidative stress. In this study, we confirmed that PG protected against small intestinal damage caused by ionizing radiation, and we investigated its protective mechanism in detail. Regeneration of intestinal crypts in the PG-treated irradiated group was significantly promoted compared with that in irradiated controls. The expression level of proapoptotic molecules such as p53, Bax, and Bak in the small intestine was downregulated and that of antiapoptotic molecules such as Bcl-2 and Bcl-XS/L was augmented in the PG-treated group. On histological observation of the small intestine, PG inhibited the immunoreactivity of p53, Bax, and Bak and increased that of Bcl-2 and Bcl-XS/L. These results demonstrate the protective mechanisms of PG in mice against intestinal damage from ionizing radiation, providing the benefit of raising the apoptosis threshold of jejunal crypt cells. PMID:23117934

  10. What are the effects of proton pump inhibitors on the small intestine?

    PubMed

    Fujimori, Shunji

    2015-06-14

    Generally, proton-pump inhibitors (PPIs) have great benefit for patients with acid related disease with less frequently occurring side effects. According to a recent report, PPIs provoke dysbiosis of the small intestinal bacterial flora, exacerbating nonsteroidal anti-inflammatory drug-induced small intestinal injury. Several meta-analyses and systematic reviews have reported that patients treated with PPIs, as well as post-gastrectomy patients, have a higher frequency of small intestinal bacterial overgrowth (SIBO) compared to patients who lack the aforementioned conditions. Furthermore, there is insufficient evidence that these conditions induce Clostridium difficile infection. At this time, PPI-induced dysbiosis is considered a type of SIBO. It now seems likely that intestinal bacterial flora influence many diseases, such as inflammatory bowel disease, diabetes mellitus, obesity, non-alcoholic fatty liver disease, and autoimmune diseases. When attempting to control intestinal bacterial flora with probiotics, prebiotics, and fecal microbiota transplantation, etc., the influence of acid suppression therapy, especially PPIs, should not be overlooked.

  11. Development and Function of Secondary and Tertiary Lymphoid Organs in the Small Intestine and the Colon

    PubMed Central

    Buettner, Manuela; Lochner, Matthias

    2016-01-01

    The immune system of the gut has evolved a number of specific lymphoid structures that contribute to homeostasis in the face of microbial colonization and food-derived antigenic challenge. These lymphoid organs encompass Peyer’s patches (PP) in the small intestine and their colonic counterparts that develop in a programed fashion before birth. In addition, the gut harbors a network of lymphoid tissues that is commonly designated as solitary intestinal lymphoid tissues (SILT). In contrast to PP, SILT develop strictly after birth and consist of a dynamic continuum of structures ranging from small cryptopatches (CP) to large, mature isolated lymphoid follicles (ILF). Although the development of PP and SILT follow similar principles, such as an early clustering of lymphoid tissue inducer (LTi) cells and the requirement for lymphotoxin beta (LTβ) receptor-mediated signaling, the formation of CP and their further maturation into ILF is associated with additional intrinsic and environmental signals. Moreover, recent data also indicate that specific differences exist in the regulation of ILF formation between the small intestine and the colon. Importantly, intestinal inflammation in both mice and humans is associated with a strong expansion of the lymphoid network in the gut. Recent experiments in mice suggest that these structures, although they resemble large, mature ILF in appearance, may represent de novo-induced tertiary lymphoid organs (TLO). While, so far, it is not clear whether intestinal TLO contribute to the exacerbation of inflammatory pathology, it has been shown that ILF provide the critical microenvironment necessary for the induction of an effective host response upon infection with enteric bacterial pathogens. Regarding the importance of ILF for intestinal immunity, interfering with the development and maturation of these lymphoid tissues may offer novel means for manipulating the immune response during intestinal infection or inflammation. PMID

  12. d-Psicose Inhibits Intestinal alpha-Glucosidase and Suppresses the Glycemic Response after Ingestion of Carbohydrates in Rats.

    PubMed

    Matsuo, Tatsuhiro; Izumori, Ken

    2009-09-01

    d-psicose is one of the rare sugars present in small quantities in commercial carbohydrates and agricultural products. In this study, we investigated the effects of d-psicose on the activities of alpha-amylases and alpha-glucosidases in vitro, and evaluated the effects of d-psicose on the in vivo postprandial glycemic response using rats. In the in vitro study, d-psicose potently inhibited the intestinal sucrase and maltase, however, slightly inhibited the intestinal and salivary alpha-amylase activities. Male Wistar rats (6 months old) were administrated 2 g/kg of sucrose, maltose or soluble starch together with 0.2 g/kg of d-psicose or d-fructose. The d-psicose significantly inhibited the increment of plasma glucose concentration induced by sucrose or maltose. The starch-induced glycemic response tended to be suppressed by d-psicose, however the suppression was not significant. These results suggest that d-psicose inhibits intestinal sucrase and maltase activities and suppresses the plasma glucose increase the normally occurs after sucrose and maltose ingestion. Thus, d-psicose may be useful in preventing postprandial hyperglycemia in diabetic patients when foods containing sucrose and maltose are ingested.

  13. Glycoconjugate histochemistry in the small and large intestine of normal and Solanum glaucophyllum-intoxicated rabbits.

    PubMed

    Zanuzzi, C N; Barbeito, C G; Ortíz, M L; Lozza, F A; Fontana, P A; Portiansky, E L; Gimeno, E J

    2010-10-01

    Vitamin D participates in mineral homeostasis, immunomodulation, cell growth and differentiation. The leaves of Solanum glaucophyllum contain high levels of 1,25-dihydroxyvitamin D3 as glycoside derivatives and their chronic ingestion generates a hypervitaminosis D-like state. We analyzed changes on carbohydrate expression as a cell differentiation indicator on samples of the small and large intestine of S. glaucophyllum-intoxicated rabbits, using conventional and lectin histochemistry. Male New Zealand white rabbits were intoxicated with S. glaucophyllum during two or four weeks and killed the day after. A group of animals ("possibly recovered group") were intoxicated during 15 days and killed at day 45 of the beginning of the experiment. We found changes in the lectin binding pattern in the small and large intestine of the intoxicated rabbits. Some of these changes were reverted in the possibly recovered group. Vitamin D could be a new regulator factor of the intestinal glycosylation process.

  14. A "living bioreactor" for the production of tissue-engineered small intestine.

    PubMed

    Levin, Daniel E; Sala, Frederic G; Barthel, Erik R; Speer, Allison L; Hou, Xiaogang; Torashima, Yasuhiro; Grikscheit, Tracy C

    2013-01-01

    Here, we describe the use of a mouse model as a living bioreactor for the generation of tissue-engineered small intestine. Small intestine is harvested from donor mice with subsequent isolation of organoid units (a cluster of mesenchymal and epithelial cells). Some of these organoid units contain pluripotent stem cells with a preserved relationship with the mesenchymal stem cell niche. A preparation of organoid units is seeded onto a biodegradable scaffold and implanted intraperitoneally within the omentum of the host animal. The cells are nourished initially via imbibition until neovascularization occurs. This technique allows the growth of fully differentiated epithelium (composed of Paneth cells, goblet cells, enterocytes and enteroendocrine cells), muscle, nerve, and blood vessels of donor origin. Variations of this technique have been used to generate tissue-engineered stomach, large intestine, and esophagus. The variations include harvest technique, length of digestion, and harvest times.

  15. Cross-sectional small intestinal surveillance of maintenance hemodialysis patients using video capsule endoscopy: SCHEMA study

    PubMed Central

    Hosoe, Naoki; Matsukawa, Shigeaki; Kanno, Yoshihiko; Naganuma, Makoto; Imaeda, Hiroyuki; Ida, Yosuke; Tsuchiya, Yoshitsugu; Hibi, Toshifumi; Ogata, Haruhiko; Kanai, Takanori

    2016-01-01

    Background and study aims: Small intestinal pathology in hemodialysis (HD) patients has been studied in only a small number of retrospective case series. One method for noninvasively surveying small intestinal disorders is video capsule endoscopy (VCE). The primary aim of this study was to investigate the prevalence of small intestinal abnormalities among asymptomatic maintenance HD outpatients using VCE. The secondary aim was to assess the clinical impact of these abnormalities. Patients and methods: This study consisted of two phases. In phase I, a cross-sectional study, a cohort of patients who received maintenance HD three times weekly at an outpatient hemodialysis clinic were studied using VCE. Phase II was a prospective cohort study with follow up for 1 year after VCE. Results: Fifty-six patients were enrolled in this study, and two were excluded from analysis due to capsule retention in the stomach. The prevalence of small bowel abnormalities in HD patients was 64.8 % (35/54) (95 % confidential interval 52.1 % – 77.6 %). Of 54 patients, 21 (38.9 %) had mucosal lesions, 10 (18.5 %) had vascular lesions, and 4 (7.4 %) had both lesion types. During the 1-year follow-up period, events occurred in four patients. A small bowel-associated event was observed in one patient, who underwent laparoscopy-assisted small intestinal partial resection 3 months after diagnosis by VCE. All patients in whom events were seen had small bowel abnormalities; no events were observed in the VCE-negative group. Conclusions: Although asymptomatic maintenance HD patients had a high prevalence of small bowel abnormalities (64.8 %), they did not have a high incidence of small bowel-associated events during the 1-year follow-up. PMID:27227120

  16. Binding Studies on Isolated Porcine Small Intestinal Mucosa and in vitro Toxicity Studies Reveal Lack of Effect of C. perfringens Beta-Toxin on the Porcine Intestinal Epithelium

    PubMed Central

    Roos, Simone; Wyder, Marianne; Candi, Ahmet; Regenscheit, Nadine; Nathues, Christina; van Immerseel, Filip; Posthaus, Horst

    2015-01-01

    Beta-toxin (CPB) is the essential virulence factor of C. perfringens type C causing necrotizing enteritis (NE) in different hosts. Using a pig infection model, we showed that CPB targets small intestinal endothelial cells. Its effect on the porcine intestinal epithelium, however, could not be adequately investigated by this approach. Using porcine neonatal jejunal explants and cryosections, we performed in situ binding studies with CPB. We confirmed binding of CPB to endothelial but could not detect binding to epithelial cells. In contrast, the intact epithelial layer inhibited CPB penetration into deeper intestinal layers. CPB failed to induce cytopathic effects in cultured polarized porcine intestinal epithelial cells (IPEC-J2) and primary jejunal epithelial cells. C. perfringens type C culture supernatants were toxic for cell cultures. This, however, was not inhibited by CPB neutralization. Our results show that, in the porcine small intestine, CPB primarily targets endothelial cells and does not bind to epithelial cells. An intact intestinal epithelial layer prevents CPB diffusion into underlying tissue and CPB alone does not cause direct damage to intestinal epithelial cells. Additional factors might be involved in the early epithelial damage which is needed for CPB diffusion towards its endothelial targets in the small intestine. PMID:25860161

  17. Reduction of Acute Rejection by Bone Marrow Mesenchymal Stem Cells during Rat Small Bowel Transplantation

    PubMed Central

    Zhang, Wen; Wu, Ben-Juan; Fu, Nan-Nan; Zheng, Wei-Ping; Don, Chong; Shen, Zhong-Yang

    2014-01-01

    Background Bone marrow mesenchymal stem cells (BMMSCs) have shown immunosuppressive activity in transplantation. This study was designed to determine whether BMMSCs could improve outcomes of small bowel transplantation in rats. Methods Heterotopic small bowel transplantation was performed from Brown Norway to Lewis rats, followed by infusion of BMMSCs through the superficial dorsal veins of the penis. Controls included rats infused with normal saline (allogeneic control), isogeneically transplanted rats (BN-BN) and nontransplanted animals. The animals were sacrificed after 1, 5, 7 or 10 days. Small bowel histology and apoptosis, cytokine concentrations in serum and intestinal grafts, and numbers of T regulatory (Treg) cells were assessed at each time point. Results Acute cellular rejection occurred soon after transplantation and became aggravated over time in the allogeneic control rats, with increase in apoptosis, inflammatory response, and T helper (Th)1/Th2 and Th17/Treg-related cytokines. BMMSCs significantly attenuated acute cellular rejection, reduced apoptosis and suppressed the concentrations of interleukin (IL)-2, IL-6, IL-17, IL-23, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ while upregulating IL-10 and transforming growth factor (TGF)-β expression and increasing Treg levels. Conclusion BMMSCs improve the outcomes of allogeneic small bowel transplantation by attenuating the inflammatory response and acute cellular rejection. Treatment with BMMSCs may overcome acute cellular rejection in small bowel transplantation. PMID:25500836

  18. Development of lntraepithelial Cells in the Porcine Small Intestine

    PubMed Central

    Arenas-Contreras, G.; Bailey, M.; González-Pozos, S.; Stokes, C. R.; Ortega, M. G.; Mondragón-Flores, R.

    2001-01-01

    The number, phenotype, localisation and development of intraepithelial lymphocytes (IEL) from duodenum (Du) and ileum (Il) were studied by immunohistochemistry (IHC) and light and electron microscopy in unweaned (0–7 weeks old) and six months-old pigs. Developmental changes at birth showed that 38% of the total lymphocytes in the villi were IEL, mainly of the CD2+CD4-CD8- double negative (DN) phenotype. That proportion rose to over 50% at week 5 after birth, resembling adult proportion, although still with fewer cells than in adult pigs. CD4+ cells appeared relatively early in life although they were confined to the lamina propria (LP) and CD8+ cells were found only in low numbers. In the villi of adult animals, almost half of the total number of lymphocytes were IEL (49% Du, 52% Il). Over half of these IEL (52% Du, 53% Il) showed the CD2+CD4-CD8+ phenotype and were localized at the epithelium's basement membrane. Numerous (43% Du, 42% Il) DN IEL were found grouped at the enterocyte nucleus level and relatively few (5% in Du and Il) granular IEL were found apically in the epithelium. These proportions were homogeneously maintained along the villi's tip, middle and bottom, suggesting that the IEL may have their origin in the LP. Therefore, the IEL compartment in the porcine intestine develops slowly with age and is actually composed by a heterogeneous population of cells (null, DN and CD8+). These results may explain the increased susceptibility of young animals to disease during the lactation period and should be taken into account when functional studies are carried out with IEL. The quantitative results of this paper established a model for studies on the effect of age, diet, normal flora, infection and oral immunization on the IEL of the gut. PMID:11589310

  19. Depletion of enteric bacteria diminishes leukocyte infiltration following doxorubicin-induced small intestinal damage in mice

    PubMed Central

    Carr, Jacquelyn S.; King, Stephanie

    2017-01-01

    Background & aims While enteric bacteria have been shown to play a critical role in other forms of intestinal damage, their role in mediating the response to the chemotherapeutic drug Doxorubicin (Doxo) is unclear. In this study, we used a mouse model of intestinal bacterial depletion to evaluate the role enteric bacteria play in mediating Doxo-induced small intestinal damage and, more specifically, in mediating chemokine expression and leukocyte infiltration following Doxo treatment. An understanding of this pathway may allow for development of intervention strategies to reduce chemotherapy-induced small intestinal damage. Methods Mice were treated with (Abx) or without (NoAbx) oral antibiotics in drinking water for four weeks and then with Doxo. Jejunal tissues were collected at various time points following Doxo treatment and stained and analyzed for apoptosis, crypt damage and restitution, and macrophage and neutrophil number. In addition, RNA expression of inflammatory markers (TNFα, IL1-β, IL-10) and cytokines (CCL2, CC7, KC) was assessed by qRT-PCR. Results In NoAbx mice Doxo-induced damage was associated with rapid induction of apoptosis in jejunal crypt epithelium and an increase weight loss and crypt loss. In addition, we observed an increase in immune-modulating chemokines CCL2, CCL7 and KC and infiltration of macrophages and neutrophils. In contrast, while still positive for induction of apoptosis following Doxo treatment, Abx mice showed neither the overall weight loss nor crypt loss seen in NoAbx mice nor the increased chemokine expression and leukocyte infiltration. Conclusion Enteric bacteria play a critical role in Doxo-induced small intestinal damage and are associated with an increase in immune-modulating chemokines and cells. Manipulation of enteric bacteria or the damage pathway may allow for prevention or treatment of chemotherapy-induced small intestinal damage. PMID:28257503

  20. Use of Ligated Segments of Rabbit Small Intestine in Experimental Shigellosis1

    PubMed Central

    Arm, H. G.; Floyd, T. M.; Faber, J. E.; Hayes, J. R.

    1965-01-01

    Arm, H. G. (Naval Medical Research Institute, Bethesda, Md.), T. M. Floyd, J. E. Faber, and J. R. Hayes. Use of ligated segments of rabbit small intestine in experimental shigellosis. J. Bacteriol. 89:803–809. 1965.—Inoculation of ligated segments of small intestine in living rabbits with broth cultures or resting-cell suspensions of recently isolated strains of Shigella caused distension of the segments by accumulation of exudate within 12 hr. Histological changes characteristic of an inflammatory response were similar to those of human bacillary dysentery. Tissue response and accumulation of exudate preceded demonstrable increase in numbers of shigellae inoculated as 2 × 1010 resting cells. Capability of shigellae to provoke intestinal response was not related to any particular serological group. The active principles concerned with eliciting intestinal response were associated only with preparations containing living organisms. Ability of recently isolated strains to elicit response diminished rapidly during culture on artificial media. The capability was preserved indefinitely by lyophilization soon after isolation from acute bacillary dysentery infections of man. Advantages of using shigellae recently isolated for investigating possible mechanisms of pathogenesis were indicated. During the summer months, the rabbit small intestine was refractory to the activity of shigellae, and positive responses were not observed. Use of ligated segments of rabbit small intestine qualified as an indicator of virulence for the rabbit; and, virulence for the rabbit showed a high degree of correlation with a short period of culture of shigellae on artificial media after isolation from human bacillary dysentery infections. Images PMID:14273664

  1. Immunological quantitation and localization of ACAT-1 and ACAT-2 in human liver and small intestine.

    PubMed

    Chang, C C; Sakashita, N; Ornvold, K; Lee, O; Chang, E T; Dong, R; Lin, S; Lee, C Y; Strom, S C; Kashyap, R; Fung, J J; Farese, R V; Patoiseau, J F; Delhon, A; Chang, T Y

    2000-09-08

    By using specific anti-ACAT-1 antibodies in immunodepletion studies, we previously found that ACAT-1, a 50-kDa protein, plays a major catalytic role in the adult human liver, adrenal glands, macrophages, and kidneys but not in the intestine. Acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity in the intestine may be largely derived from a different ACAT protein. To test this hypothesis, we produced specific polyclonal anti-ACAT-2 antibodies that quantitatively immunodepleted human ACAT-2, a 46-kDa protein expressed in Chinese hamster ovary cells. In hepatocyte-like HepG2 cells, ACAT-1 comprises 85-90% of the total ACAT activity, with the remainder attributed to ACAT-2. In adult intestines, most of the ACAT activity can be immunodepleted by anti-ACAT-2. ACAT-1 and ACAT-2 do not form hetero-oligomeric complexes. In differentiating intestinal enterocyte-like Caco-2 cells, ACAT-2 protein content increases by 5-10-fold in 6 days, whereas ACAT-1 protein content remains relatively constant. In the small intestine, ACAT-2 is concentrated at the apices of the villi, whereas ACAT-1 is uniformly distributed along the villus-crypt axis. In the human liver, ACAT-1 is present in both fetal and adult hepatocytes. In contrast, ACAT-2 is evident in fetal but not adult hepatocytes. Our results collectively suggest that in humans, ACAT-2 performs significant catalytic roles in the fetal liver and in intestinal enterocytes.

  2. 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

  3. Fatty Acid-Binding Protein in Small Intestine IDENTIFICATION, ISOLATION, AND EVIDENCE FOR ITS ROLE IN CELLULAR FATTY ACID TRANSPORT

    PubMed Central

    Ockner, Robert K.; Manning, Joan A.

    1974-01-01

    A soluble fatty acid-binding protein (FABP), mol wt ∼ 12,000 is present in intestinal mucosa and other tissues that utilize fatty acids, including liver, myocardium, adipose, and kidney. This protein binds long chain fatty acids both in vivo and in vitro. FABP was isolated from rat intestine by gel filtration and isoelectric focusing. It showed a reaction of complete immunochemical identity with proteins in the 12,000 mol wt fatty acid-binding fractions of liver, myocardium, and adipose tissue supernates. (The presence of immunochemically nonidentical 12,000 mol wt FABP in these tissues is not excluded.) By quantitative radial immunodiffusion, supernatant FABP concentration in mucosa from proximal and middle thirds of jejuno-ileum significantly exceeded that in distal third, duodenum, and liver, expressed as micrograms per milligram soluble protein, micrograms per gram DNA, and micrograms per gram tissue. FABP concentration in villi was approximately three times greater than in crypts. Small quantities of FABP were present in washed nuclei-cell membrane, mitochondrial and microsomal fractions. However, the amount of FABP solubilized per milligram membrane protein was similar for all particulate fractions, and total membrane-associated FABP was only about 16% of supernatant FABP. Intestinal FABP concentration was significantly greater in animals maintained on high fat diets than on low fat; saturated and unsaturated fat diets did not differ greatly in this regard. The preponderance of FABP in villi from proximal and middle intestine, its ability to bind fatty acids in vivo as well as in vitro, and its response to changes in dietary fat intake support the concept that this protein participates in cellular fatty acid transport during fat absorption. Identical or closely related 12,000 mol wt proteins may serve similar functions in other tissues. Images PMID:4211161

  4. Bifocal metastasis of melanoma to the small intestine from an unknown primary with intestinal obstruction – case report

    PubMed Central

    Bandurski, Jędrzej; Lewandowski, Andrzej

    2013-01-01

    A 64-year-old woman was hospitalized at an internal care unit, due to growing weakness, dizziness, lack of appetite, anemia and abdominal pain. In anamnesis: past myocardial infarction, post-operative hypothyroidism, type 2 diabetes insulin-dependent, stroke, left kidney cirrhosis, gout and anemia. The physical examination did not reveal pathological changes except for skin paleness. The biochemical tests showed iron deficiency anemia and elevated Ca 125 (54.5 U/ml) (normal range: 0.00–35.00). Other markers were normal. An abdominal CT revealed a bifocal infiltration of the small intestine. Due to the increasing obstruction symptoms, the patient was operated on. A bifocal small bowel tumor was found intra-surgically. A partial resection of the jejunum and distal ileum was made. The intestines were joined end to end. The histopathological diagnosis corresponded to metastases of malignant melanoma. The postoperative course was uncomplicated. She received two cycles of dacarbazine 1000 mg/day. Due to drug intolerance, the chemotherapy was discontinued. Now, she is receiving hospice care. PMID:24596522

  5. Lactobacillus fermentum BR11 and fructo-oligosaccharide partially reduce jejunal inflammation in a model of intestinal mucositis in rats.

    PubMed

    Smith, Cassie L; Geier, Mark S; Yazbeck, Roger; Torres, Diana M; Butler, Ross N; Howarth, Gordon S

    2008-01-01

    Although probiotics are beginning to enter mainstream medicine for disorders of the colon, their effects on the small bowel remain largely unexplored. We investigated the recently identified probiotic, Lactobacillus fermentum (L. fermentum) BR11 (BR11) and the prebiotic, fructo-oligosaccharide (FOS), both individually and in synbiotic combination, for their potential to alleviate intestinal mucositis. From Days 0-9, rats consumed skim milk (SM; saline + SM), low dose (LD-BR11; 1 x 10(6)cfu/ml), high dose (HD-BR11; 1 x 10(9)cfu/ml), LD-FOS (3%), HD-FOS (6%), or synbiotic (HD-BR11/FOS). On Day 7, rats were injected with 5-fluorouracil (5-FU; 150 mg/kg). All rats were sacrificed on Day 10. Intestinal tissues were collected for quantitative histology, sucrase, and myeloperoxidase (MPO) determinations. 5-FU decreased sucrase activity, villus height, crypt depth, and crypt cell proliferation compared to controls. Compared to 5-FU + SM, histological damage severity scores were increased for all treatments, although all were effective at reducing jejunal inflammation, indicated by reduced MPO activity (P < 0.05). The combination of BR11 and FOS did not provide additional protection. Moreover, HD-FOS and the synbiotic actually increased clinical mucositis severity (P < 0.05). We conclude that L. fermentum BR11 has the potential to reduce inflammation of the upper small intestine. However, its combination with FOS does not appear to confer any further therapeutic benefit for the alleviation of mucositis.

  6. Oral curcumin has anti-arthritic efficacy through somatostatin generation via cAMP/PKA and Ca(2+)/CaMKII signaling pathways in the small intestine.

    PubMed

    Yang, Yan; Wu, Xin; Wei, Zhifeng; Dou, Yannong; Zhao, Di; Wang, Ting; Bian, Difei; Tong, Bei; Xia, Ying; Xia, Yufeng; Dai, Yue

    2015-01-01

    Curcumin (CUR) has been proven to be clinically effective in rheumatoid arthritis (RA) therapy, but its low oral bioavailability eclipses existent evidence that attempts to explain the underlying mechanism. Small intestine, the only organ exposed to a relatively high concentration of CUR, is the main site that generates gut hormones which are involved in the pathogenesis of RA. This study aims at addressing the hypothesis that one or more gut hormones serve as an intermediary agent for the anti-arthritic action of CUR. The protein and mRNA levels of gut hormones in CUR-treated rats were analyzed by ELISA and RT-PCR. Somatostatin (SOM) depletor and receptor antagonist were used to verify the key role of SOM in CUR-mediated anti-arthritic effect. The mechanisms underlying CUR-induced upregulation of SOM levels were explored by cellular experiments and immunohistochemical staining. The data showed that oral administration of CUR (100 mg/kg) for consecutive two weeks in adjuvant-induced arthritis rats still exhibited an extremely low plasma exposure despite of a dramatic amelioration of arthritis symptoms. When injected intraperitoneally, CUR lost anti-arthritic effect in rats, suggesting that it functions in an intestine-dependent manner. CUR elevated SOM levels in intestines and sera, and SOM depletor and non-selective SOM receptor antagonist could abolish the inhibitory effect of CUR on arthritis. Immunohistochemical assay demonstrated that CUR markedly increased the number of SOM-positive cells in both duodenum and jejunum. In vitro experiments demonstrated that CUR could augment SOM secretion from intestinal endocrine cells, and this effect could be hampered by either MEK1/2 or Ca(2+)/calmodulin-dependent kinase II (CAMKII) inhibitor. In summary, oral administration of CUR exhibits anti-arthritic effect through augmenting SOM secretion from the endocrine cells in small intestines via cAMP/PKA and Ca(2+)/CaMKII signaling pathways.