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Sample records for human intestinal transit

  1. Relationship between postprandial motor activity in the human small intestine and the gastrointestinal transit of food

    Profiles for gastric emptying and colonic filling were determined in 20 normal volunteers by means of a gamma camera and dedicated minicomputer after ingestion of a radiolabeled solid meal. These were compared with intraluminal pressure activity, recorded simultaneously from three sites (each separated by 50 cm) in the small intestine by infusion manometry. Recordings were continued for at least 8 h or until all the radioactivity appeared in the colon. Colonic filling was approximately linear, occurring at an average rate of 16% of the meal residues per hour. There were significant inverse correlations (p less than 0.01) between the pressure activity in the proximal jejunum during the first 3 h after ingestion and the times taken for 50% and 80% of the meal residues to enter the colon, and direct correlations between total small intestinal pressure activity and the half-time for gastric emptying. Phase III of the interdigestive migrating motor complex appeared between 3 and 9 h after ingestion (when between 15% and 80% of the meal remained in the small intestine), but did not necessarily migrate to the next recording site until much later. The time of appearance of phase III in the proximal jejunum was directly correlated with the half-time for gastric emptying (p less than 0.05) and with the intraluminal pressure activity recorded at that site during the first 3 h after food ingestion (p less than 0.01). The time at which 80% of the meal residues had entered the colon was significantly shorter in 6 subjects, in whom a postprandial activity front appeared to migrate throughout the small bowel, compared with 13 subjects, in whom this did not occur (5.0 +/- 0.5 h vs. 7.0 +/- 0.4 h, p less than 0.01). These studies have shown that gastrointestinal transit of a solid meal is related to both fed and fasted intraluminal pressure activity in the small intestine

  2. Shiga Toxin Interaction with Human Intestinal Epithelium

    Stephanie Schüller

    2011-01-01

    After ingestion via contaminated food or water, enterohaemorrhagic E. coli colonises the intestinal mucosa and produces Shiga toxins (Stx). No Stx-specific secretion system has been described so far, and it is assumed that Stx are released into the gut lumen after bacterial lysis. Human intestinal epithelium does not express the Stx receptor Gb3 or other Stx binding sites, and it remains unknown how Stx cross the intestinal epithelial barrier and gain access to the systemic circulation. This ...

  3. Radioimmunoassay of human intestinal alkaline phosphatase

    A new method of radioimmunoassay using the double antibody method for human intestinal alkaline phosphatase (ALP) was first elaborated. The following results were obtained: 1) In this system, the optimal antibody concentration is 10,000 times the dilution of the original anti-serum, and the optimal assay range is 0.5 to 25 ng. Enzymatic activity of 1 ng intestinal ALP is 4.1 King-Armstrong units. 2) In this system, the sera including intestinal ALP are divided to two groups. One group shows a dose response curve similar to that of purified intestinal ALP, and the other shows a lesser one. This reason is not clear. Hepatic ALP, osseous ALP and placental ALP in the sera show no response in this system. 3) In this system, the B/T value of 50 μg of purified human placental ALP is almost equal to 1 ng of purified human intestinal ALP. Similarly, the B/T value of 50 μg of purified human intestinal ALP is equal to almost 5 ng of purified human placental ALP. This shows that cross-reaction exists between intestinal and placental ALPs at high concentrations. (J.P.N.)

  4. Accurate measurement of intestinal transit in the rat

    A new method for quantifying intestinal transit was evaluated by comparison with two other popular techniques. The distribution of radiochromium (51Cr) throughout the small intestine of rats previously treated with saline (1.0 ml/kg s.c.), capsaicin (10 mg/kg s.c.), hexamethonium (20 mg/kg i.p.), D-ala2-met-enkephalinamide (1.0 microgram i.c.v.), or neostigmine (0.1 mg/kg i.p.) was quantified by (1) measuring the most distal intestinal segment reached by chromium, (2) calculating the slope produced by linear regression analysis on cumulative percent chromium that had passed through each segment, and (3) determining the geometric center of the distribution of chromium throughout the small intestine. It was concluded that the geometric center methods for quantifying intestinal transit provides the most sensitive and reliable measure of intestinal transit. Less sensitive techniques often fail to detect important effects of drugs on intestinal transit

  5. Accurate measurement of intestinal transit in the rat

    Miller, M.S.; Galligan, J.J.; Burks, T.F.

    1981-11-01

    A new method for quantifying intestinal transit was evaluated by comparison with two other popular techniques. The distribution of radiochromium (51Cr) throughout the small intestine of rats previously treated with saline (1.0 ml/kg s.c.), capsaicin (10 mg/kg s.c.), hexamethonium (20 mg/kg i.p.), D-ala2-met-enkephalinamide (1.0 microgram i.c.v.), or neostigmine (0.1 mg/kg i.p.) was quantified by (1) measuring the most distal intestinal segment reached by chromium, (2) calculating the slope produced by linear regression analysis on cumulative percent chromium that had passed through each segment, and (3) determining the geometric center of the distribution of chromium throughout the small intestine. It was concluded that the geometric center methods for quantifying intestinal transit provides the most sensitive and reliable measure of intestinal transit. Less sensitive techniques often fail to detect important effects of drugs on intestinal transit.

  6. Shiga Toxin Interaction with Human Intestinal Epithelium

    Stephanie Schüller

    2011-06-01

    Full Text Available After ingestion via contaminated food or water, enterohaemorrhagic E. coli colonises the intestinal mucosa and produces Shiga toxins (Stx. No Stx-specific secretion system has been described so far, and it is assumed that Stx are released into the gut lumen after bacterial lysis. Human intestinal epithelium does not express the Stx receptor Gb3 or other Stx binding sites, and it remains unknown how Stx cross the intestinal epithelial barrier and gain access to the systemic circulation. This review summarises current knowledge about the influence of the intestinal environment on Stx production and release, Stx interaction with intestinal epithelial cells and intracellular uptake, and toxin translocation into underlying tissues. Furthermore, it highlights gaps in understanding that need to be addressed by future research.

  7. Tipping elements in the human intestinal ecosystem

    Lahti, L.; Salojarvi, J.; Salonen, A.; Scheffer, M.; De Vos

    2014-01-01

    The microbial communities living in the human intestine can have profound impact on our well-being and health. However, we have limited understanding of the mechanisms that control this complex ecosystem. Here, based on a deep phylogenetic analysis of the intestinal microbiota in a thousand western adults, we identify groups of bacteria that exhibit robust bistable abundance distributions. These bacteria are either abundant or nearly absent in most individuals, and exhibit decreased temporal ...

  8. Acquired macrolide resistance in the human intestinal strain Lactobacillus rhamnosus E41 associated with a transition mutation in 23S rRNA genes

    Flórez García, Ana Belén; Ladero Losada, Víctor Manuel; Álvarez Martín, Pablo; Ammor, Mohammed Salim; Álvarez González, Miguel Ángel; Mayo Pérez, Baltasar

    2007-01-01

    Restriction fragment length polymorphism and DNA sequencing of polymerase chain reaction (PCR) products showed that a Lactobacillus rhamnosus strain of human origin resistant to macrolides, from which no resistance determinants have been detected by specific PCR and microarray screening, contained a heterozygous A → G transition mutation at position 2058 (Escherichia coli numbering) of its 23S rRNA genes.

  9. A deconvolution technique for processing small intestinal transit data

    The deconvolution technique can be used to compute small intestinal impulse response curves from scintigraphic data. Previously suggested approaches, however, are sensitive to noise from the data. We investigated whether deconvolution based on a new simple iterative convolving technique can be recommended. Eight healthy volunteers ingested a meal that contained indium-111 diethylene triamine penta-acetic acid labelled water and technetium-99m stannous colloid labelled omelette. Imaging was performed at 30-min intervals until all radioactivity was located in the colon. A Fermi function=(1+e-αβ)/(1+e(t-α)β) was chosen to characterize the small intestinal impulse response function. By changing only two parameters, α and β, it is possible to obtain configurations from nearly a square function to nearly a monoexponential function. Small intestinal input function was obtained from the gastric emptying curve and convolved with the Fermi function. The sum of least squares was used to find α and β yielding the best fit of the convolved curve to the observed small intestinal time-activity curve. Finally, a small intestinal mean transit time was calculated from the Fermi function referred to. In all cases, we found an excellent fit of the convolved curve to the observed small intestinal time-activity curve, that is the Fermi function reflected the small intestinal impulse response curve. Small intestinal mean transit time of liquid marker (median 2.02 h) was significantly shorter than that of solid marker (median 2.99 h; P<0.02). The iterative convolving technique seems to be an attractive alternative to ordinary approaches for the processing of small intestinal transit data. (orig.)

  10. A deconvolution technique for processing small intestinal transit data

    Brinch, K. [Department of Clinical Physiology and Nuclear Medicine, Glostrup Hospital, University Hospital of Copenhagen (Denmark); Larsson, H.B.W. [Danish Research Center of Magnetic Resonance, Hvidovre Hospital, University Hospital of Copenhagen (Denmark); Madsen, J.L. [Department of Clinical Physiology and Nuclear Medicine, Hvidovre Hospital, University Hospital of Copenhagen (Denmark)

    1999-03-01

    The deconvolution technique can be used to compute small intestinal impulse response curves from scintigraphic data. Previously suggested approaches, however, are sensitive to noise from the data. We investigated whether deconvolution based on a new simple iterative convolving technique can be recommended. Eight healthy volunteers ingested a meal that contained indium-111 diethylene triamine penta-acetic acid labelled water and technetium-99m stannous colloid labelled omelette. Imaging was performed at 30-min intervals until all radioactivity was located in the colon. A Fermi function=(1+e{sup -{alpha}{beta}})/(1+e{sup (t-{alpha}){beta}}) was chosen to characterize the small intestinal impulse response function. By changing only two parameters, {alpha} and {beta}, it is possible to obtain configurations from nearly a square function to nearly a monoexponential function. Small intestinal input function was obtained from the gastric emptying curve and convolved with the Fermi function. The sum of least squares was used to find {alpha} and {beta} yielding the best fit of the convolved curve to the oberved small intestinal time-activity curve. Finally, a small intestinal mean transit time was calculated from the Fermi function referred to. In all cases, we found an excellent fit of the convolved curve to the observed small intestinal time-activity curve, that is the Fermi function reflected the small intestinal impulse response curve. Small intestinal mean transit time of liquid marker (median 2.02 h) was significantly shorter than that of solid marker (median 2.99 h; P<0.02). The iterative convolving technique seems to be an attractive alternative to ordinary approaches for the processing of small intestinal transit data. (orig.) With 2 figs., 13 refs.

  11. Icariin Metabolism by Human Intestinal Microflora.

    Wu, Hailong; Kim, Mihyang; Han, Jaehong

    2016-01-01

    Icariin is a major bioactive compound of Epimedii Herba, a traditional oriental medicine exhibiting anti-cancer, anti-inflammatory and anti-osteoporosis activities. Recently, the estrogenic activities of icariin drew significant attention, but the published scientific data seemed not to be so consistent. To provide fundamental information for the study of the icaritin metabolism, the biotransformation of icariin by the human intestinal bacteria is reported for the first time. Together with human intestinal microflora, the three bacteria Streptococcus sp. MRG-ICA-B, Enterococcus sp. MRG-ICA-E, and Blautia sp. MRG-PMF-1 isolated from human intestine were reacted with icariin under anaerobic conditions. The metabolites including icariside II, icaritin, and desmethylicaritin, but not icariside I, were produced. The MRG-ICA-B and E strains hydrolyzed only the glucose moiety of icariin, and icariside II was the only metabolite. However, the MRG-PMF-1 strain metabolized icariin further to desmethylicaritin via icariside II and icaritin. From the results, along with the icariin metabolism by human microflora, it was evident that most icariin is quickly transformed to icariside II before absorption in the human intestine. We propose the pharmacokinetics of icariin should focus on metabolites such as icariside II, icaritin and desmethylicaritin to explain the discrepancy between the in vitro bioassay and pharmacological effects. PMID:27589718

  12. Faecalibacterium prausnitzii and human intestinal health

    Miquel, S.; Martin, R.; Rossi, O.; Bermudez-Humaran, L.G.; Chatel, J.M.; Sokol, H.; Thomas, M.; Wells, J.M.; Langella, P.

    2013-01-01

    Faecalibacterium prausnitzii is the most abundant bacterium in the human intestinal microbiota of healthy adults, representing more than 5% of the total bacterial population. Over the past five years, an increasing number of studies have clearly described the importance of this highly metabolically

  13. Intestinal transit of solid and liquid components of a meal in health.

    Malagelada, J R; Robertson, J S; Brown, M L; Remington, M; Duenes, J A; Thomforde, G M; Carryer, P W

    1984-12-01

    The aim of this study was to test the hypothesis that, under physiologic conditions, the human small bowel discriminates between the solid and aqueous components of chyme, that is, that in a fashion analogous to the stomach, the intestine would allow the liquid fraction to progress at a faster rate than solid particles. To evaluate this hypothesis, we took advantage of a gamma-emitting solid marker, 131I-fiber, previously developed in our laboratory, that is recognized by the stomach as a solid and that is emptied at a slower rate than liquid markers. Thus, 131I-fiber enters the intestine during feeding at a slower rate than a liquid marker, being eventually excreted in the feces physically and chemically unchanged. We also developed a mathematical method to calculate the intestinal transit spectrum based on scintigraphic data obtained from 6 healthy individuals who ingested 131I-fiber and technetium 99m (99mTc)-diethylenetriaminepentaacetic acid (DTPA)-water with a meal. The results disprove the hypothesis by showing that whereas 131I-fiber, as expected, leaves the stomach at a much slower rate than 99mTc-DTPA-water, both markers progress along the small bowel separately but at similar speeds. Our method for measuring intestinal transit provides a more comprehensive quantification of chyme transit in the human small bowel than earlier methods and should prove a useful technique for further noninvasive studies of transit after feeding. PMID:6092195

  14. Intestinal transit of solid and liquid components of a meal in health

    Malagelada, J.R.; Robertson, J.S.; Brown, M.L.; Remington, M.; Duenes, J.A.; Thomforde, G.M.; Carryer, P.W.

    1984-12-01

    The aim of this study was to test the hypothesis that, under physiologic conditions, the human small bowel discriminates between the solid and aqueous components of chyme, that is, that in a fashion analogous to the stomach, the intestine would allow the liquid fraction to progress at a faster rate than solid particles. To evaluate this hypothesis, the authors took advantage of a gamma-emitting solid marker, /sup 131/I-fiber, previously developed in their laboratory, that is recognized by the stomach as a solid and that is emptied at a slower rate than liquid markers. Thus, /sup 131/I-fiber enters the intestine during feeding at a slower rate than a liquid marker, being eventually excreted in the feces physically and chemically unchanged. We also developed a mathematical method was also developed to calculate the intestinal transit spectrum based on scintigraphic data obtained from 6 healthy individuals who ingested /sup 131/I-fiber and technetium /sup 99m/ (/sup 99m/Tc)-diethylenetriaminepentaacetic acid (DTPA)-water with a meal. The results disprove the hypothesis by showing that whereas /sup 131/I-fiber, as expected, leaves the stomach at a much slower rate than /sup 99m/Tc-DTPA-water, both markers progress along the small bowel separately but at similar speeds. This method for measuring intestinal transit provides a more comprehensive quantification of chyme transit in the human small bowel than earlier methods and should prove a useful technique for further noninvasive studies of transit after feeding.

  15. Intestinal transit of solid and liquid components of a meal in health

    The aim of this study was to test the hypothesis that, under physiologic conditions, the human small bowel discriminates between the solid and aqueous components of chyme, that is, that in a fashion analogous to the stomach, the intestine would allow the liquid fraction to progress at a faster rate than solid particles. To evaluate this hypothesis, the authors took advantage of a gamma-emitting solid marker, 131I-fiber, previously developed in their laboratory, that is recognized by the stomach as a solid and that is emptied at a slower rate than liquid markers. Thus, 131I-fiber enters the intestine during feeding at a slower rate than a liquid marker, being eventually excreted in the feces physically and chemically unchanged. We also developed a mathematical method was also developed to calculate the intestinal transit spectrum based on scintigraphic data obtained from 6 healthy individuals who ingested 131I-fiber and technetium /sup 99m/ (/sup 99m/Tc)-diethylenetriaminepentaacetic acid (DTPA)-water with a meal. The results disprove the hypothesis by showing that whereas 131I-fiber, as expected, leaves the stomach at a much slower rate than /sup 99m/Tc-DTPA-water, both markers progress along the small bowel separately but at similar speeds. This method for measuring intestinal transit provides a more comprehensive quantification of chyme transit in the human small bowel than earlier methods and should prove a useful technique for further noninvasive studies of transit after feeding

  16. Cholesterol esterase activity of human intestinal mucosa

    It has been suggested that cholesterol absorption in humans is dependent on bile acid pool composition and that expansion of the cholic acid pool size is followed by an increase of the absorption values. Similar observations were reported in rats. In the present study, therefore, the authors investigated some general properties of human intestinal cholesterol esterase, with particular emphasis on the effect of bile acids on this enzymatic activity. Twenty-nine segments of small intestine were taken during operations; the enzymatic activity was studied by using mucosal homogenate as a source of enzyme and oleic acid, cholesterol, and 14C-labeled cholesterol as substrates. The time-activity relationship was linear within the first two hours; optimal pH for esterification ranged between 5 and 6.2. There was little difference between the esterifying activity of the jejunal and ileal mucosa. Esterification of cholesterol was observed with all the investigated fatty acids but was maximal with oleic acid. Bile acids did not affect cholesterol esterase activity when present in the incubation mixture at 0.1 and 1.0 mM; the enzymatic activity, however, was significantly inhibited when bile acids were added at 20 mM. In conclusion, this study has shown that the human intestinal mucosa possesses a cholesterol esterase activity; at variance with the rat, however, the human enzyme does not seem to be stimulated by trihydroxy bile acids

  17. Compartmentalization of Aquaporins in the Human Intestine

    Rajendram V. Rajnarayanan

    2008-06-01

    Full Text Available Improper localization of water channel proteins called aquaporins (AQP induce mucosal injury which is implicated in Crohn’s disease and ulcerative colitis. The amino acid sequences of AQP3 and AQP10 are 79% similar and belong to the mammalian aquaglyceroporin subfamily. AQP10 is localized on the apical compartment of the intestinal epithelium called the glycocalyx while AQP3 is selectively targeted to the basolateral membrane. Despite the high sequence similarity and evolutionary relatedness, the molecular mechanism involved in the polarity, selective targeting and function of AQP3 and AQP10 in the intestine is largely unknown. Our hypothesis is that the differential polarity and selective targeting of AQP3 and AQP10 in the intestinal epithelial cells is influenced by amino acid signal motifs. We performed sequence and structural alignments to determine differences in signals for localization and posttranslational glycosylation. The basolateral sorting motif “YRLL” is present in AQP3 but absent in AQP10; while Nglycosylation signals are present in AQP10 but absent in AQP3. Furthermore, the C-terminal region of AQP3 is longer compared to AQP10. The sequence and structural differences between AQP3 and AQP10 provide insights into the differential compartmentalization and function of these two aquaporins commonly expressed in human intestines.

  18. Intestinal subepithelial myofibroblasts support in vitro and in vivo growth of human small intestinal epithelium.

    Nicholas Lahar

    Full Text Available The intestinal crypt-niche interaction is thought to be essential to the function, maintenance, and proliferation of progenitor stem cells found at the bases of intestinal crypts. These stem cells are constantly renewing the intestinal epithelium by sending differentiated cells from the base of the crypts of Lieberkühn to the villus tips where they slough off into the intestinal lumen. The intestinal niche consists of various cell types, extracellular matrix, and growth factors and surrounds the intestinal progenitor cells. There have recently been advances in the understanding of the interactions that regulate the behavior of the intestinal epithelium and there is great interest in methods for isolating and expanding viable intestinal epithelium. However, there is no method to maintain primary human small intestinal epithelium in culture over a prolonged period of time. Similarly no method has been published that describes isolation and support of human intestinal epithelium in an in vivo model. We describe a technique to isolate and maintain human small intestinal epithelium in vitro from surgical specimens. We also describe a novel method to maintain human intestinal epithelium subcutaneously in a mouse model for a prolonged period of time. Our methods require various growth factors and the intimate interaction between intestinal sub-epithelial myofibroblasts (ISEMFs and the intestinal epithelial cells to support the epithelial in vitro and in vivo growth. Absence of these myofibroblasts precluded successful maintenance of epithelial cell formation and proliferation beyond just a few days, even in the presence of supportive growth factors. We believe that the methods described here can be used to explore the molecular basis of human intestinal stem cell support, maintenance, and growth.

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

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

  20. Intestinal transit and bacterial translocation in obstructive pancreatitis.

    Moody, F G; Haley-Russell, D; Muncy, D M

    1995-08-01

    Pancreatic infection from gut-derived bacteria has emerged as the major cause of death in necrotizing pancreatitis. Bacterial overgrowth of indigenous enteric organisms as a consequence of guts stasis (ileus) represents a potential initial event in this process. The present study was designed to examine the interrelationships between intestinal transit, enteric bacteriology, and the translocation of bacteria from the gut lumen to mesenteric lymph nodes and splanchnic viscera during experimentally induced acute pancreatitis. Male rats underwent pancreaticobiliary duct ligation (PBDL) or sham surgery and were sacrificed after 24, 48, or 96 hr. Severity of pancreatitis was assessed with histology, tissue water content, and amylase and lipase levels. Intestinal transit was measured with fluorescent tracers. Blood, mesenteric lymph nodes (MLNs), splanchnic organs, and gut luminal contents were subjected to bacteriologic analysis. PBDL was followed by biochemical and histologic evidence of progressive pancreatic injury at each time interval. Enteric bacteria within the gut and in adjacent MLNs increased as intestinal transit decreased after PBDL-induced pancreatic inflammation. Surprisingly, all parameters returned to control levels by 96 hr in spite of progression of pancreatic inflammation. PMID:7648983

  1. Alternative Functional In Vitro Models of Human Intestinal Epithelia

    Amanda L Kauffman

    2013-07-01

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

  2. [Comparative study of 2 methods of measuring intestinal transit time].

    Vidal-Neira, L; León-Barúa, R

    1981-01-01

    In 20 healthy volunteers, intestinal transit times, obtained following a simple method, recently described, in which a small liquid-containing rubber bag is used as a marker, were compared with the times obtained following, simultaneously, another method, already universally accepted, in which small barium-impregnated pellets are used as markers. The intestinal transit determined with the rubber bag (TTI-B) (14.1 - 79.2 hours; mean +/- s.d.: 42.4 +/- 20.7 hours) were significantly shorter than the times determined with the plastic pellets (TTI) (26.4 - 88.1 hours; mean +/- s.d.: 60.2 +/- 25.5 hours (P less than 0.001). But, TTI-B and TTI correlate closely (r: + 0.86), and, furthermore, TTI-B results may be converted to TTI results with the help of a simple regression equation: TTI (in minutes) = 831 + 1.09 TTI-B (in minutes). After analyzing what has been observed in the present work and in previous works, it was concluded that the new method to measure intestinal transient time using the small rubber bag is reliable and simple, and that it may help to better understand what happens in some important gastrointestinal problems. PMID:7342626

  3. Farewell to Animal Testing: Innovations on Human Intestinal Microphysiological Systems

    Tae Hyun Kang

    2016-06-01

    Full Text Available The human intestine is a dynamic organ where the complex host-microbe interactions that orchestrate intestinal homeostasis occur. Major contributing factors associated with intestinal health and diseases include metabolically-active gut microbiota, intestinal epithelium, immune components, and rhythmical bowel movement known as peristalsis. Human intestinal disease models have been developed; however, a considerable number of existing models often fail to reproducibly predict human intestinal pathophysiology in response to biological and chemical perturbations or clinical interventions. Intestinal organoid models have provided promising cytodifferentiation and regeneration, but the lack of luminal flow and physical bowel movements seriously hamper mimicking complex host-microbe crosstalk. Here, we discuss recent advances of human intestinal microphysiological systems, such as the biomimetic human “Gut-on-a-Chip” that can employ key intestinal components, such as villus epithelium, gut microbiota, and immune components under peristalsis-like motions and flow, to reconstitute the transmural 3D lumen-capillary tissue interface. By encompassing cutting-edge tools in microfluidics, tissue engineering, and clinical microbiology, gut-on-a-chip has been leveraged not only to recapitulate organ-level intestinal functions, but also emulate the pathophysiology of intestinal disorders, such as chronic inflammation. Finally, we provide potential perspectives of the next generation microphysiological systems as a personalized platform to validate the efficacy, safety, metabolism, and therapeutic responses of new drug compounds in the preclinical stage.

  4. Human intestinal microbial metabolism of naringin.

    Zou, Wei; Luo, Yulong; Liu, Menghua; Chen, Si; Wang, Sheng; Nie, Yichu; Cheng, Guohua; Su, Weiwei; Zhang, Kejian

    2015-09-01

    Naringin, a major flavonoid in citrus fruits, has been proved to be a promising antitussive candidate. It undertakes complicated metabolism. In this study, human intestinal microbial metabolism of naringin was studied in vitro. Six persons' fecal water, which have intestinal microbial enzyme, were used in the first experiment. Naringin was metabolized by fecal water into naringenin. Subsequently, 3-(4-hydroxyphenyl)propionic acid (4-HPPA) was produced with naringenin degradation by a person's fecal water. However, 4-HPPA was not detected after naringenin degradation by the other 5 subjects' fecal water and the reason might be that the degrading velocity of 4-HPPA exceeded the producing velocity. To confirm the difference in degrading 4-HPPA among human feces, 22 healthy persons' feces were used for incubation. In this second experiment, 15 persons' feces could degrade 4-HPPA, but the other 7 subjects' could not. Human feces showed different ability of degrading 4-HPPA, and there are no gender differences. These results may be helpful for explaining findings in pharmacological and toxicological studies and are groundwork for clinical studies. PMID:24935725

  5. Nutrient regulation of human intestinal sugar transporter (SGLT1) expression.

    Dyer, J; Hosie, K B; Shirazi-Beechey, S P

    1997-01-01

    BACKGROUND: The activity of most intestinal nutrient transporters is adaptively regulated by the type and amounts of nutrients entering the intestinal lumen. The concentration and activity of the intestinal Na+/glucose cotransporter (SGLT1) are regulated by dietary sugars in most animal species. The activity and abundance of SGLT1 in biopsy specimens removed from human jejunal regions exposed to, and having limited access to, luminal nutrients have been measured and compared. AIMS: To study t...

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

    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

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

    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.

  8. Human placental alkaline phosphatase in liver and intestine

    Three distinct forms of human alkaline phosphatase, presumably isozymes, are known, each apparently associated with a specific tissue. These are placental, intestinal, and liver (kidney and bone). The authors have used a specific immunoassay and HPLC to show that placental alkaline phosphatase is also present in extracts of liver and intestine in appreciable amounts

  9. Extensive Intestinal Resection Triggers Behavioral Adaptation, Intestinal Remodeling and Microbiota Transition in Short Bowel Syndrome

    Camille Mayeur

    2016-03-01

    Full Text Available Extensive resection of small bowel often leads to short bowel syndrome (SBS. SBS patients develop clinical mal-absorption and dehydration relative to the reduction of absorptive area, acceleration of gastrointestinal transit time and modifications of the gastrointestinal intra-luminal environment. As a consequence of severe mal-absorption, patients require parenteral nutrition (PN. In adults, the overall adaptation following intestinal resection includes spontaneous and complex compensatory processes such as hyperphagia, mucosal remodeling of the remaining part of the intestine and major modifications of the microbiota. SBS patients, with colon in continuity, harbor a specific fecal microbiota that we called “lactobiota” because it is enriched in the Lactobacillus/Leuconostoc group and depleted in anaerobic micro-organisms (especially Clostridium and Bacteroides. In some patients, the lactobiota-driven fermentative activities lead to an accumulation of fecal d/l-lactates and an increased risk of d-encephalopathy. Better knowledge of clinical parameters and lactobiota characteristics has made it possible to stratify patients and define group at risk for d-encephalopathy crises.

  10. Intestinal fructose transport and malabsorption in humans.

    Jones, Hilary F; Butler, Ross N; Brooks, Doug A

    2011-02-01

    Fructose is a hexose sugar that is being increasingly consumed in its monosaccharide form. Patients who exhibit fructose malabsorption can present with gastrointestinal symptoms that include chronic diarrhea and abdominal pain. However, with no clearly established gastrointestinal mechanism for fructose malabsorption, patient analysis by the proxy of a breath hydrogen test (BHT) is controversial. The major transporter for fructose in intestinal epithelial cells is thought to be the facilitative transporter GLUT5. Consistent with a facilitative transport system, we show here by analysis of past studies on healthy adults that there is a significant relationship between fructose malabsorption and fructose dose (r = 0.86, P fructose malabsorption with age have been observed in human infants, and this may parallel the developmental regulation of GLUT5 expression. Moreover, a GLUT5 knockout mouse has displayed the hallmarks associated with profound fructose malabsorption. Fructose malabsorption appears to be partially modulated by the amount of glucose ingested. Although solvent drag and passive diffusion have been proposed to explain the effect of glucose on fructose malabsorption, this could possibly be a result of the facilitative transporter GLUT2. GLUT5 and GLUT2 mRNA have been shown to be rapidly upregulated by the presence of fructose and GLUT2 mRNA is also upregulated by glucose, but in humans the distribution and role of GLUT2 in the brush border membrane are yet to be definitively decided. Understanding the relative roles of these transporters in humans will be crucial for establishing a mechanistic basis for fructose malabsorption in gastrointestinal patients. PMID:21148401

  11. Cholinergic mediation of small intestinal transit in the rat

    It has been reported that small intestinal transit (SIT) in the rat is not cholinergically mediated. The geometric mean of a marker may be a more powerful method for SIT studies. Therefore, it was their goal to evaluate the effect of muscarinic blockade in normal and prostaglandin E2 (PGE2)-enhanced SIT using this method. Male, food-fasted rats (190 to 240 g) were first dosed subcutaneously with atropine. 30 min after the atropine the rats received an oral dose of PGE2 at 5.0 mg/kg. 5 min after PGE2, a 51Cr-labeled marker was dosed intraduodenally, and a 25 min transit period followed. The results are: (1) 5.0 mg/kg of PGE2 significantly stimulates the geometric mean of the marker in agreement with previous findings and (2) atropine is inhibitory at doses as low as 0.20 mg/kg for basal SIT and 0.10 mg/kg for PGE2-stimulated SIT. This indicates (1) the rat has cholinergically mediated SIT, and (2) cholinergic activation may be important for PGE2 effects on SIT in the rat

  12. Apoptosis of human intestinal epithelial cells after bacterial invasion.

    Kim, J. M.; Eckmann, L; Savidge, T. C.; Lowe, D C; Witthöft, T; Kagnoff, M F

    1998-01-01

    Epithelial cells that line the human intestinal mucosa are the initial site of host invasion by bacterial pathogens. The studies herein define apoptosis as a new category of intestinal epithelial cell response to bacterial infection. Human colon epithelial cells are shown to undergo apoptosis following infection with invasive enteric pathogens, such as Salmonella or enteroinvasive Escherichia coli. In contrast to the rapid onset of apoptosis seen after bacterial infection of mouse monocyte-ma...

  13. Distribution of vasoactive intestinal polypeptide and substance P receptors in human colon and small intestine

    Vasoactive intestinal polypeptide (VIP) and substance P are found in neurons in the lamina propria and submucosa and muscularis propria of human small intestine and colon. VIP receptors coupled to adenylate cyclase are present on epithelial, smooth muscle, and mononuclear cells. This study analyzes the distribution of [125I]VIP binding and [125I]substance P in human colon and small intestine using autoradiographic techniques. [125I]VIP binding was present in high density in the mucosal layer of colon and small intestine. [125I]VIP binding was not significantly greater than nonspecific binding in smooth muscle layers or the lymphoid follicles. In contrast, [125I]substance P binding was present in high density over the colonic muscle but was not present over the mucosal layer. In human colon cancer, [125I]VIP grain density over the malignant tissue was only slightly higher than background. These autoradiographic studies of [125I]VIP binding indicate that the highest density of VIP receptors was found in the small intestine and superficial colonic mucosa, whereas the density of substance P receptors was highest over the smooth muscle layers. These findings suggest a mismatch between immunochemical content of the peptide and autoradiographic density of the receptor

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

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

  15. Drug Transport and Metabolism in Rat and Human Intestine

    Berggren, Sofia

    2006-01-01

    One of the aims of this thesis was to investigate the involvement of efflux proteins, such as the P-glycoprotein (Pgp), in the drug transport in different regions of the rat and the human intestine. The intestinal extrusion of intracellularly formed CYP3A4 metabolites, including whether this extrusion might be mediated by Pgp, was also studied. The model drugs used were local anaesthetics (LA), which have been evaluated for inflammatory bowel disease, such as ropivacaine, lidocaine and bupiva...

  16. Major transitions in human evolution.

    Foley, Robert A; Martin, Lawrence; Mirazón Lahr, Marta; Stringer, Chris

    2016-07-01

    Evolutionary problems are often considered in terms of 'origins', and research in human evolution seen as a search for human origins. However, evolution, including human evolution, is a process of transitions from one state to another, and so questions are best put in terms of understanding the nature of those transitions. This paper discusses how the contributions to the themed issue 'Major transitions in human evolution' throw light on the pattern of change in hominin evolution. Four questions are addressed: (1) Is there a major divide between early (australopithecine) and later (Homo) evolution? (2) Does the pattern of change fit a model of short transformations, or gradual evolution? (3) Why is the role of Africa so prominent? (4) How are different aspects of adaptation-genes, phenotypes and behaviour-integrated across the transitions? The importance of developing technologies and approaches and the enduring role of fieldwork are emphasized.This article is part of the themed issue 'Major transitions in human evolution'. PMID:27298461

  17. Induction of metabolism and transport in human intestine : Validation of precision-cut slices as a tool to study induction of drug metabolism in human intestine in vitro

    van de Kerkhof, Esther; De Graaf, Inge A. M.; Ungell, Anna-Lena B.; Groothuis, Geny M. M.

    2008-01-01

    Induction of drug enzyme activity in the intestine can strongly determine plasma levels of drugs. It is therefore important to predict drug-drug interactions in human intestine in vitro. We evaluated the applicability of human intestinal precision-cut slices for induction studies in vitro. Morpholog

  18. Reprogramming of the human intestinal epigenome by surgical tissue transposition

    Lay, Fides D.; Triche, Timothy J.; Tsai, Yvonne C.; Su, Sheng-Fang; Martin, Sue Ellen; Daneshmand, Siamak; Skinner, Eila C.; Liang, Gangning; Chihara, Yoshitomo; Jones, Peter A.

    2014-01-01

    Extracellular cues play critical roles in the establishment of the epigenome during development and may also contribute to epigenetic perturbations found in disease states. The direct role of the local tissue environment on the post-development human epigenome, however, remains unclear due to limitations in studies of human subjects. Here, we use an isogenic human ileal neobladder surgical model and compare global DNA methylation levels of intestinal epithelial cells pre- and post-neobladder construction using the Infinium HumanMethylation450 BeadChip. Our study is the first to quantify the effect of environmental cues on the human epigenome and show that the local tissue environment directly modulates DNA methylation patterns in normal differentiated cells in vivo. In the neobladder, the intestinal epithelial cells lose their tissue-specific epigenetic landscape in a time-dependent manner following the tissue’s exposure to a bladder environment. We find that de novo methylation of many intestine-specific enhancers occurs at the rate of 0.41% per month (P < 0.01, Pearson = 0.71), while demethylation of primarily non-intestine-specific transcribed regions occurs at the rate of −0.37% per month (P < 0.01, Pearson = −0.57). The dynamic resetting of the DNA methylome in the neobladder not only implicates local environmental cues in the shaping and maintenance of the epigenome but also illustrates an unexpected cross-talk between the epigenome and the cellular environment. PMID:24515120

  19. Dietary protein absorption of the small intestine in human neonates

    Schaart, Maaike W.; de Bruijn, Adrianus C. J. M.; Tibboel, Dick; Renes, Ingrid B.; van Goudoever, Johannes B.

    2007-01-01

    Background: The intestine plays a key role in the absorption of dietary proteins, which determines growth of human neonates. Bowel resection in the neonatal period brings loss of absorptive and protective surface and may consequently lead to malabsorption of dietary nutrients. However, there are no

  20. Molecular Epidemiology of Human Intestinal Amoebas in Iran

    M Rezaian

    2012-09-01

    Full Text Available Many microscopic-based epidemiological surveys on the prevalence of human intestinal pathogenic and non-pathogenic protozoa including intestinal amoeba performed in Iran show a high prevalence of human intestinal amoeba in different parts of Iran. Such epidemiological studies on amoebiasis are confusing, mainly due to recently appreciated distinction between the Entamoeba histolytica, E. dispar and E. moshkovskii. Differential diagnosis can be done by some methods such as PCR-based methods, monoclonal antibodies and the analysis of isoenzyme typing, however the molecular study of these protozoa in Iran is low. Based on molecular studies, it seems that E. dispar is predominant species especially in the central and northern areas of Iran and amoebiasis due to E. histolytica is a rare infection in the country. It is suggested that infection with E. moshkovskii may be common among Iranians. Considering the importance of molecular epidemiology of amoeba in Iran and also the current data, the present study reviews the data currently available on the molecular distribution of intestinal human amoeba in Iran.

  1. Slow intestinal transit: a motor disorder contributing to cholesterol gallstone formation in the ground squirrel.

    Xu, Q W; Scott, R B; Tan, D T; Shaffer, E A

    1996-06-01

    Impaired gallbladder motility is an established factor in cholesterol gallstone formation. We assessed whether altered small intestinal smooth muscle contractility with slow transit might potentiate gallstone formation by further impeding enterohepatic cycling of bile acids. Ground squirrels were fed a 1% or a trace (controls) cholesterol diet. Small intestinal transit was evaluated from 51Cr distribution in conscious, fasted animals 20 minutes after infusion into the proximal jejunum. Small intestinal and gallbladder smooth muscle contractility was determined in vitro. Biliary lipid secretion was measured from the cannulated common duct and the bile salt pool size calculated by isotope dilution. Gas-liquid chromatography (GLC) assessed bile salt profile. In animals on the 1% cholesterol diet, aboral transit was significantly delayed, the maximal contractile response to bethanechol was markedly increased (P <.05) with no change in median effective concentration in either circular or longitudinal muscle strips from both the jejunum and ileum, and the gallbladder contractile responses to bethanechol and cholecystokinin (CCK) were decreased. Cholesterol saturation index and the fraction of deoxycholic acid in the pool doubled, whereas the total bile salt pool size remained unchanged in cholesterol-fed animals. In this model, a high-cholesterol diet is associated with altered small intestinal smooth muscle contractility and prolonged small intestinal transit, in addition to diminished gallbladder contractility. The resulting sluggish enterohepatic cycling of bile salts, associated with expanded deoxycholate pool, contributes to cholesterol gallstone formation. PMID:8675191

  2. Infant intestinal Enterococcus faecalis down-regulates inflammatory responses in human intestinal cell lines

    Shugui Wang; Lydia Hui Mei Ng; Wai Ling Chow; Yuan Kun Lee

    2008-01-01

    AIM:To investigate the ability of Lactic acid bacteria (LAB)to modulate inflammatory reaction in human intestinal celllines(Caco-2,HT-29 and HCT 116).Different strains of LAB isolatedfrom new born infants and fermented milk,together withthestrains obtained from culture collectionsweretested.METHODS:LABs were treated with human intestinal cell lines.ELISA was used to detect IL-8 and TGF-β protein secretion.Cytokines and Toll like receptors (TLRs) gene expression were assessed using RT-PCR.Conditional medium,sonicated bacteria and UV killed bacteria were used to find the effecter molecules on the bacteria.Carbohydrate oxidation and protein digestion were applied to figure out the molecules'residues.Adhesion assays were further carried out.RESULTS:It was found that Enterococcus faecalis is the main immune modulator among the LABs by downregulation of IL-8 secretion and upregulation of TGF-β.Strikingly,the effect was only observed in four strains of E.faecalis out of the 27 isolated and tested.This implies strain dependent immunomodulation in the host.In addition,E.faecalis may regulate inflammatory responses through TLR3,TLR4,TLR9 and TRAF6.Carbohydrates on the bacterial cell surface are involved in both its adhesion to intestinal cells and regulation of inflammatory responses in the host.CONCLUSION:These data provide a case for the modulation of intestinal mucosal immunity in which specific strains of E.faecalis have uniquely evolved to maintain colonic homeostasis and regulate inflammatoryresponses.

  3. Ricin crosses polarized human intestinal cells and intestines of ricin-gavaged mice without evident damage and then disseminates to mouse kidneys.

    Alyssa D Flora

    Full Text Available Ricin is a potent toxin found in the beans of Ricinus communis and is often lethal for animals and humans when aerosolized or injected and causes significant morbidity and occasional death when ingested. Ricin has been proposed as a bioweapon because of its lethal properties, environmental stability, and accessibility. In oral intoxication, the process by which the toxin transits across intestinal mucosa is not completely understood. To address this question, we assessed the impact of ricin on the gastrointestinal tract and organs of mice after dissemination of toxin from the gut. We first showed that ricin adhered in a specific pattern to human small bowel intestinal sections, the site within the mouse gut in which a variable degree of damage has been reported by others. We then monitored the movement of ricin across polarized human HCT-8 intestinal monolayers grown in transwell inserts and in HCT-8 cell organoids. We observed that, in both systems, ricin trafficked through the cells without apparent damage until 24 hours post intoxication. We delivered a lethal dose of purified fluorescently-labeled ricin to mice by oral gavage and followed transit of the toxin from the gastrointestinal tracts to the internal organs by in vivo imaging of whole animals over time and ex vivo imaging of organs at various time points. In addition, we harvested organs from unlabeled ricin-gavaged mice and assessed them for the presence of ricin and for histological damage. Finally, we compared serum chemistry values from buffer-treated versus ricin-intoxicated animals. We conclude that ricin transverses human intestinal cells and mouse intestinal cells in situ prior to any indication of enterocyte damage and that ricin rapidly reaches the kidneys of intoxicated mice. We also propose that mice intoxicated orally with ricin likely die from distributive shock.

  4. Are Human Intestinal Eukaryotes Beneficial or Commensals?

    Lukeš, Julius; Stensvold, C.R.; Jirků-Pomajbíková, Kateřina; Parfrey, L.W.

    2015-01-01

    Roč. 11, č. 8 (2015), e1005039. E-ISSN 1553-7374 R&D Projects: GA ČR GAP305/12/2261 EU Projects: European Commission(XE) 316304 Institutional support: RVO:60077344 Keywords : human gut microbiota * Blastocystis * infection * diversity * parasites * impact Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 8.057, year: 2013

  5. Broad-spectrum antimicrobial activity of human intestinal defensin 5.

    Porter, E M; van Dam, E; Valore, E V; Ganz, T

    1997-01-01

    Defensins are antibiotic peptides expressed in human and animal myeloid and epithelial cells. Due to the limited availability of natural peptides, the properties of human epithelial defensins have not been studied. We assayed the microbicidal activity of recombinant human intestinal defensin 5 (rHD-5) in the presence of salt (O to 150 mM NaCl) with varied pH (pH 5.5 to pH 8.5) and trypsin (25 and 250 microg/ml). rHD-5 exhibits microbicidal activity against Listeria monocytogenes, Escherichia ...

  6. Multiscale analysis of the murine intestine for modeling human diseases

    Lyons, Jesse; Herring, Charles A; Banerjee, Amrita; Simmons, Alan J.; Ken S. Lau

    2015-01-01

    When functioning properly, the intestine is one of the key interfaces between the human body and its environment. It is responsible for extracting nutrients from our food and excreting our waste products. It provides an environment for a host of healthful microbes and serves as a first defense against pathogenic ones. These processes require tight homeostatic controls, which are provided by the interactions of a complex mix of epithelial, stromal, neural and immune cells, as well as the resid...

  7. Selective Growth Responses of Human Intestinal Bacteria to Araliaceae Extracts

    Ahn, Y-J.; Kim, M-J; Yamamoto, T.; Fujisawa, T; Mitsuoka, T.

    2011-01-01

    The growth responses of a variety of human intestinal bacteria to extracts of Panax ginseng and five other oriental medicinal Araliaceae were evaluated in vitro. The extracts enhanced the growth of Bifidobacterium breve and B. longum in media with or without carbon sources, suggesting that bifidus factor(s) might be involved in the phenomenon. This effect was most pronounced with water extract of P. ginseng, the growth of 27 bifidobacteria strains belonging to B. adolescentis, B. longum, B. b...

  8. An iterative workflow for mining the human intestinal metaproteome.

    Beauvallet Christian; Galan Pilar; Boeren Sjef; de Been Mark; Doré Joël; Juste Catherine; Kolmeder Carolin; Rooijers Koos; de Vos Willem M; Schaap Peter J

    2011-01-01

    Abstract Background Peptide spectrum matching (PSM) is the standard method in shotgun proteomics data analysis. It relies on the availability of an accurate and complete sample proteome that is used to make interpretation of the spectra feasible. Although this procedure has proven to be effective in many proteomics studies, the approach has limitations when applied on complex samples of microbial communities, such as those found in the human intestinal tract. Metagenome studies have indicated...

  9. An iterative workflow for mining the human intestinal metaproteome

    Rooijers, K.; Kolmeder, C.; Juste, C; Doré, J.; Been, de, M.W.H.J.; Boeren, S.; Galan, P; Vos, de, N.M.; Schaap, P.J.; Beauvallet, C.

    2011-01-01

    Background - Peptide spectrum matching (PSM) is the standard method in shotgun proteomics data analysis. It relies on the availability of an accurate and complete sample proteome that is used to make interpretation of the spectra feasible. Although this procedure has proven to be effective in many proteomics studies, the approach has limitations when applied on complex samples of microbial communities, such as those found in the human intestinal tract. Metagenome studies have indicated that t...

  10. Metabolism of green tea catechins in the human small intestine

    Schantz, Markus; Erk, Thomas; Richling, Elke

    2010-01-01

    Abstract 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 presented here was to examine in detail the microbial metabolism and chemical stability of these po...

  11. Molecular characterisation of non-absorptive and absorptive enterocytes in human small intestine

    Gassler, N; Newrzella, D; Böhm, C; Lyer, S; Li, L; Sorgenfrei, O; van Laer, L; Sido, B; Mollenhauer, J; Poustka, A; Schirmacher, P; Gretz, N

    2006-01-01

    BACKGROUND AND AIMS: Perturbation of differentiation of the crypt-villus axis of the human small intestine is associated with several intestinal disorders of clinical importance. At present, differentiation of small intestinal enterocytes in the crypt-villus axis is not well characterised. SUBJECTS...... about the physiology of the crypt-villus architecture in human small intestine and provide new insights into pathophysiological phenomena, such as villus atrophy, which is clinically important....

  12. Effect of intestinal transit on the formation of cholesterol gallstones in hamsters

    Ying Fan; Shuo-Dong Wu; Bei-Bei Fu

    2007-01-01

    BACKGROUND: The effect of "intestinal transit" has become a new ifeld of interest in the study of the pathogenesis of cholesterol gallstones. This study was undertaken to further test this notion and ascertain the relationship between impaired intestinal transit function and cholesterol gallstones. METHODS: A total of 64 hamsters were divided into 2 groups, experimental and control. Each was subdivided into 4 subgroups for sacriifce at different time. A high-cholesterol diet and a standard diet were fed to each group. The geometric center, which represents the intestinal transit function was calculated. RESULTS: The growth of all hamsters was normal. Cholesterol gallstones were found in 2 hamsters at the end of the 4th week. The geometric center values for the experimental and control groups were 2.3891±0.3923 vs. 2.7730±0.5283, at the end of week 3;1.8148±0.4312 vs. 3.2294±1.1613 at week 4;1.8451±0.3700 vs. 2.9075±0.3756 at week 5;and 1.8025±0.3413 vs. 3.0920±0.5622 at week 6. CONCLUSION: A high cholesterol diet can signiifcantly reduce the intestinal transit function and facilitate the formation of cholesterol gallstones.

  13. Rates of intestinal absorption of molybdenum in humans

    The intestinal absorption of molybdenum in healthy human volunteers has been measured by simultaneous oral and intravenous administration of the stable isotopes 95Mo and 96Mo, and the results were analysed using the convolution integral technique. The results showed that molybdenum ingested in liquid form was rapidly and totally absorbed into the circulation under ordinary intake regimes. The rates and extent of absorption were lower for composite meals, and also for increasing levels of administration. This information can be helpful in the application of the new ICRP model of the human alimentary tract

  14. Rates of intestinal absorption of molybdenum in humans

    Giussani, Augusto [Dipartimento di Fisica, Universita degli Studi di Milano, and INFN, Sezione di Milano, via Celoria 16, 20133 Milan (Italy)]. E-mail: augusto.giussani@gsf.de; Arogunjo, Adeseye M. [Department of Physics, Federal University of Technology, P.M.B. 704, Akure, Ondo State (Nigeria); Claire Cantone, Marie [Dipartimento di Fisica, Universita degli Studi di Milano, and INFN, Sezione di Milano, via Celoria 16, 20133 Milan (Italy); Tavola, Federico [Dipartimento di Fisica, Universita degli Studi di Milano, and INFN, Sezione di Milano, via Celoria 16, 20133 Milan (Italy); Veronese, Ivan [Dipartimento di Fisica, Universita degli Studi di Milano, and INFN, Sezione di Milano, via Celoria 16, 20133 Milan (Italy)

    2006-06-15

    The intestinal absorption of molybdenum in healthy human volunteers has been measured by simultaneous oral and intravenous administration of the stable isotopes {sup 95}Mo and {sup 96}Mo, and the results were analysed using the convolution integral technique. The results showed that molybdenum ingested in liquid form was rapidly and totally absorbed into the circulation under ordinary intake regimes. The rates and extent of absorption were lower for composite meals, and also for increasing levels of administration. This information can be helpful in the application of the new ICRP model of the human alimentary tract.

  15. An iterative workflow for mining the human intestinal metaproteome

    Beauvallet Christian

    2011-01-01

    Full Text Available Abstract Background Peptide spectrum matching (PSM is the standard method in shotgun proteomics data analysis. It relies on the availability of an accurate and complete sample proteome that is used to make interpretation of the spectra feasible. Although this procedure has proven to be effective in many proteomics studies, the approach has limitations when applied on complex samples of microbial communities, such as those found in the human intestinal tract. Metagenome studies have indicated that the human intestinal microbiome contains over 100 times more genes than the human genome and it has been estimated that this ecosystem contains over 5000 bacterial species. The genomes of the vast majority of these species have not yet been sequenced and hence their proteomes remain unknown. To enable data analysis of shotgun proteomics data using PSM, and circumvent the lack of a defined matched metaproteome, an iterative workflow was developed that is based on a synthetic metaproteome and the developing metagenomic databases that are both representative for but not necessarily originating from the sample of interest. Results Two human fecal samples for which metagenomic data had been collected, were analyzed for their metaproteome using liquid chromatography-mass spectrometry and used to benchmark the developed iterative workflow to other methods. The results show that the developed method is able to detect over 3,000 peptides per fecal sample from the spectral data by circumventing the lack of a defined proteome without naive translation of matched metagenomes and cross-species peptide identification. Conclusions The developed iterative workflow achieved an approximate two-fold increase in the amount of identified spectra at a false discovery rate of 1% and can be applied in metaproteomic studies of the human intestinal tract or other complex ecosystems.

  16. Survivability of Kudoa septempunctata in human intestinal conditions.

    Ohnishi, Takahiro; Fujiwara, Marina; Tomaru, Akiko; Yoshinari, Tomoya; Sugita-Konishi, Yoshiko

    2016-06-01

    To elucidate whether Kudoa septempunctata was able to live in the human intestine, we assessed viability of K. septempunctata sporoplasms under conditions that mimicked human and ragworm digestive tracts. To study the effect of osmotic pressure on viability, sporoplasms were incubated in 0.9 or 3.4 % sodium chloride solutions, which roughly corresponded to the osmotic pressure in human or ragworm tissues, respectively. While viability in 3.4 % sodium chloride did not change after 72 h, it dropped to 21 % in 0.9 % sodium chloride. To study the effect of temperature on viability, sporoplasms were incubated at 37, 15, or 25 °C, which were representative of human, winter ragworm, or summer ragworm temperatures, respectively. Viability decreased sharply to 8.4 % after 48 h at 37 °C, but remained essentially unchanged at 15 and 25 °C. In addition, sporoplasms showed strong susceptibility to bile. These results indicate that K. septempunctata could not live in the human intestine for a long time. PMID:27038250

  17. Human intestinal mucus proteins isolated by transanal irrigation and proctosigmoidoscopy

    Paola Andrea Gómez Buitrago

    2015-10-01

    Full Text Available Human intestinal mucus essentially consistsof a network of Mucin2 glycoproteinsembedded in many lower molecularweight proteins. This paper contributes tothe proteomic study of human intestinalmucus by comparing two sample collectionmethods (transanal irrigation and brushcytology during proctosigmoidoscopy andanalysis techniques (electrophoresis anddigestion in solution. The entire samplecollection and treatment process is explained,including protein extraction, digestion anddesalination and peptide characterisationusing a nanoAcquity UPLC chromatographcoupled to an HDMS spectrometer equippedwith a nanoESI source. Collecting mucus viatransanal irrigation provided a larger samplevolume and protein concentration from asingle patient. The proctosigmoidoscopysample could be analysed via digestion insolution after depleting albumin. The analysisindicates that a simple mucus lysis methodcan evaluate the electrophoresis and digestionin solution techniques. Studying humanintestinal mucus complexes is importantbecause they perform two essential survivalfunctions for humans as the first biochemicaland physical defences for the gastrointestinaltract and a habitat for intestinal microbiota,which are primarily hosted in the colon andexceeds the human genetic information andcell number 100- and 10-fold (1.

  18. Gastric emptying, small intestinal transit and fecal output in dystrophic (mdx) mice.

    Mulè, Flavia; Amato, Antonella; Serio, Rosa

    2010-01-01

    Duchenne muscular dystrophy (DMD), which results from deficiency in dystrophin, a sarcolemma protein of skeletal, cardiac and smooth muscle, is characterized by progressive striated muscle degeneration, but various gastrointestinal clinical manifestations have been observed. The aim was to evaluate the possible impact of the dystrophin loss on the gastrointestinal propulsion in mdx mice (animal model for DMD). The gastric emptying of a carboxymethyl cellulose/phenol red dye non-nutrient meal was not significantly different at 20 min from gavaging between wild-type and mdx mice. The intestinal transit and the fecal output were significantly decreased in mdx versus normal animals, although the length of the intestine was similar in both animals. The present results provide evidence for motor intestinal alterations in mdx mice in in vivo conditions. PMID:19784719

  19. Functional Characterization of Cholera Toxin Inhibitors Using Human Intestinal Organoids.

    Zomer-van Ommen, Domenique D; Pukin, Aliaksei V; Fu, Ou; Quarles van Ufford, Linda H C; Janssens, Hettie M; Beekman, Jeffrey M; Pieters, Roland J

    2016-07-28

    Preclinical drug testing in primary human cell models that recapitulate disease can significantly reduce animal experimentation and time-to-the-clinic. We used intestinal organoids to quantitatively study the potency of multivalent cholera toxin inhibitors. The method enabled the determination of IC50 values over a wide range of potencies (15 pM to 9 mM). The results indicate for the first time that an organoid-based swelling assay is a useful preclinical method to evaluate inhibitor potencies of drugs that target pathogen-derived toxins. PMID:27347611

  20. Vasoactive intestinal peptide signaling axis in human leukemia

    Glenn; Paul; Dorsam; Keith; Benton; Jarrett; Failing; Sandeep; Batra

    2011-01-01

    The vasoactive intestinal peptide (VIP) signaling axis constitutes a master "communication coordinator" between cells of the nervous and immune systems.To date,VIP and its two main receptors expressed in T lymphocytes,vasoactive intestinal peptide receptor (VPAC)1 and VPAC2,mediate critical cellular functions regulating adaptive immunity,including arresting CD4 T cells in G 1 of the cell cycle,protection from apoptosis and a potent chemotactic recruiter of T cells to the mucosa associated lymphoid compartment of the gastrointestinal tissues.Since the discovery of VIP in 1970,followed by the cloning of VPAC1 and VPAC2 in the early 1990s,this signaling axis has been associated with common human cancers,including leukemia.This review highlights the present day knowledge of the VIP ligand and its receptor expression profile in T cell leukemia and cell lines.Also,there will be a discussion describing how the anti-leukemic DNA binding transcription factor,Ikaros,regulates VIP receptor expression in primary human CD4 T lymphocytes and T cell lymphoblastic cell lines (e.g.Hut-78).Lastly,future goals will be mentioned that are expected to uncover the role of how the VIP signaling axis contributes to human leukemogenesis,and to establish whether the VIP receptor signature expressed by leukemic blasts can provide therapeutic and/or diagnostic information.

  1. Transgenic Expression of Human Lysophosphatidic Acid Receptor LPA2 in Mouse Intestinal Epithelial Cells Induces Intestinal Dysplasia.

    Michihiro Yoshida

    Full Text Available Lysophosphatidic acid (LPA acts on LPA2 receptor to mediate multiple pathological effects that are associated with tumorigenesis. The absence of LPA2 attenuates tumor progression in rodent models of colorectal cancer, but whether overexpression of LPA2 alone can lead to malignant transformation in the intestinal tract has not been studied. In this study, we expressed human LPA2 in intestinal epithelial cells (IECs under control of the villin promoter. Less than 4% of F1-generation mice had germline transmission of transgenic (TG human LPA2; as such only 3 F1 mice out of 72 genotyped had TG expression. These TG mice appeared anemic with hematochezia and died shortly after birth. TG mice were smaller in size compared with the wild type mouse of the same age and sex. Morphological analysis showed that TG LPA2 colon had hyper-proliferation of IECs resulting in increased colonic crypt depth. Surprisingly, TG small intestine had villus blunting and decreased IEC proliferation and dysplasia. In both intestine and colon, TG expression of LPA2 compromised the terminal epithelial differentiation, consistent with epithelial dysplasia. Furthermore, we showed that epithelial dysplasia was observed in founder mouse intestine, correlating LPA2 overexpression with epithelial dysplasia. The current study demonstrates that overexpression of LPA2 alone can lead to intestinal dysplasia.

  2. Cell dedifferentiation and epithelial to mesenchymal transitions during intestinal regeneration in H. glaberrima

    Rivera-Cruz Angélica

    2011-10-01

    Full Text Available Abstract Background Determining the type and source of cells involved in regenerative processes has been one of the most important goals of researchers in the field of regeneration biology. We have previously used several cellular markers to characterize the cells involved in the regeneration of the intestine in the sea cucumber Holothuria glaberrima. Results We have now obtained a monoclonal antibody that labels the mesothelium; the outer layer of the gut wall composed of peritoneocytes and myocytes. Using this antibody we studied the role of this tissue layer in the early stages of intestinal regeneration. We have now shown that the mesothelial cells of the mesentery, specifically the muscle component, undergo dedifferentiation from very early on in the regeneration process. Cell proliferation, on the other hand, increases much later, and mainly takes place in the mesothelium or coelomic epithelium of the regenerating intestinal rudiment. Moreover, we have found that the formation of the intestinal rudiment involves a novel regenerative mechanism where epithelial cells ingress into the connective tissue and acquire mesenchymal phenotypes. Conclusions Our results strongly suggest that the dedifferentiating mesothelium provides the initial source of cells for the formation of the intestinal rudiment. At later stages, cell proliferation supplies additional cells necessary for the increase in size of the regenerate. Our data also shows that the mechanism of epithelial to mesenchymal transition provides many of the connective tissue cells found in the regenerating intestine. These results present some new and important information as to the cellular basis of organ regeneration and in particular to the process of regeneration of visceral organs.

  3. Nonsteroidal antiinflammatory drug-induced intestinal inflammation in humans

    Bjarnason, I.; Zanelli, G.; Smith, T.; Prouse, P.; Williams, P.; Smethurst, P.; Delacey, G.; Gumpel, M.J.; Levi, A.J.

    1987-09-01

    This study examines the effects of nonsteroidal antiinflammatory drugs on the small intestine in humans. Using an /sup 111/In-leukocyte technique in patients with rheumatoid arthritis (n = 90) and osteoarthritis (n = 7), it appears that nonsteroidal antiinflammatory drugs cause small intestinal inflammation in two-thirds of patients on long-term treatment and on discontinuation, the inflammation may persist for up to 16 mo. The prevalence and magnitude of the intestinal inflammation was unrelated to the type and dose of nonsteroidal drugs and previous or concomitant second-line drug treatment. There was a significant inverse correlation (r = -0.29, p less than 0.05) between fecal /sup 111/In excretion and hemoglobin levels in patients treated with nonsteroidal antiinflammatory drugs. The kinetics of fecal indium 111 excretion in patients treated with nonsteroidal antiinflammatory drugs was almost identical to that of patients with small bowel Crohn's disease. Eighteen patients on nonsteroidal antiinflammatory drugs underwent a radiologic examination of the small bowel and 3 were found to have asymptomatic ileal disease with ulceration and strictures. Nineteen patients on nonsteroidal antiinflammatory drugs, 20 healthy controls, and 13 patients with Crohn's ileitis underwent a dual radioisotopic ileal function test with tauro 23 (/sup 75/Se) selena-25-homocholic acid and cobalt 58-labeled cyanocobalamine. On day 4, more than half of the patients with rheumatoid arthritis had evidence of bile acid malabsorption, but the ileal dysfunction was much milder than seen in patients with Crohn's ileitis.

  4. INTESTINAL VIROME AND NORMAL MICROFLORA OF HUMAN: FEATURES OF INTERACTION

    Bobyr V.V.

    2015-05-01

    Full Text Available Summary: Intestinal bacteria defend the host organism and narrow pathogenic bacterial colonization. However, the microbiome effect to enteric viruses is unexplored largely as well as role of microbiota in the pathogenesis of viral infections in general. This review focuses on precisely these issues. Keywords: microbiome, virome, normal microflora, enteric viruses, contagiousness. In this review article, facts about viral persistence in the human gut are summarized. It is described the role of viral populations during health and diseases. After analyzing of the literary facts it was concluded that the gastrointestinal tract is an environment for one from the most complex microbial ecosystems, which requires of more deeper study of its composition, role in physiological processes, as well as the dynamics of changes under influence of the environment. Normal microflora performs a different important functions providing the physiological homeostasis of the human body, including, in particular, an important role in the human metabolic processes, supporting of homeostasis, limiting of colonization by infectious bacteria. The multifactorial significance of the normal gastrointestinal microflora can be divided into immunological, structural and metabolic functions. At the same time, interaction between intestinal microflora and enteric viruses has not been studied largely. In recent years, much attention is paid to study of viruses-bacteria associations, and it is possible, obtained results should change our understanding of microbiota role in the systematic pathogenesis of the diseases with viral etiology. In contrast to the well-known benefits of normal microflora to the host, the viruses can use intestinal microflora as a trigger for replication at the optimal region. Recent studies give a reason for assumption that depletion of normal microflora with antibiotics can determining the antiviral effect. Thus, the role of commensal bacteria in viral

  5. Intestinal microbiota in human health and disease: the impact of probiotics

    Gerritsen, J.; Smidt, H.; Rijkers, G.T.; Vos

    2011-01-01

    The complex communities of microorganisms that colonise the human gastrointestinal tract play an important role in human health. The development of culture-independent molecular techniques has provided new insights in the composition and diversity of the intestinal microbiota. Here, we summarise the present state of the art on the intestinal microbiota with specific attention for the application of high-throughput functional microbiomic approaches to determine the contribution of the intestin...

  6. Effect of nonabsorbed amounts of a fructose-sorbitol mixture on small intestinal transit in healthy volunteers

    Madsen, Jan L; Linnet, Jan; Rumessen, Jüri J

    2006-01-01

    Although malabsorption of small amounts of fructose-sorbitol mixtures occurs frequently in healthy humans, insights into their effects on gastrointestinal motility are poor. The present study addresses the hypothesis that malabsorption of a fructose-sorbitol challenge changes the small intestinal...... solution. Breath hydrogen and methane concentrations and gastrointestinal progress of the radiolabeled marker were followed for the next 6-hr period. Malabsorption of small amounts of the fructose-sorbitol mixture was evident in all subjects. The area under the gastric radioactivity-time curve after...... than after ingestion of glucose (P = 0.0128). In healthy humans, malabsorption of small amounts of a fructose-sorbitol mixture accelerates small bowel transit....

  7. Common occurrence of antibacterial agents in human intestinal microbiota

    Fatima eDrissi

    2015-05-01

    Full Text Available Laboratory experiments have revealed many active mechanisms by which bacteria can inhibit the growth of other organisms. Bacteriocins are a diverse group of natural ribosomally-synthesized antimicrobial peptides produced by a wide range of bacteria and which seem to play an important role in mediating competition within bacterial communities. In this study, we have identified and established the structural classification of putative bacteriocins encoded by 317 microbial genomes in the human intestine. On the basis of homologies to available bacteriocin sequences, mainly from lactic acid bacteria, we report the widespread occurrence of bacteriocins across the gut microbiota: 175 bacteriocins were found to be encoded in Firmicutes, 79 in Proteobacteria, 34 in Bacteroidetes and 25 in Actinobacteria. Bacteriocins from gut bacteria displayed wide differences among phyla with regard to class distribution, net positive charge, hydrophobicity and secondary structure, but the α-helix was the most abundant structure. The peptide structures and physiochemical properties of bacteriocins produced by the most abundant bacteria in the gut, the Firmicutes and the Bacteroidetes, seem to ensure low antibiotic activity and participate in permanent intestinal host defence against the proliferation of harmful bacteria. Meanwhile, the potentially harmful bacteria, including the Proteobacteria, displayed highly effective bacteriocins, probably supporting the virulent character of diseases. These findings highlight the eventual role played by bacteriocins in gut microbial competition and their potential place in antibiotic therapy.

  8. Functional Metagenomic Investigations of the Human Intestinal Microbiota

    Moore, Aimee M.; Munck, Christian; Sommer, Morten Otto Alexander;

    2011-01-01

    of this microbial community, its recalcitrance to standard cultivation, and the immense diversity of its encoded genes has necessitated the development of novel molecular, microbiological, and genomic tools. Functional metagenomics is one such culture-independent technique, used for decades to study environmental...... microorganisms, but relatively recently applied to the study of the human commensal microbiota. Metagenomic functional screens characterize the functional capacity of a microbial community, independent of identity to known genes, by subjecting the metagenome to functional assays in a genetically tractable host....... Here we highlight recent work applying this technique to study the functional diversity of the intestinal microbiota, and discuss how an approach combining high-throughput sequencing, cultivation, and metagenomic functional screens can improve our understanding of interactions between this complex...

  9. Effect of pregnancy on intestinal transit: comparison of results using radioactive and non-radioactive test meals

    Studies were performed to determine the effect of pregnancy on both gastrointestinal transit and small intestinal transit. Gastrointestinal transit was examined by determining the leading edge of distribution within the small intestine of a charcoal marker placed directly into the stomach. Intestinal transit was evaluated by quantifying the distribution of a radiolabelled marker placed dirrectly into the duodenum. The distribution of the marker was determined (1) by calculating the slope of the distribution curve and (2) by calculating the geometric center of distribution of the radioisotope. In all studies the data from animals in either the second or third trimester of pregnancy were compared with the results obtained from non-pregnant females. The results confirm previous observations that gastrointestinal transit is reduced during the latter stages of pregnancy. This can be explained, at least in part, by a decreased intestinal transit. The data also suggest that analysis of the geometric center of distribution provides a more sensitive and reliable measure of intestinal transit than does analysis of the slope of the distribution curve

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

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

    2010-07-01

    This study aimed to establish a practical and convenient method of predicting intestinal availability (F(g)) in humans for highly permeable compounds at the drug discovery stage, with a focus on CYP3A4-mediated metabolism. We constructed a "simplified F(g) model," described using only metabolic parameters, assuming that passive diffusion is dominant when permeability is high and that the effect of transporters in epithelial cells is negligible. Five substrates for CYP3A4 (alprazolam, amlodipine, clonazepam, midazolam, and nifedipine) and four for both CYP3A4 and P-glycoprotein (P-gp) (nicardipine, quinidine, tacrolimus, and verapamil) were used as model compounds. Observed fraction of drug absorbed (F(a)F(g)) values for these compounds were calculated from in vivo pharmacokinetic (PK) parameters, whereas in vitro intestinal intrinsic clearance (CL(int,intestine)) was determined using human intestinal microsomes. The CL(int,intestine) for the model compounds corrected with that of midazolam was defined as CL(m,index) and incorporated into a simplified F(g) model with empirical scaling factor. Regardless of whether the compound was a P-gp substrate, the F(a)F(g) could be reasonably fitted by the simplified F(g) model, and the value of the empirical scaling factor was well estimated. These results suggest that the effects of P-gp on F(a) and F(g) are substantially minor, at least in the case of highly permeable compounds. Furthermore, liver intrinsic clearance (CL(int,liver)) can be used as a surrogate index of intestinal metabolism based on the relationship between CL(int,liver) and CL(m,index). F(g) can be easily predicted using a simplified F(g) model with the empirical scaling factor, enabling more confident selection of drug candidates with desirable PK profiles in humans. PMID:20354105

  11. Direct In Vivo Human Intestinal Permeability (Peff ) Determined with Different Clinical Perfusion and Intubation Methods.

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

    2015-09-01

    Regional in vivo human intestinal effective permeability (Peff ) is calculated by measuring the disappearance rate of substances during intestinal perfusion. Peff is the most relevant parameter in the prediction of rate and extent of drug absorption from all parts of the intestine. Today, human intestinal perfusions are not performed on a routine basis in drug development. Therefore, it would be beneficial to increase the accuracy of the in vitro and in silico tools used to evaluate the intestinal Peff of novel drugs. This review compiles historical Peff data from 273 individual measurements of 80 substances from 61 studies performed in all parts of the human intestinal tract. These substances include: drugs, monosaccharaides, amino acids, dipeptides, vitamins, steroids, bile acids, ions, fatty acids, and water. The review also discusses the determination and prediction of Peff using in vitro and in silico methods such as quantitative structure-activity relationship, Caco-2, Ussing chamber, animal intestinal perfusion, and physiologically based pharmacokinetic (PBPK) modeling. Finally, we briefly outline how to acquire accurate human intestinal Peff data by deconvolution of plasma concentration-time profiles following regional intestinal bolus dosing. PMID:25410736

  12. Tracking the cell hierarchy in the human intestine using biochemical signatures derived by mid-infrared microspectroscopy.

    Walsh, Michael J; Hammiche, Azzedine; Fellous, Tariq G; Nicholson, James M; Cotte, Marine; Susini, Jean; Fullwood, Nigel J; Martin-Hirsch, Pierre L; Alison, Malcolm R; Martin, Francis L

    2009-07-01

    Markers of gastrointestinal (GI) stem cells remain elusive. We employed synchrotron Fourier-transform infrared (FTIR) microspectroscopy to derive mid-infrared (IR) spectra along the length of human GI crypts. Tissue sections (10-μm thick) were floated onto BaF2 windows and image maps were acquired of small intestine and large bowel crypts in transmission mode with an aperture of ≤10 μm×10 μm. Counting upwards in a step-size (≤10 μm) fashion from the crypt base, IR spectra were extracted from the image maps and each spectrum corresponding to a particular location was identified. Spectra were analyzed using principal component analysis plus linear discriminant analysis. Compared to putative crypt base columnar/Paneth cells, those assigned as label-retaining cells were chemically more similar to putative large bowel stem cells and, the small intestine transit-amplifying cells were closest to large bowel transit-amplifying cells; interestingly, the base of small intestine crypts was the most chemically-distinct. This study suggests that in the complex cell lineage of human GI crypts, chemical similarities as revealed by FTIR microspectroscopy between regions putatively assigned as stem cell, transit-amplifying and terminally-differentiated facilitates identification of cell function. PMID:19393589

  13. Microbial Eco-Physiology of the human intestinal tract: a flow cytometric approach

    Amor, Ben, K.

    2004-01-01

    This thesis describes a multifaceted approach to further enhance our view of the complex human intestinal microbial ecosystem. This approach combines me advantages of flow cyrometry (FCM), a single cell and high-throughput technology, and molecular techniques that have proven themselves to be invaluabIe tools in studying the microbial diversity and structure of the intestinal microbiota. The ultimate aim was to relate the genetic biodiversity of the intestinal microbiota with their in situ ph...

  14. TNFalpha regulates sugar transporters in the human intestinal epithelial cell line Caco-2

    Barrenetxe, J; Barber, A; Lostao, M P; Rodriguez-Yoldi, M.J. (M.J.); Gascon, S. (S.); Sanchez, O.

    2013-01-01

    PURPOSE: During intestinal inflammation TNFα levels are increased and as a consequence malabsorption of nutrients may occur. We have previously demonstrated that TNFα inhibits galactose, fructose and leucine intestinal absorption in animal models. In continuation with our work, the purpose of the present study was to investigate in the human intestinal epithelial cell line Caco-2, the effect of TNFα on sugar transport and to identify the intracellular mechanisms involved. METHODS: ...

  15. Effects of casoxin 4 on morphine inhibition of small animal intestinal contractility and gut transit in the mouse

    Glen S Patten

    2011-02-01

    Full Text Available Glen S Patten1,2, Richard J Head1, Mahinda Y Abeywardena1,21CSIRO Preventative Health National Research Flagship, Adelaide, Australia; 2CSIRO Food and Nutritional Sciences, Adelaide, AustraliaBackground and aims: Chronic opioid analgesia has the debilitating side-effect of constipation in human patients. The major aims of this study were to: 1 characterize the opioid-specific antagonism of morphine-induced inhibition of electrically driven contraction of the small intestine of mice, rats, and guinea pigs; and 2 test if the oral delivery of small milk-derived opioid antagonist peptides could block morphine-induced inhibition of intestinal transit in mice.Methods: Mouse, rat, and guinea pig intact ileal sections were electrically stimulated to contract and inhibited with morphine in vitro. Morphine inhibition was then blocked by opioid subtype antagonists in the mouse and guinea pig. Using a polymeric dye, Poly R-478, the opioid antagonists casoxin 4 and lactoferroxin A were tested orally for blocking activity of morphine inhibition of gut transit in vivo by single or double gavage techniques.Results: The guinea pig tissue was more sensitive to morphine inhibition compared with the mouse or the rat (IC50 [half maximal inhibitory concentration] values as nmol/L ± SEM were 34 ± 3, 230 ± 13, and 310 ± 14 respectively (P < 0.01. The inhibitory influence of opioid agonists (IC50 in electrically driven ileal mouse preparations were DADLE ([D-Ala2, D-Leu5]-enkephalin ≥ met-enkephalin ≥ dynorphin A ≥ DAMGO ([D-Ala2, N-Me-Phe4, Gly-ol5]-enkephalin > morphine > morphiceptin as nmol/L 13.9, 17.3, 19.5, 23.3, 230, and 403 respectively. The mouse demonstrated predominantly Κ- and δ-opioid receptor activity with a smaller µ-opioid receptor component. Both mouse and guinea pig tissue were sensitive to casoxin 4 antagonism of morphine inhibition of contraction. In contrast to naloxone, relatively high oral doses of the µ-opioid receptor antagonists

  16. Innovative methods to study human intestinal drug metabolism in vitro : Precision-cut slices compared with Ussing chamber preparations

    van de Kerkhof, Esther G.; Ungell, Anna-Lena B.; Sjoberg, Asa K.; de Jager, Marina H.; Hilgendorf, Constanze; de Graaf, Inge A. M.; Groothuis, Geny M. M.

    2006-01-01

    Predictive in vitro methods to investigate drug metabolism in the human intestine using intact tissue are of high importance. Therefore, we studied the metabolic activity of human small intestinal and colon slices and compared it with the metabolic activity of the same human intestinal segments usin

  17. Scintigraphic Small Intestinal Transit Time and Defaecography in Patients with J-Pouch

    Mie Dilling Kjaer

    2015-10-01

    Full Text Available Objective methods for examination of pouch function are warranted for a better understanding of the functional result and treatment of dysfunction. The objective of this study was to evaluate the results of scintigraphic intestinal transit time and defaecography compared to the results of pouch function, mucosal condition and a questionnaire on quality of life (QoL. This cross-sectional study included 21 patients. Scintigraphic transit time and defaecography was determined with the use of Tc-99m. Pouch function was assessed by number of bowel movements, pouch volume, and continence. Pouch mucosal condition was evaluated by endoscopy and histology. Median transit time was 189 min (105–365. Median ejection fraction at defaecography (EF was 49% (3–77 and 62% (17–98 after first and second defecation. Median pouch volume was 223 mL (100–360. A median daily stool frequency of nine (4–25 was reported and three (14% patients suffered from daytime incontinence. No patients had symptomatic or endoscopic pouchitis; however, the histology showed unspecific inflammation in 19 (90% patients. There was no correlation between transit time, evacuation fraction (EF and pouch function in univariate analysis. However, we found a high body mass index (BMI and a low bowel movement frequency to be associated with a longer transit time by multivariate analysis. Scintigraphic determination of transit time and defaecography are feasible methods in patients with ileal pouch anal anastomosis, but the clinical relevance is yet doubtful.

  18. Inhibition of gastric emptying and intestinal transit in anesthetized rats by a Tityus serrulatus scorpion toxin

    L.E.A. Troncon; A.A. Santos; V.L. Garbacio; M. Secaf; A.V. Verceze; Cunha-Melo, J R

    2000-01-01

    The effects of a fraction (T1) of Tityus serrulatus scorpion venom prepared by gel filtration on gastric emptying and small intestinal transit were investigated in male Wistar rats. Fasted animals were anesthetized with urethane, submitted to tracheal intubation and right jugular vein cannulation. Scorpion toxin (250 µg/kg) or saline was injected iv and 1 h later a bolus of saline (1.0 ml/100 g) labeled with 99m technetium-phytate (10 MBq) was administered by gavage. After 15 min, animals wer...

  19. Human intestinal dendritic cells as controllers of mucosal immunity

    David Bernardo

    2013-06-01

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

  20. Distribution of the IgG Fc Receptor, FcRn, in the Human Fetal Intestine

    Shah, Uzma; Dickinson, Bonny L.; Blumberg, Richard S.; Simister, Neil E.; Lencer, Wayne I.; Walker, W. Allan

    2003-01-01

    The intestinal Fc receptor, FcRn, functions in the maternofetal transfer of gamma globulin (IgG) in the neonatal rodent. In humans, most of this transfer is presumed to occur in utero via the placenta. Although the fetus swallows amniotic fluid that contains immunoglobulin, it is unknown whether this transfer also occurs via the fetal intestine. A human FcRn has been identified in the syncytiotrophoblast that mediates the maternofetal transfer of antibody. It has also been identified in human...

  1. Apical Gene Transfer into Quiescent Human and Canine Polarized Intestinal Epithelial Cells by Lentivirus Vectors

    Seppen, Jurgen; Barry, Simon C.; Klinkspoor, J. Henriette; Katen, Louis J.; Lee, Sum P; Garcia, J. Victor; Osborne, William R. A.

    2000-01-01

    Intestinal epithelial cells secrete a protective luminal mucus barrier inhibiting viral gene transfer. Quiescent, polarized monolayers of primary epithelial cells from dog gallbladder and human colon are efficiently transduced through the apical mucus side by lentivirus vectors, suggesting their application to intestinal gene therapy.

  2. Formation and blood supply of the large intestine in human neonates

    Haina N.I.

    2008-01-01

    Full Text Available A study of the large intestine has been carried out on 24 specimens of human newborns. It has been established that the form and size of the neonates large intestine demonstrated a sidnificant individual variability. The hepatic and splenic flexures of the colon had different relations with the inferior border of the liver and spleen.

  3. High-throughput analysis of the impact of antibiotics on the human intestinal microbiota composition

    Ladirat, S.E.; Schols, H.A.; Nauta, A.; Schoterman, M.H.C.; Keijser, B.J.F.; Montijn, R.C.; Gruppen, H.; Schuren, F.H.J.

    2013-01-01

    Antibiotic treatments can lead to a disruption of the human microbiota. In this in-vitro study, the impact of antibiotics on adult intestinal microbiota was monitored in a new high-throughput approach: a fermentation screening-platform was coupled with a phylogenetic microarray analysis (Intestinal-

  4. The scintigraphic determination of small intestinal transit time in patients with irritable bowel syndrome

    Marano, A.R.; Caride, V.J.; Shah, R.V.; Prokop, E.K.; Troncale, F.J.; McCallum, R.W.

    1984-01-01

    Diffuse disturbance in gastrointestinal motility may be present in patients with irritable bowel syndrome (IBS). To further investigate small intestinal motility in IBS patients small intestinal transit time (SITT) was determined and related to the symptom status. 11 female patients with IBS (mean age 29 years) were divided into those whose predominate symptom was diarrhea (N=6), and those with only constipation (N=5). All subjects ingested an isosmotic solution of lactulose (10 gm in 150cc of water) labeled with 99m-Tc-DTPA (Sn). The patient was studied supine under a 25 inch gamma camera with data collected at 1 frame per minute for 180 minutes or until activity appeared in the ascending colon. Regions of interest were selected over the cecum and ascending colon. The time of first appearance of radioactivity in the region of the cecum was taken as the small intestinal transit time. SITT in the 5 normal females was 98.7 +- 13 min (mean +- SEM). SITT in the IBS patients with diarrhea, 67.3 +- 7 min was significantly faster (p< 0.08). SITT in the constipated IBS patients, 126 +- 12 min, was slower than normals and significantly different from diarrhea patients (p< 0.001). These studies show that IBS patients with diarrhea have significantly faster SITT than normals while constipated IBS patients have significantly slower SITT than the diarrhea subgroup. Further, this study emphasizes the need to study the various symptomatic subgroups of IBs patients independently and indicates a possible role for abnormal SITT in the pathogenesis of IBS.

  5. Clinical features of human intestinal capillariasis in Taiwan

    Ming-Jong Bair; Kao-Pin Hwang; Tsang-En Wang; Tai-Cherng Liou; Shee-Chan Lin; Chin-Roa Kao; Tao-Yeuan Wang; Kwok-Kuen Pang

    2004-01-01

    Human intestinal capillariasis is a rare parasitosis that was first recognized in the Philippines in the 1960 s. Parasitosis is a life threatening disease and has been reported from Thailand, Japan, South of Taiwan (Kaoh-Siung), Korea,Tran, Egypt, Italy and Spain. Its clinical symptoms are characterized by chronic diarrhea, abdominal pain,borborygmus, marked weight loss, protein and electrolyte loss and cachexia. Capillariasis may be fatal if early treatment is not given. We reported 14 cases living in rural areas of Taiwan. Three cases had histories of travelling to Thailand. They might have been infected in Thailand while stayed there. Two cases had the diet of raw freshwater fish before. Three cases received emergency laparotomy due to peritonitis and two cases were found of enteritis cystica profunda. According to the route of transmission,freshwater and brackish-water fish may act as the intermediate host of the parasite. The most simple and convenient method of diagnosing capillariasis is stool examination. Two cases were diagnosed by histology.Mebendazole or albendezole 200 mg orally twice a day for 20-30 d is the treatment of choice. All the patients were cured, and relapses were not observed within 12 mo.

  6. Production of human intestinal trefoil factor in Pichia pastoris

    SUN Yong; PENG Xi; Lü Shang-jun; ZHANG Yong; WANG Shi-liang

    2006-01-01

    Objective:To construct a Pichia pastoris (P. Pastoris) expression vector of human intestinal trefoil factor (hITF) and study its expression and purification procedures. Methods:hITF gene encoding mature peptide was modified with a polyhistidine tag sequence at the N-terminal, and then inserted into the P. Pastoris expression vector pGAPZαA at the ownstream of the α-mating factor signal. After gene sequencing, the recombinant pGAPZαA-hITF was transformed into the P. Pastoris strain X-33 with lithium chloride. rhITF was induced to constitutively express in shake flask, and then analyzed with Tricine SDS-PAGE and Western blotting. The obtained rhITF was isolated from the cultured supernatants y ammonium sulfate precipitation, Ni-NTA affinity chromatography, and ultrafiltration. Results:The correctness and integrity of rhITF were identified by restriction digestion and gene sequencing. rhITF was successfully expressed to 50 mg/L as a secretive protein. After purification, the purity was above 95%.Tricine SDS-PAGE and Western-blot analysis howed that rhITF presented as a single band with a molecular weight of 10 kDa, a little larger than 7 879 Da as assayed by mass spectrometry analysis. Conclusion:hITF P. Pastoris expression vector is successfully constructed and rhITF is expressed in P. Pastoris at commercially relevant level. This research lays foundation for the further functional tudying of hITF.

  7. Permeability of rhynchophylline across human intestinal cell in vitro.

    Ma, Bo; Wang, Jing; Sun, Jing; Li, Ming; Xu, Huibo; Sun, Guibo; Sun, Xiaobo

    2014-01-01

    Rhynchophylline (Rhy) is the major component of Uncaria species, which is used in Chinese traditional medicine for the treatment of central nervous system disorders. However, its oral bioavailability has not been known. This study aims to investigate the intestinal permeability and related mechanisms of Rhy using cultured human epithelial Caco-2 cells. The cytotoxicity of Rhy on Caco-2 cells was evaluated with MTT assay. The effect of Rhy on the integrity of Caco-2 cell monolayer was assayed with transepithelial electrical resistance. The permeability of Rhy across cell monolayer was assayed by measuring Rhy quantity in received side with HPLC. The effect of Rhy on the expression of P-glycoprotein and MDR1 was detected with Western blot and flow cytometry, respectively. In the concentration of Rhy, which did not produce toxicity on cell viability and integrity of Caco-2 cell monolayer, Rhy crossed the monolayer with velocity 2.76~5.57×10^-6 cm/sec and 10.68~15.66×10^-6 cm/sec from apical to basolateral side and from basolateral to apical side, respectively. The permeability of Rhy was increased by verapamil, a P-glycoprotein inhibitor, or rhodamine123, a P-glycoprotein substrate. Rhy revealed an induction effect on P-glycoprotein expression in Caco-2 cells. These results demonstrate the low permeability of Rhy in intro, and suggest that P-glycoprotein may underlie the mechanism. PMID:24966905

  8. Human Rights and Transitional Societies: Contemporary Challenges

    Hansen, Thomas Obel

    2008-01-01

    This paper will assess how alternative approaches to transitional justice have the potential for overcoming tensions in between human rights standards. A rule in international law prescribing that states have a duty to prosecute gross human rights violations has emerged. Accordingly, transitional...... societies are said to have an obligation to apply criminal justice in dealing with such past violations. In Rwanda, the transitional government decided to prosecute the perpetrators of the 1994 genocide. As a result of widespread participation in the genocide and a devastated legal sector, difficulties in...... respecting the rights of the accused arose. A group of paralegals known as the "Corps of Judicial Defenders" was thus relied upon as to provide legal assistance for genocide suspects, but also for civil parties. This paper describes the work of these paralegals relating to the transitional trials, and, more...

  9. Characterization of intracellular pteroylpolyglutamate hydrolase (PPH) from human intestinal mucosa

    Wang, T.T.Y.; Chandler, C.J.; Halsted, C.H.

    1986-03-01

    There are two forms of pteroylpolyglutamate hydrolase (PPH) in the human intestinal mucosa, one in the brush border membrane and the other intracellular; brush border PPH is an exopeptidase with optimal activity at pH 6.5 and a requirement for zinc. The presence study characterized human intracellular PPH and compared its properties to those of brush border PPH. Intracellular PPH was purified 30-fold. The enzyme had a MW of 75,000 by gel filtration, was optimally active at pH 4.5, and had an isoelectric point at pH 8.0. In contrast to brush border PPH, intracellular PPH was unstable at increasing temperatures, was unaffected by dialysis against chelating agents and showed no requirement for Zn/sup 2 +/. Using PteGlu/sub 2/(/sup 14/C)Glu as substrate, they demonstrated a K/sub m/ of 1.2 ..mu..M and increasing affinity for folates with longer glutamate chains. Intracellular PPH required the complete folic acid (PteGlu) moiety and a ..gamma..-glutamyl linkage for activity. Using ion exchange chromatography and an HPLC method to determine the hydrolytic products of the reaction, they found intracellular PPH could cleave both internal and terminal ..gamma..-glutamyl linkages, with PteGlu as an end product. After subcellular fractionation of the mucosa, PPH was found in the lysosomes. In summary, the distinct characteristics of brush border and intracellular PPH suggest that the two hydrolases serve different roles in folate metabolism.

  10. Lactobacillus reuteri Inhibition of Enteropathogenic Escherichia coli Adherence to Human Intestinal Epithelium

    Alistair eWalsham; Donald eMacKenzie; Vivienne eCook; Simon eWemyss-Holden; Claire eHews; Nathalie eJuge; Stephanie eSchüller

    2016-01-01

    Enteropathogenic E. coli (EPEC) is a major cause of diarrheal infant death in developing countries, and probiotic bacteria have been shown to provide health benefits in gastrointestinal infections. In this study, we have investigated the influence of the gut symbiont Lactobacillus reuteri on EPEC adherence to the human intestinal epithelium. Different host cell model systems including non-mucus-producing HT-29 and mucus-producing LS174T intestinal epithelial cell lines as well as human small ...

  11. Direct In Vivo Human Intestinal Permeability (P-eff) Determined with Different Clinical Perfusion and Intubation Methods

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

    2015-01-01

    Regional in vivo human intestinal effective permeability (P-eff) is calculated by measuring the disappearance rate of substances during intestinal perfusion. P-eff is the most relevant parameter in the prediction of rate and extent of drug absorption from all parts of the intestine. Today, human intestinal perfusions are not performed on a routine basis in drug development. Therefore, it would be beneficial to increase the accuracy of the in vitro and in silico tools used to evaluate the inte...

  12. Biovolatilization of metal(loid)s by intestinal microorganisms in the simulator of the human intestinal microbial ecosystem.

    Diaz-Bone, Roland A; van de Wiele, Tom R

    2009-07-15

    Methylation and hydrogenation of metal(loid)s by microorganisms are widespread and well-known processes in the environment by which mobility and in most cases toxicity are significantly enhanced in comparison to inorganic species. The human gut contains highly diverse and active microbiocenosis, yet little is known about the occurrence and importance of microbial metal(loid) methylation and hydrogenation. In this study, an in vitro gastrointestinal model, the Simulator of the Human Intestinal Microbial Ecosystem (SHIME),was used for investigating volatilization of metal(loid)s by intestinal microbiota. Suspensions from different compartments of the SHIME system analogous to different parts of the human intestinal tract were incubated with different concentrations of inorganic Ge, As, Se, Sn, Sb, Te, Hg, Pb, and Bi and analyzed by gas chromatography and inductively coupled plasma mass spectrometry (GC-ICP-MS). Significant volatilization was found for Se, As, and Te (maximal hourly production rates relative to the amount spiked; 0.6, 2, and 9 ng/mg/h, respectively). In addition, volatile species of Sb and Bi were detected. The occurrence of AsH3 and (CH3)2Te was toxicologically important. Furthermore, mixed Se/S and mixed As/S metabolites were detected in significant amounts in the gas phase of the incubation experiments of which two metabolites, (CH3)2AsSSCH3 and CH3As(SCH3)2, are described for the first time in environmental matrices. The toxicology of these species is unknown. These data show that the intestinal microbiota may increase the mobility of metal(loid)s, suggesting a significant modulation of their toxicity. Our research warrants further studies to investigate the extent of this process as well as the availability of metal(loid)s from different sources for microbial transformations. PMID:19708349

  13. Decreased gastric emptying and gastrointestinal and intestinal transits of liquid after complete spinal cord transection in awake rats

    Gondim F. de-A.A.

    1998-01-01

    Full Text Available We studied the effect of complete spinal cord transection (SCT on gastric emptying (GE and on gastrointestinal (GI and intestinal transits of liquid in awake rats using the phenol red method. Male Wistar rats (N = 65 weighing 180-200 g were fasted for 24 h and complete SCT was performed between C7 and T1 vertebrae after a careful midline dorsal incision. GE and GI and intestinal transits were measured 15 min, 6 h or 24 h after recovery from anesthesia. A test meal (0.5 mg/ml phenol red in 5% glucose solution was administered intragastrically (1.5 ml and the animals were sacrificed by an iv thiopental overdose 10 min later to evaluate GE and GI transit. For intestinal transit measurements, 1 ml of the test meal was administered into the proximal duodenum through a cannula inserted into a gastric fistula. GE was inhibited (P<0.05 by 34.3, 23.4 and 22.7%, respectively, at 15 min, 6 h and 24 h after SCT. GI transit was inhibited (P<0.05 by 42.5, 19.8 and 18.4%, respectively, at 15 min, 6 h and 24 h after SCT. Intestinal transit was also inhibited (P<0.05 by 48.8, 47.2 and 40.1%, respectively, at 15 min, 6 h and 24 h after SCT. Mean arterial pressure was significantly decreased (P<0.05 by 48.5, 46.8 and 41.5%, respectively, at 15 min, 6 h and 24 h after SCT. In summary, our report describes a decreased GE and GI and intestinal transits in awake rats within the first 24 h after high SCT.

  14. Development and validation of a new dynamic computer-controlled model of the human stomach and small intestine.

    Guerra, Aurélie; Denis, Sylvain; le Goff, Olivier; Sicardi, Vincent; François, Olivier; Yao, Anne-Françoise; Garrait, Ghislain; Manzi, Aimé Pacifique; Beyssac, Eric; Alric, Monique; Blanquet-Diot, Stéphanie

    2016-06-01

    For ethical, regulatory, and economic reasons, in vitro human digestion models are increasingly used as an alternative to in vivo assays. This study aims to present the new Engineered Stomach and small INtestine (ESIN) model and its validation for pharmaceutical applications. This dynamic computer-controlled system reproduces, according to in vivo data, the complex physiology of the human stomach and small intestine, including pH, transit times, chyme mixing, digestive secretions, and passive absorption of digestion products. Its innovative design allows a progressive meal intake and the differential gastric emptying of solids and liquids. The pharmaceutical behavior of two model drugs (paracetamol immediate release form and theophylline sustained release tablet) was studied in ESIN during liquid digestion. The results were compared to those found with a classical compendial method (paddle apparatus) and in human volunteers. Paracetamol and theophylline tablets showed similar absorption profiles in ESIN and in healthy subjects. For theophylline, a level A in vitro-in vivo correlation could be established between the results obtained in ESIN and in humans. Interestingly, using a pharmaceutical basket, the swelling and erosion of the theophylline sustained release form was followed during transit throughout ESIN. ESIN emerges as a relevant tool for pharmaceutical studies but once further validated may find many other applications in nutritional, toxicological, and microbiological fields. Biotechnol. Bioeng. 2016;113: 1325-1335. © 2015 Wiley Periodicals, Inc. PMID:26616643

  15. Scintigraphic determination of the effect of metoclopramide and morphine on small intestinal transit time

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

    1988-01-01

    To determine if a scintigraphic method could detect pharmacologic changes in small intestinal transit time (SITT), 10 male volunteers were studied at baseline and after intravenously administered metoclopramide (10 mg) and morphine (8 mg). Five of these volunteers were studied with the hydrogen breath test method for comparison. For each of the scintigraphic studies, the volunteers were positioned supine under a large-field-of-view gamma camera after ingesting an isosmotic lactulose solution containing 99mtechnetium-diethylenetriaminepentaacetic acid (DTPA). Data were collected and stored in a computer. Both gastric emptying and SITT were determined. SITT was 81 +/- 11 min (mean +/- S.E.M.; N = 10) during baseline studies, was decreased significantly to 50 +/- 6 min (N = 10; P less than 0.01) after metoclopramide, and was increased significantly to 161 +/- 15 min (N = 8; P less than 0.01) after morphine. Baseline mean values were 86.3 +/- 15 min (N = 15) for the hydrogen breath tests, 47 +/- 8 min (N = 5) for metoclopramide, and 183 +/- 16 min (N = 5) for morphine. For gastric emptying, there was no significant difference in percentage emptying at 1 hr for baseline and metochopramide (82 +/- 5% vs. 88 +/- 4%). Morphine prolonged gastric emptying at 1 hr to 63 +/- 8%. We conclude that the scintigraphic method for measuring SITT permits accurate investigation of the pharmacologic effects on intestinal motility and, in addition, may be a useful research and clinical method for SITT determination.

  16. Scintigraphic determination of the effect of metoclopramide and morphine on small intestinal transit time

    To determine if a scintigraphic method could detect pharmacologic changes in small intestinal transit time (SITT), 10 male volunteers were studied at baseline and after intravenously administered metoclopramide (10 mg) and morphine (8 mg). Five of these volunteers were studied with the hydrogen breath test method for comparison. For each of the scintigraphic studies, the volunteers were positioned supine under a large-field-of-view gamma camera after ingesting an isosmotic lactulose solution containing 99mtechnetium-diethylenetriaminepentaacetic acid (DTPA). Data were collected and stored in a computer. Both gastric emptying and SITT were determined. SITT was 81 +/- 11 min (mean +/- S.E.M.; N = 10) during baseline studies, was decreased significantly to 50 +/- 6 min (N = 10; P less than 0.01) after metoclopramide, and was increased significantly to 161 +/- 15 min (N = 8; P less than 0.01) after morphine. Baseline mean values were 86.3 +/- 15 min (N = 15) for the hydrogen breath tests, 47 +/- 8 min (N = 5) for metoclopramide, and 183 +/- 16 min (N = 5) for morphine. For gastric emptying, there was no significant difference in percentage emptying at 1 hr for baseline and metochopramide (82 +/- 5% vs. 88 +/- 4%). Morphine prolonged gastric emptying at 1 hr to 63 +/- 8%. We conclude that the scintigraphic method for measuring SITT permits accurate investigation of the pharmacologic effects on intestinal motility and, in addition, may be a useful research and clinical method for SITT determination

  17. Slow intestinal transit contributes to elevate urinary p-cresol level in Italian autistic children.

    Gabriele, Stefano; Sacco, Roberto; Altieri, Laura; Neri, Cristina; Urbani, Andrea; Bravaccio, Carmela; Riccio, Maria Pia; Iovene, Maria Rosaria; Bombace, Francesca; De Magistris, Laura; Persico, Antonio M

    2016-07-01

    The uremic toxin p-cresol (4-methylphenol) is either of environmental origin or can be synthetized from tyrosine by cresol-producing bacteria present in the gut lumen. Elevated p-cresol amounts have been previously found in the urines of Italian and French autism spectrum disorder (ASD) children up until 8 years of age, and may be associated with autism severity or with the intensity of abnormal behaviors. This study aims to investigate the mechanism producing elevated urinary p-cresol in ASD. Urinary p-cresol levels were thus measured by High Performance Liquid Chromatography in a sample of 53 Italian ASD children assessed for (a) presence of Clostridium spp. strains in the gut by means of an in vitro fecal stool test and of Clostridium difficile-derived toxin A/B in the feces, (b) intestinal permeability using the lactulose/mannitol (LA/MA) test, (c) frequent use of antibiotics due to recurrent infections during the first 2 years of postnatal life, and (d) stool habits with the Bristol Stool Form Scale. Chronic constipation was the only variable significantly associated with total urinary p-cresol concentration (P p-cresol levels are elevated in young ASD children with increased intestinal transit time and chronic constipation. Autism Res 2016, 9: 752-759. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. PMID:26437875

  18. QSAR Study and VolSurf Characterization of Human Intestinal Absorption of Druge

    胡桂香; 商志才; 等

    2003-01-01

    The prediction of human intestinal absorption is a major goal in the design,optimization,and selection of candidates for the develoment of oral drugs.In this study,a computerized method(VolSurf with GRID) was used as a novel tool for predicting human intestinal absorption of test compound,and for determining the critical molecular properties needed for human intestinal absorption.The tested molecules consisted of 20 diverse drug-like compounds.Partial least squares(PLS) discriminant analysis was used to correlate the experimental data with the theoretical molecular properties of human intestinal absorption.A good correlation(r2=0.95,q2=0.86) between the molecular modeling results and the experimental data demonstrated that human intestinal absorption could be predicted from the three-dimensional(3D) molecular structure of a compound .Favorable structureal properties identified for the potent intestinal absorption of drugs included strong imbalance between the center of mass of a molecule and the barycentre of its hydrophilic and hydrophobic regions and a definitive hydrophobic region as well as less hydrogen bonding donors and acceptors in the molecule.

  19. Comparative proteomic analysis of cell lines and scrapings of the human intestinal epithelium

    Renes Johan

    2007-04-01

    Full Text Available Abstract Background In vitro models are indispensable study objects in the fields of cell and molecular biology, with advantages such as accessibility, homogeneity of the cell population, reproducibility, and growth rate. The Caco-2 cell line, originating from a colon carcinoma, is a widely used in vitro model for small intestinal epithelium. Cancer cells have an altered metabolism, making it difficult to infer their representativity for the tissue from which they are derived. This study was designed to compare the protein expression pattern of Caco-2 cells with the patterns of intestinal epithelial cells from human small and large intestine. HT-29 intestinal cells, Hep G2 liver cells and TE 671 muscle cells were included too, the latter two as negative controls. Results Two-dimensional gel electrophoresis was performed on each tissue and cell line protein sample. Principal component and cluster analysis revealed that global expression of intestinal epithelial scrapings differed from that of intestinal epithelial cell lines. Since all cultured cell lines clustered together, this finding was ascribed to an adaptation of cells to culture conditions and their tumor origin, and responsible proteins were identified by mass spectrometry. When investigating the profiles of Caco-2 cells and small intestinal cells in detail, a considerable overlap was observed. Conclusion Numerous proteins showed a similar expression in Caco-2 cells, HT-29 cells, and both the intestinal scrapings, of which some appear to be characteristic to human intestinal epithelium in vivo. In addition, several biologically significant proteins are expressed at comparable levels in Caco-2 cells and small intestinal scrapings, indicating the usability of this in vitro model. Caco-2 cells, however, appear to over-express as well as under-express certain proteins, which needs to be considered by scientists using this cell line. Hence, care should be taken to prevent misinterpretation of

  20. Contribution of Listeria monocytogenes RecA to acid and bile survival and invasion of human intestinal Caco-2 cells

    Veen, van der S.; Abee, T.

    2011-01-01

    The food-borne pathogen Listeria monocytogenes is able to colonize the human gastro-intestinal tract and subsequently cross the intestinal barrier. Thus, for L. monocytogenes to become virulent, it must survive the low pH of the stomach, high bile concentrations in the small intestine, and invade th

  1. Nucleotide and amino acid sequences of human intestinal alkaline phosphatase: close homology to placental alkaline phosphatase

    A cDNA clone for human adult intestinal alkaline phosphatase (ALP) [orthophosphoric-monoester phosphohydrolase (alkaline optimum); EC 3.1.3.1] was isolated from a λgt11 expression library. The cDNA insert of this clone is 2513 base pairs in length and contains an open reading frame that encodes a 528-amino acid polypeptide. This deduced polypeptide contains the first 40 amino acids of human intestinal ALP, as determined by direct protein sequencing. Intestinal ALP shows 86.5% amino acid identity to placental (type 1) ALP and 56.6% amino acid identity to liver/bone/kidney ALP. In the 3'-untranslated regions, intestinal and placental ALP cDNAs are 73.5% identical (excluding gaps). The evolution of this multigene enzyme family is discussed

  2. Lactobacillus reuteri Inhibition of Enteropathogenic Escherichia coli Adherence to Human Intestinal Epithelium

    Walsham, Alistair D. S.; MacKenzie, Donald A.; Cook, Vivienne; Wemyss-Holden, Simon; Hews, Claire L.; Juge, Nathalie; Schüller, Stephanie

    2016-01-01

    Enteropathogenic Escherichia coli (EPEC) is a major cause of diarrheal infant death in developing countries, and probiotic bacteria have been shown to provide health benefits in gastrointestinal infections. In this study, we have investigated the influence of the gut symbiont Lactobacillus reuteri on EPEC adherence to the human intestinal epithelium. Different host cell model systems including non-mucus-producing HT-29 and mucus-producing LS174T intestinal epithelial cell lines as well as hum...

  3. Growth inhibition of Streptococcus mutans by cellular extracts of human intestinal lactic acid bacteria.

    Ishihara, K; Miyakawa, H; Hasegawa, A.; Takazoe, I; Kawai, Y.

    1985-01-01

    The in vitro growth of Streptococcus mutans was completely inhibited by water-soluble extracts from cells of various intestinal lactic acid bacteria identified as Streptococcus faecium, Streptococcus equinus, Lactobacillus fermentum, and Lactobacillus salivarius. The growth inhibition was dependent on the concentrations of the extracts. In contrast, the extracts did not inhibit the growth of the major indigenous intestinal lactic acid bacteria isolated from humans. These lactic acid bacteria ...

  4. Ecological Effects of Antimicrobial Agents on the Human Intestinal Microflora

    Nord, C E; Edlund, C

    2011-01-01

    Administration of antimicrobial agents may seriously disturb the balance of the normal intestinal microflora. This may cause bacterial overgrowth and emergence of resistant microorganisms which may lead to serious infections and also encourage transfer of resistance factors among bacteria. This review article summarises published scientific reports on the ecological effect of penicillins, cephalosporins, monobactams, carbapenems, macrolides, tetracyclines, nitroimidazoles, clindamycin and qui...

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

    Joshua D Rouch

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

  6. Assessing DNA methylation in the developing human intestinal epithelium: potential link to inflammatory bowel disease.

    Kraiczy, J; Nayak, K; Ross, A; Raine, T; Mak, T N; Gasparetto, M; Cario, E; Rakyan, V; Heuschkel, R; Zilbauer, M

    2016-05-01

    DNA methylation is one of the major epigenetic mechanisms implicated in regulating cellular development and cell-type-specific gene expression. Here we performed simultaneous genome-wide DNA methylation and gene expression analysis on purified intestinal epithelial cells derived from human fetal gut, healthy pediatric biopsies, and children newly diagnosed with inflammatory bowel disease (IBD). Results were validated using pyrosequencing, real-time PCR, and immunostaining. The functional impact of DNA methylation changes on gene expression was assessed by employing in-vitro assays in intestinal cell lines. DNA methylation analyses allowed identification of 214 genes for which expression is regulated via DNA methylation, i.e. regulatory differentially methylated regions (rDMRs). Pathway and functional analysis of rDMRs suggested a critical role for DNA methylation in regulating gene expression and functional development of the human intestinal epithelium. Moreover, analysis performed on intestinal epithelium of children newly diagnosed with IBD revealed alterations in DNA methylation within genomic loci, which were found to overlap significantly with those undergoing methylation changes during intestinal development. Our study provides novel insights into the physiological role of DNA methylation in regulating functional maturation of the human intestinal epithelium. Moreover, we provide data linking developmentally acquired alterations in the DNA methylation profile to changes seen in pediatric IBD. PMID:26376367

  7. Expression, Distribution and Role of Aquaporin Water Channels in Human and Animal Stomach and Intestines

    Cui Zhu

    2016-08-01

    Full Text Available Stomach and intestines are involved in the secretion of gastrointestinal fluids and the absorption of nutrients and fluids, which ensure normal gut functions. Aquaporin water channels (AQPs represent a major transcellular route for water transport in the gastrointestinal tract. Until now, at least 11 AQPs (AQP1–11 have been found to be present in the stomach, small and large intestines. These AQPs are distributed in different cell types in the stomach and intestines, including gastric epithelial cells, gastric glands cells, absorptive epithelial cells (enterocytes, goblet cells and Paneth cells. AQP1 is abundantly distributed in the endothelial cells of the gastrointestinal tract. AQP3 and AQP4 are mainly distributed in the basolateral membrane of epithelial cells in the stomach and intestines. AQP7, AQP8, AQP10 and AQP11 are distributed in the apical of enterocytes in the small and large intestines. Although AQP-null mice displayed almost no phenotypes in gastrointestinal tracts, the alterations of the expression and localization of these AQPs have been shown to be associated with the pathology of gastrointestinal disorders, which suggests that AQPs play important roles serving as potential therapeutic targets. Therefore, this review provides an overview of the expression, localization and distribution of AQPs in the stomach, small and large intestine of human and animals. Furthermore, this review emphasizes the potential roles of AQPs in the physiology and pathophysiology of stomach and intestines.

  8. Nerveless and gutsy: intestinal nutrient sensing from invertebrates to humans

    Miguel-Aliaga, Irene

    2012-01-01

    The increasingly recognized role of gastrointestinal signals in the regulation of food intake, insulin production and peripheral nutrient storage has prompted a surge of interest in studying how the gastrointestinal tract senses and responds to nutritional information. Identification of metabolically important intestinal nutrient sensors could provide potential new drug targets for the treatment of diabetes, obesity and gastrointestinal disorders. From a more fundamental perspective, the stud...

  9. The human small intestinal microbiota is driven by rapid uptake and conversion of simple carbohydrates

    Zoetendal, Erwin G; Raes, Jeroen; van den Bogert, Bartholomeus;

    2012-01-01

    The human gastrointestinal tract (GI tract) harbors a complex community of microbes. The microbiota composition varies between different locations in the GI tract, but most studies focus on the fecal microbiota, and that inhabiting the colonic mucosa. Consequently, little is known about the...... microbiota at other parts of the GI tract, which is especially true for the small intestine because of its limited accessibility. Here we deduce an ecological model of the microbiota composition and function in the small intestine, using complementing culture-independent approaches. Phylogenetic microarray...... analyses demonstrated that microbiota compositions that are typically found in effluent samples from ileostomists (subjects without a colon) can also be encountered in the small intestine of healthy individuals. Phylogenetic mapping of small intestinal metagenome of three different ileostomy effluent...

  10. Lineage-specific expression of bestrophin-2 and bestrophin-4 in human intestinal epithelial cells

    Ito, Go; Okamoto, Ryuichi; Murano, Tatsuro;

    2013-01-01

    Intestinal epithelial cells (IECs) regulate the absorption and secretion of anions, such as HCO3(-) or Cl(-). Bestrophin genes represent a newly identified group of calcium-activated Cl(-) channels (CaCCs). Studies have suggested that, among the four human bestrophin-family genes, bestrophin-2...... (BEST2) and bestrophin-4 (BEST4) might be expressed within the intestinal tissue. Consistently, a study showed that BEST2 is expressed by human colonic goblet cells. However, their precise expression pattern along the gastrointestinal tract, or the lineage specificity of the cells expressing these genes...

  11. Contributions of microbiome and mechanical deformation to intestinal bacterial overgrowth and inflammation in a human gut-on-a-chip

    Kim, Hyun Jung; Li, Hu; Collins, James J.; Donald E. Ingber

    2015-01-01

    The main advance of this study is the development of a microengineered model of human intestinal inflammation and bacterial overgrowth that permits analysis of individual contributors to the pathophysiology of intestinal diseases, such as ileus and inflammatory bowel disease, over a period of weeks in vitro. By studying living human intestinal epithelium, with or without vascular and lymphatic endothelium, immune cells, and mechanical deformation, as well as living microbiome and pathogenic m...

  12. Effects of progesterone on gastric emptying and intestinal transit in male rats

    Chuan-Yong Liu; Lian-Bi Chen; Pei-Yi Liu; Dong-Ping Xie; Paulus S. Wang

    2002-01-01

    AIM: To study the dose-dependent of progesterone (P) effect and the interaction between the oxytocin (OT) and Pon gastrointestinal motility.METHODS: In order to monitor the gastric emptying andintestinal transit, the SD male rats were intubated via acatheter with normal saline (3 mi/kg) containing Na251 CrO4(0.5 μCi/ml) and 10 % charcoal.OT was dissolved intonormal saline and P was dissolved into 75 % alcohol.RESULTS: Low does of P (1 mg/kg, i. p. ) enhanced thegastric emptying (75 ± 3 %, P< 0.05) and high dose of P (5mg/kg, i.p. ) inhibit it (42± 11.2 %, P< 0.01). P (1 rog/kg)increased the intestinal transit (4.2 ± 0. 3, P < 0.05) whilethe higher dose ( 10-20 mg/kg) had no effect. OT (0.8 mg/kg, i.p. ) inhibited the gastric emptying (23.5 ± 9.8 %, P <0.01). The inhibitory effects of P (20 mg/kg) (32± 9.7 %, P< 0.05) and OT (0.8 mg/kg) on gastric emptying enhancedeach other when the two chemicals were administratedsimultaneously ( 17 ± 9.4 %, P < 0.01).CONCLUSION: Low dose of P increased Gl motility whilehigh dose of P decreased it. During the later period ofpregnancy, elevated plasma level of OT may also participatein the gastrointestinal inhibition.

  13. Kinematics of transition during human accelerated sprinting

    Ryu Nagahara

    2014-07-01

    Full Text Available This study investigated kinematics of human accelerated sprinting through 50 m and examined whether there is transition and changes in acceleration strategies during the entire acceleration phase. Twelve male sprinters performed a 60-m sprint, during which step-to-step kinematics were captured using 60 infrared cameras. To detect the transition during the acceleration phase, the mean height of the whole-body centre of gravity (CG during the support phase was adopted as a measure. Detection methods found two transitions during the entire acceleration phase of maximal sprinting, and the acceleration phase could thus be divided into initial, middle, and final sections. Discriminable kinematic changes were found when the sprinters crossed the detected first transition—the foot contacting the ground in front of the CG, the knee-joint starting to flex during the support phase, terminating an increase in step frequency—and second transition—the termination of changes in body postures and the start of a slight decrease in the intensity of hip-joint movements, thus validating the employed methods. In each acceleration section, different contributions of lower-extremity segments to increase in the CG forward velocity—thigh and shank for the initial section, thigh, shank, and foot for the middle section, shank and foot for the final section—were verified, establishing different acceleration strategies during the entire acceleration phase. In conclusion, there are presumably two transitions during human maximal accelerated sprinting that divide the entire acceleration phase into three sections, and different acceleration strategies represented by the contributions of the segments for running speed are employed.

  14. Genomic and ecological studies to understand bifidobacterial adaptation to the human gastro-intestinal tract

    Turroni, Francesca

    2010-01-01

    The Bifidobacterium genus comprises a high GC Gram positive bacteria belonging to the Actinobacteria phylum, which has been found to represent a common inhabitant of the gastro-intestinal tract (GIT) of mammals. In particular focusing on the GIT of human, the overall microorganisms that colonize such environment represent the “gut microbiota”. The human gut microbiota is an extremely complex microbial community whose functions are believed to have a significant impact on human physiology. Dif...

  15. Isolation and identification of intestinal steroid-desulfating bacteria from rats and humans.

    Van Eldere, J.; Robben, J; De Pauw, G.; Merckx, R.; Eyssen, H.

    1988-01-01

    We isolated 12 strictly anaerobic steroid-3-sulfate-desulfating strains from the intestinal floras of rats and humans. Two strains (S1 and S2) of the same atypical Clostridium species and an atypical Lactobacillus strain (termed R9) were obtained from rats. The human isolates were identified as Eubacterium cylindroides (two strains, H1 and H2), Peptococcus niger (two strains, H4 and H89), and Clostridium clostridiiforme. We also isolated, from different human fecal samples, four strains of ph...

  16. Human Intestinal Cells Modulate Conjugational Transfer of Multidrug Resistance Plasmids between Clinical Escherichia coli Isolates

    Machado, Ana Manuel; SOMMER, Morten

    2014-01-01

    Bacterial conjugation in the human gut microbiota is believed to play a major role in the dissemination of antibiotic resistance genes and virulence plasmids. However, the modulation of bacterial conjugation by the human host remains poorly understood and there is a need for controlled systems to study this process. We established an in vitro co-culture system to study the interaction between human intestinal cells and bacteria. We show that the conjugation efficiency of a plasmid encoding an...

  17. Effects of laxative and N-acetylcysteine on mucus accumulation, bacterial load, transit, and inflammation in the cystic fibrosis mouse small intestine.

    De Lisle, Robert C; Roach, Eileen; Jansson, Kyle

    2007-09-01

    The accumulation of mucus in affected organs is characteristic of cystic fibrosis (CF). The CF mouse small intestine has dramatic mucus accumulation and exhibits slower interdigestive intestinal transit. These factors are proposed to play cooperative roles that foster small intestinal bacterial overgrowth (SIBO) and contribute to the innate immune response of the CF intestine. It was hypothesized that decreasing the mucus accumulation would reduce SIBO and might improve other aspects of the CF intestinal phenotype. To test this, solid chow-fed CF mice were treated with an osmotic laxative to improve gut hydration or liquid-fed mice were treated orally with N-acetylcysteine (NAC) to break mucin disulfide bonds. Treatment with laxative or NAC reduced mucus accumulation by 43% and 50%, respectively, as measured histologically as dilation of the intestinal crypts. Laxative and NAC also reduced bacterial overgrowth in the CF intestine by 92% and 63%, respectively. Treatment with laxative normalized small intestinal transit in CF mice, whereas NAC did not. The expression of innate immune response-related genes was significantly reduced in laxative-treated CF mice, whereas there was no significant effect in NAC-treated CF mice. In summary, laxative and NAC treatments of CF mice reduced mucus accumulation to a similar extent, but laxative was more effective than NAC at reducing bacterial load. Eradication of bacterial overgrowth by laxative treatment was associated with normalized intestinal transit and a reduction in the innate immune response. These results suggest that both mucus accumulation and slowed interdigestive small intestinal transit contribute to SIBO in the CF intestine. PMID:17615175

  18. CD4+CD25bright T cells in human intestinal lamina propria as regulatory cells.

    Makita, Shin; Kanai, Takanori; Oshima, Shigeru; Uraushihara, Koji; Totsuka, Teruji; Sawada, Taisuke; Nakamura, Tetsuya; Koganei, Kazutaka; Fukushima, Tsuneo; Watanabe, Mamoru

    2004-09-01

    It is well known that immune responses in the intestine remain in a state of controlled inflammation, suggesting that not only active suppression by regulatory T cells plays an important role in the normal intestinal homeostasis, but also its dysregulation leads to the development of inflammatory bowel disease. In this study, we demonstrate that the CD4(+)CD25(bright) T cells reside in the human intestinal lamina propria (LP) and functionally retain regulatory activities. All human LP CD4(+) T cells regardless of CD25 expression constitutively expressed CTLA-4, glucocorticoid-induced TNFR family-related protein, and Foxp3 and proliferate poorly. Although LP CD4(+)CD25(-) T cells showed an activated and anergic/memory phenotype, they did not retain regulatory activity. In LP CD4(+)CD25(+) T cells, however, cells expressing CD25 at high levels (CD4(+)CD25(bright)) suppressed the proliferation and various cytokine productions of CD4(+)CD25(-) T cells. LP CD4(+)CD25(bright) T cells by themselves produced fewer amounts of IL-2, IFN-gamma, and IL-10. Interestingly, LP CD4(+)CD25(bright) T cells with regulatory T activity were significantly increased in patients with active inflammatory bowel disease. These results suggest that CD4(+)CD25(bright) T cells found in the normal and inflamed intestinal mucosa selectively inhibit the host immune response and therefore may contribute to the intestinal immune homeostasis. PMID:15322172

  19. Microbial Eco-Physiology of the human intestinal tract: a flow cytometric approach

    Amor, Ben K.

    2004-01-01

    This thesis describes a multifaceted approach to further enhance our view of the complex human intestinal microbial ecosystem. This approach combines me advantages of flow cyrometry (FCM), a single cell and high-throughput technology, and molecular techniques that have proven themselves to be invalu

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

    Moda, Tiago L; Andricopulo, Adriano D

    2012-04-15

    Consistent in silico models for ADME properties are useful tools in early drug discovery. Here, we report the hologram QSAR modeling of human intestinal absorption using a dataset of 638 compounds with experimental data associated. The final validated models are consistent and robust for the consensus prediction of this important pharmacokinetic property and are suitable for virtual screening applications. PMID:22425566

  1. Complete amino acid sequence of human intestinal aminopeptidase N as deduced from cloned cDNA

    Cowell, G M; Kønigshøfer, E; Danielsen, E M;

    1988-01-01

    The complete primary structure (967 amino acids) of an intestinal human aminopeptidase N (EC 3.4.11.2) was deduced from the sequence of a cDNA clone. Aminopeptidase N is anchored to the microvillar membrane via an uncleaved signal for membrane insertion. A domain constituting amino acid 250...

  2. Associations between common intestinal parasites and bacteria in humans as revealed by qPCR

    O'Brien Andersen, L.; Karim, A. B.; Roager, Henrik Munch;

    2016-01-01

    Several studies have shown associations between groups of intestinal bacterial or specific ratios between bacterial groups and various disease traits. Meanwhile, little is known about interactions and associations between eukaryotic and prokaryotic microorganisms in the human gut. In this work, we...

  3. E durans strain M4-5 isolated from human colonic flora attenuates intestinal inflammation

    Avram-Hananel, Liraz; Stock, Julia; Parlesak, Alexandr;

    2010-01-01

    PURPOSE: The aim of this study was to evaluate in vitro and in vivo effects of a unique high-butyrate-producing bacterial strain from human colonic flora, Enterococcus durans, in prevention and treatment of intestinal inflammation. METHODS: A compartmentalized Caco-2/leukocyte coculture model was...

  4. Small-intestinal dysfunction accompanies the complex endocrinopathy of human proprotein convertase 1 deficiency

    Jackson, Robert S; Creemers, John W M; Farooqi, I Sadaf;

    2003-01-01

    , some mature ACTH and glucagon-like peptide 17-36(amide) were detectable in her plasma, suggesting that the production of these hormones, at least in humans, does not have an absolute dependence on PC1. The presence of severe obesity and the absence of growth retardation in both subjects contrast......We have previously described the only reported case of human proprotein convertase 1 (PC1) deficiency, in a female (Subject A) with obesity, hypogonadism, hypoadrenalism, and reactive hypoglycemia. We now report the second case of human PC1 deficiency (Subject B), also due to compound...... in type. Subsequent investigation of Subject A revealed marked small-intestinal absorptive dysfunction, which was not previously clinically suspected. We postulate that PC1, presumably in the enteroendocrine cells, is essential for the normal absorptive function of the human small intestine. The...

  5. Inhibition of human pancreatic and biliary output but not intestinal motility by physiological intraileal lipid loads

    Keller, Jutta; Holst, Jens Juul; Layer, Peter

    2005-01-01

    Lipid perfusion into the distal ileal lumen at supraphysiological loads inhibits pancreatic exocrine secretion and gastrointestinal motility in humans. In the present study, we sought to determine the effects of physiological postprandial intraileal lipid concentrations on endogenously stimulated....... Physiological postprandial ileal lipid concentrations dose dependently inhibited human digestive pancreatic protease and bile acid output, but not intestinal motor activity. Thus physiological postprandial ileal nutrient exposure may be of importance for the termination of digestive secretory responses...

  6. Metagenomics of the human intestinal tract: from who is there to what is done there

    Lapaque, Nicolas; Doré, Joël; Blottière, Hervé

    2015-01-01

    The human gastro-intestinal tract is colonized by 10(6)-10(14) microorganisms from the three domains, eukaria, archaea and bacteria that are collectively referred as the human gut microbiota. Gut microbiota actively contributes to the digestion of the nutrients, mainly the fibers otherwise undigested by the host, and participate to the host capacity of energy recovery from food. It plays also a key role in gut homeostasis, impacting on its barrier function and regulating the immune and metabo...

  7. A cost-effective system for differentiation of intestinal epithelium from human induced pluripotent stem cells

    Soichiro Ogaki; Mayu Morooka; Kaito Otera; Shoen Kume

    2015-01-01

    The human intestinal epithelium is a useful model for pharmacological studies of absorption, metabolism, drug interactions, and toxicology, as well as for studies of developmental biology. We established a rapid and cost effective system for differentiation of human induced pluripotent stem (iPS) cells into definitive endoderm (DE) cells. In the presence of dimethyl sulfoxide (DMSO), a low concentration of Activin at 6.25 ng/ml is sufficient to give a similar differentiation efficiency with t...

  8. Recombinant Human Epidermal Growth Factor Accelerates Recovery of Mouse Small Intestinal Mucosa After Radiation Damage

    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

  9. Autoradiographic and enzyme histochemical studies of intestinal metaplasia in human stomach

    The relationship between growth potency and alkaline phosphatase activity of intestinal metaplasia of human stomach was studied using enzyme histochemical and autoradiographic technique. Both alkaline phosphatase positive and negative glands were seen in the intestinal metaplasia. Two types of alkaline phosphatase positive glands were observed, one in which alkaline phosphatase positive cells were distributed from the lower part to the surface of the gland and the other in which alkaline phosphatase positive cells were localized only at the surface of the gland. 3H-Thymidine labelled cells in the former gland were localized only at the bottom but the labelled cells in the latter were distributed in the lower part of the gland. 3H-Thymidine labelled cells in alkaline phosphatase negative gland were distributed from the bottom to middle part of the gland. These results imply that the intestinal metaplasia in which cell proliferative zone was localized at the bottom of the gland showed alkaline phosphatase activity just like the activity in the small intestine, however the gland in which the cell proliferative zone was prolonged showed the alkaline phosphatase activity different from the small intestine. (author)

  10. Comparative quantification of human intestinal bacteria based on cPCR and LDR/LCR

    Zhou-Rui Tang; Kai Li; Yu-Xun Zhou; Zhen-Xian Xiao; Jun-Hua Xiao; Rui Huang; Guo-Hao Gu

    2012-01-01

    AIM: To establish a multiple detection method based on comparative polymerase chain reaction (cPCR) and ligase detection reaction (LDR)/ligase chain reaction (LCR) to quantify the intestinal bacterial components.METHODS: Comparative quantification of 16S rDNAs from different intestinal bacterial components was used to quantify multiple intestinal bacteria. The 16S rDNAs of different bacteria were amplified simultaneously by cPCR. The LDR/LCR was examined to actualize the genotyping and quantification. Two beneficial (Bifidobacterium, Lactobacillus) and three conditionally pathogenic bacteria (Enterococcus, Enterobacterium and Eubacterium) were used in this detection. With cloned standard bacterial 16S rDNAs, standard curves were prepared to validate the quantitative relations between the ratio of original concentrations of two templates and the ratio of the fluorescence signals of their final ligation products. The internal controls were added to monitor the whole detection flow. The quantity ratio between two bacteria was tested.RESULTS: cPCR and LDR revealed obvious linear correlations with standard DNAs, but cPCR and LCR did not. In the sample test, the distributions of the quantity ratio between each two bacterial species were obtained. There were significant differences among these distributions in the total samples. But these distributions of quantity ratio of each two bacteria remained stable among groups divided by age or sex.CONCLUSION: The detection method in this study can be used to conduct multiple intestinal bacteria genotyping and quantification, and to monitor the human intestinal health status as well.

  11. Phase transitions in models of human cooperation

    Perc, Matjaž

    2016-08-01

    If only the fittest survive, why should one cooperate? Why should one sacrifice personal benefits for the common good? Recent research indicates that a comprehensive answer to such questions requires that we look beyond the individual and focus on the collective behavior that emerges as a result of the interactions among individuals, groups, and societies. Although undoubtedly driven also by culture and cognition, human cooperation is just as well an emergent, collective phenomenon in a complex system. Nonequilibrium statistical physics, in particular the collective behavior of interacting particles near phase transitions, has already been recognized as very valuable for understanding counterintuitive evolutionary outcomes. However, unlike pairwise interactions among particles that typically govern solid-state physics systems, interactions among humans often involve group interactions, and they also involve a larger number of possible states even for the most simplified description of reality. Here we briefly review research done in the realm of the public goods game, and we outline future research directions with an emphasis on merging the most recent advances in the social sciences with methods of nonequilibrium statistical physics. By having a firm theoretical grip on human cooperation, we can hope to engineer better social systems and develop more efficient policies for a sustainable and better future.

  12. Circulating intestine-derived exosomal miR-328 in plasma, a possible biomarker for estimating BCRP function in the human intestines

    Gotanda, Keisuke; Hirota, Takeshi; Saito, Jumpei; Fukae, Masato; Egashira, Yu; Izumi, Noritomo; Deguchi, Mariko; Kimura, Miyuki; Matsuki, Shunji; Irie, Shin; Ieiri, Ichiro

    2016-01-01

    A variant in the breast cancer resistance protein (BCRP) gene, 421C> A is a useful biomarker for describing large inter-individual differences in the pharmacokinetics of sulfasalazine (SASP), a BCRP substrate. However, large intra-genotypic variability still exists in spite of the incorporation of this variant into the pharmacokinetics of SASP. Since miR-328 negatively regulates BCRP expression in human tissues, we hypothesized that exosomal miR-328 in plasma, which leaks from the intestines, is a possible biomarker for estimating BCRP activity in the human intestines. We established an immunoprecipitation-based quantitative method for circulating intestine-derived miR-328 in plasma using an anti-glycoprotein A33 antibody. A clinical study was conducted with an open-label, non-randomized, and single-arm design involving 33 healthy participants. Intestine-derived exosomal miR-328 levels positively correlated (P exosomal miR-328 in plasma has potential as a possible biomarker for estimating BCRP function in the human intestines. PMID:27571936

  13. Human intestinal cells modulate conjugational transfer of multidrug resistance plasmids between clinical Escherichia coli isolates.

    Ana Manuel Dantas Machado

    Full Text Available Bacterial conjugation in the human gut microbiota is believed to play a major role in the dissemination of antibiotic resistance genes and virulence plasmids. However, the modulation of bacterial conjugation by the human host remains poorly understood and there is a need for controlled systems to study this process. We established an in vitro co-culture system to study the interaction between human intestinal cells and bacteria. We show that the conjugation efficiency of a plasmid encoding an extended spectrum beta-lactamase is reduced when clinical isolates of Escherichia coli are co-cultured with human intestinal cells. We show that filtered media from co-cultures contain a factor that reduces conjugation efficiency. Protease treatment of the filtered media eliminates this inhibition of conjugation. This data suggests that a peptide or protein based factor is secreted on the apical side of the intestinal cells exposed to bacteria leading to a two-fold reduction in conjugation efficiency. These results show that human gut epithelial cells can modulate bacterial conjugation and may have relevance to gene exchange in the gut.

  14. Antibiotic residues and drug resistance in human intestinal flora.

    Corpet, D. E.

    1987-01-01

    The effect of residual levels of ampicillin on the drug resistance of fecal flora was studied in human volunteers given 1.5 mg of ampicillin orally per day for 21 days. This treatment failed to have any significant reproducible effect on the number of resistant Escherichia coli in their feces. The effect of continuous administration of small doses of ampicillin, chlortetracycline, or streptomycin in the drinking water was studied in gnotobiotic mice inoculated with a human fecal flora. In thi...

  15. Lactobacillus reuteri Inhibition of Enteropathogenic Escherichia coli Adherence to Human Intestinal Epithelium.

    Walsham, Alistair D S; MacKenzie, Donald A; Cook, Vivienne; Wemyss-Holden, Simon; Hews, Claire L; Juge, Nathalie; Schüller, Stephanie

    2016-01-01

    Enteropathogenic Escherichia coli (EPEC) is a major cause of diarrheal infant death in developing countries, and probiotic bacteria have been shown to provide health benefits in gastrointestinal infections. In this study, we have investigated the influence of the gut symbiont Lactobacillus reuteri on EPEC adherence to the human intestinal epithelium. Different host cell model systems including non-mucus-producing HT-29 and mucus-producing LS174T intestinal epithelial cell lines as well as human small intestinal biopsies were used. Adherence of L. reuteri to HT-29 cells was strain-specific, and the mucus-binding proteins CmbA and MUB increased binding to both HT-29 and LS174T cells. L. reuteri ATCC PTA 6475 and ATCC 53608 significantly inhibited EPEC binding to HT-29 but not LS174T cells. While pre-incubation of LS174T cells with ATCC PTA 6475 did not affect EPEC attaching/effacing (A/E) lesion formation, it increased the size of EPEC microcolonies. ATCC PTA 6475 and ATCC 53608 binding to the mucus layer resulted in decreased EPEC adherence to small intestinal biopsy epithelium. Our findings show that L. reuteri reduction of EPEC adhesion is strain-specific and has the potential to target either the epithelium or the mucus layer, providing further rationale for the selection of probiotic strains. PMID:26973622

  16. Lactobacillus reuteri Inhibition of Enteropathogenic Escherichia coli Adherence to Human Intestinal Epithelium

    Alistair eWalsham

    2016-03-01

    Full Text Available Enteropathogenic E. coli (EPEC is a major cause of diarrheal infant death in developing countries, and probiotic bacteria have been shown to provide health benefits in gastrointestinal infections. In this study, we have investigated the influence of the gut symbiont Lactobacillus reuteri on EPEC adherence to the human intestinal epithelium. Different host cell model systems including non-mucus-producing HT-29 and mucus-producing LS174T intestinal epithelial cell lines as well as human small intestinal biopsies were used. Adherence of L. reuteri to HT-29 cells was strain-specific, and the mucus-binding proteins CmbA and MUB increased binding to both HT-29 and LS174T cells. L. reuteri ATCC PTA 6475 and ATCC 53608 significantly inhibited EPEC binding to HT-29 but not LS174T cells. While pre-incubation of LS174T cells with ATCC PTA 6475 did not affect EPEC A/E lesion formation, it increased the size of EPEC microcolonies. ATCC PTA 6475 and ATCC 53608 binding to the mucus layer resulted in decreased EPEC adherence to small intestinal biopsy epithelium. Our findings show that L. reuteri reduction of EPEC adhesion is strain-specific and has the potential to target either the epithelium or the mucus layer, providing further rationale for the selection of probiotic strains.

  17. The Modulatory Effect of Anthocyanins from Purple Sweet Potato on Human Intestinal Microbiota in Vitro.

    Zhang, Xin; Yang, Yang; Wu, Zufang; Weng, Peifang

    2016-03-30

    In order to investigate the modulatory effect of purple sweet potato anthocyanins (PSPAs) on human intestinal microbiota, PSPAs were prepared by column chromatography and their influence on intestinal microbiota was analyzed by monitoring the bacterial populations and analyzing short-chain fatty acid (SCFA) concentrations at different time points. The numbers (log10 cell/mL) of Bifidobacterium and Lactobacillus/Enterococcus spp., Bacteroides-Prevotella, Clostridium histolyticum, and total bacteria after 24 h of culture in anaerobic fermentation broth containing PSPAs were 8.44 ± 0.02, 8.30 ± 0.01, 7.80 ± 0.03, 7.60 ± 0.03, and 9.00 ± 0.02, respectively, compared with 8.21 ± 0.03, 8.12 ± 0.02, 7.95 ± 0.02, 7.77 ± 0.02, and 9.01 ± 0.03, respectively, in the controls. The results showed that PSPAs induced the proliferation of Bifidobacterium and Lactobacillus/Enterococcus spp., inhibited the growth of Bacteroides-Prevotella and Clostridium histolyticum, and did not affect the total bacteria number. Total SCFA concentrations in the cultures with PSPAs were significantly higher than in the controls (P acids, which may exert a better effect on intestinal microecology, suggesting that PSPAs may have prebiotic-like activity by generating SCFAs and modulating the intestinal microbiota, contributing to improvements in human health. PMID:26975278

  18. Activation of Intestinal Human Pregnane X Receptor Protects against Azoxymethane/Dextran Sulfate Sodium–Induced Colon Cancer

    Cheng, Jie; Fang, Zhong-Ze; Nagaoka, Kenjiro; Okamoto, Minoru; Qu, Aijuan; Tanaka, Naoki; Kimura, Shioko; Frank J. Gonzalez

    2014-01-01

    The role of intestinal human pregnane X receptor (PXR) in colon cancer was determined through investigation of the chemopreventive role of rifaximin, a specific agonist of intestinal human PXR, toward azoxymethane (AOM)/dextran sulfate sodium (DSS)–induced colon cancer. Rifaximin treatment significantly decreased the number of colon tumors induced by AOM/DSS treatment in PXR-humanized mice, but not wild-type or Pxr-null mice. Additionally, rifaximin treatment markedly increased the survival r...

  19. Comparative Genomics Analysis of Streptococcus Isolates from the Human Small Intestine Reveals their Adaptation to a Highly Dynamic Ecosystem

    Bogert, van den B.; Boekhorst, te J.; Herrmann, R.; Smid, E.J.; Zoetendal, E.G.; Kleerebezem, M.

    2013-01-01

    The human small-intestinal microbiota is characterised by relatively large and dynamic Streptococcus populations. In this study, genome sequences of small-intestinal streptococci from S. mitis, S. bovis, and S. salivarius species-groups were determined and compared with those from 58 Streptococcus s

  20. Expression of acyl-CoA synthetase 5 reflects the state of villus architecture in human small intestine

    Gassler, Nikolaus; Kopitz, Jürgen; Tehrani, Arman;

    2004-01-01

    -CoA synthetase 5 pattern correlate with conversion of intestinal epithelial cells to a gastric phenotype. These results suggest that deranged acyl-CoA synthetase 5 expression, synthesis, and activity are closely related to the state of villus architecture and epithelial homeostasis in human small intestine.......Several disorders of the small intestine are associated with disturbances in villus architecture. Thus, an understanding of the molecular mechanisms associated with the differentiation of villi represents an important step in the improvement of the understanding of small intestinal pathology...

  1. Human ghrelin mitigates intestinal injury and mortality after whole body irradiation in rats.

    Zhimin Wang

    Full Text Available Widespread use of ionizing radiation has led to the realization of the danger associated with radiation exposure. Although studies in radiation countermeasures were initiated a half century ago, an effective therapy for a radiomitigator has not been identified. Ghrelin is a gastrointestinal hormone, and administration of ghrelin is protective in animal models of injuries including radiation combined injury. To test whether ghrelin can be protective in whole body irradiaton (WBI alone, male Sprague Dawley (SD rats were treated with human ghrelin (20 nmol/rat daily for 6 days starting at either 24 h or 48 h after 10 Gray (Gy WBI and survival outcome was examined. The 10 Gy WBI produced a LD70/30 model in SD rats (30% survival in 30 days. The survival rate in rats treated with ghrelin starting at 24 h was significantly improved to 63% and when treatment was initiated at 48 h, the survival remained at 61%. At 7 days post WBI, plasma ghrelin was significantly reduced from the control value. Ghrelin treatment starting at 24 h after WBI daily for 6 days improved histological appearance of the intestine, reduced gut permeability, serum endotoxin levels and bacterial translocation to the liver by 38%, 42% and 61%, respectively at day 7 post WBI. Serum glucose and albumin were restored to near control levels with treatment. Ghrelin treatment also attenuated WBI-induced intestinal apoptosis by 62% as evidenced by TUNEL staining. The expression of anti-apoptotic cell regulator Bcl-xl was decreased by 38% in the vehicle and restored to 75% of the control with ghrelin treatment. Increased expression of intestinal CD73 and pAkt were observed with ghrelin treatment, indicating protection of the intestinal epithelium after WBI. These results indicate that human ghrelin attenuates intestinal injury and mortality after WBI. Thus, human ghrelin can be developed as a novel mitigator for radiation injury.

  2. Expression and significance of C-fos and proliferating cell nuclear antigen in the small intestinal tissue of human fetus

    Xue-hong LIU

    2011-02-01

    Full Text Available Objective To explore the expression rule of proliferating cell nuclear antigen(PCNA,C-fos proteins and apoptosis genes in the small intestinal tissue of human fetus.Methods At the second-to fourth-month of gestation,the expressions of cell proliferation and apoptosis were observed in 16 specimens of human fetal small intestinal tissue by using the immunohistochemical methods and terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling(TUNEL.Results At the second to fourth month of gestation,all the PCNA and C-fos proteins were positively expressed in the small intestinal tissues and cells of human fetus.With the increase in gestational period,the positive cell number and average intensity(AI of PCNA protein increased gradually(P < 0.01.The positive cell number of C-fos protein increased first,and then decreased,while the AI of C-fos protein stably increased in the small intestinal tissues and cells of human fetus(P < 0.01.At the second to fourth month of gestation,TUNEL positive cells were seen to distribute in each layer of the small intestinal tissues of human fetus.With the increase of age,all the positive cell number and AI of TUNEL positive cells showed a tendency of decrease following increase in the small intestine of human fetus(P < 0.01.Conclusions PCNA,C-fos and apoptosis gene participate in adjusting the growth and development of the cells and tissues in the small intestine of human fetus.In the third month of gestation,especially,proliferation and apoptosis are significantly increased in the small intestinal tissue of human fetus,which may be the key period of intestinal tissue development.

  3. Human intestinal metagenomics: state of the art and future

    Blottière, H.M.; Vos, de W.M.; Ehrlich, S.D.; Doré, J.

    2013-01-01

    Over the last few years our understanding of human biology has undergone profound transformation. The key role of the 'world inside us', namely the gut microbiota, once considered a forgotten organ, has been revealed, with strong impact on our health and well-being. The present review highlights the

  4. Extensive diversity of intestinal trichomonads of non-human primates

    Smejkalová, P.; Petrželková, Klára Judita; Pomajbíková, K.; Modrý, David; Čepička, I.

    2012-01-01

    Roč. 139, č. 1 (2012), s. 92-102. ISSN 0031-1820 R&D Projects: GA ČR GA206/09/0927 Institutional research plan: CEZ:AV0Z60930519; CEZ:AV0Z60220518 Keywords : trichomonads * Parabasalia * non-human primates * diversity * host specificity Subject RIV: EG - Zoology Impact factor: 2.355, year: 2012

  5. Human Intestinal Cells Modulate Conjugational Transfer of Multidrug Resistance Plasmids between Clinical Escherichia coli Isolates

    Machado, Ana Manuel; Sommer, Morten

    2014-01-01

    Bacterial conjugation in the human gut microbiota is believed to play a major role in the dissemination of antibiotic resistance genes and virulence plasmids. However, the modulation of bacterial conjugation by the human host remains poorly understood and there is a need for controlled systems to...... the intestinal cells exposed to bacteria leading to a two-fold reduction in conjugation efficiency. These results show that human gut epithelial cells can modulate bacterial conjugation and may have relevance to gene exchange in the gut....

  6. Cellular and molecular mechanism study of declined intestinal transit function in the cholesterol gallstone formation process of the guinea pig

    Fan, Ying; Wu, Shuodong; YIN, ZHENHUA; Fu, Bei-Bei

    2014-01-01

    The aim of this study was to investigate the cellular and molecular mechanisms of declined intestinal transit (IT) function in the cholesterol gallstone (CG) formation process. Forty guinea pigs were divided into an experimental group (EG) and a control group (CoG), and the reverse transcription-polymerase chain reaction (RT-PCR) was performed for the analysis of c-kit and stem cell factor (scf) mRNA expression in the small bowel. In addition, immunofluorescence staining and confocal laser mi...

  7. Metabolomics analysis of Cistus monspeliensis leaf extract on energy metabolism activation in human intestinal cells.

    Shimoda, Yoichi; Han, Junkyu; Kawada, Kiyokazu; Smaoui, Abderrazak; Isoda, Hiroko

    2012-01-01

    Energy metabolism is a very important process to improve and maintain health from the point of view of physiology. It is well known that the intracellular ATP production is contributed to energy metabolism in cells. Cistus monspeliensis is widely used as tea, spices, and medical herb; however, it has not been focusing on the activation of energy metabolism. In this study, C. monspeliensis was investigated as the food resources by activation of energy metabolism in human intestinal epithelial cells. C. monspeliensis extract showed high antioxidant ability. In addition, the promotion of metabolites of glycolysis and TCA cycle was induced by C. monspeliensis treatment. These results suggest that C. monspeliensis extract has an ability to enhance the energy metabolism in human intestinal cells. PMID:22523469

  8. Diagnosis of edema and inflammation in human intestines using ultrawideband radar

    Smith, Sonny; Narayanan, Ram M.; Messaris, Evangelos

    2015-05-01

    Human intestines are vital organs, which are often subjected to chronic issues. In particular, Crohn's disease is a bowel aliment resulting in inflammation along the lining of one's digestive tract. Moreover, such an inflammatory condition causes changes in the thickness of the intestines; and we posit induce changes in the dielectric properties detectable by radar. This detection hinges on the increase in fluid content in the afflicted area, which is described by effective medium approximations (EMA). In this paper, we consider one of the constitutive parameters (i.e. relative permittivity) of different human tissues and introduce a simple numerical, electromagnetic multilayer model. We observe how the increase in water content in one layer can be approximated to predict the effective permittivity of that layer. Moreover, we note trends in how such an accumulation can influence the total effective reflection coefficient of the multiple layers.

  9. Metabolomics Analysis of Cistus monspeliensis Leaf Extract on Energy Metabolism Activation in Human Intestinal Cells

    Yoichi Shimoda

    2012-01-01

    Full Text Available Energy metabolism is a very important process to improve and maintain health from the point of view of physiology. It is well known that the intracellular ATP production is contributed to energy metabolism in cells. Cistus monspeliensis is widely used as tea, spices, and medical herb; however, it has not been focusing on the activation of energy metabolism. In this study, C. monspeliensis was investigated as the food resources by activation of energy metabolism in human intestinal epithelial cells. C. monspeliensis extract showed high antioxidant ability. In addition, the promotion of metabolites of glycolysis and TCA cycle was induced by C. monspeliensis treatment. These results suggest that C. monspeliensis extract has an ability to enhance the energy metabolism in human intestinal cells.

  10. Localisation of hyaluronan in the human intestinal wall.

    Gerdin, B; Hällgren, R

    1991-01-01

    By using biotin labelled proteoglycan core protein and an avidin enzyme system, hyaluronan (hyaluronic acid) was visualised in specimens of human jejunum. Intense staining for hyaluronan was seen in the loose connective tissue of the villi and of lamina propria while the epithelial layer was unstained. The muscularis mucosae showed only faint staining. The accumulation of hyaluronan in the subepithelial layer of the jejunal mucosa indicates that the previously reported high jejunal secretion ...

  11. Human-derived probiotic Lactobacillus reuteri strains differentially reduce intestinal inflammation

    Liu, Yuying; Fatheree, Nicole Y.; Mangalat, Nisha; Rhoads, Jon Marc

    2010-01-01

    Lactobacillus reuteri (L. reuteri) is a probiotic that inhibits the severity of enteric infections and modulates the immune system. Human-derived L. reuteri strains DSM17938, ATCC PTA4659, ATCC PTA 5289, and ATCC PTA 6475 have demonstrated strain-specific immunomodulation in cultured monocytoid cells, but information about how these strains affect inflammation in intestinal epithelium is limited. We determined the effects of the four different L. reuteri strains on lipopolysaccharide (LPS)-in...

  12. Assessing DNA methylation in the developing human intestinal epithelium: potential link to inflammatory bowel disease

    Kraiczy, J; Nayak, K.(National Institute of Science Education and Research, Bhubaneswar, India); Ross, A.; Raine, T; Mak, T N; Gasparetto, M.; Cario, E; Rakyan, V; Heuschkel, R; Zilbauer, M.

    2015-01-01

    DNA methylation is one of the major epigenetic mechanisms implicated in regulating cellular development and cell-type-specific gene expression. Here we performed simultaneous genome-wide DNA methylation and gene expression analysis on purified intestinal epithelial cells derived from human fetal gut, healthy pediatric biopsies, and children newly diagnosed with inflammatory bowel disease (IBD). Results were validated using pyrosequencing, real-time PCR, and immunostaining. The functional impa...

  13. Profiles of the human intestinal microbiota during antibiotic perturbation and resilience

    Heinsen, Femke-Anouska

    2012-01-01

    Each human being harbors an individual and quite stable community of microorganisms within the gastrointestinal tract, whereas the highest density can be found in the large intestine. The ability of the microbiota to recover after an external perturbation is referred to as the resilience phenomenon. The aim of this study was the investigation of resilience of the colonic microbiota after a three day course of antibiotic perturbation with paromomycin and a subsequent therapy with probiotic ...

  14. A metagenomic β-glucuronidase uncovers a core adaptive function of the human intestinal microbiome

    Gloux, Karine; Berteau, Olivier; El oumami, Hanane; Béguet, Fabienne; Leclerc, Marion; Doré, Joël

    2010-01-01

    In the human gastrointestinal tract, bacterial β-D-glucuronidases (BG; E.C. 3.2.1.31) are involved both in xenobiotic metabolism and in some of the beneficial effects of dietary compounds. Despite their biological significance, investigations are hampered by the fact that only a few BGs have so far been studied. A functional metagenomic approach was therefore performed on intestinal metagenomic libraries using chromogenic glucuronides as probes. Using this strategy, 19 positive metagenomic cl...

  15. The human intestinal microbiota and its relationship to energy balance

    Bäckhed, Fredrik; Ley, Ruth E.; Sonnenburg, Justin L.; Jeffrey I Gordon

    2006-01-01

    The human gut microbiota can be pictured as a microbial organ placed within a host organ: it is composed of different cell lineages that have the capacity to communicate with one another and with the host. One major function of the microbiota is to degrade complex and otherwise indigestible components of the diet, such as polysaccharides. This process results in production of short-chain fatty acids that are readily absorbed and used as an energy source by the host. Studies in gnotobiotic mou...

  16. Transcriptome-wide Analysis Reveals Hallmarks of Human Intestine Development and Maturation In Vitro and In Vivo

    Stacy R. Finkbeiner; David R. Hill; Christopher H. Altheim; Priya H. Dedhia; Matthew J. Taylor; Yu-Hwai Tsai; Alana M. Chin; Maxime M. Mahe; Carey L. Watson; Jennifer J. Freeman; Roy Nattiv; Matthew Thomson; Ophir D. Klein; Noah F. Shroyer; Michael A. Helmrath

    2015-01-01

    Summary Human intestinal organoids (HIOs) are a tissue culture model in which small intestine-like tissue is generated from pluripotent stem cells. By carrying out unsupervised hierarchical clustering of RNA-sequencing data, we demonstrate that HIOs most closely resemble human fetal intestine. We observed that genes involved in digestive tract development are enriched in both fetal intestine and HIOs compared to adult tissue, whereas genes related to digestive function and Paneth cell host de...

  17. Human intestinal microbiota and diseases%人体肠道细菌群落与疾病

    翁幸鐾; 糜祖煌

    2011-01-01

    肠道定植有100万亿细菌,这占到了人体细菌总量的绝大多数.一旦肠道菌群失调,就会产生一系列疾病.本文介绍了人体肠道细菌群落异常与5种肠道疾病和5种肠道外疾病的关系,并推荐用益生菌和益生素来治疗人体肠道细菌群落异常.为了解人体肠道细菌群落和人体健康的关系,美国国立卫生研究院已启动了人类微生物组计划,欧洲委员会也正在资助人类肠道宏基因组学项目,而中国在此项目中亦取得了可喜进步.基于肠道宏基因组的个体化医疗时代已不再遥远.%Gut homes 100 trillion microorganisms-the vast majority of our complement of microbes.Shifts in the microbial species that reside in our intestines have been associated with a long list of pathologies.The review introduces a strong correlation between disrupted microbial composition and 5 kinds of gastrointestinal problems as well as 5 kinds of extra-gastrointestinal problems, and recommends probiotics and prebiotics to treat microbiota-associated illness.In order to find out the relationship between human intestinal microbiota and diseases, the National Institutes of Health launched the Human Microbiome Project at the end of 2007, and the European Commission is funding a related effort, called Metagenomics of the Human Intestinal Tract, in which China makes delightful progress.In sum, individual therapy based on intestinal metagenomics is coming.

  18. Supplementation transgenic cow's milk containing recombinant human lactoferrin enhances systematic and intestinal immune responses in piglets.

    Li, Qiuling; Hu, Wenping; Zhao, Jie; Wang, Jianwu; Dai, Yunping; Zhao, Yaofeng; Meng, Qingyong; Li, Ning

    2014-01-01

    Lactoferrin (LF) plays an important role in the body's immune system. However, the immunomodulatory effects of supplementation transgenic cow's milk containing recombinant human LF (rhLF) on the systemic and intestinal immune systems in infants remain unclear. Our laboratory has used genetic engineer to produce transgenic cow secreted rhLF. To assess the immune responses we took piglets as an animal model for infants. Eighteen piglets at 7 days of age were fed ordinary milk, 1:1 mix of ordinary and rhLF milk, or rhLF milk (LFM) for 30 days. The incidence of diarrhea in piglets in natural condition was observed. The protein abundances of immunoglobulin (Ig)G, IgA, IgM, IgE, histamine, interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12 interferon, tumor necrosis factor in the plasma, spleen or intestine were measured by enzyme-linked immunosorbent assay. Intestinal structure was assessed by hematoxylin and eosin. The mRNA levels of immune and allergy-related genes were measured by quantitative reverse transcription-polymerase chain reaction. The results showed that LFM-fed significantly reduced incidence of diarrhea, enhanced humoral immunity, T helper (Th) 1, and Th2 cell responses, improved the structure of the intestinal mucosal and did not induce food allergy. LFM increased mRNA levels of toll-like receptor 2 and nuclear factor-κB p65 and decreased that of FCεRI β. In conclusion, rhLF-enriched formula could improve systematic and intestinal immune responses and did not elicit food allergies in neonatal piglets. PMID:24420858

  19. Carrageenan Induces Cell Cycle Arrest in Human Intestinal Epithelial Cells in Vitro1–3

    Bhattacharyya, Sumit; Borthakur, Alip; Dudeja, Pradeep K.; Tobacman, Joanne K.

    2016-01-01

    Multiple studies in animal models have shown that the commonly used food additive carrageenan (CGN) induces inflammation and intestinal neoplasia. We performed the first studies to determine the effects of CGN exposure on human intestinal epithelial cells (IEC) in tissue culture and tested the effect of very low concentrations (1–10 mg/L) of undegraded, high-molecular weight CGN. These concentrations of CGN are less than the anticipated exposure of the human colon to CGN from the average Western diet. In the human colonic epithelial cell line NCM460 and in primary human colonic epithelial cells that were exposed to CGN for 1–8 d, we found increased cell death, reduced cell proliferation, and cell cycle arrest compared with unexposed control cells. After 6–8 d of CGN exposure, the percentage of cells reentering G0–G1 significantly decreased and the percentages of cells in S and G2-M phases significantly increased. Increases in activated p53, p21, and p15 followed CGN exposure, consistent with CGN-induced cell cycle arrest. Additional data, including DNA ladder, poly ADP ribose polymerase Western blot, nuclear DNA staining, and activities of caspases 3 and 7, indicated no evidence of increased apoptosis following CGN exposure and were consistent with CGN-induced necrotic cell death. These data document for the first time, to our knowledge, marked adverse effects of low concentrations of CGN on survival of normal human IEC and suggest that CGN exposure may have a role in development of human intestinal pathology. PMID:18287351

  20. Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of a health claim related to sugar beet fibre and decreasing intestinal transit time pursuant to Article 13(5) of Regulation (EC) No 1924/2006

    Tetens, Inge

    Following an application from Nordic Sugar A/S, submitted pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Denmark, the Panel on Dietetic Products, Nutrition and Allergies was asked to deliver an opinion on the scientific substantiation of a health claim...... weaknesses whereas one human intervention study showed no effect of the consumption of sugar beet fibre on decreasing intestinal (orofaecal) transit time. In weighing the evidence the Panel took into account that one human study from which conclusions could be drawn for the scientific substantiation of the...

  1. Human-derived probiotic Lactobacillus reuteri strains differentially reduce intestinal inflammation.

    Liu, Yuying; Fatheree, Nicole Y; Mangalat, Nisha; Rhoads, Jon Marc

    2010-11-01

    Lactobacillus reuteri (L. reuteri) is a probiotic that inhibits the severity of enteric infections and modulates the immune system. Human-derived L. reuteri strains DSM17938, ATCC PTA4659, ATCC PTA 5289, and ATCC PTA 6475 have demonstrated strain-specific immunomodulation in cultured monocytoid cells, but information about how these strains affect inflammation in intestinal epithelium is limited. We determined the effects of the four different L. reuteri strains on lipopolysaccharide (LPS)-induced inflammation in small intestinal epithelial cells and in the ileum of newborn rats. IPEC-J2 cells (derived from the jejunal epithelium of a neonatal piglet) and IEC-6 cells (derived from the rat crypt) were treated with L. reuteri. Newborn rat pups were gavaged cow milk formula supplemented with L. reuteri strains in the presence or absence of LPS. Protein and mRNA levels of cytokines and histological changes were measured. We demonstrate that even though one L. reuteri strain (DSM 17938) did not inhibit LPS-induced IL-8 production in cultured intestinal cells, all strains significantly reduced intestinal mucosal levels of KC/GRO (∼IL-8) and IFN-γ when newborn rat pups were fed formula containing LPS ± L. reuteri. Intestinal histological damage produced by LPS plus cow milk formula was also significantly reduced by all four strains. Cow milk formula feeding (without LPS) produced mild gut inflammation, evidenced by elevated mucosal IFN-γ and IL-13 levels, a process that could be suppressed by strain 17938. Other cytokines and chemokines were variably affected by the different strains, and there was no toxic effect of L. reuteri on intestinal cells or mucosa. In conclusion, L. reuteri strains differentially modulate LPS-induced inflammation. Probiotic interactions with both epithelial and nonepithelial cells in vivo must be instrumental in modulating intrinsic anti-inflammatory effects in the intestine. We suggest that the terms anti- and proinflammatory be used only

  2. Expression of Tn, sialosyl-Tn and T antigens in human foetal large intestine

    Barresi, G; Tuccari, G; Giuffrè, G.; Vitarelli, E.; Grosso, M.

    2009-01-01

    Tn, sialosyl-Tn and T antigens are simple mucintype carbohydrate antigens that may be expressed in human neoplasies due to alteration of the glycoprotein biosynthetic pathway. Utilising specific monoclonal antibodies (HB-Tn1, HB-STn1 and HB-T1), we have investigated the expression of these simple mucin-type carbohydrate antigens in large intestine of 8 human foetuses at early gestational age (9-10 weeks), obtained after therapeutic abortion. In all cases the expression of Tn antigen was mainl...

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

    Sumsakul, Wiriyaporn; Na-Bangchang, Kesara

    2016-03-01

    Plumbagin is the active compound isolated from plants used in traditional medicine for treatment of various diseases such as activities malaria, leishmaniasis, viral infections and cancers. The aim of the study was to investigate the permeability of plumbagin across Caco-2 (human epithelial colorectal adenocarcinoma) cell monolayer and its effects on the expression and function of P-glycoprotein. The integrity of Caco-2 cell monolayer was evaluated by measuring trans-epithelial electrical resistance and permeation (Papp) of Lucifer yellow across the cell monolayer. The effect of plumbagin on P-glycoprotein was detected by measuring its interference with the transport of the P-glycoprotein substrate (R123) and the effect on MDR-1 mRNA expression was detected by RT-PCR. The Papp of plumbagin (2-8 µM) for the apical to basolateral and basolateral to apical directions were 10.29-15.96 × 10(-6) and 7.40-9.02 × 10(-6) cm/s, respectively, with the efflux ratios of 0.57-0.73. Plumbagin is not either a substrate or inhibitor of P-glycoprotein. It did not interfere with the P-glycoprotein-mediated R123 transport across Caco-2 cell monolayer, as well as the function of P-glycoprotein and the expression of MDR-1 mRNA. Results suggest moderate permeability of plumbagin across the Caco-2 cell monolayer in both directions. The transport mechanism is likely to be a passive transport. PMID:26620575

  4. Radioprotection of the intestinal crypts of mice by recombinant human interleukin-1 alpha

    Recombinant human interleukin-1 alpha (rHIL-1 alpha or IL-1) protected the intestinal crypt cells of mice against X-ray-induced damage. The survival of crypt cells measured in terms of their ability to form colonies of regenerating duodenal epithelium in situ was increased when IL-1 was given either before or after irradiation. The maximum degree of radioprotection was seen when the drug was given between 13 and 25 h before irradiation. The IL-1 dose producing maximum protection was about 6.3 micrograms/kg. This is the first report indicating that the cytokine IL-1 has a radioprotective effect in the intestine. The finding suggests that IL-1 may be of potential value in preventing radiation injury to the gut in the clinic

  5. Studies on the determination of extracellular galactosyltransferase in human intestinal tissue

    The determination of extracellular galactosyl transferase (EC 2.4.1.38) activity in human intestinal tissue by assessment of the incorporation of label after incubation with UDP[3H]galactose was evaluated. Intestinal biopsy specimens were incubated with membrane-permeable L-[1-14C]fucose and non-permeable UDP-D-[6-3H]galactose (UDP[3H]Gal). Comparison of the amounts of 3H- and 14C-label incorporated into subcellular fractions showed uptake and incorporation of galactose formed by the hydrolysis of UDP[3H]Gal by brush-border enzymes. The results indicate that incorporation of galactose after incubation of the tissue with UDP[3H]Gal is not exclusively attributable to extracellular galactosyl transferase. (Auth.)

  6. A Human Breast Cell Model of Preinvasive to Invasive Transition

    Rizki, Aylin; Weaver, Valerie M.; Lee, Sun-Young; Rozenberg, Gabriela I.; Chin, Koei; Myers, Connie A.; Bascom, Jamie L.; Mott, Joni D.; Semeiks, Jeremy R.; Grate, Leslie R.; Mian, I. Saira; Borowsky, Alexander D; Jensen, Roy A; Idowu, Michael O.; Chen, Fanqing

    2008-01-01

    A crucial step in human breast cancer progression is the acquisition of invasiveness. There is a distinct lack of human cell culture models to study the transition from preinvasive to invasive phenotype as it may occur “spontaneously” in vivo. To delineate molecular alterations important for this transition, we isolated human breast epithelial cell lines that showed partial loss of tissue polarity in three-dimensional reconstituted basement membrane cultures. These cells remained noninvasive;...

  7. Commensal Streptococcus salivarius Modulates PPARγ Transcriptional Activity in Human Intestinal Epithelial Cells.

    Benoît Couvigny

    Full Text Available The impact of commensal bacteria in eukaryotic transcriptional regulation has increasingly been demonstrated over the last decades. A multitude of studies have shown direct effects of commensal bacteria from local transcriptional activity to systemic impact. The commensal bacterium Streptococcus salivarius is one of the early bacteria colonizing the oral and gut mucosal surfaces. It has been shown to down-regulate nuclear transcription factor (NF-кB in human intestinal cells, a central regulator of the host mucosal immune system response to the microbiota. In order to evaluate its impact on a further important transcription factor shown to link metabolism and inflammation in the intestine, namely PPARγ (peroxisome proliferator-activated receptor, we used human intestinal epithelial cell-lines engineered to monitor PPARγ transcriptional activity in response to a wide range of S. salivarius strains. We demonstrated that different strains from this bacterial group share the property to inhibit PPARγ activation independently of the ligand used. First attempts to identify the nature of the active compounds showed that it is a low-molecular-weight, DNase-, proteases- and heat-resistant metabolite secreted by S. salivarius strains. Among PPARγ-targeted metabolic genes, I-FABP and Angptl4 expression levels were dramatically reduced in intestinal epithelial cells exposed to S. salivarius supernatant. Both gene products modulate lipid accumulation in cells and down-regulating their expression might consequently affect host health. Our study shows that species belonging to the salivarius group of streptococci impact both host inflammatory and metabolic regulation suggesting a possible role in the host homeostasis and health.

  8. Commensal Streptococcus salivarius Modulates PPARγ Transcriptional Activity in Human Intestinal Epithelial Cells.

    Couvigny, Benoît; de Wouters, Tomas; Kaci, Ghalia; Jacouton, Elsa; Delorme, Christine; Doré, Joël; Renault, Pierre; Blottière, Hervé M; Guédon, Eric; Lapaque, Nicolas

    2015-01-01

    The impact of commensal bacteria in eukaryotic transcriptional regulation has increasingly been demonstrated over the last decades. A multitude of studies have shown direct effects of commensal bacteria from local transcriptional activity to systemic impact. The commensal bacterium Streptococcus salivarius is one of the early bacteria colonizing the oral and gut mucosal surfaces. It has been shown to down-regulate nuclear transcription factor (NF-кB) in human intestinal cells, a central regulator of the host mucosal immune system response to the microbiota. In order to evaluate its impact on a further important transcription factor shown to link metabolism and inflammation in the intestine, namely PPARγ (peroxisome proliferator-activated receptor), we used human intestinal epithelial cell-lines engineered to monitor PPARγ transcriptional activity in response to a wide range of S. salivarius strains. We demonstrated that different strains from this bacterial group share the property to inhibit PPARγ activation independently of the ligand used. First attempts to identify the nature of the active compounds showed that it is a low-molecular-weight, DNase-, proteases- and heat-resistant metabolite secreted by S. salivarius strains. Among PPARγ-targeted metabolic genes, I-FABP and Angptl4 expression levels were dramatically reduced in intestinal epithelial cells exposed to S. salivarius supernatant. Both gene products modulate lipid accumulation in cells and down-regulating their expression might consequently affect host health. Our study shows that species belonging to the salivarius group of streptococci impact both host inflammatory and metabolic regulation suggesting a possible role in the host homeostasis and health. PMID:25946041

  9. Splitting the scotoperiod: effects on feeding behaviour, intestinal fill and digestive transit time in broiler chickens

    Duve, Linda Rosager; Steenfeldt, Sanna; Thodberg, Karen;

    2011-01-01

    1. The aim of this study was to evaluate how splitting the dark period (scotoperiod) affects feeding behaviour and associated intestinal measures in broilers. 2. Ross 308 broilers were reared to 37 d in groups given either a daily 8-h continuous scotoperiod (DARK 8) or an intermittent light...... schedule with two equally spaced 4-h scotoperiods (DARK 4þ4), which yielded the same total duration of darkness per 24 h. 3. Feeding behaviour was recorded weekly from 24-h video recordings of 24 groups each of 64 birds. Empty intestinal weights as well as their contents were measured weekly at 4 time...... activity across the day. However, DARK 4þ4 had a higher feed intake and weight gain. The occurrence and severity of foot pad dermatitis was similar between treatments. 6. In conclusion, broilers modify their feeding behaviour according to the prevailing light schedule. Eight consecutive hours of darkness...

  10. Intestinal Coccidia

    MJ Ggaravi

    2007-01-01

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

  11. Mast cell expression of the serotonin1A receptor in guinea pig and human intestine.

    Wang, Guo-Du; Wang, Xi-Yu; Zou, Fei; Qu, Meihua; Liu, Sumei; Fei, Guijun; Xia, Yun; Needleman, Bradley J; Mikami, Dean J; Wood, Jackie D

    2013-05-15

    Serotonin [5-hydroxytryptamine (5-HT)] is released from enterochromaffin cells in the mucosa of the small intestine. We tested a hypothesis that elevation of 5-HT in the environment of enteric mast cells might degranulate the mast cells and release mediators that become paracrine signals to the enteric nervous system, spinal afferents, and secretory glands. Western blotting, immunofluorescence, ELISA, and pharmacological analysis were used to study expression of 5-HT receptors by mast cells in the small intestine and action of 5-HT to degranulate the mast cells and release histamine in guinea pig small intestine and segments of human jejunum discarded during Roux-en-Y gastric bypass surgeries. Mast cells in human and guinea pig preparations expressed the 5-HT1A receptor. ELISA detected spontaneous release of histamine in guinea pig and human preparations. The selective 5-HT1A receptor agonist 8-hydroxy-PIPAT evoked release of histamine. A selective 5-HT1A receptor antagonist, WAY-100135, suppressed stimulation of histamine release by 5-HT or 8-hydroxy-PIPAT. Mast cell-stabilizing drugs, doxantrazole and cromolyn sodium, suppressed the release of histamine evoked by 5-HT or 8-hydroxy-PIPAT in guinea pig and human preparations. Our results support the hypothesis that serotonergic degranulation of enteric mast cells and release of preformed mediators, including histamine, are mediated by the 5-HT1A serotonergic receptor. Association of 5-HT with the pathophysiology of functional gastrointestinal disorders (e.g., irritable bowel syndrome) underlies a question of whether selective 5-HT1A receptor antagonists might have therapeutic application in disorders of this nature. PMID:23518679

  12. Meta-analysis of the turnover of intestinal epithelia in preclinical animal species and humans.

    Darwich, Adam S; Aslam, Umair; Ashcroft, Darren M; Rostami-Hodjegan, Amin

    2014-12-01

    Due to the rapid turnover of the small intestinal epithelia, the rate at which enterocyte renewal occurs plays an important role in determining the level of drug-metabolizing enzymes in the gut wall. Current physiologically based pharmacokinetic (PBPK) models consider enzyme and enterocyte recovery as a lumped first-order rate. An assessment of enterocyte turnover would enable enzyme and enterocyte renewal to be modeled more mechanistically. A literature review together with statistical analysis was employed to establish enterocyte turnover in human and preclinical species. A total of 85 studies was identified reporting enterocyte turnover in 1602 subjects in six species. In mice, the geometric weighted combined mean (WX) enterocyte turnover was 2.81 ± 1.14 days (n = 169). In rats, the weighted arithmetic mean enterocyte turnover was determined to be 2.37 days (n = 501). Humans exhibited a geometric WX enterocyte turnover of 3.48 ± 1.55 days for the gastrointestinal epithelia (n = 265), displaying comparable turnover to that of cytochrome P450 enzymes in vitro (0.96-4.33 days). Statistical analysis indicated humans to display longer enterocyte turnover as compared with preclinical species. Extracted data were too sparse to support regional differences in small intestinal enterocyte turnover in humans despite being indicated in mice. The utilization of enterocyte turnover data, together with in vitro enzyme turnover in PBPK modeling, may improve the predictions of metabolic drug-drug interactions dependent on enzyme turnover (e.g., mechanism-based inhibition and enzyme induction) as well as absorption of nanoparticle delivery systems and intestinal metabolism in special populations exhibiting altered enterocyte turnover. PMID:25233858

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

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

    2005-01-01

    The intestinal alkaline phosphatase gene (ALPI) encodes a digestive brush-border enzyme, which is highly upregulated during small intestinal epithelial cell differentiation. To identify new putative promoter motifs responsible for the regulation of ALPI expression during differentiation of the...... of HNF-4alpha to stimulate the expression from the ALPI promoter was investigated in the nonintestinal Hela cell line. Cotransfection with an HNF-4alpha expression vector demonstrated a direct activation of the ALPI promoter through this -94 to -82 element. EMSA showed that HNF-4alpha from nuclear...... extracts of differentiated intestinal epithelial cells (Caco-2) bound with high affinity to the predicted HNF-4 binding site. A 521 bp promoter fragment containing the HNF-4 binding site demonstrated a differentiation-dependent increase in promoter activity in Caco-2 cells. The presence of the HNF-4...

  14. Beneficial effect of recombinant human growth hormone on the intestinal mucosa barrier of septic rats

    C. Yi

    2007-01-01

    Full Text Available The objective of the present study was to investigate the effects of recombinant human growth hormone (rhGH on the intestinal mucosa barrier of septic rats and explore its possible mechanism. Female Sprague-Dawley rats were randomized into three groups: control, Escherichia coli-induced sepsis (S and treatment (T groups. Groups S and T were subdivided into subgroups 1d and 3d, respectively. Expression of liver insulin-like growth factor-1 (IGF-1 mRNA, Bcl-2 and Bax protein levels and the intestinal Bax/Bcl-2 ratio, and plasma GH and IGF-1 levels were determined. Histological examination of the intestine was performed and bacterial translocation was determined. rhGH significantly attenuated intestinal mucosal injuries and bacterial translocation in septic rats, markedly decreased Bax protein levels, inhibited the decrease of Bcl-2 protein expression and maintained the Bax/Bcl-2 ratio in the intestine. rhGH given after sepsis significantly improved levels of plasma GH (T1d: 1.28 ± 0.24; T3d: 2.14 ± 0.48 µg/L vs S1d: 0.74 ± 0.12; S3d: 0.60 ± 0.18 µg/L; P < 0.05 and IGF-1 (T1d: 168.94 ± 65.67; T3d: 201.56 ± 64.98 µg/L vs S1d: 116.72 ± 13.96; S3d: 107.50 ± 23.53 µg/L; P < 0.05 and expression of liver IGF-1 mRNA (T1d: 0.98 ± 0.20; T3d: 1.76 ± 0.17 vs S1d: 0.38 ± 0.09; S3d: 0.46 ± 0.10; P < 0.05. These findings indicate that treatment with rhGH had beneficial effects on the maintenance of the integrity of the intestinal mucosa barrier in septic rats.

  15. Bovine and soybean milk bioactive compounds: Effects on inflammatory response of human intestinal Caco-2 cells.

    Calvello, Rosa; Aresta, Antonella; Trapani, Adriana; Zambonin, Carlo; Cianciulli, Antonia; Salvatore, Rosaria; Clodoveo, Maria Lisa; Corbo, Filomena; Franchini, Carlo; Panaro, Maria Antonietta

    2016-11-01

    In this study the effects of commercial bovine and soybean milks and their bioactive compounds, namely genistein, daidzein and equol, on the inflammatory responses induced by lipopolysaccharide (LPS) treatment of human intestinal Caco-2 cells were examined, in terms of nitric oxide (NO) release and inducible nitric oxide synthetase (iNOS) expression. Both milks and their bioactive compounds significantly inhibited, dose-dependently, the expression of iNOS mRNA and protein, resulting in a decreased NO production. The NF-κB activation in LPS-stimulated intestinal cells was also examined. In all cases we observed that cell pre-treatment before LPS activation inhibited the IkB phosphorylation. Accordingly, quantification of bioactive compounds by solid phase microextraction coupled with liquid chromatography has shown that they were absorbed, metabolized and released by Caco-2 cells in culture media. In conclusion, we demonstrated that milks and compounds tested are able to reduce LPS-induced inflammatory responses from intestinal cells, interfering with NF-kB dependent molecular mechanisms. PMID:27211648

  16. Poliovirus mutants excreted by a chronically infected hypogammaglobulinemic patient establish persistent infections in human intestinal cells

    Immunodeficient patients whose gut is chronically infected by vaccine-derived poliovirus (VDPV) may excrete large amounts of virus for years. To investigate how poliovirus (PV) establishes chronic infections in the gut, we tested whether it is possible to establish persistent VDPV infections in human intestinal Caco-2 cells. Four type 3 VDPV mutants, representative of the viral evolution in the gut of a hypogammaglobulinemic patient over almost 2 years [J. Virol. 74 (2000) 3001], were used to infect both undifferentiated, dividing cells, and differentiated, polarized enterocytes. A VDPV mutant excreted 36 days postvaccination by the patient was lytic in both types of intestinal cell cultures, like the parental Sabin 3 (S3) strain. In contrast, three VDPVs excreted 136, 442, and 637 days postvaccination, established persistent infections both in undifferentiated cells and in enterocytes. Thus, viral determinants selected between day 36 and 136 conferred on VDPV mutants the capacity to infect intestinal cells persistently. The percentage of persistently VDPV-infected cultures was higher in enterocytes than in undifferentiated cells, implicating cellular determinants involved in the differentiation of enterocytes in persistent VDPV infections. The establishment of persistent infections in enterocytes was not due to poor replication of VDPVs in these cells, but was associated with reduced viral adsorption to the cell surface

  17. Specific-sized hyaluronan fragments promote expression of human β-defensin 2 in intestinal epithelium.

    Hill, David R; Kessler, Sean P; Rho, Hyunjin K; Cowman, Mary K; de la Motte, Carol A

    2012-08-31

    Hyaluronan (HA) is a glycosaminoglycan polymer found in the extracellular matrix of virtually all mammalian tissues. Recent work has suggested a role for small, fragmented HA polymers in initiating innate defense responses in immune cells, endothelium, and epidermis through interaction with innate molecular pattern recognition receptors, such as TLR4. Despite these advances, little is known regarding the effect of fragmented HA at the intestinal epithelium, where numerous pattern recognition receptors act as sentinels of an innate defense response that maintains epithelial barrier integrity in the presence of abundant and diverse microbial challenges. Here we report that HA fragments promote expression of the innate antimicrobial peptide human β-defensin 2 (HβD2) in intestinal epithelial cells. Treatment of HT-29 colonic epithelial cells with HA fragment preparations resulted in time- and dose-dependent up-regulated expression of HβD2 protein in a fragment size-specific manner, with 35-kDa HA fragment preparations emerging as the most potent inducers of intracellular HβD2. Furthermore, oral administration of specific-sized HA fragments promotes the expression of an HβD2 ortholog in the colonic epithelium of both wild-type and CD44-deficient mice but not in TLR4-deficient mice. Together, our observations suggest that a highly size-specific, TLR4-dependent, innate defense response to fragmented HA contributes to intestinal epithelium barrier defense through the induction of intracellular HβD2 protein. PMID:22761444

  18. Exogenous HIV-1 Nef upsets the IFN-γ-induced impairment of human intestinal epithelial integrity.

    Maria Giovanna Quaranta

    Full Text Available BACKGROUND: The mucosal tissues play a central role in the transmission of HIV-1 infection as well as in the pathogenesis of AIDS. Despite several clinical studies reported intestinal dysfunction during HIV infection, the mechanisms underlying HIV-induced impairments of mucosal epithelial barrier are still unclear. It has been postulated that HIV-1 alters enterocytic function and HIV-1 proteins have been detected in several cell types of the intestinal mucosa. In the present study, we analyzed the effect of the accessory HIV-1 Nef protein on human epithelial cell line. METHODOLOGY/PRINCIPAL FINDINGS: We used unstimulated or IFN-γ-stimulated Caco-2 cells, as a model for homeostatic and inflamed gastrointestinal tracts, respectively. We investigated the effect of exogenous recombinant Nef on monolayer integrity analyzing its uptake, transepithelial electrical resistance, permeability to FITC-dextran and the expression of tight junction proteins. Moreover, we measured the induction of proinflammatory mediators. Exogenous Nef was taken up by Caco-2 cells, increased intestinal epithelial permeability and upset the IFN-γ-induced reduction of transepithelial resistance, interfering with tight junction protein expression. Moreover, Nef inhibited IFN-γ-induced apoptosis and up-regulated TNF-α, IL-6 and MIP-3α production by Caco-2 cells while down-regulated IL-10 production. The simultaneous exposure of Caco-2 cells to Nef and IFN-γ did not affect cytokine secretion respect to untreated cells. Finally, we found that Nef counteracted the IFN-γ induced arachidonic acid cascade. CONCLUSION/SIGNIFICANCE: Our findings suggest that exogenous Nef, perturbing the IFN-γ-induced impairment of intestinal epithelial cells, could prolong cell survival, thus allowing for accumulation of viral particles. Our results may improve the understanding of AIDS pathogenesis, supporting the discovery of new therapeutic interventions.

  19. Butyrate Produced by Commensal Bacteria Potentiates Phorbol Esters Induced AP-1 Response in Human Intestinal Epithelial Cells

    Nepelska, Malgorzata; Cultrone, Antonietta; Béguet-Crespel, Fabienne; Le Roux, Karine; Doré, Joël; Arulampalam, Vermulugesan; Blottière, Hervé M.

    2012-01-01

    The human intestine is a balanced ecosystem well suited for bacterial survival, colonization and growth, which has evolved to be beneficial both for the host and the commensal bacteria. Here, we investigated the effect of bacterial metabolites produced by commensal bacteria on AP-1 signaling pathway, which has a plethora of effects on host physiology. Using intestinal epithelial cell lines, HT-29 and Caco-2, stably transfected with AP-1-dependent luciferase reporter gene, we tested the effect...

  20. Metabolism of Kaempferia parviflora polymethoxyflavones by human intestinal bacterium Bautia sp. MRG-PMF1.

    Kim, Mihyang; Kim, Nayoung; Han, Jaehong

    2014-12-24

    Poylmethoxyflavones (PMFs) are major bioactive flavonoids, which exhibit various biological activities, such as anticancer effects. The biotransformation of PMFs and characterization of a PMF-metabolizing human intestinal bacterium were studied herein for the first time. Hydrolysis of aryl methyl ether functional groups by human fecal samples was observed from the bioconversion of various PMFs. Activity-guided screening for PMF-metabolizing intestinal bacteria under anaerobic conditions resulted in the isolation of a strict anaerobic bacterium, which was identified as Blautia sp. MRG-PMF1. The isolated MRG-PMF1 was able to metabolize various PMFs to the corresponding demethylated flavones. The microbial conversion of bioactive 5,7-dimethoxyflavone (5,7-DMF) and 5,7,4'-trimethoxyflavone (5,7,4'-TMF) was studied in detail. 5,7-DMF and 5,7,4'-TMF were completely metabolized to 5,7-dihydroxyflavone (chrysin) and 5,7,4'-trihydroxyflavone (apigenin), respectively. From a kinetics study, the methoxy group on the flavone C-7 position was found to be preferentially hydrolyzed. 5-Methoxychrysin, the intermediate of 5,7-DMF metabolism by Blautia sp. MRG-PMF1, was isolated and characterized by nuclear magnetic resonance spectroscopy. Apigenin was produced from the sequential demethylation of 5,7,4'-TMF, via 5,4'-dimethoxy-7-hydroxyflavone and 7,4'-dihydroxy-5-methoxyflavone (thevetiaflavone). Not only demethylation activity but also deglycosylation activity was exhibited by Blautia sp. MRG-PMF1, and various flavonoids, including isoflavones, flavones, and flavanones, were found to be metabolized to the corresponding aglycones. The unprecedented PMF demethylation activity of Blautia sp. MRG-PMF1 will expand our understanding of flavonoid metabolism in the human intestine and lead to novel bioactive compounds. PMID:25437273

  1. Generation of L-cells in mouse and human small intestine organoids

    Petersen, Natalia; Reimann, Frank; Bartfeld, Sina; Farin, Henner F.; Ringnalda, Femke C.; Vries, Robert G J; van den Brink, Stieneke; Clevers, Hans; Gribble, Fiona M.; de Koning, Eelco J. P.

    2013-01-01

    Upon a nutrient challenge, L-cells produce glucagon-like peptide 1 (GLP-1), a powerful stimulant of insulin release. Strategies to augment endogenous GLP-1 production include promoting L-cell differentiation and increasing L-cell number. Here we present a novel in vitro platform to generate functional L-cells from 3D cultures of mouse and human intestinal crypts. We show that short-chain fatty acids (SCFAs) selectively increase the number of L-cells resulting in an elevation of GLP-1 release....

  2. Combined Effects of Lipophilic Phycotoxins (Okadaic Acid, Azapsiracid-1 and Yessotoxin on Human Intestinal Cells Models

    Pierre-Jean Ferron

    2016-02-01

    Full Text Available Phycotoxins are monitored in seafood because they can cause food poisonings in humans. Phycotoxins do not only occur singly but also as mixtures in shellfish. The aim of this study was to evaluate the in vitro toxic interactions of binary combinations of three lipophilic phycotoxins commonly found in Europe (okadaic acid (OA, yessotoxin (YTX and azaspiracid-1 (AZA-1 using the neutral red uptake assay on two human intestinal cell models, Caco-2 and the human intestinal epithelial crypt-like cells (HIEC. Based on the cytotoxicity of individual toxins, we studied the interactions between toxins in binary mixtures using the combination index-isobologram equation, a method widely used in pharmacology to study drug interactions. This method quantitatively classifies interactions between toxins in mixtures as synergistic, additive or antagonistic. AZA-1/OA, and YTX/OA mixtures showed increasing antagonism with increasing toxin concentrations. In contrast, the AZA-1/YTX mixture showed increasing synergism with increasing concentrations, especially for mixtures with high YTX concentrations. These results highlight the hazard potency of AZA-1/YTX mixtures with regard to seafood intoxication.

  3. Combined Effects of Lipophilic Phycotoxins (Okadaic Acid, Azapsiracid-1 and Yessotoxin) on Human Intestinal Cells Models

    Ferron, Pierre-Jean; Dumazeau, Kevin; Beaulieu, Jean-François; Le Hégarat, Ludovic; Fessard, Valérie

    2016-01-01

    Phycotoxins are monitored in seafood because they can cause food poisonings in humans. Phycotoxins do not only occur singly but also as mixtures in shellfish. The aim of this study was to evaluate the in vitro toxic interactions of binary combinations of three lipophilic phycotoxins commonly found in Europe (okadaic acid (OA), yessotoxin (YTX) and azaspiracid-1 (AZA-1)) using the neutral red uptake assay on two human intestinal cell models, Caco-2 and the human intestinal epithelial crypt-like cells (HIEC). Based on the cytotoxicity of individual toxins, we studied the interactions between toxins in binary mixtures using the combination index-isobologram equation, a method widely used in pharmacology to study drug interactions. This method quantitatively classifies interactions between toxins in mixtures as synergistic, additive or antagonistic. AZA-1/OA, and YTX/OA mixtures showed increasing antagonism with increasing toxin concentrations. In contrast, the AZA-1/YTX mixture showed increasing synergism with increasing concentrations, especially for mixtures with high YTX concentrations. These results highlight the hazard potency of AZA-1/YTX mixtures with regard to seafood intoxication. PMID:26907345

  4. Naturally occurring products of proglucagon 111-160 in the porcine and human small intestine

    Buhl, T; Thim, L; Kofod, Hans;

    1988-01-01

    proglucagon (proglucagon 111-160) using radioimmunoassays against proglucagon 111-123 and 126-160. Two peptides were isolated from acid ethanol extracts of porcine ileal mucosa and sequenced: one corresponding to proglucagon 126-158 and one probably corresponding to proglucagon 111-158. By comparing human and...... porcine proglucagon sequences, Ala117 is replaced by Thr, and Ile138, Ala144, Ile152 and Gln153 are replaced by Val, Thr, Leu, and His. By gel filtration and radioimmunoassay of intestinal extracts it was established that a large part of porcine and virtually all of human proglucagon are processed to...... release proglucagon 111-123 (designated spacer peptide 2), which, like proglucagon 126-158 must be considered a potential hormonal entity. By isocratic high pressure liquid chromatography human spacer peptide 2 was indistinguishable from synthetic proglucagon 111-122 amide, suggesting that this is the...

  5. Radiolabeled keratin: an undigestible marker for gastro-intestinal transit investigations

    A new marker for undigestible food is described in this paper. Labeling of keratin fibers with radioactive chromium 51 was operated by a simple process. A 90 % labeling efficiency was obtained. Assessment of in vitro chromium binding stability was performed by incubating fibers in different solutions (24 hours, 370C). Remaining activity on fibers was found to be 92+-2% in a pepsin solution, and 97+-1% in a pancreatic extract solution. Acid or basic solutions (pH 1 to pH 11) did not yield significant elution. In Man, scintigraphic views displayed a focal distribution of the radioactivity in the digestive tractus. Patient's irradiation during such an exploration was estimated by dosimetric calculation and found to be acceptable. Scintigraphic survey of fibers progression was possible throughout the whole digestive tractus, particularly in the intestine. This marker should become mainly interesting for intestinal studies, since it is one of the only two undigestible markers, with radiolabeled alpha-cellulose. Properties related to its original structure, and advantages of a simple labeling process should be valuable in a promizing way of exploration

  6. Endoscopic ultrasonography: Transition towards the future of gastro-intestinal diseases.

    De Lisi, Stefania; Giovannini, Marc

    2016-02-01

    Endoscopic ultrasonography (EUS) is a technique with an established role in the diagnosis and staging of gastro-intestinal tumors. In recent years, the spread of new devices dedicated to tissue sampling has improved the diagnostic accuracy of EUS fine-needle aspiration. The development of EUS-guided drainage of the bilio-pancreatic region and abdominal fluid collections has allowed EUS to evolve into an interventional tool that can replace more invasive procedures. Emerging techniques applying EUS in pancreatic cancer treatment and in celiac neurolysis have been described. Recently, confocal laser endomicroscopy has been applied to EUS as a promising technique for the in vivo histological diagnosis of gastro-intestinal, bilio-pancreatic and lymph node lesions. In this state-of-the-art review, we report the most recent data from the literature regarding EUS devices, interventional EUS, EUS-guided confocal laser endomicroscopy and EUS pancreatic cancer treatment, and we also provide an overview of their principles, clinical applications and limitations. PMID:26855537

  7. Comparative Study on Cancer Cell Apoptosis between Gastric and Intestinal-type Human Gastric Carcinoma

    2006-01-01

    Apoptosis of cancer cells between the gastric and intestinal-type human gastric carcinoma were compared in terms of the expression of oncogene MDM2 and CD68, the histological types, the infiltration depth, and lymph node metastasis. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay was employed to stain apoptotic cells.Histochemical method(AB-PAS) was applied to stain mucus that is neutral or acidic in nature. Immunohistochemical method (SABC) was used to detect expression of MDM2 and CD6. The results showed that the mean apoptosis index (AI) of total 48 cases was 8.60±2.60. AI in the 30 intestinal type cases was significantly higher than that in the 18 gastric type cases (t=4.67, P<0.01). In the 30intestinal type cases, the spontaneous apoptosis index of MDM2 negative cases was significantly higher than that of the positive cases (t=7.16, P<0.01). And in the 18 gastric type cases, the same result was found. (t=11.39, P<0.01). The MDM2 positive ratio in gastric type cases was higher than that in intestinal type cases (x2=4.68, P<0.05). There is no significant difference in AI between cases of lymph node metastasis and non-metastasis cases in intestinal type cases (t=0.26, P>0.05). But in the gastric type cases, a significant difference existed (t=5.87, P<0.01). A significant difference in lymph node metastasis ratio was found between the two gastric carcinoma types (x2=4.48, P<0.05).The CD68 expression ratio in the 30 intestinal type cases was much lower than that in the 18 gastric type cases (t=4.29, P<0.01). AI of 25 MDM2-positive cases was much lower than that of the 23MDM2-negative cases (t=7.80, P<0.01). CD68 positive ratio in the 25 MDM2-negative cases was much lower than that in the 23 negative cases. The difference was statistically significant (t=10.90,P<0.01). Except for few cells scattering within the cancer nest, most CD68 positive cells infiltrated in the interstitium around the cancer

  8. A comparative analysis of the intestinal metagenomes present in guinea pigs (Cavia porcellus) and humans (Homo sapiens)

    Hildebrand, Falk; Ebersbach, Tine; Nielsen, Henrik Bjørn;

    2012-01-01

    Background: Guinea pig (Cavia porcellus) is an important model for human intestinal research. We have characterized the faecal microbiota of 60 guinea pigs using Illumina shotgun metagenomics, and used this data to compile a gene catalogue of its prevalent microbiota. Subsequently, we compared...... the guinea pig microbiome to existing human gut metagenome data from the MetaHIT project. Results: We found that the bacterial richness obtained for human samples was lower than for guinea pig samples. The intestinal microbiotas of both species were dominated by the two phyla Bacteroidetes and Firmicutes...

  9. Receptor-Mediated Transcytosis of Leptin through Human Intestinal Cells In Vitro

    Émile Levy

    2010-01-01

    Full Text Available Gastric Leptin is absorbed by duodenal enterocytes and released on the basolateral side towards the bloodstream. We investigated in vitro some of the mechanisms of this transport. Caco-2/15 cells internalize leptin from the apical medium and release it through transcytosis in the basal medium in a time- temperature-dependent and saturable fashion. Leptin receptors are revealed on the apical brush-border membrane of the Caco-2 cells. RNA-mediated silencing of the receptor led to decreases in the uptake and basolateral release. Leptin in the basal medium was found bound to the soluble form of its receptor. An inhibitor of clathrin-dependent endocytosis (chlorpromazine decreased leptin uptake. Confocal immunocytochemistry and the use of brefeldin A and okadaic acid revealed the passage of leptin through the Golgi apparatus. We propose that leptin transcytosis by intestinal cells depends on its receptor, on clathrin-coated vesicles and transits through the Golgi apparatus.

  10. A cost-effective system for differentiation of intestinal epithelium from human induced pluripotent stem cells.

    Ogaki, Soichiro; Morooka, Mayu; Otera, Kaito; Kume, Shoen

    2015-01-01

    The human intestinal epithelium is a useful model for pharmacological studies of absorption, metabolism, drug interactions, and toxicology, as well as for studies of developmental biology. We established a rapid and cost effective system for differentiation of human induced pluripotent stem (iPS) cells into definitive endoderm (DE) cells. In the presence of dimethyl sulfoxide (DMSO), a low concentration of Activin at 6.25 ng/ml is sufficient to give a similar differentiation efficiency with that using Activin at 100 ng/ml at the presence of Wnt activator. In the presence of DMSO, Activin at low concentration triggered hiPS cells to undergo differentiation through G1 arrest, reduce apoptosis, and potentiate activation of downstream targets, such as SMAD2 phosphorylation and SOX17 expression. This increased differentiation into CDX2 + SOX17 + DE cells. The present differentiation procedure therefore permits rapid and efficient derivation of DE cells, capable of differentiating into intestinal epithelium upon BIO and DAPT treatment and of giving rise to functional cells, such as enterocytes. PMID:26616277

  11. Sugars increase non-heme iron bioavailability in human epithelial intestinal and liver cells.

    Tatiana Christides

    Full Text Available Previous studies have suggested that sugars enhance iron bioavailability, possibly through either chelation or altering the oxidation state of the metal, however, results have been inconclusive. Sugar intake in the last 20 years has increased dramatically, and iron status disorders are significant public health problems worldwide; therefore understanding the nutritional implications of iron-sugar interactions is particularly relevant. In this study we measured the effects of sugars on non-heme iron bioavailability in human intestinal Caco-2 cells and HepG2 hepatoma cells using ferritin formation as a surrogate marker for iron uptake. The effect of sugars on iron oxidation state was examined by measuring ferrous iron formation in different sugar-iron solutions with a ferrozine-based assay. Fructose significantly increased iron-induced ferritin formation in both Caco-2 and HepG2 cells. In addition, high-fructose corn syrup (HFCS-55 increased Caco-2 cell iron-induced ferritin; these effects were negated by the addition of either tannic acid or phytic acid. Fructose combined with FeCl3 increased ferrozine-chelatable ferrous iron levels by approximately 300%. In conclusion, fructose increases iron bioavailability in human intestinal Caco-2 and HepG2 cells. Given the large amount of simple and rapidly digestible sugars in the modern diet their effects on iron bioavailability may have important patho-physiological consequences. Further studies are warranted to characterize these interactions.

  12. Expression of Tn, sialosyl-Tn and T antigens in human foetal large intestine

    G Barresi

    2009-12-01

    Full Text Available Tn, sialosyl-Tn and T antigens are simple mucintype carbohydrate antigens that may be expressed in human neoplasies due to alteration of the glycoprotein biosynthetic pathway. Utilising specific monoclonal antibodies (HB-Tn1, HB-STn1 and HB-T1, we have investigated the expression of these simple mucin-type carbohydrate antigens in large intestine of 8 human foetuses at early gestational age (9-10 weeks, obtained after therapeutic abortion. In all cases the expression of Tn antigen was mainly localised as a thin rim at the cell membrane and occasionally in the supranuclear region of epithelial cells, while sialosyl-Tn antigen was documented in some goblet cell vacuoles and occasionally in the cytoplasm of columnar cells. T antigen was not expressed in any case. These results indicate that Tn and sialosyl-Tn antigens are expressed as early as nine weeks of gestation, further supporting the notion that they may be considered as oncodevelopmental cancerassociated antigens in the large intestine.

  13. Isolation and Identification of Intestinal CYP3A Inhibitors from Cranberry (Vaccinium macrocarpon) using Human Intestinal Microsomes

    Kim, Eunkyung; Sy-Cordero, Arlene; Graf, Tyler N.; Brantley, Scott J; Paine, Mary F.; Oberlies, Nicholas H

    2010-01-01

    Cranberry juice is used routinely, especially among women and the elderly, to prevent and treat urinary tract infections. These individuals are likely to be taking medications concomitantly with cranberry juice, leading to concern about potential drug-dietary substance interactions, particularly in the intestine, which, along with the liver, is rich in expression of the prominent drug metabolizing enzyme, cytochrome P450 3A (CYP3A). Using a systematic in vitro-in vivo approach, a cranberry ju...

  14. Contributions of microbiome and mechanical deformation to intestinal bacterial overgrowth and inflammation in a human gut-on-a-chip.

    Kim, Hyun Jung; Li, Hu; Collins, James J; Ingber, Donald E

    2016-01-01

    A human gut-on-a-chip microdevice was used to coculture multiple commensal microbes in contact with living human intestinal epithelial cells for more than a week in vitro and to analyze how gut microbiome, inflammatory cells, and peristalsis-associated mechanical deformations independently contribute to intestinal bacterial overgrowth and inflammation. This in vitro model replicated results from past animal and human studies, including demonstration that probiotic and antibiotic therapies can suppress villus injury induced by pathogenic bacteria. By ceasing peristalsis-like motions while maintaining luminal flow, lack of epithelial deformation was shown to trigger bacterial overgrowth similar to that observed in patients with ileus and inflammatory bowel disease. Analysis of intestinal inflammation on-chip revealed that immune cells and lipopolysaccharide endotoxin together stimulate epithelial cells to produce four proinflammatory cytokines (IL-8, IL-6, IL-1β, and TNF-α) that are necessary and sufficient to induce villus injury and compromise intestinal barrier function. Thus, this human gut-on-a-chip can be used to analyze contributions of microbiome to intestinal pathophysiology and dissect disease mechanisms in a controlled manner that is not possible using existing in vitro systems or animal models. PMID:26668389

  15. Nitric oxide mediates increased P-glycoprotein activity in interferon-{gamma}-stimulated human intestinal cells.

    Dixit, Santosh G; Zingarelli, Basilia; Buckley, Donna J; Buckley, Arthur R; Pauletti, Giovanni M

    2005-03-01

    Patients with refractory inflammatory bowel disease (IBD) exhibit increased expression of intestinal P-glycoprotein (P-gp) as well as elevated luminal IFN-gamma and nitric oxide (NO) levels. Using the in vitro Caco-2 cell culture model, we investigated whether these pathological mediators associated with the etiology of IBD affect functional activity of intestinal efflux systems. IFN-gamma reduced cellular uptake of cyclosporin A (CysA) but not methotrexate (MTX) in a time- and concentration-dependent manner. Simultaneously, P-gp expression increased by approximately twofold. Coincubation with the inducible NO synthase inhibitor l-N(6)-(1-iminoethyl)lysine (l-NIL) dramatically reduced production of intracellular NO in response to IFN-gamma stimulus. The presence of l-NIL also abrogated the cytokine-mediated increase in P-gp expression and function suggesting that NO is required for IFN-gamma-mediated activation of this efflux system. Exposure of Caco-2 cells to the chemical NO donor S-nitroso-N-acetylpenicillamine (SNAP) produced a concentration-dependent decrease in intracellular CysA accumulation that was paralleled by an increase in P-gp expression. Both IFN-gamma and SNAP enhanced DNA binding of NF-kappaB, whereas inclusion of l-NIL dramatically decreased this cytokine-induced effect on NF-kappaB binding. These results suggest that NO mediates IFN-gamma-induced increase in expression and function of intestinal P-gp in the human Caco-2 cell culture model by altering DNA binding of NF-kappaB, which may enhance transcription of the ABCB1 gene encoding for this efflux system. PMID:15486347

  16. Intestinal steroidogenesis.

    Bouguen, Guillaume; Dubuquoy, Laurent; Desreumaux, Pierre; Brunner, Thomas; Bertin, Benjamin

    2015-11-01

    Steroids are fundamental hormones that control a wide variety of physiological processes such as metabolism, immune functions, and sexual characteristics. Historically, steroid synthesis was considered a function restricted to the adrenals and the gonads. In the past 20 years, a significant number of studies have demonstrated that steroids could also be synthesized or metabolized by other organs. According to these studies, the intestine appears to be a major source of de novo produced glucocorticoids as well as a tissue capable of producing and metabolizing sex steroids. This finding is based on the detection of steroidogenic enzyme expression as well as the presence of bioactive steroids in both the rodent and human gut. Within the intestinal mucosa, the intestinal epithelial cell layer is one of the main cellular sources of steroids. Glucocorticoid synthesis regulation in the intestinal epithelial cells is unique in that it does not involve the classical positive regulator steroidogenic factor-1 (SF-1) but a closely related homolog, namely the liver receptor homolog-1 (LRH-1). This local production of immunoregulatory glucocorticoids contributes to intestinal homeostasis and has been linked to pathophysiology of inflammatory bowel diseases. Intestinal epithelial cells also possess the ability to metabolize sex steroids, notably estrogen; this mechanism may impact colorectal cancer development. In this review, we contextualize and discuss what is known about intestinal steroidogenesis and regulation as well as the key role these functions play both in physiological and pathological conditions. PMID:25560486

  17. Human intestinal parasites in the past: new findings and a review

    Marcelo Luiz Carvalho Gonçalves

    2003-01-01

    Full Text Available Almost all known human specific parasites have been found in ancient feces. A review of the paleoparasitological helminth and intestinal protozoa findings available in the literature is presented. We also report the new paleoparasitologic findings from the examination performed in samples collected in New and Old World archaeological sites. New finds of ancylostomid, Ascaris lumbricoides, Trichuris trichiura, Enterobius vermicularis, Trichostrongylus spp., Diphyllobothrium latum, Hymenolepis nana and Acantocephalan eggs are reported. According to the findings, it is probable that A. lumbricoides was originally a human parasite. Human ancylostomids, A. lumbricoides and T. trichiura, found in the New World in pre-Columbian times, have not been introduced into the Americas by land via Beringia. These parasites could not supported the cold climate of the region. Nomadic prehistoric humans that have crossed the Bering Land Bridge from Asia to the Americas in the last glaciation, probably during generations, would have lost these parasites, which life cycles need warm temperatures in the soil to be transmitted from host to host. Alternative routes are discussed for human parasite introduction into the Americas.

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

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

    2013-01-01

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

  19. Vitamin A metabolism in the human intestinal Caco-2 cell line

    The human intestinal Caco-2 cell line, described as enterocyte-like in a number of studies, was examined for its ability to carry out the metabolism of vitamin A normally required in the absorptive process. Caco-2 cells contained cellular retinol-binding protein II, a protein which is abundant in human villus-associated enterocytes and may play an important role in the absorption of vitamin A. Microsomal preparations from Caco-2 cells contained retinal reductase, acyl-CoA-retinol acyltransferase (ARAT), and lecithin-retinol acyltransferase (LRAT) activites, which have previously been proposed to be involved in the metabolism of dietary vitamin A in the enterocyte. When intact Caco-2 cells were provided with β-carotene, retinyl acetate, or retinyl acetate, or retinol, synthesis of retinyl palmitoleate, oleate, palmitate, and small amounts of stearate resulted. However, exogenous retinyl palmitate or stearate was not used by Caco-2 cells as a source of retinol for ester synthesis. While there was a disproportionate synthesis of monoenoic fatty acid esters of retinol in Caco-2 cells compared to the retinyl esters typically found in human chylomicrons or the esters normally synthesized in rat intestine, the pattern was consistent with the substantial amount of unsaturated fatty acids, particularly 18:1 and 16:1, found in the sn-1 position of Caco-2 microsomal phosphatidylcholine, the fatty acyl donor for LRAT. Both ARAT and LRAT have been proposed to be responsible for retinyl ester synthesis in the enterocyte. These data suggest the LRAT may be the physiologically important enzyme for the esterification of retinol in Caco-2 cells

  20. Partial Characterization of Bacteriocins Produced by Two New Enterococcus faecium Isolated from Human Intestine.

    Turgis, Mélanie; Vu, Khanh Dang; Lacroix, Monique

    2013-06-01

    This study aimed at characterizing two novel bacteriocin-producing enterococcal strains isolated from human intestine. A total of 200 lactic acid bacteria were isolated from a woman stool sample. Two of them were selected for characterization due to their high antimicrobial activity against five strains of Listeria monocytogenes. The selected bacteria were identified as two different strains of Enterococcus faecium and designated MT 104 and MT 162. The bacteriocins produced by MT 104 and MT 162 were stable at different pH ranging from 2 to 11 and were active after different treatments such as heat, enzymes, detergents, and γ-irradiation. The two isolated strains exhibited some probiotic properties such as survival in simulated gastric fluid and intestinal fluid, lack of expression of bile salt hydrolase or hemolytic activity, adhesion to Caco-2 cells efficiently, and sensitivity to clinical antimicrobial agents. Thus, the two isolated strains of E. faecium could become new probiotic bacteria and their bacteriocins could be used for controlling L. monocytogenes in combination with irradiation for food preservation. PMID:26782736

  1. Study of opportunistic intestinal parasitic infections in human immunodeficiency virus/acquired immunodeficiency syndrome patients

    Manish Kumar Mathur

    2013-01-01

    Full Text Available Introduction: Intestinal parasites predominantly coccidian parasites are a common cause for diarrhea in human immunodeficiency virus (HIV-positive patients. Materials and Methods: The study was conducted during January 2009-December 2010. A total of 1,088 stool samples from 544 seropositive HIV positive cases were examined microscopically for ova and cyst using wet mount preparations and stained smears. Out of 544 patients, 343 had prolonged diarrhea for more than 4 weeks, 57 had acute diarrhea of lesser than 7 days and 144 were asymptomatic cases who attended out-patient department; included in this study after taking consent from patients. Enteric pathogens were detected in 274 (50.36% of the 544 patients. Results and Conclusions: The parasites identified were Cryptosporidium (135, Isospora belli (42, Cyclospora (12, Microsporidia (02, Entamoeba histolytica (49, Hookworm (34. Intestinal parasites in chronic diarrhea were significantly higher than the acute diarrhea (63.05% vs. 7.35%; P < 0.05. Parasitic pathogens were frequently associated with HIV-positive patients with diarrhea in Western India. Stools of all HIV-positive patients with diarrhea should thoroughly be investigated to identify etiologic agents for proper management.

  2. Metabolic activation of lignans to estrogenic and antiestrogenic substances by human intestinal bacteria

    GAO, Jiang Jing; Hattori, Masao

    2005-01-01

    ヒト腸内細菌は広く自然界に存在する植物エストロゲンの前駆体の代謝活性化に必須である。本総説ではin vitroの実験に基づいた植物エストロゲン前駆体secoisolariciresinol diglucoside (SDG), arctiin, pinoresinol diglucoside (PDG)やそれらのアグリコンの動物リグナン, enterodiol (END), enterolactone (ENL)への変換に関する最近の研究成果を概説している。また, これら関連反応に関与する腸内細菌の単離や性質についても言及している。The role of human intestinal bacteria is indispensable for the metabolic activation of phytoestrogenic precursor lignans. This review summarized recent researches on the in vitro intestinal bacteria transformation of lignan prec...

  3. Glutamine and recombinant human growth hormone protect intestinal barrier function following portal hypertension surgery

    Zhao-Feng Tang; Yun-Biao Ling; Nan Lin; Zheng Hao; Rui-Yun Xu

    2007-01-01

    AIM: To evaluate the effects of combined treatment of glutamine (Gln) and recombinant human growth hormone(rhGH) on intestinal barrier function following portal hypertension surgery.METHODS: This study was designed as a prospective,randomized and controlled clinical trial. Forty two patients after portal hypertension surgery were randomly assigned into 2 groups: control group (n = 20) and supplemental group (adding Gin and rhGH, n = 22). Every patient received isocaloric and isonitrogenous standard total parenteral nutrition (TPN) starting 3 d after surgery for 7 d. Blood samples were obtained before surgery and at the 3rd and 10th day postoperatively. Host immunity was evaluated by measuring levels of CD4, CD8, CD4/CD8, IgG, IgM and IgA, and the inflammatory responses were determined by assessing IL-2, TNF-α and C-reactive protein (CRP) levels. Intestinal permeability and integrity was evaluated by L/M test and histological examination, respectively.RESULTS: On postoperative d 10, CD4, CD4/CD8, IgG and IL-2 levels in supplemental group were significantly higher than those in control group (33.7 ± 5.5 vs 31.0± 5.4, P < 0.05, (1.17 ± 0.32 vs 1.05 ± 0.15, P < 0.05,13.94 ± 1.09 vs 12.33±1.33, P < 0.05, and 368.12± 59.25 vs 318.12 ± 45.65, P < 0.05, respectively),whereas the increase in serum TNF-α concentration was significantly reduced (41.02 ± 27.56 vs 160.09 ± 35.17,P < 0.05). The increase in L/M ratio was significantly lower in the supplemental group than in the control group (0.0166 ± 0.0017 vs 0.0339 ± 0.0028, P < 0.05).Moreover, mucosal integrity in the supplemental group was better than in the control group.CONCLUSION: Postoperative administration of TPN supplemented with Gin and rhGH in patients after portal hypertension surgery improves immune function,modulates inflammatory response, prevents the intestinal mucous membrane from atrophy and preserves intestinal integrity.

  4. Functional Comparison of Human Colonic Carcinoma Cell Lines and Primary Small Intestinal Epithelial Cells for Investigations of Intestinal Drug Permeability and First-Pass Metabolism.

    Yamaura, Yoshiyuki; Chapron, Brian D; Wang, Zhican; Himmelfarb, Jonathan; Thummel, Kenneth E

    2016-03-01

    To further the development of a model for simultaneously assessing intestinal absorption and first-pass metabolism in vitro, Caco-2, LS180, T84, and fetal human small intestinal epithelial cells (fSIECs) were cultured on permeable inserts, and the integrity of cell monolayers, CYP3A4 activity, and the inducibility of enzymes and transporters involved in intestinal drug disposition were measured. Caco-2, T84, and fSIECs all formed tight junctions, as assessed by immunofluorescence microscopy for zonula occludens-1, which was well organized into circumscribing strands in T84, Caco-2, and fSIECs but was diffuse in LS180 cells. The transepithelial electrical resistance value for LS180 monolayers was lower than that for Caco-2, T84, and fSIECs. In addition, the apical-to-basolateral permeability of the paracellular marker Lucifer yellow across LS180 monolayers was greater than in fSIECs, T84, and Caco-2 monolayers. The transcellular marker propranolol exhibited similar permeability across all cells. With regard to metabolic capacity, T84 and LS180 cells showed comparable basal midazolam hydroxylation activity and was inducible by rifampin and 1α,25(OH)2D3 in LS180 cells, but only marginally so in T84 cells. The basal CYP3A4 activity of fSIECs and Caco-2 cells was much lower and not inducible. Interestingly, some of the drug transporters expressed in LS180 and Caco-2 cells were induced by either 1α,25(OH)2D3 or rifampin or both, but effects were limited in the other two cell lines. These results suggest that none of the cell lines tested fully replicated the drug disposition properties of the small intestine and that the search for an ideal screening tool must continue. PMID:26700954

  5. Human capital, Demographic Transition and Economic Growth

    Haitham Issa

    2003-01-01

    This paper extends the literature on economic growth and demographic change by developing a neo-classical model of endogenous growth in which both economic and demographic outcomes are jointly determined. The key point in this model is the endogenisation of child mortality rate by linking it to parents¡¯ human capital, defined in a broad sense to include both education and health. The numerical simulation of this model confirms that as economic development takes place there will be a decline ...

  6. A Monoclonal Antibody to the Amebic Lipophosphoglycan-Proteophosphoglycan Antigens Can Prevent Disease in Human Intestinal Xenografts Infected with Entamoeba histolytica

    Zhang, Zhi; Duchêne, Michael; Stanley, Samuel L.

    2002-01-01

    Entamoeba histolytica trophozoites are covered by lipophosphoglycan-peptidoglycan molecules which may be key virulence factors. We found that pretreatment of severe combined immunodeficient mice bearing human intestinal xenografts with a monoclonal antibody to the amebic lipophosphoglycan-peptidoglycan molecules can prevent or significantly reduce the human intestinal inflammation and tissue damage that are normally seen with E. histolytica colonic infection.

  7. Cooperation between MEF2 and PPARγ in human intestinal β,β-carotene 15,15'-monooxygenase gene expression

    Yan Bingfang

    2006-02-01

    Full Text Available Abstract Background Vitamin A and its derivatives, the retinoids, are essential for normal embryonic development and maintenance of cell differentiation. β, β-carotene 15,15'-monooxygenase 1 (BCMO1 catalyzes the central cleavage of β-carotene to all-trans retinal and is the key enzyme in the intestinal metabolism of carotenes to vitamin A. However, human and various rodent species show markedly different efficiencies in intestinal BCMO1-mediated carotene to retinoid conversion. The aim of this study is to identify potentially human-specific regulatory control mechanisms of BCMO1 gene expression. Results We identified and functionally characterized the human BCMO1 promoter sequence and determined the transcriptional regulation of the BCMO1 gene in a BCMO1 expressing human intestinal cell line, TC-7. Several functional transcription factor-binding sites were identified in the human promoter that are absent in the mouse BCMO1 promoter. We demonstrate that the proximal promoter sequence, nt -190 to +35, confers basal transcriptional activity of the human BCMO1 gene. Site-directed mutagenesis of the myocyte enhancer factor 2 (MEF2 and peroxisome proliferator-activated receptor (PPAR binding elements resulted in decreased basal promoter activity. Mutation of both promoter elements abrogated the expression of intestinal cell BCMO1. Electrophoretic mobility shift and supershift assays and transcription factor co-expression in TC-7 cells showed MEF2C and PPARγ bind to their respective DNA elements and synergistically transactivate BCMO1 expression. Conclusion We demonstrate that human intestinal cell BCMO1 expression is dependent on the functional cooperation between PPARγ and MEF2 isoforms. The findings suggest that the interaction between MEF2 and PPAR factors may provide a molecular basis for interspecies differences in the transcriptional regulation of the BCMO1 gene.

  8. Vasoactive intestinal polypeptide and peptide histidine methionine. Presence in human follicular fluid and effects on DNA synthesis and steroid secretion in cultured human granulosa/lutein cells

    Gräs, S; Ovesen, P; Andersen, A N;

    1994-01-01

    Vasoactive intestinal polypeptide (VIP) and peptide histidine methionine (PHM) originate from the same precursor molecule, prepro VIP. In the present study we examined the concentrations of VIP and PHM in human follicular fluid and their effects on cultured human granulosa/lutein cells. Follicular...

  9. Somatostatin, substance P and calcitonin gene-related peptide-positive intramural nerve structures of the human large intestine affected by carcinoma.

    Jerzy Kaleczyc

    2010-11-01

    Full Text Available The aim of this study was to investigate the arrangement and chemical coding of enteric nerve structures in the human large intestine affected by cancer. Tissue samples comprising all layers of the intestinal wall were collected during surgery form both morphologically unchanged and pathologically altered segments of the intestine (n=15, and fixed by immersion in buffered paraformaldehyde solution. The cryostat sections were processed for double-labelling immunofluorescence to study the distribution of the intramural nerve structures (visualized with antibodies against protein gene-product 9.5 and their chemical coding using antibodies against somatostatin (SOM, substance P (SP and calcitonin gene-related peptide (CGRP. The microscopic observations revealed distinct morphological differences in the enteric nerve system structure between the region adjacent to the cancer invaded area and the intact part of the intestine. In general, infiltration of the cancer tissue resulted in the gradual (depending on the grade of invasion first decomposition and reduction to final partial or complete destruction and absence of the neuronal elements. A comparative analysis of immunohistochemically labeled sections (from the unchanged and pathologically altered areas revealed a statistically significant decrease in the number of CGRP-positive neurons and nerve fibres in both submucous and myenteric plexuses in the transitional zone between morphologically unchanged and cancer-invaded areas. In this zone, a decrease was also observed in the density of SP-positive nerve fibres in all intramural plexuses. Conversely, the investigations demonstrated statistically insignificant differences in number of SP- and SOM-positive neurons and a similar density of SOM-positive nerve fibres in the plexuses of the intact and pathologically changed areas. The differentiation between the potential adaptive changes in ENS or destruction of its elements by cancer invasion should be

  10. Phase Transition in a Healthy Human Heart Rate

    Kiyono, Ken; Struzik, Zbigniew R.; Aoyagi, Naoko; Togo, Fumiharu; Yamamoto, Yoshiharu

    2005-07-01

    A healthy human heart rate displays complex fluctuations which share characteristics of physical systems in a critical state. We demonstrate that the human heart rate in healthy individuals undergoes a dramatic breakdown of criticality characteristics, reminiscent of continuous second order phase transitions. By studying the germane determinants, we show that the hallmark of criticality—highly correlated fluctuations—is observed only during usual daily activity, and a breakdown of these characteristics occurs in prolonged, strenuous exercise and sleep. This finding is the first reported discovery of the dynamical phase transition phenomenon in a biological control system and will be a key to understanding the heart rate control system in health and disease.

  11. E Durans Strain M4-5 Isolated From Human Colonic Flora Attenuates Intestinal Inflammation

    Avram-Hananel, L.; Stock, J.; Parlesak, Alexandr;

    2010-01-01

    PURPOSE: The aim of this study was to evaluate in vitro and in vivo effects of a unique high-butyrate-producing bacterial strain from human colonic flora, Enterococcus durans, in prevention and treatment of intestinal inflammation. METHODS: A compartmentalized Caco-2/leukocyte coculture model was...... examine in vivo effects of prevention and therapy with E durans on clinical, biochemical, and histologic parameters of inflammation. RESULTS: In the coculture model, treatment with E durans and with butyrate reduced basal as well as E coli stimulated secretion of IL-8, IL-6, and TNF-α and increased...... inflammation, and inhibited colonic transcription of proinflammatory immune factors. The effect of therapeutic treatment alone on these parameters was more moderate but still significant. CONCLUSIONS: We conclude that E durans strain M4 to 5 and its metabolic product butyrate induce significant anti...

  12. The Influence of Different Apple Based Supplements on the Intestinal Microbiota of Humans

    Bergström, Anders; Wilcks, Andrea; Ravn-Haren, Gitte;

    restriction diet during the control period, and in the four other periods it was supplied with four different apple based supplements. Between the diets there was a 2-week wash-out period still on the restriction diet. The four apple based supplements were: 1) whole apples, 2) clear apple juice (pectin......Background and objective: The present project is part of the large ISAFRUIT project, where one of the objectives is to identify effects of apple and apple product on parameters related to gut health. In a previous rat study we observed changes in the intestinal microbiota of rats fed whole apples......, pomace or apple pectin ([1], and we were interested in finding out if the same effect can be observed in humans. Method: The study was conducted as a randomized, controlled 5 x 28 days cross-over study with 24 healthy persons of both genders. The persons were following a pectin- and polyphenol free...

  13. The epidemiology of human intestinal helminthiasis in Ibadan, South Western Nigeria.

    Ayanwale, F O; Esuruoso, G O; Dipeolu, O O

    1982-06-01

    An epidemiological survey of human faeces collected from open places in native quarters and from volunteers in modern housing areas was conducted so as to ascertain the intestinal helminth infections in Ibadan a town in South Western Nigeria. Out of four hundred and seventy eight stool samples examined between February 1980 and January 1981 in twenty nine localities grouped into 7 zones, Ascaris (Round worm) Trichuris (Whip worm) and hookworm were most prevalent. Ascaris and hookworms were three times as prevalent in native areas as in modern quarters. Two local dispensary records confirmed many reported cases of 'stomach aches' that responded to deworming therapy. The public health significance of open field defecation is discussed. The need to resuscitate the public sanitary inspectors' act as practiced prior to the country's independence in 1960 is also advocated. PMID:7174237

  14. CONTROL AND CANCEROUS TISSUES OF HUMAN STOMACH, SMALL INTESTINE AND LARGE INTESTINE - THE AVERAGE CONTENT OF SODIUM AND POTASSIUM

    Marta Głogowska

    2015-02-01

    Full Text Available Sodium and potassium regulate the total amount of water in the body and the transmission of sodium into and out of individual cells also plays a role in critical body functions. The movement of sodium is critical in generation of these electrical signals. Research was conducted on samples taken from women and men aged 20-90 years, derived from the stomach, small intestine and large intestine. Samples were dried at 80ºC for 24 hours, and then increased temperature to 105ºC and dried for seven days until dry mass was obtained. All dry material of each sample was weighted and placed in a separate mineralization tubes and mixed with 1 cm3 of 65% HNO3 and heated at 105°C for 120 minutes in a thermostat-controlled digestion block, VELP Scientifica DK 20. Metals such as sodium and potassium were detected using FAAS method. The average content of sodium in patients diagnosed with stomach cancer is lower, than in healthy person. Indicate higher mean content of sodium in the control tissues of stomach (2151,730 μg•g-1d.m., compared to a sodium content in tissues adjacent to the tumor (1813,958 μg•g-1d.m. and tumor tissues (2029,442 μg•g-1d.m.. In the case of colon, control tissues have lower average content of sodium (2160,886 μg•g-1d.m., than the tissues surrounding the tumor (3325,963 μg•g-1d.m. and tumor tissues (3037,121 μg•g-1d.m.. The potassium level is higher in the control tissues of stomach (1428,993 μg•g-1d.m., than in the tissues adjacent to the tumor (1091,544 μg•g-1d.m. and tumor tissues (1220,471 μg•g-1d.m.. In the large intestine higher average content of potassium is characterized by tumor tissues (2307,234 μg•g-1d.m. and tissues adjacent to the tumor (1712,779 μg•g-1d.m., than control tissue (1389,703 μg•g-1d.m.. Comparing this relationship with data on potassium channels, it can be assumed that in the some case of malignant transformation in the colon, potassium channels also play a big role.

  15. Transport of Aflatoxin M1 in human intestinal Caco-2/TC7 cells

    Francesca eCaloni

    2012-06-01

    Full Text Available Aflatoxin M1 (AFM1 is a hydroxylated metabolite of aflatoxin B1 (AFB1. After it is formed, it is secreted in the milk of mammals.Despite the potential risk of human exposure to AFM1, data reported in literature on the metabolism, toxicity and bioavailability of this molecule are limited and out of date. The aim of the present research was to study the absorption profile of AFM1 and possible damage to tight junctions of the intestinal Caco-2/TC7 clone grown on microporous filter supports. These inserts allowed for the separation of the apical and basolateral compartments which correspond to the in vivo lumen and the interstitial space/vascular systems of intestinal mucosa respectively.In this study, the Caco-2/TC7 cells were treated with different AFM1 concentrations (10-10,000 ng/kg for short (40 minutes and long periods of time (48 hours. The AFM1 influx/efflux transport and effects on tight junctions were evaluated by measuring trans-epithelial electrical resistance and observing tight junction protein (Zonula occludens-1 and occludin localization.The results showed that: i when introduced to the apical and basolateral compartments, AFM1 was poorly absorbed by the Caco-2/TC7 cells but its transport across the cell monolayer occurred very quickly (Papp value of 105.10 ± 7.98 cm/s x 10-6. ii The integrity of tight junctions was not permanently compromised after exposure to the mycotoxin. Viability impairment or barrier damage did not occur either.The present results contribute to the evaluation of human risk exposure to AFM1, although the AFM1 transport mechanism need to be clarified.

  16. Maintaining human productivity during Mars transit

    Statler, Irving C.; Billings, Charles E.

    1989-01-01

    This paper addresses the special nature of the human-machine relationship during a trip to Mars. In particular, the potential for monotony and boredom during a long-duration space voyage and the effect on motivation and productivity can be important considerations to the health and welfare of the crew. For the voyage to Mars, a design may be considered that will purposefully maintain some level of workload for the crew as a preventive measure for the deterioration of productivity that comes with boredom. This paper speculates on these considerations, on the appropriate level of workload for maximum productivity, and on what might be done during the mission to alleviate the problems caused by monotony and boredom.

  17. L-lysine dose dependently delays gastric emptying and increases intestinal fluid volume in humans and rats

    Baruffol, C; Jordi, J; Camargo, S.; RADOVIC, T; Herzog, B.; Fried, M; Schwizer, W; Verrey, F; Lutz, T. A.; Steingoetter, A

    2014-01-01

    BACKGROUND: Novel sensory inputs for the control of food intake and gastrointestinal (GI) function are of increasing interest due to the rapid increase in nutrition-related diseases. The essential amino acid L-lysine was demonstrated to have a selective impact on food intake, gastric emptying, and intestinal transit in rats, thus indicating a potential novel direct sensory input to assess dietary protein content and quality. The aim of this study was to assess translational aspects of this fi...

  18. The Intestine Plays a Substantial Role in Human Vitamin B6 Metabolism: A Caco-2 Cell Model

    Albersen, Monique; Bosma, Marjolein; Knoers, Nine V. V. A. M.; de Ruiter, Berna H. B.; Diekman, Eugène F.; de Ruijter, Jessica; Visser, Wouter F.; de Koning, Tom J.; Verhoeven-Duif, Nanda M.

    2013-01-01

    Background Vitamin B6 is present in various forms (vitamers) in the diet that need to be metabolized to pyridoxal phosphate (PLP), the active cofactor form of vitamin B6. In literature, the liver has been reported to be the major site for this conversion, whereas the exact role of the intestine remains to be elucidated. Objective To gain insight into the role of the intestine in human vitamin B6 metabolism. Materials and Methods Expression of the enzymes pyridoxal kinase (PK), pyridox(am)ine ...

  19. Transitions in Oral and Intestinal Microflora Composition and Innate Immune Receptor-Dependent Stimulation during Mouse Development▿ †

    Hasegawa, Mizuho; Osaka, Toshifumi; Tawaratsumida, Kazuki; Yamazaki, Takashi; Tada, Hiroyuki; Chen, Grace Y.; Tsuneda, Satoshi; Núñez, Gabriel; Inohara, Naohiro

    2009-01-01

    Commensal bacteria possess immunostimulatory activities that can modulate host responses to affect development and homeostasis in the intestine. However, how different populations of resident bacteria stimulate the immune system remains largely unknown. We characterized here the ability of intestinal and oral microflora to stimulate individual pattern recognition receptors (PRRs) in bone marrow-derived macrophages and mesothelial cells. The intestinal but not oral microflora elicited age- and...

  20. Vasoactive intestinal polypeptide (VIP) receptor scintigraphy in humans using an [123l] iodinated derivative of VIP

    Full text: VIP labelled with iodine-123 has recently been reported to be useful ligand for the in vivo localisation of various tumours, including colorectal, pancreatic, gastric adenocarcinomas, and both Iymph node and liver metastases. The aim of this investigation was to determine the dosimetry and biodistribution of [123I] iodo VIP in humans. Synthetic human VIP was reacted with [123I]Nal in the presence of lodogen to afford, after purification of the reaction mixture using HPLC, two isomeric [123I] iodotyrosylMet(O) vasoactive intestinal polypeptides, both of which are ligands for VIP receptors. After intravenous administration of these two iodinated peptides (160-200 MBq, 123l]iodo VIP was rapidly cleared from the blood and primarily localised in the lungs, which accounted for 30. per cent of the injected dose at times 2,4 and 24 h post-injection, respectively. The radioactivity measured in the urine amounted to 30 per cent of the injected dose at 6 h and 80 per cent at 24 h postinjection. The effective dose was calculated to be 3.7 mSv/160 MBq. The dosimetry and biodistribution of the [123I]iodo VIP prepared in our institution is similar to that reported in the literature. Furthermore, the dosimetry of this radiolabelled peptide is such that it is safe to use in humans

  1. Investigation of general and cytoskeletal markers to estimate numbers and proportions of neurons in the human intestine

    Ganns, D.; Schrödl, F.; Neuhuber, W.; Brehmer, A

    2006-01-01

    An important requirement in pathological diagnostics in the human enteric nervous system (ENS) is the estimation of the total numbers of neurons and of proportions of distinct subpopulations. In this study, we compared the suitability of two suggested panneuronal markers, cuprolinic blue (CB) and anti-Hu-protein (HU), for staining and counting human myenteric neurons in wholemounts, derived from small and large intestinal samples. Furthermore, the proportional ...

  2. Advancing the use of Lactobacillus acidophilus surface layer protein A for the treatment of intestinal disorders in humans.

    Sahay, Bikash; Ge, Yong; Colliou, Natacha; Zadeh, Mojgan; Weiner, Chelsea; Mila, Ashley; Owen, Jennifer L; Mohamadzadeh, Mansour

    2015-01-01

    Intestinal immunity is subject to complex and fine-tuned regulation dictated by interactions of the resident microbial community and their gene products with host innate cells. Deterioration of this delicate process may result in devastating autoinflammatory diseases, including inflammatory bowel disease (IBD), which primarily comprises Crohn's disease (CD) and ulcerative colitis (UC). Efficacious interventions to regulate proinflammatory signals, which play critical roles in IBD, require further scientific investigation. We recently demonstrated that rebalancing intestinal immunity via the surface layer protein A (SlpA) from Lactobacillus acidophilus NCFM potentially represents a feasible therapeutic approach to restore intestinal homeostasis. To expand on these findings, we established a new method of purifying bacterial SlpA, a new SlpA-specific monoclonal antibody, and found no SlpA-associated toxicity in mice. Thus, these data may assist in our efforts to determine the immune regulatory efficacy of SlpA in humans. PMID:26647142

  3. An ex-vivo human intestinal model to study Entamoeba histolytica pathogenesis.

    Devendra Bansal

    Full Text Available Amoebiasis (a human intestinal infection affecting 50 million people every year is caused by the protozoan parasite Entamoeba histolytica. To study the molecular mechanisms underlying human colon invasion by E. histolytica, we have set up an ex vivo human colon model to study the early steps in amoebiasis. Using scanning electron microscopy and histological analyses, we have established that E. histolytica caused the removal of the protective mucus coat during the first two hours of incubation, detached the enterocytes, and then penetrated into the lamina propria by following the crypts of Lieberkühn. Significant cell lysis (determined by the release of lactodehydrogenase and inflammation (marked by the secretion of pro-inflammatory molecules such as interleukin 1 beta, interferon gamma, interleukin 6, interleukin 8 and tumour necrosis factor were detected after four hours of incubation. Entamoeba dispar (a closely related non-pathogenic amoeba that also colonizes the human colon was unable to invade colonic mucosa, lyse cells or induce an inflammatory response. We also examined the behaviour of trophozoites in which genes coding for known virulent factors (such as amoebapores, the Gal/GalNAc lectin and the cysteine protease 5 (CP-A5, which have major roles in cell death, adhesion (to target cells or mucus and mucus degradation, respectively were silenced, together with the corresponding tissue responses. Our data revealed that the signalling via the heavy chain Hgl2 or via the light chain Lgl1 of the Gal/GalNAc lectin is not essential to penetrate the human colonic mucosa. In addition, our study demonstrates that E. histolytica silenced for CP-A5 does not penetrate the colonic lamina propria and does not induce the host's pro-inflammatory cytokine secretion.

  4. Solution structure of human intestinal fatty acid binding protein: Implications for ligand entry and exit

    Zhang Fengli [Boston University School of Medicine, Department of Biophysics (United States); Luecke, Christian [Johann Wolfgang Goethe-Universitaet (Germany); Baier, Leslie J. [NIDDK, NIH, Phoenix Epidemiology and Clinical Research Branch (United States); Sacchettini, James C. [Texas A and M University, Department of Biochemistry and Biophysics (United States); Hamilton, James A. [Boston University School of Medicine, Department of Biophysics (United States)

    1997-04-15

    The human intestinal fatty acid binding protein (I-FABP) is a small (131 amino acids) protein which binds dietary long-chain fatty acids in the cytosol of enterocytes. Recently, an alanine to threonine substitution at position 54 in I-FABP has been identified which affects fatty acid binding and transport, and is associated with the development of insulin resistance in several populations including Mexican-Americans and Pima Indians. To investigate the molecular basis of the binding properties of I-FABP, the 3D solution structure of the more common form of human I-FABP (Ala54) was studied by multidimensional NMR spectroscopy.Recombinant I-FABP was expressed from E. coli in the presence and absence of 15N-enriched media. The sequential assignments for non-delipidated I-FABP were completed by using 2D homonuclear spectra (COSY, TOCSY and NOESY) and 3D heteronuclear spectra(NOESY-HMQC and TOCSY-HMQC). The tertiary structure of human I-FABP was calculated by using the distance geometry program DIANA based on 2519 distance constraints obtained from the NMR data. Subsequent energy minimization was carried out by using the program SYBYL in the presence of distance constraints. The conformation of human I-FABP consists of 10 antiparallel {beta}-strands which form two nearly orthogonal {beta}-sheets of five strands each, and two short {alpha}-helices that connect the {beta}-strands A and B. The interior of the protein consists of a water-filled cavity between the two {beta}-sheets. The NMR solution structure of human I-FABP is similar to the crystal structure of rat I-FABP.The NMR results show significant conformational variability of certain backbone segments around the postulated portal region for the entry and exit of fatty acid ligand.

  5. A comparative analysis of the intestinal metagenomes present in guinea pigs (Cavia porcellus and humans (Homo sapiens

    Hildebrand Falk

    2012-09-01

    Full Text Available Abstract Background Guinea pig (Cavia porcellus is an important model for human intestinal research. We have characterized the faecal microbiota of 60 guinea pigs using Illumina shotgun metagenomics, and used this data to compile a gene catalogue of its prevalent microbiota. Subsequently, we compared the guinea pig microbiome to existing human gut metagenome data from the MetaHIT project. Results We found that the bacterial richness obtained for human samples was lower than for guinea pig samples. The intestinal microbiotas of both species were dominated by the two phyla Bacteroidetes and Firmicutes, but at genus level, the majority of identified genera (320 of 376 were differently abundant in the two hosts. For example, the guinea pig contained considerably more of the mucin-degrading Akkermansia, as well as of the methanogenic archaea Methanobrevibacter than found in humans. Most microbiome functional categories were less abundant in guinea pigs than in humans. Exceptions included functional categories possibly reflecting dehydration/rehydration stress in the guinea pig intestine. Finally, we showed that microbiological databases have serious anthropocentric biases, which impacts model organism research. Conclusions The results lay the foundation for future gastrointestinal research applying guinea pigs as models for humans.

  6. Toxic mechanisms induced by fumonisin b1 mycotoxin on human intestinal cell line.

    Minervini, Fiorenza; Garbetta, Antonella; D'Antuono, Isabella; Cardinali, Angela; Martino, Nicola Antonio; Debellis, Lucantonio; Visconti, Angelo

    2014-07-01

    The gastrointestinal tract is the main target of exposure to mycotoxin fumonisin B1 (FB1), common natural contaminant in food. Previous studies reported that proliferating cells are more sensitive than confluent cells to the toxic effect of FB1. This study aims to investigate, by dose- and time-dependent experiments on human colon proliferating intestinal cell line (HT-29), the modifications induced by FB1 at concentrations ranging from 0.25 to 69 μM. The choice of highest FB1 concentration considered the low toxicity previously reported on intestinal cell lines, whereas the lowest one corresponded to the lower FBs levels permitted by European Commission Regulation. Different functional parameters were tested such as cell proliferation, oxidative status, immunomodulatory effect and changes in membrane microviscosity. In addition FB1-FITC localization in this cell line was assessed by using confocal laser scanning microscopy. Lipid peroxidation induction was the main and early (12 h) effect induced by FB1 at concentrations ranging from 0.5 to 69 μM, followed by inhibition of cell proliferation (up to 8.6 μM), the immunomodulatory effect (up to 17.2 μM), by assessing IL-8 secretion, and increase in membrane microviscosity (up to 34.5 μM). The toxic effects observed in different functional parameters were not dose-dependent and could be the consequence of the FB1 intracytoplasmatic localization as confirmed by confocal microscopy results. The different timescales and concentrations active of different functional parameters could suggest different cellular targets of FB1. PMID:24549592

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

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

  8. Phase Transitions in Antibody Solutions: from Pharmaceuticals to Human Disease

    Wang, Ying; Lomakin, Aleksey; Benedek, George; Dana Farber Cancer Institute Collaboration; Amgen Inc. Collaboration

    2014-03-01

    Antibodies are very important proteins. Natural antibodies play essential role in the immune system of human body. Pharmaceutical antibodies are used as drugs. Antibodies are also indispensable tools in biomedical research and diagnostics. Recently, a number of observations of phase transitions of pharmaceutical antibodies have been reported. These phase transitions are undesirable from the perspective of colloid stability of drug solutions in processing and storage, but can be used for protein purification, X-ray crystallography, and improving pharmokinetics of drugs. Phase transitions of antibodies can also take place in human body, particularly in multiple myeloma patients who overproduce monoclonal antibodies. These antibodies, in some cases, crystallize at body temperature and cause severe complications called cryoglobulinemia. I will present the results of our current studies on phase transitions of both pharmaceutical antibodies and cryoglobulinemia-associated antibodies. These studies have shown that different antibodies have different propensity to undergo phase transitions, but their phase behavior has universal features which are remarkably different from those of spherical proteins. I will discuss how studies of phase behavior can be useful in assessing colloid stability of pharmaceutical antibodies and in early diagnostics of cryoglobulinemia, as well as general implications of the fact that some antibodies can precipitate at physiological conditions.

  9. A Layered Model of a Virtual Human Intestine for Surgery Simulation

    France, Laure; Lenoir, Julien; Angelidis, Alexis; Meseure, P.; Cani, Marie-Paule; Faure, François; Chaillou, Christophe

    2005-01-01

    In this paper, we propose a new approach to simulate the small intestine in a context of laparoscopic surgery. The ultimate aim of this work is to simulate the training of a basic surgical gesture in real-time: moving aside the intestine to reach hidden areas of the abdomen. The main problem posed by this kind of simulation is animating the intestine. The problem comes from the nature of the intestine: a very long tube which is not isotropically elastic, and is contained in a volume that is s...

  10. Challenges of culturing human norovirus in three-dimensional organoid intestinal cell culture models.

    Efstathia Papafragkou

    Full Text Available Human noroviruses are the most common cause of acute gastroenteritis worldwide. Recently, cell culture systems have been described using either human embryonic intestinal epithelial cells (Int-407 or human epithelial colorectal adenocarcinoma cells (Caco-2 growing on collagen-I porous micro carrier beads in a rotating bioreactor under conditions of physiological fluid shear. Here, we describe the efforts from two independent laboratories to implement this three dimensional (3D cell culture system for the replication of norovirus. Int-407 and Caco-2 were grown in a rotating bioreactor for up to 28 days. Prior to infection, cells were screened for the presence of microvilli by electron microscopy and stained for junction proteins (zonula occludens-1, claudin-1, and β-catenin. Differentiated 3D cells were transferred to 24-well plates and infected with bacteria-free filtrates of various norovirus genotypes (GI.1, GI.3, GI.8, GII.2, GII.4, GII.7, and GII.8. At 12 h, 24 h, and 48 h post inoculation, viral RNA from both cells and supernatants were collected and analyzed for norovirus RNA by real-time reverse transcription PCR. Despite observations of high expression of junction proteins and microvilli development in stained thin sections, our data suggest no significant increase in viral titer based on norovirus RNA copy number during the first 48 h after inoculation for the different samples and virus culture conditions tested. Our combined efforts demonstrate that 3D cell culture models using Int-407 or Caco-2 cells do not support norovirus replication and highlight the complexity and difficulty of developing a reproducible in vitro cell culture system for human norovirus.

  11. Optical properties of human normal small intestine tissue determined by Kubelka-Munk method in vitro

    Hua-Jiang Wei; Da Xing; Guo-Yong Wu; Ying Jin; Huai-Min Gu

    2003-01-01

    AIM: To study the optical properties of human normal small intestine tissue at 476.5 nm, 488 nm, 496.5 nm, 514.5 nm,532 nm, 808 nm wavelengths of laser irradiation.METHODS: A double-integrating-sphere system, the basic principle of measuring technology of light radiation, and an optical model of biological tissues were used in the study.RESULTS: The results of measurement showed that there were no significant differences in the absorption coefficients of human normal small intestine tissue at 476.5 nm, 488 nm,496.5 nm laser in the Kubelka-Munk two-flux model (P>0.05).The absorption coefficients of the tissue at 514.5 nm, 532 nm,808 nm laser irradiation were obviously increased with the decrease of these wavelengths. The scattering coefficients of the tissue at 476.5 nm, 488 nm, 496.5 nm laser irradiation were increased with the decrease of these wavelengths.The scattering coefficients at 496.5 nm, 514.5 nm, 532 nm laser irradiation were obviously increased with the increase of these wavelengths. The scattering coefficient of the tissue at 532 nm laser irradiation was bigger than that at 808 nm.There were no significant differences in the total attenuation coefficient of the tissue at 476.5 nm and 488 nm laser irradiation (P>0.05). The total attenuation coefficient of the tissue at 488 nm, 496.5 nm, 514.5 nm, 532 nm, 808 nm laser irradiation was obviously increased with the decrease of these wavelengths, and their effective attenuation coefficient revealed the same trend. There were no significant differences among the forward scattered photon fluxe,backward scattered photon fiuxe, and total scattered photon fiuxe of the tissue at 476.5 nm, 488 nm, 496.5 nm laser irradiation. They were all obviously increased with attenuation of tissue thickness. The attenuations of forward and backward scattered photon fluxes, and the total scattered photon fiuxe of the tissue at 514.5 nm laser irradiation were slower than those at 476.5 nm, 488 nm, 496.5 nm laser irradiation

  12. An inherent acceleratory effect of insulin on small intestinal transit and its pharmacological characterization in normal mice

    Murali Krishna Reddy Peddyreddy; Steven Aibor Dkhar; Subramanian Ramaswamy; Amrithraj Theophilus Naveen; Deepak Gopal Shewade

    2006-01-01

    AIM: To study an inherent effect of insulin on small intestinal transit and to explore involvement of various systems/mechanisms in normal mice.METHODS: Insulin at the doses of 2 μU/kg, 2 mU/kg,2 U/kg or vehicle was subcutaneously administered to four groups of overnight fasted normal male mice.Blood glucose (BG) levels were measured 2 min before insulin administration and 2 min before sacrificing the animals for the measurement of small intestinal transit (SIT). Charcoal meal was administered (0.3 mL) intragastrically 20 min after insulin administration and animals were sacrificed after 20 min and SIT was determined. For exploration of the various mechanisms involved in insulin-induced effect on SIT, the dose of insulin which can produce a significant acceleration of SIT without altering BG levels was determined.The following drugs, atropine (1 mg/kg), clonidine (0.1 mg/kg), ondansetron (1 mg/kg), naloxone (5mg/kg), verapamil (8 mg/kg) and glibenclamide (10 mg/kg), were administered intravenously 10 min prior to the administration of insulin (2 μU/kg).RESULTS: The lower doses of insulin (2 μU/kg and 2 mU/kg) produced a significant acceleration of SIT from 52.0% to 70.7% and 73.5% without lowering blood glucose levels (P< 0.01), while the highest dose of insulin (2 U/kg) produced a fall in blood glucose levels which was also associated with significant acceleration of SIT (P< 0.01). After pretreatment of insulin (2 μU/kg)group with atropine, insulin could reverse 50% of the inhibition produced by atropine. In clonidine-pretreated group, insulin administration could reverse only 37%of the inhibition produced by clonidine and inhibition of SIT was significant compared with vehicle + insulintreated group, i.e. from 74.7% to 27.7% (P<0.01). In ondansetron-pretreated group, insulin administration could produce only mild acceleration of SIT (23.5%). In naloxone-pretreated group, insulin administration could significantly reverse the inhibition of SIT produced

  13. Mast cells modulate transport of CD23/IgE/antigen complex across human intestinal epithelial barrier

    Ping-Chang Yang

    2009-06-01

    Full Text Available Background: Food allergy and chronic intestinal inflammation are common in western countries. The complex of antigen/IgE is taken up into the body from the gut lumen with the aid of epithelial cell-derived CD23 (low affinity IgE receptor II that plays an important role in the pathogenesis of intestinal allergy. This study aimed to elucidate the role of mast cell on modulation of antigen/IgE complex transport across intestinal epithelial barrier. Methods: Human intestinal epithelial cell line HT29 cell monolayer was used as a study platform. Transepithelial electric resistance (TER and permeability to ovalbumin (OVA were used as the markers of intestinal epithelial barrier function that were recorded in response to the stimulation of mast cell-derived chemical mediators. Results: Conditioned media from naïve mast cell line HMC-1 cells or monocyte cell line THP-1 cells significantly upregulated the expression of CD23 and increased the antigen transport across the epithelium. Treatment with stem cell factor (SCF, nerve growth factor (NGF, retinoic acid (RA or dimethyl sulphoxide (DMSO enhanced CD23 expression in HT29 cells. Conditioned media from SCF, NGF or RA-treated HMC-1 cells, and SCF, NGF, DMSO or RA-treated THP-1 cells enhanced immune complex transport via enhancing the expression of the CD23 in HT29 cells and the release of inflammatory mediator TNF-α. Nuclear factor kappa B inhibitor, tryptase and TNF-α inhibited the increase in CD23 in HT29 cells and prevents the enhancement of epithelial barrier permeability. Conclusions: Mast cells play an important role in modulating the intestinal CD23 expression and the transport of antigen/IgE/CD23 complex across epithelial barrier.

  14. Determination of tolerable fatty acids and cholera toxin concentrations using human intestinal epithelial cells and BALB/c mouse macrophages.

    Tamari, Farshad; Tychowski, Joanna; Lorentzen, Laura

    2013-01-01

    The positive role of fatty acids in the prevention and alleviation of non-human and human diseases have been and continue to be extensively documented. These roles include influences on infectious and non-infectious diseases including prevention of inflammation as well as mucosal immunity to infectious diseases. Cholera is an acute intestinal illness caused by the bacterium Vibrio cholerae. It occurs in developing nations and if left untreated, can result in death. While vaccines for cholera exist, they are not always effective and other preventative methods are needed. We set out to determine tolerable concentrations of three fatty acids (oleic, linoleic and linolenic acids) and cholera toxin using mouse BALB/C macrophages and human intestinal epithelial cells, respectively. We solubilized the above fatty acids and used cell proliferation assays to determine the concentration ranges and specific concentrations of the fatty acids that are not detrimental to human intestinal epithelial cell viability. We solubilized cholera toxin and used it in an assay to determine the concentration ranges and specific concentrations of cholera toxin that do not statistically decrease cell viability in BALB/C macrophages. We found the optimum fatty acid concentrations to be between 1-5 ng/μl, and that for cholera toxin to be < 30 ng per treatment. This data may aid future studies that aim to find a protective mucosal role for fatty acids in prevention or alleviation of cholera infections. PMID:23748896

  15. Selective FFA2 Agonism Appears to Act via Intestinal PYY to Reduce Transit and Food Intake but Does Not Improve Glucose Tolerance in Mouse Models.

    Forbes, Sarah; Stafford, Stuart; Coope, Gareth; Heffron, Helen; Real, Katia; Newman, Robert; Davenport, Richard; Barnes, Matt; Grosse, Johannes; Cox, Helen

    2015-11-01

    Free fatty acid receptor 2 (FFA2) is expressed on enteroendocrine L cells that release glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) when activated by short-chain fatty acids (SCFAs). Functionally GLP-1 and PYY inhibit gut transit, increase glucose tolerance, and suppress appetite; thus, FFA2 has therapeutic potential for type 2 diabetes and obesity. However, FFA2-selective agonists have not been characterized in vivo. Compound 1 (Cpd 1), a potent FFA2 agonist, was tested for its activity on the following: GLP-1 release, modulation of intestinal mucosal ion transport and transit in wild-type (WT) and FFA2(-/-) tissue, and food intake and glucose tolerance in lean and diet-induced obese (DIO) mice. Cpd 1 stimulated GLP-1 secretion in vivo, but this effect was only detected with dipeptidyl peptidase IV inhibition, while mucosal responses were PYY, not GLP-1, mediated. Gut transit was faster in FFA2(-/-) mice, while Cpd 1 slowed WT transit and reduced food intake and body weight in DIO mice. Cpd 1 decreased glucose tolerance and suppressed plasma insulin in lean and DIO mice, despite FFA2(-/-) mice displaying impaired glucose tolerance. These results suggest that FFA2 inhibits intestinal functions and suppresses food intake via PYY pathways, with limited GLP-1 contribution. Thus, FFA2 may be an effective therapeutic target for obesity but not for type 2 diabetes. PMID:26239054

  16. Transcriptome-wide Analysis Reveals Hallmarks of Human Intestine Development and Maturation In Vitro and In Vivo

    Stacy R. Finkbeiner

    2015-06-01

    Full Text Available Human intestinal organoids (HIOs are a tissue culture model in which small intestine-like tissue is generated from pluripotent stem cells. By carrying out unsupervised hierarchical clustering of RNA-sequencing data, we demonstrate that HIOs most closely resemble human fetal intestine. We observed that genes involved in digestive tract development are enriched in both fetal intestine and HIOs compared to adult tissue, whereas genes related to digestive function and Paneth cell host defense are expressed at higher levels in adult intestine. Our study also revealed that the intestinal stem cell marker OLFM4 is expressed at very low levels in fetal intestine and in HIOs, but is robust in adult crypts. We validated our findings using in vivo transplantation to show that HIOs become more adult-like after transplantation. Our study emphasizes important maturation events that occur in the intestine during human development and demonstrates that HIOs can be used to model fetal-to-adult maturation.

  17. Human behavioral regularity, fractional Brownian motion, and exotic phase transition

    Li, Xiaohui; Yang, Guang; An, Kenan; Huang, Jiping

    2016-08-01

    The mix of competition and cooperation (C&C) is ubiquitous in human society, which, however, remains poorly explored due to the lack of a fundamental method. Here, by developing a Janus game for treating C&C between two sides (suppliers and consumers), we show, for the first time, experimental and simulation evidences for human behavioral regularity. This property is proved to be characterized by fractional Brownian motion associated with an exotic transition between periodic and nonperiodic phases. Furthermore, the periodic phase echoes with business cycles, which are well-known in reality but still far from being well understood. Our results imply that the Janus game could be a fundamental method for studying C&C among humans in society, and it provides guidance for predicting human behavioral activity from the perspective of fractional Brownian motion.

  18. Effect of linear alkylbenzene sulfonate (LAS) on human intestinal Caco-2 cells at non cytotoxic concentrations.

    Bradai, Mohamed; Han, Junkyu; Omri, Abdelfatteh El; Funamizu, Naoyuki; Sayadi, Sami; Isoda, Hiroko

    2016-08-01

    Linear alkylbenzene sulfonate (LAS) is a cytotoxic synthetic anionic surfactant widely present in the environment due to its large-scale production and intensive use in the detergency field. In this study, we investigated the effect of LAS (CAS No. 25155-30-0) at non cytotoxic concentrations on human intestinal Caco-2 cells using different in vitro bioassays. As results, LAS increased Caco-2 cell proliferation at concentrations ranging from 1 to 15 ppm, more significantly for shorter exposure time (24 h), confirmed using flow cytometry and trypan blue exclusion methods. Moreover, proteomics analysis revealed that this effect was associated with an over-expression of elongation factor 2 and dipeptidyl peptidase 3, and a down-regulation of 14-3-3 protein theta, confirmed at mRNA level using real-time PCR. These findings suggest that LAS at non cytotoxic concentrations, similar to those observed at wastewater treatment plants outlets, increases the growth rate of colon cancer cells, raising thereby its tumor promotion effect potential. PMID:25999174

  19. In vitro extraction and fermentation of polyphenols from grape seeds (Vitis vinifera) by human intestinal microbiota.

    Zhou, Li; Wang, Wei; Huang, Jun; Ding, Yu; Pan, Zhouqiang; Zhao, Ya; Zhang, Renkang; Hu, Bing; Zeng, Xiaoxiong

    2016-04-20

    The effects of several parameters on the extraction yield of total polyphenols from grape seeds by pressurized liquid extraction were investigated. The highest recovery of total polyphenols occurred at 80 °C within 5 min, and a single extraction allowed a recovery of more than 97% of total polyphenols. Following the purification with macroporous resin, the effects of grape polyphenols (>94.8%) on human intestinal microbiota were monitored over 36 h incubation by fluorescence in situ hybridization, and short-chain fatty acids (SCFAs) were measured by HPLC. The result showed that the grape polyphenols promoted the changes in the relevant microbial populations and shifted the profiles of SCFAs. Fermentation of grape polyphenols resulted in a significant increase in the numbers of Bifidobacterium spp. and Lactobacillus-Enterococcus group and inhibition in the growth of the Clostridium histolyticum group and the Bacteroides-Prevotella group, with no significant effect on the population of total bacteria. The findings suggest that grape polyphenols have potential prebiotic effects on modulating the gut microbiota composition and generating SCFAs that contribute to the improvements of host health. PMID:26980065

  20. Functional alterations induced by the food contaminant furazolidone on the human tumoral intestinal cell line Caco-2.

    Vincentini, O; De Angelis, I; Stammati, A; Zucco, F

    1993-07-01

    Caco-2 cells, which are derived from a human colon carcinoma and are able to differentiate in culture, have been used to study the effect of furazolidone (FZ), a chemical belonging to the nitrofuran family which is frequently used for the prevention of animal infections. Its potentially toxic residues could remain in some food products of animal origin and affect human health. Toxicity has been measured by different parameters, either in undifferentiated cells (day 7 of culture), or on differentiated cells (day 21 of culture). Our results indicate that FZ may seriously affect the proliferating portion of the intestinal mucosa, while the differentiated cells appear to be more resistant. However, the slight effect recorded on the aspecific and specific functions of the differentiated cells may suggest that the specialized portion of the intestine can also be compromised by the drug. Caco 2 cells seem a good model for a deeper investigation of the mechanism involved in the toxic action of FZ. PMID:20732223

  1. Intestine Transplant

    ... Heart/Lung Kidney Pancreas Kidney/Pancreas Liver Intestine Intestine Transplant Although it is possible for a living donor to donate an intestine segment, most intestine transplants involve a whole organ ...

  2. Anti inflammatory and anti angiogenic effect of black raspberry extract on human esophageal and intestinal microvascular endothelial cells

    Medda, Rituparna; Lyros, Orestis; Schmidt, Jamie L.; Jovanovic, Nebojsa; Nie, Linghui; Link, Benjamin J.; Otterson, Mary F.; Stoner, Gary D.; Shaker, Reza; Rafiee, Parvaneh

    2014-01-01

    Polyphenolic compounds (anthocyanins, flavonoid glycosides) in berries prevent the initiation, promotion, and progression of carcinogenesis in rat’s digestive tract and esophagus, in part, via anti-inflammatory pathways. Angiogenesis has been implicated in the pathogenesis of chronic inflammation and tumorigenesis. In this study, we investigated the anti-inflammatory and anti-angiogenic effects of black raspberry extract (BRE) on two organ specific primary human intestinal microvascular endot...

  3. For Application to Human Spaceflight and ISS Experiments: VESGEN Mapping of Microvascular Network Remodeling during Intestinal Inflammation

    Parsons-Wingerter, Patricia; Reinecker, Hans-Christian

    2012-01-01

    Challenges to long-duration space exploration and colonization in microgravity and cosmic radiation environments by humans include poorly understood risks for gastrointestinal function and cancer. Nonetheless, constant remodeling of the intestinal microvasculature is critical for tissue viability, healthy wound healing, and successful prevention or recovery from vascular-mediated inflammatory or ischemic diseases such as cancer. Currently no automated image analysis programs provide quantitat...

  4. Development of 3D human intestinal equivalents for substance testing in microliter-scale on a multi-organ-chip

    Jaenicke, Annika; Tordy, Dominique; Groeber, Florian; Hansmann, Jan; Nietzer, Sarah; Tripp, Carolin; Walles, Heike; Lauster, Roland; Marx, Uwe

    2013-01-01

    First published by BioMed Central: Jaenicke, Annika; Tordy, Dominique; Groeber, Florian; Hansmann, Jan; Nietzer, Sarah; Tripp, Carolin; Walles, Heike; Lauster, Roland; Marx, Uwe: Development of 3D human intestinal equivalents for substance testing in microliter-scale on a multi-organ-chip. - In: BMC Proceedings. - ISSN 1753-6561 (online). - 7 (2013), suppl. 6, P65. - doi:10.1186/1753-6561-7-S6-P65.

  5. The shaping of human diversity: filters, boundaries and transitions.

    Mirazón Lahr, Marta

    2016-07-01

    The evolution of modern humans was a complex process, involving major changes in levels of diversity through time. The fossils and stone tools that record the spatial distribution of our species in the past form the backbone of our evolutionary history, and one that allows us to explore the different processes-cultural and biological-that acted to shape the evolution of different populations in the face of major climate change. Those processes created a complex palimpsest of similarities and differences, with outcomes that were at times accelerated by sharp demographic and geographical fluctuations. The result is that the population ancestral to all modern humans did not look or behave like people alive today. This has generated questions regarding the evolution of human universal characters, as well as the nature and timing of major evolutionary events in the history of Homo sapiens The paucity of African fossils remains a serious stumbling block for exploring some of these issues. However, fossil and archaeological discoveries increasingly clarify important aspects of our past, while breakthroughs from genomics and palaeogenomics have revealed aspects of the demography of Late Quaternary Eurasian hominin groups and their interactions, as well as those between foragers and farmers. This paper explores the nature and timing of key moments in the evolution of human diversity, moments in which population collapse followed by differential expansion of groups set the conditions for transitional periods. Five transitions are identified (i) at the origins of the species, 240-200 ka; (ii) at the time of the first major expansions, 130-100 ka; (iii) during a period of dispersals, 70-50 ka; (iv) across a phase of local/regional structuring of diversity, 45-25 ka; and (v) during a phase of significant extinction of hunter-gatherer diversity and expansion of particular groups, such as farmers and later societies (the Holocene Filter), 15-0 ka.This article is part of the

  6. Conversion of 5-fluorocytosine to 5-fluorouracil by human intestinal microflora

    5-Fluorocytosine (FC) is used to treat systemic fungal infections in man. Its clinical effectiveness has been limited by hematologic toxicity which may be secondary to the formation of 5-fluorouracil (FU). It is unclear how FU is formed since human cells lack cytosine deaminase. The present study examined if intestinal microflora (IMF) could convert FC to FU in man. An in vitro semicontinuous culture system was inoculated with human feces and maintained with sterile nutrient suspension. The microbial community was assessed for cell count and anaerobes as well as formation of volatile fatty acids and CH4. The system approximated that believed to occur in vivo. The study was initiated with addition of purified [6-14C]-FC. Unlabelled FC was then added to the system daily for 2 weeks following which [6-14C]-FC was again added. Following each addition of [6-14C]-FC, samples were removed at 2,4,8,24,48,72, and 96 hr. Utilizing HPLC, FC and FU could be separated with quantitation of radioactivity in each peak. Following the initial dose, no detectable FU was observed during the first 8 hr, but after 24 hr increasing levels were detected (9.42 μg FU/ml after 4 days). Following chronic administration of FC, increased levles of FU were noted without an 8 hr lag time in the production of FU (31.86 μg FU/ml after 4 days). In summary, these studies demonstrate that IMF can convert FC to FU possibly accounting for toxicity observed following administration of FC

  7. Characterization of calcium transport by basolateral membrane vesicles of human small intestine

    The present studies investigated the mechanism of Ca2+ transport across basolateral membrane vesicles (BLMVs) prepared from human small intestine. Ca2+ uptake represented transport into the intravesicular space as evident by osmolality study and by the demonstration of Ca2+ efflux from the intravesicular space by Ca2+ ionophore A23187. Ca2+ uptake was stimulated by Mg2+-ATP. Kinetic parameters for ATP-dependent Ca2+ uptake revealed a Michaelis constant (Km) of 0.02±0.01 μM and a maximum rate of uptake (Vmax) of 1.00±0.03 nmol·mg protein-1·min-1. Ca2+ uptake in the presence of Mg2+ was inhibited by 75%. The Km of ATP concentration required for half-maximal Ca2+ uptake was 0.50±0.1 mM. Basolateral membranes depleted of calmodulin by EDTA osmotic shock decreased ATP-dependent Ca2+ uptake by 65%. Trifluoperazine, an anticalmodulin drug, inhibited ATP-dependent Ca2+ uptake by 50%, while no inhibition was noted in calmodulin-depleted membranes. Efflux of Ca2+ in the BLMVs was stimulated by trans-Na+. Na+-dependent Ca2+ uptake was saturable with respect to Ca2+ concentration and exhibited a Km of 0.09±0.03 μM and a Vmax of 1.08±0.01 nmol·mg protein-1·min-1. These results are consistent with the existence of a Na+-Ca2+ exchange system and ATP and Mg2+-dependent, calmodulin-regulated Ca2+, transport mechanism in BLMVs of human enterocytes

  8. Comparison of DNA extraction kits for PCR-DGGE analysis of human intestinal microbial communities from fecal specimens

    Nakatsu Cindy H

    2010-05-01

    Full Text Available Abstract Background The influence of diet on intestinal microflora has been investigated mainly using conventional microbiological approaches. Although these studies have advanced knowledge on human intestinal microflora, it is imperative that new methods are applied to facilitate scientific progress. Culture-independent molecular fingerprinting method of Polymerase Chain Reaction and Denaturing Gradient Gel Electrophoresis (PCR-DGGE has been used to study microbial communities in a variety of environmental samples. However, these protocols must be optimized prior to their application in order to enhance the quality and accuracy of downstream analyses. In this study, the relative efficacy of four commercial DNA extraction kits (Mobio Ultra Clean® Fecal DNA Isolation Kit, M; QIAamp® DNA Stool Mini Kit, Q; FastDNA® SPIN Kit, FSp; FastDNA® SPIN Kit for Soil, FSo were evaluated. Further, PCR-DGGE technique was also assessed for its feasibility in detecting differences in human intestinal bacterial fingerprint profiles. Method Total DNA was extracted from varying weights of human fecal specimens using four different kits, followed by PCR amplification of bacterial 16S rRNA genes, and DGGE separation of the amplicons. Results Regardless of kit, maximum DNA yield was obtained using 10 to 50 mg (wet wt of fecal specimens and similar DGGE profiles were obtained. However, kits FSp and FSo extracted significantly larger amounts of DNA per g dry fecal specimens and produced more bands on their DGGE profiles than kits M and Q due to their use of bead-containing lysing matrix and vigorous shaking step. DGGE of 16S rRNA gene PCR products was suitable for capturing the profiles of human intestinal microbial community and enabled rapid comparative assessment of inter- and intra-subject differences. Conclusion We conclude that extraction kits that incorporated bead-containing lysing matrix and vigorous shaking produced high quality DNA from human fecal

  9. Development of microfluidic cell culture devices towards an in vitro human intestinal barrier model

    Tan, Hsih-Yin

    displaying folds that closely resembled the intestinal villi and formation of a tight barrier. Furthermore, the microelectrodes embedded in the microchip also allow real-time monitoring of the barrier integrity by means of measuring the trans-epithelial electrical resistance. Demonstrations of transport...... enable real-time detection of cell responses, adjustment of cellular stimulation etc. leading to establishment of conditional experiments. In this project, microfluidic systems engineering was leveraged to develop an eight chamber multi-layer microchip for intestinal barrier studies. Sandwiched between...... without compromising the epithelial cell viability and barrier function. Such a platform paves the way towards an alternative in vitro intestinal model for high throughput screening of drugs, chemicals, pathogens, intestinal diseases as well as toxicological studies....

  10. Human intestinal epithelial cells in innate immunity : interactions with normal microbiota and pathogenic bacteria

    Ou, Gangwei

    2009-01-01

    Rod-shaped bacteria were previously shown to be associated with the small intestinal epithelium of children with celiac disease (CD). Using culture-dependent and independent methods, we characterized the microbiota of small intestine in children with CD and controls. The normal microbiota constitutes an unique organ-specific biofilm. Dominant bacteria are Streptococcus, Neisseria, Veillonella, Gemella, Actinomyces, Rothia and Haemophilus. Altogether 162 Genus Level Operational Taxonomic Units...

  11. Rapid conversion of the ester prodrug abiraterone acetate results in intestinal supersaturation and enhanced absorption of abiraterone: in vitro, rat in situ and human in vivo studies.

    Stappaerts, Jef; Geboers, Sophie; Snoeys, Jan; Brouwers, Joachim; Tack, Jan; Annaert, Pieter; Augustijns, Patrick

    2015-02-01

    The aim of this study was to evaluate the intestinal disposition of abiraterone acetate, an ester prodrug of the anticancer agent abiraterone. Stability of the prodrug and solubility and dissolution characteristics of both abiraterone and abiraterone acetate were monitored in vitro. Moreover, the in vivo intraluminal concentrations of abiraterone and abiraterone acetate upon intake of one tablet of 250 mg abiraterone acetate were assessed in healthy volunteers. The intestinal absorption resulting from the intraluminal behavior of the ester prodrug was determined using the rat in situ intestinal perfusion technique with mesenteric blood sampling. Simulated and aspirated human intestinal fluids of the fasted state were used as solvent systems. Upon incubation of abiraterone acetate in human intestinal fluids in vitro, rapid hydrolysis of the prodrug was observed, generating abiraterone concentrations largely exceeding the apparent solubility of abiraterone, suggesting the existence of intestinal supersaturation. These findings were confirmed in vivo, by intraluminal sampling of duodenal fluids upon oral intake of an abiraterone acetate tablet by healthy volunteers. Rat in situ intestinal perfusion experiments performed with suspensions of abiraterone and abiraterone acetate in human intestinal fluids of the fasted state revealed significantly higher flux values upon perfusion with the prodrug than with abiraterone. Moreover, rat in situ intestinal perfusion with abiraterone acetate suspensions in simulated fluids of the fasted state in presence or absence of esterases demonstrated that increased hydrolytic activity of the perfusion medium was beneficial to the intestinal absorption of abiraterone. In conclusion, the rapid hydrolysis of abiraterone acetate in the intraluminal environment appears to result in fast and extensive generation of abiraterone supersaturation, creating a strong driving force for abiraterone absorption. PMID:25592324

  12. Human factors issues for resolving adverse effects of human work underload and workload transitions in complex human-machine systems

    A workshop was conducted whose specific purpose was to build on earlier work of the United States National Research Council, United States Federal government agencies, and the larger human factors community to: (1) clarify human factors issues pertaining to degraded performance in advanced human-machine systems (e.g., nuclear production, transportation, aerospace) due to human work underload and workload transition, and (2) develop strategies for resolving these issues. Recent history demonstrates that: (1) humans often react adversely to their diminishing roles in advanced human-machine systems, and therefore (2) new allocation models and strategies are required if humans are to be willing and able to assume diminishing and shifting roles assigned to them in these systems, and are to accept new technologies making up these systems. Problems associated with theses diminishing and shifting human roles are characterized as work underload and workload transitions. The workshop affirmed that: (1) work underload and workload transition are issues that will have to be addressed by designers of advanced human-machine systems, especially those relying on automation, if cost, performance, safety, and operator acceptability are to be optimized, (2) human machine allocation models, standards, and guidelines which go beyond simple capability approaches will be needed to preclude or seriously diminish the work underload and workload transition problems, and (3) the 16 workload definition, measurement, situational awareness, and trust issues identified during the workshop, need resolution if these models, standards, and guidelines are to be achieved. (author)

  13. Antibodies and antisense oligodeoxynucleotides to μ-opioid receptors, selectively block the effects of μ-opioid agonists on intestinal transit and permeability in mice

    Pol, Olga; Valle, Lluís; Sánchez-Blázquez, Pilar; Garzón, Javier; Puig, Margarita M.

    1999-01-01

    We have studied the effects of μ and δ opioids on intestinal function (permeability, PER; gastrointestinal transit, GIT), and their antagonism after the intracerebroventricular (i.c.v.) administration of specific antibodies (ABs) or antisense oligodeoxynucleotides (ODN) to μ-receptors (OR). Central versus peripheral site/s of action of subcutaneous (s.c.) μ-opioids, were also assessed.Male Swiss CD-1 mice were used. GIT was measured with charcoal and PER by the passage of 51Cr-EDTA from blood...

  14. Reduced expression of aquaporins in human intestinal mucosa in early stage inflammatory bowel disease

    Ricanek P

    2015-01-01

    -dimensional structures of AQP1, 3, 7, and 8 were modeled. Results: AQP1, 3, 7, and 8 mRNAs were detected in all parts of the intestinal mucosa. Notably, AQP1 and AQP3 mRNA levels were reduced in the ileum of patients with Crohn's disease, and AQP7 and AQP8 mRNA levels were reduced in the ileum and the colon of patients with ulcerative colitis. Immunofluorescence confocal microscopy showed localization of AQP3, 7, and 8 at the mucosal epithelium, whereas the expression of AQP1 was mainly confined to the endothelial cells and erythrocytes. The reduction in the level of AQP3, 7, and 8 mRNA was confirmed by immunofluorescence, which also indicated a reduction of apical immunolabeling for AQP8 in the colonic surface epithelium and crypts of the IBD samples. This could indicate loss of epithelial polarity in IBD, leading to disrupted barrier function. Conclusion: AQPs 1 and 8 and the aquaglyceroporins AQPs 3 and 7 are the AQPs predominantly expressed in the lower intestinal tract of humans. Their expression is significantly reduced in patients with IBD, and they are differentially expressed in specific bowel segments in patients with Crohn's disease and ulcerative colitis. The data present a link between gut inflammation and water/solute homeostasis, suggesting that AQPs may play a significant role in IBD pathophysiology. Keywords: inflammatory bowel disease, Crohn's disease, ulcerative colitis, aquaporins, aquaglyceroporins

  15. Efficacy of a single dose albendazole chemotherapy on human intestinal helminthiasis among school children in selected rural tropical communities

    Ekaette Godwin Edelduok

    2013-01-01

    Full Text Available Introduction: The impact of chemotherapy on human intestinal helminthiasis among school children in semi-urban tropical communities of Igbo-Eze South Local Government Area of Enugu State, South-Eastern Nigeria, was investigated. Materials and Methods: Stool samples were obtained from 1296 school children (ages 4-15 years from six schools randomly selected from the study area. Helminth eggs were recovered from stool samples. Those infected were treated with single oral dose of 400 mg albendazole tablets and re-examined for helminth eggs 4 weeks post-treatment. Results: Out of 1296 school children examined, 106 (8.1% of the children were significantly (P < 0.05 infected with human intestinal helminths thus: 64 (4.9% with Ascaris lumbricoides, 33 (2.5% with hookworm and 9 (0.7% with Trichuris trichiura. Out of the 64 children infected with A. lumbricoides, there was a reduction in the prevalence of infection by 18.8%. Furthermore, out of the 33 children infected with hookworm, there was a reduction in the prevalence of infection by 15.1%. Out of the nine children infected with T. trichiura, there was a reduction in the prevalence of infection by 22.2%. Conclusion: These findings suggest intestinal helminth specificity to the efficacy of albendazole. Thus, further research into the development of more effective antihelminthic drugs is necessary.

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

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

  17. Production of enterodiol from defatted flaxseeds through biotransformation by human intestinal bacteria

    Ma Miao

    2010-04-01

    Full Text Available Abstract Background The effects of enterolignans, e.g., enterodiol (END and particularly its oxidation product, enterolactone (ENL, on prevention of hormone-dependent diseases, such as osteoporosis, cardiovascular diseases, hyperlipemia, breast cancer, colon cancer, prostate cancer and menopausal syndrome, have attracted much attention. To date, the main way to obtain END and ENL is chemical synthesis, which is expensive and inevitably leads to environmental pollution. To explore a more economic and eco-friendly production method, we explored biotransformation of enterolignans from precursors contained in defatted flaxseeds by human intestinal bacteria. Results We cultured fecal specimens from healthy young adults in media containing defatted flaxseeds and detected END from the culture supernatant. Following selection through successive subcultures of the fecal microbiota with defatted flaxseeds as the only carbon source, we obtained a bacterial consortium, designated as END-49, which contained the smallest number of bacterial types still capable of metabolizing defatted flaxseeds to produce END. Based on analysis with pulsed field gel electrophoresis, END-49 was found to consist of five genomically distinct bacterial lineages, designated Group I-V, with Group I strains dominating the culture. None of the individual Group I-V strains produced END, demonstrating that the biotransformation of substrates in defatted flaxseeds into END is a joint work by different members of the END-49 bacterial consortium. Interestingly, Group I strains produced secoisolariciresinol, an important intermediate of END production; 16S rRNA analysis of one Group I strain established its close relatedness with Klebsiella. Genomic analysis is under way to identify all members in END-49 involved in the biotransformation and the actual pathway leading to END-production. Conclusion Biotransformation is a very economic, efficient and environmentally friendly way of mass

  18. Anatomical study on The Arm Greater Yang Small Intestine Meridian Muscle in Human

    Kyoung-Sik, Park

    2004-06-01

    Full Text Available This study was carried to identify the component of Small Intestine Meridian Muscle in human, dividing the regional muscle group into outer, middle, and inner layer. the inner part of body surface were opened widely to demonstrate muscles, nerve, blood vessels and the others, displaying the inner structure of Small Intestine Meridian Muscle. We obtained the results as follows; 1. Small Intestine Meridian Muscle is composed of the muscle, nerve and blood vessels. 2. In human anatomy, it is present the difference between a term of nerve or blood vessels which control the muscle of Meridian Muscle and those which pass near by Meridian Muscle. 3. The inner composition of meridian muscle in human arm is as follows ; 1 Muscle ; Abd. digiti minimi muscle(SI-2, 3, 4, pisometacarpal lig.(SI-4, ext. retinaculum. ext. carpi ulnaris m. tendon.(SI-5, 6, ulnar collateral lig.(SI-5, ext. digiti minimi m. tendon(SI-6, ext. carpi ulnaris(SI-7, triceps brachii(SI-9, teres major(SI-9, deltoid(SI-10, infraspinatus(SI-10, 11, trapezius(Sl-12, 13, 14, 15, supraspinatus(SI-12, 13, lesser rhomboid(SI-14, erector spinae(SI-14, 15, levator scapular(SI-15, sternocleidomastoid(SI-16, 17, splenius capitis(SI-16, semispinalis capitis(SI-16, digasuicus(SI-17, zygomaticus major(Il-18, masseter(SI-18, auriculoris anterior(SI-19 2 Nerve ; Dorsal branch of ulnar nerve(SI-1, 2, 3, 4, 5, 6, br. of mod. antebrachial cutaneous n.(SI-6, 7, br. of post. antebrachial cutaneous n.(SI-6,7, br. of radial n.(SI-7, ulnar n.(SI-8, br. of axillary n.(SI-9, radial n.(SI-9, subscapular n. br.(SI-9, cutaneous n. br. from C7, 8(SI-10, 14, suprascapular n.(SI-10, 11, 12, 13, intercostal n. br. from T2(SI-11, lat. supraclavicular n. br.(SI-12, intercostal n. br. from C8, T1(SI-12, accessory n. br.(SI-12, 13, 14, 15, 16, 17, intercostal n. br. from T1,2(SI-13, dorsal scapular n.(SI-14, 15, cutaneous n. br. from C6, C7(SI-15, transverse cervical n.(SI-16, lesser occipital n. & great auricular n. from

  19. For Application to Human Spaceflight and ISS Experiments: VESGEN Mapping of Microvascular Network Remodeling during Intestinal Inflammation.

    Parsons-Wingerter, Patricia; Reinecker, Hans-Christian

    2012-10-01

    Challenges to long-duration space exploration and colonization in microgravity and cosmic radiation environments by humans include poorly understood risks for gastrointestinal function and cancer. Nonetheless, constant remodeling of the intestinal microvasculature is critical for tissue viability, healthy wound healing, and successful prevention or recovery from vascular-mediated inflammatory or ischemic diseases such as cancer. Currently no automated image analysis programs provide quantitative assessments of the complex structure of the mucosal vascular system that are necessary for tracking disease development and tissue recovery. Increasing abnormalities to the microvascular network geometry were therefore mapped with VESsel GENeration Analysis (VESGEN) software from 3D tissue reconstructions of developing intestinal inflammation in a dextran sulfate sodium (DSS) mouse model. By several VESGEN parameters and a novel vascular network linking analysis, inflammation strongly disrupted the regular, lattice-like geometry that defines the normal microvascular network, correlating positively with the increased recruitment of dendritic cells during mucosal defense responses. PMID:25143705

  20. Regional Human Development in transition economics: the role of institutions

    Pasquale Tridico

    2007-01-01

    The aim of this paper is to analyse regional difference yield in terms of Human Development (HD) in Poland. During transition, western Polish regions grew more than eastern regions, and differences in terms of GDP per capita are evident. Nevertheless, higher GDP per capita in the West did not produce a higher level of non-income dimension indicators (i.e., Education and Life expectancy). On the contrary eastern regions, although they have a lower level of GDP per capita, have a higher level o...

  1. In vivo gene expression profiling of human intestinal epithelial cells: analysis by laser microdissection of formalin fixed tissues

    Sabir Sadiah

    2008-05-01

    Full Text Available Abstract Background The small intestinal epithelium mediates vital functions of nutrient absorption and host defense. The spatial organization of the epithelial cells along the crypt-villus axis segregates them into regions of specialized function. However, the differences in transcriptional programming and the molecular machinery that governs the migration, adhesion, and differentiation of intestinal epithelial cell lineages in humans remain under-explored. To increase our understanding of these mechanisms, we have evaluated gene expression patterns of ileal epithelial cells isolated by laser capture microdissection from either the villus epithelial or crypt cell regions of healthy human small intestinal mucosa. Expression profiles in villus and crypt epithelium were determined by DNA microarray, quantitative real-time PCR, and immunohistochemistry based methods. The expression levels of selected epithelial biomarkers were also compared between gastrointestinal tissues. Results Previously established biomarkers as well as a novel and distinct set of genes believed to be linked to epithelial cell motility, adhesion, and differentiation were found to be enriched in each of the two corresponding cell populations (GEO accession: GSE10629. Additionally, high baseline expression levels of innate antimicrobials, alpha defensin 5 (HD5 and regenerating islet-derived 3 alpha (Reg3A, were detected exclusively within the small bowel crypt, most notably in the ileum in comparison to other sites along the gastrointestinal tract. Conclusion The elucidation of differential gene expression patterns between crypt and villus epithelial cell lineages in human ileal tissue provides novel insights into the molecular machinery that mediates their functions and spatial organization. Moreover, our findings establish an important framework of knowledge for future investigations of human gastrointestinal diseases.

  2. Cloning and sequencing of human intestinal alkaline phosphatase cDNA

    Partial protein sequence data obtained on intestinal alkaline phosphatase indicated a high degree of homology with the reported sequence of the placental isoenzyme. Accordingly, placental alkaline phosphatase cDNA was cloned and used as a probe to clone intestinal alkaline phosphatase cDNA. The latter is somewhat larger (3.1 kilobases) than the cDNA for the placental isozyme (2.8 kilobases). Although the 3' untranslated regions are quite different, there is almost 90% homology in the translated regions of the two isozymes. There are, however, significant differences at their amino and carboxyl termini and a substitution of an alanine in intestinal alkaline phosphatase for a glycine in the active site of the placental isozyme

  3. Central role of the gut epithelial barrier in the pathogenesis of chronic intestinal inflammation: lessons learned from animal models and human genetics.

    Pastorelli, Luca; De Salvo, Carlo; Mercado, Joseph R; Vecchi, Maurizio; Pizarro, Theresa T

    2013-01-01

    The gut mucosa is constantly challenged by a bombardment of foreign antigens and environmental microorganisms. As such, the precise regulation of the intestinal barrier allows the maintenance of mucosal immune homeostasis and prevents the onset of uncontrolled inflammation. In support of this concept, emerging evidence points to defects in components of the epithelial barrier as etiologic factors in the pathogenesis of inflammatory bowel diseases (IBDs). In fact, the integrity of the intestinal barrier relies on different elements, including robust innate immune responses, epithelial paracellular permeability, epithelial cell integrity, as well as the production of mucus. The purpose of this review is to systematically evaluate how alterations in the aforementioned epithelial components can lead to the disruption of intestinal immune homeostasis, and subsequent inflammation. In this regard, the wealth of data from mouse models of intestinal inflammation and human genetics are pivotal in understanding pathogenic pathways, for example, that are initiated from the specific loss of function of a single protein leading to the onset of intestinal disease. On the other hand, several recently proposed therapeutic approaches to treat human IBD are targeted at enhancing different elements of gut barrier function, further supporting a primary role of the epithelium in the pathogenesis of chronic intestinal inflammation and emphasizing the importance of maintaining a healthy and effective intestinal barrier. PMID:24062746

  4. Central role of the gut epithelial barrier in pathogenesis of chronic intestinal inflammation: Lessons learned from animal models and human genetics

    Luca ePastorelli

    2013-09-01

    Full Text Available The gut mucosa is constantly challenged by a bombardment of foreign antigens and environmental microorganisms. As such, the precise regulation of the intestinal barrier allows the maintenance of mucosal immune homeostasis and prevents the onset of uncontrolled inflammation. In support of this concept, emerging evidence points to defects in components of the epithelial barrier as etiologic factors in the pathogenesis of inflammatory bowel diseases (IBDs. In fact, the integrity of the intestinal barrier relies on different elements, including robust innate immune responses, epithelial paracellular permeability, epithelial cell integrity, as well as the production of mucus. The purpose of this review is to systematically evaluate how alterations in the aforementioned epithelial components can lead to the disruption of intestinal immune homeostasis, and subsequent inflammation. In this regard, the wealth of data from mouse models of intestinal inflammation and human genetics are pivotal in understanding pathogenic pathways, for example, that are initiated from the specific loss of function of a single protein leading to the onset of intestinal disease. On the other hand, several recently proposed therapeutic approaches to treat human IBD are targeted at enhancing different elements of gut barrier function, further supporting a primary role of the epithelium in the pathogenesis of chronic intestinal inflammation and emphasizing the importance of maintaining a healthy and effective intestinal barrier.

  5. The intestine is a blender

    Yang, Patricia; Lamarca, Morgan; Kravets, Victoria; Hu, David

    According to the U.S. Department of Health and Human Services, digestive disease affects 60 to 70 million people and costs over 140 billion annually. Despite the significance of the gastrointestinal tract to human health, the physics of digestion remains poorly understood. In this study, we ask a simple question: what sets the frequency of intestinal contractions? We measure the frequency of intestinal contractions in rats, as a function of distance down the intestine. We find that intestines Contract radially ten times faster than longitudinally. This motion promotes mixing and, in turn, absorption of food products by the intestinal wall. We calculate viscous dissipation in the intestinal fluid to rationalize the relationship between frequency of intestinal contraction and the viscosity of the intestinal contents. Our findings may help to understand the evolution of the intestine as an ideal mixer.

  6. Comparative Analysis of the Cytotoxic Effects of Okadaic Acid-Group Toxins on Human Intestinal Cell Lines

    Pierre-Jean Ferron

    2014-08-01

    Full Text Available The phycotoxin, okadaic acid (OA and dinophysistoxin 1 and 2 (DTX-1 and -2 are protein phosphatase PP2A and PP1 inhibitors involved in diarrhetic shellfish poisoning (DSP. Data on the toxicity of the OA-group toxins show some differences with respect to the in vivo acute toxicity between the toxin members. In order to investigate whether OA and congeners DTX-1 and -2 may induce different mechanisms of action during acute toxicity on the human intestine, we compared their toxicological effects in two in vitro intestinal cell models: the colorectal adenocarcinoma cell line, Caco-2, and the intestinal muco-secreting cell line, HT29-MTX. Using a high content analysis approach, we evaluated various cytotoxicity parameters, including apoptosis (caspase-3 activation, DNA damage (phosphorylation of histone H2AX, inflammation (translocation of NF-κB and cell proliferation (Ki-67 production. Investigation of the kinetics of the cellular responses demonstrated that the three toxins induced a pro-inflammatory response followed by cell cycle disruption in both cell lines, leading to apoptosis. Our results demonstrate that the three toxins induce similar effects, as no major differences in the cytotoxic responses could be detected. However DTX-1 induced cytotoxic effects at five-fold lower concentrations than for OA and DTX-2.

  7. Short-Chain Fatty Acids Regulate Secretion of IL-8 from Human Intestinal Epithelial Cell Lines in vitro.

    Asarat, M; Vasiljevic, T; Apostolopoulos, V; Donkor, O

    2015-01-01

    Short-chain fatty acids (SCFAs) including acetate, propionate and butyrate play an important role in the physiological functions of epithelial cells and colonocytes, such as immune response regulation. Human intestinal epithelial cells (IECs) contribute in intestinal immune response via different ways, such as production of different immune factors including Interleukin (IL) IL-8, which act as chemoattractant for neutrophils, and subsequently enhance inflammation. Therefore, we aimed to evaluate the effects of SCFAs on IECs viability and production of IL-8 in vitro. SCFAs were co-cultured with either normal intestinal epithelial (T4056) or adenocarcinoma derived (HT-29) cell lines for 24-96 h in the presence of E.coli lipopolysaccharides (LPS). Cell viability, proliferation, production of IL-8 and expression of IL-8 mRNA were determined in the cell cultures. The result showed that 20 mM of SCFAs was non-cytotoxic to T4056 and enhanced their growth, whereas the growth of HT-29 was inhibited. The SCFAs down regulated LPS-stimulated IL-8 secretion with different response patterns, but no obvious effects on the release of IL-8 from non LPS- stimulated cells. In conclusion, SCFAs showed regulatory effect on release of LPS-stimulated IL-8 as well as the expression of mRNA of IL-8; these might explain the anti-inflammatory and anti-carcinogenic mechanism of SCFAs. PMID:26436853

  8. [Human intestinal parasites in Subsaharan Africa. II. Sao Tomé and Principe].

    Pampiglione, S; Visconti, S; Pezzino, G

    1987-04-01

    In 1983 the authors carried out a survey in the Democratic Republic of São Tomé and Principe, analysing 1050 specimens of stools collected among the population from apparently healthy subjects chosen at random and in a number proportional to the distribution of the population in the regions of the country (about 1% of the population was examined). The examined subjects were divided into 3 age groups (0-3, 4-12, more than 12 years old), to have homogeneous groups in relation principally to modalities of life and nutritional patterns. There were 488 male subjects and 562 females. The survey was preceded by a sensitization of the people to the problem of intestinal parasites and by two preliminary surveys about the number of existing latrines and about people's believes and attitudes in relation to helmintiasis. The tests were made according to the modified Ritchie technique on fecal specimens preserved with 10% formol solution. The following results were found: a) Protozoa: Entamoeba coli, 43.0%; Iodamoeba buetschlii, 9.0%; Giardia intestinalis, 8.8%; Endolimax nana, 7.0%; E. histolytica, 5.5%; E. hartmanni, 2.5%; Chilomastix mesnili, 2.3%; Trichomonas intestinalis, 0.2%; Balantidium coli, 0.1%. b) Helminths: Trichuris trichiura, 87.7%; Ascaris lumbricoides, 64.3%; Ancylostomatidae, 40.5%; Strongyloides stercoralis, 6.8%; Hymenolepis diminuta, 0.3%; H. nana, 0.2%; Schistosoma haematobium, 0.2%. In 28.2% of the specimens (with more than 50% of subjects in some villages) eggs of Heterophyidae were found, very similar to Metagonimus yokogawai, but not yet identified by us, with the following characteristics: elliptical shape, average size 25 mu (22.2-27.7) X 18.5 mu (17-21), thick wall, operculum difficult to see, not sticking out from the outline but visible by focusing being in a different refractiveness, presence of a small polar knob, colour slightly brownish, asymmetric miracidium. Further investigations are necessary to identify the species of this trematode and

  9. Prevalence and Predictors of Intestinal Helminth Infections Among Human Immunodeficiency Virus Type 1–Infected Adults in an Urban African Setting

    Modjarrad, Kayvon; Zulu, Isaac; Redden, David T.; Njobvu, Lungowe; Freedman, David O; Vermund, Sten H.

    2005-01-01

    Sub-Saharan Africa is disproportionately burdened by intestinal helminth and human immunodeficiency virus (HIV)-1 infection. Recent evidence suggests detrimental immunologic effects from concomitant infection with the two pathogens. Few studies, however, have assessed the prevalence of and predictors for intestinal helminth infection among HIV-1–infected adults in urban African settings where HIV infection rates are highest. We collected and analyzed sociodemographic and parasitologic data fr...

  10. Functional studies of human intestinal alkaline sphingomyelinase by deglycosylation and mutagenesis

    Wu, Jun; Hansen, Gert H; Nilsson, Ake;

    2005-01-01

    Intestinal alk-SMase (alkaline sphingomyelinase) is an ectoenzyme related to the NPP (nucleotide phosphodiesterase) family. It has five potential N-glycosylation sites and predicated transmembrane domains at both the N- and C-termini. The amino acid residues forming the two metal-binding sites...

  11. Bone marrow derivation of pericryptal myofibroblasts in the mouse and human small intestine and colon

    Brittan, M; Hunt, T.; Jeffery, R.; Poulsom, R.; Forbes, S.J.; K. Hodivala-Dilke; Goldman, J.; Alison, M R; Wright, N. A.

    2002-01-01

    Background and aims: In order to establish whether extraintestinal cells contribute to the turnover and repair of gastrointestinal tissues, we studied the colons and small intestines of female mice that had received a male bone marrow transplant, together with gastrointestinal biopsies from female patients that had developed graft versus host disease after receiving a bone marrow transplant from male donors.

  12. Microbial communities in the human small intestine - coupling diversity to metagenomics

    Booijink, C.C.G.M.; Zoetendal, E.G.; Kleerebezem, M.; Vos, de W.M.

    2007-01-01

    The gastrointestinal tract is the main site where the conversion and absorption of food components takes place. The host-derived physiological processes and the residing microorganisms, especially in the small intestine, contribute to this nutrient supply. To circumvent sampling problems of the smal

  13. Human intestinal P-glycoprotein activity estimated by the model substrate digoxin

    Larsen, U L; Hyldahl Olesen, L; Nyvold, Charlotte Guldborg;

    2007-01-01

    P-glycoprotein (Pgp) plays a part in the intestinal uptake of xenobiotics and has been associated with susceptibility to ulcerative colitis. The aim of this study was to examine Pgp activity in relation to age, gender, medical treatment (rifampicin or ketoconazole) and the multidrug resistance (M...

  14. Intestinal Cancer

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

  15. Analysis of the human intestinal epithelial cell transcriptional response to Lactobacillus acidophilus, Lactobacillus salivarius, Bifidobacterium lactis and Escherichia coli

    Putaala, H; Barrangou, R; Leyer, G J;

    2010-01-01

    comparative analysis of the global in vitro transcriptional response of human intestinal epithelial cells to Lactobacillus acidophilus NCFM™, Lactobacillus salivarius Ls-33, Bifidobacterium animalis subsp. lactis 420, and enterohaemorrhagic Escherichia coli O157:H7 (EHEC). Interestingly, L. salivarius Ls-33...... regulation of apoptosis and adipogenesis, and lipid-metabolism related regulation by the probiotics. Specific changes such as regulation of cell-cell adhesion by B. lactis 420, superoxide metabolism by L. salivarius Ls-33, and regulation of MAPK pathway by L. acidophilus NCFM™ were noted. Furthermore...

  16. Affinity isolation of the extracellular chitinolytic enzymes from culture fluids of the human intestinal bacterium Clostridium paraputrificum J4

    Tishchenko, Galina; Šimůnek, Jiří; Dohnálek, Jan; Dušková, Jarmila; Koppová, Ingrid; Rozhetsky, K.

    Praha : Česká společnost chemického inženýrství, 2012. 0785. ISBN 978-80-905035-1-9. [International Congress of Chemical and Process Engineering CHISA 2012 /20./ and Conference PRES 2012 /15./. 25.08.2012-29.08.2012, Praha] R&D Projects: GA ČR GA310/09/1407 Institutional research plan: CEZ:AV0Z40500505; CEZ:AV0Z50450515 Institutional support: RVO:61389013 ; RVO:67985904 Keywords : low-molecular-weight chitosans * chitinolytic enzymes * human intestinal bacterium Clostridium paraputrificum J4 Subject RIV: EE - Microbiology, Virology

  17. VESGEN Mapping of Bioactive Protection against Intestinal Inflammation: Application to Human Spaceflight and ISS Experiments

    Parsons-Wingerter, P. A.; Chen, X.; Kelly, C. P.; Reinecker, H. C.

    2011-01-01

    Challenges to successful space exploration and colonization include adverse physiological reactions to micro gravity and space radiation factors. Constant remodeling of the microvasculature is critical for tissue preservation, wound healing, and recovery after ischemia. Regulation of the vascular system in the intestine is particularly important to enable nutrient absorption while maintaining barrier function and mucosal defense against micro biota. Although tremendous progress has been made in understanding the molecular circuits regulating neovascularization, our knowledge of the adaptations of the vascular system to environmental challenges in the intestine remains incomplete. This is in part because of the lack of methods to observe and quantify the complex processes associated with vascular responses in vivo. Developed by GRC as a mature beta version, pre-release research software, VESsel GENeration Analysis (VESGEN) maps and quantifies the fractal-based complexity of vascular branching for novel insights into the cytokine, transgenic and therapeutic regulation of angiogenesis, lymphangiogenesis and microvascular remodeling. Here we demonstrate that VESGEN can be used to characterize the dynamic vascular responses to acute intestinal inflammation and mucosal recovery from in vivo confocal microscopic 3D image series. We induced transient intestinal inflammation in mice by DSS treatment and investigated whether the ability of the pro biotic yeast Saccharomyces boulardii (Sb) to protect against intestinal inflammation was due to regulation of vascular remodeling. A primary characteristic of inflammation is excessive neovascularization (angiogenesis) resulting in fragile vessels prone to bleeding. Morphological parameters for triplicate specimens revealed that Sb treatment greatly reduced the inflammatory response of vascular networks by an average of 78%. This resulted from Sb inhibition of vascular endothelial growth factor receptor signaling, a major

  18. Intestinal Coccidia

    MJ Ggaravi

    2007-06-01

    Full Text Available Intestinal Coccidia are a subclass of Apicomplexa phylum. Eucoccidida are facultative heteroxenous, but some of them are monoxenous. They have sexual and asexual life cycle. Some coccidia are human pathogens, for example: Cryptosporidium: Cryptosporidiums has many species that are mammalian intestinal parasites.C. Parvum specie is a human pathogenic protozoa. Cryptosporidum has circle or ellipse shapes and nearly 4-6 mm. It is transmitted in warm seasons. Oocyst is obtained insexual life cycle that has 20% thin layer and 80% thick layer. Oocyst with thick layer is able to live a long time in nature. They are the third or forth of gastroentritis disease that have digestive disorder like anorexia, nausea, persistent diarrhoea, malabsorption and leanness. The disease forms choronic and acute stages and it is able to kill the immunodeficiency cases. Sometimes it has HIV symptoms similar to pneumonia and respiratory track infection. Laboratory diagnosis is based on Oocyst finding in stool exam and that shitter floatation and Cr (KOH2 are the best methods. Modified zyh-lnelson and fleocroum are the best staining methods too. This parasite is transmitted by zoonotic and Antroponotic origin. Molecular studies have shown two Genotypes (I&II. Genotype I is aquatic and II is zoonotic. The prevalence rate is 3% in infants and 10% in calves. Cyclospora: This parasite is novel and is bigger than cryptosporidium.It isn't known a clear life cycle but is transmitted by water, vegetables and fruits as raspberries. and mulberries. Human is a specific host. When a parasite is in the intestine it causes inflammatory reaction in Entrocyte.The patient shows watery diarrhoea with nausea, vomitting, pain, Stomach cramp, anorexia, malabsorption and cachexia. The disease period is 3 monthes in immunodeficiency cases but it is selflimited in normal cases. Autofluorescence characteristic is differential diagnosis, prevalence rate of disease is unknown. Isospora: This

  19. Understanding the human dimensions of a sustainable energy transition

    Linda eSteg

    2015-06-01

    Full Text Available Global climate change threatens the health, economic prospects, and basic food and water sources of people. A wide range of changes in household energy behaviour is needed to realise a sustainable energy transition. We propose a general framework to understand and encourage sustainable energy behaviours, comprising four key issues. First, we need to identify which behaviours need to be changed. A sustainable energy transition involves changes in a wide range of energy behaviours, including the adoption of sustainable energy sources and energy-efficient technology, investments in energy efficiency measures in buildings, and changes in direct and indirect energy use behaviour. Second, we need to understand which factors underlie these different types of sustainable energy behaviours. We discuss three main factors that influence sustainable energy behaviours: knowledge, motivations, and contextual factors. Third, we need to test the effects of interventions aimed to promote sustainable energy behaviours. Interventions can be aimed at changing the actual costs and benefits of behaviour, or at changing people’s perceptions and evaluations of different costs and benefits of behavioural options. Fourth, it is important to understand which factors affect the acceptability of energy policies and energy systems changes. We discuss important findings from psychological studies on these four topics, and propose a research agenda to further explore these topics. We emphasise the need of an integrated approach in studying the human dimensions of a sustainable energy transition that increases our understanding of which general factors affect a wide range of energy behaviours as well as the acceptability of different energy policies and energy system changes.

  20. Comparative metaproteomics and diversity analysis of human intestinal microbiota testifies for its temporal stability and expression of core functions.

    Carolin A Kolmeder

    Full Text Available The human intestinal tract is colonized by microbial communities that show a subject-specific composition and a high-level temporal stability in healthy adults. To determine whether this is reflected at the functional level, we compared the faecal metaproteomes of healthy subjects over time using a novel high-throughput approach based on denaturing polyacrylamide gel electrophoresis and liquid chromatography-tandem mass spectrometry. The developed robust metaproteomics workflow and identification pipeline was used to study the composition and temporal stability of the intestinal metaproteome using faecal samples collected from 3 healthy subjects over a period of six to twelve months. The same samples were also subjected to DNA extraction and analysed for their microbial composition and diversity using the Human Intestinal Tract Chip, a validated phylogenetic microarray. Using metagenome and single genome sequence data out of the thousands of mass spectra generated per sample, approximately 1,000 peptides per sample were identified. Our results indicate that the faecal metaproteome is subject-specific and stable during a one-year period. A stable common core of approximately 1,000 proteins could be recognized in each of the subjects, indicating a common functional core that is mainly involved in carbohydrate transport and degradation. Additionally, a variety of surface proteins could be identified, including potential microbes-host interacting components such as flagellins and pili. Altogether, we observed a highly comparable subject-specific clustering of the metaproteomic and phylogenetic profiles, indicating that the distinct microbial activity is reflected by the individual composition.

  1. Short-chain fructo-oligosaccharides modulate intestinal microbiota and metabolic parameters of humanized gnotobiotic diet induced obesity mice.

    Frederique Respondek

    Full Text Available Prebiotic fibres like short-chain fructo-oligosaccharides (scFOS are known to selectively modulate the composition of the intestinal microbiota and especially to stimulate Bifidobacteria. In parallel, the involvement of intestinal microbiota in host metabolic regulation has been recently highlighted. The objective of the study was to evaluate the effect of scFOS on the composition of the faecal microbiota and on metabolic parameters in an animal model of diet-induced obesity harbouring a human-type microbiota. Forty eight axenic C57BL/6J mice were inoculated with a sample of faecal human microbiota and randomly assigned to one of 3 diets for 7 weeks: a control diet, a high fat diet (HF, 60% of energy derived from fat or an isocaloric HF diet containing 10% of scFOS (HF-scFOS. Mice fed with the two HF gained at least 21% more weight than mice from the control group. Addition of scFOS partially abolished the deposition of fat mass but significantly increased the weight of the caecum. The analysis of the taxonomic composition of the faecal microbiota by FISH technique revealed that the addition of scFOS induced a significant increase of faecal Bifidobacteria and the Clostridium coccoides group whereas it decreased the Clostridium leptum group. In addition to modifying the composition of the faecal microbiota, scFOS most prominently affected the faecal metabolome (e.g. bile acids derivatives, hydroxyl monoenoic fatty acids as well as urine, plasma hydrophilic and plasma lipid metabolomes. The increase in C. coccoides and the decrease in C. leptum, were highly correlated to these metabolic changes, including insulinaemia, as well as to the weight of the caecum (empty and full but not the increase in Bifidobacteria. In conclusion scFOS induce profound metabolic changes by modulating the composition and the activity of the intestinal microbiota, that may partly explain their effect on the reduction of insulinaemia.

  2. Identification of interstitial cells of Cajal. Significance for studies of human small intestine and colon

    Rumessen, J J

    1994-01-01

    Interstitial cells of Cajal (ICC) were described a century ago by Ramón y Cajal a.o. as primitive neurons in the intestines. In the period 1900-1960 a large number of light microscopical studies of ICC were published, in which ICC were identified by heir characteristic morphology. After 1960...... electron microscopical studies emphasized similarities between ICC and fibroblasts. In our early studies of ICC in the external musculature of mouse small intestine, we identified ICC by their characteristic morphology and topography, and we analyzed the relation between ICC, autonomic nerves and smooth...... muscle. These studies strongly suggested that ICC were fundamental regulators of external muscle function. These hypotheses have since been supported by independent morphological and electrophysiological evidence, strongly suggesting a pacemaker role of some ICC populations as well as other regulatory...

  3. Identification of human cytochrome P450 enzymes involved in the hepatic and intestinal biotransformation of 20(S)-protopanaxadiol.

    Chiu, Nga Ting Colette; Tomlinson Guns, Emma S; Adomat, Hans; Jia, William; Deb, Subrata

    2014-03-01

    20(S)-Protopanaxadiol (aPPD), a ginseng sapogenin, has been shown to be a promising anti-cancer compound and anti-depressant agent. Although the bacterial biotransformation of ginsenosides has been studied thoroughly, few have reported on the cytochrome P450 (P450) mediated metabolism of aPPD. Taken orally, aPPD must first undergo absorption and metabolism in the intestine before further metabolism in the liver. The present study investigated the comparative biotransformation profile of aPPD in human intestinal microsomes (HIM) and human liver microsomes (HLM) and characterized the human P450 enzymes involved in aPPD metabolism. Three major monooxygenated metabolites and five minor dioxygenated metabolites were identified as the predominant products in aPPD incubations with HIM and HLM using liquid chromatography-mass spectrometry. Reaction phenotyping studies were performed with a panel of specific P450 chemical inhibitors, antibody inhibition and human recombinant P450 enzymes. Ketoconazole, a CYP3A inhibitor, blocked the formation of oxygenated metabolites of aPPD in both HIM and HLM in a concentration dependent manner. Among the human recombinant P450 enzymes assayed, CYP3A4 exhibited the highest activity towards aPPD oxidative metabolite formation, followed by CYP3A5. In summary, the results have shown that aPPD is extensively metabolized by HIM and the metabolite profile following in vitro incubations is similar in HIM and HLM. CYP3A4 and CYP3A5 isoforms are the predominant enzymes responsible for oxygenation of aPPD in HIM and HLM. The characterization of aPPD as a CYP3A substrate may facilitate better prediction of drug-herb interactions when aPPD is taken concomitantly with other therapeutic agents. PMID:24151189

  4. Vasoactive Intestinal Peptide Induction by Ciliary Neurotrophic Factor in Donor Human Corneal Endothelium in situ

    Koh, Shay-Whey M.; Guo, Yan; Bernstein, Steve L.; Waschek, James A.; Liu, Xiuhuai; Symes, Aviva J

    2007-01-01

    After peripheral nerve axotomy, vasoactive intestinal peptide (VIP) gene expression is upregulated in neurons, whereas ciliary neurotrophic factor (CNTF) accumulates extracellularly at the lesion site. Although CNTF-induced VIP gene expression has been reported in cultured sympathetic neurons and neuroblastoma cells, it still remains to be determined if CNTF and VIP play interrelated roles in nerve injury. The corneal endothelium, like sympathetic neurons, derives from the neural crest. Previ...

  5. Digestion of “Resistant” Starch Sources in the Human Small Intestine

    RoelJ.Vonk; Yue-XinYang; 等

    2001-01-01

    Background:Resistant starch sources,which are only partially digested in the small intestine,can be used to increase colonic avalialbiltiy of short chain fatty acids.Objective:To study the characteristics of the fermentiation of resistant starch,fist its small intestinal digestion has to be quantified.In our study,we performed this by comparing the metalbolic fate of highley digestible corn starch(DCS) ,Hylon VII and Novelose ,which are of corn origin and therefore naturally enriched in 13C.Design:After administration of 40g starch or glucose to seven healthy volunteers,glucose and exogenous glucose concentrations in serum and 13CO2 excretion in breasth were analyzed for 6hr.Carbon-13 abundance of CO2 was analyzed by Isotope Ratio Mass Spectormtry(IRMS) and 13C abundance of glucose by Gas Chromatography/Combustion/IRMS.Results:comparing the area under the curve(2hr) or exgenous glucose concentration in serum(13C-glycemic index)after intake of starch or glucos.digestion percentages for DCS,hylon VII and Novelose were calcualted to be 82%±23%,44%±16%and 43%±15%,Comparing 6h cumulative percentage dose recovery in breath revealed that 119%±28% of DCS,55%±23%of Hylon VII and 50±26% of Novelose is digested in the small intestine.Conclusion:Theses data show that the exogenous glucose reponse in serum and the 13CO2 excretion in breath can be used to estimate smlall intestinal digestion of resistant starch,which amounts approximately 50%.

  6. FOXA2 regulates a network of genes involved in critical functions of human intestinal epithelial cells.

    Gosalia, Nehal; Yang, Rui; Kerschner, Jenny L; Harris, Ann

    2015-07-01

    The forkhead box A (FOXA) family of pioneer transcription factors is critical for the development of many endoderm-derived tissues. Their importance in regulating biological processes in the lung and liver is extensively characterized, though much less is known about their role in intestine. Here we investigate the contribution of FOXA2 to coordinating intestinal epithelial cell function using postconfluent Caco2 cells, differentiated into an enterocyte-like model. FOXA2 binding sites genome-wide were determined by ChIP-seq and direct targets of the factor were validated by ChIP-qPCR and siRNA-mediated depletion of FOXA1/2 followed by RT-qPCR. Peaks of FOXA2 occupancy were frequent at loci contributing to gene ontology pathways of regulation of cell migration, cell motion, and plasma membrane function. Depletion of both FOXA1 and FOXA2 led to a significant reduction in the expression of multiple transmembrane proteins including ion channels and transporters, which form a network that is essential for maintaining normal ion and solute transport. One of the targets was the adenosine A2B receptor, and reduced receptor mRNA levels were associated with a functional decrease in intracellular cyclic AMP. We also observed that 30% of FOXA2 binding sites contained a GATA motif and that FOXA1/A2 depletion reduced GATA-4, but not GATA-6 protein levels. These data show that FOXA2 plays a pivotal role in regulating intestinal epithelial cell function. Moreover, that the FOXA and GATA families of transcription factors may work cooperatively to regulate gene expression genome-wide in the intestinal epithelium. PMID:25921584

  7. Mast cell expression of the serotonin1A receptor in guinea pig and human intestine

    Wang, Guo-Du; Wang, Xi-Yu; Zou, Fei; Qu, Meihua; Liu, Sumei; Fei, Guijun; Xia, Yun; Needleman, Bradley J.; Mikami, Dean J.; Wood, Jackie D.

    2013-01-01

    Serotonin [5-hydroxytryptamine (5-HT)] is released from enterochromaffin cells in the mucosa of the small intestine. We tested a hypothesis that elevation of 5-HT in the environment of enteric mast cells might degranulate the mast cells and release mediators that become paracrine signals to the enteric nervous system, spinal afferents, and secretory glands. Western blotting, immunofluorescence, ELISA, and pharmacological analysis were used to study expression of 5-HT receptors by mast cells i...

  8. Attachment of Giardia lamblia trophozoites to a cultured human intestinal cell line.

    Katelaris, P H; Naeem, A; Farthing, M J

    1995-01-01

    Attachment of Giardia lamblia trophozoites to enterocytes is essential for colonisation of the small intestine and is considered a prerequisite for giardia induced enterocyte damage. The precise mechanisms involved are still being debated and some earlier work has been performed in models of uncertain biological relevance. In this study, co-incubation of giardia with enterocyte-like differentiated Caco-2 cells was used as a model to study the influence of physical and chemical factors on atta...

  9. Mucin degradation by Bifidobacterium strains isolated from the human intestinal microbiota.

    Ruas-Madiedo, Patricia; Gueimonde, Miguel; Fernández-García, María; de los Reyes-Gavilán, Clara G; Margolles, Abelardo

    2008-03-01

    The presence of the genes engBF (endo-alpha-N-acetylgalactosaminidase) and afcA (1,2-alpha-L-fucosidase) was detected in several intestinal Bifidobacterium isolates. Two strains of Bifidobacterium bifidum contained both genes, and they were able to degrade high-molecular weight porcine mucin in vitro. The expression of both genes was highly induced in the presence of mucin. PMID:18223105

  10. Changes of E-cadherin and á-catenin in human and mouse intestinal tumours

    Šloncová, Eva; Frič, P.; Kučerová, Dana; Lojda, Z.; Tuháčková, Zdena; Sovová, Vlasta

    2001-01-01

    Roč. 33, č. 1 (2001), s. 13-17. ISSN 0018-2214 R&D Projects: GA ČR GV312/96/K205; GA ČR GA301/00/0269; GA MZd IZ4217 Institutional research plan: CEZ:AV0Z5052915 Keywords : E-cadherin * beta-catenin * intestinal tumours Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.169, year: 2001

  11. Polarity of fatty acid uptake and metabolism in a human intestinal cell line (CACO-2)

    Free fatty acids (ffa) can enter the intestinal cell via the apical (AP) or basolateral (BL) membrane. The authors are using the Caco-2 intestinal cell line to examine the polarity of ffa uptake and metabolism in the enterocyte. Cells are grown on permeable polycarbonate Transwell filters in order to obtain access to both AP and BL compartments. Differentiated Caco-2 cells form tight polarized monolayers which express small intestine-specific enzymes and are impermeable to the fluid phase marker Lucifer Yellow. Submicellar concentrations of 3H-palmitic acid (2uM) were added to AP or BL sides of Caco-2 monolayers at 37 degrees C and cells were incubated for various times between 2 and 120 minutes. Total AP and BL uptake is similar; however, when relative membrane surface areas are accounted for, AP uptake is about 2-fold higher. The metabolism of AP and BL ffa is not significantly different: triacylglycerol and phosphatidylcholine account for most of the metabolites (32±4 and 24±2% respectively at 5 minutes). Little ffa oxidation is observed. Preincubation with albumin-bound 2-monoolein (100uM) and palmitate (50uM) increases the level of TG metabolites. The results suggest that in this cell line the uptake of AP ffa may be greater than BL ffa, but that AP (dietary) ffa and BL (plasma) ffa are metabolized similarly

  12. Polarity of fatty acid uptake and metabolism in a human intestinal cell line (CACO-2)

    Trotter, P.J.; Storch, J. (Harvard School of Public Health, Boston, MA (United States))

    1990-02-26

    Free fatty acids (ffa) can enter the intestinal cell via the apical (AP) or basolateral (BL) membrane. The authors are using the Caco-2 intestinal cell line to examine the polarity of ffa uptake and metabolism in the enterocyte. Cells are grown on permeable polycarbonate Transwell filters in order to obtain access to both AP and BL compartments. Differentiated Caco-2 cells form tight polarized monolayers which express small intestine-specific enzymes and are impermeable to the fluid phase marker Lucifer Yellow. Submicellar concentrations of {sup 3}H-palmitic acid (2uM) were added to AP or BL sides of Caco-2 monolayers at 37{degrees}C and cells were incubated for various times between 2 and 120 minutes. Total AP and BL uptake is similar; however, when relative membrane surface areas are accounted for, AP uptake is about 2-fold higher. The metabolism of AP and BL ffa is not significantly different: triacylglycerol and phosphatidylcholine account for most of the metabolites (32{plus minus}4 and 24{plus minus}2% respectively at 5 minutes). Little ffa oxidation is observed. Preincubation with albumin-bound 2-monoolein (100uM) and palmitate (50uM) increases the level of TG metabolites. The results suggest that in this cell line the uptake of AP ffa may be greater than BL ffa, but that AP (dietary) ffa and BL (plasma) ffa are metabolized similarly.

  13. Farnesoid X receptor signal is involved in deoxycholic acid-induced intestinal metaplasia of normal human gastric epithelial cells.

    Li, Shu; Chen, Xin; Zhou, Lu; Wang, Bang-Mao

    2015-11-01

    The farnesoid X receptor (FXR) signaling pathway is known to be involved in the metabolism of bile acid, glucose and lipid. In the present study, we demonstrated that 400 µmol/l deoxycholic acid (DCA) stimulation promotes the proliferation of normal human gastric epithelial cells (GES-1). In addition, DCA activated FXR and increased the expression of intestinal metaplasia genes, including caudal-related homeobox transcription factor 2 (Cdx2) and mucin 2 (MUC2). The treatment of FXR agonist GW4064/antagonist guggulsterone (Gug.) significantly increased/decreased the expression levels of FXR, Cdx2 and MUC2 protein in DCA-induced GES-1 cells. GW4064/Gug. also enhanced/reduced the nuclear factor-κB (NF-κB) activity and binding of the Cdx2 promoter region and NF-κB, the most common subunit p50 protein. Taken together, the results indicated that DCA is capable of modulating the expression of Cdx2 and the downstream MUC2 via the nuclear receptor FXR-NF-κB activity in normal gastric epithelial cells. FXR signaling pathway may therefore be involved in the intestinal metaplasia of human gastric mucosa. PMID:26324224

  14. Study on human intestinal bacterium Blautia sp. AUH-JLD56 for the conversion of arctigenin to (-)-3'-desmethylarctigenin.

    Liu, Ming-Yue; Li, Meng; Wang, Xiu-Ling; Liu, Peng; Hao, Qing-Hong; Yu, Xiu-Mei

    2013-12-11

    Arctium lappa L. (A. lappa) is a popularly used vegetable as well as herbal medicine. Human intestinal microflora was reported to convert arctiin, the lignan compound with highest content in the dried fruits of Arctium lappa, to a series of metabolites. However, the specific bacterium responsible for the formation of 3'-desmethylarctigenin (3'-DMAG), the most predominant metabolite of arctiin by rat or human intestinal microflora, has not been isolated yet. In the present study, we isolated one single bacterium, which we named Blautia sp. AUH-JLD56, capable of solely biotransforming arctiin or arctigenin to (-)-3'-DMAG. The structure of the metabolite 3'-DMAG was elucidated by electrospray ionization mass spectrometry (ESI-MS) and (1)H and (13)C nuclear magnetic resonance spectroscopy. The biotransforming kinetics and maximum biotransforming capacity of strain AUH-JLD56 was investigated. In addition, the metabolite 3'-DMAG showed significantly higher 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity than that of the substrate arctigenin at the concentrations tested. PMID:24236649

  15. Scintigraphy of the small intestine: a simplified standard for study of transit with reference to normal values

    Evaluation of small bowel transit, which should preferably be performed using non-invasive techniques, is complex owing to the anatomical position of the small bowel. In order to avoid any influence of the gastric emptying rate on scintigraphic results, we have used 99mTc-HIDA, an intravenous tracer that is excreted in bile and thereby delivered directly into the duodenum. Thirty healthy subjects were studied after an overnight fast. Immediately after administration of 120 MBq 99mTc-HIDA, dynamic 1-min image acquisitions were begun. The duodenum and caecum were easily identified on the digitised images. Small bowel transit time was determined from the difference in the arrival times of the radiopharmaceutical in the proximal duodenum and caecum, as assessed by evaluation of the count rate against background activity (Scint 1) and by the visual appearance of activity (Scint 2). Hydrogen breath test was performed simultaneously to evaluate scintigraphic transit. Scintigraphic transit tests were also performed in 23 patients with motility disorders who had undergone manometry of the small bowel. In healthy subjects, the transit time of 99mTc-HIDA was 77.9±31.1 min (Scint 1) or 79.3±30.9 min (Scint 2) and the lactulose transit time was 100.1±43.4 min. Seventeen of the 23 patients had a dysmotility pattern verified by manometry, and in 14 of these patients, 99mTc-HIDA transit was prolonged. 99mTc-HIDA small bowel transit is a readily available method for the detection of transit abnormalities in the clinical setting. The method is clinically feasible and the transit time of 99mTc-HIDA shows a good correlation with results of the hydrogen breath test (lactulose transit time) in healthy volunteers. (orig.)

  16. Scintigraphy of the small intestine: a simplified standard for study of transit with reference to normal values

    Grybaeck, P.; Jacobsson, H. [Dept. of Radiology and Nuclear Medicine, Karolinska Hospital, Stockholm (Sweden); Blomquist, L.; Hellstroem, P.M. [Dept. of Gastroenterology and Hepatology, Karolinska Hospital, Stockholm (Sweden); Schnell, P.O. [Dept. of Hospital Physics, Karolinska Hospital, Stockholm (Sweden)

    2002-01-01

    Evaluation of small bowel transit, which should preferably be performed using non-invasive techniques, is complex owing to the anatomical position of the small bowel. In order to avoid any influence of the gastric emptying rate on scintigraphic results, we have used {sup 99m}Tc-HIDA, an intravenous tracer that is excreted in bile and thereby delivered directly into the duodenum. Thirty healthy subjects were studied after an overnight fast. Immediately after administration of 120 MBq {sup 99m}Tc-HIDA, dynamic 1-min image acquisitions were begun. The duodenum and caecum were easily identified on the digitised images. Small bowel transit time was determined from the difference in the arrival times of the radiopharmaceutical in the proximal duodenum and caecum, as assessed by evaluation of the count rate against background activity (Scint 1) and by the visual appearance of activity (Scint 2). Hydrogen breath test was performed simultaneously to evaluate scintigraphic transit. Scintigraphic transit tests were also performed in 23 patients with motility disorders who had undergone manometry of the small bowel. In healthy subjects, the transit time of {sup 99m}Tc-HIDA was 77.9{+-}31.1 min (Scint 1) or 79.3{+-}30.9 min (Scint 2) and the lactulose transit time was 100.1{+-}43.4 min. Seventeen of the 23 patients had a dysmotility pattern verified by manometry, and in 14 of these patients, {sup 99m}Tc-HIDA transit was prolonged. {sup 99m}Tc-HIDA small bowel transit is a readily available method for the detection of transit abnormalities in the clinical setting. The method is clinically feasible and the transit time of {sup 99m}Tc-HIDA shows a good correlation with results of the hydrogen breath test (lactulose transit time) in healthy volunteers. (orig.)

  17. Multiple forms of human intestinal alkaline phosphatase: chemical and enzymatic properties, and circulating clearances of the fast- and slow-moving enzymes

    Two forms of alkaline phosphatase orthophosphoric monoester phosphohydrolase (alkaline optimum, EC 3.1.3.1) have been purified from human small intestine by column chromatography on DEAE-cellulose and tyraminyl derivative affinity gel, and by preparative disc gel electrophoresis. Intestinal phosphatases were electrophoretically separated into two components, fast- and slow-moving enzymes, with apparent molecular weights of 140000 and 168000 and with subunit weights of 68000 and 80000, respectively. Organ distribution of injected 125I-labelled enzymes indicates that the desialylated hepatic enzyme was selectively distributed in liver, while the degalactosylated intestinal enzyme was incorporated into liver, lymph fluid, and small intestine. These results suggest that the pathway of circulating clearance of alkaline phosphatase has several routes. (Auth.)

  18. Fate and effect of ingested Bacillus cereus spores and vegetative cells in the intestinal tract of human-flora-associated rats

    Wilcks, Andrea; Hansen, Bjarne Munk; Hendriksen, Niels Bohse; Licht, Tine Rask

    2006-01-01

    The fate and effect of Bacillus cereus F4433/73R in the intestine of human-flora-associated rats was studied using bacteriological culturing techniques and PCR-denaturing gradient gel electrophoresis in combination with cell assays and immunoassays for detection of enterotoxins. In faecal samples...... from animals receiving vegetative cells, only few B. cereus cells were detected. Spores survived the gastric barrier well, and were in some cases detected up to 2 weeks after ingestion. Selective growing revealed no major changes in the intestinal flora during passage of B. cereus. However, denaturing...... gradient gel electrophoresis analysis with universal 16S rRNA gene primers revealed significant changes in the intestinal microbiota of animals dosed with spores. Vero cell assays and a commercial kit (BCET-RPLA) did not reveal any enterotoxin production from B. cereus F4433/73R in the intestinal tract....

  19. Effect of CpG-ODN combined with radiation on micronuclei cell of the human intestinal crypt epithelial cell

    In order study the changes of micronuclei cell frequency in the non-immune cell types, the human intestinal crypt epithelial cell (HIEC) was treated by CpG-ODN after radiation. MTT assay and micronuclei assay were used in this research. The result of MTT assay shows that CpG-ODN does not have any toxicity to HIEC in the concentration range of 0.00-1.25 μmol/L. Micronuclei assay measurement indicates that CpG-ODN can protect HIEC from radiation damage by reducing the micronucleus frequency (MNF) and the micronucleus cell frequency (MNCF). The experiment results reveal that CpG-ODN is safe and may have radioprotection effect on some non-immune human cell types. (authors)

  20. Sulphation of the heterocyclic amine 1,2,3,4-tetrahydroisoquinoline in the human liver and intestinal mucosa: interindividual variability.

    Pacifici, G M; D'alessandro, C; Gucci, A; Giuliani, L

    1997-01-01

    The sulphation rate of 1,2,3,4-tetrahydroisoquinoline (TIQ) was measured in the human liver and in the intestinal mucosa isolated from the transverse colon, ileum and duodenum. The rate (mean +/- SD) of hepatic TIQ sulphation was 500 +/- 174 pmol/min per mg in women (n = 61) and 591 +/- 201 in men (n = 39; P = 0.0087), varying over one order of magnitude in men and women. The sulphation rate of testosterone showed the same sex-dependent pattern and was correlated (r = 0.6055; P < 0.001) with that of TIQ. The frequency distribution of TIQ sulphation rate in human liver was bimodal: 70% of the population fell into the low-activity subgroup and the remaining 30% feel into the high-activity subgroup. In the colon (n = 56), the rate of TIQ sulphation was 30.4 +/- 15.6 pmol/min per mg and the values were similar in men and women (29.8 and 30.9 pmol/min per mg, respectively) but, varied over one order of magnitude and correlated (r = 0.7231; P < 0.001) with that of 4-nitrophenol. The rate of TIQ sulphation changed along the human bowel and mean (+/-SD) estimates for duodenum, ileum and transverse colon were 444 +/- 25, 182 +/- 87 and 30.4 +/- 15.6 pmol/ min per mg, respectively. The present results are consistent with the view that the heterocyclic amine TIQ is sulphated in the human liver and intestinal mucosa. TIQ-sulphotransferase activity varies among subjects and is mostly associated with the liver and duodenum. PMID:9248624

  1. Small intestinal bacterial overgrowth syndrome

    Jan; Bures; Jiri; Cyrany; Darina; Kohoutova; Miroslav; Frstl; Stanislav; Rejchrt; Jaroslav; Kvetina; Viktor; Vorisek; Marcela; Kopacova

    2010-01-01

    Human intestinal microbiota create a complex polymi-crobial ecology. This is characterised by its high population density, wide diversity and complexity of interaction. Any dysbalance of this complex intestinal microbiome, both qualitative and quantitative, might have serious health consequence for a macro-organism, including small intestinal bacterial overgrowth syndrome (SIBO).SIBO is defined as an increase in the number and/or alteration in the type of bacteria in the upper gastro-intestinal tract. There...

  2. Human cysticercosis and intestinal parasitism amongst the Ekari people of Irian Jaya.

    Muller, R; Lillywhite, J; Bending, J J; Catford, J C

    1987-12-01

    A random sample of 242 people showed that 42 had palpable cysts of Taenia solium. Faecal examination recovered eggs of T. solium in seven (3%), while Trichuris (83%), Ascaris (83%), hookworms (76%), Strongyloides stercoralis (10%) and Strongyloides sp. (29%), Entamoeba histolytica (14%), Entamoeba coli (22%), Entamoeba hartmanni (7%), Entamoeba polecki (7%), Balantidium coli (9%) and Dientamoeba fragilis (21%) were the most common other intestinal parasites encountered. ELISA tests, using antigens prepared from adults and eggs of T. solium and from cysticerci of T. saginata were not very sensitive, the last diagnosing less than half of known positives while still retaining good specificity. PMID:3430662

  3. The Influence of Different Apple Based Supplements on the Intestinal Microbiota of Humans

    Bergström, Anders; Wilcks, Andrea; Ravn-Haren, Gitte;

    2010-01-01

    Background and objective: The present project is part of the large ISAFRUIT project, where one of the objectives is to identify effects of apple and apple product on parameters related to gut health. In a previous rat study we observed changes in the intestinal microbiota of rats fed whole apples......-free), 3) cloudy juice (apple juice with pulp), and 4) pomace (press cake from the cloudy juice production process). Fecal samples were taken before and after each diet period. After DNA extraction, Denaturing Gradient Gel Electrophoresis (DGGE) with universal primers and specific primers for...

  4. Cytokine modulation (IL-6, IL-8, IL-10) by human breast milk lipids on intestinal epithelial cells (Caco-2).

    Barrera, Girolamo J; Sánchez, Gabriela

    2016-08-01

    Human breast milk is the best form of nourishment for infants during the first year of life. It is composed by a complex mixture of carbohydrates, proteins and fats. Breast milk provides nutrients and bioactive factors that themselves modulate maturation and development of the gastrointestinal tract. Many studies have shown that it provides protection against gastrointestinal tract inflammation. In this sense, this study aimed to evaluate the effect of human breast milk lipids on epithelial intestinal cells (Caco-2) cytokine regulation and the fatty acid transporter protein (FATP) involved in this process. Caco-2 cells were cultivated and stimulated with different concentration of human milk lipids from healthy human mothers (18-30-year-olds) or single commercial lipids for 48 h. We measured the concentrations and mRNA levels of IL-6, IL-8 and IL-10 cytokines by immunoassay (ELISA) and quantitative-PCR (qRT-PCR) technique, respectively. We observed a two to three times decrease in pro-inflammatory cytokine levels (p < 0.01) as well as an increase in anti-inflammatory IL-10 levels in cells stimulated with increasing concentrations of breast milk lipids. These results suggest that human breast milk lipids could have an important role on the cytokine modulation in the newborn bowel. PMID:26441050

  5. Analysis of the human intestinal epithelial cell transcriptional response to Lactobacillus acidophilus, Lactobacillus salivarius, Bifidobacterium lactis and Escherichia coli.

    Putaala, H; Barrangou, R; Leyer, G J; Ouwehand, A C; Hansen, E Bech; Romero, D A; Rautonen, N

    2010-09-01

    The complex microbial population residing in the human gastrointestinal tract consists of commensal, potential pathogenic and beneficial species, which are probably perceived differently by the host and consequently could be expected to trigger specific transcriptional responses. Here, we provide a comparative analysis of the global in vitro transcriptional response of human intestinal epithelial cells to Lactobacillus acidophilus NCFM™, Lactobacillus salivarius Ls-33, Bifidobacterium animalis subsp. lactis 420, and enterohaemorrhagic Escherichia coli O157:H7 (EHEC). Interestingly, L. salivarius Ls-33 DCE-induced changes were overall more similar to those of B. lactis 420 than to L. acidophilus NCFM™, which is consistent with previously observed in vivo immunomodulation properties. In the gene ontology and pathway analyses both specific and unspecific changes were observed. Common to all was the regulation of apoptosis and adipogenesis, and lipid-metabolism related regulation by the probiotics. Specific changes such as regulation of cell-cell adhesion by B. lactis 420, superoxide metabolism by L. salivarius Ls-33, and regulation of MAPK pathway by L. acidophilus NCFM™ were noted. Furthermore, fundamental differences were observed between the pathogenic and probiotic treatments in the Toll-like receptor pathway, especially for adapter molecules with a lowered level of transcriptional activation of MyD88, TRIF, IRAK1 and TRAF6 by probiotics compared to EHEC. The results in this study provide insights into the relationship between probiotics and human intestinal epithelial cells, notably with regard to strain-specific responses, and highlight the differences between transcriptional responses to pathogenic and probiotic bacteria. PMID:21831765

  6. Hes1 promotes the IL-22-mediated antimicrobial response by enhancing STAT3-dependent transcription in human intestinal epithelial cells

    Murano, Tatsuro [Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo (Japan); Okamoto, Ryuichi, E-mail: rokamoto.gast@tmd.ac.jp [Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo (Japan); Department of Advanced GI Therapeutics, Graduate School, Tokyo Medical and Dental University, Tokyo (Japan); Ito, Go; Nakata, Toru; Hibiya, Shuji; Shimizu, Hiromichi; Fujii, Satoru; Kano, Yoshihito; Mizutani, Tomohiro; Yui, Shiro; Akiyama-Morio, Junko; Nemoto, Yasuhiro [Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo (Japan); Tsuchiya, Kiichiro; Nakamura, Tetsuya [Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo (Japan); Department of Advanced GI Therapeutics, Graduate School, Tokyo Medical and Dental University, Tokyo (Japan); Watanabe, Mamoru [Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo (Japan)

    2014-01-17

    Highlights: •Hes1 enhances IL-22-STAT3 signaling in human intestinal epithelial cells. •Hes1 enhances REG family gene induction by IL-22-STAT3 signaling. •Protein level of Hes1 restricts the response to IL-22. •Present regulation of a cytokine signal represents a new mode of Hes1 function. -- Abstract: Notch signaling plays an essential role in the proliferation and differentiation of intestinal epithelial cells (IECs). We have previously shown that Notch signaling is up-regulated in the inflamed mucosa of ulcerative colitis (UC) and thereby plays an indispensable role in tissue regeneration. Here we show that in addition to Notch signaling, STAT3 signaling is highly activated in the inflamed mucosa of UC. Forced expression of the Notch target gene Hes1 dramatically enhanced the IL-22-mediated STAT3-dependent transcription in human IECs. This enhancement of STAT3-dependent transcription was achieved by the extended phosphorylation of STAT3 by Hes1. Microarray analysis revealed that Hes1-mediated enhancement of IL-22-STAT3 signaling significantly increased the induction of genes encoding antimicrobial peptides, such as REG1A, REG3A and REG3G, in human IECs. Conversely, the reduction of Hes1 protein levels with a γ-secretase inhibitor significantly down-regulated the induction of those genes in IECs, resulting in a markedly poor response to IL-22. Our present findings identify a new role for the molecular function of Hes1 in which the protein can interact with cytokine signals and regulate the immune response of IECs.

  7. Hes1 promotes the IL-22-mediated antimicrobial response by enhancing STAT3-dependent transcription in human intestinal epithelial cells

    Highlights: •Hes1 enhances IL-22-STAT3 signaling in human intestinal epithelial cells. •Hes1 enhances REG family gene induction by IL-22-STAT3 signaling. •Protein level of Hes1 restricts the response to IL-22. •Present regulation of a cytokine signal represents a new mode of Hes1 function. -- Abstract: Notch signaling plays an essential role in the proliferation and differentiation of intestinal epithelial cells (IECs). We have previously shown that Notch signaling is up-regulated in the inflamed mucosa of ulcerative colitis (UC) and thereby plays an indispensable role in tissue regeneration. Here we show that in addition to Notch signaling, STAT3 signaling is highly activated in the inflamed mucosa of UC. Forced expression of the Notch target gene Hes1 dramatically enhanced the IL-22-mediated STAT3-dependent transcription in human IECs. This enhancement of STAT3-dependent transcription was achieved by the extended phosphorylation of STAT3 by Hes1. Microarray analysis revealed that Hes1-mediated enhancement of IL-22-STAT3 signaling significantly increased the induction of genes encoding antimicrobial peptides, such as REG1A, REG3A and REG3G, in human IECs. Conversely, the reduction of Hes1 protein levels with a γ-secretase inhibitor significantly down-regulated the induction of those genes in IECs, resulting in a markedly poor response to IL-22. Our present findings identify a new role for the molecular function of Hes1 in which the protein can interact with cytokine signals and regulate the immune response of IECs

  8. Clostridium difficile-mediated effects on human intestinal epithelia: Modelling host-pathogen interactions in a vertical diffusion chamber.

    Jafari, Nazila V; Kuehne, Sarah A; Minton, Nigel P; Allan, Elaine; Bajaj-Elliott, Mona

    2016-02-01

    Clostridium difficile infection is one of the leading causes of healthcare associated diarrhoea in the developed world. Although the contribution of C. difficile toxins to disease pathogenesis is now well understood, many facets of host-pathogen interactions between the human intestinal epithelia and the C. difficile bacterium that may contribute to asymptomatic carriage and/or clinical disease remain less clear. Herein, we tested the hypothesis that C. difficile strains mediate intestinal epithelial cell (IEC) antimicrobial immunity via toxin dependent and independent means and that the 'anaerobic' environment has a significant impact on bacterial-IEC interactions. Crosstalk between three C. difficile PCR ribotypes (RT) [RT027 (strain R20291), RT012 (strain 630) and RT017 (strains M68 and CF5)] and IEC cell-lines were investigated. All RTs showed significant engagement with human Toll-like receptors (TLR)-5, TLR2-CD14 and TLR2/6 as measured by IL-8 release from TLR-transfected HEK cells. Co-culture studies indicated minimal impact of R20291 and 630 TcdA and TcdB on bacterial adherence to Caco-2 cells. An apical anaerobic environment had a major effect on C. difficile-T84 crosstalk as significantly greater cytokine immunity and trans-epithelial electrical resistance (TEER) dysfunction was recorded when co-cultures were performed in an Ussing chamber system compared to standard 5% CO2 conditions. Overall, this study suggests that anaerobic C. difficile engagement with human IECs is a complex interplay that involves bacterial and toxin-mediated cellular events. PMID:26708704

  9. Transport of quercetin di-sodium salt in the human intestinal epithelial Caco-2 cell monolayer 139.

    Milane, H A; Al Ahmad, A; Naitchabane, M; Vandamme, T F; Jung, L; Ubeaud, G

    2007-01-01

    Quercetin di-sodium salt (QDS), a water-soluble derivative of quercetin (Q), is a potent free radical scavenger. The aim of this study was to examine the in vitro intestinal transport of QDS compared to that of Q using the Caco-2 human intestinal epithelial cell line. The apical (A) to basolateral (B) transport of QDS was found to be higher than the B to A transport of this compound. This polarized transport involved the presence of a carrier protein system. The involvement of the sodium/glucose transporter-1 (SGLT-1) was shown by using phloridzin, a selective inhibitor of this conveyor system. However, the transport of Q was not affected by this inhibitor. Moreover, the influx of QDS was pH-sensitive and decreased at pH 5.5 compared with that observed at pH 7.4 and 6.5. The permeability of QDS was 10-fold higher than that of Q. This could be explained by the involvement of SLGT-1 and the absence of an active efflux pump in the absorption of QDS in comparison with Q. This finding was supported by comparing the solubility of Q with that of QDS. This study indicates that both the higher solubility of QDS and its dependence on the SGLT-1 transport system resulted in more efficient permeability compared to Q. PMID:18062406

  10. Association between the human herpesvirus 8 and the diffuse nodular lymphoid hyperplasia of the small intestine in common variable immunodeficiency

    The common variable immunodeficiency (CVID) is the more frequent primary immunodeficiency in clinical field and its presentation forms are very variable. We describe the case of a women presenting with adult CVID with chronic diarrhea syndrome, weight loss and diffuse lymphadenopathies, where the more marked immunologic features were a deep hypogammaglobulinemia of the three major kinds of immunoglobulins and numerical decrease of B cells (CD19+) and NK cells (CD3-CD56+) in peripheral blood. Biopsy of small intestine obtained by video-assisted panendoscope, showed the presence of a multinodular lymphoid hyperplasia with partial atrophy of hairinesses. Immunohistochemistry showed that nodules were high germinal centers with distribution of B cells (CD20+) and T cells (CD3+), similar to that of normal follicle. There was not differential expression of the K and λ light chains. The real time polymerase chain reaction (QRT-PCR) method detected many copies from the genome of type 8 human herpesvirus (VHH-8) (133 copies/μL of DNA) in biopsy of intestinal nodule DNA. VHH-8 infection may to be a significant factor in pathogenesis of lymphoproliferative disorders in patients presenting with CVID

  11. Interleukin-17 is a potent immuno-modulator and regulator of normal human intestinal epithelial cell growth

    Upregulation of the T-cell derived cytokine interleukin (IL-17) was reported in the inflamed intestinal mucosa of patients with inflammatory bowel disorders. In this study, we analyzed the effect of IL-17 on human intestinal epithelial cell (HIEC) turnover and functions. Proliferation and apoptosis in response to IL-17 was monitored in HIEC (cell counts, [3H]thymidine incorporation method, and annexinV-PI-apoptosis assay). Signalling pathways were analyzed by Western blots, electromobility shift assay, and immunofluorescence studies. IL-17 proved to be a potent inhibitor of HIEC proliferation without any pro-apoptotic/necrotic effect. The growth inhibitory effect of IL-17 was mediated via the p38 stress kinase. Consequently, the p38-SAPkinase-inhibitor SB203580 abrogated this anti-mitotic effect. In parallel, IL-17 provoked the degradation of IκBα, allowing nuclear translocation of the p65 NF-κB subunit and induction of the NF-κB-controlled genes IL-6 and -8. IL-17 potently blocks epithelial cell turnover while at the same time amplifying an inflammatory response in a positive feedback manner

  12. Butyrate produced by commensal bacteria potentiates phorbol esters induced AP-1 response in human intestinal epithelial cells.

    Malgorzata Nepelska

    Full Text Available The human intestine is a balanced ecosystem well suited for bacterial survival, colonization and growth, which has evolved to be beneficial both for the host and the commensal bacteria. Here, we investigated the effect of bacterial metabolites produced by commensal bacteria on AP-1 signaling pathway, which has a plethora of effects on host physiology. Using intestinal epithelial cell lines, HT-29 and Caco-2, stably transfected with AP-1-dependent luciferase reporter gene, we tested the effect of culture supernatant from 49 commensal strains. We observed that several bacteria were able to activate the AP-1 pathway and this was correlated to the amount of short chain fatty acids (SCFAs produced. Besides being a major source of energy for epithelial cells, SCFAs have been shown to regulate several signaling pathways in these cells. We show that propionate and butyrate are potent activators of the AP-1 pathway, butyrate being the more efficient of the two. We also observed a strong synergistic activation of AP-1 pathway when using butyrate with PMA, a PKC activator. Moreover, butyrate enhanced the PMA-induced expression of c-fos and ERK1/2 phosphorylation, but not p38 and JNK. In conclusion, we showed that SCFAs especially butyrate regulate the AP-1 signaling pathway, a feature that may contribute to the physiological impact of the gut microbiota on the host. Our results provide support for the involvement of butyrate in modulating the action of PKC in colon cancer cells.

  13. Nutraceutical Improvement Increases the Protective Activity of Broccoli Sprout Juice in a Human Intestinal Cell Model of Gut Inflammation.

    Ferruzza, Simonetta; Natella, Fausta; Ranaldi, Giulia; Murgia, Chiara; Rossi, Carlotta; Trošt, Kajetan; Mattivi, Fulvio; Nardini, Mirella; Maldini, Mariateresa; Giusti, Anna Maria; Moneta, Elisabetta; Scaccini, Cristina; Sambuy, Yula; Morelli, Giorgio; Baima, Simona

    2016-01-01

    Benefits to health from a high consumption of fruits and vegetables are well established and have been attributed to bioactive secondary metabolites present in edible plants. However, the effects of specific health-related phytochemicals within a complex food matrix are difficult to assess. In an attempt to address this problem, we have used elicitation to improve the nutraceutical content of seedlings of Brassica oleracea grown under controlled conditions. Analysis, by LC-MS, of the glucosinolate, isothiocyanate and phenolic compound content of juices obtained from sprouts indicated that elicitation induces an enrichment of several phenolics, particularly of the anthocyanin fraction. To test the biological activity of basal and enriched juices we took advantage of a recently developed in vitro model of inflamed human intestinal epithelium. Both sprouts' juices protected intestinal barrier integrity in Caco-2 cells exposed to tumor necrosis factor α under marginal zinc deprivation, with the enriched juice showing higher protection. Multivariate regression analysis indicated that the extent of rescue from stress-induced epithelial dysfunction correlated with the composition in bioactive molecules of the juices and, in particular, with a group of phenolic compounds, including several anthocyanins, quercetin-3-Glc, cryptochlorogenic, neochlorogenic and cinnamic acids. PMID:27529258

  14. Structural Stability of Human Fibroblast Growth Factor-1 Is Essential for Protective Effects Against Radiation-Induced Intestinal Damage

    Purpose: Human fibroblast growth factor-1 (FGF1) has radioprotective effects on the intestine, although its structural instability limits its potential for practical use. Several stable FGF1 mutants were created increasing stability in the order, wild-type FGF1, single mutants (Q40P, S47I, and H93G), Q40P/S47I, and Q40P/S47I/H93G. This study evaluated the contribution of the structural stability of FGF1 to its radioprotective effect. Methods and Materials: Each FGF1 mutant was administered intraperitoneally to BALB/c mice in the absence of heparin 24 h before or after total body irradiation (TBI) with γ-rays at 8-12 Gy. Several radioprotective effects were examined in the jejunum. Results: Q40P/S47I/H93G could activate all subtypes of FGF receptors in vitro much more strongly than the wild-type without endogenous or exogenous heparin. Preirradiation treatment with Q40P/S47I/H93G significantly increased crypt survival more than wild-type FGF1 after TBI at 10 or 12 Gy, and postirradiation treatment with Q40P/S47I/H93G was effective in promoting crypt survival after TBI at 10, 11, or 12 Gy. In addition, crypt cell proliferation, crypt depth, and epithelial differentiation were significantly promoted by postirradiation treatment with Q40P/S47I/H93G. The level of stability of FGF1 mutants correlated with their mitogenic activities in vitro in the absence of heparin; however, preirradiation treatment with the mutants increased the crypt number to almost the same level as Q40P/S47I/H93G. When given 24 h after TBI at 10 Gy, all FGF1 mutants increased crypt survival more than wild-type FGF1, and Q40P/S47I/H93G had the strongest mitogenic effects in intestinal epithelial cells after radiation damage. Moreover, Q40P/S47I/H93G prolonged mouse survival after TBI because of the repair of intestinal damage. Conclusion: These findings suggest that the structural stability of FGF1 can contribute to the enhancement of protective effects against radiation-induced intestinal damage

  15. Structural Stability of Human Fibroblast Growth Factor-1 Is Essential for Protective Effects Against Radiation-Induced Intestinal Damage

    Nakayama, Fumiaki, E-mail: f_naka@nirs.go.jp [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Umeda, Sachiko [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Yasuda, Takeshi [Department of Radiation Emergency Medicine, Research Center for Radiation Emergency Medicine, National Institute of Radiological Sciences, Chiba (Japan); Asada, Masahiro; Motomura, Kaori; Suzuki, Masashi [Signaling Molecules Research Laboratory, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki (Japan); Zakrzewska, Malgorzata [Faculty of Biotechnology, University of Wroclaw (Poland); Imamura, Toru [Signaling Molecules Research Laboratory, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki (Japan); Imai, Takashi [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan)

    2013-02-01

    Purpose: Human fibroblast growth factor-1 (FGF1) has radioprotective effects on the intestine, although its structural instability limits its potential for practical use. Several stable FGF1 mutants were created increasing stability in the order, wild-type FGF1, single mutants (Q40P, S47I, and H93G), Q40P/S47I, and Q40P/S47I/H93G. This study evaluated the contribution of the structural stability of FGF1 to its radioprotective effect. Methods and Materials: Each FGF1 mutant was administered intraperitoneally to BALB/c mice in the absence of heparin 24 h before or after total body irradiation (TBI) with {gamma}-rays at 8-12 Gy. Several radioprotective effects were examined in the jejunum. Results: Q40P/S47I/H93G could activate all subtypes of FGF receptors in vitro much more strongly than the wild-type without endogenous or exogenous heparin. Preirradiation treatment with Q40P/S47I/H93G significantly increased crypt survival more than wild-type FGF1 after TBI at 10 or 12 Gy, and postirradiation treatment with Q40P/S47I/H93G was effective in promoting crypt survival after TBI at 10, 11, or 12 Gy. In addition, crypt cell proliferation, crypt depth, and epithelial differentiation were significantly promoted by postirradiation treatment with Q40P/S47I/H93G. The level of stability of FGF1 mutants correlated with their mitogenic activities in vitro in the absence of heparin; however, preirradiation treatment with the mutants increased the crypt number to almost the same level as Q40P/S47I/H93G. When given 24 h after TBI at 10 Gy, all FGF1 mutants increased crypt survival more than wild-type FGF1, and Q40P/S47I/H93G had the strongest mitogenic effects in intestinal epithelial cells after radiation damage. Moreover, Q40P/S47I/H93G prolonged mouse survival after TBI because of the repair of intestinal damage. Conclusion: These findings suggest that the structural stability of FGF1 can contribute to the enhancement of protective effects against radiation-induced intestinal

  16. Transcriptional Modulation of Intestinal Innate Defense/Inflammation Genes by Preterm Infant Microbiota in a Humanized Gnotobiotic Mouse Model

    Lu, Lei; Yu, Yueyue; Guo, Yuee; Wang, Yunwei; Chang, Eugene B; Claud, Erika C.

    2015-01-01

    Background and Aims It is known that postnatal functional maturation of the small intestine is facilitated by microbial colonization of the gut. Preterm infants exhibit defects in gut maturation, weak innate immunity against intestinal infection and increased susceptibility to inflammatory disorders, all of which may be related to the inappropriate microbial colonization of their immature intestines. The earliest microbes to colonize the preterm infant gut encounter a naïve, immature intestin...

  17. Heparin modulates human intestinal smooth muscle (HISM) cell proliferation and matrix production

    (HISM) cell proliferation and collagen production may play a role in the pathogenesis of intestinal stricture in Crohn's disease. The present studies were performed to evaluate the effects of heparin, a known modulator of vascular smooth muscle cells, on HISM cell proliferation and collagen production. Heparin (100 μg/ml) was added daily to HISM cell cultures for cell proliferation studies and for 24 hours at various time points during culture for collagen synthesis studies. Collagen synthesis was determined by the uptake of 3H proline into collagenase-sensitive protein. Heparin completely inhibited cell proliferation for 7 days, after which cell numbers increased but at a slower rate than controls. Cells released from heparin inhibition demonstrated catch-up growth to control levels. Collagen production was significantly inhibited by 24 hours exposure to heparin but only at those times during culture when collagen synthesis was maximal (8 to 12 days). Non-collagen protein synthesis was inhibited by heparin at all time points during culture. Heparin through its modulation of HISM cells may play an important role in the control of the extracellular matrix of the intestinal wall

  18. Epidemiological study of human intestinal parasitosis in the Hospital of Oran (Algeria

    A. Benouis

    2013-04-01

    Full Text Available Objective: This investigation was undertaken to evaluate the prevalence of intestinal parasitosis in patient addressed to the hospital of Oran and to identify parasites causing this infection. Design: The survey was made on 1042 individuals, external and hospitalized, having between one month and 80 years old, addressed te H.U.C. of Oran. For every patient, an analysis of stool sample was done including direct and complementary methods. Results: The prevalence is about 19,96%. Adultes (71,15% are more parasited than children (28,84%. The sex ratio is equal to 1. It is essentially Protozoa parasitism with 95,7% and Helminth represent only 4,3%. The intestinal parasites founded are : Blastocystis hominis 47,17% Entamoeba coli 18,95%, Giardia intestinalis 15,32%, Endolimax nana 5,24%, Entamoeba histolytica 4 ,83%, Pseudolimax butschlii 4,43%, Enterobius vermicularis 2,82%, Cryptosporidium sp 0,4%, Ascaris lumbricoides 0,4% and Taenia saginata 0,4%. Statistically, it was no significant to the distribution of parasites species by sex. But according to age, it was significant for Giardia intestinalis which infects more children than adults, for Endolimax nana and Blastocystis hominis with the most infection of adults. Conclusion: The majority of parasites listed are not pathological. Their epidemiology is linked to faulty hygiene; this is why developing countries are the most concerned.

  19. Differentially expressed genes related with injury of human intestinal epithelium cell by γ-ray

    In order to isolate differentially expressed genes of intestinal epithelium cell related with γ radiation, by using HIEC cell line in vitro culture as research target, the cell line was irradiated by 8 Gy of γ ray and was continued to culture for 24 h as radiation group, the cell line without γ radiation was as control group. The authors isolated the differentially expressed genes between radiation group and control group by mRNA differential display. The authors obtained 101 fragments of differentially expressed genes, 31 of which were new expressed genes from radiation group, 29 of which were over expressed genes which was higher expressed in radiation group than in control group, 41 of which were no expression in radiation group and expression in control group, 31 of which were from the group of D-T11G as anchored primer, 59 of which were from the group of D-T11A as anchored primer, 32 of which were from the group of D-T11C as anchored primer. In summary, the authors obtained 101 fragments of differentially expressed genes related with γ radiation, 31 among them may be closely correlated with radiation damage to intestinal

  20. Raloxifene glucuronidation in liver and intestinal microsomes of humans and monkeys: contribution of UGT1A1, UGT1A8 and UGT1A9.

    Kishi, Naoki; Takasuka, Akane; Kokawa, Yuki; Isobe, Takashi; Taguchi, Maho; Shigeyama, Masato; Murata, Mikio; Suno, Manabu; Hanioka, Nobumitsu

    2016-04-01

    1. Raloxifene is an antiestrogen that has been marketed for the treatment of osteoporosis, and is metabolized into 6- and 4'-glucuronides by UDP-glucuronosyltransferase (UGT) enzymes. In this study, the in vitro glucuronidation of raloxifene in humans and monkeys was examined using liver and intestinal microsomes and recombinant UGT enzymes (UGT1A1, UGT1A8 and UGT1A9). 2. Although the Km and CLint values for the 6-glucuronidation of liver and intestinal microsomes were similar between humans and monkeys, and species differences in Vmax values (liver microsomes, humans > monkeys; intestinal microsomes, humans  UGT1A8 >UGT1A9 for humans, and UGT1A8 > UGT1A1 > UGT1A9 for monkeys. The activities of 4'-glucuronidation were UGT1A8 > UGT1A1 > UGT1A9 in humans and monkeys. 4. These results demonstrated that the profiles for the hepatic and intestinal glucuronidation of raloxifene by microsomes were moderately different between humans and monkeys. PMID:26247833

  1. Comparative study of human intestinal and hepatic esterases as related to enzymatic properties and hydrolizing activity for ester-type drugs.

    Inoue, M; Morikawa, M; Tsuboi, M; Ito, Y; Sugiura, M

    1980-08-01

    In attempts to determine the exact role of intestinal esterase in the body, we purified esterases from human intestinal mucosa and liver, and compared the enzymatic properties and substrate specificities with those of purified esterases. Esterase from human liver was purified 58-fold, by treatment with butanol, DE-52 and DEAE Sephadex A-50 column chromatographies, Sephadex G-200 gel filtration, and isoelectric focusing. The purified preparation showed a single band by polyacylamide gel electrophoresis. The molecular weights of intestinal and hepatic esterases were determined to be 53,000-55,000 and 180,000, respectively, by gel filtration on Sephadex G-200. The activity of the purified intestinal and hepatic esterases was strongly inhibited by diethyl-p-nitrophenyl phosphate and diisopropyl fluorophosphate, and was not inhibited by eserine sulfate and p-chloromercuribenzoate. Moreover, the purified esterases hydrolyzed ester-type drugs such as aspirin, clofibrate, indanyl carbenicillin and procaine. Hepatic esterase had properties similar to those of intestinal esterase with respect to the sensitivity to organophosphate and the substrate specificity. However, the two purified esterases differed in properties such as molecular weight, isoelectric point, thermostability and optimal pH. PMID:7206363

  2. Inulin-type fructan fermentation by bifidobacteria depends on the strain rather than the species and region in the human intestine.

    Selak, Marija; Rivière, Audrey; Moens, Frédéric; Van den Abbeele, Pieter; Geirnaert, Annelies; Rogelj, Irena; Leroy, Frédéric; De Vuyst, Luc

    2016-05-01

    Inulin-type fructans (ITF) are known to cause a health-promoting bifidogenic effect, although the ITF degradation capacity of bifidobacteria in different intestinal regions remains unclear. The present study aims at offering new insights into this link, making use of a collection of 190 bifidobacterial strains, encompassing strains from gut biopsies (terminal ileum and proximal colon; mucosa-associated strains) and the simulator of the human intestinal microbial ecosystem (SHIME®; proximal and distal colon vessels; lumen-associated strains). A multivariate data analysis of all fermentation data revealed four clusters corresponding with different types of ITF degradation fingerprints, which were not correlated with the region in the intestine, suggesting that the degradation of ITF is uniform along the human intestine. Strains from cluster 1 consumed fructose, while strains from cluster 2 consumed more oligofructose than fructose. Higher fructose and oligofructose consumption was characteristic for clusters 3 and 4 strains, which degraded inulin too. In general, the mucosa-associated strains from biopsy origin seemed to be more specialized in the consumption of fructose and oligofructose, while the lumen-associated strains from SHIME origin displayed a higher degradation degree of inulin. Further, intra-species variability in ITF degradation was found, indicating strain-specific variations. The coexistence of different bifidobacterial strains with different ITF degradation fingerprints within the same intestinal region suggests cooperation for the degradation of ITF, with opportunities for cross-feeding on strain and/or species level. PMID:26861055

  3. Cyclical DNA Methylation and Histone Changes Are Induced by LPS to Activate COX-2 in Human Intestinal Epithelial Cells

    Brancaccio, Mariarita; Coretti, Lorena; Florio, Ermanno; Pezone, Antonio; Calabrò, Viola; Falco, Geppino; Keller, Simona; Lembo, Francesca; Avvedimento, Vittorio Enrico; Chiariotti, Lorenzo

    2016-01-01

    Bacterial lipopolysaccharide (LPS) induces release of inflammatory mediators both in immune and epithelial cells. We investigated whether changes of epigenetic marks, including selected histone modification and DNA methylation, may drive or accompany the activation of COX-2 gene in HT-29 human intestinal epithelial cells upon exposure to LPS. Here we describe cyclical histone acetylation (H3), methylation (H3K4, H3K9, H3K27) and DNA methylation changes occurring at COX-2 gene promoter overtime after LPS stimulation. Histone K27 methylation changes are carried out by the H3 demethylase JMJD3 and are essential for COX-2 induction by LPS. The changes of the histone code are associated with cyclical methylation signatures at the promoter and gene body of COX-2 gene. PMID:27253528

  4. Inhibition of intestinal absorption and decorporation of radiocaesium in humans by hexacyanoferrates(II)

    The effect of hexacyanoferrate (II) preparations, KFe[Fe(CN)6], (KFeHCF) anol Fe4[Fe(N)6 ]3, (FeHCF) on intestinal radiocaesium absorption was studied in two male volunteers. The 134Cs absorption was decreased from 100 to 3-10% when 500-1000 mg KFeHCF or FeHCF were administered 10 min before the 134Cs-labelled test meal. However, when HCF was administered simultaneously with the test meal, the 134Cs absorption was decreased to only 38-63%. The biological half-time of previously absorbed 134Cs was reduced from 106 (73) to 44 (46) days by daily administration of 3 times 0.5 g KFeHCF. The 134Cs dose conversion factors lie below the values recommended by IRCP 30, indicating that the IRCP model represents a cautious description of the Cs biokinetics in our study. (author)

  5. When Does A Gait Transition Occur During Human Locomotion?

    Alan Hreljac; Rodney T. Imamura; Escamilla, Rafael F.; Brent Edwards, W.

    2007-01-01

    When a treadmill accelerates continuously, the walk-run transition has generally been assumed to occur at the instant when a flight phase is first observed, while the run-walk transition has been assumed to occur at the instant of the first double support period. There is no theoretical or empirical evidence to suggest that gait transitions occur at the instant of these events, nor even whether transitions are abrupt events. The purpose of this study was to determine whether the gait transiti...

  6. Inflammation Controls Sensitivity of Human and Mouse Intestinal Epithelial Cells to Galectin-1.

    Muglia, Cecilia I; Papa Gobbi, Rodrigo; Smaldini, Paola; Orsini Delgado, María Lucía; Candia, Martín; Zanuzzi, Carolina; Sambuelli, Alicia; Rocca, Andrés; Toscano, Marta A; Rabinovich, Gabriel A; Docena, Guillermo H

    2016-07-01

    Galectins play key roles in the inflammatory cascade. In this study, we aimed to analyze the effect of galectin-1 (Gal-1) in the function of intestinal epithelial cells (IECs) isolated from healthy and inflamed mucosa. IECs isolated from mice or patients with inflammatory bowel diseases (IBD) were incubated with different pro-inflammatory cytokines, and Gal-1 binding, secretion of homeostatic factors and viability were assessed. Experimental models of food allergy and colitis were used to evaluate the in vivo influence of inflammation on Gal-1 binding and modulation of IECs. We found an enhanced binding of Gal-1 to: (a) murine IECs exposed to IL-1β, TNF, and IL-13; (b) IECs from inflamed areas in intestinal tissue from IBD patients; (c) small bowel of allergic mice; and (d) colon from mice with experimental colitis. Our results showed that low concentrations of Gal-1 favored a tolerogenic micro-environment, whereas high concentrations of this lectin modulated viability of IECs through mechanisms involving activation of caspase-9 and modulation of Bcl-2 protein family members. Our results showed that, when added in the presence of diverse pro-inflammatory cytokines such as tumor necrosis factor (TNF), IL-13 and IL-5, Gal-1 differentially promoted the secretion of growth factors including thymic stromal lymphopoietin (TSLP), epidermal growth factor (EGF), IL-10, IL-25, and transforming growth factor (TGF-β1 ). In conclusion, we found an augmented binding of Gal-1 to IECs when exposed in vitro or in vivo to inflammatory stimuli, showing different effects depending on Gal-1 concentration. These findings highlight the importance of the inflammatory micro-environment of mucosal tissues in modulating IECs susceptibility to the immunoregulatory lectin Gal-1 and its role in epithelial cell homeostasis. J. Cell. Physiol. 231: 1575-1585, 2016. © 2015 Wiley Periodicals, Inc. PMID:26566180

  7. Lactobacillus acidophilus alleviates platelet-activating factor-induced inflammatory responses in human intestinal epithelial cells.

    Alip Borthakur

    Full Text Available Probiotics have been used as alternative prevention and therapy modalities in intestinal inflammatory disorders including inflammatory bowel diseases (IBD and necrotizing enterocolitis (NEC. Pathophysiology of IBD and NEC includes the production of diverse lipid mediators, including platelet-activating factor (PAF that mediate inflammatory responses in the disease. PAF is known to activate NF-κB, however, the mechanisms of PAF-induced inflammation are not fully defined. We have recently described a novel PAF-triggered pathway of NF-κB activation and IL-8 production in intestinal epithelial cells (IECs, requiring the pivotal role of the adaptor protein Bcl10 and its interactions with CARMA3 and MALT1. The current studies examined the potential role of the probiotic Lactobacillus acidophilus in reversing the PAF-induced, Bcl10-dependent NF-κB activation and IL-8 production in IECs. PAF treatment (5 µM×24 h of NCM460 and Caco-2 cells significantly increased nuclear p65 NF-κB levels and IL-8 secretion (2-3-fold, P<0.05, compared to control, which were blocked by pretreatment of the cells for 6 h with L. acidophilus (LA or its culture supernatant (CS, followed by continued treatments with PAF for 24 h. LA-CS also attenuated PAF-induced increase in Bcl10 mRNA and protein levels and Bcl10 promoter activity. LA-CS did not alter PAF-induced interaction of Bcl10 with CARMA3, but attenuated Bcl10 interaction with MALT1 and also PAF-induced ubiquitination of IKKγ. Efficacy of bacteria-free CS of LA in counteracting PAF-induced inflammatory cascade suggests that soluble factor(s in the CS of LA mediate these effects. These results define a novel mechanism by which probiotics counteract PAF-induced inflammation in IECs.

  8. Effect of recombinant human interleukin-11 on expressions of interleukin-11 receptor α-chain and glycoprotein 130 in intestinal epithelium cell line-6 after neutron irradiation

    Wang, Rui-Juan; Peng, Rui-Yun; Fu, Kai-Fei; Gao, Ya-Bing; Han, Rui-Gang; Hu, Wen-Hua; Luo, Qing-Liang; Ma, Jun-Jie

    2006-01-01

    AIM: To explore the effect of recombinant human interleukin-11 (rhIL-11) on the expressions of interleukin-11 receptor α-chain (IL-11Rα) and an additional signal transducer glycoprotein 130 (gp130) in intestinal epithelium cell line-6 (IEC-6) after neutron irradiation.

  9. Genome sequence of Victivallis vadensis ATCC BAA-548, an anaerobic bacterium from the phylum Lentisphaerae, isolated from the human gastro-intestinal tract

    Van Passel, Mark W.J. [Wageningen University and Research Centre, The Netherlands; Kant, Ravi [University of Helsinki; Palva, Airi [University of Helsinki; Lucas, Susan [U.S. Department of Energy, Joint Genome Institute; Copeland, A [U.S. Department of Energy, Joint Genome Institute; Lapidus, Alla L. [U.S. Department of Energy, Joint Genome Institute; Glavina Del Rio, Tijana [U.S. Department of Energy, Joint Genome Institute; Dalin, Eileen [U.S. Department of Energy, Joint Genome Institute; Tice, Hope [U.S. Department of Energy, Joint Genome Institute; Bruce, David [Los Alamos National Laboratory (LANL); Goodwin, Lynne A. [Los Alamos National Laboratory (LANL); Pitluck, Sam [U.S. Department of Energy, Joint Genome Institute; Davenport, Karen W. [Los Alamos National Laboratory (LANL); Sims, David [Los Alamos National Laboratory (LANL); Detter, J. Chris [U.S. Department of Energy, Joint Genome Institute; Han, Cliff [Los Alamos National Laboratory (LANL); Larimer, Frank W [ORNL; Land, Miriam L [ORNL; Hauser, Loren John [ORNL; Kyrpides, Nikos C [U.S. Department of Energy, Joint Genome Institute; Ovchinnikova, Galina [U.S. Department of Energy, Joint Genome Institute; Richardson, Paul [U.S. Department of Energy, Joint Genome Institute; De Vos, Willem M. [Wageningen University and Research Centre, The Netherlands; Smidt, Hauke [Wageningen University and Research Centre, The Netherlands; Zoetendal, Erwin G. [Wageningen University and Research Centre, The Netherlands

    2011-01-01

    Victivallis vadensis ATCC BAA-548 represents the first cultured representative from the novel phylum Lentisphaerae, a deep-branching bacterial lineage. Few cultured bacteria from this phylum are known, and V. vadensis therefore represents an important organism for evolutionary studies. V. vadensis is a strictly anaerobic sugar-fermenting isolate from the human gastro-intestinal tract.

  10. Human intestinal maltase-glucoamylase: crystal structure of the N-terminal catalytic subunit and basis of inhibition and substrate specificity

    Human maltase-glucoamylase (MGAM) is one of the two enzymes responsible for catalyzing the last glucose-releasing step in starch digestion. MGAM is anchored to the small-intestinal brush-border epithelial cells and contains two homologous glycosyl hydrolase family 31 catalytic subunits: an N-termina...

  11. Intestinal obstruction

    ... of the major causes of intestinal obstruction in infants and children. Causes of paralytic ileus may include: Bacteria or viruses that cause intestinal infections ( gastroenteritis ) Chemical, electrolyte, or mineral imbalances (such as decreased ...

  12. Localizations of Na(+)-D-glucose cotransporters SGLT1 and SGLT2 in human kidney and of SGLT1 in human small intestine, liver, lung, and heart.

    Vrhovac, Ivana; Balen Eror, Daniela; Klessen, Dirk; Burger, Christa; Breljak, Davorka; Kraus, Ognjen; Radović, Nikola; Jadrijević, Stipe; Aleksic, Ivan; Walles, Thorsten; Sauvant, Christoph; Sabolić, Ivan; Koepsell, Hermann

    2015-09-01

    Novel affinity-purified antibodies against human SGLT1 (hSGLT1) and SGLT2 (hSGLT2) were used to localize hSGLT2 in human kidney and hSGLT1 in human kidney, small intestine, liver, lung, and heart. The renal locations of both transporters largely resembled those in rats and mice; hSGLT2 and SGLT1 were localized to the brush border membrane (BBM) of proximal tubule S1/S2 and S3 segments, respectively. Different to rodents, the renal expression of hSGLT1 was absent in thick ascending limb of Henle (TALH) and macula densa, and the expression of both hSGLTs was sex-independent. In small intestinal enterocytes, hSGLT1 was localized to the BBM and subapical vesicles. Performing double labeling with glucagon-like peptide 1 (GLP-1) or glucose-dependent insulinotropic peptide (GIP), hSGLT1 was localized to GLP-1-secreting L cells and GIP-secreting K cells as has been shown in mice. In liver, hSGLT1 was localized to biliary duct cells as has been shown in rats. In lung, hSGLT1 was localized to alveolar epithelial type 2 cells and to bronchiolar Clara cells. Expression of hSGLT1 in Clara cells was verified by double labeling with the Clara cell secretory protein CC10. Double labeling of human heart with aquaporin 1 immunolocalized the hSGLT1 protein in heart capillaries rather than in previously assumed myocyte sarcolemma. The newly identified locations of hSGLT1 implicate several extra renal functions of this transporter, such as fluid absorption in the lung, energy supply to Clara cells, regulation of enteroendocrine cells secretion, and release of glucose from heart capillaries. These functions may be blocked by reversible SGLT1 inhibitors which are under development. PMID:25304002

  13. The prevalence and diversity of intestinal parasitic infections in humans and domestic animals in a rural Cambodian village.

    Schär, Fabian; Inpankaew, Tawin; Traub, Rebecca J; Khieu, Virak; Dalsgaard, Anders; Chimnoi, Wissanuwat; Chhoun, Chamnan; Sok, Daream; Marti, Hanspeter; Muth, Sinuon; Odermatt, Peter

    2014-08-01

    In Cambodia, intestinal parasitic infections are prevalent in humans and particularly in children. Yet, information on potentially zoonotic parasites in animal reservoir hosts is lacking. In May 2012, faecal samples from 218 humans, 94 dogs and 76 pigs were collected from 67 households in Dong village, Preah Vihear province, Cambodia. Faecal samples were examined microscopically using sodium nitrate and zinc sulphate flotation methods, the Baermann method, Koga Agar plate culture, formalin-ether concentration technique and Kato Katz technique. PCR was used to confirm hookworm, Ascaris spp., Giardia spp. and Blastocystis spp. Major gastrointestinal parasitic infections found in humans included hookworms (63.3%), Entamoeba spp. (27.1%) and Strongyloides stercoralis (24.3%). In dogs, hookworm (80.8%), Spirometra spp. (21.3%) and Strongyloides spp. (14.9%) were most commonly detected and in pigs Isospora suis (75.0%), Oesophagostomum spp. (73.7%) and Entamoeba spp. (31.6%) were found. Eleven parasite species were detected in dogs (eight helminths and three protozoa), seven of which have zoonotic potential, including hookworm, Strongyloides spp., Trichuris spp., Toxocara canis, Echinostoma spp., Giardia duodenalis and Entamoeba spp. Five of the parasite species detected in pigs also have zoonotic potential, including Ascaris spp., Trichuris spp., Capillaria spp., Balantidium coli and Entamoeba spp. Further molecular epidemiological studies will aid characterisation of parasite species and genotypes and allow further insight into the potential for zoonotic cross transmission of parasites in this community. PMID:24704609

  14. Contributions of NanI sialidase to Caco-2 cell adherence by Clostridium perfringens type A and C strains causing human intestinal disease.

    Li, Jihong; McClane, Bruce A

    2014-11-01

    Previous studies showed that Clostridium perfringens type D animal disease strain CN3718 uses NanI sialidase for adhering to enterocyte-like Caco-2 cells. The current study analyzed whether NanI is similarly important when type A and C human intestinal disease strains attach to Caco-2 cells. A PCR survey determined that the nanI gene was absent from typical type A food poisoning (FP) strains carrying a chromosomal enterotoxin (CPE) gene or the genetically related type C Darmbrand (Db) strains. However, the nanI gene was present in type A strains from healthy humans, type A strains causing CPE-associated antibiotic-associated diarrhea (AAD) or sporadic diarrhea (SD), and type C Pig-Bel strains. Consistent with NanI sialidase being the major C. perfringens sialidase when produced, FP and Db strains had little supernatant sialidase activity compared to other type A or C human intestinal strains. All type A and C human intestinal strains bound to Caco-2 cells, but NanI-producing strains had higher attachment levels. When produced, NanI can contribute to host cell attachment of human intestinal disease strains, since a nanI null mutant constructed in type A SD strain F4969 had lower Caco-2 cell adhesion than wild-type F4969 or a complemented strain. Further supporting a role for NanI in host cell attachment, sialidase inhibitors reduced F4969 adhesion to Caco-2 cells. Collectively, these results suggest that NanI may contribute to the intestinal attachment and colonization needed for the chronic diarrhea of CPE-associated AAD and SD, but this sialidase appears to be dispensable for the acute pathogenesis of type A FP or type C enteritis necroticans. PMID:25135687

  15. The human neonatal small intestine has the potential for arginine synthesis; developmental changes in the expression of arginine-synthesizing and -catabolizing enzymes

    Ruijter Jan M

    2008-11-01

    Full Text Available Abstract Background Milk contains too little arginine for normal growth, but its precursors proline and glutamine are abundant; the small intestine of rodents and piglets produces arginine from proline during the suckling period; and parenterally fed premature human neonates frequently suffer from hypoargininemia. These findings raise the question whether the neonatal human small intestine also expresses the enzymes that enable the synthesis of arginine from proline and/or glutamine. Carbamoylphosphate synthetase (CPS, ornithine aminotransferase (OAT, argininosuccinate synthetase (ASS, arginase-1 (ARG1, arginase-2 (ARG2, and nitric-oxide synthase (NOS were visualized by semiquantitative immunohistochemistry in 89 small-intestinal specimens. Results Between 23 weeks of gestation and 3 years after birth, CPS- and ASS-protein content in enterocytes was high and then declined to reach adult levels at 5 years. OAT levels declined more gradually, whereas ARG-1 was not expressed. ARG-2 expression increased neonatally to adult levels. Neurons in the enteric plexus strongly expressed ASS, OAT, NOS1 and ARG2, while varicose nerve fibers in the circular layer of the muscularis propria stained for ASS and NOS1 only. The endothelium of small arterioles expressed ASS and NOS3, while their smooth-muscle layer expressed OAT and ARG2. Conclusion The human small intestine acquires the potential to produce arginine well before fetuses become viable outside the uterus. The perinatal human intestine therefore resembles that of rodents and pigs. Enteral ASS behaves as a typical suckling enzyme because its expression all but disappears in the putative weaning period of human infants.

  16. Associations between the human intestinal microbiota, Lactobacillus rhamnosus GG and serum lipids indicated by integrated analysis of high-throughput profiling data

    Leo Lahti

    2013-02-01

    , Actinobacteria and Proteobacteria may be involved in the metabolism of dietary and endogenous lipids, and provide a scientific rationale for further human studies to explore the role of intestinal microbes in host lipid metabolism.

  17. Associations between the human intestinal microbiota, Lactobacillus rhamnosus GG and serum lipids indicated by integrated analysis of high-throughput profiling data.

    Lahti, Leo; Salonen, Anne; Kekkonen, Riina A; Salojärvi, Jarkko; Jalanka-Tuovinen, Jonna; Palva, Airi; Orešič, Matej; de Vos, Willem M

    2013-01-01

    Proteobacteria may be involved in the metabolism of dietary and endogenous lipids, and provide a scientific rationale for further human studies to explore the role of intestinal microbes in host lipid metabolism. PMID:23638368

  18. Impact of probiotic drugs, based on Enterobacter faecium autostrains, on human intestinal microflora in confined habitat

    Viacheslav, Ilyin; Batov, Alexey; Usanova, Nonna

    The aim of research: Investigation of influence of probiotic drugs based on autostrains of Enter-obacter faecium, selected from the crew in long term isolation experiment in confined habitat. It is known that during long-term presence in confined habitat the risk of infectious diseases increases. One of the main infectious risk occurs during first 20 days of isolation as a result of exchange of strains and stress-mediated disbacterioses. Therefore it is necessary to evaluate activities of probiotics to avoid this risk. Furthermore, in case of super long term autonomous flight there should be possibilities of application of autochthonous microflora strains as pro-biotics to strengthen colonial resistance of crews. Materials and methods: In the experiment there were used probiotic drugs based on autostrains of E. faecium, selected from the crew before the experiment. Probiotic drugs were consumed during 30 days since the beginning of the experiment with the break of consumption between 10th to 19th day. Results: Comparing the state of intestinal microflora of the crew on the baseline and 14th day of experiment re-vealed remarkable changes of microflora: the increasing of concentration of bifidobacteria and E. faecium (approximately 10 times), elimination of hemolytic streptococcus, yeasts, reduction of the rate of S.aureus, hemolytic gramnegative non-fermenting rods, lactobacilli and normal E.coli. On the 45th day of isolation, 15 days after finishing of auto-strains administration, there fere signs of restoration of disbacteriosis: the quantitative decreasing lactobacilli, bifidobacteria and normal E.coli, increasing of the rate of S.aureus, hemolytic gramnegative nonfermentive rods. Conclusion: Thus we managed to avoid risk of pathogenicity potential growth in first 2 decades of isolation. Application of probiotic, based on the autostrains of E. faecium leads to insignificant changes of concentration of lactobacteries, bifidobacteries, normal E. coli and to

  19. The impact of in vitro digestion on bioaccessibility of polyphenols from potatoes and sweet potatoes and their influence on iron absorption by human intestinal cells.

    Miranda, Lisa; Deußer, Hannah; Evers, Danièle

    2013-11-01

    The composition of potatoes as determined by chemical extraction has been described extensively. It is thus quite well known that, among other compounds, potato is rich in polyphenols, vitamins and in some minerals. This paper underlines the important role of simulated gastro-intestinal in vitro digestion in the bioaccessibility of polyphenols (chlorogenic acid and derivatives, and rutin) from potatoes and sweet potatoes and their impact on iron uptake. Concentrations of polyphenols in the flesh of two potato cultivars (Nicola, white potato, and Vitelotte, purple potato) and sweet potato were measured by Ultra Performance Liquid Chromatography after boiling and after in vitro digestion. Chemical extraction underestimates polyphenol amounts that can be released during digestion and that are actually bioaccessible. Iron uptake, as evaluated by a ferritin assay, by intestinal human cells was decreased after incubation with the intestinal phase of in vitro digestion, presumably due to the presence of polyphenols. PMID:24056541

  20. Microbial diversity in the human intestine and novel insights from metagenomics

    Ventura, Marco; Turroni, Francesca; Canchaya, Carlos; Vaughan, Elaine E.; O'Toole, Paul W.; Van Sinderen, Douwe

    2009-01-01

    Bacterial communities reside in very different ecological niches on and within the human host, such as those associated with the alimentary tract. The human gastrointestinal tract is populated with as many as 100 trillion bacterial cells, whose collective genome likely reflects the co-evolution between the microbial community and its host. Recent progress has highlighted the intriguing diversity of these bacterial populations and their important contributions to human physiology. Thus, a thor...

  1. Endometriosis intestinal Intestinal endometriosis

    C.I. González; M. Cires; F. J. Jiménez; Rubio, T.

    2008-01-01

    La endometriosis es un trastorno ginecológico crónico, benigno y frecuente entre las mujeres en edad fértil, estimándose que existe algún grado de endometriosis hasta en el 15% de las mujeres premenopáusicas, asociándose a historia de infertilidad, antecedente de cesárea, dismenorrea y anormalidad en el sangrado uterino. Se cree que es debida al ascenso por las trompas de Falopio de contenido menstrual (menstruación retrógrada). En la afectación intestinal, el colon es el segmento más frecuen...

  2. Endometriosis intestinal Intestinal endometriosis

    C.I. González

    2008-08-01

    Full Text Available La endometriosis es un trastorno ginecológico crónico, benigno y frecuente entre las mujeres en edad fértil, estimándose que existe algún grado de endometriosis hasta en el 15% de las mujeres premenopáusicas, asociándose a historia de infertilidad, antecedente de cesárea, dismenorrea y anormalidad en el sangrado uterino. Se cree que es debida al ascenso por las trompas de Falopio de contenido menstrual (menstruación retrógrada. En la afectación intestinal, el colon es el segmento más frecuentemente afectado, sobre todo a nivel rectosigmodeo. La clínica de presentación es inespecífica, siendo lo más frecuente el dolor abdominal y/o pélvico de tipo cólico que coincide o se exacerba con la menstruación. El diagnóstico diferencial incluye la enfermedad inflamatoria intestinal, diverticulitis, colitis isquémica y procesos neoplásicos, siendo el diagnóstico definitivo anatomopatológico. En cuanto al tratamiento, éste dependerá de la clínica y de la edad de la paciente, así como de sus deseos de embarazo.Endometriosis is a chronic, benign gynaecological disorder that is frequent in women of a child-bearing age. It is estimated that there is some degree of endometriosis in as many as 15% of pre-menopausal women, associated with a history of infertility, caesarean antecedents, dysmenorrhoea and abnormality in uterine bleeding. It is believed to be due to the rise of menstrual contents through the Fallopian tubes (retrograde menstruation. In the intestinal affectation, the colon is the segment most frequently affected, above all at the rectosigmoidal level. The clinical features are unspecific, with abdominal pain the most frequent and/or pelvic pain of a cholic type that coincides with, or is exacerbated by, menstruation. Differential diagnosis includes intestinal inflammatory disease, diverticulitis, ischemic colitis and neoplastic processes, with the definitive diagnosis being anatomopathological. With respect to treatment

  3. New small-intestine modeling method for surface-based computational human phantoms.

    Yeom, Yeon Soo; Kim, Han Sung; Nguyen, Thang Tat; Choi, Chansoo; Han, Min Cheol; Kim, Chan Hyeong; Lee, Jai Ki; Zankl, Maria; Petoussi-Henss, Nina; Bolch, Wesley E; Lee, Choonsik; Chung, Beom Sun

    2016-06-01

    When converting voxel phantoms to a surface format, the small intestine (SI), which is usually not accurately represented in a voxel phantom due to its complex and irregular shape on one hand and the limited voxel resolutions on the other, cannot be directly converted to a high-quality surface model. Currently, stylized pipe models are used instead, but they are strongly influenced by developer's subjectivity, resulting in unacceptable geometric and dosimetric inconsistencies. In this paper, we propose a new method for the construction of SI models based on the Monte Carlo approach. In the present study, the proposed method was tested by constructing the SI model for the polygon-mesh version of the ICRP reference male phantom currently under development. We believe that the new SI model is anatomically more realistic than the stylized SI models. Furthermore, our simulation results show that the new SI model, for both external and internal photon exposures, leads to dose values that are more similar to those of the original ICRP male voxel phantom than does the previously constructed stylized SI model. PMID:27007802

  4. Chip-based human liver-intestine and liver-skin co-cultures--A first step toward systemic repeated dose substance testing in vitro.

    Maschmeyer, Ilka; Hasenberg, Tobias; Jaenicke, Annika; Lindner, Marcus; Lorenz, Alexandra Katharina; Zech, Julie; Garbe, Leif-Alexander; Sonntag, Frank; Hayden, Patrick; Ayehunie, Seyoum; Lauster, Roland; Marx, Uwe; Materne, Eva-Maria

    2015-09-01

    Systemic repeated dose safety assessment and systemic efficacy evaluation of substances are currently carried out on laboratory animals and in humans due to the lack of predictive alternatives. Relevant international regulations, such as OECD and ICH guidelines, demand long-term testing and oral, dermal, inhalation, and systemic exposure routes for such evaluations. So-called "human-on-a-chip" concepts are aiming to replace respective animals and humans in substance evaluation with miniaturized functional human organisms. The major technical hurdle toward success in this field is the life-like combination of human barrier organ models, such as intestine, lung or skin, with parenchymal organ equivalents, such as liver, at the smallest biologically acceptable scale. Here, we report on a reproducible homeostatic long-term co-culture of human liver equivalents with either a reconstructed human intestinal barrier model or a human skin biopsy applying a microphysiological system. We used a multi-organ chip (MOC) platform, which provides pulsatile fluid flow within physiological ranges at low media-to-tissue ratios. The MOC supports submerse cultivation of an intact intestinal barrier model and an air-liquid interface for the skin model during their co-culture with the liver equivalents respectively at (1)/100.000 the scale of their human counterparts in vivo. To increase the degree of organismal emulation, microfluidic channels of the liver-skin co-culture could be successfully covered with human endothelial cells, thus mimicking human vasculature, for the first time. Finally, exposure routes emulating oral and systemic administration in humans have been qualified by applying a repeated dose administration of a model substance - troglitazone - to the chip-based co-cultures. PMID:25857839

  5. Vasoactive intestinal peptide has a direct positive inotropic effect on isolated human myocardial trabeculae

    Saetrum Opgaard, O; Knutsson, M; de Vries, R; Tom, B; Saxena, P R; Edvinsson, L

    2001-01-01

    . This effect was almost completely blocked by the VIP-receptor antagonist VIP-(6-28). mRNAs encoding the human VPAC(1), VPAC(2) and PAC(1) receptors were detected in human myocardial trabeculae from both the right atrium and the left ventricle. In conclusion, VIP has a direct positive inotropic effect...

  6. Effect of nonabsorbed amounts of a fructose-sorbitol mixture on small intestinal transit in healthy volunteers

    Madsen, Jan L; Linnet, Jan; Rumessen, Jüri J

    2006-01-01

    transit rate. Eleven healthy volunteers participated in a double-blind crossover investigation. In random order, the subjects ingested 30 g glucose or a mixture of 25 g fructose and 5 g sorbitol as 10% solutions. As a radiolabeled marker, (99m)Tc-diethylenetriaminepentaacetic acid was added to each test...... solution. Breath hydrogen and methane concentrations and gastrointestinal progress of the radiolabeled marker were followed for the next 6-hr period. Malabsorption of small amounts of the fructose-sorbitol mixture was evident in all subjects. The area under the gastric radioactivity-time curve after...

  7. Identification of TRPM7 channels in human intestinal interstitial cells of Cajal

    Byung Joo Kim; Kyu Joo Park; Hyung Woo Kim; Seok Choi; Jae Yeoul Jun; In Youb Chang; Ju-Hong Jeon; Insuk So; Seon Jeong Kim

    2009-01-01

    AIM: To investigate the characteristics of slow electrical waves and the presence of transient receptor potential melastatin-type 7 (TRPM7) in the human gastrointestinal (GI) tract. METHODS: Conventional microelectrode techniques were used to record intracellular electrical responses from human GI smooth muscle tissue. Immunohistochemistry was used to identify TRPM7 channels in interstitial cells of Cajal (ICCs). RESULTS: The human GI tract generated slow electrical waves and had ICCs which functioned as pacemaker cells. Flufenamic acid, a nonselective cation channel blocker, and 2-APB (2-aminoethoxydiphenyl borate) and La3~+, TRPM7 channel blockers, inhibited the slow waves. Also, TRPM7 channels were expressed in ICCs in human tissue. CONCLUSION: These results suggest that the human GI tract generates slow waves and that TRPM7 channels expressed in the ICCs may be involved in the generation of the slow waves.

  8. Human rights, transitional justice, public health and social reconstruction.

    Pham, Phuong Ngoc; Vinck, Patrick; Weinstein, Harvey M

    2010-01-01

    Mass violence, armed conflict, genocide, and complex humanitarian emergencies continue to create major social and public health disasters at the dawn of the 21st Century. Transitional justice, a set of policies designed to address the effects of war on traumatized communities and bring justice, lies at the nexus of public health, conflict, and social reconstruction. Despite the paucity of empirical evidence, advocates of transitional justice have claimed that it can alleviate the effects of trauma, deter future violence, and bring about social reconstruction in war-affected communities. Empirical evidence--including new data and analyses presented in this article--suggests a link between trauma, mental health and attitudes towards and responses to transitional justice programs, but there has been little theoretical discussion about the intersection between public health and transitional justice, and even less empirical research to generate discussion between these two fields. Yet, public health professionals have an important role to play in assessing the impact of transitional justice on communities affected by mass violence. In this paper, we offer a conceptual model for future research that seeks to examine the relationship between transitional justice programs and their potential value to the fields of medicine and public health and discuss the methodological issues and challenges to a comprehensive evaluation of this relationship. To illustrate the discussion, we examine new data and analyses from two cases of contemporary conflicts, eastern Democratic Republic of Congo (DRC) and northern Uganda. PMID:19833426

  9. Differential Regulation of TLR Signaling on the Induction of Antiviral Interferons in Human Intestinal Epithelial Cells Infected with Enterovirus 71

    Wang, Chunyang; Ji, Lianfu; Yuan, Xinhui; Jin, Yu; Cardona, Carol J.; Xing, Zheng

    2016-01-01

    Enterovirus 71 (EV71) causes hand-foot-and-mouth disease, which can lead to fatal neurological complications in young children and infants. Few gastrointestinal symptoms are observed clinically, suggesting the presence of a unique immunity to EV71 in the gut. We reported a robust induction of interferons (IFNs) in human intestinal epithelial cells (HT-29), which was suppressed in other types such as RD and HeLa cells. The underlying mechanism for the apparent difference remains obscure. In this study we report that in EV71-infected HT-29 cells, TLR/TRIF signaling was essential to IFN induction; viral replication increased and the induction of IFN-α, -β, -ω, -κ, and -ε decreased markedly in TRIF-silenced HT-29 cells. Importantly, TRIF was degraded by viral 3Cpro in RD cells, but resisted cleavage, and IRF3 was activated and translocated into the nucleus in HT-29 cells. Taken together, our data suggest that IFNs were induced differentially in human HT-29 cells through an intact TLR/TRIF signaling, which differs from other cell types and may be implicated in viral pathogenesis in EV71 infection. PMID:27007979

  10. Differential Regulation of TLR Signaling on the Induction of Antiviral Interferons in Human Intestinal Epithelial Cells Infected with Enterovirus 71.

    Wang, Chunyang; Ji, Lianfu; Yuan, Xinhui; Jin, Yu; Cardona, Carol J; Xing, Zheng

    2016-01-01

    Enterovirus 71 (EV71) causes hand-foot-and-mouth disease, which can lead to fatal neurological complications in young children and infants. Few gastrointestinal symptoms are observed clinically, suggesting the presence of a unique immunity to EV71 in the gut. We reported a robust induction of interferons (IFNs) in human intestinal epithelial cells (HT-29), which was suppressed in other types such as RD and HeLa cells. The underlying mechanism for the apparent difference remains obscure. In this study we report that in EV71-infected HT-29 cells, TLR/TRIF signaling was essential to IFN induction; viral replication increased and the induction of IFN-α, -β, -ω, -κ, and -ε decreased markedly in TRIF-silenced HT-29 cells. Importantly, TRIF was degraded by viral 3Cpro in RD cells, but resisted cleavage, and IRF3 was activated and translocated into the nucleus in HT-29 cells. Taken together, our data suggest that IFNs were induced differentially in human HT-29 cells through an intact TLR/TRIF signaling, which differs from other cell types and may be implicated in viral pathogenesis in EV71 infection. PMID:27007979

  11. Localization of receptors for vasoactive intestinal peptide, somatostatin, and substance P in distinct compartments of human lymphoid organs.

    Reubi, J C; Horisberger, U; Kappeler, A; Laissue, J A

    1998-07-01

    Regulatory peptides, such as vasoactive intestinal peptide (VIP), somatostatin (SS), or substance P (SP), are considered to play a role in immune regulation. To localize the targets of these peptides in the human immune system, their receptors have been evaluated with in vitro receptor autoradiography in lymph nodes, tonsils, appendix, Peyer's patches, spleen, and thymus. The three peptide receptors were detected in all lymphoid tissues tested, but, unexpectedly, usually in distinct compartments. In lymph nodes, palatine tonsils, vermiform appendix, and Peyer's patches, VIP receptors were found in the CD3 positive zone around lymphoid follicles; SS receptors in the germinal centers of secondary follicles; and SP receptors mainly in interfollicular blood vessels. In the spleen, VIP receptors were detected in periarterial lymphatic sheaths, SS receptors in the red pulp, and SP receptors in the central arteries. In the thymus, VIP receptors were present in cortex and medulla, SS receptors in the medulla, and SP receptors in blood vessels. For comparison, cholecystokinin (CCK)-A and -B receptors were not demonstrated in any of these tissues. These results suggest a strong compartmentalization of the three peptide receptors in human lymphoid tissues and represent the molecular basis for the understanding of a very complex and interactive mode of action of these peptides. PMID:9639516

  12. Motor response of the human isolated small intestine and urinary bladder to porcine neuromedin U-8.

    Maggi, C. A.; Patacchini, R.; S. Giuliani; Turini, D; Barbanti, G.; ROVERO P; Meli, A.

    1990-01-01

    1. Porcine neuromedin U-8 produced a concentration (0.3 nM-1 microM)-dependent contraction of the longitudinal muscle of the human isolated ileum, which was unaffected by either atropine (1 microM) or tetrodotoxin (1 microM). 2. By contrast, neuromedin U-8 had only a weak effect on the circular muscle of the human isolated ileum. 3. Neuromedin U-8 also produced a concentration-dependent contraction of mucosa-free muscle strips from the dome of the human isolated urinary bladder, its action be...

  13. Coated capsules for drug targeting to proximal and distal part of human intestine.

    Dvorácková, Katerina; Rabisková, Miloslava; Gajdziok, Jan; Vetchý, David; Muselík, Jan; Bernatoniene, Jurga; Bajerová, Martina; Drottnerová, Pavlína

    2010-01-01

    Coated hard capsules are becoming increasingly important for a number of reasons such as administration of new active ingredients, oral vaccination, colon drug delivery or their use in preclinical and clinical trials. The independency of coating composition on capsules filling is the major advantage of this dosage form. In our study, two types of hard capsules (gelatin and hypromellose) were coated by non-aqueous solutions of Eudragit L and S 12.5, respectively, to achieve intestinal and distal ileic drug delivery. Gelatin hard capsules were coated with Eudragit film either directly or using hydroxypropyl cellulose sub-coating prior to the final coating. Hypromellose capsules were coated directly. Coated capsules were evaluated for coating thickness by optical microscope and for dissolution in different pH media. Gelatin capsules do not seem to be suitable for direct coating with Eudragit due to insufficient film adhesion to the smooth capsule surface and a brittleness of formed films. These problems can be solved by hydroxypropyl celullose interlayer application. Hypromellose hard capsules could be directly easily coated with both Eudragit solutions. Dissolution of caffeine from coated capsules showed the potency for enteric delivery in gelatin capsules with interlayer and Eudragit L film in 7.5 and 10.0% concentrations and in hypromellose capsules coated with EudragitL in 5-17.5% coating levels. Gelatine capsules with interlayer and 10% Eudragit S film and hypromellose capsules only with high coating level (20%) provided potential distal ileum targeting of incorporated drug. Eudragit S film sprayed onto hypromellose capsules surface was brittle especially in the junction zone between capsule cap and body. Better plasticity of Eudragit S coating could be probably achieved using a different plasticizer. PMID:20369797

  14. The Juvenile Transition: A Developmental Switch Point in Human Life History

    Del Giudice, Marco; Angeleri, Romina; Manera, Valeria

    2009-01-01

    This paper presents a new perspective on the transition from early to middle childhood (i.e., human juvenility), investigated in an integrative evolutionary framework. Juvenility is a crucial life history stage, when social learning and interaction with peers become central developmental functions; here it is argued that the "juvenile transition"…

  15. Enhanced uptake and transport of (+-catechin and (--epigallocatechin gallate in niosomal formulation by human intestinal Caco-2 cells

    Song Q

    2014-05-01

    Full Text Available Qinxin Song,1–3 Danhui Li,3 Yongzhi Zhou,3 Jie Yang,1 Wanqi Yang,1 Guohua Zhou,2 Jingyuan Wen31Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, School of Pharmacy, China Pharmaceutical University, 2Department of Pharmacology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, People’s Republic of China; 3School of Pharmacy, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New ZealandAbstract: The aim of this study was to evaluate (+-catechin and (−-epigallocatechin gallate (EGCG cellular uptake and transport across human intestinal Caco-2 cell monolayer in both the absence and presence of niosomal carrier in variable conditions. The effect of free drugs and drug-loaded niosomes on the growth of Caco-2 cells was studied. The effects of time, temperature, and concentration on drug cellular uptake in the absence or presence of its niosomal delivery systems were investigated. The intestinal epithelial membrane transport of the drug-loaded niosomes was examined using the monolayer of the human Caco-2 cells. The kinetics of transport, and the effect of temperature, adenosine triphosphate inhibitor, permeability glycoprotein inhibitor, multidrug resistance-associated protein 2 inhibitor, and the absorption enhancer on transport mechanism were investigated. It was found that the uptake of catechin, EGCG, and their niosomes by Caco-2 cells was 1.22±0.16, 0.90±0.14, 3.25±0.37, and 1.92±0.22 µg/mg protein, respectively (n=3. The apparent permeability coefficient values of catechin, EGCG, and their niosomes were 1.68±0.16, 0.88±0.09, 2.39±0.31, and 1.42±0.24 cm/second (n=3 at 37°C, respectively. The transport was temperature- and energy-dependent. The inhibitors of permeability glycoprotein and multidrug resistance-associated protein 2 and the absorption enhancer significantly enhanced the uptake amount. Compared with the free drugs, niosomal formulation

  16. Regulation of VDR expression in rat and human intestine and liver - Consequences for CYP3A expression

    Khan, Ansar A.; Dragt, Bieuwke S.; Porte, Robert J.; Groothuis, Geny M. M.

    2010-01-01

    The vitamin D receptor (VDR) regulates the expression of drug metabolizing enzymes and transporters in intestine and liver, but the regulation of VDR expression in intestine and liver is incompletely understood. We studied the regulation of VDR mRNA expression by ligands for VDR, farnesoid X recepto

  17. Neolithic transitions: can genetic data help us understand a major demographic event in human prehistory?

    Rasteiro, Rita

    2012-01-01

    The Neolithic transition is probably the most important cultural, economic and demographic revolution in human prehistory. It profoundly modified the distribution of human genes, languages and cultures worldwide. However, the study of the transition from hunting and gathering to farming societies has generated major controversies among archaeologists and geneticists alike, with one side favouring demic diffusion models and the other the cultural diffusion models. As a first ...

  18. Aloe vera non-decolorized whole leaf extract-induced large intestinal tumors in F344 rats share similar molecular pathways with human sporadic colorectal tumors.

    Pandiri, Arun R; Sills, Robert C; Hoenerhoff, Mark J; Peddada, Shyamal D; Ton, Thai-Vu T; Hong, Hue-Hua L; Flake, Gordon P; Malarkey, David E; Olson, Greg R; Pogribny, Igor P; Walker, Nigel J; Boudreau, Mary D

    2011-12-01

    Aloe vera is one of the most commonly used botanicals for various prophylactic and therapeutic purposes. Recently, NTP/NCTR has demonstrated a dose-dependent increase in large intestinal tumors in F344 rats chronically exposed to Aloe barbadensis Miller (Aloe vera) non-decolorized whole leaf extract (AVNWLE) in drinking water. The morphological and molecular pathways of AVNWLE-induced large intestinal tumors in the F344 rats were compared to human colorectal cancer (hCRC) literature. Defined histological criteria were used to compare AVNWLE-induced large intestinal tumors with hCRC. The commonly mutated genes (Kras, Ctnnb1, and Tp53) and altered signaling pathways (MAPK, WNT, and TGF-β) important in hCRC were evaluated within AVNWLE-induced large intestinal tumors. Histological evaluation of the large intestinal tumors indicated eight of twelve adenomas (Ads) and four of twelve carcinomas (Cas). Mutation analysis of eight Ads and four Cas identified point mutations in exons 1 and 2 of the Kras gene (two of eight Ads, two of four Cas), and in exon 2 of the Ctnnb1 gene (three of eight Ads, one of four Cas). No Tp53 (exons 5-8) mutations were found in Ads or Cas. Molecular pathways important in hCRC such as MAPK, WNT, and TGF-β signaling were also altered in AVNWLE-induced Ads and Cas. In conclusion, the AVNWLE-induced large intestinal tumors in F344 rats share several similarities with hCRC at the morphological and molecular levels. PMID:21937742

  19. Human intestinal dendritic cells decrease cytokine release against Salmonella infection in the presence of Lactobacillus paracasei upon TLR activation.

    Miriam Bermudez-Brito

    Full Text Available Probiotic bacteria have been shown to modulate immune responses and could have therapeutic effects in allergic and inflammatory disorders. However, little is known about the signalling pathways that are engaged by probiotics. Dendritic cells (DCs are antigen-presenting cells that are involved in immunity and tolerance. Monocyte-derived dendritic cells (MoDCs and murine DCs are different from human gut DCs; therefore, in this study, we used human DCs generated from CD34+ progenitor cells (hematopoietic stem cells harvested from umbilical cord blood; those DCs exhibited surface antigens of dendritic Langerhans cells, similar to the lamina propria DCs in the gut. We report that both a novel probiotic strain isolated from faeces of exclusively breast-fed newborn infants, Lactobacillus paracasei CNCM I-4034, and its cell-free culture supernatant (CFS decreased pro-inflammatory cytokines and chemokines in human intestinal DCs challenged with Salmonella. Interestingly, the supernatant was as effective as the bacteria in reducing pro-inflammatory cytokine expression. In contrast, the bacterium was a potent inducer of TGF-β2 secretion, whereas the supernatant increased the secretion of TGF-β1 in response to Salmonella. We also showed that both the bacteria and its supernatant enhanced innate immunity through the activation of Toll-like receptor (TLR signalling. These treatments strongly induced the transcription of the TLR9 gene. In addition, upregulation of the CASP8 and TOLLIP genes was observed. This work demonstrates that L. paracasei CNCM I-4034 enhanced innate immune responses, as evidenced by the activation of TLR signalling and the downregulation of a broad array of pro-inflammatory cytokines. The use of supernatants like the one described in this paper could be an effective and safe alternative to using live bacteria in functional foods.

  20. Adaptive function of soil consumption: An in vitro study modeling the human stomach and small intestine

    Dominy, N.J.; Davoust, E.; Minekus, M.

    2004-01-01

    Despite occurring in a wide variety of taxa, deliberate soil consumption (geophagy) is a poorly understood behavior. In humans, geophagy is sometimes considered aberrant or a sign of metabolic dysfunction. However, geophagy is normally assigned an adaptive function in nonhuman primates and various o

  1. The ecology of social transitions in human evolution

    FOLEY, Robert; Gamble, Clive

    2009-01-01

    We know that there are fundamental differences between humans and living apes, and also between living humans and their extinct relatives. It is also probably the case that the most significant and divergent of these differences relate to our social behaviour and its underlying cognition, as much as to fundamental differences in physiology, biochemistry or anatomy. In this paper, we first attempt to demarcate what are the principal differences between human and other societies in terms of soc...

  2. Small intestinal bacterial overgrowth syndrome

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

    2010-01-01

    Human intestinal microbiota create a complex polymicrobial ecology. This is characterised by its high population density, wide diversity and complexity of interaction. Any dysbalance of this complex intestinal microbiome, both qualitative and quantitative, might have serious health consequence for a macro-organism, including small intestinal bacterial overgrowth syndrome (SIBO). SIBO is defined as an increase in the number and/or alteration in the type of bacteria in the upper gastrointestina...

  3. Small intestinal bacterial overgrowth syndrome.

    Bures, J.; Cyrany, J.; Kohoutova, D.; Förstl, M.; Rejchrt, S.; Kvetina, J.; Vorisek, V.; Kopacova, M.

    2010-01-01

    Human intestinal microbiota create a complex polymicrobial ecology. This is characterised by its high population density, wide diversity and complexity of interaction. Any dysbalance of this complex intestinal microbiome, both qualitative and quantitative, might have serious health consequence for a macro-organism, including small intestinal bacterial overgrowth syndrome (SIBO). SIBO is defined as an increase in the number and/or alteration in the type of bacteria in the upper gastrointestina...

  4. An experimental platform using human intestinal epithelial cell lines to differentiate between hazardous and non-hazardous proteins.

    Hurley, Bryan P; Pirzai, Waheed; Eaton, Alex D; Harper, Marc; Roper, Jason; Zimmermann, Cindi; Ladics, Gregory S; Layton, Raymond J; Delaney, Bryan

    2016-06-01

    Human intestinal epithelial cell lines (T84, Caco-2, and HCT-8) grown on permeable Transwell™ filters serve as models of the gastrointestinal barrier. In this study, this in vitro model system was evaluated for effectiveness at distinguishing between hazardous and non-hazardous proteins. Indicators of cytotoxicity (LDH release, MTT conversion), monolayer barrier integrity ([(3)H]-inulin flux, horseradish peroxidase flux, trans-epithelial electrical resistance [TEER]), and inflammation (IL-8, IL-6 release) were monitored following exposure to hazardous or non-hazardous proteins. The hazardous proteins examined include streptolysin O (from Streptococcus pyogenes), Clostridium difficile Toxins A and B, heat-labile toxin from enterotoxigenic Escherichia coli, listeriolysin O (from Listeria monocytogenes), melittin (from bee venom), and mastoparan (from wasp venom). Non-hazardous proteins included bovine and porcine serum albumin, bovine fibronectin, and ribulose bisphosphate carboxylase/oxygenase (RuBisco) from spinach. Food allergenic proteins bovine milk β-lactoglobulin and peanut Ara h 2 were also tested as was the anti-nutritive food protein wheat germ agglutinin. Results demonstrated that this model system effectively distinguished between hazardous and non-hazardous proteins through combined analysis of multiple cells lines and assays. This experimental strategy may represent a useful adjunct to multi-component analysis of proteins with unknown hazard profiles. PMID:27060235

  5. Demonstration of Brachyspira aalborgi lineages 2 and 3 in human colonic biopsies with intestinal spirochaetosis by specific fluorescent in situ hybridization

    Jensen, Tim Kåre; Teglbjærg, Peter S.; Lindboe, Christian F.;

    2004-01-01

    organisms in human intestinal spirochaetosis. Seventeen human colonic biopsies from Norway and Denmark with intestinal spirochaetosis caused by Brachyspira-like organisms different from the type strain of B. aalborgi (lineage 1) were examined. Application of the probe gave a positive signal in two Norwegian......Sequences of known 16S rRNA genes, derived from sequence analysis of cloned 16S rDNA, were used to design a specific oligonucleotide probe targeting spirochaetes of Brachyspira aalborgi lineages 2 and 3. The probe was used with fluorescent in situ hybridization to study the involvement of these...... biopsies, whereas the 15 other biopsies were hybridization-negative. The positive reaction visualized the spirochaetes as a fluorescent, 3-5 mum-high fringe on the surface epithelium, extending into the crypts. The study verified the presence of B. aalborgi lineages 2 and 3 and identified the bacteria as...

  6. Purification, crystallization and diffraction studies of the methyltransferases BT-2972 and BVU-3255 from antibiotic-resistant pathogens of the genus Bacteroides from the human intestine

    The expression, purification, crystallization and diffraction of two methyltransferases BT-2972 and BVU-3255 from two Bacteroides species of antibiotic-resistant pathogens from the human intestine are reported. The methyltransferases BT-2972 and BVU-3255 from two different Bacteroides species that are antibiotic-resistant pathogens from the human intestine were cloned, overexpressed and purified, yielding approximately 120 mg of each protein from 1 l culture. Apo BT-2972 and BVU-3255 and their complexes with S-adenosylmethionine or S-adenosylhomocysteine were crystallized in four different crystal forms using the hanging-drop vapour-diffusion method. These crystals diffracted to resolutions ranging from 2.8 to 2.2 Å. Sequence analysis suggested that the two proteins are homologous small-molecule methyltransferases

  7. On the trail of milk bioactive peptides in human and animal intestinal tracts during digestion

    Boutrou, Rachel; Henry, Gwenaele; Sanchez Rivera, Laura

    2015-01-01

    Digestion of proteins leads to the release of numerous peptides in the gastrointestinal tract, among them several bioactive peptides. This review compiles, organises and critically analyses the information available on bioactive peptides present in vivo in the digestive tract of adult humans and animals. It focuses on milk proteins, which are recognised as one of the main sources of bioactive peptides with different biological functions. To date, few studies have been performed on the pres...

  8. Effects of amoxicillin-clavulanate combination on the motility of the small intestine in human beings.

    Caron, F.; Ducrotte, P; Lerebours, E.; Colin, R; Humbert, G; Denis, P

    1991-01-01

    The amoxicillin-clavulanate combination (Augmentin) frequently induces gastric complaints and diarrhea by an unknown mechanism. The aim of this study was to assess the effects of two orally therapeutic regimens of amoxicillin-clavulanate on small bowel motility in human beings. Duodeno-jejunal manometric recordings were performed in six healthy subjects treated in a cross-over double-blind study with placebo; amoxicillin-clavulanate, 1 g plus 250 mg per os every 12 h for 3 days; or amoxicilli...

  9. The genome of Bifidobacterium pseudocatenulatum IPLA 36007, a human intestinal strain with isoflavone-activation activity

    Alegría, Ángel; Delgado, Susana; Guadamuro, Lucía; Flórez García, Ana Belén; Felis, Giovanna E.; Torriani, Sandra; Mayo Pérez, Baltasar

    2014-01-01

    Background Bifidobacterium species, including Bifidobacterium pseudocatenulatum, are among the dominant microbial populations of the human gastrointestinal tract. They are also major components of many commercial probiotic products. Resident and transient bifidobacteria are thought to have several beneficial health effects. However, our knowledge of how these bacteria interact and communicate with host cells remains poor. This knowledge is essential for scientific support of their purported h...

  10. The dose-response relation in human volunteers for gastro-intestinal pathogens

    Teunis PFM; van der Heijden OG; Giessen JWB van der; Havelaar AH; MGB

    1996-01-01

    Gepubliceerde gegevens omtrent infectie van humane proefpersonen met pathogene micro-organismen die gastro-enteritis veroorzaken (protozoa, bacterien en virussen), worden gebruikt om een kwantitatieve relatie vast te stellen tussen de ingenomen dosis en het risico op infectie. Voor alle bestudeerde datasets wordt deze relatie bepaald door het fitten van een exponentiele curve dan wel een beta-poisson curve. Deze relaties kunnen b.v. worden toegepast bij het vaststellen van het risico op infec...

  11. Human intestinal microbiota and metabolites they produce in relation to host health

    Russell, David A.

    2014-01-01

    The aim of this thesis was to identify selected potential probiotic characteristics of Bifidobacterium longum strains isolated from human sources, and to examine these characteristics in detail using genomic and phenotypic techniques. One strain in particular Bifidobacterium longum DPC 6315 was the main focus of the thesis and this strain was used in both the manufacture of yoghurt and an animal study. In total, 38 B. longum strains, obtained from infants and adults, were assessed in vitro fo...

  12. First molecular identification of the zoonotic parasite Anisakis pegreffii (Nematoda: Anisakidae in a paraffin-embedded granuloma taken from a case of human intestinal anisakiasis in Italy

    Palumbo Massimo

    2011-03-01

    Full Text Available Abstract Background Anisakiasis is an important fish-borne zoonosis provoked by larval stages of nematodes belonging to the genus Anisakis. The detection and identification of human infections is difficult. This is due to: a the low specificity of the clinical features and symptomatology related to human infections; b the paucity of diagnostic features of larvae found in granulomatous lesions characteristic of "invasive anisakiasis"; and c the lack morphological characters diagnostic at the specific level when larvae of Anisakis are detected. Thus, molecular-based diagnostic approaches are warranted. Method We have developed a PCR method that amplifies the DNA of Anisakis spp. in fixed paraffin-embedded tissues. This method was applied to a granuloma removed from a human case of intestinal anisakiasis in Italy. Specific primers of the mtDNA cox2 gene were used and sequence analysis was performed according to the procedures already established for species of Anisakis. Results The sequence obtained (629 bp was compared with those of the other species of Anisakis which have so far been genetically characterized and with sequences obtained from larval stages of Anisakis collected from the Mediterranean fish Engraulis encrasicolus. This enabled the genetic identification of the larva in the human tissue as A. pegreffii. This is the first instance of human intestinal anisakiasis diagnosed using PCR of DNA purified from a fixed eosinophilic granuloma embedded in paraffin. Conclusion The case of human anisakiasis presented reinforces the pathological significance of the species A. pegreffii to humans. The molecular/genetic methodological approach based on mtDNA cox2 sequence analysis, described here, can allow easy and rapid identification of Anisakis spp. in formalin-fixed and paraffin embedded tissues removed from cases of either gastric or intestinal human anisakiasis.

  13. Before and After: Gender Transitions, Human Capital, and Workplace Experiences

    Schilt Kristen; Wiswall Matthew

    2008-01-01

    We use the workplace experiences of transgender people individuals who change their gender typically with hormone therapy and surgery to provide new insights into the long-standing question of what role gender plays in shaping workplace outcomes. Using an original survey of male-to-female and female-to-male transgender people, we document the earnings and employment experiences of transgender people before and after their gender transitions. We find that while transgender people have the same...

  14. Recombinant human MFG-E8 attenuates intestinal injury and mortality in severe whole body irradiation in rats.

    Michael A Ajakaiye

    Full Text Available The gastrointestinal (GI syndrome component of acute radiation syndrome (ARS results from depletion of immature parenchymal stem cells after high dose irradiation and contributes significantly to early mortality. It is associated with severe, irreparable damage in the GI tract and extremely low survival. There is a need for the development of viable mitigators of whole body irradiation (WBI due to the possibility of unexpected high level radiation exposure from nuclear accidents or attacks. We therefore examined the effect of recombinant human milk fat globule-EGF factor 8 (rhMFG-E8 in mitigating damage after WBI. Male Sprague-Dawley rats were exposed to 10 Gy WBI using Cesium-137 as the radiation source. The animals in the treatment group received rhMFG-E8 (166 µg/kg BW subcutaneously once a day with the first dose given 6 h after WBI. Blood and tissue samples from the ileum were collected after 3 days of treatment. A separate cohort of animals was treated for 7 days and the 21 day mortality rate was determined. Treatment with rhMFG-E8 significantly improved the survival from 31% to 75% over 21 days. Furthermore, rhMFG-E8 treatment resulted in a 36% reduction in the radiation injury intestinal mucosal damage score, corresponding to visible histological changes. MFG-E8 gene expression was significantly decreased in WBI-induced animals as compared to sham controls. Treatment with rhMFG-E8 increased p53 and p21 expression by 207% and 84% compared to untreated controls. This was accompanied by an 80% increase in the expression of anti-apoptotic cell regulator Bcl-2. p53 and p21 levels correlate with improved survival after radiation injury. These cell regulators arrest the cell after DNA damage and enable DNA repair as well as optimize cell survival. Taken together, these results indicate that rhMFG-E8 ameliorates the GI syndrome and improves survival after WBI by minimizing intestinal cell damage and optimizing recovery.

  15. Apramycin treatment affects selection and spread of a multidrug-resistant Escherichia coli strain able to colonize the human gut in the intestinal microbiota of pigs

    Herrero-Fresno, Ana; Zachariasen, Camilla; Hansen, Monica Hegstad;

    2016-01-01

    The effect of apramycin treatment on transfer and selection of an Escherichia coli strain (E. coli 912) in the intestine of pigs was analyzed through an in vivo experiment. The strain was sequenced and assigned to the sequence type ST101 and serotype O11. It carried resistance genes to apramycin......-resistant E. coli. Since gentamicin is a first-choice drug for human bacteremia, this is of concern....

  16. The SKW 6.4 line of human B lymphocytes specifically binds and responds to vasoactive intestinal peptide.

    Cheng, P P; Sreedharan, S P; Kishiyama, J L; Goetzl, E J

    1993-05-01

    Vasoactive intestinal peptide (VIP1-28) is a neuromediator recognized by high-affinity receptors on human lymphocytes, which inhibits T-cell proliferation and cytokine secretion, and suppresses immunoglobulin production by mitogen-stimulated mixed mononuclear leucocytes. The direct interactions of VIP1-28 with B cells were studied in the SKW 6.4 line of EBV-transformed human B cells, that express a mean (+/- SD) of 6116 +/- 969 receptors for [125I]VIP1-28 with a mean Kd of 59 nM, that decreases to 12 nM after exposure to phorbol 12-myristate 13-acetate (PMA). The secretion of IgM by SKW 6.4 B cells stimulated optimally with 100 ng/ml of PMA, but not unstimulated secretion of IgM, was suppressed significantly by 10(-12) M to 10(-9) M VIP1-28 and up to a mean maximum (+/- SD) of 40 +/- 2% by 10(-10) M VIP1-28. VIP1-28 elicited concomitant increases in intracellular cyclic AMP up to a mean maximum of 163% at 10(-10) M VIP1-28. The requirement for specific signal transduction by the occupied VIP receptors to inhibit IgM secretion was demonstrated by the lack of effect of VIP4-28 on both cyclic AMP concentration and IgM secretion, despite the equal affinity of binding of VIP4-28 and VIP1-28. The effects of VIP on immunoglobulin secretion by stimulated mixed mononuclear leucocytes thus may be due in part to a direct action on B cells. PMID:8509142

  17. GUTSS: An Alignment-Free Sequence Comparison Method for Use in Human Intestinal Microbiome and Fecal Microbiota Transplantation Analysis

    Heltshe, Sonya L.; Hayden, Hillary S.; Radey, Matthew C.; Weiss, Eli J.; Damman, Christopher J.; Zisman, Timothy L.; Suskind, David L.; Miller, Samuel I.

    2016-01-01

    Background Comparative analysis of gut microbiomes in clinical studies of human diseases typically rely on identification and quantification of species or genes. In addition to exploring specific functional characteristics of the microbiome and potential significance of species diversity or expansion, microbiome similarity is also calculated to study change in response to therapies directed at altering the microbiome. Established ecological measures of similarity can be constructed from species abundances, however methods for calculating these commonly used ecological measures of similarity directly from whole genome shotgun (WGS) metagenomic sequence are lacking. Results We present an alignment-free method for calculating similarity of WGS metagenomic sequences that is analogous to the Bray–Curtis index for species, implemented by the General Utility for Testing Sequence Similarity (GUTSS) software application. This method was applied to intestinal microbiomes of healthy young children to measure developmental changes toward an adult microbiome during the first 3 years of life. We also calculate similarity of donor and recipient microbiomes to measure establishment, or engraftment, of donor microbiota in fecal microbiota transplantation (FMT) studies focused on mild to moderate Crohn's disease. We show how a relative index of similarity to donor can be calculated as a measure of change in a patient's microbiome toward that of the donor in response to FMT. Conclusion Because clinical efficacy of the transplant procedure cannot be fully evaluated without analysis methods to quantify actual FMT engraftment, we developed a method for detecting change in the gut microbiome that is independent of species identification and database bias, sensitive to changes in relative abundance of the microbial constituents, and can be formulated as an index for correlating engraftment success with clinical measures of disease. More generally, this method may be applied to clinical

  18. Effects of phenol on barrier function of a human intestinal epithelial cell line correlate with altered tight junction protein localization

    Phenol contamination of soil and water has raised concerns among people living near phenol-producing factories and hazardous waste sites containing the chemical. Phenol, particularly in high concentrations, is an irritating and corrosive substance, making mucosal membranes targets of toxicity in humans. However, few data on the effects of phenol after oral exposure exist. We used an in vitro model employing human intestinal epithelial cells (SK-CO15) cultured on permeable supports to examine effects of phenol on epithelial barrier function. We hypothesized that phenol disrupts epithelial barrier by altering tight junction (TJ) protein expression. The dose-response effect of phenol on epithelial barrier function was determined using transepithelial electrical resistance (TER) and FITC-dextran permeability measurements. We studied phenol-induced changes in cell morphology and expression of several tight junction proteins by immunofluorescence and Western blot analysis. Effects on cell viability were assessed by MTT, Trypan blue, propidium iodide and TUNEL staining. Exposure to phenol resulted in decreased TER and increased paracellular flux of FITC-dextran in a dose-dependent manner. Delocalization of claudin-1 and ZO-1 from TJs to cytosol correlated with the observed increase in permeability after phenol treatment. Additionally, the decrease in TER correlated with changes in the distribution of a membrane raft marker, suggesting phenol-mediated effects on membrane fluidity. Such observations were independent of effects of phenol on cell viability as enhanced permeability occurred at doses of phenol that did not cause cell death. Overall, these findings suggest that phenol may affect transiently the lipid bilayer of the cell membrane, thus destabilizing TJ-containing microdomains.

  19. Modulation of pathogen-induced CCL20 secretion from HT-29 human intestinal epithelial cells by commensal bacteria.

    Sibartie, Shomik

    2009-01-01

    BACKGROUND: Human intestinal epithelial cells (IECs) secrete the chemokine CCL20 in response to infection by various enteropathogenic bacteria or exposure to bacterial flagellin. CCL20 recruits immature dendritic cells and lymphocytes to target sites. Here we investigated IEC responses to various pathogenic and commensal bacteria as well as the modulatory effects of commensal bacteria on pathogen-induced CCL20 secretion. HT-29 human IECs were incubated with commensal bacteria (Bifidobacterium infantis or Lactobacillus salivarius), or with Salmonella typhimurium, its flagellin, Clostridium difficile, Mycobacterium paratuberculosis, or Mycobacterium smegmatis for varying times. In some studies, HT-29 cells were pre-treated with a commensal strain for 2 hr prior to infection or flagellin stimulation. CCL20 and interleukin (IL)-8 secretion and nuclear factor (NF)-kappaB activation were measured using enzyme-linked immunosorbent assays. RESULTS: Compared to untreated cells, S. typhimurium, C. difficile, M. paratuberculosis, and flagellin activated NF-kappaB and stimulated significant secretion of CCL20 and IL-8 by HT-29 cells. Conversely, B. infantis, L. salivarius or M. smegmatis did not activate NF-kappaB or augment CCL20 or IL-8 production. Treatment with B. infantis, but not L. salivarius, dose-dependently inhibited the baseline secretion of CCL20. In cells pre-treated with B. infantis, C. difficile-, S. typhimurium-, and flagellin-induced CCL20 were significantly attenuated. B. infantis did not limit M. Paratuberculosis-induced CCL20 secretion. CONCLUSION: This study is the first to demonstrate that a commensal strain can attenuate CCL20 secretion in HT-29 IECs. Collectively, the data indicate that M. paratuberculosis may mediate mucosal damage and that B. infantis can exert immunomodulatory effects on IECs that mediate host responses to flagellin and flagellated enteric pathogens.

  20. The importance of determining human leucocyte antigens in preventing intestinal lymphoma in patients with celiac disease

    Gabriel Samasca; Mihaela Iancu; Angela Butnariu; Andreica Mariana; Ileana Constantinescu; Doru Dejica

    2010-01-01

    Identification of celiac disease, by determining human leucocyte antigens DQ2/DQ8, is important since recent long-term studies have shown that the mortality of celiac disease is increased, if it is unrecognized and untreated. In this sense, we wanted to see the usefulness of genetic tests in celiac disease diagnosis and screening. Material and methods. During 2010 we determined by PCR, DQ2/DQ8 haplotype, in a group of 27 children with celiac disease and 9 of their brothers, serolo...

  1. Prebiotic effect of fructooligosaccharide in the simulator of the human intestinal microbial ecosystem (SHIME® model).

    Sivieri, Katia; Morales, Martha L Villarreal; Saad, Susana M I; Adorno, Maria A Tallarico; Sakamoto, Isabel Kimiko; Rossi, Elizeu A

    2014-08-01

    Maintaining "gut health" is a goal for scientists throughout the world. Therefore, microbiota management models for testing probiotics, prebiotics, and synbiotics have been developed. The SHIME(®) model was used to study the effect of fructooligosaccharide (FOS) on the fermentation pattern of the colon microbiota. Initially, an inoculum prepared from human feces was introduced into the reactor vessels and stabilized over 2 weeks using a culture medium. This stabilization period was followed by a 2-week control period during which the microbiota was monitored. The microbiota was then subjected to a 4-week treatment period by adding 5 g/day-1 FOS to vessel one (the "stomach" compartment). Plate counts, Denaturing Gradient Gel Electrophoresis (DGGE), short-chain fatty acid (SCFA), and ammonium analyses were used to observe the influence of FOS treatment in simulated colon compartments. A significant increase (PFOS induced increase of the SCFA concentration (P<.05) during the treatment period, mainly due to significant increased levels of acetic and butyric acids. However, ammonium concentrations increased during the same period (P<.01). This study indicates the usefulness of in vitro methods that simulate the colon region as part of research towards the improvement of human health. PMID:24654949

  2. Interaction of graphene-related materials with human intestinal cells: an in vitro approach

    Kucki, M.; Rupper, P.; Sarrieu, C.; Melucci, M.; Treossi, E.; Schwarz, A.; León, V.; Kraegeloh, A.; Flahaut, E.; Vázquez, E.; Palermo, V.; Wick, P.

    2016-04-01

    Graphene-related materials (GRM) inherit unique combinations of physicochemical properties which offer a high potential for technological as well as biomedical applications. It is not clear which physicochemical properties are the most relevant factors influencing the behavior of GRM in complex biological environments. In this study we have focused on the interaction of GRM, especially graphene oxide (GO), and Caco-2 cells in vitro. We mimiked stomach transition by acid-treatment of two representative GRM followed by analysis of their physicochemical properties. No significant changes in the material properties or cell viability of exposed Caco-2 cells in respect to untreated GRM could be detected. Furthermore, we explored the interaction of four different GO and Caco-2 cells to identify relevant physicochemical properties for the establishment of a material property-biological response relationship. Despite close interaction with the cell surface and the formation of reactive oxygen species (ROS), no acute toxicity was found for any of the applied GO (concentration range 0-80 μg ml-1) after 24 h and 48 h exposure. Graphene nanoplatelet aggregates led to low acute toxicity at high concentrations, indicating that aggregation, the number of layers or the C/O ratio have a more pronounced effect on the cell viability than the lateral size alone.Graphene-related materials (GRM) inherit unique combinations of physicochemical properties which offer a high potential for technological as well as biomedical applications. It is not clear which physicochemical properties are the most relevant factors influencing the behavior of GRM in complex biological environments. In this study we have focused on the interaction of GRM, especially graphene oxide (GO), and Caco-2 cells in vitro. We mimiked stomach transition by acid-treatment of two representative GRM followed by analysis of their physicochemical properties. No significant changes in the material properties or cell

  3. Transitive responding in animals and humans : exaptation rather than adaptation?

    Delius, Juan; Siemann, Martina

    1998-01-01

    In order to survive and reproduce, individual animals need to navigate through a multidimensional utility landscape in a near-optimal way. There is little doubt that the behaviourally more advanced species can bring cognitive competencies to bear on this difficult task. Among the cognitive abilities that are helpful in this context is transitive inference. This is typically the competency to derive the conclusion B>D from the premises A>B, B>C, C>D and D>E that imply the series A>B>C>D>E. In ...

  4. Curcumin affects cell survival and cell volume regulation in human renal and intestinal cells

    Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1E,6E-heptadiene-3,5-dione or diferuloyl methane) is a polyphenol derived from the Curcuma longa plant, commonly known as turmeric. This substance has been used extensively in Ayurvedic medicine for centuries for its anti-oxidant, analgesic, anti-inflammatory and antiseptic activity. More recently curcumin has been found to possess anti-cancer properties linked to its pro-apoptotic and anti-proliferative actions. The underlying mechanisms of these diverse effects are complex, not fully elucidated and subject of intense scientific debate. Despite increasing evidence indicating that different cation channels can be a molecular target for curcumin, very little is known about the effect of curcumin on chloride channels. Since, (i) the molecular structure of curcumin indicates that the substance could potentially interact with chloride channels, (ii) chloride channels play a role during the apoptotic process and regulation of the cell volume, and (iii) apoptosis is a well known effect of curcumin, we set out to investigate whether or not curcumin could (i) exert a modulatory effect (direct or indirect) on the swelling activated chloride current IClswell in a human cell system, therefore (ii) affect cell volume regulation and (iii) ultimately modulate cell survival. The IClswell channels, which are essential for regulating the cell volume after swelling, are also known to be activated under isotonic conditions as an early event in the apoptotic process. Here we show that long-term exposure of a human kidney cell line to extracellular 0.1–10 μM curcumin modulates IClswell in a dose-dependent manner (0.1 μM curcumin is ineffective, 0.5–5.0 μM curcumin increase, while 10 μM curcumin decrease the current), and short-term exposure to micromolar concentrations of curcumin does not affect IClswell neither if applied from the extracellular nor from the intracellular side – therefore, a direct effect of curcumin on IClswell

  5. Sequence of an intestinal cDNA encoding human gastric inhibitory polypeptide precursor

    Gastric inhibitory polypeptide (GIP) is a 42-amino acid hormone that stimulates insulin secretion in the presence of glucose. Complementary DNA clones encoding human GIP were isolated from a library prepared with RNA from duodenum. The predicted amino acid sequence indicates that GIP is derived by proteolytic processing of a 153-residue precursor, preproGIP. The GIP moiety is flanked by polypeptide segments of 51 and 60 amino acids at its NH2 and COOH termini, respectively. The former includes a signal peptide of about 21 residues and an NH2-terminal propeptide of 30 amino acids. GIP is released from the precursor by processing at single arginine residues. There is a region of nine amino acids in the COOH-terminal propeptide of the GIP precursor that has partial homology with a portion of chromogranin A as well as pancreastatin

  6. The Vibrio cholerae cytolysin promotes chloride secretion from intact human intestinal mucosa.

    Lucantonio Debellis

    Full Text Available BACKGROUND: The pathogenicity of the Vibrio cholerae strains belonging to serogroup O1 and O139 is due to the production of virulence factors such as cholera toxin (CT and the toxin-coregulated pilus (TCP. The remaining serogroups, which mostly lack CT and TCP, are more frequently isolated from aquatic environmental sources than from clinical samples; nevertheless, these strains have been reported to cause human disease, such as sporadic outbreaks of watery diarrhoea and inflammatory enterocolitis. This evidence suggested the possibility that other virulence factor(s than cholera toxin might be crucial in the pathogenesis of Vibrio cholerae-induced diarrhoea, but their nature remains unknown. VCC, the hemolysin produced by virtually all Vibrio cholerae strains, has been proposed as a possible candidate, though a clear-cut demonstration attesting VCC as crucial in the pathogenesis of Vibrio cholerae-induced diarrhoea is still lacking. METHODOLOGY/PRINCIPAL FINDINGS: Electrophysiological parameters and paracellular permeability of stripped human healthy colon tissues, obtained at subtotal colectomy, mounted in Ussing chamber were studied in the presence or absence of VCC purified from culture supernatants of V. cholerae O1 El Tor strain. Short circuit current (I(SC and transepithelial resistance (R(T were measured by a computerized voltage clamp system. The exposure of sigmoid colon specimens to 1 nM VCC resulted in an increase of I(SC by 20.7%, with respect to the basal values, while R(T was reduced by 12.3%. Moreover, increase in I(SC was abolished by bilateral Cl(- reduction. CONCLUSION/SIGNIFICANCE: Our results demonstrate that VCC, by forming anion channels on the apical membrane of enterocytes, triggers an outward transcellular flux of chloride. Such an ion movement, associated with the outward movement of Na(+ and water, might be responsible for the diarrhoea caused by the non-toxigenic strains of Vibrio cholerae.

  7. Cell surface glycopeptides from human intestinal epithelial cell lines derived from normal colon and colon adenocarcinomas

    The cell surface glycopeptides from an epithelial cell line (CCL 239) derived from normal human colon were compared with those from three cell lines (HCT-8R, HCT-15, and CaCo-2) derived independently from human colonic adenocarcinomas. Cells were incubated with D-[2-3H]mannose or L-[5,6-3H]fucose for 24 h and treated with trypsin to release cell surface components which were then digested exhaustively with Pronase and fractionated on Bio-Gel P-6 before and after treatment with endo-beta-N-acetylglucosaminidase H. The most noticeable difference between the labeled glycopeptides from the tumor and CCL 239 cells was the presence in the former of an endo-beta-N-acetylglucosaminidase H-resistant high molecular weight glycopeptide fraction which was eluted in the void volume of Bio-Gel P-6. This fraction was obtained with both labeled mannose and fucose as precursors. However, acid hydrolysis of this fraction obtained after incubation with [2-3H]mannose revealed that as much as 60-90% of the radioactivity was recovered as fucose. Analysis of the total glycopeptides (cell surface and cell pellet) obtained after incubation with [2-3H]mannose showed that from 40-45% of the radioactivity in the tumor cells and less than 10% of the radioactivity in the CCL 239 cells was recovered as fucose. After incubation of the HCT-8R cells with D-[1,6-3H]glucosamine and L-[1-14C]fucose, strong acid hydrolysis of the labeled glycopeptide fraction excluded from Bio-Gel P-6 produced 3H-labeled N-acetylglucosamine and N-acetylgalactosamine

  8. The human intestinal microbiome at extreme ages of life. Dietary intervention as a way to counteract alterations

    Salazar, Nuria; Arboleya, Silvia; Valdés, Lorena; Stanton, Catherine; Ross, Paul; Ruiz, Lorena; Gueimonde, Miguel; de los Reyes-Gavilán, Clara G.

    2014-01-01

    The intestinal microbiome is defined as the assembly of genomes from microorganisms inhabiting the gut. This microbial ecosystem regulates important functions of the host and its correct composition and functionality is essential for a “healthy status.” Metagenomic studies have highlighted variations of the intestinal microbiota as a function of age and diet. Colonization of the infant gut starts at birth and is influenced by feeding habits (formula vs. breast-feeding), birth mode and antibio...

  9. Anti-acids lead to immunological and morphological changes in the intestine of BALB/c mice similar to human food allergy.

    Pali-Schöll, Isabella; Yildirim, Ali O; Ackermann, Ute; Knauer, Tanja; Becker, Christoph; Garn, Holger; Renz, Harald; Jensen-Jarolim, Erika; Fehrenbach, Heinz

    2008-08-01

    We have shown that anti-acid medication for treating dyspeptic disorders can block protein digestion and induce a higher risk for food sensitization. This mechanism was confirmed in human and animal studies on the humoral as well as the cellular level. Here we aimed to investigate the outcome of the treatment with the anti-acid drug sucralfate on the intestine in our murine model, assuming that morphological and immunological changes will occur. BALB/c mice were fed codfish extract plus sucralfate. Antibodies were examined in ELISA, RBL assay and Western blot. Quantitative morphological analysis of the intestine was performed by design-based stereology, focussing on epithelium, lamina propria, smooth muscle, eosinophils and CD3(+) cells. Histological analyses were performed after H&E-, PAS- and Congo red-staining, while immune histochemistry was done for detection of CD3(+) cells. Codfish-specific IgE and its activity in RBL assay confirmed the Th2-response after treatment with sucralfate. The reactivity pattern of murine IgE in Western blot was similar to allergic patients' IgE. Histological examination showed more slender villi in the duodenum, and increased goblet cell mucus in the cecum after sucralfate treatment. Stereological analyses of the intestine revealed higher eosinophil/CD3(+) ratios, decreased mean thickness of the epithelium of duodenum and cecum, and thinner smooth muscle cell layer in the colon of food allergic mice. Anti-acid treatment with sucralfate induces changes in the structure of epithelium and villi, and an increase in eosinophils and mucus-producing cells in the intestine. Therefore, this medication leads to sensitization against food with changes typical for food allergy also in the intestine. PMID:18524557

  10. Biotransformation and metabolic profile of buddleoside with human intestinal microflora by ultrahigh-performance liquid chromatography coupled to hybrid linear ion trap/orbitrap mass spectrometer.

    Tao, Jin-Hua; Duan, Jin-Ao; Jiang, Shu; Qian, Yi-Yun; Qian, Da-Wei

    2016-07-01

    Buddleoside (also known as linarin) as the major flavonoid in Chrysanthemum morifolium Ramat., has been reported to possess a wide range of pharmacological activities. The human intestinal microbiota might have an important impact on drug metabolism and ultimately on the drug oral bioavailability. However, the interaction of the buddleoside with human intestinal bacteria remains unknown. In this study, the conversion of buddleoside by different bacteria from human feces was firstly investigated. A reliable, sensitive and rapid analytical method, ultra performance liquid chromatography was established and successfully applied to investigate the metabolites and metabolic profile of buddleoside by human intestinal bacteria. Among the isolated bacteria, four strains including Escherichia sp. 4, Escherichia sp. 34, Enterococcus sp. 45 and Bacillus sp. 46 showed more powerful conversion capability. Based on the accurate mass data and the characteristic MS(n) product ions, the parent and six metabolites were detected and tentatively identified compared with blank samples. The metabolites were produced by four main metabolic pathways including deglycosylation, acetylation, methylation and hydroxylation. Buddleoside could be firstly converted to its aglycon acacetin (M2) by the majority of the isolated intestinal bacteria. Subsequently, M2 was further metabolize to its methylated (M3), acetylated (M4), hydroxylated (M5) and hydrogenated product (M6). However, acacetin-7-glucosid (M1) was obtained only from the minor bacterial samples like Bacillus sp. 46. To further explain the metabolism of buddleoside, the β-d-glucosidase and α-l-rhamnosidase activities of four strains were analyzed. Bacillus sp. 46 could only produce α-l-rhamnosidase, while the other three strains showed two kinds of enzyme activities. Furthermore, the activities of α-l-rhamnosidase and β-d-glucosidase reached the highest level at 12-18h and 10-12h, respectively. The metabolic routes and metabolites

  11. Altered Enthalpy-Entropy Compensation in Picomolar Transition State Analogues of Human Purine Nucleoside Phosphorylase†

    Edwards, Achelle A.; Mason, Jennifer M.; Clinch, Keith; Tyler, Peter C.; Evans, Gary B.; Schramm, Vern L.

    2009-01-01

    Human purine nucleoside phosphorylase (PNP) belongs to the trimeric class of PNPs and is essential for catabolism of deoxyguanosine. Genetic deficiency of PNP in humans causes a specific T-cell immune deficiency and transition state analogue inhibitors of PNP are in development for treatment of T-cell cancers and autoimmune disorders. Four generations of Immucillins have been developed, each of which contains inhibitors binding with picomolar affinity to human PNP. Full inhibition of PNP occu...

  12. Altered growth patterns in vitro of human papillary transitional carcinoma cells.

    Reznikoff, C. A.; Gilchrist, K. W.; Norback, D. H.; Cummings, K. B.; ERTÜRK, E.; Bryan, G. T.

    1983-01-01

    In vitro growth patterns and morphologic characteristics of five low-grade human papillary transitional cell carcinomas (TCCs) were compared and contrasted with those of normal human urothelial cells in culture. Biopsies of TCC were performed by transurethral resection. Specimens of normal human ureters were obtained surgically. Singly dispersed TCC cells grew in 0.3% agarose semisolid medium with a cloning efficiency ranging from 0.02% to 0.71%. Singly dispersed normal ureteral urothelial ce...

  13. Interaction between oblongifolin C and UDP-glucuronosyltransferase isoforms in human liver and intestine microsomes.

    Gao, Cui; Shi, Rong; Wang, Tianming; Tan, Hongsheng; Xu, Hongxi; Ma, Yueming

    2015-01-01

    1. Oblongifolin C (OC) is a potential natural anticancer candidate, and its metabolic profile has not yet been established. 2. One major OC glucuronidation metabolite (OCG) has been identified in a pool of human liver microsomes (HLMs). Chemical inhibition experiments suggested that OCG was mainly formed by UGT1A. A screen of recombinant UDP-glucuronosyltransferase isoforms (UGTs) indicated that UGT1A1 primarily mediates OC conjugation, with minor contributions from UGT1A3 and UGT1A8. Enzyme kinetic studies showed that UGT1A1 was the main UGT isoform involved in OCG in HLMs. 3. Further investigation suggested that OC is a broad inhibitor of UGTs. Additionally, OC competitively inhibited UGT1A6 with a Ki value of 3.49 ± 0.57 μM, whereas non-competitively inhibited UGT1A10 with a Ki value of 2.12 ± 0.18 μM. 4. Understanding the interaction between OC and UGTs will greatly contribute to future investigations regarding the inter-individual differences in OC metabolism in clinical trials and potential drug-drug interactions. PMID:25714435

  14. Connexin 26-mediated gap junctional intercellular communication suppresses paracellular permeability of human intestinal epithelial cell monolayers

    In some cell types, gap junctional intercellular communication (GJIC) is associated with tight junctions. The present study was performed to determine the roles of GJIC in regulation of the barrier function of tight junctions. Caco-2 human colonic cells were used as a monolayer model, and barrier function was monitored by measuring mannitol permeability and transepithelial electrical resistance (TER). The monolayers were chemically disrupted by treatment with oleic acid and taurocholic acid. Western blotting analyses were performed to evaluate the protein levels of connexins, which are components of gap junctional intercellular channels. Cx26 expression was detected in preconfluent Caco-2 cells, and its level increased gradually after the monolayer reached confluency. These results prompted us to examine whether overexpression of Cx26 affects barrier function. Monolayers of Caco-2 cells stably expressing Cx26 showed significantly lower mannitol permeability and higher TER than mock transfectants when the monolayers were chemically disrupted. The levels of claudin-4, an important component of tight junctions, were significantly increased in the stable Cx26 transfectant. These results suggest that Cx26-mediated GJIC may play a crucial role in enhancing the barrier function of Caco-2 cell monolayers

  15. A Novel Tightly Regulated Gene Expression System for the Human Intestinal Symbiont Bacteroides thetaiotaomicron

    Horn, Nikki; Carvalho, Ana L.; Overweg, Karin; Wegmann, Udo; Carding, Simon R.; Stentz, Régis

    2016-01-01

    There is considerable interest in studying the function of Bacteroides species resident in the human gastrointestinal (GI)-tract and the contribution they make to host health. Reverse genetics and protein expression techniques, such as those developed for well-characterized Escherichia coli cannot be applied to Bacteroides species as they and other members of the Bacteriodetes phylum have unique promoter structures. The availability of useful Bacteroides-specific genetic tools is therefore limited. Here we describe the development of an effective mannan-controlled gene expression system for Bacteroides thetaiotaomicron containing the mannan-inducible promoter–region of an α-1,2-mannosidase gene (BT_3784), a ribosomal binding site designed to modulate expression, a multiple cloning site to facilitate the cloning of genes of interest, and a transcriptional terminator. Using the Lactobacillus pepI as a reporter gene, mannan induction resulted in an increase of reporter activity in a time- and concentration-dependent manner with a wide range of activity. The endogenous BtcepA cephalosporinase gene was used to demonstrate the suitability of this novel expression system, enabling the isolation of a His-tagged version of BtCepA. We have also shown with experiments performed in mice that the system can be induced in vivo in the presence of an exogenous source of mannan. By enabling the controlled expression of endogenous and exogenous genes in B. thetaiotaomicron this novel inducer-dependent expression system will aid in defining the physiological role of individual genes and the functional analyses of their products. PMID:27468280

  16. Comparison study of oral iron preparations using a human intestinal model.

    Zariwala, Mohammed Gulrez; Somavarapu, Satyanarayana; Farnaud, Sebastien; Renshaw, Derek

    2013-12-01

    Iron deficiency and related iron deficiency anaemia (IDA) are the most prevalent nutritional disorders worldwide. The standard treatment involves supplementation with solid or liquid iron supplement preparations, usually based on a ferrous salt such as ferrous sulphate, ferrous fumarate, or ferrous gluconate. In the present study, we compared iron uptake and absorption from various solid and liquid iron supplement preparations currently available in the United Kingdom using the well-characterised human epithelial adenocarcinoma cell line Caco-2. Intracellular ferritin protein formation by the Caco-2 cell was considered an indicator of cellular iron uptake and absorption. We investigated the effects of formulation ingredients at a defined pH on iron uptake and absorption, and designed a novel two-stage dissolution-absorption protocol that mimicked physiological conditions. Our experiments revealed wide variations in the rate of dissolution between the various solid iron preparations. Conventional-release ferrous iron tablets dissolved rapidly (48 ± 4 mins to 64 ± 4 mins), whereas modified-released tablets and capsules took significantly longer to undergo complete dissolution (274 ± 8 to 256 ± 8 mins). Among the solid iron preparations, ferrous sulphate conventional-release tablets demonstrated the highest iron absorption, whereas modified-release ferrous preparations demonstrated uniformly low iron absorption, as compared to the control (P < 0.05). Taken together, our results demonstrate that there are wide-ranging variations in dissolution times and iron uptake from oral iron preparations, with the physical characteristics of the preparation as well as the form of iron playing a key role. PMID:24482777

  17. Screening in a Lactobacillus delbrueckii subsp. bulgaricus Collection to select a strain able to survive to the human intestinal tract

    Clotilde Vázquez

    2013-08-01

    Full Text Available Objectives: Genetic diversity and resistance of Lactobacillus bulgaricus sbsp. delbrueckii collection with 100 isolates from different home-made yogurt in rural Bulgarian areas were determined. Methods: The strain K98 was the most resistant to bile salts and low pH. Survival and effects on short chain fatty acids production were tested in 20 healthy volunteers. High genetic diversity was observed in the L. bulgaricus collection by RAPD, whereas the ability of tolerate high deoxycholic acid concentrations, and different acid pHs was variable. The strain K98 was selected and used to prepare a homemade yogurt which was administered to 20 healthy volunteers (500 ml/day during 15d. A basal faecal sample and another after yogurt intake were recovered. Results: DGGE experiments, using both universal and Lactic Acid Bacteria (LAB primers, demonstrated no significant changes in the qualitative composition of gut microbiota. A band corresponding to L. bulgaricus was observed in all 20 samples. Viable L. bulgaricus K98 strain was only recovered in one volunteer. After yogurt intake we found an increase of LAB and Clostridium perfringens, and a decrease of Bacteroides-Prevotella-Porphyromonas. In addition, increases of acetic, butyric and 2-hydroxybutyric acids in faeces were detected. Conclusions: Genetic diversity of L. delbrueckii subsp. bulgaricus especie is high We have isolated a probiotic resistant strain to bile and high acidity, L. delbrueckii subsp. bulgaricus-K98. Qualitative and quantitative changes in the intestinal microbiota are found after ingestion of a homemade yogurt containing this strain, with a concomitant increase in faecal SCFA. Our findings support the interest in developing further studies providing different amounts of L. delbrueckii subsp. bulgaricus-K98, and should evaluate its clinical effects in human disease.

  18. Genome sequences and comparative genomics of two Lactobacillus ruminis strains from the bovine and human intestinal tracts

    2011-08-30

    Abstract Background The genus Lactobacillus is characterized by an extraordinary degree of phenotypic and genotypic diversity, which recent genomic analyses have further highlighted. However, the choice of species for sequencing has been non-random and unequal in distribution, with only a single representative genome from the L. salivarius clade available to date. Furthermore, there is no data to facilitate a functional genomic analysis of motility in the lactobacilli, a trait that is restricted to the L. salivarius clade. Results The 2.06 Mb genome of the bovine isolate Lactobacillus ruminis ATCC 27782 comprises a single circular chromosome, and has a G+C content of 44.4%. In silico analysis identified 1901 coding sequences, including genes for a pediocin-like bacteriocin, a single large exopolysaccharide-related cluster, two sortase enzymes, two CRISPR loci and numerous IS elements and pseudogenes. A cluster of genes related to a putative pilin was identified, and shown to be transcribed in vitro. A high quality draft assembly of the genome of a second L. ruminis strain, ATCC 25644 isolated from humans, suggested a slightly larger genome of 2.138 Mb, that exhibited a high degree of synteny with the ATCC 27782 genome. In contrast, comparative analysis of L. ruminis and L. salivarius identified a lack of long-range synteny between these closely related species. Comparison of the L. salivarius clade core proteins with those of nine other Lactobacillus species distributed across 4 major phylogenetic groups identified the set of shared proteins, and proteins unique to each group. Conclusions The genome of L. ruminis provides a comparative tool for directing functional analyses of other members of the L. salivarius clade, and it increases understanding of the divergence of this distinct Lactobacillus lineage from other commensal lactobacilli. The genome sequence provides a definitive resource to facilitate investigation of the genetics, biochemistry and host

  19. Cox2 and β-Catenin/T-cell Factor Signaling Intestinalize Human Esophageal Keratinocytes When Cultured under Organotypic Conditions

    Jianping Kong

    2011-09-01

    Full Text Available The incidence of esophageal adenocarcinoma (EAC is rising in the United States. An important risk factor for EAC is the presence of Barrett esophagus (BE. BE is the replacement of normal squamous esophageal epithelium with a specialized columnar epithelium in response to chronic acid and bile reflux. However, the emergence of BE from squamous keratinocytes has not yet been demonstrated. Our research has focused on this. Wnt and cyclooxygenase 2 (Cox2 are two pathways whose activation has been associated with BE and progression to EAC, but their role has not been tested experimentally. To explore their contribution, we engineered a human esophageal keratinocyte cell line to express either a dominant-active Wnt effector CatCLef or a Cox2 complementary DNA. In a two-dimensional culture environment, Cox2 expression increases cell proliferation and migration, but neither transgene induces known BE markers. In contrast, when these cells were placed into three-dimensional organotypic culture conditions, we observed more profound effects. CatCLef-expressing cells were more proliferative, developed a thicker epithelium, and upregulated Notch signaling and several BE markers including NHE2. Cox2 expression also increased cell proliferation and induced a thicker epithelium. More importantly, we observed cysts form within the epithelium, filled with intestinal mucins including Muc5B and Muc17. This suggests that Cox2 expression in a three-dimensional culture environment induces a lineage of mucin-secreting cells and supports an important causal role for Cox2 in BE pathogenesis. We conclude that in vitro modeling of BE pathogenesis can be improved by enhancing Wnt signaling and Cox2 activity and using three-dimensional organotypic culture conditions.

  20. Perfil epidemiológico e morbimortalidade dos pacientes submetidos à reconstrução de trânsito intestinal: experiência de um centro secundário do Nordeste Brasileiro Epidemiologic profile and morbimortality of patients undergoing reconstruction intestinal transit: experience of a secundary health service in the Northeast of Brazil

    Jeany Borges e Silva

    2010-09-01

    Full Text Available RACIONAL: A reconstrução do trânsito intestinal não está isenta de riscos cirúrgicos e apresenta taxas consideráveis de complicações pós-operatórias, sendo que a infecção continua a ser um dos maiores desafios existentes neste procedimento. OBJETIVO: Perfil epidemiológico e morbimortalidade dos pacientes submetidos à reconstrução de trânsito intestinal. MÉTODOS: Foram analisados retrospectivamente 86 prontuários de pacientes com colostomia ou ileostomia, através de fatores que tivessem impacto sobre a morbimortalidade após a reconstrução de trânsito intestinal, de janeiro de 2003 a abril de 2009. RESULTADOS: Houve 20 mulheres e 60 homens, com idade média de 43 anos. A colostomia em alça (n=34 e o trauma abdominal indicando colostomia ou ileostomia foram as condições mais frequentes. O intervalo médio entre a confecção do estoma e a reconstrução de trânsito intestinal foi 15,7 meses. O índice de morbidade foi 56,8%, sendo a infecção incisional a complicação mais comum (27.47%. A permanência hospitalar média foi 7,6 dias. Houve regressão linear positiva entre permanência hospitalar pós-operatória e a idade do paciente. Demonstrou-se associação estatisticamente significativa entre o prolongamento da permanência hospitalar e a ocorrência de complicações (pBACKGROUND: The reconstruction of the intestinal tract is not surgical complications risk-free and is associated to postoperative complications high rates; furthermore, infection remains the hardest challenge in this procedure. AIM: Epidemiological profile and mortality and morbidity in patients undergoing reconstruction of intestinal transit. METHODS: Retrospectively, 86 patients with intestinal stomas were analyzed through factors that impact on the morbimortality afterwards intestinal transit reconstruction, since January 2003 to April 2009. RESULTS: Loop colostomy (n=34 and abdominal trauma implicating 38.2% of indications to colostomy or

  1. IMPACT OF INSTITUTIONAL QUALITY ON HUMAN RIGHTS ABUSES IN TRANSITION ECONOMIES

    Vadlamannati, Krishna Chaitanya; Tamazian, Artur

    2008-01-01

    This purpose of this paper is to examine the direct effects of institutional quality on human rights abuses in transition economies. We make use of an alternative empirical approach for evaluation of institutional system’s development in transition economies developed by Chousa et al. (2005). To assess this relationship, along with institutional quality index, which is an operational indicator of institutional system dynamics to observe institutional reforms-economic growth interdependence, w...

  2. Hydrolytic Fate of 3/15-Acetyldeoxynivalenol in Humans: Specific Deacetylation by the Small Intestine and Liver Revealed Using in Vitro and ex Vivo Approaches.

    Ajandouz, El Hassan; Berdah, Stéphane; Moutardier, Vincent; Bege, Thierry; Birnbaum, David Jérémie; Perrier, Josette; Di Pasquale, Eric; Maresca, Marc

    2016-01-01

    In addition to deoxynivalenol (DON), acetylated derivatives, i.e., 3-acetyl and 15-acetyldexynivalenol (or 3/15ADON), are present in cereals leading to exposure to these mycotoxins. Animal and human studies suggest that 3/15ADON are converted into DON after their ingestion through hydrolysis of the acetyl moiety, the site(s) of such deacetylation being still uncharacterized. We used in vitro and ex vivo approaches to study the deacetylation of 3/15ADON by enzymes and cells/tissues present on their way from the food matrix to the blood in humans. We found that luminal deacetylation by digestive enzymes and bacteria is limited. Using human cells, tissues and S9 fractions, we were able to demonstrate that small intestine and liver possess strong deacetylation capacity compared to colon and kidneys. Interestingly, in most cases, deacetylation was more efficient for 3ADON than 15ADON. Although we initially thought that carboxylesterases (CES) could be responsible for the deacetylation of 3/15ADON, the use of pure human CES1/2 and of CES inhibitor demonstrated that CES are not involved. Taken together, our original model system allowed us to identify the small intestine and the liver as the main site of deacetylation of ingested 3/15ADON in humans. PMID:27483321

  3. Phase transition of the microvascular network architecture in human pathologies.

    Bianciardi, Giorgio; Traversi, Claudio; Cattaneo, Ruggero; De Felice, Claudia; Monaco, Annalisa; Tosi, Gianmarco; Parrini, Stefano; Latini, Giuseppe

    2012-01-01

    We have investigated the microvascular pattern in acquired or genetic diseases in humans. The lower gingival and vestibular oral mucosa, as well as the optic nerve head, was chosen to characterize the vascular pattern complexity due to the simple accessibility and visibility Local fractal dimensions, fractal dimension of the minimum path and Lempel-Ziv complexity have been used as operational numerical tools to characterize the microvascular networks. In the normal healthy subjects microvascular networks show nonlinear values corresponding to the complexity of a diffusion limited aggregation (DLA) model, while in several acquired or genetic diseases they are approaching the ones of an invasion percolation model. PMID:23193796

  4. Intestinal Obstruction

    ... 2 Diabetes, Heart Disease a Dangerous Combo Are 'Workaholics' Prone to OCD, Anxiety? ALL NEWS > Resources First ... inflammation and infection of the abdominal cavity ( peritonitis ). Causes Causes of intestinal obstruction differ depending on the ...

  5. Intestinal Malrotation

    ... to maintain adequate nutrition (a condition known as short bowel syndrome). They may be dependent on intravenous nutrition for a time after surgery (or even permanently if too little intestine remains) ...

  6. Growth-Inhibiting and morphostructural effects of constituents identified in Asarum heterotropoides root on human intestinal bacteria

    2013-01-01

    the antimicrobial susceptibility of the harmful Gram-positive bacteria and the harmful and nonpathogenic Gram-negative bacteria was not observed. Scanning electron microscopy observations showed different degrees of physical damage and morphological alteration to both Gram-positive and Gram-negative bacteria treated with α-asarone, δ-3-carene, pellitorine, or ciprofloxacin, indicating that they do not share a common mode of action. Conclusion A. heterotropoides root-derived materials described merit further study as potential antibacterial products or lead molecules for the prevention or eradication from humans from diseases caused by harmful intestinal bacteria. PMID:24083511

  7. Transition in the Human Exploration of Space at NASA

    Koch, Carla A.; Cabana, Robert

    2011-01-01

    NASA is taking the next step in human exploration, beyond low Earth orbit. We have been going to low Earth orbit for the past 50 years and are using this experience to work with commercial companies to perform this function. This will free NASA resources to develop the systems necessary to travel to a Near Earth Asteroid, the Moon, Lagrange Points, and eventually Mars. At KSC, we are positioning ourselves to become a multi-user launch complex and everything we are working on is bringing us closer to achieving this goal. A vibrant multi-use spaceport is to the 21st Century what the airport was to the 20th Century - an invaluable transportation hub that supports government needs while promoting economic development and commercial markets beyond Earth's atmosphere. This past year saw the end of Shuttle, but the announcements of NASA's crew module, Orion, and heavy-lift rocket, the SLS, as well as the establishment of the Commercial Crew Program. We have a busy, but very bright future ahead of us and KSC is looking forward to playing an integral part in the next era of human space exploration. The future is SLS, 21st Century Ground Systems Program, and the Commercial Crew Program; and the future is here.

  8. Law in Transition Biblioessay: Globalization, Human Rights, Environment, Technology

    Michael Marien

    2012-04-01

    Full Text Available As globalization continues, many transformations in international and domestic laws areunderway or called for. There are too many laws and too few, too much law that is inadequateor obsolete, and too much law-breaking. This biblioessay covers some 100 recentbooks, nearly all recently published, arranged in four categories. 1 International Lawincludes six overviews/textbooks on comparative law, laws related to warfare and security,pushback against demands of globalization, and gender perspectives; 2 Human Rightsencompasses general overviews and normative visions, several books on how some statesviolate human rights, five items on how good laws can end poverty and promote prosperity,and laws regulating working conditions and health rights; 3 Environment/Resources coversgrowth of international environmental law, visions of law for a better environmental future,laws to govern genetic resources and increasingly stressed water resources, two books onprospects for climate change liability, and items on toxic hazards and problems of compliance;4 Technology, Etc. identifies eight books on global crime and the failed war on drugs,books on the response to terrorism and guarding privacy and mobility in our high-tech age,seven books on how infotech is changing law and legal processes while raising intellectualproperty questions, biomedical technologies and the law, and general views on the need forupdated laws and constitutions. In sum, this essay suggests the need for deeper and timelyanalysis of the many books on changes in law.

  9. Transitions in pathways of human development and carbon emissions

    Countries are known to follow diverse pathways of life expectancy and carbon emissions, but little is known about factors driving these dynamics. In this letter we estimate the cross-sectional economic, demographic and geographic drivers of consumption-based carbon emissions. Using clustering techniques, countries are grouped according to their drivers, and analysed with respect to a criteria of one tonne of carbon emissions per capita and a life expectancy over 70 years (Goldemberg’s Corner). Five clusters of countries are identified with distinct drivers and highly differentiated outcomes of life expectancy and carbon emissions. Representatives from four clusters intersect within Goldemberg’s Corner, suggesting diverse combinations of drivers may still lead to sustainable outcomes, presenting many countries with an opportunity to follow a pathway towards low-carbon human development. By contrast, within Goldemberg’s Corner, there are no countries from the core, wealthy consuming nations. These results reaffirm the need to address economic inequalities within international agreements for climate mitigation, but acknowledge plausible and accessible examples of low-carbon human development for countries that share similar underlying drivers of carbon emissions. In addition, we note differences in drivers between models of territorial and consumption-based carbon emissions, and discuss interesting exceptions to the drivers-based cluster analysis. (paper)

  10. Human intestinal parasites in Karakuak, West Flores, Indonesia and the effect of treatment with mebendazole and pyrantel pamoate.

    Purnomo; Partono, F; Soewarta, A

    1980-09-01

    A survey for intestinal parasites and mass-treatment with a combination of mebendazole and pyrantel pamoate were conducted in Karakuak, West Flores in 1977. A total of 198 stool specimens from 104 males and 94 females ranging in age from less than 1 to 70 years were examined and 72% harbored one or more intestinal parasites. Ascaris lumbricoides (43%) and Entamoeba histolytica (21%) were the most common, followed by Entamoeba coli (19%), hookworm (18%), Iodamoeba bütschlii (8%), Giardia lamblia (5%) and Trichuris trichiura (4%). Other intestinal parasites infrequently found were: Entamoeba hartmanni (2%), Chilomastix mesnili (2%), Endolimax nana (1%), Enterobius vermicularis (1%) and a heterophyid sp. (1%). A combination of mebendazole base at 200 mg/day and pyrantel pamoate salt at 60 mg/day for three consecutive days was 100% effective. PMID:7444573

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

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

    2011-01-07

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

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

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

  13. Bridging the bonding gap: the transition from primates to humans.

    Dunbar, R I M

    2012-07-01

    Primate societies are characterized by bonded social relationships of a kind that are rare in other mammal taxa. These bonded relationships, which provide the basis for coalitions, are underpinned by an endorphin mechanism mediated by social grooming. However, bonded relationships of this kind impose constraints on the size of social groups that are possible. When ecological pressures have demanded larger groups, primates have had to evolve new mechanisms to facilitate bonding. This has involved increasing the size of vocal and visual communication repertoires, increasing the time devoted to social interaction and developing a capacity to manage two-tier social relationships (strong and weak ties). I consider the implications of these constraints for the evolution of human social communities and argue that laughter was an early evolutionary innovation that helped bridge the bonding gap between the group sizes characteristic of chimpanzees and australopithecines and those in later hominins. PMID:22641822

  14. Bridging the bonding gap: the transition from primates to humans

    Dunbar, R. I. M.

    2012-01-01

    Primate societies are characterized by bonded social relationships of a kind that are rare in other mammal taxa. These bonded relationships, which provide the basis for coalitions, are underpinned by an endorphin mechanism mediated by social grooming. However, bonded relationships of this kind impose constraints on the size of social groups that are possible. When ecological pressures have demanded larger groups, primates have had to evolve new mechanisms to facilitate bonding. This has involved increasing the size of vocal and visual communication repertoires, increasing the time devoted to social interaction and developing a capacity to manage two-tier social relationships (strong and weak ties). I consider the implications of these constraints for the evolution of human social communities and argue that laughter was an early evolutionary innovation that helped bridge the bonding gap between the group sizes characteristic of chimpanzees and australopithecines and those in later hominins. PMID:22641822

  15. Marmoset cytochrome P450 2J2 mainly expressed in small intestines and livers effectively metabolizes human P450 2J2 probe substrates, astemizole and terfenadine.

    Uehara, Shotaro; Uno, Yasuhiro; Inoue, Takashi; Okamoto, Eriko; Sasaki, Erika; Yamazaki, Hiroshi

    2016-11-01

    1. Common marmoset (Callithrix jacchus), a New World Monkey, has potential to be a useful animal model in preclinical studies. However, drug metabolizing properties have not been fully understood due to insufficient information on cytochrome P450 (P450), major drug metabolizing enzymes. 2. Marmoset P450 2J2 cDNA was isolated from marmoset livers. The deduced amino acid sequence showed a high-sequence identity (91%) with cynomolgus monkey and human P450 2J2 enzymes. A phylogenetic tree revealed that marmoset P450 2J2 was evolutionarily closer to cynomolgus monkey and human P450 2J2 enzymes, than P450 2J forms in pigs, rabbits, rats or mice. 3. Marmoset P450 2J2 mRNA was abundantly expressed in the small intestine and liver, and to a lesser extent in the brain, lung and kidney. Immunoblot analysis also showed expression of marmoset P450 2J2 protein in the small intestine and liver. 4. Enzyme assays using marmoset P450 2J2 protein heterologously expressed in Escherichia coli indicated that marmoset P450 2J2 effectively catalyzed astemizole O-demethylation and terfenadine t-butyl hydroxylation, similar to human and cynomolgus monkey P450 2J2 enzymes. 5. These results suggest the functional characteristics of P450 2J2 enzymes are similar among marmosets, cynomolgus monkeys and humans. PMID:26899760

  16. Tuning the inflammatory response to silver nanoparticles via quercetin in Caco-2 (co-)cultures as model of the human intestinal mucosa.

    Martirosyan, Alina; Grintzalis, Konstantinos; Polet, Madeleine; Laloux, Laurie; Schneider, Yves-Jacques

    2016-06-24

    Interaction of nanoparticles with food matrix components may cause unpredictable health complications. Using an improved Caco-2 cell-based in vitro (co-)culture model the potential of quercetin as one of the major food flavonoids to alter the effect of silver nanoparticles (Ag-NPs) <20 nm in the human intestinal mucosa at real life concentrations was investigated. Ag-NPs (15-90 μg/ml) decreased cell viability and reduced thiol groups, induced oxidative/nitrosative stress and lipid peroxidation and led to activity changes of various antioxidant enzymes after 3h exposure. The contribution of Ag(+) ions within the concentrations released from nanoparticles was shown to be less important, compared to Ag-NPs. While leading to inflammatory response in the intestines, Ag-NPs, paradoxically, also showed a potential anti-infammatory effect manifested in down-regulated IL-8 levels. Quercetin, co-administered with Ag-NPs, led to a reduction of cytotoxicity, oxidative stress, and recovered metabolic activity of Caco-2 cells, suggesting the protective effects of this flavonoid against the harmful effect of Ag-NPs. Quercetin not only alleviated the effect of Ag-NPs on the gastrointestinal cells, but also demonstrated a potential to serve as a tool for reversible modulation of intestinal permeability. PMID:27113704

  17. Small Intestine Disorders

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

  18. Insider ownership, human resource strategies and performance in a transition economy

    Buck, T.; Filatotchev, I.; N Demina; Wright, M

    2003-01-01

    Researchers and potential investors in transition economies need to understand the Human Resource Management (HRM) strategies of target firms, since human resources are arguably their most valuable assets. Understanding is difficult, however, because HRM strategies help to determine firms' performance, but are in turn influenced by corporate governance, particularly insider ownership. This paper employs a structural equation modeling methodology to examine the relations between governance, HR...

  19. Does human resource management matter in a transitional economy? China as an example

    Law, K. S.; D K Tse; Zhou, N.

    2003-01-01

    This paper investigates the significance of how firms manage their human resources (HRs) within the confines of powerful social institutions in a transitional economy, the People's Republic of China (China). We propose that two dimensions, the role of human resource management (RHR) and followers' perception of the leader (TOP), are important contributors to firm performance as are the influences of the regional economy and firm ownership. We tested our hypotheses with a survey of 180 firms f...

  20. Human capital accumulation and the transition from specialization to multi-tasking

    Boucekkine, Raouf; Crifo, Patricia

    2003-01-01

    This paper provides theoretical foundations to the contemporaneous increase in computer usage, human capital and multi-tasking observed in many OECD countries during the 1990s. The links between work organization, technology and human capital is modelled by establishing the conditions under which firms allocate the workers time among several productive tasks. Organizational change is then analysed in a dynamic perspective as the transition from specialization towards multi-tasking emphasizing...

  1. Human Capital Accumulation and the Transition from Specialisation to Multi-tasking

    Raouf, BOUCEKKINE; Patricia, CRIFO

    2003-01-01

    This paper provides theoretical foundations to the contemporaneous increase in computer usage, human capital and multi-tasking observed in many OECD countries during the 1990s. The links between work organization, technology and human capital is modelled by establishing the conditions under which firms allocate the workers’ time among several productive tasks. Organizational change is then analysed in a dynamic perspective as the transition from specialization towards multi-tasking emphasizin...

  2. The pyrohealth transition: how combustion emissions have shaped health through human history.

    Johnston, Fay H; Melody, Shannon; Bowman, David M J S

    2016-06-01

    Air pollution from landscape fires, domestic fires and fossil fuel combustion is recognized as the single most important global environmental risk factor for human mortality and is associated with a global burden of disease almost as large as that of tobacco smoking. The shift from a reliance on biomass to fossil fuels for powering economies, broadly described as the pyric transition, frames key patterns in human fire usage and landscape fire activity. These have produced distinct patters of human exposure to air pollution associated with the Agricultural and Industrial Revolutions and post-industrial the Earth global system-wide changes increasingly known as the Anthropocene. Changes in patterns of human fertility, mortality and morbidity associated with economic development have been previously described in terms of demographic, epidemiological and nutrition transitions, yet these frameworks have not explicitly considered the direct consequences of combustion emissions for human health. To address this gap, we propose a pyrohealth transition and use data from the Global Burden of Disease (GBD) collaboration to compare direct mortality impacts of emissions from landscape fires, domestic fires, fossil fuel combustion and the global epidemic of tobacco smoking. Improving human health and reducing the environmental impacts on the Earth system will require a considerable reduction in biomass and fossil fuel combustion.This article is part of the themed issue 'The interaction of fire and mankind'. PMID:27216506

  3. Effect of Spore-bearing Lactic Acid-forming Bacteria (Bacillus coagulans SANK 70258) Administration on the Intestinal Environment, Defecation Frequency, Fecal Characteristics and Dermal Characteristics in Humans and Rats

    Ara, Katsutoshi; Meguro, Shinichi; Hase, Tadasi; Tokimitsu, Ichirou; OTSUJI, Kazuya; Kawai, Shuji; Ito, Susumu; Iino, Hisakazu

    2011-01-01

    The effects of spore-bearing lactic acid-forming bacteria (Bacillus coagulans SANK 70258) on intestinal flora and decomposition products in the intestine, as well as on various dermal characteristics were determined in healthy humans and rats. Improvement of fecal shape, change of fecal color from dark brown to yellowish brown, decrease of fecal odor and fecal pH and an increase in defecation frequency in persons whose defecation frequency was relatively low were observed after administration...

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

    Rumessen, J J; Thuneberg, L

    1991-01-01

    studied. Freshly resected intestine was examined by light and electron microscopy. The interstitial cells of Cajal resembled modified smooth muscle cells. They had caveolae and dense bodies, an incomplete basal lamina, a very well-developed smooth endoplasmic reticulum, and abundant intermediate (10 nm...

  5. The Intestine Plays a Substantial Role in Human Vitamin B6 Metabolism : A Caco-2 Cell Model

    Albersen, Monique; Bosma, Marjolein; Knoers, Nine V. V. A. M.; de Ruiter, Berna H. B.; Diekman, Eugene F.; de Ruijter, Jessica; Visser, Wouter F.; de Koning, Tom J.; Verhoeven-Duif, Nanda M.

    2013-01-01

    Background: Vitamin B6 is present in various forms (vitamers) in the diet that need to be metabolized to pyridoxal phosphate (PLP), the active cofactor form of vitamin B6. In literature, the liver has been reported to be the major site for this conversion, whereas the exact role of the intestine rem

  6. Returns to the market: valuing human capital in the post-transition Czech and Slovak Republics

    Filer, R.; Jurajda, Štěpán; Plánovský, J.

    -, č. 125 (1999), s. 1-26. ISSN 1211-3298 Institutional research plan: CEZ:AV0Z7085904 Keywords : human capital * post-transition Czech and Slovak Republics Subject RIV: AH - Economics http://www.cerge-ei.cz/pdf/wp/Wp125.pdf

  7. Contributions of NanI Sialidase to Caco-2 Cell Adherence by Clostridium perfringens Type A and C Strains Causing Human Intestinal Disease

    Li, Jihong; McClane, Bruce A.

    2014-01-01

    Previous studies showed that Clostridium perfringens type D animal disease strain CN3718 uses NanI sialidase for adhering to enterocyte-like Caco-2 cells. The current study analyzed whether NanI is similarly important when type A and C human intestinal disease strains attach to Caco-2 cells. A PCR survey determined that the nanI gene was absent from typical type A food poisoning (FP) strains carrying a chromosomal enterotoxin (CPE) gene or the genetically related type C Darmbrand (Db) strains...

  8. The Effect of Lactulose on the Survival of Lactobacillus rhamnosus in the Simulator of the Human Intestinal Microbial Ecosystem (SHIME) and in vivo

    Kontula, Pia; Nollet, Lode; Saarela, Maria; Vilpponen-Salmela, Terttu; Verstraete, Willy; Mattila-Sandholm, Tiina; von Wright, Atte

    2011-01-01

    The effect of lactulose on the survival of Lactobacillus rhamnosus VTT E-97800 and on the colon microbiota and its metabolic activity was studied using the Simulator of the Human Intestinal Microbial Ecosystem (SHIME) model. L. rhamnosus VTT E-97800 and lactulose together enhanced the production of butyric acid and decreased ammonium concentration in the model. The numbers of Bacteroides were observed to decrease 2.5–2.0 log10 cfu:ml during the SHIME experiment. In the subsequent in viv...

  9. Enteral nutrients potentiate glucagon-like peptide-2 action and reduce dependence on parenteral nutrition in a rat model of human intestinal failure

    Brinkman, Adam S; Murali, Sangita G; Hitt, Stacy;

    2012-01-01

    Glucagon-like peptide-2 (GLP-2) is a nutrient-dependent, proglucagon-derived gut hormone that shows promise for the treatment of short bowel syndrome (SBS). Our objective was to investigate how combination GLP-2 + enteral nutrients (EN) affects intestinal adaption in a rat model that mimics severe...... human SBS and requires parenteral nutrition (PN). Male Sprague-Dawley rats were assigned to one of five groups and maintained with PN for 18 days: total parenteral nutrition (TPN) alone, TPN + GLP-2 (100 μg·kg(-1)·day(-1)), PN + EN + GLP-2(7 days), PN + EN + GLP-2(18 days), and a nonsurgical oral...

  10. Colonization of the streptomycin-treated mouse large intestine by a human fecal Escherichia coli strain: role of growth in mucus.

    Wadolkowski, E A; Laux, D C; Cohen, P S

    1988-01-01

    The relative colonizing abilities of Escherichia coli F-18, isolated from the feces of a healthy human, and E. coli F-18col-, a strain derived from it which does not make the E. coli F-18 colicin, were studied. In a previous report, it was shown that when each strain was fed individually to streptomycin-treated mice, at approximately 10(10) CFU per mouse, each colonized the large intestine at between 10(7) and 10(8) CFU/g of feces indefinitely. However, when simultaneously fed to mice, althou...

  11. Human microsomal cyttrochrome P450-mediated reduction of oxysophocarpine, an active and highly toxic constituent derived from Sophora flavescens species, and its intestinal absorption and metabolism in rat.

    Wu, Lili; Zhong, Wanping; Liu, Junjin; Han, Weichao; Zhong, Shilong; Wei, Qiang; Liu, Shuwen; Tang, Lan

    2015-09-01

    Oxysophocarpine (OSC), an active and toxic quinolizidine alkaloid, is highly valued in Sophora flavescens Ait. and Subprostrate sophora Root. OSC is used to treat inflammation and hepatitis for thousands of years in China. This study aims to investigate the CYP450-mediated reduction responsible for metabolizing OSC and to evaluate the absorption and metabolism of OSC in rat in situ. Four metabolites were identified, with sophocarpine (SC) as the major metabolite. SC formation was rapid in human and rat liver microsomes (HLMs and RLMs, respectively). The reduction rates in the liver are two fold higher than in the intestine, both in humans and rats. In HLMs, inhibitors of CYP2C9, 3A4/5, 2D6, and 2B6 had strong inhibitory effects on SC formation. Meanwhile, inhibitors of CYP3A and CYP2D6 had significant inhibition on SC formation in RLMs. Human recombinant CYP3A4/5, 2B6, 2D6, and 2C9 contributed significantly to SC production. The permeability in rat intestine and the excretion rates of metabolites were highest in the duodenum (pCYP3A inhibitor ketoconazole. In conclusion, the liver was the main organ responsible for OSC metabolism. First-pass metabolism via CYP3A4/5, 2B6, 2D6, and 2C9 may be the main reason for the poor OSC bioavailability. PMID:26045316

  12. Evaluation by computerized morphometry of histopathological alterations of the colon wall in segments with and without intestinal transit in rats Avaliação por morfometria computadorizada das alterações histopatológicas da parede cólica em segmentos com e sem trânsito intestinal em ratos

    Marcos Vieira de Sousa

    2008-10-01

    Full Text Available PURPOSE: To evaluate histopathological alterations of the colon wall in segments with and without intestinal transit, by computer-assisted imaging, and to correlate these with the length of time diversion. METHODS: Thirty male Wistar rats were subjected to intestinal transit diversion by a proximal colostomy and distal mucosa fistula. The animals were divided into three experimental groups according to how long after the initial surgical procedure they were sacrificed: six, twelve and eighteen weeks. Colon segments with and without transit were subjected to histopathological study. The variables colon crypt length, mucosal ulceration, muscle layer thickness of the muscularis mucosa, submucosa and muscularis propria, vascular congestion, number of caliciform cells, inflammatory grade and degree of inflammation, comparing the two colon segments in the different experimental groups were studied. Intestinal crypt length, muscle layer thickness of the mucosa, submucosa and muscularis propria and caliciform cells were measured by computer-assisted imaging method. Mean equality, variance analysis and correlation tests were used in the statistical analysis, and the significance level was set at 5%. RESULTS: Comparison between segments with and without transit showed that the latter presented reduced length of colon crypts and increased muscle layer thickness of the muscularis mucosa, submucosa and muscularis propria. There were greater quantities of ulceration of the mucosal and greater degree of inflammation with increasing time without transit. Mucosal ulceration, submucosal vascular congestion, increased thickness of the submucosal and muscularis propria layers, presence of caliciform cells, inflammatory infiltrate and inflammatory grade correlated significantly with the length of time without transit. CONCLUSIONS: Histological alterations occurred in all layers of the colon wall, in the segments without intestinal transit. Ulcerations in the

  13. Biomechanics of the human walk-to-run gait transition in persons with unilateral transtibial amputation.

    Giest, Tracy N; Chang, Young-Hui

    2016-06-14

    Propulsive force production (indicative of intrinsic force-length-velocity characteristics of the plantar flexor muscles) has been shown to be a major determinant of the human walk-to-run transition. The purpose of this work was to determine the gait transition speed of persons with unilateral transtibial amputation donning a passive-elastic prosthesis and assess whether a mechanical limit of their intact side plantar flexor muscles is a major determinant of their walk-to-run transition. We determined each individual׳s gait transition speed (GTS) via an incremental protocol and assessed kinetics and kinematics during walking at speeds 50%, 60%, 70%, 80%, 90%, 100%, 120%, and 130% of that gait transition speed (100%:GTS). Unilateral transtibial amputees transitioned between gaits at significantly slower absolute speeds than matched able-bodied controls (1.73±0.13 and 2.09±0.05m/s respectively, p120%: 0.23±0.05BW, p<0.05). In contrast, amputee subjects' intact side generated significantly higher peak anterior-posterior propulsive forces while walking at speeds above their preferred gait transition speed (100%: 0.28±0.04<110%: 0.30±0.04BW, p<0.05). Changes in propulsive force production were found to be a function of changes in absolute speed, rather than relative to the walk-to-run transition speed. Therefore, the walk-to-run transition in unilateral transtibial amputees is not likely dictated by propulsive force production or the force-length-velocity characteristics of the intact side plantar flexor muscles. PMID:27087677

  14. Small & Large Intestine

    ... the large intestine produces no digestive enzymes. Chemical digestion is completed in the small intestine before the chyme reaches the large intestine. Functions of the large intestine include the absorption of water and electrolytes and the elimination of ...

  15. INTERRELATIONSHIPS BETWEEN HUMAN CAPITAL AND SOCIAL CAPITAL: IMPLICATIONS FOR ECONOMIC DEVELOPMENT IN TRANSITION ECONOMIES

    Eve Parts

    2003-01-01

    One of the main tasks of the transition economies is to catch up with the advanced levels of highly developed economies. The lack of social capital is a major impediment to this process, as it does not allow taking advantage of the comparatively high level of human capital in these countries. The purpose of the current paper is to study the interrelationships between human capital and social capital, with the main emphasis on how social capital affects the accumulation of human capital. In ge...

  16. The origins of the Acheulean: past and present perspectives on a major transition in human evolution.

    de la Torre, Ignacio

    2016-07-01

    The emergence of the Acheulean from the earlier Oldowan constitutes a major transition in human evolution, the theme of this special issue. This paper discusses the evidence for the origins of the Acheulean, a cornerstone in the history of human technology, from two perspectives; firstly, a review of the history of investigations on Acheulean research is presented. This approach introduces the evolution of theories throughout the development of the discipline, and reviews the way in which cumulative knowledge led to the prevalent explanatory framework for the emergence of the Acheulean. The second part presents the current state of the art in Acheulean origins research, and reviews the hard evidence for the appearance of this technology in Africa around 1.7 Ma, and its significance for the evolutionary history of Homo erectusThis article is part of the themed issue 'Major transitions in human evolution'. PMID:27298475

  17. Inhibition of the NF-kappaB pathway in human intestinal epithelial cells by commensal Streptococcus salivarius.

    Kaci, Ghalia; Lakhdari, Omar; Doré, Joël; Ehrlich, S Dusko; Renault, Pierre; Blottière, Hervé M; Delorme, Christine

    2011-07-01

    Streptococcus salivarius exhibited an anti-inflammatory effect on intestinal epithelial cells (IECs) and monocytes. Strains were screened using a reporter clone, HT-29/kB-luc-E, induced by tumor necrosis factor alpha (TNF-α). Supernatant from each strain downregulated NF-κB activation. The two most efficient strains produced an active metabolite (<3 kDa) which was able to downregulate the secretion of the proinflammatory chemokine interleukin-8 (IL-8). PMID:21602373

  18. Inhibition of the NF-κB Pathway in Human Intestinal Epithelial Cells by Commensal Streptococcus salivarius ▿ †

    Kaci, Ghalia; Lakhdari, Omar; Doré, Joël; Ehrlich, S. Dusko; Renault, Pierre; Blottière, Hervé M.; Delorme, Christine

    2011-01-01

    Streptococcus salivarius exhibited an anti-inflammatory effect on intestinal epithelial cells (IECs) and monocytes. Strains were screened using a reporter clone, HT-29/kB-luc-E, induced by tumor necrosis factor alpha (TNF-α). Supernatant from each strain downregulated NF-κB activation. The two most efficient strains produced an active metabolite (<3 kDa) which was able to downregulate the secretion of the proinflammatory chemokine interleukin-8 (IL-8). PMID:21602373

  19. Pancreatoduodenectomy as a source of human small intestine for Ussing Chamber Investigations and comparative studies with rat tissue

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

    2011-01-01

    Abstract A clear understanding of oral drug absorption is an important aspect of the drug development process. The permeability of drug compounds across intact sections of small intestine from numerous species, including man, has often been investigated using modified Ussing Chambers. The maintenance of viable, intact tissue is critical to the success of this technique. This study therefore aimed to assess the viability and integrity of tissue from patients undergoing pancreatod...

  20. Antagonism between two intestinal parasites in humans: the importance of co-infection for infection risk and recovery dynamics

    Blackwell, AD; Martin, M.; Kaplan, H.; Gurven, M

    2013-01-01

    Co-infection may affect transmission and recovery from infection, but remains an understudied element of disease ecology, particularly with regard to antagonism between parasites sharing a host. Helminth and giardia infections are often endemic in the same populations and both occupy the small intestine; yet few studies have examined interactions between these parasites. We report on helminth-giardia co-infections in a panel study of forager-horticulturalists in the Bolivian lowlands. Parasit...

  1. Modulators of intestinal alkaline phosphatase.

    Bobkova, Ekaterina V; Kiffer-Moreira, Tina; Sergienko, Eduard A

    2013-01-01

    Small molecule modulators of phosphatases can lead to clinically useful drugs and serve as invaluable tools to study functional roles of various phosphatases in vivo. Here, we describe lead discovery strategies for identification of inhibitors and activators of intestinal alkaline phosphatases. To identify isozyme-selective inhibitors and activators of the human and mouse intestinal alkaline phosphatases, ultrahigh throughput chemiluminescent assays, utilizing CDP-Star as a substrate, were developed for murine intestinal alkaline phosphatase (mIAP), human intestinal alkaline phosphatase (hIAP), human placental alkaline phosphatase (PLAP), and human tissue-nonspecific alkaline phosphatase (TNAP) isozymes. Using these 1,536-well assays, concurrent HTS screens of the MLSMR library of 323,000 compounds were conducted for human and mouse IAP isozymes monitoring both inhibition and activation. This parallel screening approach led to identification of a novel inhibitory scaffold selective for murine intestinal alkaline phosphatase. SAR efforts based on parallel testing of analogs against different AP isozymes generated a potent inhibitor of the murine IAP with IC50 of 540 nM, at least 65-fold selectivity against human TNAP, and >185 selectivity against human PLAP. PMID:23860652

  2. Identification and Characterization of a Novel Nontranslated Sequence Variant of the Human Intestinal Di-/Tripeptide Transporter, hPEPT1

    Helle Bach Søndergaard

    2012-01-01

    Full Text Available The human H+-coupled di-/tripeptide transporter (hPEPT1 mediates intestinal absorption of dietary di- and tripeptides, as well as several peptidomimetic drug compounds. The aim of the present study was to investigate the possible role of the hPEPT1 variant hPEPT1-RF in hPEPT1 regulation. However, the proposed hPEPT1-RF mRNA sequence could not be detected in Caco-2 cells or in human intestinal samples. Instead, a new sequence variant, hPEPT1-RFI, was found, which is almost identical to the proposed hPEPT1-RF, except for two nucleotide insertions and one deletion that resulted in a changed open reading frame as compared to hPEPT1-RF. In vitro translation analysis showed that hPEPT1-RFI was not translated. In conclusion, the existence of hPEPT1-RF could not be confirmed; furthermore, the identified sequence variant, hPEPT1-RFI, does not appear to be translated and is therefore unlikely to have a regulatory effect on hPEPT1 transport activity.

  3. Human intestinal mucosa-associated Lactobacillus and Bifidobacterium strains with probiotic properties modulate IL-10, IL-6 and IL-12 gene expression in THP-1 cells.

    Čitar, M; Hacin, B; Tompa, G; Štempelj, M; Rogelj, I; Dolinšek, J; Narat, M; Matijašić, B Bogovič

    2015-01-01

    Lactobacilli and bifidobacteria are considered one of the permanent genera of the physiological human intestinal microbiota and represent an enormous pool of potential probiotic candidates. Approximately 450 isolates of presumptive Lactobacillus or Bifidobacterium strains were obtained from bioptic samples of colonic and ileal mucosa from 15 adolescents aged 12 to 18 years. On the basis of randomly amplified polymorphic DNA (RAPD)-PCR analysis, 20 strains were selected for further taxonomic classification and characterisation, as well as assessment of probiotic properties and safety. Importantly, selected strains showed the capability of colonising different parts of the intestine. The most frequently isolated species was Lactobacillus paracasei followed by Lactobacillus fermentum. The majority of isolates were susceptible to antimicrobials of human and veterinary importance, however, tetracycline and/or erythromycin resistance was observed in Lactobacillus plantarum and L. fermentum strains. Thirteen strains were able to ferment more than 19 different carbon sources and three out of five tested strains exerted antagonistic activity against several different indicator strains. Two Lactobacillus isolates (L. paracasei L350 and L. fermentum L930 bb) and one Bifidobacterium isolate (Bifidobacterium animalis subsp. animalis IM386) fulfilled in vitro selection criteria for probiotic strains and exhibited strong downregulation of pro-inflammatory cytokines IL-6 and IL-12 and upregulation of anti-inflammatory IL-10. The selected strains represent suitable candidates for further studies regarding their positive influence on host health and could play an important role in ameliorating the symptoms of inflammatory bowel diseases. PMID:25391349

  4. Perfil epidemiológico e morbimortalidade dos pacientes submetidos à reconstrução de trânsito intestinal: experiência de um centro secundário do nordeste Brasileiro Epidemiologic profile and morbimortality of patients undergoing to intestinal transit reconstruction: experience of a secundary health service in Brazil northeast

    Jeany Borges e Silva

    2010-09-01

    Full Text Available Racional- A reconstrução do trânsito intestinal não está isenta de riscos cirúrgicos e apresenta taxas consideráveis de complicações pós-operatórias, sendo que a infecção continua a ser um dos maiores desafios existentes neste procedimento. Métodos- Foram analisados retrospectivamente 86 prontuários de pacientes com colostomia ou ileostomia, através de fatores que tivessem impacto sobre a morbimortalidade após a reconstrução de trânsito intestinal, de janeiro de 2003 a abril de 2009. Resultados- Houve 20 mulheres e 60 homens, com idade média de 43 anos. A colostomia em alça (n: 34 e o trauma abdominal indicando colostomia ou ileostomia foram as condições mais frequentes. O intervalo médio entre a confecção do estoma e a reconstrução de trânsito intestinal foi 15,7 meses. O índice de morbidade foi 56,8%, sendo a infecção incisional a complicação mais comum (27.47%. A permanência hospitalar média foi 7,6 dias. Houve regressão linear positiva entre permanência hospitalar pós-operatória e a idade do paciente. Demonstrou-se associação estatisticamente significativa entre o prolongamento da permanência hospitalar e a ocorrência de complicações (pBackground - The reconstruction of the intestinal tract is not surgical complications risk-free and is associated to postoperative complications high rates; furthermore, infection remains the hardest challenge in this procedure. Methods - Retrospectively, eighty-six patients with intestinal stomas were analyzed through factors that impact on the morbimortality afterwards intestinal transit reconstruction, since January 2003 to April 2009. Results - Loop colostomy (n=34 and abdominal trauma implicating 38.2% of indications to colostomy or ileostomy were the most frequent conditions. The mean interval between stoma confection and intestinal transit reconstruction was 15.7 months. The morbidity frequency was 56.8% and incisional infection was its commonest

  5. Both direct and indirect effects account for the pro-inflammatory activity of enteropathogenic mycotoxins on the human intestinal epithelium: Stimulation of interleukin-8 secretion, potentiation of interleukin-1β effect and increase in the transepithelial passage of commensal bacteria

    Mycotoxins are fungal secondary metabolites responsible of food-mediated intoxication in animals and humans. Deoxynivalenol, ochratoxin A and patulin are the best known enteropathogenic mycotoxins able to alter intestinal functions resulting in malnutrition, diarrhea, vomiting and intestinal inflammation in vivo. Although their effects on intestinal barrier and transport activities have been extensively characterized, the mechanisms responsible for their pro-inflammatory effect are still poorly understood. Here we investigated if mycotoxin-induced intestinal inflammation results from a direct and/or indirect pro-inflammatory activity of these mycotoxins on human intestinal epithelial cells, using differentiated Caco-2 cells as model and interleukin 8 (IL-8) as an indicator of intestinal inflammation. Deoxynivalenol was the only mycotoxin able to directly increase IL-8 secretion (10- to 15-fold increase). We also investigated if these mycotoxins could indirectly stimulate IL-8 secretion through: (i) a modulation of the action of pro-inflammatory molecules such as the interleukin-1beta (IL-1β), and/or (ii) an increase in the transepithelial passage of non-invasive commensal Escherichia coli. We found that deoxynivalenol, ochratoxin A and patulin all potentiated the effect of IL-1β on IL-8 secretion (ranging from 35% to 138% increase) and increased the transepithelial passage of commensal bacteria (ranging from 12- to 1544-fold increase). In addition to potentially exacerbate established intestinal inflammation, these mycotoxins may thus participate in the induction of sepsis and intestinal inflammation in vivo. Taken together, our results suggest that the pro-inflammatory activity of enteropathogenic mycotoxins is mediated by both direct and indirect effects

  6. Src-mediated cross-talk between farnesoid X and epidermal growth factor receptors inhibits human intestinal cell proliferation and tumorigenesis.

    Zhongsheng Peng

    Full Text Available Besides its essential role in controlling bile acid and lipid metabolism, the farnesoid X receptor (FXR protects against intestinal tumorigenesis by promoting apoptosis and inhibiting cell proliferation. However, the mechanisms underlying these anti-proliferative actions of FXR remain to be elucidated. In the present study, we examined the effects of FXR activation (FXR overexpression and treatment with an FXR agonist GW4064 and inactivation (treatment with FXR siRNA and an FXR antagonist guggulsterone on colon cancer cell proliferation in vitro using human colon cancer cell lines (H508, SNU-C4 and HT-29 and in vivo using xenografts in nude mice. Blocking FXR activity with guggulsterone stimulated time- and dose-dependent EGFR (Tyr845 phosphorylation and ERK activation. In contrast, FXR overexpression and activation with GW4064 attenuated cell proliferation by down-regulating EGFR (Tyr845 phosphorylation and ERK activation. Treatment with guggulsterone and GW4064 also caused dose-dependent changes in Src (Tyr416 phosphorylation. In stably-transfected human colon cancer cells, overexpression of FXR reduced EGFR, ERK, Src phosphorylation and cell proliferation, and in nude mice attenuated the growth of human colon cancer xenografts (64% reduction in tumor volume; 47% reduction in tumor weight; both P<0.01. Moreover, guggulsterone-induced EGFR and ERK phosphorylation and cell proliferation were abolished by inhibiting activation of Src, EGFR and MEK. Collectively these data support the novel conclusion that in human colon cancer cells Src-mediated cross-talk between FXR and EGFR modulates ERK phosphorylation, thereby regulating intestinal cell proliferation and tumorigenesis.

  7. DNA repair following ultraviolet and N-ethyl-N-nitrosourea treatment of cells cultured from human fetal brain, intestine, kidney, liver, and skin

    Gibson-D' Ambrosio, R.E.; Leong, Y.; D' Ambrosio, S.M.

    1983-12-01

    DNA excision repair was measured in cell cultures derived from human fetal brain, intestine, kidney, liver, and skin following ultraviolet (UV) irradiation and N-ethyl-N-nitrosourea (ENU) treatment. Cells in early passages were exposed to 5 or 10 J of UV radiation per sq m or to 25 microM to 3.5 mM ENU. DNA excision repair was determined by (a) scintillation counting and autoradiography to measure unscheduled DNA synthesis (UDS) and (b) the UV-endonuclease-sensitive site assay to measure pyrimidine dimers directly. The level of UDS following treatment of these cell cultures with UV was both time and dose dependent. UDS also increased with increasing doses of ENU up to 350 microM but decreased at doses greater than 500 microM. Cells derived from human fetal brain, kidney, and liver appeared to exhibit lower (50 to 80%) levels of UDS following UV irradiation or ENU treatment than did cells cultured from human fetal skin or intestine. The loss of UV-endonuclease-sensitive sites assayed in skin, liver, and kidney cells over a 24-hr period confirmed the differences observed by UDS in these cells. Skin cells removed 50% of the initial pyrimidine dimers from their DNA within an 8-hr period and 65 to 86% in 24 hr. Kidney and liver cells, on the other hand, removed only 28 and 32% of the initial dimers, respectively, over a 24-hr period. The data suggest differential excision repair responses following UV irradiation and ENU treatment of cells derived from different human fetal organs.

  8. Intra-urban human mobility and activity transition: evidence from social media check-in data.

    Lun Wu

    Full Text Available Most existing human mobility literature focuses on exterior characteristics of movements but neglects activities, the driving force that underlies human movements. In this research, we combine activity-based analysis with a movement-based approach to model the intra-urban human mobility observed from about 15 million check-in records during a yearlong period in Shanghai, China. The proposed model is activity-based and includes two parts: the transition of travel demands during a specific time period and the movement between locations. For the first part, we find the transition probability between activities varies over time, and then we construct a temporal transition probability matrix to represent the transition probability of travel demands during a time interval. For the second part, we suggest that the travel demands can be divided into two classes, locationally mandatory activity (LMA and locationally stochastic activity (LSA, according to whether the demand is associated with fixed location or not. By judging the combination of predecessor activity type and successor activity type we determine three trip patterns, each associated with a different decay parameter. To validate the model, we adopt the mechanism of an agent-based model and compare the simulated results with the observed pattern from the displacement distance distribution, the spatio-temporal distribution of activities, and the temporal distribution of travel demand transitions. The results show that the simulated patterns fit the observed data well, indicating that these findings open new directions for combining activity-based analysis with a movement-based approach using social media check-in data.

  9. Radioimmunoimaging in human transitional cell carcinoma xenografted nude mice with monoclonal antibody L4B4

    The monoclonal antibody L4B4 against transitional cell carcinoma (TCC) was prepared and radioimmunoimaging (RII) was studied in nude mice bearing human TCC using L4B4. L4B4 was identified in vitro by immunohistochemistry. Radioimmunoimaging was performed in human transitional cell carcinoma xenografted nude mice. Immunohistochemistry study showed that L4B4 had high specificity for TCC (23/24), compared to that for other malignant tumors (2/24) and benign tumors (0/7). RII study showed that xenografted tumor was demonstrated clearly on the 3rd and 5th day after injection of 125I labeled L4B4. The T/NT was greater than 4 on the 5th day. The results indicated that L4B4 might be useful in the study of TCC and is worthy to do further investigation

  10. Dysregulated expression of arginine metabolic enzymes in human intestinal tissues of necrotizing enterocolitis and response of CaCO2 cells to bacterial components.

    Leung, Kam Tong; Chan, Kathy Yuen Yee; Ma, Terence Ping Yuen; Yu, Jasmine Wai Sum; Tong, Joanna Hung Man; Tam, Yuk Him; Cheung, Hon Ming; To, Ka Fai; Lam, Hugh Simon; Lee, Kim Hung; Li, Karen; Ng, Pak Cheung

    2016-03-01

    The small intestine is the exclusive site of arginine synthesis in neonates. Low levels of circulating arginine have been associated with the occurrence of necrotizing enterocolitis (NEC) but the mechanism of arginine dysregulation has not been fully elucidated. We aimed to investigate (i) expressional changes of arginine synthesizing and catabolic enzymes in human intestinal tissues of NEC, spontaneous intestinal perforation (SIP) and noninflammatory surgical conditions (Surg-CTL) and to investigate the (ii) mechanisms of arginine dysregulation and enterocyte proliferation upon stimulation by bacterial components, arginine depletion, ARG1 overexpression and nitric oxide (NO) supplementation. Our results showed that expressions of arginine synthesizing enzymes ALDH18A1, ASL, ASS1, CPS1, GLS, OAT and PRODH were significantly decreased in NEC compared with Surg-CTL or SIP tissues. Catabolic enzyme ARG1 was increased (>100-fold) in NEC tissues and histologically demonstrated to be expressed by infiltrating neutrophils. No change in arginine metabolic enzymes was observed between SIP and Surg-CTL tissues. In CaCO2 cells, arginine metabolic enzymes were differentially dysregulated by lipopolysaccharide or lipoteichoic acid. Depletion of arginine reduced cell proliferation and this phenomenon could be partially rescued by NO. Overexpression of ARG1 also reduced enterocyte proliferation. We provided the first expressional profile of arginine metabolic enzymes at the tissue level of NEC. Our findings suggested that arginine homeostasis was severely disturbed and could be triggered by inflammatory responses of enterocytes and infiltrating neutrophils as well as bacterial components. Such reactions could reduce arginine and NO, resulting in mucosal damage. The benefit of arginine supplementation for NEC prophylaxis merits further clinical evaluation. PMID:26895666

  11. Intestinal volvulus in cetaceans.

    Begeman, L; St Leger, J A; Blyde, D J; Jauniaux, T P; Lair, S; Lovewell, G; Raverty, S; Seibel, H; Siebert, U; Staggs, S L; Martelli, P; Keesler, R I

    2013-07-01

    Intestinal volvulus was recognized as the cause of death in 18 cetaceans, including 8 species of toothed whales (suborder Odontoceti). Cases originated from 11 institutions from around the world and included both captive (n = 9) and free-ranging (n = 9) animals. When the clinical history was available (n = 9), animals consistently demonstrated acute dullness 1 to 5 days prior to death. In 3 of these animals (33%), there was a history of chronic gastrointestinal illness. The pathological findings were similar to those described in other animal species and humans, and consisted of intestinal volvulus and a well-demarcated segment of distended, congested, and edematous intestine with gas and bloody fluid contents. Associated lesions included congested and edematous mesentery and mesenteric lymph nodes, and often serofibrinous or hemorrhagic abdominal effusion. The volvulus involved the cranial part of the intestines in 85% (11 of 13). Potential predisposing causes were recognized in most cases (13 of 18, 72%) but were variable. Further studies investigating predisposing factors are necessary to help prevent occurrence and enhance early clinical diagnosis and management of the condition. PMID:23150643

  12. Spontaneous quaternary and tertiary T-R transitions of human hemoglobin in molecular dynamics simulation.

    Jochen S Hub

    2010-05-01

    Full Text Available We present molecular dynamics simulations of unliganded human hemoglobin (Hb A under physiological conditions, starting from the R, R2, and T state. The simulations were carried out with protonated and deprotonated HC3 histidines His(beta146, and they sum up to a total length of 5.6 micros. We observe spontaneous and reproducible T-->R quaternary transitions of the Hb tetramer and tertiary transitions of the alpha and beta subunits, as detected from principal component projections, from an RMSD measure, and from rigid body rotation analysis. The simulations reveal a marked asymmetry between the alpha and beta subunits. Using the mutual information as correlation measure, we find that the beta subunits are substantially more strongly linked to the quaternary transition than the alpha subunits. In addition, the tertiary populations of the alpha and beta subunits differ substantially, with the beta subunits showing a tendency towards R, and the alpha subunits showing a tendency towards T. Based on the simulation results, we present a transition pathway for coupled quaternary and tertiary transitions between the R and T conformations of Hb.

  13. Tissue engineering the small intestine.

    Spurrier, Ryan G; Grikscheit, Tracy C

    2013-04-01

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

  14. Transitions between dynamical states of differing stability in the human brain

    Meyer-Lindenberg, Andreas; Ziemann, Ulf; Hajak, Göran; Cohen, Leonardo; Berman, Karen Faith

    2002-01-01

    What mechanisms underlie the flexible formation, adaptation, synchronization, and dissolution of large-scale neural assemblies from the 1010 densely interconnected, continuously active neurons of the human brain? Nonlinear dynamics provides a unifying perspective on self-organization. It shows that the emergence of patterns in open, nonequilibrium systems is governed by their stability in response to small disturbances and predicts macroscopic transitions between patterns of differing stabili...

  15. All in transition - Human resource management and labour relations in the Chinese industrial sector

    Yu, Nan

    2012-01-01

    This discussion paper is a literature study reviewing the development of human resource management in China, with a particular focus (where possible) on the automobile industry. It presents the Chinese context for HRM discussing the normative debate about the adaptation of Western management methods and the heritage of Chinese philosophy and values, and it describes the economic, cultural, and transition-specific factors which influence HRM in China. In more detail, the paper deals with work ...

  16. Cyclophilin D-Sensitive Mitochondrial Permeability Transition in Adult Human Brain and Liver Mitochondria

    Hansson, Magnus; Morota, Saori; Li CHEN; Matsuyama, Nagahisa; SUZUKI, YOSHIAKI; Nakajima, Satoshi; Tanoue, Tadashi; Omi, Akibumi; Shibasaki, Futoshi; Shimazu, Motohide; IKEDA, Yukio; Uchino, Hiroyuki; Elmér, Eskil

    2011-01-01

    The mitochondrial permeability transition (mPT) is considered to be a major cause of cell death under a variety of pathophysiological conditions of the central nervous system (CNS) and other organs. Pharmacological inhibition or genetic knockout of the matrix protein cyclophilin D (CypD) prevents mPT and cell degeneration in several models of brain injury. If these findings in animal models are translatable to human disease, pharmacological inhibition of mPT offers a promising therapeutic tar...

  17. Triclosan Potentiates Epithelial-To-Mesenchymal Transition in Anoikis-Resistant Human Lung Cancer Cells

    Winitthana, Thidarat; Lawanprasert, Somsong; Chanvorachote, Pithi

    2014-01-01

    Alteration of cancer cell toward mesenchymal phenotype has been shown to potentiate tumor aggressiveness by increasing cancer cell metastasis. Herein, we report the effect of triclosan, a widely used antibacterial agent found in many daily products, in enhancing the epithelial-to-mesenchymal transition (EMT) in aggressive anoikis resistant human H460 lung cancer cells. EMT has been long known to increase abilities of the cells to increase migration, invasion, and survival in circulating syste...

  18. Ultra-High Field MRI: Transition to Human 7 T in Finland - Workshop Memorandum

    Auranen, Toni; Carlson, Synnöve; Hämäläinen, Matti; Jousmäki, Veikko; Renvall, Ville; Salmelin, Riitta

    2016-01-01

    A workshop “Ultra-High Field MRI: Transition to Human 7 T in Finland” was organized at Aalto University on October 8–9, 2015. The organizers included Aalto University School of Science, Finnish Infrastructures for Functional Imaging (FIFI), Aalto NeuroImaging (ANI), Aalto Brain Centre (ABC), and Department of Neuroscience and Biomedical Engineering (NBE). The purpose of the workshop was to demonstrate scientific achievements and possibilities enabled by ultra-high field (UHF) magnetic resonan...

  19. How institutions shaped the last major evolutionary transition to large-scale human societies.

    Powers, Simon T; van Schaik, Carel P; Lehmann, Laurent

    2016-02-01

    What drove the transition from small-scale human societies centred on kinship and personal exchange, to large-scale societies comprising cooperation and division of labour among untold numbers of unrelated individuals? We propose that the unique human capacity to negotiate institutional rules that coordinate social actions was a key driver of this transition. By creating institutions, humans have been able to move from the default 'Hobbesian' rules of the 'game of life', determined by physical/environmental constraints, into self-created rules of social organization where cooperation can be individually advantageous even in large groups of unrelated individuals. Examples include rules of food sharing in hunter-gatherers, rules for the usage of irrigation systems in agriculturalists, property rights and systems for sharing reputation between mediaeval traders. Successful institutions create rules of interaction that are self-enforcing, providing direct benefits both to individuals that follow them, and to individuals that sanction rule breakers. Forming institutions requires shared intentionality, language and other cognitive abilities largely absent in other primates. We explain how cooperative breeding likely selected for these abilities early in the Homo lineage. This allowed anatomically modern humans to create institutions that transformed the self-reliance of our primate ancestors into the division of labour of large-scale human social organization. PMID:26729937

  20. Intestinal Helminths Recovered from Humans in Xieng Khouang Province, Lao PDR with a Particular Note on Haplorchis pumilio Infection

    Chai, Jong-Yil; Sohn, Woon-Mok; Jung, Bong-Kwang; Yong, Tai-Soon; Eom, Keeseon S.; Min, Duk-Young; Insisiengmay, Bounnaloth; Insisiengmay, Sithat; Phommasack, Bounlay; Rim, Han-Jong

    2015-01-01

    A survey of intestinal helminths was undertaken in riparian people in Xieng Khouang Province, Lao PDR. Fecal specimens were collected from 643 people (289 males and 354 females) residing in 4 districts (Nonghet, Kham, Phoukout, and Pek) and were examined by the Kato-Katz technique. The overall helminth egg positive rate was 41.2%, and hookworms revealed the highest prevalence (32.7%) followed by Trichuris trichiura (7.3%) and Ascaris lumbricoides (5.6%). The positive rate for small trematode ...

  1. Metabolic Activities of Ginseng and Its Constituents, Ginsenoside Rb1 and Rg1, by Human Intestinal Microflora

    Choi, Jong-Ryul; Hong, Sung-Woon; Kim, Yuri; Jang, Se-Eun; Kim, Nam-Jae; Han, Myung Joo; Kim, Dong-Hyun

    2011-01-01

    To evaluate the difference in expressing pharmacological effects of ginseng by intestinal microflora between Koreans, metabolic activities of ginseng, ginsenoside Rb1 and Rg1 by 100 fecal specimens were measured. The β-glucosidase activity for p-nitrophenyl- β-D-glucopyranoside was 0 to 0.42 μmol/min/mg and its average activity (mean±SD) was 0.10±0.07 μmol/min/mg. The metabolic activities of ginsenosides Rb1 and Rg1 were 0.01 to 0.42 and 0.01 to 0.38 pmol/min/mg, respectively. Their average a...

  2. Human rights in the transition to a 'green economy' – Norway and a 'just transition' to a low-carbon society

    2013-01-01

    Climate change challenges human rights (HRs) "as the dominant language of justice." A HRs and climate change discourse has accepted this challenge but this discourse remains marginal – both in traditionally-technocratic international climate policy and debates around transitions to ‘green economies’ (the transition discourse). This reflects HRs’ marginal status vis-à-vis the environment, development and economics generally. Suggesting these are HRs issues is a reframing of traditional approac...

  3. [Intestinal endometriosis].

    González Rodríguez, C I; Cires, M; Jiménez, F J; Rubio, T

    2008-01-01

    Endometriosis is a chronic, benign gynaecological disorder that is frequent in women of a child-bearing age. It is estimated that there is some degree of endometriosis in as many as 15% of pre-menopausal women, associated with a history of infertility, caesarean antecedents, dysmenorrhoea and abnormality in uterine bleeding. It is believed to be due to the rise of menstrual contents through the Fallopian tubes (retrograde menstruation). In the intestinal affectation, the colon is the segment most frequently affected, above all at the rectosigmoidal level. The clinical features are unspecific, with abdominal pain the most frequent and/or pelvic pain of a cholic type that coincides with, or is exacerbated by, menstruation. Differential diagnosis includes intestinal inflammatory disease, diverticulitis, ischemic colitis and neoplastic processes, with the definitive diagnosis being anatomopathological. With respect to treatment, this will depend on the clinical features and the age of the patient, as well as her wishes with regard to pregnancy. PMID:18953367

  4. Intestinal steroidogenesis

    Bouguen, Guillaume; Dubuquoy, Laurent; Desreumaux, Pierre; Brunner, Thomas; Bertin, Benjamin

    2015-01-01

    Steroids are fundamental hormones that control a wide variety of physiological processes such as metabolism, immune functions, and sexual characteristics. Historically, steroid synthesis was considered a function restricted to the adrenals and the gonads. In the past 20 years, a significant number of studies have demonstrated that steroids could also be synthesized or metabolized by other organs. According to these studies, the intestine appears to be a major source of de novo produced glucoc...

  5. Fermentation by gut microbiota cultured in a simulator of the human intestinal microbial ecosystem is improved by probiotic Enterococcus faecium CRL 183

    Elizeu A. Rossi

    2011-10-01

    Full Text Available Background: Enterococci are used in a large number of dairy products, such as starter cultures in food supplements and in foods considered functional. In vitro gut fermentation models present an unmatched opportunity of performing studies frequently allenged in humans and animals owing to ethical concerns. A dynamic model of the human intestinal microbial ecosystem (SHIME was designed to better simulate conditions intestinal microbiota.Methods: The SHIME model was used to study the effect of Enterococuus faecium CRL 183 on the fermentation pattern of the colon microbiota. Initially, an inoculum prepared from human feces was introduced into the reactor vessels and stabilized over 2 wk using a culture medium. This stabilization period was followed by a 2-wk control period during which the microbiota were monitored. The microbiota were then subjected to a 4-wk treatment period by adding 108 CFU/mL of the Enterococcus faecium CRL 183 to vessel one (the stomach compartment.Results: The addition resulted into an overall increase of bacterial marker populations (Enterobacteriaceae, Lactobacillus spp., Bifidobacterium spp. and Clostridium spp., with a significant increase of the Lactobacillus sp. and Bifidobacterium sp populations. The short-chain fatty acid (SCFA concentration increased during the supplementation period; this was due mainly to a significant increase in the levels of acetic, butyric and propionic acids. Ammonium concentrations increased during the supplementation period.Conclusions: Results showed that the major effect of E. faecium CRL 183 was found in the ascendant and transverse colonFunctional Foods in Health and Disease 2011; 10:389-402

  6. Characterization of tight junction disruption and immune response modulation in a miniaturized Caco-2/U937 coculture-based in vitro model of the human intestinal barrier.

    Ramadan, Qasem; Jing, Lin

    2016-02-01

    A microfluidic-based dynamic in vitro model of the human intestinal barrier has been constructed and characterized. The intestinal epithelial monolayer was mimicked by culturing caco-2 cells on a porous membrane in a double-layered microfluidic chip and interfaced with a co-culture of U937 as a model of immune responsive cells. The physiological flow was also mimicked by a continuous perfusion of culture media from the apical and basolateral side of the porous membrane. This dynamic "in vivo-like" environment maintains a continuous supply of cell nutrient and waste removal and create mechanical shear stress within the physiological ranges which promotes uniform cell growth and tight junction formation. The monolayer permeability to soluble ion changes after treating with LPS, and TNF α as indicated by the reduction of the TEER value. In addition, the immune competent caco-2/U937-based model allowed the investigating the role of the epithelial layer as a protection barrier to biological hazards as indicated by the suppressing of the pro-inflammatory cytokine expression. PMID:26809386

  7. Arabinogalactan and fructo-oligosaccharides have a different fermentation profile in the Simulator of the Human Intestinal Microbial Ecosystem (SHIME ®).

    Terpend, Kathleen; Possemiers, Sam; Daguet, David; Marzorati, Massimo

    2013-08-01

    Current prebiotics, such as fructo-oligosaccharides (FOS), are limited in their persistence in the distal colon and are predominantly fermented in the proximal colon. In order to identify a potential alternative, the differences in the fermentation profile of arabinogalactan (AG) and FOS have been assessed in the Simulator of the Human Intestinal Microbial Ecosystem. The effect of each product on the composition and activity of the microbial community was analysed during a 3-week treatment period at a dose of 5 g day(-1). While FOS indeed was mainly fermented in the simulated proximal colon, AG was still available for fermentation in the simulated distal colon as shown by pH profiles, size exclusion chromatography and analyses of specific enzymatic activities. As a consequence, the main effect of the products (increase in propionate and butyrate and decrease in ammonium production) occurred in different intestinal areas. DGGE and qPCR analyses confirmed that the main modulation of the microbiota by the two products occurred in different areas of the gut. AG was associated with a statistically significant increase in the concentration of total bacteria, Bacteroidetes, Faecalibacterium prausnitzii, a delayed bifidogenic effect and a decrease of the pathogenic Clostridium perfringens. FOS led to a strong lactobacillogenic effect. PMID:23864575

  8. Inhibitiory properties of cytoplasmic extract of Lactobacilli isolated from common carp intestine on human chronic myelocytic leukemia K562 cell line: an in vitro study

    Kabiri F

    2011-03-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 st1":*{behavior:url(#ieooui } /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Lactobacillus species are genetically diverse groups of Lactic Acid Bacteria (LAB that have been introduced as probiotics, because of some characteristics such as their anti-tumor properties, helping the intestinal flora balance, production of antibiotics, stimulation of host immune response, etc. The aim of this study was to investigate the effects of cytoplasmic extraction and cell wall of Lactobacillus species isolated from the intestine of common carp on human chronic myelocytic leukemia or K562 cancer cell lines."n"nMethods: The intestinal contents of 115 common carp captured from the natural resources of West Azerbaijan province in Iran were examined for LAB. After isolation, the identification of Lactobacilli was done according to traditional and molecular bacteriological tests. Subsequently, a suspension of each bacterium was prepared and the protein content of the cytoplasm was extracted. Cell wall disintegration was done by cell lysis buffer and sonication. The effects of cytoplasmic extraction and cell wall on K562 cell line proliferation were investigated by MTT assays."n"nResults: The cytoplasmic extraction of the isolated Lactobacilli had significant (p<0.05 anti

  9. Associations between the human intestinal microbiota, Lactobacillus rhamnosus GG and serum lipids indicated by integrated analysis of high-throughput profiling data

    Leo Lahti; Anne Salonen; Kekkonen, Riina A.; Jarkko Salojärvi; Jonna Jalanka-Tuovinen; Airi Palva; Matej Orešič; Willem M. de Vos

    2013-01-01

    Accumulating evidence indicates that the intestinal microbiota regulates our physiology and metabolism. Bacteria marketed as probiotics confer health benefits that may arise from their ability to affect the microbiota. Here high-throughput screening of the intestinal microbiota was carried out and integrated with serum lipidomic profiling data to study the impact of probiotic intervention on the intestinal ecosystem, and to explore the associations between the intestinal bacteria and serum li...

  10. Calcium bioaccessibility and uptake by human intestinal like cells following in vitro digestion of casein phosphopeptide-calcium aggregates.

    Perego, Silvia; Del Favero, Elena; De Luca, Paola; Dal Piaz, Fabrizio; Fiorilli, Amelia; Cantu', Laura; Ferraretto, Anita

    2015-06-01

    Casein phosphopeptides (CPPs), derived by casein proteolysis, can bind calcium ions and keep them in solution. In vitro studies have demonstrated CPP-induced cell calcium uptake, depending on the formation of (CPP + calcium) complexes and on the degree of differentiation of the intestinal cells. With the present study, we address the persistence of the complexes and of the CPP-induced calcium uptake in intestinal like cells after the digestion process, thus examining their eligibility to serve as nutraceuticals. A calcium-preloaded CPP preparation of commercial origin (Ca-CPPs) was subjected to in vitro digestion. The evolution of the supramolecular structure of the Ca-CPP complexes was studied using laser-light and X-ray scattering. The bioactivity of the pre- and post-digestion Ca-CPPs was determined in differentiated Caco2 and HT-29 cells by video imaging experiments using Fura-2. We found that Ca-CPP aggregates keep a complex supramolecular organization upon digestion, despite getting smaller in size and increasing internal calcium dispersion. Concomitantly and most interestingly, digested Ca-CPPs clearly enhance the uptake of calcium ions, especially in Caco2 cells. In contrast, digestion depletes the ability of post-loaded decalcified-CPPs (Ca-dekCPPs), with a weaker internal structure, to induce calcium uptake. The enhanced bioactivity reached upon digestion strongly suggests a recognized role of Ca-CPPs, in the form used here, as nutraceuticals. PMID:25927875

  11. Intestinal acariasis in Anhui Province

    Chao-Pin Li; Jian Wang

    2000-01-01

    The mites found in stored food and house comprise a large group of subclass Acari, belonging to the suborder Acardida of the order Acarifornes. They can be found in dust and vacuum samples from floors, furniture, mattresses, Chinese herbal medicine, dry fruit, grain, flour, sugar, and bedding. These mites are nidicolous and feed on organic debris, including sloughed human skin, fungi, spilled food, pollen, etc. These mites are particularly prevalent in Chinese herbal medicine, dry fruit, grain, flour, sugar, beds, though carpeted floors near beds or couches may also have large numbers. The most common species are Acarus siro, Tyrophagus putrescentiae , Dermatophagoides farinae , D . pteronyssinus, Glycyphagus domesticus, G. Ornatus, Carpoglyphus lactis and Tarsonemus granarius, etc. The viability of mites in storage is quite strong and they can invade and parasitize the intestines of humans[1 -15]. They can cause pulmonary acariasis[16-25] , urinary acariasis[26-33] and so on. The dejecta of mites is a quite strong allergen and can cause different allergic diseases[34-44]. Intestinal acariasis can be caused by some mites related to the way of diet intake and invading against intestinal mucosa, intestinal muscle[45-5a]. The first report of intestinal acariasis caused by these mites was made by Hinman et al (1934)[45]. From then on, all kinds of studies on the disease have been reported gradually. In order to make an epidemiological survey of intestinal acariasis the investigation of the disease was taken in some areas of Anhui Province from 1989 to 1996.

  12. Noise-induced phase transition in the model of human virtual stick balancing

    Zgonnikov, Arkady

    2016-01-01

    Humans face the task of balancing dynamic systems near an unstable equilibrium repeatedly throughout their lives. Much research has been aimed at understanding the mechanisms of intermittent control in the context of human balance control. The present paper deals with one of the recent developments in the theory of human intermittent control, namely, the double-well model of noise-driven control activation. We demonstrate that the double-well model can reproduce the whole range of experimentally observed distributions under different conditions. Moreover, we show that a slight change in the noise intensity parameter leads to a sudden shift of the action point distribution shape, that is, a phase transition is observed.

  13. Body temperature-related structural transitions of monotremal and human hemoglobin.

    Digel, I; Maggakis-Kelemen, Ch; Zerlin, K F; Linder, Pt; Kasischke, N; Kayser, P; Porst, D; Temiz Artmann, A; Artmann, G M

    2006-10-15

    In this study, temperature-related structural changes were investigated in human, duck-billed platypus (Ornithorhynchus anatinus, body temperature T(b) = 31-33 degrees C), and echidna (Tachyglossus aculeatus, body temperature T(b) = 32-33 degrees C) hemoglobin using circular dichroism spectroscopy and dynamic light scattering. The average hydrodynamic radius (R(h)) and fractional (normalized) change in the ellipticity (F(obs)) at 222 +/- 2 nm of hemoglobin were measured. The temperature was varied stepwise from 25 degrees C to 45 degrees C. The existence of a structural transition of human hemoglobin at the critical temperature T(c) between 36-37 degrees C was previously shown by micropipette aspiration experiments, viscosimetry, and circular dichroism spectroscopy. Based on light-scattering measurements, this study proves the onset of molecular aggregation at T(c). In two different monotremal hemoglobins (echidna and platypus), the critical transition temperatures were found between 32-33 degrees C, which are close to the species' body temperature T(b). The data suggest that the correlation of the structural transition's critical temperature T(c) and the species' body temperature T(b) is not mere coincidence but, instead, is a more widespread structural phenomenon possibly including many other proteins. PMID:16844747

  14. Enhanced Wound Healing by Recombinant Escherichia coli Nissle 1917 via Human Epidermal Growth Factor Receptor in Human Intestinal Epithelial Cells: Therapeutic Implication Using Recombinant Probiotics

    Choi, Hye Jin; Ahn, Jung Hoon; Park, Seong-Hwan; Do, Kee Hun; Kim, Juil; Moon, Yuseok

    2012-01-01

    The gastrointestinal mucosa has a remarkable ability to repair damage with the support of epidermal growth factor (EGF), which stimulates epithelial migration and proliferative reepithelialization. For the treatment of mucosal injuries, it is important to develop efficient methods for the localized delivery of mucoactive biotherapeutics. The basic idea in the present study came from the assumption that an intestinal probiotic vehicle can carry and deliver key recombinant medicinal proteins to...

  15. Investigations on the method of in vitro accumulation measurements of 14C phenylalanine on human small intestine biopsies, illustrated by the example of Diabetes mellitus

    A method was developed, by which actively transported substrates can accumulationarily be measured out in vitro on biopsy material. The applicability of this method as index for an active transport performance could then be examined on the example of a control group with sound small intestine and on patients with diabetes mellitus. In order to complete this parameter of the transport function, the specific saccharase activity in the overall homogenate of the mucous membrane was determined. The basis of this determination were the previous investigations on the experimental diabetes mellitus, in which morphologic and functional alterations had been detected. The various influences are discussed, which may be important for the detected alterations. However, a comparison with the results obtained in animal experiments is possible only to a very limited extent, since the situation in human diabetes mellitus is very complicated. (orig./MG)

  16. Returns to human capital under the communist wage grid and during the transition to a market economy

    Münich, Daniel; Švejnar, Jan; Terrell, K.

    Praha : CERGE-EI, 2011 - (Dušek, L.; Lízal, L.), s. 127-174 ISBN 978-80-7344-238-5 Institutional research plan: CEZ:AV0Z70850503 Keywords : human capital * wages * transition Subject RIV: AH - Economics http://www.cerge-ei.cz/pdf/books/cerge-ei-tackles-transition.pdf

  17. Intestinal Helminths Recovered from Humans in Xieng Khouang Province, Lao PDR with a Particular Note on Haplorchis pumilio Infection.

    Chai, Jong-Yil; Sohn, Woon-Mok; Jung, Bong-Kwang; Yong, Tai-Soon; Eom, Keeseon S; Min, Duk-Young; Insisiengmay, Bounnaloth; Insisiengmay, Sithat; Phommasack, Bounlay; Rim, Han-Jong

    2015-08-01

    A survey of intestinal helminths was undertaken in riparian people in Xieng Khouang Province, Lao PDR. Fecal specimens were collected from 643 people (289 males and 354 females) residing in 4 districts (Nonghet, Kham, Phoukout, and Pek) and were examined by the Kato-Katz technique. The overall helminth egg positive rate was 41.2%, and hookworms revealed the highest prevalence (32.7%) followed by Trichuris trichiura (7.3%) and Ascaris lumbricoides (5.6%). The positive rate for small trematode eggs (STE), which may include Opisthorchis viverrini, heterophyids, and lecithodendriids, was 4.4%. For recovery of adult helminths, 12 STE or nematode/cestode egg-positive people were treated with 40 mg/kg praziquantel and 15 mg/kg pyrantel pamoate, and then purged. Mixed infections with 2 Haplorchis species (H. pumilio and H. taichui), Centrocestus formosanus, Opisthorchis viverrini, a species of cestode (Taenia saginata), and several species of nematodes including hookworms and Enterobius vermicularis were detected. The worm load for trematodes was the highest for H. pumilio with an average of 283.5 specimens per infected person followed by C. formosanus, H. taichui, and O. viverrini. The worm load for nematodes was the highest for hookworms (21.5/infected case) followed by E. vermicularis (3.2/infected case). The results revealed that the surveyed areas of Xieng Khouang Province, Lao PDR are endemic areas of various species of intestinal helminths. The STE found in the surveyed population were verified to be those of heterophyids, particularly H. pumilio. PMID:26323842

  18. Large intestine (colon) (image)

    The large intestine is the portion of the digestive system most responsible for absorption of water from the indigestible ... the ileum (small intestine) passes material into the large intestine at the cecum. Material passes through the ...

  19. Graded effects of unregulated smooth muscle myosin on intestinal architecture, intestinal motility and vascular function in zebrafish.

    Abrams, Joshua; Einhorn, Zev; Seiler, Christoph; Zong, Alan B; Sweeney, H Lee; Pack, Michael

    2016-05-01

    Smooth muscle contraction is controlled by the regulated activity of the myosin heavy chain ATPase (Myh11). Myh11 mutations have diverse effects in the cardiovascular, digestive and genitourinary systems in humans and animal models. We previously reported a recessive missense mutation, meltdown (mlt), which converts a highly conserved tryptophan to arginine (W512R) in the rigid relay loop of zebrafish Myh11. The mlt mutation disrupts myosin regulation and non-autonomously induces invasive expansion of the intestinal epithelium. Here, we report two newly identified missense mutations in the switch-1 (S237Y) and coil-coiled (L1287M) domains of Myh11 that fail to complement mlt Cell invasion was not detected in either homozygous mutant but could be induced by oxidative stress and activation of oncogenic signaling pathways. The smooth muscle defect imparted by the mlt and S237Y mutations also delayed intestinal transit, and altered vascular function, as measured by blood flow in the dorsal aorta. The cell-invasion phenotype induced by the three myh11 mutants correlated with the degree of myosin deregulation. These findings suggest that the vertebrate intestinal epithelium is tuned to the physical state of the surrounding stroma, which, in turn, governs its response to physiologic and pathologic stimuli. Genetic variants that alter the regulation of smooth muscle myosin might be risk factors for diseases affecting the intestine, vasculature, and other tissues that contain smooth muscle or contractile cells that express smooth muscle proteins, particularly in the setting of redox stress. PMID:26893369

  20. A human breast cell model of pre-invasive to invasive transition

    Bissell, Mina J; Rizki, Aylin; Weaver, Valerie M.; Lee, Sun-Young; Rozenberg, Gabriela I.; Chin, Koei; Myers, Connie A.; Bascom, Jamie L.; Mott, Joni D.; Semeiks, Jeremy R.; Grate, Leslie R.; Mian, I. Saira; Borowsky, Alexander D.; Jensen, Roy A.; Idowu, Michael O.; Chen, Fanqing; Chen, David J.; Petersen, Ole W.; Gray, Joe W.; Bissell, Mina J.

    2008-03-10

    A crucial step in human breast cancer progression is the acquisition of invasiveness. There is a distinct lack of human cell culture models to study the transition from pre-invasive to invasive phenotype as it may occur 'spontaneously' in vivo. To delineate molecular alterations important for this transition, we isolated human breast epithelial cell lines that showed partial loss of tissue polarity in three-dimensional reconstituted-basement membrane cultures. These cells remained non-invasive; however, unlike their non-malignant counterparts, they exhibited a high propensity to acquire invasiveness through basement membrane in culture. The genomic aberrations and gene expression profiles of the cells in this model showed a high degree of similarity to primary breast tumor profiles. The xenograft tumors formed by the cell lines in three different microenvironments in nude mice displayed metaplastic phenotypes, including squamous and basal characteristics, with invasive cells exhibiting features of higher grade tumors. To find functionally significant changes in transition from pre-invasive to invasive phenotype, we performed attribute profile clustering analysis on the list of genes differentially expressed between pre-invasive and invasive cells. We found integral membrane proteins, transcription factors, kinases, transport molecules, and chemokines to be highly represented. In addition, expression of matrix metalloproteinases MMP-9,-13,-15,-17 was up regulated in the invasive cells. Using siRNA based approaches, we found these MMPs to be required for the invasive phenotype. This model provides a new tool for dissection of mechanisms by which pre-invasive breast cells could acquire invasiveness in a metaplastic context.

  1. Fasting inhibits human cancer progression via the epithelial-mesenchymal transition process: Important evidence unraveled

    Ala-Eddin Al Moustafa

    2012-01-01

    Metastatic cancer disease is responsible for the majority of cancer-related deaths in human cancer patients. In parallel, recently it was pointed-out that fasting could play an important role during cancer treatment and progression via the deregulation of insulin-like growth factor-1 (IGF-1) as well as others growth factors and genes. Meanwhile, it is established that the epithelial-mesenchymal transition (EMT) is a major process for the progression of cancer cells from non-invasive to invasi...

  2. Perfluorinated compounds: Levels, trophic web enrichments and human dietary intakes in transitional water ecosystems

    Highlights: • PFOA/S levels in a trophic web of a heavily human-stressed lagoon are measured. • High levels were found in mussels, clams and crabs. • The principal PFCs inflow sources for the ecosystem is the river. • Biota (i.e. macroalgae proliferation) contributes to redistribute pollutants in the lagoon. • Human daily dietary intakes are below maximum tolerable levels suggested by the EFSA. -- Abstract: The results of a study on levels of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), analyzed in terms of HPLC-ESI-MS in water, sediment, macrophyte, bivalve, crustacean and fish samples, are reported here. The aim of the research is to define, for the first time, PFOA/S levels in a heavily human-stressed transitional water ecosystem (Orbetello lagoon, Italy) and evaluate trophic web enrichments and human dietary intakes. The results obtained show that: (i) levels significantly higher than those reported in the literature were found in mussels, clams and crabs; (ii) the river is a significant pollution source; (iii) although absolute levels are relatively low, macroalgae proliferation contributes to redistribute pollutants from river-affected areas throughout the entire lagoon basin; (iv) to the best of our current knowledge, water-filtering species considered in this study are the most exposed to PFOA/S pollution; (v) human daily dietary intakes of PFOA/S through Slow Food-endorsed product consumption are below maximum tolerable levels suggested by the EFSA

  3. The genomics of probiotic intestinal microorganisms

    Salminen, Seppo; Nurmi, Jussi; Gueimonde, Miguel

    2005-01-01

    An intestinal population of beneficial commensal microorganisms helps maintain human health, and some of these bacteria have been found to significantly reduce the risk of gut-associated disease and to alleviate disease symptoms. The genomic characterization of probiotic bacteria and other commensal intestinal bacteria that is now under way will help to deepen our understanding of their beneficial effects.

  4. Bovine colostrum improves intestinal function following formula-induced gut inflammation in preterm pigs

    Støy, Ann Cathrine Findal; Heegaard, Peter M. H.; Thymann, Thomas;

    2014-01-01

    exposure to formula feeding after some days of total parenteral nutrition (TPN). Methods After receiving TPN for 2 days, preterm pigs were fed formula (FORM, n = 14), bovine colostrum (COLOS, n = 6), or formula (6 h) followed by bovine colostrum (FCOLOS, n = 14). Intestinal lesions, function, and structure...... preterm pigs. Further studies are required to test if bovine colostrum may also benefit preterm infants during the challenging transition from total parenteral nutrition to enteral nutrition, when human milk is unavailable....

  5. Evaluation of Intestinal Protozoan Morphology in Human Fecal Specimens Preserved in EcoFix: Comparison of Wheatley’s Trichrome Stain and EcoStain

    Garcia, Lynne S.; Shimizu, Robyn Y.

    1998-01-01

    As a result of disposal problems related to the use of mercury compounds, many laboratories have switched from mercuric chloride-based Schaudinn’s and polyvinyl alcohol (PVA) stool preservatives to other, non-mercury-based preservatives. A comparison of organism recoveries and morphologies of the intestinal protozoa was undertaken with PVA containing the EcoFix zinc-based Schaudinn’s preservative (Meridian Diagnostics, Inc.); both Wheatley’s modification of Gomori’s trichrome stain (WT) and EcoStain (ES) were used to stain 51 human fecal specimens. Morphology, clarity of nuclear and cytoplasmic detail, overall color differences, and the ease or difficulty in detecting intestinal protozoa in fecal debris were assessed for the two permanent stained smears. Overall, organism morphology of the intestinal protozoa stained with WT and that of protozoa stained with ES were not equal in nuclear and cytoplasmic detail or range of color. However, the same organisms were identified in stained fecal smears with either WT or ES, with the exception of situations in which organism numbers were characterized as rare. Included were 67 protozoan challenges (number of organisms): Entamoeba histolytica-Entamoeba dispar (5), Entamoeba coli (9), Entamoeba hartmanni (6), Endolimax nana (12), Iodamoeba bütschlii (8), Blastocystis hominis (19), Giardia lamblia (6), Dientamoeba fragilis (2), yeast (2), and leukocytes (2). Five specimens were negative for parasites but contained fecal debris that was compared for morphologic detail and color range. The ES produces a more gray-green monotone with very little pink or red tone; contrast among the various colors is less than that seen with WT. Stain intensity for all organisms was acceptable, and there were no problems with stain deposition. The quality of the protozoan morphology with ES was often comparable to that with WT (36 of 67 [53.7%]) and, in some cases, better (24 of 67 [35.8%]). Organisms on the WT-stained smear exhibited

  6. Evaluation of intestinal protozoan morphology in human fecal specimens preserved in EcoFix: comparison of Wheatley's trichrome stain and EcoStain.

    Garcia, L S; Shimizu, R Y

    1998-07-01

    As a result of disposal problems related to the use of mercury compounds, many laboratories have switched from mercuric chloride-based Schaudinn's and polyvinyl alcohol (PVA) stool preservatives to other, non-mercury-based preservatives. A comparison of organism recoveries and morphologies of the intestinal protozoa was undertaken with PVA containing the EcoFix zinc-based Schaudinn's preservative (Meridian Diagnostics, Inc.); both Wheatley's modification of Gomori's trichrome stain (WT) and EcoStain (ES) were used to stain 51 human fecal specimens. Morphology, clarity of nuclear and cytoplasmic detail, overall color differences, and the ease or difficulty in detecting intestinal protozoa in fecal debris were assessed for the two permanent stained smears. Overall, organism morphology of the intestinal protozoa stained with WT and that of protozoa stained with ES were not equal in nuclear and cytoplasmic detail or range of color. However, the same organisms were identified in stained fecal smears with either WT or ES, with the exception of situations in which organism numbers were characterized as rare. Included were 67 protozoan challenges (number of organisms): Entamoeba histolytica-Entamoeba dispar (5), Entamoeba coli (9), Entamoeba hartmanni (6), Endolimax nana (12), Iodamoeba bütschlii (8), Blastocystis hominis (19), Giardia lamblia (6), Dientamoeba fragilis (2), yeast (2), and leukocytes (2). Five specimens were negative for parasites but contained fecal debris that was compared for morphologic detail and color range. The ES produces a more gray-green monotone with very little pink or red tone; contrast among the various colors is less than that seen with WT. Stain intensity for all organisms was acceptable, and there were no problems with stain deposition. The quality of the protozoan morphology with ES was often comparable to that with WT (36 of 67 [53.7%]) and, in some cases, better (24 of 67 [35.8%]). Organisms on the WT-stained smear exhibited better

  7. 吉林市人体肠道寄生虫感染调查%Investigation of human intestine parasitization in Jilin City

    王典瑞; 梁兆祥; 侯毅鞠; 许国战; 赵大力; 陈芬

    2000-01-01

    Objective:To investigate the human intestine parasitization in Jilin City.Methods: Mass survey of feces and epidemiological survey were carried out in 1389 persons.Results:Nine kinds of intestinal parasites had been detected and the total infection rate was71.13%. From high to low, the infection rates were respectively(64.07%)for ascaris lumbri-coides(2.23%) for clonorchis sinensis, (1.94%) for giardia lamblia(1.51%) for entamoe-ba coli (0.74%) for trichuris trichiura(0.28%) for iodamoeba bvetschlii (0.14%) fortrichomonas hominis(0.07%) for entamoeba histolytica and ancylostoma duodenale. Conclusion :The intestinal parasitization rate is higher in Jilin City, and this result suggests that we setup a series of prophylectico-therapeutic measures.%目的:调查吉林市肠道寄生虫感染情况。方法:对1389人进行粪便普查和流行病学调查。结果:共检出肠道寄生虫9种,总感染率为71.13%,感染率从高到低依次为蛔虫(64.07%)、肝吸虫(2.23%)、贾第鞭毛虫(1.94%)、结肠阿米巴(1.51%)、鞭虫(0.79%)、嗜碘阿米巴(0.28%)、肠人毛滴虫(0.14%)、痢疾阿米巴及钩虫(均为0.07%)。结论:吉林市人体肠道寄生虫感染率较高,应注意建立一套完整的防治措施。

  8. Numerical simulation of transitional flow in a human upper airway segment in the presence of uncertainty

    Marxen, Olaf

    2011-11-01

    The flow in human airways may be laminar, transitional, or turbulent in different airway segments. Specifically, laminar-turbulent transition is believed to occur in the larynx or in the trachea. Present approaches to simulate such flows typically employ numerical methods solving the steady Reynolds-averaged Navier-Stokes equations. However, natural airway deformations or pathological obstructions such as tumors may generate recirculation zones and lead to highly unsteady flow features that are not well captured by these numerical methods. We perform direct numerical simulations of transitional flow through a pipe-like canonical geometry representative of an airway segment. The incompressible Navier-Stokes equations in conjunction with an immersed boundary method are solved to simulate the unsteady flow. In order to model perturbations present in the incoming flow, small-amplitude disturbances are forced to explicitly trigger flow instabilities. Time-dependent inflow profiles are applied to model the change in flow velocity during the breathing process. In order to account for natural variability during breathing, the inflow profile is treated as an uncertain function. Resulting uncertainty in the flow field is quantified using stochastic collocation.

  9. Epidermal Growth Factor and Intestinal Barrier Function

    Liu, Hu; Yang, Shufen; Li, Zuohua; Zhong, Jinfeng

    2016-01-01

    Epidermal growth factor (EGF) is a 53-amino acid peptide that plays an important role in regulating cell growth, survival, migration, apoptosis, proliferation, and differentiation. In addition, EGF has been established to be an effective intestinal regulator helping to protect intestinal barrier integrity, which was essential for the absorption of nutrients and health in humans and animals. Several researches have demonstrated that EGF via binding to the EGF receptor and subsequent activation of Ras/MAPK, PI3K/AKT, PLC-γ/PKC, and STATS signal pathways regulates intestinal barrier function. In this review, the relationship between epidermal growth factor and intestinal development and intestinal barrier is described, to provide a better understanding of the effects of EGF on intestine development and health. PMID:27524860

  10. Human tetraspanin transmembrane 4 superfamily member 4 or intestinal and liver tetraspan membrane protein is overexpressed in hepatocellular carcinoma and accelerates tumor cell growth

    Ying Li; Leiming Wang; Jie Qiu; Liang Da; Pierre Tiollais; Zaiping Li; Mujun Zhao

    2012-01-01

    The human transmembrane 4 superfamily member 4 or intestinal and liver tetraspan membrane protein (TM4SF4/il-TMP) was originally cloned as an intestinal and liver tetraspan membrane protein and mediates density-dependent cell proliferation.The rat homolog of TM4SF4 was found to be up-regulated in regenerating liver after two-thirds hepatectomy and overexpression of TM4SF4 could enhance liver injury induced by CCl4.However,the expression and significance of TM4SF4/il-TMP in liver cancer remain unknown.Here,we report that TM4SF4/il-TMP is frequently and significantly overexpressed in hepatocellular carcinoma (HCC).Real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) and western blot analysis showed that TM4SF4/il-TMP mRNA and protein levels were upregulated in ~80% of HCC tissues,Immunohistochemical analysis of a 75 paired HCC tissue microarray revealed that TM4SF4/il-TMP was significantly overexpressed in HCC tissues (P < 0.001),and high immunointensity of TM4SF4/iI-TMP tended to be in well-to-moderately differentiated HCC compared with poorly differentiated tumors.Functional studies showed that overexpression of TM4SF4/il-TMP in QGY-7701 and BEL-7404 HCC cell lines through stable transfection of TM4SF4 expression plasmid significantly promoted both cell growth and colony formation of HCC cells.Reduction of TM4SF4/il-TMP expression in QGY-7701 and BEL-7404 cells by stably transfecting TM4SF4 antisense plasmid caused great inhibition of cell proliferation.Our findings suggest that TM4SF4/il-TMP has the potential to be biomarker in HCC and plays a crucial role in promotion of cancer cell proliferation.

  11. Gait Transitions in Human Infants: Coping with Extremes of Treadmill Speed.

    Vasudevan, Erin V; Patrick, Susan K; Yang, Jaynie F

    2016-01-01

    Spinal pattern generators in quadrupedal animals can coordinate different forms of locomotion, like trotting or galloping, by altering coordination between the limbs (interlimb coordination). In the human system, infants have been used to study the subcortical control of gait, since the cerebral cortex and corticospinal tract are immature early in life. Like other animals, human infants can modify interlimb coordination to jump or step. Do human infants possess functional neuronal circuitry necessary to modify coordination within a limb (intralimb coordination) in order to generate distinct forms of alternating bipedal gait, such as walking and running? We monitored twenty-eight infants (7-12 months) stepping on a treadmill at speeds ranging between 0.06-2.36 m/s, and seventeen adults (22-47 years) walking or running at speeds spanning the walk-to-run transition. Six of the adults were tested with body weight support to mimic the conditions of infant stepping. We found that infants could accommodate a wide range of speeds by altering stride length and frequency, similar to adults. Moreover, as the treadmill speed increased, we observed periods of flight during which neither foot was in ground contact in infants and in adults. However, while adults modified other aspects of intralimb coordination and the mechanics of progression to transition to a running gait, infants did not make comparable changes. The lack of evidence for distinct walking and running patterns in infants suggests that the expression of different functional, alternating gait patterns in humans may require neuromuscular maturation and a period of learning post-independent walking. PMID:26828941

  12. Hepatic and intestinal glucuronidation of mono(2-ethylhexyl) phthalate, an active metabolite of di(2-ethylhexyl) phthalate, in humans, dogs, rats, and mice: an in vitro analysis using microsomal fractions.

    Hanioka, Nobumitsu; Isobe, Takashi; Kinashi, Yu; Tanaka-Kagawa, Toshiko; Jinno, Hideto

    2016-07-01

    Mono(2-ethylhexyl) phthalate (MEHP) is an active metabolite of di(2-ethylhexyl) phthalate (DEHP) and has endocrine-disrupting effects. MEHP is metabolized into glucuronide by UDP-glucuronosyltransferase (UGT) enzymes in mammals. In the present study, the hepatic and intestinal glucuronidation of MEHP in humans, dogs, rats, and mice was examined in an in vitro system using microsomal fractions. The kinetics of MEHP glucuronidation by liver microsomes followed the Michaelis-Menten model for humans and dogs, and the biphasic model for rats and mice. The K m and V max values of human liver microsomes were 110 µM and 5.8 nmol/min/mg protein, respectively. The kinetics of intestinal microsomes followed the biphasic model for humans, dogs, and mice, and the Michaelis-Menten model for rats. The K m and V max values of human intestinal microsomes were 5.6 µM and 0.40 nmol/min/mg protein, respectively, for the high-affinity phase, and 430 µM and 0.70 nmol/min/mg protein, respectively, for the low-affinity phase. The relative levels of V max estimated by Eadie-Hofstee plots were dogs (2.0) > mice (1.4) > rats (1.0) ≈ humans (1.0) for liver microsomes, and mice (8.5) > dogs (4.1) > rats (3.1) > humans (1.0) for intestinal microsomes. The percentages of the V max values of intestinal microsomes to liver microsomes were mice (120 %) > rats (57 %) > dogs (39 %) > humans (19 %). These results suggest that the metabolic abilities of UGT enzymes expressed in the liver and intestine toward MEHP markedly differed among species, and imply that these species differences are strongly associated with the toxicity of DEHP. PMID:26514348

  13. Selection of bacteria originating from a human intestinal microbiota in the gut of previously germ-free rats

    Licht, Tine Rask; Madsen, Bodil; Wilcks, Andrea

    2007-01-01

    Denaturing gradient gel electrophoresis (DGGE) was applied to separate PCR-amplified 16S rRNA genes originating from human microbiota associated (HMA) rat faeces as well as from the human faecal sample used for inoculation of the animals. Subsequently, a total of 15 dominant bands were excised fr...

  14. Nuclear Thermal Propulsion (NTP): A Proven, Growth Technology for Fast Transit Human Missions to Mars

    Borowski, Stanley K.; McCurdy, David R.; Packard, Thomas W.

    2014-01-01

    The "fast conjunction" long surface stay mission option was selected for NASA's recent Mars Design Reference Architecture (DRA) 5.0 study because it provided adequate time at Mars (approx. 540 days) for the crew to explore the planet's geological diversity while also reducing the "1-way" transit times to and from Mars to approx. 6 months. Short transit times are desirable in order to reduce the debilitating physiological effects on the human body that can result from prolonged exposure to the zero-gravity (0-gE) and radiation environments of space. Recent measurements from the RAD detector attached to the Curiosity rover indicate that astronauts would receive a radiation dose of approx. 0.66 Sv (approx. 66 rem)-the limiting value established by NASA-during their 1-year journey in deep space. Proven nuclear thermal rocket (NTR) technology, with its high thrust and high specific impulse (Isp approx. 900 s), can cut 1-way transit times by as much as 50 percent by increasing the propellant capacity of the Mars transfer vehicle (MTV). No large technology scale-ups in engine size are required for these short transit missions either since the smallest engine tested during the Rover program-the 25 klbf "Pewee" engine is sufficient when used in a clustered arrangement of three to four engines. The "Copernicus" crewed MTV developed for DRA 5.0 is a 0-gE design consisting of three basic components: (1) the NTP stage (NTPS); (2) the crewed payload element; and (3) an integrated "saddle truss" and LH2 propellant drop tank assembly that connects the two elements. With a propellant capacity of approx. 190 t, Copernicus can support 1-way transit times ranging from approx. 150 to 220 days over the 15-year synodic cycle. The paper examines the impact on vehicle design of decreasing transit times for the 2033 mission opportunity. With a fourth "upgraded" SLS/HLV launch, an "in-line" LH2 tank element can be added to Copernicus allowing 1-way transit times of 130 days. To achieve 100

  15. Research progress in mechanism of intestinal microorganisms in human diseases%肠道菌群与人体疾病发病机制的研究进展

    林璋; 祖先鹏; 谢海胜; 金慧子; 杨鸟; 刘心如; 张卫东

    2016-01-01

    2007年国际联合研究项目人类微生物组计划(The Human Microbiome Project,HMP)和人类肠道元基因(或宏基因)组学计划(Metagenomics of The Human Intestinal Tract,MetaHIT)正式启动,标志着肠道宏基因组研究的时代已经到来.人是由90%的共生微生物组成的超级生物体,微生物尤其是肠道微生物参与了人体的营养吸收和代谢,通过这种相互作用方式影响着人体的健康和疾病的发展.本文从多种途径综述肠道菌群对疾病发病机制的研究进展,旨在为寻找人类的健康和疾病的治疗靶点提供一些新的思路.

  16. Expression of recombinant human α-lactalbumin in milk of transgenic cloned pigs is sufficient to enhance intestinal growth and weight gain of suckling piglets.

    Ma, Jin; Li, Qiuyan; Li, Yan; Wen, Xiao; Li, Zhiyuan; Zhang, Zaihu; Zhang, Jiuming; Yu, Zhengquan; Li, Ning

    2016-06-10

    Human α-lactalbumin (HLA) has very high nutritional value and important physiological functions during the neonatal period. The peptides derived from HLA provide diverse health benefits including antimicrobial, antiviral, immune-modulating, and antihypertensive effects. Thus, it is worth investigating the effects on offspring development of increasing HLA in milk. In this study, we found that recombinant human α-lactalbumin (rHLA) exhibits efficient inhibition of dipeptidyl peptidase-IV (DPP-IV) activity in an in vitro simulated gastrointestinal digestion system. Using a BAC clone containing the complete HLA gene as a candidate vector, we generated two lines of transgenic cloned sows via somatic cell nuclear transfer that over-expressed rHLA. The average concentrations of rHLA in milk from the two lines of transgenic cloned sows were 2.24±0.71mg/ml and 2.67±1.29mg/ml. The feeding experiments revealed that rHLA represses dipeptidyl peptidase-IV (DPP-IV) activity in vivo. Furthermore, the piglets reared by rHLA transgenic cloned sows exhibit better performance in gain of body weight and intestine growth than the control piglets reared by non-transgenic sows. Therefore, these findings indicate that rHLA could serve as a natural precursor for a DPP-IV inhibitor, and the transgenic technology that produced the over-expression of rHLA could be a useful method for pig breeders to improve lactation performance. PMID:26899869

  17. Evaluation of intestinal absorption enhancement and local mucosal toxicity of two promoters. I. Studies in isolated rat and human colonic mucosae.

    Maher, Sam; Kennelly, Rory; Bzik, Victoria A; Baird, Alan W; Wang, Xuexuan; Winter, Desmond; Brayden, David J

    2009-11-01

    The effects of two absorption promoters, (sodium caprate (C(10)) and melittin), on intestinal permeability and viability were measured in intact rat and human colonic epithelia mounted in Ussing chambers. Apical-side addition of C(10) (10 mM) and melittin (10-50 microM) rapidly reduced the transepithelial electrical resistance (TEER) and increased the apparent permeability coefficient (Papp) of [(14)C]-mannitol and FITC-dextran-4 kDa (FD4) across colonic mucosae from both species. Effects of C(10) on flux were greater than those of melittin at the concentrations selected. C(10) irreversibly decreased TEER, but the effects of melittin were partially reversible. Enhanced permeability of polar sugars (0.18-70 kDa) in colonic mucosae with C(10) was accompanied by significant release of lactate dehydrogenase (LDH) from the luminal surface as well as by inhibition of electrogenic chloride secretion induced by the muscarinic agonist, carbachol (0.1-10 microM). Although melittin did not alter electrogenic chloride secretion in rat or human colonic mucosae, it caused leakage of LDH from rat tissue. Gross histology and electron microscopy of rat and human colonic mucosae demonstrated that each permeation enhancer can induce colonic epithelial damage at concentrations required to increase marker fluxes. C(10) led to more significant mucosal damage than melittin, characterised by sloughing and mucosal erosion. Overall, these results indicate that while C(10) and melittin increase transport of paracellular flux markers across isolated human and rat colonic mucosae in vitro, these effects are associated with some cytotoxicity. PMID:19737613

  18. Expressions of sonic hedgehog, patched, smoothened and Gli-1 in human intestinal stromal tumors and their correlation with prognosis

    Yoshizaki, Ayumi; Nakayama, Toshiyuki; Naito, Shinji; Wen, Chun-Yang; Sekine, Ichiro

    2006-01-01

    AIM: To investigate the role that the hedgehog (Hh) signaling pathway, which includes sonic hedgehog (Shh), Patched (Ptc), Smoothened (Smo) and Gli-1, plays in human gastrointestinal stromal tumors (GISTs).

  19. Pulmonary clearance of vasoactive intestinal peptide.

    Barrowcliffe, M P; Morice, A; Jones, J G; Sever, P S

    1986-01-01

    Vasoactive intestinal peptide causes bronchodilatation when given intravenously but is less effective in both animals and man when given by inhalation. This difference may be due to poor transit of the peptide across the bronchial epithelium. To test this hypothesis pulmonary clearance of radiolabelled vasoactive intestinal peptide was measured in Sprague Dawley rats and compared with that of pertechnetate (TcO4-) and diethylene triamine pentaacetate (DTPA). Despite a molecular weight (MW) of...

  20. Up-regulation of early growth response gene 1 (EGR-1) via ERK1/2 signals attenuates sulindac sulfide-mediated cytotoxicity in the human intestinal epithelial cells

    Non-steroidal anti-inflammatory drugs (NSAIDs) are used to relieve pain and inflammation and have also received considerable attention because of their preventive effects against human cancer. However, the drug application is sometimes limited by the severe gastrointestinal ulcers and mucosal complications. In the present study, NSAID sulindac sulfide was investigated for the cytotoxic injury in the intestinal epithelial cells in association with an immediate inducible factor, early growth response gene 1 (EGR-1). Previously we reported that sulindac sulfide can suppress tumor cell invasion by inducing EGR-1. Extending the previous study, EGR-1 induction by sulindac sulfide was observed both in the non-transformed and transformed human intestinal epithelial cell lines. In terms of signaling pathway, ERK1/2 MAP kinases and its substrate Elk-1 transcription factor were involved in the sulindac sulfide-induced EGR-1 gene expression. Moreover, sulindac sulfide stimulated the nuclear translocation of the transcription factor EGR-1, which was also mediated by ERK1/2 signaling pathway. The roles of EGR-1 signals in the apoptotic cell death were assessed in the intestinal epithelial cells. Suppression of EGR-1 expression retarded cellular growth and colony forming activity in the intestinal epithelial cells. Moreover, induced EGR-1 ameliorated sulindac sulfide-mediated apoptotic cell death and enhanced the cellular survival. Taken all together, sulindac sulfide activated ERK1/2 MAP kinases which then mediated EGR-1 induction and nuclear translocation, all of which played important roles in the cellular survival from NSAID-mediated cytotoxicity in the human intestinal epithelial cells, implicating the protective roles of EGR-1 in the NSAID-mediated mucosal injuries