WorldWideScience

Sample records for human intestinal transit

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

    International Nuclear Information System (INIS)

    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 colo 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. Human anaerobic intestinal "rope" parasites

    OpenAIRE

    Volinsky, Alex A.; Gubarev, Nikolai V.; Orlovskaya, Galina M.; Marchenko, Elena V.

    2013-01-01

    Human intestinal helminths are described in this paper. They can be over a meter long, with an irregular cylindrical shape, resembling a rope. These anaerobic intestinal "rope" parasites differ significantly from other well-known intestinal parasites. Rope parasites can leave human body with enemas, and are often mistaken for intestinal lining, feces, or decayed remains of other parasites. Rope parasites can attach to intestinal walls with suction bubbles, which later develo...

  3. Model experiments mimicking the human intestinal transit and metabolism of D-galacturonic acid and amidated pectin.

    Science.gov (United States)

    Knaup, Bastian; Kempf, Michael; Fuchs, Jan; Valotis, Anagnostis; Kahle, Kathrin; Oehme, Anett; Richling, Elke; Schreier, Peter

    2008-07-01

    In order to study the human intestinal transit and metabolism of D-galacturonic acid and amidated pectin a number of model experiments were carried out. Both substrates were incubated under aerobic conditions at 37 degrees C using saliva (2 min) and simulated gastric juice (4 h). Under anaerobic conditions the substrates were incubated at 37 degrees C using human ileostomy and colostomy fluids, each obtained from three different donors, for 10 and for 24 h, respectively. D-Galacturonic acid, SCFA (acetic acid, propionic acid, and butyric acid), as well as methanol were analyzed photometrically after carbazole reaction, GC-flame ionization detection (GC-FID), and headspace solid-phase microextraction GC/MS (HS-SPME-GC/MS), respectively. D-Galacturonic acid and amidated pectin were found to be stable during incubations with saliva and simulated gastric juice, whereas both substrates underwent degradation in the course of human ileostomy and colostomy fluid incubations. D-Galacturonic acid was practically completely decomposed within 10 h and SCFA, with acetic acid as the major representative, were formed up to 98% of the incubated substrate in colostomy effluent. The amidated pectin was only degraded in part, revealing stable amounts of 22-35% and 3-17% in ileostomy (after 10 h) and colostomy fluid (after 24 h), respectively. SCFA were generated up to 59% of the applied amidated pectin. In parallel, 19-60% and 52-67% of the available methyl ester groups were cleaved in the course of incubations with ileostomy and colostomy fluids, respectively. The results demonstrate for the first time that D-galacturonic acid and amidated pectin are stable in human saliva and simulated gastric juice. The degradation of both compounds during incubation with ileostomy effluent is highlighted, providing evidence for a considerable metabolic potential of the small intestine. PMID:18618479

  4. Effects of methotrexate on intestinal transit in rats

    International Nuclear Information System (INIS)

    A study was designed to determine the effects of methotrexate (MTX) on rat intestinal transit. Adult male rats were implanted with indwelling cannulas in the proximal duodenum 5 to 7 days prior to experimentation. After recovery from surgery, groups of animals were treated with either saline (1.0 ml/kg/day) or MTX at 0.5, 1.25, 3.125, or 7.8 mg/kg/day (ip) for 3 consecutive days (Days 1-3). On each of the next 5 consecutive days (Days 4-8) weight and intestinal transit determinations were made in animals from each test group following a 24-hr fast. Intestinal transit was determined by measuring the progression of an intraduodenally administered bolus of radioactive chromium (Na251CrO4, 0.5 mu Ci) through the small intestine. When compared with saline-treated controls, intestinal transit was significantly (p less than 0.05) increased on 1 or more of the 5 test days in animals treated with doses of MTX greater than 0.5 mg/kg/day. When compared with animals treated with saline, animals treated with MTX lost a greater percentage of their initial body weight after the fast period. Plasma concentrations of MTX, determined at various time intervals after 3.125 mg/kg given daily for 1 to 3 consecutive days, peaked at 15 and 30 min after each injection and diminished to undetectable levels after 4 hr. The results indicate that 3 days of parenteral therapy with MTX significantly increases rat intestinal transit. The intestinal effects appear to transit. The intestinal effects appear to be transient and are proportional to the total dose of drug administered over the 3-day period. The intestinal effects of MTX occur from 1 to several days after peak plasma concentrations of drug and are associated with a reduced ability to sustain body weight after a 24-hr fast

  5. Accurate measurement of intestinal transit in the rat

    International Nuclear Information System (INIS)

    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. Cholesterol esterase activity of human intestinal mucosa

    International Nuclear Information System (INIS)

    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 acids

  7. Compartmentalization of Aquaporins in the Human Intestine

    Directory of Open Access Journals (Sweden)

    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.

  8. Alternative Functional In Vitro Models of Human Intestinal Epithelia

    Directory of Open Access Journals (Sweden)

    AmandaLKauffman

    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.

  9. Inflammation-Induced Endothelial-to-Mesenchymal Transition: A Novel Mechanism of Intestinal Fibrosis

    OpenAIRE

    Rieder, Florian; Kessler, Sean P.; WEST, GAIL A.; Bhilocha, Shardul; de la Motte, Carol; Sadler, Tammy M.; Gopalan, Banu; Stylianou, Eleni; Fiocchi, Claudio

    2011-01-01

    In addition to mesenchymal cells, endothelial cells may contribute to fibrosis through the process of endothelial-to-mesenchymal transition (EndoMT). We investigated whether human intestinal microvascular endothelial cells (HIMEC) undergo EndoMT and contribute to fibrosis in human and experimental inflammatory bowel disease (IBD). HIMEC were exposed to TGF-?1, IL-1?, and TNF-? or supernatants of lamina propria mononuclear cells (LPMC) and evaluated for morphological, phenotypic, and functi...

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

    International Nuclear Information System (INIS)

    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

  11. Dynamic efficiency of the human intestinal microbiota.

    Science.gov (United States)

    Candela, Marco; Biagi, Elena; Turroni, Silvia; Maccaferri, Simone; Figini, Paolo; Brigidi, Patrizia

    2015-06-01

    The emerging dynamic dimensions of the human intestinal microbiota (IM) are challenging the traditional definition of healthy gut microbiota, principally based on the static concepts of phylogenetic and functional core. On the other hand, recent researches are revealing that the microbiota plasticity is strategic for several aspects of our biology, addressing the different immunological and metabolic needs at various ages, and adjusting the ecosystem services in response to different lifestyle, physiological states or diets. In light of these studies, we propose to revise the traditional concept of healthy human IM, including its degree of plasticity among the fundamental requisites for providing host health. In order to make a model taking into account the relative importance of IM core functions and plasticity for the maintenance of host health, we address to Economics, where the efficiency of a productive system is measured by computing static and dynamic parameters. PMID:25168339

  12. Gastric transit and small intestinal transit time and motility assessed by a magnet tracking system

    DEFF Research Database (Denmark)

    Worsoe, Jonas; Fynne, Lotte

    2011-01-01

    ABSTRACT: BACKGROUND: Tracking an ingested magnet by the Magnet Tracking System MTS-1 (Motilis, Lausanne, Switzerland) is an easy and minimally-invasive method to assess gastrointestinal transit. The aim was to test the validity of MTS-1 for assessment of gastric transit time and small intestinal transit time, and to illustrate transit patterns detected by the system. Methods: A small magnet was ingested and tracked by an external matrix of 16 magnetic field sensors (4x4) giving a position defined by 5 coordinates (position: x, y, z, and angle: theta, phi). Eight healthy subjects were each investigated three times: (1) with a small magnet mounted on a capsule endoscope (PillCam); (2) with the magnet alone and the small intestine in the fasting state; and (3) with the magnet alone and the small intestine in the postprandial state. Results: Experiment (1) showed good agreement and no systematic differences between MTS-1 and capsule endoscopy when assessing gastric transit (median difference 1 min; range: 0-6 min) and small intestinal transit time (median difference 0.5 min; range: 0-52 min). Comparing experiments (1) and (2) there were no systematic differences in gastric transit or small intestinal transit when using the magnet-PillCam unit and the much smaller magnetic pill. In experiments (2) and (3), short bursts of very fast movements lasting less than 5% of the time accounted for more than half the distance covered during the first two hours in the small intestine, irrespective of whether the small intestine was in the fasting or postprandial state. The mean contraction frequency in the small intestine was significantly lower in the fasting state than in the postprandial state (9.90 min-1 vs. 10.53 min-1) (p=0.03). Conclusion: MTS-1 is reliable for determination of gastric transit and small intestinal transit time. It is possible to distinguish between the mean contraction frequency of small intestine in the fasting state and in the postprandial state.

  13. Inhibition of human intestinal ?-glucosidases by calystegines.

    Science.gov (United States)

    Jockovi?, Neboja; Fischer, Wiebke; Brandsch, Matthias; Brandt, Wolfgang; Drger, Birgit

    2013-06-12

    Calystegines are polyhydroxylated nortropane alkaloids found in Convolvulaceae, Solanaceae, and other plant families. These plants produce common fruits and vegetables. The calystegine structures resemble sugars and suggest interaction with enzymes of carbohydrate metabolism. Maltase and sucrase are ?-glucosidases contributing to human carbohydrate degradation in the small intestine. Inhibition of these enzymes by orally administered drugs is one option for treatment of diabetes mellitus type 2. In this study, inhibition of maltase and sucrase by calystegines A3 and B2 purified from potatoes was investigated. In silico docking studies confirmed binding of both calystegines to the active sites of the enzymes. Calystegine A3 showed low in vitro enzyme inhibition; calystegine B2 inhibited mainly sucrose activity. Both compounds were not transported by Caco-2 cells indicating low systemic availability. Vegetables rich in calystegine B2 should be further investigated as possible components of a diet preventing a steep increase in blood glucose after a carbohydrate-rich meal. PMID:23697377

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2005-02-28

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

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

    International Nuclear Information System (INIS)

    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

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

    Science.gov (United States)

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

    2013-04-11

    Food can have a significant impact on the pharmacokinetics of orally administered drugs, as it may affect drug solubility as well as permeability. Since fed state conditions cannot easily be implemented in the presently available permeability tools, including the frequently used Caco-2 system, exploring food effects during drug development can be quite challenging. In this study, we investigated the effect of fasted and fed state conditions on the intestinal absorption of the HIV protease inhibitor indinavir using simulated and human intestinal fluids in the in situ intestinal perfusion technique in mice. Although the solubility of indinavir was 6-fold higher in fed state human intestinal fluids (FeHIF) as compared to fasted state HIF (FaHIF), the intestinal permeation of indinavir was 22-fold lower in FeHIF as compared to FaHIF. Dialysis experiments showed that only a small fraction of indinavir is accessible for absorption in FeHIF due to micellar entrapment, possibly explaining its low intestinal permeation. The presence of ritonavir, a known P-gp inhibitor, increased the intestinal permeation of indinavir by 2-fold in FaHIF, while there was no increase when using FeHIF. These data confirm that drug-food interactions form a complex interplay between solubility and permeability effects. The use of HIF in in situ intestinal perfusions holds great promise for biorelevant absorption evaluation as it allows to directly explore this complex solubility/permeability interplay on drug absorption. PMID:23402972

  17. Intestinal behavior of the ester prodrug tenofovir DF in humans.

    Science.gov (United States)

    Geboers, Sophie; Haenen, Steven; Mols, Raf; Brouwers, Joachim; Tack, Jan; Annaert, Pieter; Augustijns, Patrick

    2015-05-15

    Tenofovir-disoproxil-fumarate (TDF) is a double ester prodrug which enables intestinal uptake of tenofovir (TFV) after oral administration in humans. In this study, prodrug stability was monitored in situ in the human intestine and in vitro using biorelevant media. In fasted state human intestinal fluids, the prodrug was completely degraded within 90min, resulting in the formation of the mono-ester intermediate and TFV; in fed state intestinal fluids, the degradation rate of TDF was slightly reduced and no TFV was formed. Intestinal fluid samples aspirated after administration of TDF confirmed extensive intraluminal degradation of TDF in fasted state conditions; a relatively fast absorption of TDF partly compensated for the degradation. Although food intake reduced intestinal degradation, the systemic exposure was not proportionally increased. The lower degradation in fed state conditions may be attributed to competing esterase substrates present in food, lower chemical degradation in the slightly more acidic environment and micellar entrapment, delaying exposure to the "degrading" intestinal environment. The results of this study demonstrate premature intestinal degradation of TDF and suggest that TFV may benefit from a more stable prodrug approach; however, fast absorption may compensate for fast degradation, indicating that prodrug selection should not be limited to stability assays. PMID:25747454

  18. Shigella Infection in a SCID Mouse-Human Intestinal Xenograft Model: Role for Neutrophils in Containing Bacterial Dissemination in Human Intestine

    OpenAIRE

    Zhang, Zhi; Jin, Lingling; Champion, Gretchen; Seydel, Karl B.; Stanley, Samuel L.

    2001-01-01

    Shigellae infect human intestine and cause intense inflammation and destruction of colonic and rectal mucosa. To model the interactions of shigella with human intestine in vivo, we have studied shigella infection in human intestinal xenografts in severe combined immunodeficient mice (SCID-HU-INT mice). Inoculation of shigella into human intestinal xenografts caused severe inflammation and mucosal damage, which was apparent as soon as 4 h following infection. Shigella infection was associated ...

  19. Correlation of contractions and transit in rat small intestine.

    Science.gov (United States)

    Scott, L D; Summers, R W

    1976-01-01

    A single strain gauge was implanted chronically in the proximal jejunum of the rat to record contractions. FAsted pentobarbital-anesthetized animals received glucagon, caerulein, or isotonic saline control infusions intravenously while contractions were recorded. In control animals, the distribution of contractions in time showed clusters, with peaks at intervals of 14.24 +/-5.6 (SD) min. Glucagon produced dose-related inhibition of contractions. Caerulein at two lower doses produced a more uniform distribution of contractions in time; a higher dose caused inhibition. In other fasted rats, an isotopically labeled bolus was given through a chronically implanted duodenal cathether, and its distribution along the small intestine was examined in animals receiving the same doses of glucagon, caerulein, and saline. Glucagon caused a dose-related delay in transit. Those doses of caerulein that produced a uniform distribution of contractions accelerated transit; the dose that inhibited contractions delayed transit. Doses of glucagon and caerulein known to affect both motility and transit did not significantly affect water movement. The fasted rat resembles the fasted go in respect to the temporal distributions of jejunal contractions at a single point. Both quantitative and qualitative changes in contractions induce changes in transit. PMID:1251898

  20. Transcytosis of cholera toxin subunits across model human intestinal epithelia.

    OpenAIRE

    Lencer, W. I.; Moe, S; Rufo, P A; Madara, J L

    1995-01-01

    Cholera toxin (CT) elicits a massive secretory response from intestinal epithelia by binding apical receptors (ganglioside GM1) and ultimately activating basolateral effectors (adenylate cyclase). The mechanism of signal transduction from apical to basolateral membrane, however, remains undefined. We have previously shown that CT action on the polarized human intestinal epithelial cell line T84 requires endocytosis and processing in multiple intracellular compartments. Our aim in the present ...

  1. Electromagnetic radiation from ingested sources in the human intestine

    OpenAIRE

    Chirwa, L. C.; Hammond, P. A.; Roy, S.; Cumming, D. R. S.

    2002-01-01

    There is currently considerable work on the development of wireless sensors that can be used in the small intestine. The radiation characteristics of sources in the gastro-intestinal (GI) tract cannot be readily calculated due to the complexity of the human body and its composite tissues, each with different electrical characteristics. This paper presents radiation characteristics for sources in the GI tract that should allow for the optimum design of more efficient telemetry systems. The cha...

  2. Effect of heat stress on intestinal barrier function of human intestinal epithelial Caco-2 cells

    Directory of Open Access Journals (Sweden)

    Gui-zhen XIAO

    2013-07-01

    Full Text Available Objective?To investigate the heat stress-induced dysfunction of intestinal barrier including intestinal tight junction and apoptosis of epithelial cells. Methods?Human intestinal epithelial Caco-2 cell monolayers, serving as the intestinal barrier model, were exposed to different temperature (37-43? for designated time. Transepithelial electrical resistance (TEER and horseradish peroxidase (HRP flux permeability were measured to evaluate barrier integrity. Level of tight junction (TJ protein occludin was analyzed by Western blotting. Cell apoptosis rate was determined using Annexin V-FITC/PI kit by flow cytometry. Results?Compared with the 37? group, TEER lowered and the permeability for HRP increased significantly after heat exposure (P<0.01 in 39?, 41? and 43? groups. The expression of occludin increased when the temperature was elevated from 37? to 41?, and it reached the maximal level at 41?. However, its expression gradually decreased with passage of time at 43?. Cell apoptosis was enhanced with elevation of the temperature (P?0.05 or P?0.01. Conclusion?Heat stress can induce damage to tight junction and enhance apoptosis of epithelial cells, thus causing dysfunction of intestinal epithelial barrier.

  3. Cholinergic mediation of small intestinal transit in the rat

    International Nuclear Information System (INIS)

    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

  4. Development stages of the "rope" human intestinal parasite

    OpenAIRE

    Volinsky, Alex A.; Gubarev, Nikolai V.; Orlovskaya, Galina M.; Marchenko, Elena V.

    2013-01-01

    This paper describes the five development stages of the rope worm, which could be human parasite. Rope worms have been discovered as a result of cleansing enemas. Thousands or people have passed the rope worms from all over the World. Adult stages live in human gastro-intestinal tract and are anaerobic. They move inside the body by releasing gas bubbles utilizing jet propulsion. These worms look like a rope, and can be over a meter long. The development stages were identifie...

  5. Sndrome estreimiento: mtodos para medir la velocidad de trnsito intestinal / Constipation syndrome: methods for measuring the speed of intestinal transit

    Scientific Electronic Library Online (English)

    Ral, Len-Bara.

    2012-01-01

    Full Text Available En el presente artculo, recuerdo lo que present, en un simposio llevado a cabo en nuestra Sociedad sobre el sndrome estreimiento, en relacin con la definicin y los factores determinantes de este sndrome, y, adems, con los mtodos que hemos creado para medir en forma fisiolgica la velocidad [...] del trnsito intestinal, especialmente colnico. Abstract in english In the present article, I remind what I presented, in a symposium performed in our Society on the constipation syndrome, in relation with the definition and the determinant factores of this syndrome, and, in addition, with the methods we have created to determine physiologically the velocity of the [...] intestinal transit, specially colonic.

  6. Molecular Epidemiology of Human Intestinal Amoebas in Iran

    Directory of Open Access Journals (Sweden)

    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.

  7. Cell and molecular aspects of human intestinal biotin absorption.

    Science.gov (United States)

    Said, Hamid M

    2009-01-01

    Humans cannot synthesize biotin and thus must obtain this vitamin from exogenous sources. The intestine is exposed to 2 sources of biotin: a dietary source and a bacterial source, which is normal microflora of the large intestine. Dietary protein-bound biotin is converted to free biotin prior to absorption. Absorption of free biotin in the small and large intestine involves a saturable and Na(+)-dependent carrier-mediated process that is shared with pantothenic acid and lipoate. For this reason, the involved transport system is referred to as the sodium-dependent multivitamin transporter (SMVT); in humans, it is designated as hSMVT. The hSMVT system has been cloned, demonstrated to be exclusively expressed at the apical membrane of enterocytes, and shown, by means of gene-specific short interfering RNA, to be the main biotin uptake system that operates in human intestinal epithelial cells. The 5'-regulatory region of the hSMVT gene has also been cloned and characterized both in vitro and in vivo. Further, the human intestinal biotin uptake process was adaptively up-regulated in biotin deficiency via a transcriptionally mediated mechanism(s) that involves Kruppel-like factor 4 sites. Studies on cell biology of hSMVT have shown a region in the cytoplasmic C-terminal domain of the polypeptide to be essential for its targeting to the apical membrane domain of epithelial cells. Intracellular trafficking of the hSMVT protein appears to involve distinct trafficking vesicles that require an intact microtubules network and the motor protein dynein for their mobility. PMID:19056639

  8. Application of the Human Intestinal Tract Chip to the non-human primate gut microbiota.

    Science.gov (United States)

    Bello Gonzlez, T D J; van Passel, M W J; Tims, S; Fuentes, S; De Vos, W M; Smidt, H; Belzer, C

    2015-01-01

    The human intestinal microbiota is responsible for various health-related functions, and its diversity can be readily mapped with the 16S ribosomal RNA targeting Human Intestinal Tract (HIT) Chip. Here we characterise distal gut samples from chimpanzees, gorillas and marmosets, and compare them with human gut samples. Our results indicated applicability of the HITChip platform can be extended to chimpanzee and gorilla faecal samples for analysis of microbiota composition and enterotypes, but not to the evolutionary more distant marmosets. PMID:25519524

  9. Ricin Crosses Polarized Human Intestinal Cells and Intestines of Ricin-Gavaged Mice without Evident Damage and Then Disseminates to Mouse Kidneys

    OpenAIRE

    Flora, Alyssa D.; Teel, Louise D.; Smith, Mark A.; Sinclair, James F.; Melton-celsa, Angela R.; Obrien, Alison D.

    2013-01-01

    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 o...

  10. Gastric emptying and intestinal transit of pancreatic enzyme supplements in cystic fibrosis

    OpenAIRE

    Taylor, C.; Hillel, P.; Ghosal, S.; Frier, M.; Senior, S.; Tindale, W.; Read, N.

    1999-01-01

    OBJECTIVETo investigate gastric emptying and intestinal transit of pelleted pancreatin in relation to food boluses. ?MethodsDual isotope scintigraphy combined with breath hydrogen sampling was used to track the concurrent gastric emptying and intestinal transit of 111indium labelled microspheres and a 99mtechnetium labelled tin colloid test meal. Twelve pancreatic insufficient cystic fibrosis patients aged 5 to 38 years performed the study.?RESULTS50% gast...

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

    OpenAIRE

    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...

  12. Effects of capsaicin on human intestinal cell line Caco-2

    OpenAIRE

    Isoda, Hiroko; Han, Junkyu; Tominaga, Makoto; Maekawa, Takaaki

    2001-01-01

    The influence of capsaicin processing on human intestinal cell line Caco-2 was examined by measuring transepithelial electrical resistance (TER). There was an increase in permeability at high concentration (200 to 500 ?M) of capsaicin, and the effect was inhibited by pretreatment of capsazepine, which is a competitive antagonist of the vanilloid receptor 1 (VR1). LDH-activity as well as changes in intracellular Ca2+ were determined to know whether or not capsaicin affected TER activity throug...

  13. Evolution of Symbiotic Bacteria in the Distal Human Intestine

    Science.gov (United States)

    Ley, Ruth E; Lozupone, Catherine A; Hamady, Micah; Martens, Eric C; Henrissat, Bernard; Coutinho, Pedro M; Minx, Patrick; Latreille, Philippe; Cordum, Holland; Van Brunt, Andrew; Kim, Kyung; Fulton, Robert S; Fulton, Lucinda A; Clifton, Sandra W; Wilson, Richard K; Knight, Robin D; Gordon, Jeffrey I

    2007-01-01

    The adult human intestine contains trillions of bacteria, representing hundreds of species and thousands of subspecies. Little is known about the selective pressures that have shaped and are shaping this community's component species, which are dominated by members of the Bacteroidetes and Firmicutes divisions. To examine how the intestinal environment affects microbial genome evolution, we have sequenced the genomes of two members of the normal distal human gut microbiota, Bacteroides vulgatus and Bacteroides distasonis, and by comparison with the few other sequenced gut and non-gut Bacteroidetes, analyzed their niche and habitat adaptations. The results show that lateral gene transfer, mobile elements, and gene amplification have played important roles in affecting the ability of gut-dwelling Bacteroidetes to vary their cell surface, sense their environment, and harvest nutrient resources present in the distal intestine. Our findings show that these processes have been a driving force in the adaptation of Bacteroidetes to the distal gut environment, and emphasize the importance of considering the evolution of humans from an additional perspective, namely the evolution of our microbiomes. PMID:17579514

  14. IL-2 receptor ?-chain molecule is critical for intestinal T-cell reconstitution in humanized mice

    DEFF Research Database (Denmark)

    Denton, Paul W.; Nochi, T

    2012-01-01

    Intestinal immune cells are important in host defense, yet the determinants for human lymphoid homeostasis in the intestines are poorly understood. In contrast, lymphoid homeostasis has been studied extensively in mice, where the requirement for a functional common ?-chain molecule has been established. We hypothesized that humanized mice could offer insights into human intestinal lymphoid homeostasis if generated in a strain with an intact mouse common ?-chain molecule. To address this hypothesis, we used three mouse strains (non-obese diabetic (NOD)/severe-combined immunodeficient (SCID) (N/S); NOD/SCID ?-chain(-/-) (NSG); and Rag2(-/-) ?-chain(-/-) (DKO)) and two humanization techniques (bone marrow liver thymus (BLT) and human CD34(+) cell bone marrow transplant of newborn mice (hu)) to generate four common types of humanized mice: N/S-BLT, NSG-BLT, NSG-hu, and DKO-hu mice. The highest levels of intestinal human T cells throughout the small and large intestines were observed in N/S-BLT mice, which have anintact common ?-chain molecule. Furthermore, the small intestine lamina propria T-cell populations of N/S-BLT mice exhibit a human intestine-specific surface phenotype. Thus, the extensive intestinal immune reconstitution of N/S-BLT mice was both quantitatively and qualitatively better when compared with the other models tested such that N/S-BLT mice are well suited for the analysis of human intestinal lymphocyte trafficking and human-specific diseases affecting the intestines.

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

    International Nuclear Information System (INIS)

    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 transinal 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

  16. Sequential cancer mutations in cultured human intestinal stem cells.

    Science.gov (United States)

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

    2015-05-01

    Crypt stem cells represent the cells of origin for intestinal neoplasia. Both mouse and human intestinal stem cells can be cultured in medium containing the stem-cell-niche factors WNT, R-spondin, epidermal growth factor (EGF) and noggin over long time periods as epithelial organoids that remain genetically and phenotypically stable. Here we utilize CRISPR/Cas9 technology for targeted gene modification of four of the most commonly mutated colorectal cancer genes (APC, P53 (also known as TP53), KRAS and SMAD4) in cultured human intestinal stem cells. Mutant organoids can be selected by removing individual growth factors from the culture medium. Quadruple mutants grow independently of all stem-cell-niche factors and tolerate the presence of the P53 stabilizer nutlin-3. Upon xenotransplantation into mice, quadruple mutants grow as tumours with features of invasive carcinoma. Finally, combined loss of APC and P53 is sufficient for the appearance of extensive aneuploidy, a hallmark of tumour progression. PMID:25924068

  17. An iterative workflow for mining the human intestinal metaproteome

    Directory of Open Access Journals (Sweden)

    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.

  18. Effect of intravenous infusion of glyceryl trinitrate on gastric and small intestinal motor function in healthy humans

    DEFF Research Database (Denmark)

    Madsen, Jan Lysgrd; Fuglsang, Stefan

    2006-01-01

    BACKGROUND: Glyceryl trinitrate is a donor of nitric oxide that relaxes smooth muscle cells of the gastrointestinal tract. Little is known about the effect of glyceryl trinitrate on gastric emptying and no data exist on the possible effect of glyceryl trinitrate on small intestinal transit. AIM: To examine the effect of intravenous infusion of glyceryl trinitrate on gastric and small intestinal motor function after a meal in healthy humans. METHODS: Nine healthy volunteers participated in a placebo-controlled, double-blind, crossover study. Each volunteer was examined during intravenous infusion of glyceryl trinitrate 1 microg/kg x min or saline. A gamma camera technique was used to measure gastric emptying and small intestinal transit after a 1600-kJ mixed liquid and solid meal. Furthermore, duodenal motility was assessed by manometry. RESULTS: Glyceryl trinitrate did not change gastric mean emptying time, gastric half emptying time, gastric retention at 15 min or small intestinal mean transit time. Glyceryltrinitrate did not influence the frequency of duodenal contractions, the amplitude of duodenal contractions or the duodenal motility index. CONCLUSIONS: Intravenous infusion of glyceryl trinitrate 1 microg/kg x min does not induce major changes in gastric or small intestinal motor function after a 1600-kJ meal in healthy volunteers.

  19. Congruent Strain Specific Intestinal Persistence of Lactobacillus plantarum in an Intestine-Mimicking In Vitro System and in Human Volunteers

    OpenAIRE

    Bokhorst-van Veen, H.; Swam, I.; Wels, M.; Bron, P. A.; Kleerebezem, M.

    2012-01-01

    BACKGROUND: An important trait of probiotics is their capability to reach their intestinal target sites alive to optimally exert their beneficial effects. Assessment of this trait in intestine-mimicking in vitro model systems has revealed differential survival of individual strains of a species. However, data on the in situ persistence characteristics of individual or mixtures of strains of the same species in the gastrointestinal tract of healthy human volunteers have not been reported to da...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1984-08-01

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

  1. Mechanisms underlying modulation of monocarboxylate transporter 1 (MCT1) by somatostatin in human intestinal epithelial cells

    OpenAIRE

    Saksena, Seema; Theegala, Saritha; Bansal, Nikhil; Gill, Ravinder K.; Tyagi, Sangeeta; Alrefai, Waddah A.; Ramaswamy, Krishnamurthy; Dudeja, Pradeep K.

    2009-01-01

    Somatostatin (SST), an important neuropeptide of the gastrointestinal tract has been shown to stimulate sodium chloride absorption and inhibit chloride secretion in the intestine. However, the effects of SST on luminal butyrate absorption in the human intestine have not been investigated. Earlier studies from our group and others have shown that monocarboxylate transporter (MCT1) plays an important role in the transport of butyrate in the human intestine. The present studies were undertaken t...

  2. Small intestinal transit in patients with liver cirrhosis and portal hypertension : a descriptive study

    DEFF Research Database (Denmark)

    Karlsen, Stine; Fynne, Lotte

    2012-01-01

    Gastrointestinal dysmotility may be involved in the development of bacterial translocation and infection in patients with liver cirrhosis. The aim of the present study was to describe gastric, small intestinal and colorectal motility and transit in patients with liver cirrhosis and portal hypertension using a magnet-based Motility Tracking System (MTS-1) and standard radiopaque markers.

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

    Scientific Electronic Library Online (English)

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

    2010-05-01

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

  4. Effect of sodium fluoride on gastric emptying and intestinal transit in mice.

    Science.gov (United States)

    Amira, Smain; Soufane, Sihem; Gharzouli, Kamel

    2005-08-01

    Fluoride, a well-recognised harmful substance, is easily absorbed by the gastrointestinal mucosa. It is therefore conceivable that any alteration of the gastrointestinal motility can affect the rate of absorption of fluoride and leads to aggravation of its toxic effects. The effects of fluoride on gastric emptying and intestinal transit were studied in the mouse using a carboxymethyl cellulose (CMC) solution as a non-nutrient meal. The participation of the cholinergic and nitrergic systems in these effects was also evaluated. Oral gavage of 5 mM NaF had no significant effect on gastric emptying and intestinal transit of the CMC meal, whereas a decrease of gastric emptying (-33%, P<0.05) and an increase in intestinal transit (+20.7%, P<0.05) were observed with 20 mM NaF. Atropine injection induced a significant decrease of gastric emptying. Combined treatment of atropine with 20 mM NaF brought about a further, but not significant decrease in gastric emptying. N-G-nitro-L-arginine-methyl ester (L-NAME) treatment with or without oral administration of NaF decreased gastric emptying. Atropine treatment significantly depressed intestinal transit from 56.5% to 37.7% in the absence of NaF and from 70.1% to 42.8% in its presence. In contrast, L-NAME administration either alone or with fluoride increased intestinal transit (P<0.05). The present results suggest that fluoride alter gastrointestinal motility, an effect that may partly involve the cholinergic pathway. PMID:16089320

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

    Science.gov (United States)

    Sjgren, Erik; Dahlgren, David; Roos, Carl; Lennerns, Hans

    2015-06-01

    Application of information on regional intestinal permeability has been identified as a key aspect of successful pharmaceutical product development. This study presents the results and evaluation of an approach for the indirect estimation of site-specific in vivo intestinal effective permeability (Peff) in humans. Plasma concentration-time profiles from 15 clinical studies that administered drug solutions to specific intestinal regions were collected and analyzed. The intestinal absorption rate for each drug was acquired by deconvolution, using historical intravenous data as reference, and used with the intestinal surface area and the dose remaining in the lumen to estimate the Peff. Forty-three new Peff values were estimated (15 from the proximal small intestine, 11 from the distal small intestine, and 17 from the large intestine) for 14 active pharmaceutical ingredients representing a wide range of biopharmaceutical properties. A good correlation (r(2) = 0.96, slope = 1.24, intercept = 0.030) was established between these indirect jejunal Peff estimates and jejunal Peff measurements determined directly using the single-pass perfusion double balloon technique. On average, Peff estimates from the distal small intestine and large intestine were 90% and 40%, respectively, of those from the proximal small intestine. These results support the use of the evaluated deconvolution method for indirectly estimating regional intestinal Peff in humans. This study presents the first comprehensive data set of estimated human regional intestinal permeability values for a range of drugs. These biopharmaceutical data can be used to improve the accuracy of gastrointestinal absorption predictions used in drug development decision-making. PMID:25919764

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

    International Nuclear Information System (INIS)

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

  7. Immunomodulatory Properties of Streptococcus and Veillonella Isolates from the Human Small Intestine Microbiota

    OpenAIRE

    Bogert, B., van den; Meijerink, M.; Zoetendal, E. G.; Wells, J. M.; Kleerebezem, M.

    2014-01-01

    The human small intestine is a key site for interactions between the intestinal microbiota and the mucosal immune system. Here we investigated the immunomodulatory properties of representative species of commonly dominant small-intestinal microbial communities, including six streptococcal strains (four Streptococcus salivarius, one S. equinus, one S. parasanguinis) one Veillonella parvula strain, one Enterococcus gallinarum strain, and Lactobacillus plantarum WCFS1 as a bench mark strain on h...

  8. Cell and Molecular Aspects of Human Intestinal Biotin Absorption13

    OpenAIRE

    Said, Hamid M

    2009-01-01

    Humans cannot synthesize biotin and thus must obtain this vitamin from exogenous sources. The intestine is exposed to 2 sources of biotin: a dietary source and a bacterial source, which is normal microflora of the large intestine. Dietary protein-bound biotin is converted to free biotin prior to absorption. Absorption of free biotin in the small and large intestine involves a saturable and Na+-dependent carrier-mediated process that is shared with panthothenic acid and lipoate. For this reaso...

  9. Precision-cut rat, mouse, and human intestinal slices as novel models for the early-onset of intestinal fibrosis.

    Science.gov (United States)

    Pham, Bao Tung; van Haaften, Wouter Tobias; Oosterhuis, Dorenda; Nieken, Judith; de Graaf, Inge Anne Maria; Olinga, Peter

    2015-04-01

    Intestinal fibrosis (IF) is a major complication of inflammatory bowel disease. IF research is limited by the lack of relevant in vitro and in vivo models. We evaluated precision-cut intestinal slices (PCIS) prepared from human, rat, and mouse intestine as ex vivo models mimicking the early-onset of (human) IF. Precision-cut intestinal slices prepared from human (h), rat (r), and mouse (m) jejunum, were incubated up to 72h, the viability of PCIS was assessed by ATP content and morphology, and the gene expression of several fibrosis markers was determined. The viability of rPCIS decreased after 24h of incubation, whereas mPCIS and hPCIS were viable up to 72h of culturing. Furthermore, during this period, gene expression of heat shock protein 47 and plasminogen activator inhibitor 1 increased in all PCIS in addition to augmented expression of synaptophysin in hPCIS, fibronectin (Fn2) and TGF-?1 in rPCIS, and Fn2 and connective tissue growth factor (Ctgf) in mPCIS. Addition of TGF-?1 to rPCIS or mPCIS induced the gene expression of the fibrosis markers Pro-collagen1a1, Fn2, and Ctgf in both species. However, none of the fibrosis markers was further elevated in hPCIS. We successfully developed a novel ex vivo model that can mimic the early-onset of fibrosis in the intestine using human, rat, and mouse PCIS. Furthermore, in rat and mouse PCIS, TGF-?1 was able to even further increase the gene expression of fibrosis markers. This indicates that PCIS can be used as a model for the early-onset of IF. PMID:25907784

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

    Directory of Open Access Journals (Sweden)

    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.

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

    International Nuclear Information System (INIS)

    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 Zn2+. Using PteGlu2[14C]Glu as substrate, they demonstrated a K/sub m/ of 1.2 ?M and increasing affinity for folates with longer glutamate chains. Intracellular PPH required the complete folic acid (PteGlu) moiety and a ?-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 ?-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

  12. CYTOKINE-INDUCED CHROMATIN MODIFICATIONS OF THE TYPE I COLLAGEN ALPHA 2 GENE DURING INTESTINAL ENDOTHELIAL-TO-MESENCHYMAL TRANSITION

    Science.gov (United States)

    Sadler, Tammy; Scarpa, Melania; Rieder, Florian; West, Gail; Stylianou, Eleni

    2013-01-01

    Background Fibrosis of the intestine is currently an irreversible complication of Inflammatory Bowel Disease yet little is understood of the underlying pathogenesis and anti-fibrotic strategies remain elusive. To develop effective therapies, knowledge of the mechanism of transcription and excessive deposition of type I collagen - a hallmark of fibrosis, is needed. We have shown previously that endothelial-to-mesenchymal transition (EndoMT) contributes to the pool of intestinal fibrotic cells and that a cytokine cocktail (IL1-?, TNF-? and TGF-?) induces Collagen I alpha 2 (COL1A2) mRNA and protein. Methods Chromatin immunoprecipitation assays on pure cultures of human intestinal mucosal endothelial cells undergoing EndoMT were performed with antibodies to specific histone modifications and RNA polymerase II. RT-PCR was used to quantify the levels of Col1A2 and endothelial specific von Willebrand factor (vWF) mRNA. Results We show that cytokines induce selective chromatin modifications (histone 4 hyperacetylation and hypermethylation of histone 3) and phosphorylated RNA polymerase II at the COL1A2 promoter. Hypoacetylated and hypomethylated histone 3 was detected on the repressed vWF gene. Prolonged exposure to cytokines (16 days) retained hyperacetylation of select lysines in H4 on the COL1A2 promoter. Removal of cytokines after 16 days and continued culture for 10 days, showed persistent hyperacetylation at lysine 16 in histone H4. Conclusion This is the first study to show that COL1A2 gene expression is associated with cytokine-induced, temporally ordered and persistent chromatin modifications and suggests that these are important determinants of gene expression in EndoMT and intestinal fibrosis. PMID:23635716

  13. Escherichia coli diversity in the lower intestinal tract of humans.

    Science.gov (United States)

    Gordon, David M; O'Brien, Claire L; Pavli, Paul

    2015-08-01

    Previous studies examining the clonal diversity of Escherichia coli populations within humans have been based on faecal isolates. In this study E.?coli were isolated from biopsies taken from the terminal ileum, ascending, transverse and descending colon, and rectum of 69 individuals. Multiple isolates from each biopsy were characterized using Rep-PCR. An average of 3.5 genotypes were recovered per host, and in hosts with two or more strains, the phylogroup membership of the second most abundant strain was significantly more likely to be the same as the dominant strain. There was no indication of a non-random distribution of E.?coli phylogroups among the regions of the lower intestine. In hosts with multiple genotypes, as defined by Repetitive extragenic palindromic-PCR, genotypes were non-randomly distributed among gut regions in over half the individuals. The phylogroup membership of an individual's numerically dominant strain explained some of the variation in the extent to which strains within an individual were heterogeneously distributed, with most heterogeneity observed when the numerically dominant strain belonged to phylogroups E or F, and the least when the dominant strain belonged to phylogroup B2. The results of this study support previous studies on pigs that demonstrated faecal sampling underestimates the genotype diversity present within a host. PMID:26034010

  14. Vasoactive intestinal peptide binding autoantibodies in autoimmune humans and mice.

    Science.gov (United States)

    Bangale, Yogesh; Cavill, Dana; Gordon, Tom; Planque, Stephanie; Taguchi, Hiroaki; Bhatia, Gita; Nishiyama, Yasuhiro; Arnett, Frank; Paul, Sudhir

    2002-12-01

    Autoantibodies capable of binding the immunoregulatory neuropeptide vasoactive intestinal peptide (VIP) were detected in the sera of a mouse strain prone to autoimmune disease due to the lpr mutation (MRL/lpr). The autoantibodies were not present in control wildtype MRL/lpr mice, but they were readily detected in humans without autoimmune disease. The binding was due to low affinity VIP recognition. Increased VIP binding activity was evident in patients with systemic lupus erythematosus but not systemic sclerosis, Sjgren's syndrome (SS), rheumatoid arthritis or autoimmune thyroiditis. Recombinant VIP binding Fv clones (fragment variable; the variable domains of the light and heavy chains antibody subunits joined with a peptide linker) were isolated from a phage display library prepared from lupus patients. One Fv clone displaying VIP-selective binding and several clones displaying cross-reactivity with unrelated peptides were identified. Replacement mutations in the VIP-selective clone were preferentially localized in the regions known to make contacts with the antigen, i.e. the complementarity determining regions, suggesting that the selective binding activity is due to immunological maturation of the antibodies. Frequent occurrences of autoantibody responses to VIP indicate that immunological tolerance to this neuropeptide can be readily broken. The depletion of VIP by specific antibodies in autoimmune disease may interfere with VIP regulation of T cells and inflammatory cells and result in further amplification of autoreactive immunological responses. PMID:12535706

  15. Evaluation of intestinal transit time of root and leaves of Ipomea sepiaria.

    Science.gov (United States)

    Majumder, Sayani; Ashok, B K; Nishteswar, K

    2013-10-01

    Ipomoea sepiaria Koenig Ex. Roxb is considered to be one of the source plants of the classical herb Lakshmana. In folklore, the herb is well known for its laxative activity. This plant belongs to Convolvulaceae family. It is observed that the plants of this family especially the species of Ipomoea are rich in purgative resins. The present experimental study was carried out to evaluate the effect of leaf and root of I. sepiaria on intestinal transit time on Swiss albino mice and the test drugs were administered in dose of 400 mg/kg. Evaluation of intestinal transit time was carried out by adopting Kaolin expulsion test and latency of onset of kaolin expulsion in fecal matter. The results shows that both root and leaf samples of I. sepiaria have marked intestinal motility enhancing property, among which leaf sample is found to be better. Hence, for the therapeutic purpose leaf can be preferred to get better activity profile and also to prevent destructive harvesting of the plant. PMID:24696582

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

    DEFF Research Database (Denmark)

    Madsen, Jan L; Linnet, Jan

    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 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 ingestion of glucose did not differ from that after ingestion of the fructose-sorbitol mixture (P = 0.7897). However, the mouth-to-cecum transit of the radiolabeled marker was faster (P = 0.0033) and the percentage content of the marker in colon was higher after ingestion of the fructose-sorbitol mixture than after ingestion of glucose (P = 0.0128). In healthy humans, malabsorption of small amounts of a fructose-sorbitol mixture accelerates small bowel transit.

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

    International Nuclear Information System (INIS)

    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

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

    Directory of Open Access Journals (Sweden)

    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 ?- and ?-opioid receptor activity with a smaller -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 -opioid receptor antagonists, casoxin 4 and lactoferroxin A, applied before and after morphine injection were unable to antagonize morphine inhibition of gut transit.Conclusions: Casoxin 4 reverses morphine-induced inhibition of contraction in mice and guinea pigs in vitro but fails to influence morphine inhibition of mouse small intestinal transit by the oral route.Keywords: lactoferroxin A, -opioid receptor antagonist, opioid agonists

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

    DEFF Research Database (Denmark)

    Zoetendal, Erwin G; Raes, Jeroen

    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 samples from a single individual indicated that Streptococcus sp., Escherichia coli, Clostridium sp. and high G+C organisms are most abundant in the small intestine. The compositions of these populations fluctuated in time and correlated to the short-chain fatty acids profiles that were determined in parallel. Comparative functional analysis with fecal metagenomes identified functions that are overrepresented in the small intestine, including simple carbohydrate transport phosphotransferase systems (PTS), central metabolism and biotin production. Moreover, metatranscriptome analysis supported high level in-situ expression of PTS and carbohydrate metabolic genes, especially those belonging to Streptococcus sp. Overall, our findings suggest that rapid uptake and fermentation of available carbohydrates contribute to maintaining the microbiota in the human small intestine.

  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

    DEFF Research Database (Denmark)

    Tetens, Inge

    2011-01-01

    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 based on newly developed scientific evidence related to sugar beet fibre and decreasing intestinal transit time. The food constituent that is the subject of the health claim is sugar beet fibre. This opinion applies to sugar beet fibre naturally present in foods and to those forms added to foods. The Panel considers that sugar beet fibre is sufficiently characterised in relation to the claimed effect. The claimed effect is decreasing intestinal transit time. The target population proposed by the applicant is people who want to improve or maintain normal bowel function. The Panel considers that decreasing intestinal (orofaecal) transit time may be a beneficial physiological effect. The applicant provided four human studies as pertinent to the health claim. The Panel considers that no conclusion can be drawn from three studies for the scientific substantiation of the claim owing to methodological 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 claim showed no effect of sugar beet fibre on intestinal (orofaecal) transit time. The Panel concludes that a cause and effect relationship has not been established between the consumption of sugar beet fibre and decreasing intestinal transit time. European Food Safety Authority, 2011

  1. Sildenafil delays the intestinal transit of a liquid meal in awake rats.

    Science.gov (United States)

    Graa, J R V; Macedo, G M; Palheta, R C; Gondim, F de A A; Nogueira, R O; Correia, J M; Rola, F H; Oliveira, R B; Souza, M A N; Santos, A A

    2008-01-01

    Sildenafil slows down the gastric emptying of a liquid test meal in awake rats and inhibits the contractility of intestinal tissue strips. We studied the acute effects of sildenafil on in vivo intestinal transit in rats. Fasted, male albino rats (180-220 g, N = 44) were treated (0.2 mL, iv) with sildenafil (4 mg/kg) or vehicle (0.01 N HCl). Ten minutes later they were fed a liquid test meal (99m technetium-labeled saline) injected directly into the duodenum. Twenty, 30 or 40 min after feeding, the rats were killed and transit throughout the gastrointestinal tract was evaluated by progression of the radiotracer using the geometric center method. The effect of sildenafil on mean arterial pressure (MAP) was monitored in a separate group of rats (N = 14). Data (medians within interquartile ranges) were compared by the Mann-Whitney U-test. The location of the geometric center was significantly more distal in vehicle-treated than in sildenafil-treated rats at 20, 30, and 40 min after test meal instillation (3.3 (3.0-3.6) vs 2.9 (2.7-3.1); 3.8 (3.4-4.0) vs 2.9 (2.5-3.1), and 4.3 (3.9-4.5) vs 3.4 (3.2-3.7), respectively; P < 0.05). MAP was unchanged in vehicle-treated rats but decreased by 25% (P < 0.05) within 10 min after sildenafil injection. In conclusion, besides transiently decreasing MAP, sildenafil delays the intestinal transit of a liquid test meal in awake rats. PMID:18157431

  2. Sildenafil delays the intestinal transit of a liquid meal in awake rats

    Directory of Open Access Journals (Sweden)

    J.R.V Graa

    2008-01-01

    Full Text Available Sildenafil slows down the gastric emptying of a liquid test meal in awake rats and inhibits the contractility of intestinal tissue strips. We studied the acute effects of sildenafil on in vivo intestinal transit in rats. Fasted, male albino rats (180-220 g, N = 44 were treated (0.2 mL, iv with sildenafil (4 mg/kg or vehicle (0.01 N HCl. Ten minutes later they were fed a liquid test meal (99m technetium-labeled saline injected directly into the duodenum. Twenty, 30 or 40 min after feeding, the rats were killed and transit throughout the gastrointestinal tract was evaluated by progression of the radiotracer using the geometric center method. The effect of sildenafil on mean arterial pressure (MAP was monitored in a separate group of rats (N = 14. Data (medians within interquartile ranges were compared by the Mann-Whitney U-test. The location of the geometric center was significantly more distal in vehicle-treated than in sildenafil-treated rats at 20, 30, and 40 min after test meal instillation (3.3 (3.0-3.6 vs 2.9 (2.7-3.1; 3.8 (3.4-4.0 vs 2.9 (2.5-3.1, and 4.3 (3.9-4.5 vs 3.4 (3.2-3.7, respectively; P < 0.05. MAP was unchanged in vehicle-treated rats but decreased by 25% (P < 0.05 within 10 min after sildenafil injection. In conclusion, besides transiently decreasing MAP, sildenafil delays the intestinal transit of a liquid test meal in awake rats.

  3. Evaluation of intestinal transit time of root and leaves of Ipomea sepiaria

    OpenAIRE

    Majumder, Sayani; Ashok, B. K.; Nishteswar, K.

    2013-01-01

    Ipomoea sepiaria Koenig Ex. Roxb is considered to be one of the source plants of the classical herb Lakshmana. In folklore, the herb is well known for its laxative activity. This plant belongs to Convolvulaceae family. It is observed that the plants of this family especially the species of Ipomoea are rich in purgative resins. The present experimental study was carried out to evaluate the effect of leaf and root of I. sepiaria on intestinal transit time on Swiss albino mice and the test drugs...

  4. Nitroreduction and formation of hemoglobin adducts in rats with a human intestinal microflora.

    OpenAIRE

    Scheepers, P T; Straetemans, M M; Koopman, J. P.; Bos, R P

    1994-01-01

    In the covalent binding of nitroarenes to macromolecules, nitroreduction is an important step. The intestinal microflora represents an enormous potential of bacterial nitroreductase activity. As a consequence, the in vivo nitroreduction of orally administered nitroarenes is primarily located in the intestine. In this study, we have investigated the nitroreduction of 2-nitrofluorene (2-NF) by a human microflora in female Wistar rats. Germ-free (GF) rats were equipped with a bacterial flora der...

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

    International Nuclear Information System (INIS)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  7. Sildenafil delays the intestinal transit of a liquid meal in awake rats

    Scientific Electronic Library Online (English)

    J.R.V, Graa; G.M, Macedo; R.C, Palheta Jr; F. de A.A, Gondim; R.O, Nogueira; J.M, Correia; F.H, Rola; R.B, Oliveira; M.A.N, Souza; A.A, Santos.

    2008-01-01

    Full Text Available Sildenafil slows down the gastric emptying of a liquid test meal in awake rats and inhibits the contractility of intestinal tissue strips. We studied the acute effects of sildenafil on in vivo intestinal transit in rats. Fasted, male albino rats (180-220 g, N = 44) were treated (0.2 mL, iv) with sil [...] denafil (4 mg/kg) or vehicle (0.01 N HCl). Ten minutes later they were fed a liquid test meal (99m technetium-labeled saline) injected directly into the duodenum. Twenty, 30 or 40 min after feeding, the rats were killed and transit throughout the gastrointestinal tract was evaluated by progression of the radiotracer using the geometric center method. The effect of sildenafil on mean arterial pressure (MAP) was monitored in a separate group of rats (N = 14). Data (medians within interquartile ranges) were compared by the Mann-Whitney U-test. The location of the geometric center was significantly more distal in vehicle-treated than in sildenafil-treated rats at 20, 30, and 40 min after test meal instillation (3.3 (3.0-3.6) vs 2.9 (2.7-3.1); 3.8 (3.4-4.0) vs 2.9 (2.5-3.1), and 4.3 (3.9-4.5) vs 3.4 (3.2-3.7), respectively; P

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

    Science.gov (United States)

    Determining the effect of selenium (Se) chemical form on uptake and transport in human intestinal cells is critical to assess Se bioavailability. In the present study, we measured the uptake and transport of various Se compounds in the human intestinal Caco-2 cell model. We found that two sources...

  9. Challenges of Culturing Human Norovirus in Three-Dimensional Organoid Intestinal Cell Culture Models

    OpenAIRE

    Papafragkou, Efstathia; Hewitt, Joanne; Park, Geun Woo; Greening, Gail; Vinje?, Jan

    2013-01-01

    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...

  10. Bioactive compounds in human milk and intestinal health and maturity in preterm newborn: an overview.

    Science.gov (United States)

    Garcia, C; Duan, R D; Brvaut-Malaty, V; Gire, C; Millet, V; Simeoni, U; Bernard, M; Armand, M

    2013-01-01

    Premature births are increasing worldwide (about 15 millions per year) due to several reasons (an advanced maternal age, fertility treatments, stress, smoking, nutritional deficiencies) and lead to a high societal overall cost. Among neonatal care procedures, the clinical nutrition practices are essential to promote the development and to minimize the sequelae. Premature newborns are at major risk of death by infections due to the immaturity of their intestine. Human milk provides not only nutrients but also a plethora of biologically active components that are tailored to contribute to the development of the intestinal tract early in postnatal life. Among them, some bioactive molecules exhibit trophic effects (LCPUFA, sphingomyelin, IGFI and IGFII, EGF, insulin, leptin, adiponectin, lactoferrin, lactadherin, probiotics, prebiotics, miRNA) or are part of the intestinal cell membranes (PUFA, LCPUFA, phospholipids, sphingolipids, cholesterol), others educate the intestine for innate microbial recognition (sCD14, sTLR2, miRNA), many of them display direct fighting against pathogens (some fatty acids and monoglycerides, some phospholipids and sphingolipids, BSSL, insulin, lactoferrin, sIgAs, MUC1, lactadherin, probiotics, prebiotics), or contribute to establish the gut microbiota (LCPUFA, lactoferrin, probiotics, prebiotics). A synergetic action exists between several bioactive molecules. All together these precious agents regulate the maturation of the intestinal mucosal barrier, and might program early in postnatal life the future adult intestinal health. This review lists the main bioactive compounds and addresses their plausible roles and mechanisms of action. PMID:25326648

  11. Effects of a new, concentrated wheat fibre preparation on intestinal transit, deoxycholic acid metabolism and the composition of bile.

    OpenAIRE

    Marcus, S N; Heaton, K W

    1986-01-01

    When the cholesterol saturation index of bile is reduced by wheat bran there is generally a fall in the deoxycholic acid content of bile. As the same effects occur with senna, bran might act on bile simply via its accelerating effect on colonic transit. We have studied the effects of a new, concentrated, wheat fibre preparation (Testa Triticum Tricum, Trifyba, which is 80% dietary fibre) upon bile composition, deoxycholic acid metabolism and intestinal transit time, and have assessed whether ...

  12. Evidence of native starch degradation with human small intestinal maltase-glucoamylase (recombinant)

    Science.gov (United States)

    Action of human small intestinal brush border carbohydrate digesting enzymes is thought to involve only final hydrolysis reactions of oligosaccharides to monosaccharides. In vitro starch digestibility assays use fungal amyloglucosidase to provide this function. In this study, recombinant N-terminal ...

  13. Retinol esterification by microsomes from the mucosa of human small intestine. Evidence for acyl-Coenzyme A retinol acyltransferase activity.

    OpenAIRE

    Helgerud, P.; Petersen, L. B.; Norum, K. R.

    1983-01-01

    The mechanism of the intestinal esterification of retinol has been obscure. Recently, an acyl-Coenzyme A (CoA):retinol acyltransferase (ARAT) was found in rat intestinal microsomes, and experiments were therefore conducted to determine whether a corresponding enzyme exists in human small intestine. When microsomes were incubated with [3H]retinol and palmitoyl-CoA, or retinol and [1-14C]palmitoyl-CoA, radioactive retinyl palmitate was formed as identified by alumina column chromatography and r...

  14. Electromagnetic radiation from ingested sources in the human intestine between 150 MHz and 1.2 GHz

    OpenAIRE

    Chirwa, L. C.; Hammond, P. A.; Roy, S.; Cumming, D. R. S.

    2003-01-01

    The conventional method of diagnosing disorders of the human gastro-intestinal (GI) tract is by sensors embedded in cannulae that are inserted through the anus, mouth, or nose. However, these cannulae cause significant patient discomfort and cannot be used in the small intestine. As a result, there is considerable ongoing work in developing wireless sensors that can be used in the small intestine. The radiation characteristics of sources in the GI tract cannot be readily calculated due to the...

  15. Progreso en el conocimiento de la microbiota intestinal humana / Progress in the knowledge of the intestinal human microbiota

    Scientific Electronic Library Online (English)

    Virginia, Robles-Alonso; Francisco, Guarner.

    2013-06-01

    Full Text Available La aparicin de nuevas tcnicas de secuenciacin as como el desarrollo de herramientas bioinformticas han permitido no slo describir la composicin de la comunidad bacteriana que habita el tracto gastrointestinal, sino tambin las funciones metablicas de las que proveen al husped. La mayora de [...] los miembros de esta amplia comunidad bacteriana pertenecen a Dominio Bacteria, aunque encontramos tambin Archaea y formas eucariotas y virus. nicamente entre 7 y 9 de las 55 Phyla del Dominio Bacteria conocidos estn presentes en flora fecal humana. Su mayora pertenecen adems a las Divisiones Bacteroidetes and Firmicutes, encontrando tambin Proteobacteria, Actinobacteria, Fusobacteria y Verrucomicrobia. Bacteroides, Faecalibacterium y Bifidobacterium son los Gneros ms abundantes aunque su abundancia relativa es muy variable entre individuos. El anlisis metagenmico de la flora intestinal ha permitido describir una coleccin de 5 millones de genes microbianos que codifican para aproximadamente 20.000 funciones biolgicas relacionadas con la vida de las bacterias. El ecosistema intestinal humano puede clasificarse en torno a tres grupos de acuerdo a la abundancia relativa de tres Gneros: Bacteroides (enterotipo 1), Prevotella (enterotipo 2) y Ruminococcus (enterotype 3). Estos grupos han sido denominados "enterotipos" y su descripcin sugiere que las variaciones entre individuos estn estratificadas. Una vez descrita la composicin bacteriana sera interesante establecer la relacin entre la alteracin de equilibrios ecolgicos con estados de enfermedad que puedan desembocar en una novedosa va teraputica. Abstract in english New sequencing technologies together with the development of bioinformatics allow a description of the full spectrum of the microbial communities that inhabit the human intestinal tract, as well as their functional contributions to host health. Most community members belong to the domain Bacteria, b [...] ut Archaea, Eukaryotes (yeasts and protists), and Viruses are also present. Only 7 to 9 of the 55 known divisions or phyla of the domain Bacteria are detected in faecal or mucosal samples from the human gut. Most taxa belong to just two divisions: Bacteroidetes and Firmicutes, and the other divisions that have been consistently found are Proteobacteria, Actinobacteria, Fusobacteria, and Verrucomicrobia. Bacteroides, Faecalibacterium and Bifidobacterium are the most abundant genera but their relative proportion is highly variable across individuals. Full metagenomic analysis has identified more than 5 million non-redundant microbial genes encoding up to 20,000 biological functions related with life in the intestinal habitat. The overall structure of predominant genera in the human gut can be assigned into three robust clusters, which are known as "enterotypes". Each of the three enterotypes is identifiable by the levels of one of three genera: Bacteroides (enterotype 1), Prevotella (enterotype 2) and Ruminococcus (enterotype 3). This suggests that microbiota variations across individuals are stratified, not continuous. Next steps include the identification of changes that may play a role in certain disease states. A better knowledge of the contributions of microbial symbionts to host health will help in the design of interventions to improve symbiosis and combat disease.

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

    Scientific Electronic Library Online (English)

    C., Yi; Y., Cao; S.R., Wang; Y.Z., Xu; H., Huang; Y.X., Cui; Y., Huang.

    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 g/L vs S1d: 0.74 0.12; S3d: 0.60 0.18 g/L; P

  17. Human small intestinal epithelial cells differentiated from adult intestinal stem cells as a novel system for predicting oral drug absorption in humans.

    Science.gov (United States)

    Takenaka, Toru; Harada, Naomoto; Kuze, Jiro; Chiba, Masato; Iwao, Takahiro; Matsunaga, Tamihide

    2014-11-01

    Adult intestinal stem cells (ISCs) possess both a long-term proliferation ability and differentiation capability into enterocytes. As a novel in vitro system for the evaluation of drug absorption, we characterized a human small intestinal epithelial cell (HIEC) monolayer that differentiated from adult ISCs. Continuous proliferation/differentiation from ISCs consistently conferred the capability of maturation of enterocytes to HIECs over 25 passages. The morphologically matured HIEC monolayer consisted of polarized columnar epithelia with dense microvilli, tight junctions, and desmosomes 8 days after seeding onto culture inserts. Transepithelial electrical resistance across the monolayer was 9-fold lower in HIECs (98.9 ? cm(2)) than in Caco-2 cells (900 ? cm(2)), which indicated that the looseness of the tight junctions in the HIEC monolayer was similar to that in the human small intestine (approximately 40 ? cm(2)). No significant differences were observed in the overall gene expression patterns of the major drug-metabolizing enzymes and transporters between the HIEC and Caco-2 cell monolayers. Furthermore, the functions of P-glycoprotein and breast cancer resistance protein in the HIEC monolayer were confirmed by the vectorial transport of marker substrates and their disappearance in the presence of specific inhibitors. The apparent drug permeability values of paracellularly transported compounds (fluorescein isothiocyanate-dextran 4000, atenolol, and terbutaline) and nucleoside transporter substrates (didanosine, ribavirin, and doxifluridine) in the HIEC monolayer were markedly higher than those of Caco-2 cells, whereas transcellularly transported drugs (pindolol and midazolam) were equally well permeated. In conclusion, the HIEC monolayer can serve as a novel and superior alternative to the conventional Caco-2 cell monolayer for predicting oral absorption in humans. PMID:25200868

  18. Diversity of halophilic archaea in fermented foods and human intestines and their application.

    Science.gov (United States)

    Lee, Han-Seung

    2013-12-01

    Archaea are prokaryotic organisms distinct from bacteria in the structural and molecular biological sense, and these microorganisms are known to thrive mostly at extreme environments. In particular, most studies on halophilic archaea have been focused on environmental and ecological researches. However, new species of halophilic archaea are being isolated and identified from high salt-fermented foods consumed by humans, and it has been found that various types of halophilic archaea exist in food products by culture-independent molecular biological methods. In addition, even if the numbers are not quite high, DNAs of various halophilic archaea are being detected in human intestines and much interest is given to their possible roles. This review aims to summarize the types and characteristics of halophilic archaea reported to be present in foods and human intestines and to discuss their application as well. PMID:24018967

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

    DEFF Research Database (Denmark)

    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 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.

  20. Nitroreduction and formation of hemoglobin adducts in rats with a human intestinal microflora.

    Science.gov (United States)

    Scheepers, P T; Straetemans, M M; Koopman, J P; Bos, R P

    1994-01-01

    In the covalent binding of nitroarenes to macromolecules, nitroreduction is an important step. The intestinal microflora represents an enormous potential of bacterial nitroreductase activity. As a consequence, the in vivo nitroreduction of orally administered nitroarenes is primarily located in the intestine. In this study, we have investigated the nitroreduction of 2-nitrofluorene (2-NF) by a human microflora in female Wistar rats. Germ-free (GF) rats were equipped with a bacterial flora derived from human feces. Nontreated GF rats and GF animals equipped with a conventional rat flora were used as controls. The composition of the human and the conventional microflora isolated from the rats were consistent with the microflora of the administered feces. In the rats receiving only sunflower seed oil, no adducts were detected. The animals equipped with a human or rat microflora that received 2-aminofluorene (2-AF) formed 2-AF hemoglobin (Hb)-adducts at average levels (mean +/- SEM) of 5.3 +/- 0.3 and 6.7 +/- 0.7 mumole/g Hb, respectively. After 2-NF administration, the adduct levels were 0.022 +/- 0.003 and 0.043 +/- 0.010 mumole/g Hb, respectively. In the GF rats, an adduct level of 0.57 +/- 0.09 was determined after 2-AF administration and no adducts were detected after 2-NF administration. The results show that nitroreduction by an acquired human intestinal microflora and subsequent adduct formation can be studied in the rat in vivo. PMID:7889856

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Immunomodulatory properties of Streptococcus and Veillonella isolates from the human small intestine microbiota.

    Science.gov (United States)

    van den Bogert, Bartholomeus; Meijerink, Marjolein; Zoetendal, Erwin G; Wells, Jerry M; Kleerebezem, Michiel

    2014-01-01

    The human small intestine is a key site for interactions between the intestinal microbiota and the mucosal immune system. Here we investigated the immunomodulatory properties of representative species of commonly dominant small-intestinal microbial communities, including six streptococcal strains (four Streptococcus salivarius, one S. equinus, one S. parasanguinis) one Veillonella parvula strain, one Enterococcus gallinarum strain, and Lactobacillus plantarum WCFS1 as a bench mark strain on human monocyte-derived dendritic cells. The different streptococci induced varying levels of the cytokines IL-8, TNF-?, and IL-12p70, while the V. parvula strain showed a strong capacity to induce IL-6. E. gallinarum strain was a potent inducer of cytokines and TLR2/6 signalling. As Streptococcus and Veillonella can potentially interact metabolically and frequently co-occur in ecosystems, immunomodulation by pair-wise combinations of strains were also tested for their combined immunomodulatory properties. Strain combinations induced cytokine responses in dendritic cells that differed from what might be expected on the basis of the results obtained with the individual strains. A combination of (some) streptococci with Veillonella appeared to negate IL-12p70 production, while augmenting IL-8, IL-6, IL-10, and TNF-? responses. This suggests that immunomodulation data obtained in vitro with individual strains are unlikely to adequately represent immune responses to mixtures of gut microbiota communities in vivo. Nevertheless, analysing the immune responses of strains representing the dominant species in the intestine may help to identify immunomodulatory mechanisms that influence immune homeostasis. PMID:25479553

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

    Science.gov (United States)

    Wang, Zhimin; Yang, Weng Lang; Jacob, Asha; Aziz, Monowar; Wang, Ping

    2015-01-01

    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. PMID:25671547

  4. Similarity of hydrolyzing activity of human and rat small intestinal disaccharidases

    Directory of Open Access Journals (Sweden)

    Oku T

    2011-06-01

    Full Text Available Tsuneyuki Oku, Kenichi Tanabe, Shigeharu Ogawa, Naoki Sadamori, Sadako NakamuraGraduate School of Human Health Science, University of Nagasaki, Siebold, Nagayo, Japan; Juzenkai Hospital, Kagomachi, Nagasaki, JapanBackground: The purpose of this study was to clarify whether it is possible to extrapolate results from studies of the hydrolyzing activity of disaccharidases from rats to humans.Materials and methods: We measured disaccharidase activity in humans and rats using identical preparation and assay methods, and investigated the similarity in hydrolyzing activity. Small intestinal samples without malignancy were donated by five patients who had undergone bladder tumor surgery, and homogenates were prepared to measure disaccharidase activity. Adult rat homogenates were prepared using small intestine.Results: Maltase activity was the highest among the five disaccharidases, followed by sucrase and then palatinase in humans and rats. Trehalase activity was slightly lower than that of palatinase in humans and was similar to that of sucrase in rats. Lactase activity was the lowest in humans, but was similar to that of palatinase in rats. Thus, the hydrolyzing activity of five disaccharidases was generally similar in humans and rats. The relative activity of sucrose and palatinase versus maltase was generally similar between humans and rats. The ratio of rat to human hydrolyzing activity of maltase, sucrase, and palatinase was 1.93.1, but this was not a significant difference. Leaf extract from Morus alba strongly inhibited the activity of maltase, sucrase, and palatinase, but not trehalase and lactase, and the degree of inhibition was similar in humans and rats. L-arabinose mildly inhibited sucrase activity, but hardly inhibited the activity of maltase, palatinase, trehalase and lactase in humans and rats. The digestibility of 1-kestose, galactosylsucrose, and panose by small intestinal enzymes was very similar between humans and rats.Conclusion: These results demonstrate that the digestibility of newly developed saccharide materials evaluated by rat small intestinal enzymes can substitute for evaluation using human enzymes.Keywords: disaccharidase, maltase, sucrase, trehalase, palatinase, digestibility

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

    DEFF Research Database (Denmark)

    Buhl, T; Thim, L

    1988-01-01

    Recent studies have revealed that the glucagon gene is expressed in the mammalian intestine. Here it codes for "glicentin" (proglucagon 1-69) and a glucagon-like peptide, proglucagon 78-107, recently isolated from porcine intestine. We studied the fate of the remaining COOH-terminal part of 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 structure of the naturally occurring human peptide.

  6. Transcriptome-wide Analysis Reveals Hallmarks of Human Intestine Development and Maturation InVitro and InVivo

    Science.gov (United States)

    Finkbeiner, StacyR.; Hill, DavidR.; Altheim, ChristopherH.; Dedhia, PriyaH.; Taylor, MatthewJ.; Tsai, Yu-Hwai; Chin, AlanaM.; Mahe, MaximeM.; Watson, CareyL.; Freeman, JenniferJ.; Nattiv, Roy; Thomson, Matthew; Klein, OphirD.; Shroyer, NoahF.; Helmrath, MichaelA.; Teitelbaum, DanielH.; Dempsey, PeterJ.; Spence, JasonR.

    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 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 inadult crypts. We validated our findings using invivo 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. PMID:26050928

  7. Transcriptome-wide Analysis Reveals Hallmarks of Human Intestine Development and Maturation InVitro and InVivo

    Directory of Open Access Journals (Sweden)

    StacyR. 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 inadult crypts. We validated our findings using invivo 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.

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

    International Nuclear Information System (INIS)

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

  9. Cytotoxic activity of human lymphocytes against differentiated intestinal tumour cell lines.

    Science.gov (United States)

    Anelli, R; Placido, R; Sambuy, Y; Bach, S; Di Massimo, A; Colizzi, V

    1993-01-01

    The natural killer (NK) and lymphokine-activated killer (LAK) cytotoxic activity of human peripheral blood lymphocytes (PBL) against various human tumour cell lines from intestinal origin (WIDR, HT29, Caco-2) has been investigated. The differentiated Caco-2 cells were then used as a model to investigate the cytotoxic activity against enterocyte-like target cells. Caco-2 were seeded on polycarbonate filters and maintained in culture for at least 15 days to allow the differentiation and formation of tight junctions. The integrity of tight junctions was assayed by measuring [3H]mannitol flux from apical to basolateral compartment. Cytotoxic analysis showed that both differentiated and undifferentiated Caco-2 cells were similarly susceptible to NK and LAK activity. The capacity of cytotoxic lymphocytes to kill enterocyte-like cells with intact junctional complex may suggest a direct role of cytotoxic lymphocytes in causing intestinal lesions under inflammatory conditions. PMID:8436403

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

    Science.gov (United States)

    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

  11. Human Rights and Transitional Societies: Contemporary Challenges

    DEFF Research Database (Denmark)

    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 generally, asserts how Judicial Defenders may have contributed to justice in other ways in post conflict Rwanda. The author argues that an efficient transitional justice policy must take sufficiently into account the context of the society in question, and aim at establishing linkages between justice in transitions and justice in the long-term.

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

    OpenAIRE

    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...

  13. Modulation of Chromatin Remodelling Induced by the Freshwater Cyanotoxin Cylindrospermopsin in Human Intestinal Caco-2 Cells

    OpenAIRE

    Huguet, Antoine; Hatton, Aure?lie; Villot, Romain; Quenault, He?le?ne; Blanchard, Yannick; Fessard, Vale?rie

    2014-01-01

    Cylindrospermopsin (CYN) is a cyanotoxin that has been recognised as an emerging potential public health risk. Although CYN toxicity has been demonstrated, the mechanisms involved have not been fully characterised. To identify some key pathways related to this toxicity, we studied the transcriptomic profile of human intestinal Caco-2 cells exposed to a sub-toxic concentration of CYN (1.6 M for 24hrs) using a non-targeted approach. CYN was shown to modulate different biological functions whi...

  14. Fermentation by the human large intestine microbial community in an in vitro semicontinuous culture system.

    OpenAIRE

    Miller, T L; Wolin, M J

    1981-01-01

    A semicontinuous culture of the microbial community of the human large intestine that was maintained over 81 days is described. The initial inoculum was feces, and about 200 ml of nutrient suspension was fed to 500 ml of fermentor contents once or twice daily. The nutrient suspension contained comminuted fibrous food, sodium deoxycholate, urea, acid-hydrolyzed casein, vitamins, and salts. The fermentation was monitored, and the major products were acetate, propionate, butyrate, methane, hydro...

  15. Ultrastructural study of adhesion of enterotoxigenic Escherichia coli to erythrocytes and human intestinal epithelial cells.

    OpenAIRE

    Knutton, S.; Lloyd, D. R.; Candy, D. C.; Mcneish, A. S.

    1984-01-01

    The adhesion to erythrocytes and human intestinal epithelial cells of enterotoxigenic Escherichia coli strains H10407, B2C, and H10407P, expressing colonization factor antigen I (CFA/I), CFA/II, and type 1 fimbriae, respectively, was examined by electron microscopy. CFA and type 1 fimbriae were visualized by negative staining in thin sections after en bloc staining with ruthenium red and by immune labeling with antisera raised against purified fimbriae. By negative and ruthenium red staining,...

  16. Analysis of diversity and function of the human small intestinal microbiota

    OpenAIRE

    Booijink, C. C. G. M.

    2009-01-01

    The gastrointestinal (GI) tract is the main site where the conversion and absorption of food components takes place in humans. As the small intestine is the first site of interaction between the microbiota and ingested food, knowledge about the microbial composition as well as functionality is essential for a complete understanding of the symbiotic interactions and to the potential modulation of metabolically important groups. Subjects carrying an ileostomy were chosen as model system and ile...

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

    OpenAIRE

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

    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 ...

  18. Stem cell biology and clonal expansion in normal and adenomatous human intestinal crypts

    OpenAIRE

    Humphries, A.

    2012-01-01

    Gastrointestinal cancer is thought to be primarily a disease of stem cells, whereby a tumorigenic stem cell clone can expand within an individual colonic crypt and then within the epithelium to form an adenoma - the pre-malignant lesion of the colon. However, data demonstrating stem cell populations and the dynamics of clonal expansion in human intestinal crypts is lacking. Naturally occurring, somatic clonal mutations in mitochondrial DNA were used to identify the progeny of a...

  19. Effect of broad-spectrum parenteral antibiotics on "colonization resistance" of intestinal microflora of humans.

    OpenAIRE

    Barza, M; Giuliano, M; Jacobus, N. V.; S. L. Gorbach

    1987-01-01

    Studies with animals have shown that the normal intestinal microflora protects against colonization by new strains ("colonization resistance") and that this protective effect may be related to the anaerobic component of the microflora. However, colonization resistance has not been shown in humans. We administered cefoxitin, piperacillin, cefoperazone, and aztreonam intravenously to healthy subjects for 9 days and monitored the acquisition of new isolates in the fecal flora. Seven of sixteen a...

  20. Mapping of liver-enriched transcription factors in the human intestine

    OpenAIRE

    Frank Lehner, Ulf Kulik, Juergen Klempnauer,Juergen Borlak

    2010-01-01

    AIM: To investigate the gene expression pattern of hepatocyte nuclear factor 6 (HNF6) and other liver-enriched transcription factors in various segments of the human intestine to better understand the differentiation of the gut epithelium.METHODS: Samples of healthy duodenum and jejunum were obtained from patients with pancreatic cancer whereas ileum and colon was obtained from patients undergoing right or left hemicolectomy or (recto)sigmoid or rectal resection. All surgical specimens were s...

  1. Development and characterization of a novel mouse line humanized for the intestinal peptide transporter PEPT1.

    Science.gov (United States)

    Hu, Yongjun; Xie, Yehua; Wang, Yuqing; Chen, Xiaomei; Smith, David E

    2014-10-01

    The proton-coupled oligopeptide transporter PEPT1 (SLC15A1) is abundantly expressed in the small intestine, but not colon, of mammals and found to mediate the uptake of di/tripeptides and peptide-like drugs from the intestinal lumen. However, species differences have been observed in both the expression (and localization) of PEPT1 and its substrate affinity. With this in mind, the objectives of this study were to develop a humanized PEPT1 mouse model (huPEPT1) and to characterize hPEPT1 expression and functional activity in the intestines. Thus, after generating huPEPT1 mice in animals previously nulled for mouse Pept1, phenotypic, PCR, and immunoblot analyses were performed, along with in situ single-pass intestinal perfusion and in vivo oral pharmacokinetic studies with a model dipeptide, glycylsarcosine (GlySar). Overall, the huPEPT1 mice had normal survival rates, fertility, litter size, gender distribution, and body weight. There was no obvious behavioral or pathological phenotype. The mRNA and protein profiles indicated that huPEPT1 mice had substantial PEPT1 expression in all regions of the small intestine (i.e., duodenum, jejunum, and ileum) along with low but measurable expression in both proximal and distal segments of the colon. In agreement with PEPT1 expression, the in situ permeability of GlySar in huPEPT1 mice was similar to but lower than wildtype animals in small intestine, and greater than wildtype mice in colon. However, a species difference existed in the in situ transport kinetics of jejunal PEPT1, in which the maximal flux and Michaelis constant of GlySar were reduced 7-fold and 2- to 4-fold, respectively, in huPEPT1 compared to wildtype mice. Still, the in vivo function of intestinal PEPT1 appeared fully restored (compared to Pept1 knockout mice) as indicated by the nearly identical pharmacokinetics and plasma concentration-time profiles following a 5.0 nmol/g oral dose of GlySar to huPEPT1 and wildtype mice. This study reports, for the first time, the development and characterization of mice humanized for PEPT1. This novel transgenic huPEPT1 mouse model should prove useful in examining the role, relevance, and regulation of PEPT1 in diet and disease, and in the drug discovery process. PMID:25148225

  2. Galectin fingerprints of DLD-1 human intestinal epithelial cell line.

    Czech Academy of Sciences Publication Activity Database

    Frolov, Lenka; Drastich, P.; Smetana, K.; Lensch, M.; Andr, S.; Kaltner, H.; Tlaskalov, Helena

    Sardinie : Porto conte research centre, 2006, s. 339-339. [ENII Mugen, Summer School in Advanced Immunology 2006. Capo Caccia (IT), 13.05.2006-20.05.2006] R&D Projects: GA ?R GD310/03/H147 Institutional research plan: CEZ:AV0Z50200510 Keywords : epithelial cell line * galectin s * human Subject RIV: EE - Microbiology, Virology

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

    Czech Academy of Sciences Publication Activity Database

    Smejkalov, P.; Petrelkov, Klra Judita; Pomajbkov, K.; Modr, David; ?epi?ka, I.

    2012-01-01

    Ro?. 139, ?. 1 (2012), s. 92-102. ISSN 0031-1820 R&D Projects: GA ?R 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

  4. Effects of human intestinal flora on mutagenicity of and DNA adduct formation from food and environmental mutagens.

    Science.gov (United States)

    Hirayama, K; Baranczewski, P; Akerlund, J E; Midtvedt, T; Mller, L; Rafter, J

    2000-11-01

    Although the intestinal flora is believed to have a critical role in carcinogenesis, little is known about the role of the human intestinal flora on the effects of mutagens in vivo. The aim of the present study was to address a possible role of the human intestinal flora in carcinogenesis, by exploiting human-flora-associated (HFA) mice. The capacity of human faeces to activate or inactivate 2-amino-3-methyl-3H:-imidazo[4,5-f]quinoline (IQ) and 2-nitrofluorene was determined using the Ames assay. Human faecal suspensions that were active in this regard were then selected and orally inoculated into germfree NMRI mice to generate HFA mice. HFA, germfree, conventionalized and conventional mice were administered IQ, 2-amino-9H:-pyrido[2,3-b]indole (2-amino-alpha-carboline; AAC) and 2-nitrofluorene. The activity of human intestinal flora against mutagens could be transferred into the mice. In comparing germfree mice and mice harbouring an intestinal flora, the presence of a flora was essential for the activities of faeces against mutagens. After administration of IQ and 2-nitrofluorene, DNA adducts were observed in the mice with a flora, while adducts were extremely low or absent in germfree animals. DNA adducts after AAC treatment were higher in germfree mice in some tissues including colon than in mice with bacteria. Differences in DNA adduct formation were also observed between HFA mice and mice with mouse flora in many tissues. These results clearly indicate that the intestinal flora have an active role in DNA adduct formation and that the role is different for the different chemicals to which the animals are exposed. The results also demonstrate that the human intestinal flora have different effects from the mouse flora on DNA adduct formation as well as in vitro metabolic activities against mutagens. Studies using HFA mice could thus provide much-needed information on the role of the human intestinal flora on carcinogenesis in vivo. PMID:11062175

  5. Analysis of small intestinal transit and colon arrival times of non-disintegrating tablets administered in the fasted state.

    Science.gov (United States)

    Pilar, Mitja; Brelih, Hana; Mrhar, Ale; Bogataj, Marija

    2015-07-30

    In this study individual data on tablet gastrointestinal transit times (i.e. gastric emptying, small intestinal transit, ileocecal junction residence, and colon arrival times) were obtained from literature in order to present and analyze their distributions and relationships. The influence of the time of food intake after tablet administration in fasted state on gastrointestinal transit times was additionally evaluated. There were 114 measurements from subjects who received the first meal at 4h after tablet administration. Approximately 32% of the tablets arrived into the colon before the meal intake at 4h. An evident increase in the frequency of colon arrival of tablets within 40min after the meal intake at 4h post-dose was observed, where approximately 39% of all tablets arrived into the colon. This is in accordance with findings described in literature where a meal ingested several hours post-dose accelerates tablet transit through the terminal ileum and shortens the transit through the small intestine. The median (min, max) of gastric emptying, small intestinal transit, and colon arrival times in the group where the first meal intake was at 4h post-dose is 35 (0,192), 215 (60,544), and 254 (117,604) minutes, respectively. The dependence of colon arrival times on gastric emptying times was described by the nonparametric regression curve, and compared with the presumed interval of colon arrival times, calculated by summation of observed gastric emptying times and frequently cited small intestinal transit time interval, i.e. 3-4h. For shorter gastric emptying times the trend of colon arrival times was within the presumed interval. At short gastric emptying times many observation points are also within the presumed interval since this interval coincides with short period after meal intake at 4h post-dose. Additionally, in numerous occasions relatively long ileocecal junction residence times were obtained, which may be important information from the point of view of drug absorption. The findings of gastrointestinal transit times are important and should be taken into consideration when predicting the in vivo performance of dosage forms after oral administration. PMID:25769525

  6. Intestinal Coccidia

    OpenAIRE

    Mj, Ggaravi

    2007-01-01

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

  7. Subversion of human intestinal mucosa innate immunity by a Crohn's disease-associated E. coli.

    Science.gov (United States)

    Jarry, A; Crmet, L; Caroff, N; Bou-Hanna, C; Mussini, J M; Reynaud, A; Servin, A L; Mosnier, J F; Livin-Le Moal, V; Laboisse, C L

    2015-05-01

    Adherent-invasive Escherichia coli (AIEC), associated with Crohn's disease, are likely candidate contributory factors in the disease. However, signaling pathways involved in human intestinal mucosa innate host response to AIEC remain unknown. Here we use a 3D model of human intestinal mucosa explant culture to explore the effects of the AIEC strain LF82 on two innate immunity platforms, i.e., the inflammasome through evaluation of caspase-1 status, and NF?B signaling. We showed that LF82 bacteria enter and survive within a few intestinal epithelial cells and macrophages, without altering the mucosa overall architecture. Although 4-h infection with a Salmonella strain caused crypt disorganization, caspase-1 activation, and mature IL-18 production, LF82 bacteria were unable to activate caspase-1 and induce IL-18 production. In parallel, LF82 bacteria activated NF?B signaling in epithelial cells through I?B? phosphorylation, NF?Bp65 nuclear translocation, and TNF? secretion. In addition, NF?B activation was crucial for the maintenance of epithelial homeostasis upon LF82 infection. In conclusion, here we decipher at the whole-mucosa level the mechanisms of the LF82-induced subversion of innate immunity that, by maintaining host cell integrity, ensure intracellular bacteria survival. PMID:25269707

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

    Science.gov (United States)

    Couvigny, Benot; de Wouters, Tomas; Kaci, Ghalia; Jacouton, Elsa; Delorme, Christine; Dor, Jol; Renault, Pierre; Blottire, Herv M; Gudon, 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-?B) 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 PPAR? (peroxisome proliferator-activated receptor), we used human intestinal epithelial cell-lines engineered to monitor PPAR? 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 PPAR? 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 PPAR?-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. Human intestinal acyl-CoA synthetase 5 is sensitive to the inhibitor triacsin C

    Directory of Open Access Journals (Sweden)

    Elke Kaemmerer

    2011-01-01

    Full Text Available AIM: To investigate whether human acyl-CoA synthetase 5 (ACSL5 is sensitive to the ACSL inhibitor triacsin C. METHODS: The ACSL isoforms ACSL1 and ACSL5 from rat as well as human ACSL5 were cloned and recombinantly expressed as 6xHis-tagged enzymes. Ni2+-affinity purified recombinant enzymes were assayed at pH 7.5 or pH 9.5 in the presence or absence of triacsin C. In addition, ACSL5 transfected CaCo2 cells and intestinal human mucosa were monitored. ACSL5 expression in cellular systems was verified using Western blot and immunofluorescence. The ACSL assay mix included TrisHCl (pH 7.4, ATP, CoA, EDTA, DTT, MgCl2, [9,10-3H] palmitic acid, and triton X-100. The 200 ?L reaction was initiated with the addition of solubilized, purified recombinant proteins or cellular lysates. Reactions were terminated after 10, 30 or 60 min of incubation with Doles medium. RESULTS: Expression of soluble recombinant ACSL proteins was found after incubation with isopropyl beta-D-1-thiogalactopyranoside and after ultracentrifugation these were further purified to near homogeneity with Ni2+-affinity chromatography. Triacsin C selectively and strongly inhibited recombinant human ACSL5 protein at pH 7.5 and pH 9.5, as well as recombinant rat ACSL1 (sensitive control, but not recombinant rat ACSL5 (insensitive control. The IC50 for human ACSL5 was about 10 ?mol/L. The inhibitory triacsin C effect was similar for different incubation times (10, 30 and 60 min and was not modified by the N- or C-terminal location of the 6xHis-tag. In order to evaluate ACSL5 sensitivity to triacsin C in a cellular environment, stable human ACSL5 CaCo2 transfectants and mechanically dissected normal human intestinal mucosa with high physiological expression of ACSL5 were analyzed. In both models, ACSL5 peak activity was found at pH 7.5 and pH 9.5, corresponding to the properties of recombinant human ACSL5 protein. In the presence of triacsin C (25 ?mol/L, total ACSL activity was dramatically diminished in human ACSL5 transfectants as well as in ACSL5-rich human intestinal mucosa. CONCLUSION: The data strongly indicate that human ACSL5 is sensitive to triacsin C and does not compensate for other triacsin C-sensitive ACSL isoforms.

  10. Scintigraphic determination of small intestinal transit time of water in man

    International Nuclear Information System (INIS)

    A method utilizing a lactulose solution to measure small intestinal transit time (SITT) has been previously reported. Lactulose is a non-absorbable sugar and is known to increase SITT. In order to determine the extent to which lactulose accelerates SITT, a group of 4 normal male volunteers were studied after the ingestion of 150cc of water to which 100 uCi of 111-In was added. To provide adequate caloric intake, as occurs physiologically, the water was drunk while ingesting a solid meal. The subject was then placed supine under a 15 inch gamma camera. Data were collected and stored in a computer at one frame every 3 minute for 240 minutes. If activity was not present in the cecal region by this time, the subject was allowed to move about for 15 minutes and then repositioned under the gamma camera. Data were first viewed in a movie format. 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 SITT. Each subject was studied on three separate occasions. The mean (+- SEM) SITT for each of the separate studies was 248 +- 58 min., 240 +- 47 min. and 232 +- 54 min. respectively (p?NS). Two previously studied groups of normal volunteers had a mean SITT of approximately 80 minutes. Water appears to have a significantly slower SITT when ingested with a solid meal when compared to lactulose. Clinically, the potential to use water as a test for SITT would not seem to be as attractive or practical as using lactulose as the test substance

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

    DEFF Research Database (Denmark)

    Ito, Go; Okamoto, Ryuichi

    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, remains largely unknown. Here, we show that BEST2 and BEST4 are expressed in vivo, each in a distinct, lineage-specific manner, in human IECs. While BEST2 was expressed exclusively in colonic goblet cells, BEST4 was expressed in the absorptive cells of both the small intestine and the colon. In addition, we found that BEST2 expression is significantly down-regulated in the active lesions of ulcerative colitis, where goblet cells were depleted, suggesting that BEST2 expression is restricted to goblet cells under both normal and pathologic conditions. Consistently, the induction of goblet cell differentiation by a Notch inhibitor, LY411575, significantly up-regulated the expression of not BEST4 but BEST2 in MUC2-positive HT-29 cells. Conversely, the induction of absorptive cell differentiation up-regulated the expression of BEST4 in villin-positive Caco-2 cells. In addition, we found that the up- or down-regulation of Notch activity leads to the preferential expression of either BEST4 or BEST2, respectively, in LS174T cells. These results collectively confirmed that BEST2 and BEST4 could be added to the lineage-specific genes of humans IECs due to their abilities to clearly identify goblet cells of colonic origin and a distinct subset of absorptive cells, respectively.

  12. Limited Expression of APRIL and its Receptors Prior to Intestinal IgA Plasma Cell Development During Human Infancy

    OpenAIRE

    Gustafson, Claire E.; Higbee, Dana; Yeckes, Alyson R.; Wilson, Cara C.; Zoeten, Edwin F.; Jedlicka, Paul; Janoff, Edward N.

    2013-01-01

    The absence of immunoglobulin A (IgA) in the intestinal tract renders young infants highly susceptible to enteric infections. However, mediators of initial IgA induction in this population are undefined. We determined the temporal acquisition of plasma cells by isotype and expression of T cell-independent (TI) and -dependent (TD) IgA class switch factors in the human intestinal tract during early infancy. We found that IgA plasma cells were largely absent in the infant intestine until after o...

  13. Human ?2-glycoprotein I attenuates mouse intestinal ischemia/reperfusion induced injury and inflammation.

    Science.gov (United States)

    Tomasi, Maurizio; Hiromasa, Yasuaki; Pope, Michael R; Gudlur, Sushanth; Tomich, John M; Fleming, Sherry D

    2012-10-01

    Intestinal ischemia-reperfusion (IR)-induced injury results from a complex cascade of inflammatory components. In the mouse model of intestinal IR, the serum protein, ?2-glycoprotein I (?2-GPI) binds to the cell surface early in the cascade. The bound ?2-GPI undergoes a conformational change which exposes a neoantigen recognized by naturally occurring antibodies and initiates the complement cascade. We hypothesized that providing additional antigen with exogenous ?2-GPI would alter IR-induced tissue injury. Administration of human but not mouse ?2-GPI attenuated IR-induced tissue damage and prostaglandin E(2) production indicating a physiological difference between ?2-GPI isolated from the two species. To investigate whether structural features were responsible for this physiological difference, we compared the chemical, physical and biochemical properties of the two proteins. Despite possessing 76% amino acid identity and 86% sequence homology, we found that mouse ?2-GPI differs from the human protein in size, carbohydrate chain location, heterogeneity and secondary structural content. These data suggest that the structural differences result in mouse Ab recognition of soluble human but not mouse ?2-GPI and attenuated IR-induced injury. We conclude that caution should be exercised in interpreting results obtained by using human ?2-GPI in a mouse model. PMID:22750067

  14. In Vitro Modulation of Human Intestinal Microbiota by Mannoligosaccharides Synthesized from Amorphophallus muelleri Glucomannan

    Directory of Open Access Journals (Sweden)

    ACHMAD DINOTO

    2013-11-01

    Full Text Available The corms of Amorphophallus muelleri Blume contain a large amount of glucomannan, a kind of polysaccharide that are commonly consumed by people as gelly foods. In order to improve the beneficial properties of glucomannan, we previously have established the enzymatic process to produce the mannoligosaccharides from flour of glucomannan using microbial mannanase. The effects of mannoligosaccharides on the growth modulation of human intestinal microbiota were investigated in this study. A set of in vitro single batch culture experiment was conducted to study the effect of mannooligosaccharides on human-origin Lactobacillus fermentum AA0014 and Lactobacillus plantarum FU0811. A modified MRS medium containing 10% (w/v sucrose, glucomannan, and mannoligosaccharide was used instead of glucose as carbon source. The results showed the highest growth rate (0.13 h-1 with both L. fermentum AA0014 and L. plantarum FU0811 in the presence of mannooligosaccharides. We confirmed this result by a similar in vitro experiment using human fecal samples of six healthy adults as innocula and analyzed the microbial population by fluorescence in situ hybridization (FISH. Lactobacilli were proliferated higher in the presence of mannoligosaccharide than other carbon sources, yielding the microbial proportion as much of 10.9% of total microbiota. Overall, this study demonstrated the potential use of mannoligosaccharides synthesized from A. muelleri glucomannan as prebiotic candidate of modulating the beneficial human intestinal microbiota.

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

    DEFF Research Database (Denmark)

    Jackson, Robert S; Creemers, John W M

    2003-01-01

    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 heterozygosity for novel missense and nonsense mutations. While both subjects shared the phenotypes of obesity, hypoadrenalism, reactive hypoglycemia, and elevated circulating levels of certain prohormones, the clinical presentation of Subject B was dominated by severe refractory neonatal diarrhea, malabsorptive 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 differences in the nature and severity of presentation between the two cases cannot readily be explained on the basis of allelic heterogeneity, as the nonsense and missense mutations from both subjects had comparably severe effects on the catalytic activity of PC1. Despite Subject A's negligible PC1 activity, 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 markedly with the phenotype of mice lacking PC1 and suggest that the precise physiological repertoire of this enzyme may vary between mammalian species.

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

    Directory of Open Access Journals (Sweden)

    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 g/L vs S1d: 0.74 0.12; S3d: 0.60 0.18 g/L; P < 0.05 and IGF-1 (T1d: 168.94 65.67; T3d: 201.56 64.98 g/L vs S1d: 116.72 13.96; S3d: 107.50 23.53 g/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.

  17. CfaE tip mutations in enterotoxigenic Escherichia coli CFA/I fimbriae define critical human intestinal binding sites

    OpenAIRE

    Baker, K. K.; Levine, M. M.; Morison, J.; Phillips, A.; Barry, E. M.

    2009-01-01

    Enterotoxigenic Escherichia coli (ETEC) use colonization factors to attach to the human intestinal mucosa, followed by enterotoxin expression that induces net secretion and diarrhoeal illness. ETEC strain H10407 expresses CFA/I fimbriae, which are composed of multiple CfaB structural subunits and a CfaE tip subunit. Currently, the contribution of these individual fimbrial subunits in intestinal binding remains incompletely defined. To identify the role of CfaE in attachment in the native ETEC...

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

    International Nuclear Information System (INIS)

    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

  19. Intestinal parasite co-infection among pulmonary tuberculosis cases without human immunodeficiency virus infection in a rural county in China.

    Science.gov (United States)

    Li, Xin-Xu; Chen, Jia-Xu; Wang, Li-Xia; Tian, Li-Guang; Zhang, Yu-Ping; Dong, Shuang-Pin; Hu, Xue-Guang; Liu, Jian; Wang, Feng-Feng; Wang, Yue; Yin, Xiao-Mei; He, Li-Jun; Yan, Qiu-Ye; Zhang, Hong-Wei; Xu, Bian-Li; Zhou, Xiao-Nong

    2014-01-01

    Epidemiologic studies of co-infection with tuberculosis (TB) and intestinal parasites in humans have not been extensively investigated in China. A cross-section study was conducted in a rural county of Henan Province, China. Pulmonary TB (PTB) case-patients receiving treatment for infection with Mycobacterium tuberculosis and healthy controls matched for geographic area, age, and sex were surveyed by using questionnaires. Fecal and blood specimens were collected for detection of intestinal parasites, routine blood examination, and infection with human immunodeficiency virus. The chi-square test was used for univariate analysis and multivariate logistic regression models were used to adjust for potential confounding factors. A total of 369 persons with PTB and 366 healthy controls were included; all participants were negative for human immunodeficiency virus. The overall prevalence of intestinal parasites in persons with PTB was 14.9%, including intestinal protozoa (7.9%) and helminthes (7.6%). The infection spectrum of intestinal parasites was Entamoeba spp. (1.4%), Blastocystis hominis (6.2%), Trichomonas hominis (0.3%), Clonorchis sinensis (0.3%), Ascaris lumbricoides (0.5%), Trichuris trichiura (2.2%), and hookworm (4.6%). The prevalence of intestinal parasites showed no significant difference between persons with PTB and healthy controls after adjusting for potential confounding factors. There was no factor that affected infection rates for intestinal parasites between the two groups. Infection with intestinal parasites of persons with PTB was associated with female sex (adjusted odds ratio [AOR] = 2.05, 95% confidence interval [CI] = 1.01-4.17), body mass index ? 19 (AOR = 3.02, 95% CI = 1.47-6.20), and anemia (AOR = 2.43, 95% CI = 1.17-5.03). Infection of healthy controls was only associated with an annual labor time in farmlands > 2 months (AOR = 4.50, 95% CI = 2.03-10.00). In addition, there was no significant trend between rates of infection with intestinal parasites and duration of receiving treatment for infection with M. tuberculosis in persons with PTB. The prevalence of intestinal parasites was not higher in persons with PTB, and there was no evidence that PTB increased susceptibility to intestinal parasites in this study. However, for patients with PTB, women and patients with comorbidities were more likely to be infected with intestinal parasites. PMID:24166044

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

    Science.gov (United States)

    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. Human in vivo regional intestinal permeability: importance for pharmaceutical drug development.

    Science.gov (United States)

    Lennerns, Hans

    2014-01-01

    Both the development and regulation of pharmaceutical dosage forms have undergone significant improvements and development over the past 25 years, due primarily to the extensive application of the biopharmaceutical classification system (BCS). The Biopharmaceutics Drug Disposition Classification System, which was published in 2005, has also been a useful resource for predicting the influence of transporters in several pharmacokinetic processes. However, there remains a need for the pharmaceutical industry to develop reliable in vitro/in vivo correlations and in silico methods for predicting the rate and extent of complex gastrointestinal (GI) absorption, the bioavailability, and the plasma concentration-time curves for orally administered drug products. Accordingly, a more rational approach is required, one in which high quality in vitro or in silico characterizations of active pharmaceutical ingredients and formulations are integrated into physiologically based in silico biopharmaceutics models to capture the full complexity of GI drug absorption. The need for better understanding of the in vivo GI process has recently become evident after an unsuccessful attempt to predict the GI absorption of BCS class II and IV drugs. Reliable data on the in vivo permeability of the human intestine (Peff) from various intestinal regions is recognized as one of the key biopharmaceutical requirements when developing in silico GI biopharmaceutics models with improved predictive accuracy. The Peff values for human jejunum and ileum, based on historical open, single-pass, perfusion studies are presented in this review. The main objective of this review is to summarize and discuss the relevance and current status of these human in vivo regional intestinal permeability values. PMID:24206063

  2. Capsaicin-enhanced Ribosomal Protein P2 Expression in Human Intestinal Caco-2 Cells

    OpenAIRE

    Han, Junkyu; Akutsu, Mitsuaki; Talorete, Terence P. N.; Maekawa, Takaaki; Tanaka, Toshiyuki; Isoda, Hiroko

    2005-01-01

    On the basis of transepithelial electrical resistance (TER) measurements, we found that capsaicin (100?M)-treated human intestinal Caco-2 cells show a momentary increase in tight-junction (TJ) permeability (decrease in TER) followed by a complete recovery. We used proteome analysis to search for proteins that are associated with the recovery of TJ permeability in capsaicin-treated Caco-2 cells. A protein with a relative molecular mass of 14kDa was found to be expressed more highly in capsai...

  3. Ultrastructure of interstitial cells of Cajal associated with deep muscular plexus of human small intestine

    DEFF Research Database (Denmark)

    Rumessen, J J; Mikkelsen, H B

    1992-01-01

    Evidence showing that interstitial cells of Cajal have important regulatory functions in the gut musculature is accumulating. In the current study, the ultrastructure of the deep muscular plexus and associated interstial cells of Cajal in human small intestine were studied to provide a reference for identification and further physiological or pathological studies. The deep muscular plexus was sandwiched between a thin inner layer of smooth muscle (one to five cells thick) and the bulk of the circular muscle. Interstitial cells of Cajal in this region very much resembled smooth muscle cells (with a continuous basal lamina, caveolae, intermediate filaments, dense bodies, dense bands, and a well-developed subsurface smooth endoplasmic reticulum), but the arrangement of organelles was clearly different, and cisternae of granular endoplasmic reticulum were abundant. Interstitial cells of Cajal were distinguished from fibroblasts or macrophages in the region. They ramified in the inner zone of the outer division ofcircular muscle, penetrated the inner-most circular layer, and were also found at the submucosal border. They were in close, synapselike contact with nerve terminals of the deep muscular plexus, and only few gap junctions with other interstitial cells of Cajal or with the musculature were observed. Compared with interstitial cells of Cajal from other mammals, those associated with the deep muscular plexus in the human small intestine more closely resemble smooth muscle cells, and their organization appears more diffuse; however, the ultrastructure and organization of interstitial cells of Cajal is compatible with modulatory actions on the circular muscle also in humans.

  4. Probiotic supplementation decreases intestinal transit time: Meta-analysis of randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Larry E Miller

    2013-01-01

    Full Text Available AIM: To determine the efficacy of probiotic supplementation on intestinal transit time (ITT and to identify factors that influence these outcomes. METHODS: A systematic review of randomized controlled trials (RCTs of probiotic supplementation that measured ITT in adults was conducted by searching MEDLINE and EMBASE using relevant key word combinations. Main search limits included RCTs of probiotic supplementation in healthy or constipated adults that measured ITT. Study quality was assessed using the Jadad scale. A random effects meta-analysis was performed with standardized mean difference (SMD of ITT between probiotic and control groups as the primary outcome. Meta-regression and subgroup analyses were conducted to examine the impact of moderator variables on ITT SMD. RESULTS: A total of 11 clinical trials with 13 treatment effects representing 464 subjects were included in this analysis. Probiotic supplementation was associated with decreased ITT in relation to controls, with an SMD of 0.40 (95%CI: 0.20-0.59, P < 0.001. Constipation (r2 = 39%, P = 0.01, higher mean age (r2 = 27%, P = 0.03, and higher percentage of female subjects (r2 = 23%, P < 0.05 were predictive of decreased ITT with probiotics in meta-regression. Subgroup analyses demonstrated statistically greater reductions in ITT with probiotics in subjects with vs without constipation and in older vs younger subjects [both SMD: 0.59 (95%CI: 0.39-0.79 vs 0.17 (95%CI: -0.08-0.42, P = 0.01]. Medium to large treatment effects were identified with Bifidobacterium Lactis (B. lactis HN019 (SMD: 0.72, 95%CI: 0.27-1.18, P < 0.01 and B. lactis DN-173 010 (SMD: 0.54, 95%CI: 0.15-0.94, P < 0.01 while other single strains and combination products yielded small treatment effects. CONCLUSION: Overall, short-term probiotic supplementation decreases ITT with consistently greater treatment effects identified in constipated or older adults and with certain probiotic strains.

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

    Science.gov (United States)

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

    2010-02-01

    Experiments with rats have produced data on the metabolism and energy value of d-psicose; however, no such data have been obtained in humans. The authors assessed the availability of d-psicose absorbed in the small intestine by measuring carbohydrate energy expenditure (CEE) by indirect calorimetry. They measured the urinary excretion rate by quantifying d-psicose in urine for 48 hours. To examine d-psicose fermentation in the large intestine, the authors measured breath hydrogen gas and fermentability using 35 strains of intestinal bacteria. Six healthy subjects participated in the CEE test, and 14 participated in breath hydrogen gas and urine tests. d-Psicose fermentation subsequent to an 8-week adaptation period was also assessed by measuring hydrogen gas in 8 subjects. d-Psicose absorbed in the small intestine was not metabolized into energy, unlike glucose, because CEE did not increase within 3 hours of d-psicose ingestion (0.35 g/kg body weight [BW]). The accumulated d-psicose urinary excretion rates were around 70% for 0.34, 0.17, and 0.08 g/kg BW of ingested d-psicose. Low d-psicose fermentability was observed in intestinal bacteria and breath hydrogen gas tests, in which fructooligosaccharide (0.34, 0.17, and 0.08 g/kg BW) was used as a positive control because its available energy is known to be 8.4 kJ/g. Based on the results of the plot of breath hydrogen concentration vs calories ingested, the energy value of d-psicose was expected to be less than 1.6 kJ/g. Incremental d-psicose fermentability subsequent to an adaptation period was not observed. PMID:19765780

  6. Climate change, human health, and epidemiological transition.

    Science.gov (United States)

    Barrett, Bruce; Charles, Joel W; Temte, Jonathan L

    2015-01-01

    The health of populations depends on the availability of clean air, water, food, and sanitation, exposure to pathogens, toxins and environmental hazards, and numerous genetic, behavioral and social factors. For many thousands of years, human life expectancy was low, and population growth was slow. The development of technology-based civilizations facilitated what Abdel Omran called "epidemiological transition," with increasing life expectancy and rapid population growth. To a large extent, the spectacular growth of human populations during the past two centuries was made possible by the energy extracted from fossil fuels. We have now learned, however, that greenhouse gases from fossil fuel combustion are warming the planet's surface, causing changes in oceanic and atmospheric systems, and disrupting weather and hydrological patterns. Climate change poses unprecedented threats to human health by impacts on food and water security, heat waves and droughts, violent storms, infectious disease, and rising sea levels. Whether or not humanity can reduce greenhouse gas emissions quickly enough to slow climate change to a rate that will allow societies to successfully adapt is not yet known. This essay reviews the current state of relevant knowledge, and points in a few directions that those interested in human health may wish to consider. PMID:25434735

  7. Human hippocampal activation during transitive inference.

    Science.gov (United States)

    Nagode, Jennifer C; Pardo, Jos V

    2002-05-24

    The medial temporal lobe contains multiple structures whose mnemonic operations need further delineation. One model posits the function of the hippocampus as a relational binder, collaborating with overlying cortices that perform encoding and retrieval operations. For instance, lesions of the hippocampus leave intact the learning of paired-associates while impairing the ability to synthesize information across pairs. We test this relational model with two PET studies of normal humans during a transitive inference task using faces that either have or lack relationships across the stimulus pairs. Both studies converge to support a relational processing model of hippocampal function. PMID:12004195

  8. Description of urolithin production capacity from ellagic acid of two human intestinal Gordonibacter species.

    Science.gov (United States)

    Selma, Mara V; Beltrn, David; Garca-Villalba, Roco; Espn, Juan C; Toms-Barbern, Francisco A

    2014-08-01

    Ellagitannin and ellagic acid metabolism to urolithins in the gut shows a large human interindividual variability and this has been associated with differences in the colon microbiota. In the present study we describe the isolation of one urolithin-producing strain from the human faeces of a healthy volunteer and the ellagic acid transformation to different urolithin metabolites by two species of intestinal bacteria. The isolate belongs to a new species described as Gordonibacter urolithinfaciens, sp. nov. The type strain of the Gordonibacter genus, Gordonibacter pamelaeae DSM 19378(T), was also demonstrated to produce urolithins. Both human intestinal bacteria grew similarly in the presence and absence of ellagic acid at 30 ?M concentration. Ellagic acid catabolism and urolithin formation occurred during the stationary phase of the growth of the bacteria under anaerobic conditions. The HPLC-MS analyses showed the sequential production of pentahydroxy-urolithin (urolithin M-5), tetrahydroxy-urolithin (urolithin M-6) and trihydroxy-urolithin (urolithin C), while dihydroxy-urolithins (urolithin A and isourolithin A), and monohydroxy-urolithin (urolithin B) were not produced in pure cultures. Consequently, either other bacteria from the gut or the physiological conditions found in vivo are necessary for completing metabolism until the final urolithins (dihydroxy and monohydroxy urolithins) are produced. This is the first time that the urolithin production capacity of pure strains has been demonstrated. The identification of the urolithin-producing bacteria is a relevant outcome as urolithin implication in health (cardiovascular protection, anti-inflammatory and anticarcinogenic properties) has been supported by different bioassays and urolithins can be used in the development of functional foods and nutraceuticals. This study represents an initial work that opens interesting possibilities of describing enzymatic activities involved in urolithin production that can help in understanding both the human interindividual differences in polyphenol metabolism, the microbial pathways involved, and the role of polyphenols in human health. The presence of urolithin producing bacteria can indirectly affect the health benefits of ellagitannin consumption. PMID:24909569

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

    Science.gov (United States)

    Christides, Tatiana; Sharp, Paul

    2013-01-01

    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. PMID:24340076

  10. Molecular mechanisms involved in the adaptive regulation of human intestinal biotin uptake: A study of the hSMVT system.

    Science.gov (United States)

    Reidling, Jack C; Nabokina, Svetlana M; Said, Hamid M

    2007-01-01

    Biotin, a water-soluble micronutrient, is vital for cellular functions, including growth and development. The human intestine utilizes the human sodium-dependent multivitamin transporter (hSMVT) for biotin uptake. Evidence exists showing that the intestinal biotin uptake process is adaptively regulated during biotin deficiency. Nothing, however, is known about molecular mechanism(s) involved during this adaptive regulation. This study compared two human-derived intestinal epithelial cell lines (HuTu-80 and Caco-2) during biotin-deficient or biotin-sufficient states and with an approach that assessed carrier-mediated biotin uptake, hSMVT protein and RNA levels, RNA stability, and hSMVT promoter activity. The results showed that during biotin deficiency, a significant and specific upregulation in carrier-mediated biotin uptake occurred in both human intestinal epithelial cell lines and that this increase was associated with an induction in protein and mRNA levels of hSMVT. The increase in mRNA levels was not due to an increase in RNA stability but was associated with an increase in activity of the hSMVT promoter in transfected human intestinal cells. Using promoter deletion constructs and mutational analysis in transiently transfected HuTu-80 and Caco-2 cells, a biotin deficiency-responsive region was mapped to a 103-bp area within the hSMVT promoter that contains gut-enriched Kruppel-like factor (GKLF) sites that confer the response to biotin deficiency. These results confirm that human intestinal biotin uptake is adaptively regulated and provide novel evidence demonstrating that the upregulation is not mediated via changes in hSMVT RNA stability but rather is due to transcriptional regulatory mechanism(s) that likely involve GKLF sites in the hSMVT promoter. PMID:16959947

  11. Biotransformation of luteoloside by a newly isolated human intestinal bacterium using UHPLC-Q-TOF/MS.

    Science.gov (United States)

    Tao, Jin-Hua; Wang, Dong-Geng; Yang, Chi; Huang, Jin-Hua; Qiu, Wen-Qian; Zhao, Xi

    2015-06-01

    To explore the metabolic pathways and metabolites of luteoloside yielded by the isolated human intestinal bacteria from healthy human feces and characterize the ?-d-glucosidase activity of the specific strain which catalyzed the breakdown of luteoloside, a preculture bacterial GAM broth and luteoloside were mixed incubated together for 48h. UHPLC-Q-TOF/MS was used for analysis of the metabolites of luteoloside in the corresponding supernatant fractions from fermentation. Aliquots of the reactive solutions were collected at different times and were measured with a microplate reader at 405nm to evaluate the enzymatic activity. Three metabolites (acetylated luteoloside, luteolin and deoxygenated luteolin) were detected in the fractions isolated from the bacterial samples. The variation of ?-d-glucosidase activity inside the bacterium was in coincidence with the changes in luteolin generation or luteoloside degradation in different time periods. PMID:25899973

  12. Similar uptake profiles of microcystin-LR and -RR in an in vitro human intestinal model

    International Nuclear Information System (INIS)

    Highlights: ? First description of in vitro cellular uptake of MCs into intestinal cells. ? OATP 3A1 and OATP 4A1 are expressed in Caco-2 cell membranes. ? MC-LR and MC-RR show similar uptake in Caco-2 cells. ? MCs are probably excreted from Caco-2 cells by an active mechanism. -- Abstract: Microcystins (MCs) are cyclic hepatotoxins produced by various species of cyanobacteria. Their structure includes two variable amino acids (AA) leading to more than 80 MC variants. In this study, we focused on the most common variant, microcystin-LR (MC-LR), and microcystin-RR (MC-RR), a variant differing by only one AA. Despite their structural similarity, MC-LR elicits higher liver toxicity than MC-RR partly due to a discrepancy in their uptake by hepatic organic anion transporters (OATP 1B1 and 1B3). However, even though ingestion is the major pathway of human exposure to MCs, intestinal absorption of MCs has been poorly addressed. Consequently, we investigated the cellular uptake of the two MC variants in the human intestinal cell line Caco-2 by immunolocalization using an anti-MC antibody. Caco-2 cells were treated for 30 min to 24 h with several concentrations (1-50 ?M) of both variants. We first confirmed the localization of OATP 3A1 and 4A1 at the cell membrane of Caco-2 cells. Our study also revealed a rapid uptake of both variants in less than 1 h. The uptake profiles of the two variants did not differ in our immunostaining study neither with respect to concentration nor the time of exposure. Furthermore, we have demonstrated for the first time the nuclear localization of MC-RR and confirmed that of MC-LR. Finally, our results suggest a facilitated uptake and an active excretion of MC-LR and MC-RR in Caco-2 cells. Further investigation on the role of OATP 3A1 and 4A1 in MC uptake should be useful to clarify the mechanism of intestinal absorption of MCs and contribute in risk assessment of cyanotoxin exposure.

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

    Directory of Open Access Journals (Sweden)

    mile 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.

  14. Biotin uptake by human intestinal and liver epithelial cells: role of the SMVT system.

    Science.gov (United States)

    Balamurugan, Krishnaswamy; Ortiz, Alvaro; Said, Hamid M

    2003-07-01

    It has been well established that human intestinal and liver epithelial cells transport biotin via an Na+-dependent carrier-mediated mechanism. The sodium-dependent multivitamin transport (SMVT), a biotin transporter, is expressed in both cell types. However, the relative contribution of SMVT toward total carrier-mediated uptake of physiological (nanomolar) concentrations of biotin by these cells is not clear. Addressing this issue is important, especially in light of the recent identification of a second human high-affinity biotin uptake mechanism that operates at the nanomolar range. Hence, we employed a physiological approach of characterizing biotin uptake by human-derived intestinal Caco-2 and HepG2 cells at the nanomolar concentration range. We also employed a molecular biology approach of selectively silencing the endogenous SMVT of these cells with specific small interfering RNAs (siRNAs), then examining carrier-mediated biotin uptake. The results showed that in both Caco-2 and HepG2 cells, the initial rate of biotin uptake as a function of concentration over the range of 0.1 to 50 nM to be linear. Furthermore, we found that the addition of 100 nM unlabeled biotin, desthiobiotin, or pantothenic acid to the incubation medium had no effect on the uptake of 2.6 nM [3H]biotin. Pretreatment of Caco-2 and HepG2 cells with SMVT specific siRNAs substantially reduced SMVT mRNA and protein levels. In addition, carrier-mediated [3H]biotin (2.6 nM) uptake by Caco-2 and HepG2 cells was severely (P 0.01) inhibited by the siRNAs pretreatment. These results demonstrate that the recently described human high-affinity biotin uptake system is not functional in intestinal and liver epithelial cells. In addition, the results provide strong evidence that SMVT is the major (if not the only) biotin uptake system that operates in these cells. PMID:12646417

  15. Mapping of liver-enriched transcription factors in the human intestine

    Directory of Open Access Journals (Sweden)

    Frank Lehner, Ulf Kulik, Juergen Klempnauer,Juergen Borlak

    2010-08-01

    Full Text Available AIM: To investigate the gene expression pattern of hepatocyte nuclear factor 6 (HNF6 and other liver-enriched transcription factors in various segments of the human intestine to better understand the differentiation of the gut epithelium.METHODS: Samples of healthy duodenum and jejunum were obtained from patients with pancreatic cancer whereas ileum and colon was obtained from patients undergoing right or left hemicolectomy or (rectosigmoid or rectal resection. All surgical specimens were subjected to histopathology. Excised tissue was shock-frozen and analyzed for gene expression of liver-enriched transcription factors by semiquantitative reverse transcription polymerase chain and compared to the human colon carcinoma cell line Caco-2. Protein expression of major liver-enriched transcription factors was determined by Western blotting while the DNA binding of HNF6 was investigated by electromobility shift assays.RESULTS: The gene expression patterning of liver-enriched transcription factors differed in the various segments of the human intestine with HNF6 gene expression being most abundant in the duodenum (P < 0.05 whereas expression of the zinc finger protein GATA4 and of the HNF6 target gene ALDH3A1 was most abundant in the jejunum (P < 0.05. Likewise, expression of FOXA2 and the splice variants 2 and 4 of HNF4? were most abundantly expressed in the jejunum (P < 0.05. Essentially, expression of transcription factors declined from the duodenum towards the colon with the most abundant expression in the jejunum and less in the ileum. The expression of HNF6 and of genes targeted by this factor, i.e. neurogenin 3 (NGN3 was most abundant in the jejunum followed by the ileum and the colon while DNA binding activity of HNF4? and of NGN3 was confirmed by electromobility shift assays to an optimized probe. Furthermore, Western blotting provided evidence of the expression of several liver-enriched transcription factors in cultures of colon epithelial cells, albeit at different levels.CONCLUSION: We describe significant local and segmental differences in the expression of liver-enriched transcription factors in the human intestine which impact epithelial cell biology of the gut.

  16. Identification of UDP-glucuronosyltransferase isoforms responsible for leonurine glucuronidation in human liver and intestinal microsomes.

    Science.gov (United States)

    Tan, Bo; Cai, Weimin; Zhang, Jinlian; Zhou, Ning; Ma, Guo; Yang, Ping; Zhu, Qing; Zhu, Yizhun

    2014-09-01

    Leonurine is a potent component of herbal medicine Herba leonuri. The detail information on leonurine metabolism in human has not been revealed so far. Two primary metabolites, leonurine O-glucuronide and demethylated leonurine, were observed and identified in pooled human liver microsomes (HLMs) and O-glucuronide is the predominant one. Among 12 recombinant human UDP-glucuronosyltransferases (UGTs), UGT1A1, UGT1A8, UGT1A9, and UGT1A10 showed catalyzing activity toward leonurine glucuronidation. The intrinsic clearance (CLint) of UGT1A1 was approximately 15-to 20-fold higher than that of UGT1A8, UGT1A9, and UGT1A10, respectively. Both chemical inhibition study and correlation study demonstrated that leonurine glucuronidation activities in HLMs had significant relationship with UGT1A1 activities. Leonurine glucuronide was the major metabolite in human liver microsomes. UGT1A1 was principal enzyme that responsible for leonurine glucuronidation in human liver and intestine microsomes. PMID:24635759

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

    Directory of Open Access Journals (Sweden)

    Marcelo Luiz Carvalho Gonalves

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

    International Nuclear Information System (INIS)

    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 ?-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 rave 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

  19. Vitamin E uptake by human intestinal cells during lipolysis in vitro.

    Science.gov (United States)

    Traber, M G; Goldberg, I; Davidson, E; Lagmay, N; Kayden, H J

    1990-01-01

    Vitamin E uptake by Caco-2 cells, a human intestinal cell line, was studied by incubating the cells with alpha-tocopherol/triglyceride emulsions with or without bile activated lipase or lipoprotein lipase. During a 1-h incubation, vitamin E was transferred to Caco-2 cells only in the presence of triglyceride hydrolysis by bile activated lipase and not by lipoprotein lipase. Incubation with either lipase resulted in hydrolysis of approximately 20% of the medium [3H]-triolein to free fatty acids and a 3-5-fold increase in cellular radioactivity. In the absence of lipases but the presence of taurocholate, addition of oleic acid in an amount equal to the molar concentration of triglyceride (5.7 mM) to triglyceride emulsions containing either alpha-tocopherol or cholesteryl ester resulted in an increase in cellular [3H]-triglyceride and alpha-tocopherol or cholesteryl ester. We suggest that the absorption of hydrophobic molecules such as vitamin E may occur in the presence of bile and amphipathic lipids via the uptake of micellar neutral lipids by the intestine. PMID:2293602

  20. Characterization of the transport of ?-methylaminoisobutyric acid by a human intestinal cell line (HT-29)

    International Nuclear Information System (INIS)

    Under certain growth conditions, the human colon adenocarcinoma cell line HT-29 exhibits intestinal enterocyte-like properties. The differentiated cells possess a brush border with the enzyme markers (aminopeptidase and sucrase) normally associated with the intestine. To aid in the characterization of the transport properties of these cells, the uptake of a non-metabolizable amino acid analog, 14C-?-methylaminoisobutyric acid (MeAIB) as examined in the HT-29-Al subclone which possesses a brush border. The cells exhibited a time-dependent uptake of MeAIB which was concentrative and sodium-dependent. The pH optimum for uptake was about 7.8. Uptake was inhibited by low temperature, 1 mM ouabain, or 0.5 mM dinitrophenol. A 1 hr-preincubation of the cells in an isotonic KCl solution resulted in a decreased uptake rate, suggesting that a negative membrane potential is important for MeAIB uptake. The rate of 0.5 mM MeABIB uptake was inhibited by 40 to 90% by 5 mM of certain small neutral amino acids such as Ala, Ser, Pro, Gly, met but not by acidic or basic amino acids such as Asp, Glu, Arg or Lys. The uptake of MeAIB appears to be mediated by an amino acid transport carrier similar to the A-system described previously for Chinese hamster ovary cells

  1. Utilizao do mtodo videolaparoscopico na reconstituio do trnsito intestinal aps a operao de Hartmann The use of videolaparoscopic approach in the intestinal transit restoration after Hartmann's procedure

    Directory of Open Access Journals (Sweden)

    Francisco Srgio P. Regadas

    2000-02-01

    Full Text Available O objetivo apresentar a padronizao da tcnica operatria e os resultados obtidos com a utilizao do acesso videolaparoscpico na reconstituio do trnsito intestinal em pacientes previamente submetidos operao de Hartmann por causas diversas. Foram analisados prospectivamente 32 pacientes, no perodo de dezembro de 1991 a junho de 1997, com distribuio semelhante com relao ao sexo e com idade mdia de 42,4 anos. Todos os pacientes foram submetidos ao mesmo preparo pr-operatrio e mesma tcnica cirrgica. Ocorreram trs (9,3% complicaes transoperatrias. Uma (3,1 % anastomose mecnica incompleta, necessitando de endossutura manual, uma (3,1 % lacerao do reto com o grampeador mecnico e uma (3,1 % leso da artria epigstrica direita. Ocorreram ainda trs (9,3% converses, sendo uma (3,1 % devido lacerao do reto com o grampeador mecnico, outra (3.1 % pela invaso tumoral na pelve e outra (3,1 % pela presena de excessivas aderncias intraperitoneais. O tempo operatrio variou de 30 a 240 minutos, na mdia de 126,2 minutos (2,1 horas. A evoluo clnica ps-operatria foi satisfatria. Nove (31,0% pacientes no referiram dor, enquanto 13 (44,8% a referiram em pequena intensidade, e apenas sete (24,0% queixaram-se de dor com maior intensidade. A dieta lquida via oral foi instituda no perodo mdio de 1,6 dias, e a primeira evacuao ocorreu na mdia de 3,2 dias de ps-operatrio. O perodo mdio de hospitalizao foi de 4,7 dias. Ocorreram complicaes ps-operatrias em oito (27,5% pacientes. Duas (6,8% infeces da ferida do estoma, dois pacientes (6,8% com dor no ombro direito, uma (3,4% deiscncia de anastomose, um (3,4% caso de peritonite por provvel contaminao do material cirrgico, uma coleo lquida plvica e uma hrnia incisional. Em concluso, a reconstituio do trnsito intestinal por videolaparoscopia apresentou-se segura e eficaz, podendo constituir-se no mtodo cirrgico de escolha, pois foi utilizada com sucesso em 90,6% dos pacientes.We present the operative technique and the results of the laparoscopic approach for Hartmann's colostomy reversal. Thirty two patients were prospectively analysed from december 1991 to june 1997. They presented a similar incidence regarding sex distribution, and a median age of 42.4 years old. Ali patients underwent the same preoperative preparation and operative technique. Three (9.3% intraoperative complications were observed: an uncompleted anastomosis (3.1%, requiring an endosuture, a rectal perforation by the mechanical stapler and a right epigastric artery lesion. There were convertion to open surgery in three (9.3% patients: one (3.1% due to rectal perforation by the mechanical staple1; one (3.1% for tumoral pelvic invasion and another because of excessive intra-peritoneal adhesions. Operative time varied from 30 to 240 minutes, with a mean time of 126;2 minutes. Nine (31.0% patients didn't present pain, while 13 (44.8% referred minimal pain and seven (24.0% complained severe pain. Oral liquid diet intake occurred within a mean time of 1.6 days and the first evacuation observed after a mean 3.2 postoperative days. Mean hospitalization time was 4.7 days. Postoperative complications occurred in eight (27.5% patients. Two (6.8% stoma wound infections, right shoulder pain in two (6.8% patients, one (3.4% anastomotic dehiscence, one peritonitis probably due to contaminationfrom surgical instruments, a liquid pelvic coliection and an incisional haernia. 1n conclusion, videolaparoscopic restoration of the intestinal transit demonstrated to be safe and effective. It could be the method of choice because of its success in 90.6 per cent of the patients.

  2. Utilizao do mtodo videolaparoscopico na reconstituio do trnsito intestinal aps a operao de Hartmann / The use of videolaparoscopic approach in the intestinal transit restoration after Hartmann's procedure

    Scientific Electronic Library Online (English)

    Francisco Srgio P., Regadas; Sthela M. Murad, Regadas; Lusmar Veras, Rodrigues.

    2000-02-01

    Full Text Available O objetivo apresentar a padronizao da tcnica operatria e os resultados obtidos com a utilizao do acesso videolaparoscpico na reconstituio do trnsito intestinal em pacientes previamente submetidos operao de Hartmann por causas diversas. Foram analisados prospectivamente 32 pacientes, [...] no perodo de dezembro de 1991 a junho de 1997, com distribuio semelhante com relao ao sexo e com idade mdia de 42,4 anos. Todos os pacientes foram submetidos ao mesmo preparo pr-operatrio e mesma tcnica cirrgica. Ocorreram trs (9,3%) complicaes transoperatrias. Uma (3,1 %) anastomose mecnica incompleta, necessitando de endossutura manual, uma (3,1 %) lacerao do reto com o grampeador mecnico e uma (3,1 %) leso da artria epigstrica direita. Ocorreram ainda trs (9,3%) converses, sendo uma (3,1 %) devido lacerao do reto com o grampeador mecnico, outra (3.1 %) pela invaso tumoral na pelve e outra (3,1 %) pela presena de excessivas aderncias intraperitoneais. O tempo operatrio variou de 30 a 240 minutos, na mdia de 126,2 minutos (2,1 horas). A evoluo clnica ps-operatria foi satisfatria. Nove (31,0%) pacientes no referiram dor, enquanto 13 (44,8%) a referiram em pequena intensidade, e apenas sete (24,0%) queixaram-se de dor com maior intensidade. A dieta lquida via oral foi instituda no perodo mdio de 1,6 dias, e a primeira evacuao ocorreu na mdia de 3,2 dias de ps-operatrio. O perodo mdio de hospitalizao foi de 4,7 dias. Ocorreram complicaes ps-operatrias em oito (27,5%) pacientes. Duas (6,8%) infeces da ferida do estoma, dois pacientes (6,8%) com dor no ombro direito, uma (3,4%) deiscncia de anastomose, um (3,4%) caso de peritonite por provvel contaminao do material cirrgico, uma coleo lquida plvica e uma hrnia incisional. Em concluso, a reconstituio do trnsito intestinal por videolaparoscopia apresentou-se segura e eficaz, podendo constituir-se no mtodo cirrgico de escolha, pois foi utilizada com sucesso em 90,6% dos pacientes. Abstract in english We present the operative technique and the results of the laparoscopic approach for Hartmann's colostomy reversal. Thirty two patients were prospectively analysed from december 1991 to june 1997. They presented a similar incidence regarding sex distribution, and a median age of 42.4 years old. Ali p [...] atients underwent the same preoperative preparation and operative technique. Three (9.3%) intraoperative complications were observed: an uncompleted anastomosis (3.1%), requiring an endosuture, a rectal perforation by the mechanical stapler and a right epigastric artery lesion. There were convertion to open surgery in three (9.3%) patients: one (3.1%) due to rectal perforation by the mechanical staple1; one (3.1%) for tumoral pelvic invasion and another because of excessive intra-peritoneal adhesions. Operative time varied from 30 to 240 minutes, with a mean time of 126;2 minutes. Nine (31.0%) patients didn't present pain, while 13 (44.8%) referred minimal pain and seven (24.0%) complained severe pain. Oral liquid diet intake occurred within a mean time of 1.6 days and the first evacuation observed after a mean 3.2 postoperative days. Mean hospitalization time was 4.7 days. Postoperative complications occurred in eight (27.5%) patients. Two (6.8%) stoma wound infections, right shoulder pain in two (6.8%) patients, one (3.4%) anastomotic dehiscence, one peritonitis probably due to contaminationfrom surgical instruments, a liquid pelvic coliection and an incisional haernia. 1n conclusion, videolaparoscopic restoration of the intestinal transit demonstrated to be safe and effective. It could be the method of choice because of its success in 90.6 per cent of the patients.

  3. Transit time heterogeneity in canine small intestine: significance for oxygen transport.

    OpenAIRE

    Connolly, H. V.; Maginniss, L. A.; Schumacker, P. T.

    1997-01-01

    We previously found that local O2 extraction efficacy in isolated pump-perfused intestine was enhanced when systemic reflex vasoconstriction was stimulated by hypovolemia (Samsel, R.W., and P.T. Schumacker. 1994. J. Appl. Physiol. 77: 2291-2298). The microvascular mechanism underlying this beneficial effect could involve a redistribution of flow between mucosa and serosa, or an adjustment in the heterogeneity of perfusion within those regions. We measured regional blood flows and distribution...

  4. Activation of intestinal human pregnane X receptor protects against azoxymethane/dextran sulfate sodium-induced colon cancer.

    Science.gov (United States)

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

    2014-12-01

    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 rate of PXR-humanized mice, but not wild-type or Pxr-null mice. These data indicated a human PXR-dependent therapeutic chemoprevention of rifaximin toward AOM/DSS-induced colon cancer. Nuclear factor ?-light-chain-enhancer of activated B cells-mediated inflammatory signaling was upregulated in AOM/DSS-treated mice, and inhibited by rifaximin in PXR-humanized mice. Cell proliferation and apoptosis were also modulated by rifaximin treatment in the AOM/DSS model. In vitro cell-based assays further revealed that rifaximin regulated cell apoptosis and cell cycle in a human PXR-dependent manner. These results suggested that specific activation of intestinal human PXR exhibited a chemopreventive role toward AOM/DSS-induced colon cancer by mediating anti-inflammation, antiproliferation, and proapoptotic events. PMID:25277138

  5. Prolonged use of aspirin alters human and rat intestinal cells and thereby limits the absorption of clopidogrel.

    Science.gov (United States)

    Jung, K-H; Chu, K; Lee, S-T; Yoon, H-J; Chang, J-Y; Nam, W-S; Yoon, S-H; Cho, J-Y; Yu, K-S; Jang, I-J; Kim, M; Lee, S K; Roh, J-K

    2011-10-01

    Clopidogrel therapy to prevent atherothrombosis faces the challenge of reduced responsiveness. The absorption of clopidogrel is regulated by multidrug-resistance protein 1 (MDR1) in the intestinal epithelium. Given that aspirin induces MDR1 in cancer cells and peripheral blood cells, it may induce MDR1 in intestinal epithelial cells as well, thereby affecting the absorption of clopidogrel. In this study, aspirin treatment induced the expression of MDR1 in human epithelial colorectal (Caco-2) cells in vitro and in rat intestine in vivo, as evidenced by dose-dependent increases in gene, protein, and efflux function. Along with the upregulation of MDR1 proteins by aspirin, clopidogrel absorption was significantly decreased in the aspirin-treated Caco-2 cells and in rat intestine. Our data provide evidence that prolonged use of aspirin may reduce the intestinal absorption of clopidogrel. Further human studies would be necessary to clarify whether these data have any relevance to prevention of stroke or myocardial infarction. PMID:21900887

  6. Moderate ferulate and diferulate levels do not impede maize cell wall degradation by human intestinal microbiota.

    Science.gov (United States)

    Funk, Carola; Braune, Annett; Grabber, John H; Steinhart, Hans; Bunzel, Mirko

    2007-03-21

    The degradation of plant fiber by human gut microbiota could be restricted by xylan substitution and cross-linking by ferulate and diferulates, for example, by hindering the association of enzymes such as xylanases with their substrates. To test the influence of feruloylation on cell wall degradability by human intestinal microbiota, nonlignified primary cell walls from maize cell suspensions, containing various degrees of ferulate substitution and diferulate cross-linking, were incubated in nylon bags in vitro with human fecal microbiota. Degradation rates were determined gravimetrically, and the cell walls were analyzed for carbohydrates, ferulate monomers, dehydrodiferulates, dehydrotriferulates, and other minor phenolic constituents. Shifting cell wall concentrations of total ferulates from 1.5 to 15.8 mg/g and those of diferulates from 0.8 to 2.6 mg/g did not alter the release of carbohydrates or the overall degradation of cell walls. After 24 h of fermentation, the degradation of xylans and pectins exceeded 90%, whereas cellulose remained undegraded. The results indicate that low to moderate levels of ferulates and diferulates do not interfere with hydrolysis of nonlignified cell walls by human gut microbiota. PMID:17319685

  7. Adherence and invasion of Bacteroidales isolated from the human intestinal tract.

    Science.gov (United States)

    Nakano, V; Piazza, R M F; Cianciarullo, A M; Bueris, V; Santos, M F; Menezes, M A; Mendes-Ledesma, M R B; Szulczewski, V; Elias, W P; Pumbwe, L; Wexler, H; Avila-Campos, M J

    2008-10-01

    Members of the genera Bacteroides and Parabacteroides are important constituents of both human and animal intestinal microbiota, and are significant facultative pathogens. In this study, the ability of Bacteroides spp. and Parabacteroides distasonis isolated from both diarrhoeal and normal stools (n = 114) to adhere to and invade HEp-2 cells was evaluated. The presence of putative virulence factors such as capsule and fimbriae was also investigated. Adherence to HEp-2 cells was observed in 75.4% of the strains, which displayed non-localized clusters. Invasion was observed in 37.5% and 26% of the strains isolated from diarrhoeal and non-diarrhoeal stools, respectively. All strains displayed a capsule, whereas none of them showed fimbriae-like structures. This is the first report of the ability of Bacteroides spp. and P. distasonis to adhere to and invade cultured HEp-2 epithelial cells. PMID:18828854

  8. Localization of ABCG5 and ABCG8 proteins in human liver, gall bladder and intestine

    Directory of Open Access Journals (Sweden)

    Chavin Kenneth D

    2004-09-01

    Full Text Available Abstract Background The molecular mechanisms that regulate the entry of dietary sterols into the body and their removal via hepatobiliary secretion are now beginning to be defined. These processes are specifically disrupted in the rare autosomal recessive disease, Sitosterolemia (MIM 210250. Mutations in either, but not both, of two genes ABCG5 or ABCG8, comprising the STSL locus, are now known to cause this disease and their protein products are proposed to function as heterodimers. Under normal circumstances cholesterol, but not non-cholesterol sterols, is preferentially absorbed from the diet. Additionally, any small amounts of non-cholesterol sterols that are absorbed are rapidly taken up by the liver and preferentially excreted into bile. Based upon the defects in sitosterolemia, ABCG5 and ABCG8 serve specifically to exclude non-cholesterol sterol entry at the intestinal level and are involved in sterol excretion at the hepatobiliary level. Methods Here we report the biochemical and immuno-localization of ABCG5 and ABCG8 in human liver, gallbladder and intestine using cell fractionation and immunohistochemical analyses. Results We raised peptide antibodies against ABCG5 and ABCG8 proteins. Using human liver samples, cell fractionation studies showed both proteins are found in membrane fractions, but they did not co-localize with caveolin-rafts, ER, Golgi or mitochondrial markers. Although their distribution in the sub-fractions was similar, they were not completely contiguous. Immunohistochemical analyses showed that while both proteins were readily detectable in the liver, ABCG5 was found predominately lining canalicular membranes, whereas ABCG8 was found in association with bile duct epithelia. At the cellular level, ABCG5 appeared to be apically expressed, whereas ABCG8 had a more diffuse expression pattern. Both ABCG5 and ABCG8 appeared to localize apically as shown by co-localization with MRP2. The distribution patterns of ABCG5 and ABCG8 in the gallbladder were very similar to each other. In the small intestine both ABCG5 and ABCG8 appear to line the brush border. However, at the level of the enterocyte, the cellular distribution patterns of ABCG5 and ABCG8 differed, such that ABCG5 was more diffuse, but ABCG8 was principally apical. Using standard deglycosylation methods, ABCG5 and ABCG8 do not appear to be glycosylated, suggesting a difference between human and mouse proteins. Conclusion We report the distribution patterns of ABCG5 and ABCG8 in human tissues. Cell fractionation studies showed that both proteins co-fractionated in general, but could also be found independent of each other. As predicted, they are expressed apically in both intestine and liver, although their intracellular expression patterns are not completely congruent. These studies support the concept of heterodimerization of ABCG5 and ABCG8, but also support the notion that these proteins may have an independent function.

  9. Use of Stable Isotopes To Measure the Metabolic Activity of the Human Intestinal Microbiota?

    Science.gov (United States)

    Reichardt, Nicole; Barclay, Andrew R.; Weaver, Lawrence T.; Morrison, Douglas J.

    2011-01-01

    The human intestinal microbiota is a complex biological system comprising a vast repertoire of microbes with considerable metabolic activity relevant to both bacterial growth and host health. Greater strides have been made in the analysis of microbial diversity than in the measurement of functional activity, particularly in vivo. Stable isotope probing offers a new approach by coupling measurements of metabolic activity with microbial identification. Using a low-enrichment labeling strategy in vitro, this study has identified metabolically active bacterial groups via magnetic-bead capture methodology and stable isotope ratio analysis. Using five probes (EUB338, Bac303, Bif164, EREC482, and Clep866), changes in the activities of key intestinal microbial groups were successfully measured by exploiting tracers of de novo RNA synthesis. Perturbation of the nutrient source with oligofructose generated changes in the activity of bifidobacteria as expected, but also in the Bacteroides-Prevotella group, the Eubacterium rectale-Clostridium coccoides group, and the Clostridium leptum subgroup. Changes in activity were also observed in response to the medium type. This study suggests that changes in the functional activity of the gut microbiota can be assessed using tracers of de novo nucleic acid synthesis combined with measurement of low isotopic enrichment in 16S rRNA. Such tracers potentially limit substrate bias because they are universally available to bacteria. This low-enrichment labeling approach does not depend on the commercial availability of specific labeled substrates and can be easily translated to in vivo probing experiments of the functional activity of the microbiota in the human gut. PMID:21948826

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

    DEFF Research Database (Denmark)

    Bergstrm, Anders; Wilcks, Andrea

    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, 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 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-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 bifidobacteria and Clostridium cluster XIVa was performed. Bands differing between the periods were sequenced, and qPCR was performed to verify the changes observed by DGGE. Results: Changes in the microbiota was observed by DGGE in persons consuming whole apples and pomace. In contrast, the two juice supplements did not show any effect on the microbiota by DGGE. Conclusion: Consumption of whole apples or pomace is able to modify the intestinal microbiota of humans.

  11. Toxicity, genotoxicity and proinflammatory effects of amorphous nanosilica in the human intestinal Caco-2 cell line.

    Science.gov (United States)

    Tarantini, Adeline; Lanceleur, Rachelle; Mourot, Annick; Lavault, Marie-Thrse; Casterou, Grald; Jarry, Grard; Hogeveen, Kevin; Fessard, Valrie

    2015-03-01

    Silica (SiO2) in its nanosized form is now used in food applications although the potential risks for human health need to be evaluated in further detail. In the current study, the uptake of 15 and 55nm colloidal SiO2 NPs in the human intestinal Caco-2 cell line was investigated by transmission electron microscopy. The ability of these NPs to induce cytotoxicity (XTT viability test), genotoxicity (?H2Ax and micronucleus assay), apoptosis (caspase 3), oxidative stress (oxidation of 2,7-dichlorodihydrofluorescein diacetate probe) and proinflammatory effects (interleukin IL-8 secretion) was evaluated. Quartz DQ12 was used as particle control. XTT and cytokinesis-block micronucleus assays revealed size- and concentration-dependent effects on cell death and chromosome damage following exposure to SiO2 nanoparticles, concomitantly with generation of reactive oxygen species (ROS), SiO2-15nm particles being the most potent. In the same way, an increased IL-8 secretion was only observed with SiO2-15nm at the highest tested dose (32?g/ml). TEM images showed that both NPs were localized within the cytoplasm but did not enter the nucleus. SiO2-15nm, and to a lower extent SiO2-55nm, exerted toxic effects in Caco-2 cells. The observed genotoxic effects of these NPs are likely to be mediated through oxidative stress rather than a direct interaction with the DNA. Altogether, our results indicate that exposure to SiO2 NPs may induce potential adverse effects on the intestinal epithelium in vivo. PMID:25448807

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

    Directory of Open Access Journals (Sweden)

    Marta G?ogowska

    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 80C for 24 hours, and then increased temperature to 105C 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 105C 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 ?gg-1d.m., compared to a sodium content in tissues adjacent to the tumor (1813,958 ?gg-1d.m. and tumor tissues (2029,442 ?gg-1d.m.. In the case of colon, control tissues have lower average content of sodium (2160,886 ?gg-1d.m., than the tissues surrounding the tumor (3325,963 ?gg-1d.m. and tumor tissues (3037,121 ?gg-1d.m.. The potassium level is higher in the control tissues of stomach (1428,993 ?gg-1d.m., than in the tissues adjacent to the tumor (1091,544 ?gg-1d.m. and tumor tissues (1220,471 ?gg-1d.m.. In the large intestine higher average content of potassium is characterized by tumor tissues (2307,234 ?gg-1d.m. and tissues adjacent to the tumor (1712,779 ?gg-1d.m., than control tissue (1389,703 ?gg-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.

  13. Cyanidin-3-Glucoside Suppresses Cytokine-Induced Inflammatory Response in Human Intestinal Cells: Comparison with 5-Aminosalicylic Acid

    OpenAIRE

    Serra, Diana; Paixo, Joana; Nunes, Carla; Dinis, Teresa C. P.; Almeida, Leonor M.

    2013-01-01

    The potential use of polyphenols in the prevention and treatment of chronic inflammatory diseases has been extensively investigated although the mechanisms involved in cellular signaling need to be further elucidated. Cyanidin-3-glucoside is a typical anthocyanin of many pigmented fruits and vegetables widespread in the human diet. In the present study, the protection afforded by cyanidin-3-glucoside against cytokine-triggered inflammatory response was evaluated in the human intestinal HT-29 ...

  14. Enterohemorrhagic Escherichia coli induce attaching and effacing lesions and hemorrhagic colitis in human and bovine intestinal xenograft models

    OpenAIRE

    Golan, Lilach; Gonen, Erez; Yagel, Simcha; Rosenshine, Ilan; Shpigel, Nahum Y.

    2010-01-01

    Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is an important cause of diarrhea, hemorrhagic colitis and hemolytic uremic syndrome in humans worldwide. The two major virulence determinants of EHEC are the Shiga toxins (Stx) and the type III secretion system (T3SS), including the injected effectors. Lack of a good model system hinders the study of EHEC virulence. Here, we investigated whether bovine and human intestinal xenografts in SCID mice can be useful for studying EHEC and host tissu...

  15. Differential modulation of human intestinal bifidobacterium populations after consumption of a wild blueberry (Vaccinium angustifolium) drink.

    Science.gov (United States)

    Guglielmetti, Simone; Fracassetti, Daniela; Taverniti, Valentina; Del Bo', Cristian; Vendrame, Stefano; Klimis-Zacas, Dorothy; Arioli, Stefania; Riso, Patrizia; Porrini, Marisa

    2013-08-28

    Bifidobacteria are gaining increasing interest as health-promoting bacteria. Nonetheless, the genus comprises several species, which can exert different effects on human host. Previous studies showed that wild blueberry drink consumption could selectively increase intestinal bifidobacteria, suggesting an important role for the polyphenols and fiber present in wild blueberries. This study evaluated the modulation of the most common and abundant bifidobacterial taxonomic groups inhabiting the human gut in the same fecal samples. The analyses carried out showed that B. adolescentis, B. breve, B. catenulatum/pseudocatelulatum, and B. longum subsp. longum were always present in the group of subjects enrolled, whereas B. bifidum and B. longum subsp. infantis were not. Furthermore, it was found that the most predominant bifidobacterial species were B. longum subsp. longum and B. adolescentis. The results obtained revealed a high interindividual variability; however, a significant increase of B. longum subsp. infantis cell concentration was observed in the feces of volunteers after the wild blueberry drink treatment. This bifidobacterial group was shown to possess immunomodulatory abilities and to relieve symptoms and promote the regression of several gastrointestinal disorders. Thus, an increased cell concentration of B. longum subsp. infantis in the human gut could be considered of potential health benefit. In conclusion, wild blueberry consumption resulted in a specific bifidogenic effect that could positively affect certain populations of bifidobacteria with demonstrated health-promoting properties. PMID:23883473

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

    Directory of Open Access Journals (Sweden)

    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.

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

    DEFF Research Database (Denmark)

    Hildebrand, Falk; Ebersbach, Tine

    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, 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 possiblyreflecting 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.

  18. Artculos originales Cultivo primario de queratinocitos humanos sembrados en submucosa intestinal porcina / Primary culture of human keratinocytes planted on pigs intestine Submucosa

    Scientific Electronic Library Online (English)

    ngela Ximena, Amrtegui; Sandra Roco, Ramrez.

    2008-12-01

    Full Text Available En el campo de la regeneracin de piel, la ingeniera de tejidos busca superar las limitaciones asociadas con el uso de autoinjertos inmediatos, dado que la eleccin de una regin donante en el paciente, constituye un riesgo para el mismo, adems de ser insuficiente cuando la lesin es extensa. Se h [...] a comprobado que el empleo de la submucosa del intestino delgado de cerdo (SIS) (por la sigla en ingls small intestinal submucosa), por su especial composicin, como biomaterial de relleno para tratar lesiones, disminuye el dolor y la inflamacin desde su primera aplicacin y favorece la movilidad temprana de la regin lesionada. Con el fin de determinar la utilidad de SIS, como sustituto epidrmico, en el presente estudio se desarroll un protocolo para el cultivo primario de queratinocitos humanos, provenientes de prepucios infantiles, sobre una matriz de SIS como soporte. Se evalu el potencial de adherencia y la capacidad de proliferacin de queratinocitos sobre este sustrato. Abstract in english Tissue engineering, in the fields of skin regeneration, seeks to overcome the limitations associated with the use of immediate auto-grafts, since choosing the donor region of the patient constitutes a risk for the patient himself and is insufficient if the injury that has to be repaired is very larg [...] e. The use of the pigs small intestine submucosa (SIS) has being proved as a filling biomaterial to treat injuries, because of its special composition, it lowers pain and inflammation since its first application and it favours early mobility to the wounded area. The present study developed a protocol for the primary culture of human keratinocytes from infant foreskins, and used small intestinal submucosa (SIS) like culture substrate. Cellular adherence potential and proliferation capability of the keratinocytes over this substrate was evaluated.

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

    DEFF Research Database (Denmark)

    Avram-Hananel, L.; Stock, J.

    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 used to examine the in vitro effects of E durans and its metabolite butyrate on basal and Escherichia colistimulated secretion of proinflammatory immune factors (IL-8, IL-6, and TNF-?) and the anti-inflammatory cytokine IL-10. A murine model of dextran sodium sulfate-induced colitis was used to 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-? and increased secretion of IL-10. In the in vivo murine model, preventive administration of E durans significantly ameliorated clinical disease activity index (weight loss, fecal bleeding, and stool consistency), reduced myeloperoxidase concentration in colon tissue extracts, improved histologic scores of colonic 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-inflammatory effects, mediated by regulation of pro- and anti-inflammatory immune factors as well as preservation of intestine epithelial integrity, suggesting that this novel anti-inflammatory bacterium may be preferentially a useful prophylactic treatment to avoid inflammatory bowel disease.

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

    Science.gov (United States)

    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?M. 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 (12h) effect induced by FB1 at concentrations ranging from 0.5 to 69?M, followed by inhibition of cell proliferation (up to 8.6?M), the immunomodulatory effect (up to 17.2?M), by assessing IL-8 secretion, and increase in membrane microviscosity (up to 34.5?M). 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

  1. In vitro glucuronidation of five rhubarb anthraquinones by intestinal and liver microsomes from humans and rats.

    Science.gov (United States)

    Wu, Wenjin; Hu, Nan; Zhang, Qingwen; Li, Yaping; Li, Peng; Yan, Ru; Wang, Yitao

    2014-08-01

    Anthraquinones naturally distribute in many plants including rhubarb and have widespread applications throughout industry and medicine. Recent studies provided new insights in potential applications of these traditional laxative constituents. Glucuronidation was the main metabolic pathway of rhubarb anthraquinones in vivo. This study examined the activity and regioselectivity of glucuronidation of rhubarb anthraquinones (aloe-emodin, emodin, chrysophanol, physcion, rhein) in liver and intestinal microsomes from rats and humans, by comparing with the core structure danthron. All anthraquinones formed mono-glucuronides and, except for rhein, the conjugation sites of the main metabolites were unambiguously identified. Two minor glucuronides of emodin were first reported together with the dominant emodin-3-O-?-D-glucuronide. The substitution on the anthraquinone ring was crucial to the activity and regioselectivity of glucuronidation. In general, the activity was decreased greatly with a ?-COOH (rhein), while enhanced dramatically with a ?-OH (emodin). Glucuronidation showed an absolute preference towards ?-OH, followed by ?-OH and ?-alcoholic OH. The glucuronidation activity and regioselectivity also varied slightly with organs and species. All glucuronides of aloe-emodin, emodin, chrysophanol and physcion were formed by multiple human UGT isoforms with 1A9 being the most prominent in most cases. The UGT2B subfamily (2B7 and 2B15) only showed high activity towards a ?-OH. In conclusion, the substitution at the anthraquinone ring was crucial to the rate and preference of glucuronidation. The high glucuronidation activity of UGT1A9 towards anthraquinones highlighted potential drug interactions. PMID:24854283

  2. Digoxin inhibition of relaxation induced by prostacyclin and vasoactive intestinal polypeptide in small human placental arteries

    DEFF Research Database (Denmark)

    Maigaard, S; Forman, Axel

    1985-01-01

    Small chorionic plate arteries were obtained from human placentae following normal vaginal delivery. Tubal vascular preparations were dissected, mounted in organ baths, and their isometric tension was recorded. Digoxin (10(-6) M) caused a rise in basic tension, reaching a maximum of 17 per cent of contractions induced by potassium (124 mM) depolarization. Pretreatment with digoxin did not significantly influence the concentration-dependent contractile responses to 5-hydroxytryptamine and prostaglandin F2 alpha (PGF2 alpha). In preparations contracted with PGF2 alpha, cumulative addition of prostacyclin (PGI2) and vasoactive intestinal polypeptide (VIP) produced concentration dependent relaxations. Digoxin (10(-8) to 10(-6) M) inhibited and finally abolished these relaxant effects of PGI2 and VIP in a concentration-dependent fashion. Pretreatment by digoxin (10(-8) to 10(-6) M) diminished the relaxant effect of sodium nitroprusside, but the effect was less pronounced than that on PGI2- and VIP-induced relaxation. As PGI2 and VIP may be of importance for the maintenance of a low resistance of the fetal placental vascular bed, the finding that digoxin decreases the vasodilating effects of these agents might imply effects on placental resistance of cardiac glycosides when used in late human pregnancy.

  3. Study of the adhesion of Bifidobacterium bifidum MIMBb75 to human intestinal cell lines.

    Science.gov (United States)

    Guglielmetti, Simone; Tamagnini, Isabella; Minuzzo, Mario; Arioli, Stefania; Parini, Carlo; Comelli, Elena; Mora, Diego

    2009-08-01

    The aim of this study was to investigate the adhesive phenotype of the human intestinal isolate Bifidobacterium bifidum MIMBb75 to human colon carcinoma cell lines. We have previously shown that the adhesion of this strain to Caco-2 cells is mediated by an abundant surface lipoprotein named BopA. In this study, we found that this strain adheres to Caco-2 and HT-29 cells, and that its adhesion strongly depends on the environmental conditions, including the presence of sugars and bile salts and the pH. Considerably more adhesion to a Caco-2 monolayer occurred in the presence of fucose and mannose and less when MIMBb75 grew in Oxgall bile salts compared to standard environmental conditions. In particular, growth in Oxgall bile salts reduced the adhesion ability of MIMBb75 and modified the SDS-PAGE profile of the cell wall associated proteins of the strain. The pH markedly affected both adhesion to Caco-2 and bacterial autoaggregation. Finally, experiments with sodium metaperiodate suggested that not only proteinaceous determinants are involved in the adhesion process of B. bifidum. In conclusion, it seems that the colonization strategy of this bacterium can be influenced by factors varying along the gastrointestinal tract, such as the presence of specific sugars and bile salts and the pH, possibly limiting the adhesion of B. bifidum to only restricted distal sites of the gut. PMID:19452211

  4. Perfil epidemiolgico e morbimortalidade dos pacientes submetidos reconstruo de trnsito intestinal: experincia de um centro secundrio do nordeste Brasileiro / Epidemiologic profile and morbimortality of patients undergoing to intestinal transit reconstruction: experience of a secundary health service in Brazil northeast

    Scientific Electronic Library Online (English)

    Jeany Borges e, Silva; Djalma Ribeiro, Costa; Francisco Julimar Correia de, Menezes; Jos Marconi, Tavares; Adryano Gonalves, Marques; Rodrigo Dornfeld, Escalante.

    2010-09-01

    Full Text Available Racional- A reconstruo do trnsito intestinal no est isenta de riscos cirrgicos e apresenta taxas considerveis de complicaes ps-operatrias, sendo que a infeco continua a ser um dos maiores desafios existentes neste procedimento. Mtodos- Foram analisados retrospectivamente 86 pronturios [...] de pacientes com colostomia ou ileostomia, atravs de fatores que tivessem impacto sobre a morbimortalidade aps a reconstruo de trnsito intestinal, de janeiro de 2003 a abril de 2009. Resultados- Houve 20 mulheres e 60 homens, com idade mdia de 43 anos. A colostomia em ala (n: 34) e o trauma abdominal indicando colostomia ou ileostomia foram as condies mais frequentes. O intervalo mdio entre a confeco do estoma e a reconstruo de trnsito intestinal foi 15,7 meses. O ndice de morbidade foi 56,8%, sendo a infeco incisional a complicao mais comum (27.47%). A permanncia hospitalar mdia foi 7,6 dias. Houve regresso linear positiva entre permanncia hospitalar ps-operatria e a idade do paciente. Demonstrou-se associao estatisticamente significativa entre o prolongamento da permanncia hospitalar e a ocorrncia de complicaes (p Abstract in english Background - 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 w [...] ere 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 complication (27.47%). The mean inpatient length of stay was 7.6 days. There was positive linear regression between post-operative inpatient length of stay and inpatient's age. Inpatient length of stay prolongation is associated to occurrence of complications (p

  5. Perfil epidemiolgico e morbimortalidade dos pacientes submetidos reconstruo de trnsito intestinal: experincia de um centro secundrio do nordeste Brasileiro Epidemiologic profile and morbimortality of patients undergoing to intestinal transit reconstruction: experience of a secundary health service in Brazil northeast

    Directory of Open Access Journals (Sweden)

    Jeany Borges e Silva

    2010-09-01

    Full Text Available Racional- A reconstruo do trnsito intestinal no est isenta de riscos cirrgicos e apresenta taxas considerveis de complicaes ps-operatrias, sendo que a infeco continua a ser um dos maiores desafios existentes neste procedimento. Mtodos- Foram analisados retrospectivamente 86 pronturios de pacientes com colostomia ou ileostomia, atravs de fatores que tivessem impacto sobre a morbimortalidade aps a reconstruo de trnsito intestinal, de janeiro de 2003 a abril de 2009. Resultados- Houve 20 mulheres e 60 homens, com idade mdia de 43 anos. A colostomia em ala (n: 34 e o trauma abdominal indicando colostomia ou ileostomia foram as condies mais frequentes. O intervalo mdio entre a confeco do estoma e a reconstruo de trnsito intestinal foi 15,7 meses. O ndice de morbidade foi 56,8%, sendo a infeco incisional a complicao mais comum (27.47%. A permanncia hospitalar mdia foi 7,6 dias. Houve regresso linear positiva entre permanncia hospitalar ps-operatria e a idade do paciente. Demonstrou-se associao estatisticamente significativa entre o prolongamento da permanncia hospitalar e a ocorrncia de complicaes (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 complication (27.47%. The mean inpatient length of stay was 7.6 days. There was positive linear regression between post-operative inpatient length of stay and inpatient's age. Inpatient length of stay prolongation is associated to occurrence of complications (p<0,001. Conclusion - Post-operative complications and age are associated to inpatient length of stay prolongation.

  6. Intestinal transit, deoxycholic acid and the cholesterol saturation of bile--three inter-related factors.

    OpenAIRE

    Marcus, S N; Heaton, K W

    1986-01-01

    There is considerable evidence that the level of deoxycholic acid in the bile influences biliary cholesterol saturation. Deoxycholic acid is formed in the colon and absorbed slowly. Hence changes in colonic transit rate might influence biliary deoxycholic acid and the cholesterol saturation of bile. When 14 constipated subjects took standardised senna tablets for six weeks in a dose sufficient to lower mean whole gut transit time from 134 to 54 hours, deoxycholic acid as a proportion of bilia...

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

    Directory of Open Access Journals (Sweden)

    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 nave 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-?. Nuclear factor kappa B inhibitor, tryptase and TNF-? 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.

  8. Intestinal uptake and lymphatic absorption of beta-carotene in ferrets: a model for human beta-carotene metabolism.

    Science.gov (United States)

    Wang, X D; Krinsky, N I; Marini, R P; Tang, G; Yu, J; Hurley, R; Fox, J G; Russell, R M

    1992-10-01

    To determine the appropriateness of the ferret as a model for human beta-carotene (beta-C) metabolism, we have perfused both 15,15'-beta-[14C]C and unlabeled beta-C through the upper 30-cm portion of the small intestine of ferrets in vivo. The effluents of a mesenteric lymph duct cannulation and a common bile duct cannulation, as well as portal vein blood periodically sampled via an indwelling catheter, were collected. Ten percent (9.5 +/- 0.06%) of the total administered beta-C was taken up by the intestine after a 4-h perfusion. Of the radioactivity taken up, 68.6 +/- 6.5% remained in the intestinal mucosa, 3.2 +/- 0.2% was recovered in the lymph, and 28.2 +/- 6.5% (calculated) was absorbed via the portal system. The total uptake/absorption of beta-C was 12.9 +/- 6.8 nmol.h-1.30 cm intestine-1. Large amounts of unchanged beta-C and relatively small amounts of both beta-apo-12'-carotenal and beta-apo-10'-carotenal were isolated in the intestinal mucosa after a 4-h perfusion with beta-C. Considerable amounts of metabolites more polar than retinol were formed and comprised 35% of the total radioactivity recovered in the intestinal mucosa. Polar metabolites were absorbed mostly into the portal venous system, whereas retinol and retinyl esters were absorbed mainly into the mesenteric lymph. Of the total absorbed radioactivity in lymph, 10 +/- 1.0% appeared as unchanged beta-C, with peak absorption occurring at 3 h after beginning the perfusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1415707

  9. Specific binding of lactoferrin to Escherichia coli isolated from human intestinal infections

    International Nuclear Information System (INIS)

    The degrees of human lactoferrin (HLf) and bovine lactoferrin (BLf) binding in 169 Escherichia coli strains isolated from human intestinal infections, and in an additional 68 strains isolated from healthy individuals, were examined in a 125I-labelled protein binding assay. The binding was expressed as a percentage calculated from the total labelled ligand added to bacteria. The HLf and BLf binding to E. coli was in the range 3.7 to 73.4% and 4.8 to 61.6%, respectively. Enterotoxigenic strains demonstrated a significantly higher HLf binding (median = 19%) than enteropathogenic, enteroinvasive, enterohaemorrhagic strains or normal intestinal E. coli isolates (medians 6 to 9). Enteropathogenic strains belonging to serotypes O44 and O127 demonstrated significantly higher HLf binding compared to O26, O55, O111, O119 and O126. No significant differences in the degree of HLf or BLf binding were found between aerobactin-producing and non-producing strains. The interaction was further characterized in a high Lf-binging EPEC strain, E34663 (serotype O127). The binding was stable in the pH range 4.0 to 7.5, did not dissociate in the presence of 2M NaCl or 2M urea, and reached saturation within two h. Unlabelled HLf and BLf displaced the 125I-HLf binding to E34663 in a dose-dependent manner. Apo- and iron-saturated forms of Lf demonstrated similar binding to E34663. Among various unlabelled subephithelial matrix proteins and carbohydrates tested (in 104eins and carbohydrates tested (in 104-fold excess) only fibronectin and fibrinogen caused a moderate inhibition of 125I-HLf binding. According to Scatchard plot analysis, 5,400 HLf-binding sites/cell, with an affinity constant (Ka) of 1.4 x 10-7 M, were estimated in strain E34663. These data establish the presence of a specific Lf-binding mechanism in E. coli. (au)

  10. Specific binding of lactoferrin to Escherichia coli isolated from human intestinal infections

    Energy Technology Data Exchange (ETDEWEB)

    Naidu, S.S.; Erdei, J.; Forsgren, A.; Naidu, A.S. (Departments of Medical Microbiology, Malmoe General Hospital (Sweden)); Czirok, E.; Gado, I. (National Institute of Hygiene, Budapest (Hungary)); Kalfas, S. (School of Dentistry, University of Lund, Malmoe (Sweden)); Thoren, A. (Infectious Diseases, Malmoe General Hospital (Sweden))

    1991-01-01

    The degrees of human lactoferrin (HLf) and bovine lactoferrin (BLf) binding in 169 Escherichia coli strains isolated from human intestinal infections, and in an additional 68 strains isolated from healthy individuals, were examined in a {sup 125}I-labelled protein binding assay. The binding was expressed as a percentage calculated from the total labelled ligand added to bacteria. The HLf and BLf binding to E. coli was in the range 3.7 to 73.4% and 4.8 to 61.6%, respectively. Enterotoxigenic strains demonstrated a significantly higher HLf binding (median = 19%) than enteropathogenic, enteroinvasive, enterohaemorrhagic strains or normal intestinal E. coli isolates (medians 6 to 9). Enteropathogenic strains belonging to serotypes O44 and O127 demonstrated significantly higher HLf binding compared to O26, O55, O111, O119 and O126. No significant differences in the degree of HLf or BLf binding were found between aerobactin-producing and non-producing strains. The interaction was further characterized in a high Lf-binging EPEC strain, E34663 (serotype O127). The binding was stable in the pH range 4.0 to 7.5, did not dissociate in the presence of 2M NaCl or 2M urea, and reached saturation within two h. Unlabelled HLf and BLf displaced the {sup 125}I-HLf binding to E34663 in a dose-dependent manner. Apo- and iron-saturated forms of Lf demonstrated similar binding to E34663. Among various unlabelled subephithelial matrix proteins and carbohydrates tested (in 10{sup 4}-fold excess) only fibronectin and fibrinogen caused a moderate inhibition of {sup 125}I-HLf binding. According to Scatchard plot analysis, 5,400 HLf-binding sites/cell, with an affinity constant (K{sub a}) of 1.4 x 10{sup -7} M, were estimated in strain E34663. These data establish the presence of a specific Lf-binding mechanism in E. coli. (au).

  11. Adherence of an enterotoxigenic Escherichia coli strain, serotype O78:H11, to purified human intestinal brush borders.

    OpenAIRE

    Cheney, C. P.; Boedeker, E. C.

    1983-01-01

    The human enterotoxigenic Escherichia coli pathogen designated H10407 expresses two different types of surface pili, one designated type 1 pili and the other designated colonization factor antigen I (CFA/I), CFA/I pili are thought to promote the adherence of H10407 to the mucosa of the human small bowel. H10407 was grown under conditions which promoted the expression of either type 1 pili or CFA/I pili, and in each case, the adherence of H10407 to purified human intestinal brush borders was q...

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

    Science.gov (United States)

    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

  13. 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

    OpenAIRE

    Kumar, Veerendra; Mallika, Nagarajan; Sivaraman, J.

    2011-01-01

    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.

  14. Evaluation by computerized morphometry of histopathological alterations of the colon wall in segments with and without intestinal transit in rats Avaliao por morfometria computadorizada das alteraes histopatolgicas da parede clica em segmentos com e sem trnsito intestinal em ratos

    Directory of Open Access Journals (Sweden)

    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 intestinal mucosa, increased number of caliciform cells, greater vascular congestion of the submucosal layer and inflammatory reaction were related to increasing length of time without transit.OBJETIVO: Avaliar por mtodo de imagem assistida por computador as alteraes histopatolgicas da parede clica em segmentos providos e desprovidos de trnsito intestinal e relacion-las ao tempo de excluso. MTODOS: Trinta ratos Wistar machos foram submetidos derivao do trnsito no clon esquerdo por meio de colostomia proximal e fstula mucosa distal. Os animais foram divididos em trs grupos experimentais segundo o sacrifcio ter sido realizado seis, doze e dezoito semanas aps o procedimento cirrgico inicial. Segmentos dos clons providos e desprovidos de trnsito foram submetidos a estudo histopatolgico. Foram analisadas as variveis: comprimento das criptas clicas, ulcerao na mucosa, espessura das camadas muscular da mucosa, submucosa e muscular prpria, congesto vascular, nmero de clulas caliciformes e graduao inflamatria comparando os dois segmentos clicos nos diferentes grupos experimentais. As variveis, comprimento das criptas intestinais, espessura das camadas muscular da mucosa, submucosa e muscular prpria foram mensuradas por mtodo de imagem assistida por computador. Na anlise estatstica foram utilizados testes de igualdade de mdias e medianas, anlise de varincia e correlao estabelecendo-se nvel de significncia de cinco por cento. RESULTADOS: A excluso de trnsito mostrou-se associada reduo do comprimento das criptas clicas, aumento da espessura das camadas muscular da mucosa, submucosa e muscular prpria. Verificou-se maior quantidade de ulceraes na mucosa e maior grau de inflamao com o progredir do tempo de excluso. Houve correlao significante entre as ulceraes da mucosa, congesto vascular da submucosa, aumento da espessura das camadas submucosa e muscular prpria, presena de clulas caliciformes, infiltrado inflamatrio, graduao inflamatria e o t

  15. Bacteroides fragilis toxin exhibits polar activity on monolayers of human intestinal epithelial cells (T84 cells) in vitro.

    OpenAIRE

    Chambers, F. G.; Koshy, S. S.; Saidi, R. F.; Clark, D. P.; Moore, R. D.; Sears, C. L.

    1997-01-01

    Strains of Bacteroides fragilis associated with diarrhea in children (termed enterotoxigenic B. fragilis, or ETBF) produce a heat-labile ca. 20-kDa protein toxin (BFT). The purpose of this study was to examine the activity of BFT on polarized monolayers of human intestinal epithelial cells (T84 cells). In Ussing chambers, BFT had two effects. First, BFT applied to either the apical or basolateral surfaces of T84 monolayers diminished monolayer resistance. However, the time course, magnitude, ...

  16. Tick-Borne Encephalitis Virus Replication, Intracellular Trafficking, and Pathogenicity in Human Intestinal Caco-2 Cell Monolayers

    OpenAIRE

    Yu, Chao; Achazi, Katharina; Mo?ller, Lars; Schulzke, Jo?rg D.; Niedrig, Matthias; Bu?cker, Roland

    2014-01-01

    Tick-borne encephalitis virus (TBEV) is one of the most important vector-borne viruses in Europe and Asia. Its transmission mainly occurs by the bite of an infected tick. However, consuming milk products from infected livestock animals caused TBEV cases. To better understand TBEV transmission via the alimentary route, we studied viral infection of human intestinal epithelial cells. Caco-2 cells were used to investigate pathological effects of TBEV infection. TBEV-infected Caco-2 monolayers sh...

  17. Modulation of chromatin remodelling induced by the freshwater cyanotoxin cylindrospermopsin in human intestinal caco-2 cells.

    Science.gov (United States)

    Huguet, Antoine; Hatton, Aurlie; Villot, Romain; Quenault, Hlne; Blanchard, Yannick; Fessard, Valrie

    2014-01-01

    Cylindrospermopsin (CYN) is a cyanotoxin that has been recognised as an emerging potential public health risk. Although CYN toxicity has been demonstrated, the mechanisms involved have not been fully characterised. To identify some key pathways related to this toxicity, we studied the transcriptomic profile of human intestinal Caco-2 cells exposed to a sub-toxic concentration of CYN (1.6 M for 24hrs) using a non-targeted approach. CYN was shown to modulate different biological functions which were related to growth arrest (with down-regulation of cdkn1a and uhrf1 genes), and DNA recombination and repair (with up-regulation of aptx and pms2 genes). Our main results reported an increased expression of some histone-modifying enzymes (histone acetyl and methyltransferases MYST1, KAT5 and EHMT2) involved in chromatin remodelling, which is essential for initiating transcription. We also detected greater levels of acetylated histone H2A (Lys5) and dimethylated histone H3 (Lys4), two products of these enzymes. In conclusion, CYN overexpressed proteins involved in DNA damage repair and transcription, including modifications of nucleosomal histones. Our results highlighted some new cell processes induced by CYN. PMID:24921660

  18. Screening and evaluation of human intestinal lactobacilli for the development of novel gastrointestinal probiotics.

    Science.gov (United States)

    Kll, Piret; Mndar, Reet; Smidt, Imbi; Htt, Pirje; Truusalu, Kai; Mikelsaar, Raik-Hiio; Shchepetova, Jelena; Krogh-Andersen, Kasper; Marcotte, Harold; Hammarstrm, Lennart; Mikelsaar, Marika

    2010-12-01

    The aim of this study was to screen intestinal lactobacilli strains for their advantageous properties to select those that could be used for the development of novel gastrointestinal probiotics. Ninety-three isolates were subjected to screening procedures. Fifty-nine percent of the examined lactobacilli showed the ability to auto-aggregate, 97% tolerated a high concentration of bile (2% w/v), 50% survived for 4 h at pH 3.0, and all strains were unaffected by a high concentration of pancreatin (0.5% w/v). One Lactobacillus buchneri strain was resistant to tetracycline. None of the tested strains caused lysis of human erythrocytes. Six potential probiotic strains were selected for safety evaluation in a mouse model. Five of 6 strains caused no translocation, and were considered safe. In conclusion, several strains belonging to different species and fermentation groups were found that have properties required for a potential probiotic strain. This study was the first phase of a multi-phase study aimed to develop a novel, safe and efficient prophylactic and therapeutic treatment system against gastrointestinal infections using genetically modified probiotic lactobacilli. PMID:20443005

  19. Transepithelial transports of rare sugar D-psicose in human intestine.

    Science.gov (United States)

    Hishiike, Takashi; Ogawa, Masahiro; Hayakawa, Shigeru; Nakajima, Daichi; O'Charoen, Siwaporn; Ooshima, Hisaka; Sun, Yuanxia

    2013-07-31

    D-Psicose (Psi), the C3-epimer of D-fructose (Fru), is a noncalorie sugar with a lower glycemic response. The trans-cellular pathway of Psi in human enterocytes was investigated using a Caco-2 cell monolayer. The permeation rate of Psi across the monolayer was not affected by the addition of phlorizin, an inhibitor of sugar transporter SGLT1, whereas it was accelerated by treatment with forskolin, a GLUT5-gene inducer, clearly showing that GLUT5 is involved in the transport of Psi. The permeability of Psi was suppressed in the presence of D-glucose (Glc) and Fru, suggesting that the three monosaccharides are transported via the same transporter. Since GLUT2, the predominant sugar transporter on the basolateral membrane of enterocytes, mediates the transport of Glc and Fru, Psi might be mediated by GLUT2. The present study shows that Psi is incorporated from the intestinal lumen into enterocytes via GLUT5 and is released to the lamina propria via GLUT2. PMID:23844903

  20. Animal models of intestinal fibrosis: new tools for the understanding of pathogenesis and therapy of human disease

    Science.gov (United States)

    Rieder, Florian; Kessler, Sean; Sans, Miquel

    2012-01-01

    Fibrosis is a serious condition complicating chronic inflammatory processes affecting the intestinal tract. Advances in this field that rely on human studies have been slow and seriously restricted by practical and logistic reasons. As a consequence, well-characterized animal models of intestinal fibrosis have emerged as logical and essential systems to better define and understand the pathophysiology of fibrosis. In point of fact, animal models allow the execution of mechanistic studies as well as the implementation of clinical trials with novel, pathophysiology-based therapeutic approaches. This review provides an overview of the currently available animal models of intestinal fibrosis, taking into consideration the methods of induction, key characteristics of each model, and underlying mechanisms. Currently available models will be classified into seven categories: spontaneous, gene-targeted, chemical-, immune-, bacteria-, and radiation-induced as well as postoperative fibrosis. Each model will be discussed in regard to its potential to create research opportunities to gain insights into the mechanisms of intestinal fibrosis and stricture formation and assist in the development of effective and specific antifibrotic therapies. PMID:22878121

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

    Directory of Open Access Journals (Sweden)

    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 specimens (10 to 50 mg, wet wt that can be resolved as bacterial community fingerprints using PCR-DGGE technique. Subsequently, PCR-DGGE technique can be applied for studying variations in human intestinal microbial communities.

  2. Evaluation by computerized morphometry of histopathological alterations of the colon wall in segments with and without intestinal transit in rats / Avaliao por morfometria computadorizada das alteraes histopatolgicas da parede clica em segmentos com e sem trnsito intestinal em ratos

    Scientific Electronic Library Online (English)

    Marcos Vieira de, Sousa; Denise Gonalves, Priolli; Adriana Valim, Portes; Izilda Aparecida, Cardinalli; Jos Aires, Pereira; Carlos Augusto Real, Martinez.

    2008-10-01

    Full Text Available OBJETIVO: Avaliar por mtodo de imagem assistida por computador as alteraes histopatolgicas da parede clica em segmentos providos e desprovidos de trnsito intestinal e relacion-las ao tempo de excluso. MTODOS: Trinta ratos Wistar machos foram submetidos derivao do trnsito no clon esque [...] rdo por meio de colostomia proximal e fstula mucosa distal. Os animais foram divididos em trs grupos experimentais segundo o sacrifcio ter sido realizado seis, doze e dezoito semanas aps o procedimento cirrgico inicial. Segmentos dos clons providos e desprovidos de trnsito foram submetidos a estudo histopatolgico. Foram analisadas as variveis: comprimento das criptas clicas, ulcerao na mucosa, espessura das camadas muscular da mucosa, submucosa e muscular prpria, congesto vascular, nmero de clulas caliciformes e graduao inflamatria comparando os dois segmentos clicos nos diferentes grupos experimentais. As variveis, comprimento das criptas intestinais, espessura das camadas muscular da mucosa, submucosa e muscular prpria foram mensuradas por mtodo de imagem assistida por computador. Na anlise estatstica foram utilizados testes de igualdade de mdias e medianas, anlise de varincia e correlao estabelecendo-se nvel de significncia de cinco por cento. RESULTADOS: A excluso de trnsito mostrou-se associada reduo do comprimento das criptas clicas, aumento da espessura das camadas muscular da mucosa, submucosa e muscular prpria. Verificou-se maior quantidade de ulceraes na mucosa e maior grau de inflamao com o progredir do tempo de excluso. Houve correlao significante entre as ulceraes da mucosa, congesto vascular da submucosa, aumento da espessura das camadas submucosa e muscular prpria, presena de clulas caliciformes, infiltrado inflamatrio, graduao inflamatria e o tempo de excluso de trnsito. CONCLUSES: Alteraes histolgicas ocorrem em todas as camadas da parede clica, em segmentos sem trnsito intestinal. Ulceraes na mucosa intestinal, aumento no nmero de clulas caliciformes, maior congesto vascular na camada submucosa e reao inflamatria estavam relacionadas com o progredir do tempo de excluso intestinal. Abstract in english 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 inflamma

  3. Comparison of the growth and metastasis of four human intestinal tumor cell line xenografts.

    Science.gov (United States)

    Joshi, S S; Jackson, J D; Sharp, J G

    1989-01-01

    The growth and metastasis of four human intestinal tumor cell lines: one duodenal adenocarcinoma (HTB-40) and three adenocarcinomas of the colon (CCL-218, CCL-222 and HT-29) have been compared in vitro and in vivo in nude mice. HTB-40 was the fastest growing cell line in vitro with a doubling time (DT) of 14.8 h. CCL-218 and CCL-222 grew more slowly in vitro with doubling times of 21.6 and 22.8 hours, respectively. All three of these tumors grew more slowly in vivo with doubling times ranging from 39.1 h (CCL-218 in male nude mice) to 65.3 h (CCL-222). The growth of CCL-218 cells was significantly slower in female nude mice DT 51.0 h). HT-29 was the slowest growing in vitro (DT 23.8 h) and in vivo (DT about 100 h). HT-29 also showed the greatest discrepancy between its DT measured in vivo as compared to in vitro, suggesting a greater clonogenic cell loss from HT-29 tumors in vivo. Histologic evaluation of these tumors grown subcutaneously in nude mice showed all to be anaplastic and to produce liver micrometastases. However, more extensive abdominal and liver metastases were observed in the nude mice injected with HT-29 cells, and some of these metastases had morphologic features of moderately well-differentiated epithelium. These results indicate the usefulness of the HT-29 tumor cell line as an experimental model of metastasis from a human colonic adenocarcinoma. PMID:2762735

  4. Changes in starch physical characteristics following digestion of foods in the human small intestine.

    Science.gov (United States)

    Zhou, Zhongkai; Topping, David L; Morell, Matthew K; Bird, Anthony R

    2010-08-01

    Factors controlling the concentration of resistant starch (RS) in foods are of considerable interest on account of the potential for this type of fibre to deliver health benefits to consumers. The present study was aimed at establishing changes in starch granule morphology as a result of human small-intestinal digestion. Volunteers with ileostomy consumed six selected foods: breakfast cereal (muesli), white bread, oven-baked French fries, canned mixed beans and a custard containing either a low-amylose maize starch (LAMS) or a high-amylose maize starch (HAMS). Analysis showed that digesta total RS (as a fraction of ingested starch) was: muesli, 8.9 %; bread, 4.8 %; fries, 4.2 %; bean mix, 35.9 %; LAMS custard, 4.0 %; HAMS custard, 29.1 %. Chromatographic analysis showed that undigested food contained three major starch fractions. These had average molecular weights (MW) of 43,500 kDa, 420 kDa and 8.5 kDa and were rich in amylopectin, higher-MW amylose and low-MW amylose, respectively. The low-MW amylose fraction became enriched preferentially in the stomal effluent while the medium-MW starch fraction showed the greatest loss. Fourier transform IR spectroscopy showed that absorbance at 1022 per cm decreased after digestion while the absorbance band at 1047 per cm became greater. Such changes have been suggested to indicate shifts from less ordered to more ordered granule structures. Further analysis of amylose composition by scanning iodine spectra indicated that the MW of amylose in ileal digesta was lower than that of undigested amylose. It appears that high-MW amylose is preferentially digested and that MW, rather than amylose content alone, is associated with resistance of starch to digestion in the upper gut of humans. PMID:20412607

  5. Intestinal spirochetosis

    OpenAIRE

    Luis Roberto Manzione Nadal; Sidney Roberto Nadal

    2011-01-01

    The intestinal spirochetosis (IS) is a histologically defined by the presence of spirochetal microorganisms connected to the apical cell membrane of the colorectal epithelium. The disease is caused by a heterogeneous group of bacteria. In humans, Brachyspira aalborgi and Brachyspira pilosicoli are prevalent. The incidence ranges from 1% in developed countries to 34% in poorer areas. It affects 62.5% of colonized areas, as well as men who have intercourse with men (MSM) and those with the huma...

  6. Formation of nitrogen-containing metabolites from the main iridoids of Harpagophytum procumbens and H. zeyheri by human intestinal bacteria.

    Science.gov (United States)

    Baghdikian, B; Guiraud-Dauriac, H; Ollivier, E; N'Guyen, A; Dumenil, G; Balansard, G

    1999-03-01

    The study of the metabolism of iridoid glycosides from Harpagophytum procumbens and Harpagophytum zeyheri by human intestinal bacteria, was realized in order to elucidate compounds responsible for the pharmacological activities of Harpagophytum. Harpagide, harpagoside and 8-O-p-coumaroyl-harpagide were transformed into the pyridine monoterpene alkaloid aucubinine B by human fecal flora and by bacteria isolated from this flora. Aucubinine B was also prepared from harpagide, harpagoside and 8-O-p-coumaroylharpagide, by beta-glucosidase in the presence of NH4+. PMID:10193209

  7. Human ?2-glycoprotein I attenuates mouse intestinal ischemia/reperfusion induced injury and inflammation

    OpenAIRE

    TOMASI, MAURIZIO; Hiromasa, Yasuaki; Pope, Michael R.; Gudlur, Sushanth; Tomich, John M.; Fleming, Sherry D

    2012-01-01

    Intestinal ischemia-reperfusion (IR)-induced injury results from a complex cascade of inflammatory components. In the mouse model of intestinal IR, the serum protein, ?2-glycoprotein I (?2-GPI) binds to the cell surface early in the cascade. The bound ?2-GPI undergoes a conformational change which exposes a neoantigen recognized by naturally occurring antibodies and initiates the complement cascade. We hypothesized that providing additional antigen with exogenous ?2-GPI would alter IR-induced...

  8. Calcitonin Receptor-Mediated CFTR Activation in Human Intestinal Epithelial Cells

    OpenAIRE

    LIU, HONGGUANG; Singla, Amika; Ao, Mei; Gill, Ravinder K; Venkatasubramanian, Jayashree; Rao, Mrinalini C.; ALREFAI, Waddah A.; DUDEJA, Pradeep K.

    2011-01-01

    High levels of calcitonin (CT) observed in medullary thyroid carcinoma and other calcitonin-secreting tumors cause severe diarrhea. Previous studies have suggested that calcitonin induces active chloride secretion. However, the involvement of calcitonin receptor (CTR) and the molecular mechanisms underlying the modulation of intestinal electrolyte secreting intestinal epithelial cells (IECs) have not been investigated. Therefore, current studies were undertaken to investigate the direct effec...

  9. Relationship between faecal character and intestinal transit time in normal dogs and diet-sensitive dogs.

    Science.gov (United States)

    Rolfe, V E; Adams, C A; Butterwick, R F; Batt, R M

    2002-07-01

    The relationship between stool character and whole gut transit time (WGTT), which is the average time for the passage of material through the lumen of the alimentary tract from ingestion to defecation, was studied in eight control dogs and 12 dogs with non-specific dietary sensitivity. Dogs were fed four diets in a cross-over design, and faecal quality was assessed daily and WGTT determined using plastic pellets. Faecal quality was unaffected by diet in the control dogs. Dogs with dietary sensitivity produced looser faeces compared with the control dogs, and this was significant for two of the diets. There was no significant effect of diet on mean WGTT within or between groups. Minimum WGTT, which was the interval to the first appearance of markers in faeces, was shorter in sensitive dogs compared with controls, and this was significant for two of the four diets. There were significant, inverse relationships between minimum WGTT and both mean faeces score and percentage unacceptable defecations. These data suggest that rapid transit of certain dietary components may impact negatively on stool quality and contribute to loose faeces in dogs with non-specific dietary sensitivity. PMID:12137148

  10. The spatial arrangement of the human large intestinal wall blood circulation.

    Science.gov (United States)

    Kachlik, David; Baca, Vaclav; Stingl, Josef

    2010-03-01

    The aim of the study was to describe and depict the spatial arrangement of the colon microcirculatory bed as a whole. Various parts of the large intestine and terminal ileum were harvested from either cadaver or section material or gained peroperatively. Samples were then injected with India ink or methylmetacrylate Mercox resin for microdissection and corrosion casting for scanning electron microscopy. The results showed that extramural vasa recta ramified to form the subserous plexus, some of them passing underneath the colon taeniae. Branches of both short and long vasa recta merged in the colon wall, pierced the muscular layer and spread out as the submucous plexus, which extended throughout the whole intestine without any interruption. The muscular layer received blood via both the centrifugal branches of the submucous plexus and the minor branches sent off by the subserous plexus. The mucosa was supplied by the mucous plexus, which sent capillaries into the walls of intestinal glands. The hexagonal arrangement of the intestinal glands reflected their vascular bed. All three presumptive critical points are only gross anatomical points of no physiological relevance in healthy individuals. Neither microscopic weak points nor regional differences were proven within the wall of the whole large intestine. The corrosion casts showed a huge density of capillaries under the mucosa of the large intestine. A regular hexagonal pattern of the vascular bed on the inner surface was revealed. No microvascular critical point proofs were confirmed and a correlation model to various pathological states was created. PMID:20447248

  11. Regulation of basal promoter activity of the human thiamine pyrophosphate transporter SLC44A4 in human intestinal epithelial cells.

    Science.gov (United States)

    Nabokina, Svetlana M; Ramos, Mel Brendan; Valle, Judith E; Said, Hamid M

    2015-05-01

    Microbiota of the large intestine synthesize considerable amount of vitamin B1 in the form of thiamine pyrophosphate (TPP). There is a specific high-affinity regulated carrier-mediated uptake system for TPP in human colonocytes (product of the SLC44A4 gene). The mechanisms of regulation of SLC44A4 gene expression are currently unknown. In this study, we characterized the SLC44A4 minimal promoter region and identified transcription factors important for basal promoter activity in colonic epithelial cells. The 5'-regulatory region of the SLC44A4 gene (1,022 bp) was cloned and showed promoter activity upon transient transfection into human colonic epithelial NCM460 cells. With the use of a series of 5'- and 3'-deletion luciferase reporter constructs, the minimal genomic region that required basal transcription of the SLC44A4 gene expression was mapped between nucleotides -178 and +88 (using the distal transcriptional start site as +1). Mutational analysis performed on putative cis-regulatory elements established the involvement of ETS/ELF3 [E26 transformation-specific sequence (ETS) proteins], cAMP-responsive element (CRE), and SP1/GC-box sequence motifs in basal SLC44A4 promoter activity. By means of EMSA, binding of ELF3 and CRE-binding protein-1 (CREB-1) transcription factors to the SLC44A4 minimal promoter was shown. Contribution of CREB into SLC44A4 promoter activity was confirmed using NCM460 cells overexpressing CREB. We also found high expression of ELF3 and CREB-1 in colonic (NCM460) compared with noncolonic (ARPE19) cells, suggesting their possible contribution to colon-specific pattern of SLC44A4 expression. This study represents the first characterization of the SLC44A4 promoter and reports the importance of both ELF3 and CREB-1 transcription factors in the maintenance of basal promoter activity in colonic epithelial cells. PMID:25715703

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

    Directory of Open Access Journals (Sweden)

    Ricanek P

    2015-01-01

    Full Text Available Petr Ricanek,1,2 Lisa K Lunde,3 Stephan A Frye,1 Mari Sten,1 Stle Nygrd,4 Jens P Morth,5,6 Andreas Rydning,2 Morten H Vatn,7,8 Mahmood Amiry-Moghaddam,3 Tone Tnjum,1,9 1Department of Microbiology, Oslo University Hospital, Rikshospitalet, Oslo, 2Department of Gastroenterology, Akershus University Hospital, Lrenskog and Campus Ahus, Institute of Clinical Medicine, University of Oslo, Lrenskog, 3Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, 4Bioinformatics Core Facility, Institute for Medical Informatics, Oslo University Hospital and University of Oslo, 5Centre for Molecular Medicine, Nordic EMBL Partnership, University of Oslo, 6Institute for Experimental Research, Oslo University Hospital (Ullevaal, Oslo, 7EpiGen Institute, Campus Ahus, Institute of Clinical Medicine, University of Oslo, Lrenskog, 8Section of Gastroenterology, Oslo University Hospital, Rikshospitalet, Oslo, 9Department of Microbiology, University of Oslo, Oslo, Norway Objectives: The aim of this study was to investigate the relationship between aquaporin (AQP water channel expression and the pathological features of early untreated inflammatory bowel disease (IBD in humans. Methods: Patients suspected to have IBD on the basis of predefined symptoms, including abdominal pain, diarrhea, and/or blood in stool for more than 10 days, were examined at the local hospital. Colonoscopy with biopsies was performed and blood samples were taken. Patients who did not meet the diagnostic criteria for IBD and who displayed no evidence of infection or other pathology in the gut were included as symptomatic non-IBD controls. AQP1, 3, 4, 5, 7, 8, and 9 messenger RNA (mRNA levels were quantified in biopsies from the distal ileum and colon by quantitative real-time polymerase chain reaction. Protein expression of selected AQPs was assessed by confocal microscopy. Through multiple alignments of the deduced amino acid sequences, the putative three-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

  13. Immunohistochemical localization of a gap junction protein (connexin43) in the muscularis externa of murine, canine, and human intestine

    DEFF Research Database (Denmark)

    Mikkelsen, H B; Huizinga, J D

    1993-01-01

    Electron-microscopic studies have revealed a heterogeneous distribution of gap junctions in the muscularis externa of mammalian intestines. This heterogeneity is observed at four different levels: among species; between small and large intestines; between longitudinal and circular muscle layers; and between subdivisions of the circular muscle layer. We correlated results obtained with two immunomethods, using an antibody to the known gap-junctional protein (connexin43) with ultrastructural findings, and further evaluated the respective sensitivity of these two approaches. For comparative reasons we also included the vascular smooth muscle of coronary arteries into our study. Two versions of the immunotechnique (peroxidase-antiperoxidase and fluorescence methods) were applied to frozen sections of murine, canine, and human small and large intestines, as well as to pig coronary artery. In the small intestine of all three species a very strong reactivity marked the outer main division of the circular muscle layer, while the longitudinal muscle layer as well as the inner thin division of the circular muscle layer were negative. In murine and human colon both muscle layers were negative, while in canine colon the border layer between the circular muscle and the submucosa reacted strongly, and scattered activity was found in the portion of the circular muscle layer (one tenth of its thickness) closest to the submucosa. The remainder of the circular muscle layer and the entire longitudinal muscle layer were negative in the canine colon. In the coronary artery we could not confirm the positive, specific labeling reported by other investigators (l.c.).(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Real-time cell analysis for monitoring cholera toxin-induced human intestinal epithelial cell response.

    Science.gov (United States)

    Ye, Julian; Luo, Yun; Fang, Weijia; Pan, Junhang; Zhang, Zheng; Zhang, Yanjun; Chen, Zhiping; Jin, Dazhi

    2015-04-01

    The pathogenic mechanism of Vibrio cholerae manifests as diarrhea and causes life-threatening dehydration. Here, we observe the human intestinal epithelial cells (HIEC) response to Cholera toxin (CT) by a real-time cell analysis (RTCA) platform, and disclose the difference from CT-induced cytotoxicity and others in HIEC. An HIEC cell of 1.0נ10(5)cells/mL was characterized as the suitable concentration for each well. For experimentation, the assay requires an inoculation of CT dissolved in Dulbecco's phosphate-buffered saline with 0.1% gelatin for a period of 18-25h. The dimensionless impedance cell index curve presented characteristic dose- and time-dependent drop responses at the first stage, and the CT-induced cytotoxicity was the most remarkable following exposure for 18-25h (P=0.0002). Following the obvious cytotoxic reaction, the CI curve gradually increased over time until the original CI value, indicating that self-recovery occurred. The CT-induced CI curve for HIEC was different from that induced by other toxins, including diphtheria and Clostridium difficile toxin. Collectively, these results suggest that the CT-induced cytotoxicity in HIEC was absolutely different from that induced by C. difficile and other toxins because of the different pathogeneses that were correlated with the specific CI curve generated by the RTCA system. In summary, our data show that the assay described here is a convenient and rapid high-throughput tool for real-time monitoring of host cellular responses to CT on the basis of the characteristic CI curve. PMID:25510171

  15. Characterization of two distinct modes of drug binding to human intestinal fatty acid binding protein.

    Science.gov (United States)

    Patil, Rahul; Laguerre, Aisha; Wielens, Jerome; Headey, Stephen J; Williams, Martin L; Hughes, Maria L R; Mohanty, Biswaranjan; Porter, Christopher J H; Scanlon, Martin J

    2014-11-21

    The aqueous cytoplasm of cells poses a potentially significant barrier for many lipophilic drugs to reach their sites of action. Fatty acid binding proteins (FABPs) bind to poorly water-soluble fatty acids (FAs) and lipophilic compounds and facilitate their intracellular transport. Several structures of FA in complex with FABPs have been described, but data describing the binding sites of other lipophilic ligands including drugs are limited. Here the environmentally sensitive fluorophores, 1-anilinonapthalene 8-sulfonic acid (ANS), and 11-dansylamino undecanoic acid (DAUDA) were used to investigate drug binding to human intestinal FABP (hIFABP). Most drugs that bound hIFABP were able to displace both ANS and DAUDA. A notable exception was ketorolac, a non-steroidal anti-inflammatory drug that bound to hIFABP and displaced DAUDA but failed to displace ANS. Isothermal titration calorimetry revealed that for the majority of ligands including FA, ANS, and DAUDA, binding to hIFABP was exothermic. In contrast, ketorolac binding to hIFABP was endothermic and entropy-driven. The X-ray crystal structure of DAUDA-hIFABP revealed a FA-like binding mode where the carboxylate of DAUDA formed a network of hydrogen bonds with residues at the bottom of the binding cavity and the dansyl group interacted with residues in the portal region. In contrast, NMR chemical shift perturbation (CSP) data suggested that ANS bound only toward the bottom of the hIFABP cavity, whereas ketorolac occupied only the portal region. The CSP data further suggested that ANS and ketorolac were able to bind simultaneously to hIFABP, consistent with the lack of displacement of ANS observed by fluorescence and supported by a model of the ternary complex. The NMR solution structure of the ketorolac-hIFABP complex therefore describes a newly characterized, hydrophobic ligand binding site in the portal region of hIFABP. PMID:25144524

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

    Directory of Open Access Journals (Sweden)

    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-producing enterodiol from defatted flaxseeds.

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

    International Nuclear Information System (INIS)

    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 ?M. 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 enerntration 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

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

    Directory of Open Access Journals (Sweden)

    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 cervical plexus(SI-16, cervical n. from C2,3(SI-16, fascial n. br.(SI-17, great auricular n. br.(SI-17, cervical n. br. from C2(SI-17, vagus n.(SI-17,hypoglossal n.(SI-17, glossopharyngeal n.(SI-17, sympathetic trunk(SI-17, zygomatic br. of fascial n.(SI-18, maxillary n. br.(SI-18, auriculotemporal n.(SI-19, temporal br. of fascial n.(SI-19 3 Blood vessels ; Dorsal digital vein.(SI-1, dorsal br. of proper palmar digital artery(SI-1, br. of dorsal metacarpal a. & v.(SI-2, 3, 4, dorsal carpal br. of ulnar a.(SI-4, 5, post. interosseous a. br.(SI-6,7, post. ulnar recurrent a.(SI-8, circuirflex scapular a.(SI-9, 11 , post. circumflex humeral a. br.(SI-10, suprascapular a.(SI-10, 11, 12, 13, first intercostal a. br.(SI-12, 14, transverse cervical a. br.(SI-12,13,14,15, second intercostal a. br.(SI-13, dorsal scapular a. br.(SI-13, 14, 15, ext. jugular v.(SI-16, 17, occipital a. br.(SI-16, Ext. jugular v. br.(SI-17, post. auricular a.(SI-17, int. jugular v.(SI-17, int. carotid a.(SI-17, transverse fascial a. & v.(SI-18,maxillary a. br.(SI-18, superficial temporal a. & v.(SI-19.

  19. The Food-Associated Ribotoxin Deoxynivalenol Modulates Inducible NO Synthase in Human Intestinal Cell Model.

    Science.gov (United States)

    Graziani, Fabien; Pujol, Ange; Nicoletti, Cendrine; Pinton, Philippe; Armand, Loriane; Di Pasquale, Eric; Oswald, Isabelle P; Perrier, Josette; Maresca, Marc

    2015-06-01

    The intestinal epithelium possesses active immune functions including the production of proinflammatory cytokines and antimicrobial molecules such as nitric oxide (NO). As observed with immune cells, the production of NO by the intestinal epithelium is mainly due to the expression of the inducible NO synthase (iNOS or NOS2). Epithelial immune functions could be affected by many factors including pathogenic microorganisms and food-associated toxins (bacterial and fungal). Among the various mycotoxins, deoxynivalenol (DON) is known to alter the systemic and intestinal immunity. However, little is known about the effect of DON on the production of NO by the intestinal epithelium. We studied the impact of DON on the intestinal expression of iNOS using the Caco-2 cell model. In line with its proinflammatory activity, we observed that DON dose-dependently up-regulates the expression of iNOS mRNA. Surprisingly, DON failed to increase the expression of iNOS protein. When testing the effects of DON on cytokine-mediated induction of iNOS, we found that very low concentrations of DON (ie, 1?M) decrease the amount of iNOS protein but not of iNOS mRNA. We demonstrated that DON's effect on iNOS protein relies on its ability to activate signal pathways and to increase iNOS ubiquitinylation and degradation through the proteasome pathway. Taken together, our results demonstrate that although DON causes intestinal inflammation, it suppresses the ability of the gut epithelium to express iNOS and to produce NO, potentially explaining the increased susceptibility of animals to intestinal infection following exposure to low doses of DON. PMID:25766886

  20. Characterization of In Vitro Glucuronidation Clearance of a Range of Drugs in Human Kidney Microsomes: Comparison with Liver and Intestinal Glucuronidation and Impact of Albumin

    OpenAIRE

    Gill, Katherine L.; Houston, J. Brian; Galetin, Aleksandra

    2012-01-01

    Previous studies have shown the importance of the addition of albumin for characterization of hepatic glucuronidation in vitro; however, no reports exist on the effects of albumin on renal or intestinal microsomal glucuronidation assays. This study characterized glucuronidation clearance (CLint, UGT) in human kidney, liver, and intestinal microsomes in the presence and absence of bovine serum albumin (BSA) for seven drugs with differential UDP-glucuronosyltransferase (UGT) 1A9 and UGT2B7 spec...

  1. Blastocystis ratti Contains Cysteine Proteases That Mediate Interleukin-8 Response from Human Intestinal Epithelial Cells in an NF-?B-Dependent Manner?

    OpenAIRE

    Puthia, Manoj K.; Lu, Jia; Tan, Kevin S.W.

    2007-01-01

    Blastocystis is a ubiquitous enteric protozoan found in the intestinal tracts of humans and a wide range of animals. Evidence accumulated over the last decade suggests association of Blastocystis with gastrointestinal disorders involving diarrhea, abdominal pain, constipation, nausea, and fatigue. Clinical and experimental studies have associated Blastocystis with intestinal inflammation, and it has been shown that Blastocystis has potential to modulate the host immune response. Blastocystis ...

  2. Intestinal Cancer

    Science.gov (United States)

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

  3. Intestinal Coccidia

    Directory of Open Access Journals (Sweden)

    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 intestinal parasite is in most parts of the world. Sometimes it is noun traveller diarrhea Syndrom. The egg shapes of Oocyst are disporic tetrazoic. It is transmitted by vegetables and fruits. Trophozoite pass through schizogony step and repeats it several times. In the end of the cycle gametogony is done and the sexual forms will be repelled the human intestine. Symptoms are persistent diarrhoea, epigastric pain, headache, fever, vomitting and leanness, especially when physiologic disorder condition is seen in patient or they are in traveling. Misdiagnosis is a problem in laboratories but floatation method with zinc sulfate or sugar syrup is recommended. Sarcocystis: Sporocyst of S.hominis and S. suihominis is in the human feces, and the cyst form is in pig and cow muscles. It founds in tha tongue, pharynx and oesophagus muscles of habitant buffalo in Iran. Because of the large size of the cyst (1cm, it is seen with naked eyes and the risk of human infection is rare. If human eats raw or uncooked cow and pig meat, he will be infected with it. Sexual cycle is in the human body and sporocyst is repelled by the intestine. The disease may or may not have any symptoms. The symptoms are diarrhoea, stomach cramp, jejenuom and ileum necrosis. Diagnosis is based on concentrated floatation. The prevalence rate is too much in domestic animals.

  4. Intestinal invagination Invaginacin intestinal.

    Directory of Open Access Journals (Sweden)

    Dayamnelys Aguilar Atanay

    2005-12-01

    Full Text Available Intestinal intussusceptions are the most frequent cause of acute surgical occlusive syndrome in infants; it is idiopathic in more than 90% of cases. Their treatment can be conservative, with reduction by means of imaging and hydrostatic procedures, or surgical. We presented the Good Clinical Practices Guideline for Intestinal intussusceptions, approved by consensus in the 3th National Good Clinical Practices Workshop in Pediatric Surgery (Camagey, Cuba; February 23 26, 2004.
    La invaginacin intestinal es la causa ms frecuente del sndrome de abdomen agudo quirrgico oclusivo en lactantes y es idioptica en ms del 90 % de los casos. Su tratamiento puede ser conservador, con reduccin mediante procedimientos hidrostticos combinados con vigilancia imaginolgica, o quirrgico. Se presenta la Gua de Buenas Prcticas Clnicas para invaginacin intestinal, aprobada por consenso en el 3er Taller Nacional de Buenas Prcticas Clnicas en Ciruga Peditrica (Camagey, 23 al 26 de febrero de 2004.

  5. Ontogeny of human hepatic and intestinal transporter gene expression during childhood: age matters.

    Science.gov (United States)

    Mooij, Miriam G; Schwarz, Ute I; de Koning, Barbara A E; Leeder, J Steven; Gaedigk, Roger; Samsom, Janneke N; Spaans, Edwin; van Goudoever, Johannes B; Tibboel, Dick; Kim, Richard B; de Wildt, Saskia N

    2014-08-01

    Many drugs prescribed to children are drug transporter substrates. Drug transporters are membrane-bound proteins that mediate the cellular uptake or efflux of drugs and are important to drug absorption and elimination. Very limited data are available on the effect of age on transporter expression. Our study assessed age-related gene expression of hepatic and intestinal drug transporters. Multidrug resistance protein 2 (MRP2), organic anion transporting polypeptide 1B1 (OATP1B1), and OATP1B3 expression was determined in postmortem liver samples (fetal n = 6, neonatal n = 19, infant n = 7, child n = 2, adult n = 11) and multidrug resistance 1 (MDR1) expression in 61 pediatric liver samples. Intestinal expression of MDR1, MRP2, and OATP2B1 was determined in surgical small bowel samples (neonates n = 15, infants n = 3, adults n = 14). Using real-time reverse-transcription polymerase chain reaction, we measured fetal and pediatric gene expression relative to 18S rRNA (liver) and villin (intestines), and we compared it with adults using the 2(-??Ct) method. Hepatic expression of MRP2, OATP1B1, and OATP1B3 in all pediatric age groups was significantly lower than in adults. Hepatic MDR1 mRNA expression in fetuses, neonates, and infants was significantly lower than in adults. Neonatal intestinal expressions of MDR1 and MRP2 were comparable to those in adults. Intestinal OATP2B1 expression in neonates was significantly higher than in adults. We provide new data that show organ- and transporter-dependent differences in hepatic and intestinal drug transporter expression in an age-dependent fashion. This suggests that substrate drug absorption mediated by these transporters may be subject to age-related variation in a transporter dependent pattern. PMID:24829289

  6. Ginsenoside-mediated blockade of 1?,25-dihydroxyvitamin D3 inactivation in human liver and intestine in vitro.

    Science.gov (United States)

    Deb, Subrata; Chin, Mei Yieng; Adomat, Hans; Guns, Emma S Tomlinson

    2014-05-01

    The beneficial effects of vitamin D3 are exerted through 1?,25-dihydroxyvitamin D3 [1?,25(OH)2D3], the dihydroxy metabolite of vitamin D3. Hepatic and intestinal biotransformation of 1?,25(OH)2D3 and modifiers of metabolic capacity could be important determinants of bioavailability in serum and tissues. Ginsenosides and their aglycones, mainly 20(S)-protopanaxadiol (aPPD) and 20(S)-protopanaxatriol (aPPT), are routinely ingested as health supplements. The purpose of the present study was to investigate the potential of ginsenosides and their aglycones to block hepatic and intestinal inactivation of 1?,25(OH)2D3, which is the most potent ligand of vitamin D receptor. In vitro biotransformation reactions were initiated with NADPH regenerating solutions following initial preincubation of pooled human hepatic or intestinal microsomal protein or human recombinant CYP3A4 supersomes with 1?,25(OH)2D3 or midazolam. Formation of hydroxylated metabolites of 1?,25(OH)2D3 or midazolam was analyzed using liquid chromatography-mass spectrometry. Co-incubation of 1?,25(OH)2D3 with various ginsenosides (Rg1, Rh2, aPPD, aPPT and total ginsenosides) led to differential inhibition (30-100%) of its hydroxylation. Results suggest that aPPD, aPPT and Rh2 strongly attenuated the hydroxylation of 1?,25(OH)2D3. Follow up inhibition studies with aPPD and aPPT at varying concentrations (0.5-100?M) led to up to 91-100% inhibition of formation of hydroxylated metabolites of 1?,25(OH)2D3 thus preventing inactivation of active vitamin D3. The IC50 values of aPPD or aPPT for the most abundant hydroxylated metabolites of 1?,25(OH)2D3 ranged from 3.3 to 9.0?M in human microsomes. The inhibitory mechanism of aPPD or aPPT for CYP3A4-mediated biotransformation of 1?,25(OH)2D3 was competitive in nature (apparent Ki: 1.7-2.9?M). Similar inhibitory effects were also observed upon addition of aPPD or aPPT into midazolam hydroxylation assay. In summary, our results suggest that ginsenosides, specifically aPPD and aPPT, inhibit the CYP3A4-mediated catabolism of active vitamin D3 in human liver and intestine, potentially providing additional vitamin D-related benefits to patients with cancer, neurodegenerative and metabolic diseases. PMID:24486455

  7. Transcriptional regulation of the human Na+/H+ exchanger NHE3 by serotonin in intestinal epithelial cells

    International Nuclear Information System (INIS)

    Serotonin (5-HT) decreases NHE2 and NHE3 activities under acute conditions in human intestinal epithelial cells. Here, we have investigated the effects of 5-HT on expression of the human NHE3 gene and the mechanisms underlying its transcriptional regulation in differentiated C2BBe1 cells. Treatment of the human intestinal epithelial cell line, C2BBe1, with 5-HT (20 ?M) resulted in a significant decrease in NHE3 mRNA and protein expression. In transient transfection studies, 5-HT repressed the NHE3 promoter activity by ?55%. The repression of the NHE3 promoter activity in response to 5-HT was accompanied by reduced DNA-binding activity of transcription factors Sp1 and Sp3 to the NHE3 promoter without alteration in their nuclear levels. Pharmacological inhibitors of protein kinase C reversed the inhibitory effect of 5-HT on the promoter activity. Our data indicate that 5-HT suppresses the transcriptional activity of the NHE3 promoter and this effect may be mediated by PKC? and modulation of DNA-binding affinities of Sp1 and Sp3.

  8. Polarized secretion of newly synthesized lipoproteins by the Caco-2 human intestinal cell line

    International Nuclear Information System (INIS)

    Lipoprotein secretion by Caco-2 cells, a human intestinal cell line, was studied in cells grown on inserts containing a Millipore filter (0.45 micron), separating secretory products from the apical and basolateral membranes into separate chambers. Under these conditions, as observed by electron microscopy, the cells formed a monolayer of columnar epithelial cells with microvilli on the apical surface and tight junctions between cells. The electrical resistances of the cell monolayers were 250-500 ohms/cm2. Both 14C-labeled lipids and 35S-labeled proteins were used to assess lipoprotein secretion. After a 24-hr incubation with [14C]oleic acid, 60-80% of the secreted triglyceride (TG) was in the basolateral chamber; 40% of the TG was present in the d less than 1.006 g/ml (chylomicron + VLDL) fraction and 50% in the 1.006 less than d less than 1.063 g/ml (LDL) fraction. After a 4-hr incubation with [35S]methionine, apolipoproteins were found to be major secretory products with 75-100% secreted to the basolateral chamber. Apolipoproteins B-100, B-48, E, A-I, A-IV, and C-III were identified by immunoprecipitation. The d less than 1.006 g/ml fraction was found to contain all of the major apolipoproteins, while the LDL fraction contained primarily apoB-100 and apoE; the HDL (1.063 less than d less than 1.21 g/ml) fraction principally contained apoA-I and apoA-IV. Mn-heparin precipitated all of the [35S]methionine-labeled of the [35S]methionine-labeled apoB-100 and B-48 and a majority of the other apolipoproteins, and 80% of the [14C]oleic acid-labeled triglyceride, but only 15% of the phospholipid, demonstrating that Caco-2 cells secrete triglyceride-rich lipoproteins containing apoB

  9. Antimicrobial activity of Phyllanthus amarus on some human intestinal facultatively anaerobic flora

    Directory of Open Access Journals (Sweden)

    Babatunde S.K

    2014-03-01

    Full Text Available Background: Phyllanthus amarus is an economic plant grown in West Africa that has antimicrobial properties. Aim: We investigated antimicrobial activity of aqueous extract of Phyllanthus amarus against some intestinal flora that are facultative anaerobes. Methods: The leaves were washed thoroughly in clean water, and rinsed in sterile distilled water, allowed to dry at room temperature for several days. It was oven dried at 45OC for about an hour until considered brittle enough to bleed. Final dilutions used were 500 mg/ml, 400 mg/ml, 300 mg/ml, 250 mg/ml and 200 mg/ml. Six intestinal organisms were isolated and identified: K. pneumoniae, P. aeruginosa, S. aureus, E. coli. P. mirabilis and E. faecalis. Both agar diffusion and broth dilution methods were used to assay antimicrobial activity against the organisms. Results: The result indicated that the growth of the organisms were inhibited at 50 mg/ml of aqueous extract by agar diffusion and broth dilution methods but varied at lower concentration. Phyllanthus amarus showed bacteriostatic action at this concentration because sub-culture yielded growth except on plate of K. pneumoniae. Consumption of cold or hot aqueous herbal preparations can alter microbial balance. The implication of ingestion of cold or hot aqueous herbal preparations against the normal intestinal flora was discussed. Conclusion: P. amarus possesses significant antimicrobial activity against normal intestinal flora.

  10. Inhibition of the NF-?B Pathway in Human Intestinal Epithelial Cells by Commensal Streptococcus salivarius ?

    OpenAIRE

    Kaci, Ghalia; Lakhdari, Omar; Dore?, Joe?l; Ehrlich, S. Dusko; Renault, Pierre; Blottie?re, Herve? 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-?). Supernatant from each strain downregulated NF-?B activation. The two most efficient strains produced an active metabolite (

  11. Oral beclomethasone dipropionate for treatment of human intestinal graft-versus-host disease.

    Science.gov (United States)

    Baehr, P H; Levine, D S; Bouvier, M E; Hockenbery, D M; Gooley, T A; Stern, J G; Martin, P J; McDonald, G B

    1995-12-15

    Intestinal graft-versus-host disease (GVHD) causes anorexia, vomiting, abdominal pain, and diarrhea. We investigated oral beclomethasone dipropionate (BDP), a potent, topically active corticosteroid, as therapy for this disease. Forty-two allogeneic marrow-graft recipients with biopsy-proven intestinal graft-versus-host disease of mild-to-moderate severity received BDP (8 mg daily) for up to 28 days. Weekly symptom scores, oral intake, and surveillance throat and stool cultures were compared with baseline values. Adrenal testing was performed serially in patients not receiving concurrent prednisone. Improvement was seen in appetite (P < 0.001), oral intake (P < 0.001), nausea (P = 0.013), and diarrhea (P = 0.02) over the course of therapy, and an overall beneficial response was observed in 72% of 40 evaluable patients. Surveillance cultures of throat and stool showed no increase in bacterial or fungal colonization over time. The adrenal axis became suppressed in 11 of 20 evaluable patients (55%) but suppression was not a prerequisite for clinical response, as 6 of 9 patients who retained normal adrenal function improved clinically. We conclude that oral BDP is a safe and effective treatment for mild-to-moderate intestinal graft-versus-host disease. Systemic absorption probably occurs, but adrenal suppression is not a prerequisite for clinical efficacy, suggesting that the biological effect is primarily topical. BDP should be further investigated as a topical therapy for intestinal GVHD. PMID:8525516

  12. Human population growth and the demographic transition

    OpenAIRE

    Bongaarts, John

    2009-01-01

    The world and most regions and countries are experiencing unprecedentedly rapid demographic change. The most obvious example of this change is the huge expansion of human numbers: four billion have been added since 1950. Projections for the next half century expect a highly divergent world, with stagnation or potential decline in parts of the developed world and continued rapid growth in the least developed regions. Other demographic processes are also undergoing extraordinary change: women's...

  13. Mouse gastric tumor models with prostaglandin E2 pathway activation show similar gene expression profiles to intestinal-type human gastric cancer

    Directory of Open Access Journals (Sweden)

    Oshima Masanobu

    2009-12-01

    Full Text Available Abstract Background Gastric cancers are generally classified into better differentiated intestinal-type tumor and poorly differentiated diffuse-type one according to Lauren's histological categorization. Although induction of prostaglandin E2 pathway promotes gastric tumors in mice in cooperation with deregulated Wnt or BMP signalings, it has remained unresolved whether the gastric tumor mouse models recapitulate either of human gastric cancer type. This study assessed the similarity in expression profiling between gastric tumors of transgenic mice and various tissues of human cancers to find best-fit human tumors for the transgenic mice models. Results Global expression profiling initially found gastric tumors from COX-2/mPGES-1 (C2mE-related transgenic mice (K19-C2mE, K19-Wnt1/C2mE, and K19-Nog/C2mE resembled gastric cancers among the several tissues of human cancers including colon, breast, lung and gastric tumors. Next, classification of the C2mE-related transgenic mice by a gene signature to distinguish human intestinal- and diffuse-type tumors showed C2mE-related transgenic mice were more similar to intestinal-type compared with diffuse one. We finally revealed that induction of Wnt pathway cooperating with the prostaglandin E2 pathway in mice (K19-Wnt1/C2mE mice further reproduce features of human gastric intestinal-type tumors. Conclusion We demonstrated that C2mE-related transgenic mice show significant similarity to intestinal-type gastric cancer when analyzed by global expression profiling. These results suggest that the C2mE-related transgenic mice, especially K19-Wnt1/C2mE mice, serve as a best-fit model to study molecular mechanism underlying the tumorigenesis of human gastric intestinal-type cancers.

  14. A microfluidic cell culture device (?FCCD) to culture epithelial cells with physiological and morphological properties that mimic those of the human intestine.

    Science.gov (United States)

    Chi, Meiying; Yi, Banya; Oh, Seunghan; Park, Dong-June; Sung, Jong Hwan; Park, Sungsu

    2015-06-01

    Physiological and morphological properties of the human intestine cannot be accurately mimicked in conventional culture devices such as well plates and petri dishes where intestinal epithelial cells form a monolayer with loose contacts among cells. Here, we report a novel microfluidic cell culture device (?FCCD) that can be used to culture cells as a human intestinal model. This device enables intestinal epithelial cells (Caco-2) to grow three-dimensionally on a porous membrane coated with fibronectin between two polydimethylsiloxane (PDMS) layers. Within 3days, Caco-2 cells cultured in the ?FCCD formed villi- and crypt-like structures with small intercellular spaces, while individual cells were tightly connected to one another through the expression of the tight junction protein occludin, and were covered with a secreted mucin, MUC-2. Caco-2 cells cultured in the ?FCCD for 3days were less susceptible to bacterial attack than those cultured in transwell plates for 21days. ?FCCD-cultured Caco-2 cells also displayed physiologically relevant absorption and paracellular transport properties. These results suggest that our intestinal model more accurately mimics the morphological and physiological properties of the intestine in vivo than the conventional transwell culture model. PMID:26002774

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

    DEFF Research Database (Denmark)

    Wilcks, Andrea; Hansen, Bjarne Munk

    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.

  16. Isquemia intestinal / Intestinal ischemia

    Scientific Electronic Library Online (English)

    Ileana, Guerra Macas; Zenn, Rodrguez Fernndez.

    2014-03-01

    Full Text Available La isquemia intestinal est considerada como la causa ms letal del sndrome de abdomen agudo; su consecuencia, el infarto del intestino delgado, ocurre por fenmenos tromboemblicos e isquemia no oclusiva. El objetivo del presente artculo es proporcionar una revisin bibliogrfica actualizada acer [...] ca del tema y facilitar la actuacin del cirujano ante este problema de salud de repercusin sistmica y que no es tan infrecuente como se piensa Abstract in english The intestinal ischemia is considered as the most lethal cause in the acute abdomen syndrome; its consequence, the small intestine infarction, takes place due to thromboembolic phenomena and non occlusive ischemia. The objective of the present work is to provide an updated literature review about th [...] e topic and to facilitate the surgeon's performance in front of this health problem of systemic repercussion which is not as uncommon as it is thought

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

    Science.gov (United States)

    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

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

    International Nuclear Information System (INIS)

    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 ?mol/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)

  19. Expression and function of the lipocalin-2 (24p3/NGAL) receptor in rodent and human intestinal epithelia

    DEFF Research Database (Denmark)

    Langelueddecke, Christian; Roussa, Eleni

    2013-01-01

    The lipocalin 2//NGAL/24p3 receptor (NGAL-R/24p3-R) is expressed in rodent distal nephron where it mediates protein endocytosis. The mechanisms of apical endocytosis and transcytosis of proteins and peptides in the intestine are poorly understood. In the present study, the expression and localization of rodent 24p3-R (r24p3-R) and human NGAL-R (hNGAL-R) was investigated in intestinal segments by immunofluorescence and confocal laser scanning microscopy, immunohistochemistry and immunoblotting. r24p3-R/hNGAL-R was also studied in human Caco-2 BBE cells and CHO cells transiently transfected with r24p3-R by immunofluorescence microscopy, RT-PCR and immunoblotting of plasma membrane enriched vesicles (PM). To assay function, endocytosis/transcytosis of putative ligands phytochelatin (PC?), metallothionein (MT) and transferrin (Tf) was assayed by measuring internalization of fluorescence-labelled ligands in Caco-2 BBE cells grown on plastic or as monolayers on Transwell inserts. The binding affinity of Alexa 488-PC? to colon-like Caco-2 BBE PM was quantified by microscale thermophoresis (MST). r24p3-R/hNGAL-R expression was detected apically in all intestinal segments but showed the highest expression in ileum and colon. Colon-like, but not duodenum-like, Caco-2 BBE cells expressed hNGAL-R on their surface. Colon-like Caco-2 BBE cells or r24p3-R transfected CHO cells internalized fluorescence-labelled PC? or MT with half-maximal saturation at submicromolar concentrations. Uptake of PC? and MT (0.7 M) by Caco-2 BBE cells was partially blocked by hNGAL (500 pM) and an EC?? of 18.6 12.2 nM was determined for binding of Alexa 488-PC? to PM vesicles by MST. Transwell experiments showed rapid (0.5-2 h) apical uptake and basolateral delivery of fluorescent PC?/MT/Tf (0.7 M). Apical uptake of ligands was significantly blocked by 500 pM hNGAL. hNGAL-R dependent uptake was more prominent with MT but transcytosis efficiency was reduced compared to PC? and Tf. Hence, r24p3-R/hNGAL-R may represent a high-affinity multi-ligand receptor for apical internalization and transcytosis of intact proteins/peptides by the lower intestine.

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

    OpenAIRE

    Benouis, A.; Bekkouche, Z.; Benmansour, Z.

    2013-01-01

    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%...

  1. Adherence of Probiotic Bacteria to Human Intestinal Mucus in Healthy Infants and during Rotavirus Infection

    OpenAIRE

    Juntunen, M.; Kirjavainen, P. V.; Ouwehand, A. C.; Salminen, S. J.; Isolauri, E.

    2001-01-01

    The concentration of fecal mucin and the adhesion of specific probiotics and their combinations in the intestinal mucus of infants during and after rotavirus diarrhea and in healthy children were determined. Mucus was prepared from fecal samples from 20 infants during and after rotavirus diarrhea and from 10 healthy age-matched children. Mucin concentration was determined, and the adhesion of five probioticsLactobacillus rhamnosus GG, Lactobacillus casei Shirota, Lactobacillus paracasei F1...

  2. Effect of Metals on ?-Actin and Total Protein Synthesis in Cultured Human Intestinal Epithelial Cells

    OpenAIRE

    Calabro, Anthony R.; Gazarian, Dmitry I.; Barile, Frank A.

    2010-01-01

    As an important structural protein, ?-actin is associated with anchoring of tight junctions (TJs) to the cell scaffold. Caco-2 cells, an immortal intestinal epithelial cell line, rely on ?-actin to form intact monolayers with high transepithelial electrical resistance in cell culture inserts. We examined the effect of six metals on expression of ?-actin mRNA and ?-actin synthesis, on total and net production of newly synthesized proteins, on paracellular transport of TJ markers, and on ce...

  3. The Probiotic Lactobacillus acidophilus Stimulates Chloride/Hydroxyl Exchange Activity in Human Intestinal Epithelial Cells12

    OpenAIRE

    Borthakur, Alip; Gill, Ravinder K.; Tyagi, Sangeeta; Koutsouris, Athanasia; Alrefai, Waddah A.; Hecht, Gail A.; Ramaswamy, Krishnamurthy; Dudeja, Pradeep K.

    2008-01-01

    Probiotics are viable nonpathogenic microorganisms that are considered to confer health benefits to the host. Recent studies indicated that some Lactobacillus species function as probiotics and have been used as alternative treatments for diarrhea, which occurs due to increased secretion, decreased absorption, or both. However, the direct effects of probiotics on intestinal electrolyte absorption are not known. Therefore, we examined the effects of Lactobacillus on luminal chloride/hydroxyl (...

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

    DEFF Research Database (Denmark)

    Larsen, U L; Hyldahl Olesen, L

    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 (MDR1) gene single nucleotide polymorphisms (SNPs) G2677T and C3435T using the model drug digoxin.

  5. Intestinal Stem Cells

    OpenAIRE

    Umar, Shahid

    2010-01-01

    Self-renewal in the intestinal epithelia is fueled by a population of undifferentiated intestinal stem cells (ISCs) that give rise to daughter or progenitor cells, which can subsequently differentiate into the mature cell types required for normal gut function. The cellular signals that regulate self-renewal are poorly understood and the factors that mediate the transition from a stem cell to a progenitor cell in the gut are unknown. Recent studies have suggested that ISCs are located either ...

  6. Immunomodulatory effect of a wild blueberry anthocyanin-rich extract in human Caco-2 intestinal cells.

    Science.gov (United States)

    Taverniti, Valentina; Fracassetti, Daniela; Del Bo', Cristian; Lanti, Claudia; Minuzzo, Mario; Klimis-Zacas, Dorothy; Riso, Patrizia; Guglielmetti, Simone

    2014-08-20

    Intestinal inflammation is a natural process crucial for the maintenance of gut functioning. However, abnormal or prolonged inflammatory responses may lead to the onset of chronic degenerative diseases, typically treated by means of pharmacological interventions. Dietary strategies for the prevention of inflammation are a safer alternative to pharmacotherapy. Anthocyanins and other polyphenols have been documented to display anti-inflammatory activity. In the present study, three bioactive fractions (anthocyanin, phenolic, and water-soluble fractions) were extracted from a wild blueberry powder. The Caco-2 intestinal model was used to test the immunomodulatory effect of the above fractions. Only the anthocyanin-rich fraction reduced the activation of NF-?B, induced by IL-1? in intestinal epithelial Caco-2 cells. Specifically, concentrations of 50 and 100 ?g mL(-1) decreased NF-?B activation by 68.9 and 85.2%, respectively (p ? 0.05). These preliminary results provide further support for the role of food bioactives as potential dietary anti-inflammatory agents. PMID:25075866

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

    Science.gov (United States)

    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.

  8. Interaction of PHM, PHI and 24-glutamine PHI with human VIP receptors from colonic epithelium: comparison with rat intestinal receptors

    International Nuclear Information System (INIS)

    PHM, the human counterpart of porcine Peptide Histidine Isoleucine amide (PHI), is shown to be a VIP agonist with low potency on human VIP receptors located in colonic epithelial cell membranes. Its potency is identical to that of PHI but by 3 orders of magnitude lower than that of VIP itself in inhibiting 125I-VIP binding and in stimulating adenylate cyclase activity. This contrasts markedly with the behavior of PHI on rat VIP receptors located in intestinal epithelial cell membranes where PHI is a potent agonist with a potency that is 1/5 that of VIP. In another connection, the authors show that 24-glutamine PHI has the same affinity as 24-glutamic acid PHI (the natural peptide) for rat or human VIP receptors. These results indicate that while PHI may exert some physiological function through its interaction with VIP receptors in rodents, its human counterpart PHM is a very poor agonist of VIP in human. Furthermore, they show that the drastic change in position 24 of PHI (neutral versus acid residue) does not affect the activity of PHI, at least on VIP receptors. 21 references, 1 figure

  9. Application of ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry to identify curcumin metabolites produced by human intestinal bacteria.

    Science.gov (United States)

    Lou, Yan; Zheng, Jinqi; Hu, Haihong; Lee, Jun; Zeng, Su

    2015-03-15

    Curcumin, a yellow pigment derived from the rhizomes of Curcuma longa Linn, is a natural antioxidant that exhibits a variety of pharmacological activities and therapeutic properties. However, as curcumin is generally conjugated when absorbed through the intestine, free curcumin is present at extremely low levels in the body. Thus, curcumin metabolites are presumed to be responsible for curcumin bioactivity. In this study, we describe a strategy using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF MS) with automated data analysis software (MetaboLynx(XS)) for rapid analysis of the metabolic profile of curcumin in human intestinal flora. The results show that curcumin undergoes extensive phase I and phase II metabolism. A total of 23 curcumin metabolites were detected and identified in vitro. Furthermore, we identified a number of novel metabolic pathways of curcumin in the human intestinal microflora system. PMID:25658514

  10. Absoro intestinal de D-xilose em crianas infectadas pelo vrus da imunodeficincia humana Intestinal absorption of D-xilose in children infected with the human immunodeficiency virus

    Directory of Open Access Journals (Sweden)

    Nilza Medeiros PERIN

    2001-10-01

    Full Text Available Objetivos - Avaliar a absoro intestinal em crianas de 18 meses a 14 anos infectadas pelo HIV, atendidas em uma unidade de ambulatrio e verificar se existe associao entre m absoro, diarria, estado nutricional, alterao imunolgica, parasitas entricos clssicos e Cryptosporidium. Metodologia - A absoro intestinal foi investigada utilizando-se a medida da D-xilose srica. Amostras fecais foram colhidas para a pesquisa de ptogenos entricos clssicos e Cryptosporidium. O tamanho da amostra foi calculado considerando a prevalncia de 30% com preciso de 5% de alterao na absoro da D-xilose em crianas infectadas pelo HIV. Os procedimentos estatsticos utilizados foram: medidas descritivas, anlise de correspondncia mltipla e regresso logstica. Resultados - Das 104 crianas estudadas, somente 8 (7,7% apresentaram o teste da D-xilose alterado e 33 (31,73% foram positivas para Cryptosporidium. A anlise de correspondncia mltipla aplicada aos dados encontrados sugeriu a associao entre o teste da D-xilose alterado e a presena de Cryptosporidium. No se encontrou associao entre o teste alterado e diarria, estado nutricional, alterao imunolgica e parasistas entricos clssicos. Concluses - A m absoro intestinal avaliada pelo teste da D-xilose foi infreqente nas crianas HIV positivas estudadas. O comprometimento intestinal, quando presente, parece estar relacionado com a presena de Cryptosporidium, porm no com diarria, estado nutricional, alterao imunolgica e parasistas entricos clssicos.Aim - To evaluate the intestinal absorption in HIV-infected children children 14 months to 14 years and to investigate its relationship to diarrhea, nutritional status, immune dysfunction, classical enteric parasites and Cryptosporidium. Methods - Intestinal absorption was investigated by measuring serum D-xylose. Fecal samples were investigated for classical pathogens and Cryptosporidium. The sample size was calculated considering a 30% prevalence of altered D-xylose absorption in HIV-infected children with a 5% accuracy. Statistical procedures used were: descriptive measurements, multiple correspondence analysis and logistic regression. Results - D-xylose absorption was altered in only 8 out of 104 (7,7% and Cryptosporidium was positive in 33 out of 104 (31,73% HIV-infected children. The multiple correspondence analysis suggested an association between an altered D-xylose test and Cryptosporidium. D-xylose malabsorption was not associated with diarrhea, nutritional status, immune disfunction and classic enteric parasites. Conclusions - Intestinal malabsorption evaluated through the D-xylose test was an uncommon finding in HIV-infected children. Intestinal dysfunction when present seems to be related to Cryptosporidium, but not to diarrhea, nutritional status, immune disfunction and classic enteric parasites.

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

    Energy Technology Data Exchange (ETDEWEB)

    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 ?-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.

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

    DEFF Research Database (Denmark)

    Putaala, H; Barrangou, R

    2010-01-01

    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.

  13. Effects of the Probiotic Enterococcus faecium and Pathogenic Escherichia coli Strains in a Pig and Human Epithelial Intestinal Cell Model.

    Science.gov (United States)

    Lodemann, Ulrike; Strahlendorf, Julia; Schierack, Peter; Klingspor, Shanti; Aschenbach, Jrg R; Martens, Holger

    2015-01-01

    The aim of this study has been to elucidate the effect of the probiotic Enterococcus faecium NCIMB 10415 on epithelial integrity in intestinal epithelial cells and whether pre- and coincubation with this strain can reproducibly prevent damage induced by enterotoxigenic (ETEC) and enteropathogenic Escherichia coli (EPEC). Porcine (IPEC-J2) and human (Caco-2) intestinal epithelial cells were incubated with bacterial strains and epithelial integrity was assessed by measuring transepithelial electrical resistance (TEER) and mannitol flux rates. E. faecium alone increased TEER of Caco-2 cells without affecting mannitol fluxes whereas the E. coli strains decreased TEER and concomitantly increased mannitol flux rates in both cell lines. Preincubation with E. faecium had no effect on the TEER decrease induced by E. coli in preliminary experiments. However, in a second set of experiments using a slightly different protocol, E. faecium ameliorated the TEER decrease induced by ETEC at 4?h in IPEC-J2 and at 2, 4, and 6?h in Caco-2 cells. We conclude that E. faecium positively affected epithelial integrity in monoinfected Caco-2 cells and could ameliorate the damage on TEER induced by an ETEC strain. Reproducibility of the results is, however, limited when experiments are performed with living bacteria over longer periods. PMID:25883829

  14. The human intestinal fatty acid binding protein (hFABP2) gene is regulated by HNF-4?

    International Nuclear Information System (INIS)

    The cytosolic human intestinal fatty acid binding protein (hFABP2) is proposed to be involved in intestinal absorption of long-chain fatty acids. The aim of this study was to investigate the regulation of hFABP2 by the endodermal hepatocyte nuclear factor 4? (HNF-4?), involved in regulation of genes of fatty acid metabolism and differentiation. Electromobility shift assays demonstrated that HNF-4? binds at position -324 to -336 within the hFABP2 promoter. Mutation of this HNF-4 binding site abolished the luciferase reporter activity of hFABP2 in postconfluent Caco-2 cells. In HeLa cells, this mutation reduced the activation of the hFABP2 promoter by HNF-4? by about 50%. Thus, binding element at position -336/-324 essentially determines the transcriptional activity of promoter and may be important in control of hFABP2 expression by dietary lipids and differentiation. Studying genotype interactions of hFABP2 and HNF-4?, that are both candidate genes for diabetes type 2, may be a powerful approach

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

    International Nuclear Information System (INIS)

    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 ? 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/?L 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

  16. Human intestinal epithelial cell-derived molecule(s) increase enterohemorrhagic Escherichia coli virulence

    OpenAIRE

    Bansal, Tarun; Kim, Dae Nyun; Slininger, Tim; Thomas K. Wood; Jayaraman, Arul

    2012-01-01

    To better understand the role of host cell-derived molecules on Enterohemorrhagic Escherichia coli (EHEC) infection, we studied EHEC virulence gene expression when exposed to cell-free spent (conditioned) medium (CM) from HCT-8 intestinal epithelial cells. Exposure to HCT-8 CM for 1 h and 3 h increased the expression of 32 out of 41 EHEC locus of enterocyte effacement (LEE) virulence genes compared to fresh medium (FM). In addition, expression of the shiga toxin 1 (stx1B) gene was up-regulate...

  17. Inhibition of gastric emptying and intestinal transit by amphetamine through a mechanism involving an increased secretion of CCK in male rats

    Science.gov (United States)

    Doong, Ming-Luen; Lu, Chien-Chen; Kau, Mei-Mei; Tsai, Shiow-Chwen; Chiao, Yu-Chung; Chen, Jiann-Jong; Yeh, Jiun-Yih; Lin, Ho; Huang, Seng-Wong; Chen, Tseng-Shing; Chang, Full-Young; Wang, Paulus S

    1998-01-01

    The effect of amphetamine on gastrointestinal (GI) transit and the plasma levels of cholecystokinin (CCK) were studied in male rats. Gastric emptying was inhibited both acutely and chronically by the administration of amphetamine. GI transit was decreased by the acute administration of amphetamine but not affected by the chronic administration of amphetamine. Plasma CCK levels were increased dose-dependently by amphetamine. Proglumide, a CCK receptor antagonist, prevented amphetamine-induced inhibition of gastric emptying and the decrease in GI transit in male rats. The selective CCKA receptor antagonist, lorglumide, dose-dependently attenuated the amphetamine-induced inhibition of gastric emptying in male rats. In contrast, the selective CCKB receptor antagonist, PD 135,158, did not reverse the effect of amphetamine on gastric emptying. Both lorglumide and PD 135,158 reversed the inhibitory effect of amphetamine on GI transit in male rats. These results suggest that amphetamine-induced inhibition of gastric emptying and intestinal transit is due in part to a mechanism associated with the hypersecretion of endogenous CCK. PMID:9720782

  18. HUMAN CARE FACING TRANSITION TO MATERNAL ROLE: PUERPERAL EXPERIENCES

    Directory of Open Access Journals (Sweden)

    Juliana Athayde

    2003-12-01

    Full Text Available It is a study on the changes the transition to maternal role brings about in the puerperal period. Itobjectified to uncover how the puerperal mother experiences transition to maternal role while care is delivered; toset up new methodological ways to implement new human care models privileging role change. It?s a qualitativestudy trailing a methodological research-care trajectory. Thirteen puerperal, several-aged primparas were interviewed.The instrument used was a semi-structured interview in the clinic. Analysis was effected by informationreading and re-reading. To become the analysis process more accurate reaching depth in understanding, meaningunits were structured through intellectual exercise. Three categories take up the apprehended. Point out the needfor nurses to be alert for the signs of transition, stressing supportive professional help facing the multiple possibilitiesof being.

  19. [Changes in fecal composition, intestinal transit, bile acid metabolism and intestinal fermentation in long-term nutrition with high molecular weight formula diet].

    Science.gov (United States)

    Kruis, W; Forstmaier, G; Scheurlen, C; Stellaard, F

    1991-05-15

    Treatment with formula diets becomes more and more popular in many patients. The influence of those diets on gut functions is as yet poorly known. We studied in ten healthy volunteers the effects of a high molecular liquid diet. Despite of a sufficient energy supply the volunteers lost significantly weight which may be related to an acceleration of small bowel transit (60 +/- 9 min vs. 31 +/- 5 min; control vs. diet period). Whole gut transit did not change significantly (52 +/- 3 h vs. 56 +/- 3 h). The fecal excretion of bile acids decreased significantly (293 +/- 35 mg/24 h vs. 151 +/- 10 mg/24 h) which was particularly due to a decrease of primary bile acids. The serum bile acid concentrations behaved in a similar way (total bile acids: 3.19 +/- 0.66 mumol/l vs. 1.71 +/- 0.21 mumol/l). Neither the determination of unconjugated serum bile acids nor hydrogen breath testing did indicate increase of bacterial growth. In conclusion, chronic nutrition with formula diets causes significant changes of gut functions. PMID:1908546

  20. Amebiasis intestinal Intestinal amebiasis

    Directory of Open Access Journals (Sweden)

    JULIO CSAR GMEZ

    2007-03-01

    Full Text Available Entamoeba histolytica es el patgeno intestinal ms frecuente en nuestro medio -despus de Giardia lamblia-, una de las principales causas de diarrea en menores de cinco aos y la cuarta causa de muerte en el mundo debida a infeccin por protozoarios. Posee mecanismos patognicos complejos que le permiten invadir la mucosa intestinal y causar colitis amebiana. El examen microscpico es el mtodo ms usado para su identificacin pero la existencia de dos especies morfolgicamente iguales, una patgena ( E. histolytica y una no patgena ( Entamoeba dispar, ha llevado al desarrollo de otros mtodos de diagnstico. El acceso al agua potable y los servicios sanitarios adecuados, un tratamiento mdico oportuno y el desarrollo de una vacuna, son los ejes para disminuir la incidencia y mortalidad de esta entidad.Entamoeba histolytica is the most frequent intestinal pathogen seen in our country, after Giardia lamblia, being one of the main causes of diarrhea in children younger than five years of age, and the fourth leading cause of death due to infection for protozoa in the world. It possesses complex pathogenic mechanisms that allow it to invade the intestinal mucosa, causing amoebic colitis. Microscopy is the most used method for its identification, but the existence of two species morphologically identical, the pathogen one ( E. histolytica, and the non pathogen one ( E. dispar, have taken to the development of other methods of diagnosis. The access to drinkable water and appropriate sanitary services, an opportune medical treatment, and the development of a vaccine are the axes to diminish the incidence and mortality of this entity.

  1. Amebiasis intestinal / Intestinal amebiasis

    Scientific Electronic Library Online (English)

    JULIO CSAR, GMEZ; JORGE ALBERTO, CORTS; SONIA ISABEL, CUERVO; MYRIAM CONSUELO, LPEZ.

    2007-03-01

    Full Text Available Entamoeba histolytica es el patgeno intestinal ms frecuente en nuestro medio -despus de Giardia lamblia-, una de las principales causas de diarrea en menores de cinco aos y la cuarta causa de muerte en el mundo debida a infeccin por protozoarios. Posee mecanismos patognicos complejos que le pe [...] rmiten invadir la mucosa intestinal y causar colitis amebiana. El examen microscpico es el mtodo ms usado para su identificacin pero la existencia de dos especies morfolgicamente iguales, una patgena ( E. histolytica) y una no patgena ( Entamoeba dispar), ha llevado al desarrollo de otros mtodos de diagnstico. El acceso al agua potable y los servicios sanitarios adecuados, un tratamiento mdico oportuno y el desarrollo de una vacuna, son los ejes para disminuir la incidencia y mortalidad de esta entidad. Abstract in english Entamoeba histolytica is the most frequent intestinal pathogen seen in our country, after Giardia lamblia, being one of the main causes of diarrhea in children younger than five years of age, and the fourth leading cause of death due to infection for protozoa in the world. It possesses complex patho [...] genic mechanisms that allow it to invade the intestinal mucosa, causing amoebic colitis. Microscopy is the most used method for its identification, but the existence of two species morphologically identical, the pathogen one ( E. histolytica), and the non pathogen one ( E. dispar), have taken to the development of other methods of diagnosis. The access to drinkable water and appropriate sanitary services, an opportune medical treatment, and the development of a vaccine are the axes to diminish the incidence and mortality of this entity.

  2. Endometriosis intestinal / Intestinal endometriosis

    Scientific Electronic Library Online (English)

    C.I., Gonzlez; M., Cires; F.J., Jimnez; T., Rubio.

    2008-08-01

    Full Text Available La endometriosis es un trastorno ginecolgico crnico, benigno y frecuente entre las mujeres en edad frtil, estimndose que existe algn grado de endometriosis hasta en el 15% de las mujeres premenopusicas, asocindose a historia de infertilidad, antecedente de cesrea, dismenorrea y anormalidad e [...] n el sangrado uterino. Se cree que es debida al ascenso por las trompas de Falopio de contenido menstrual (menstruacin retrgrada). En la afectacin intestinal, el colon es el segmento ms frecuentemente afectado, sobre todo a nivel rectosigmodeo. La clnica de presentacin es inespecfica, siendo lo ms frecuente el dolor abdominal y/o plvico de tipo clico que coincide o se exacerba con la menstruacin. El diagnstico diferencial incluye la enfermedad inflamatoria intestinal, diverticulitis, colitis isqumica y procesos neoplsicos, siendo el diagnstico definitivo anatomopatolgico. En cuanto al tratamiento, ste depender de la clnica y de la edad de la paciente, as como de sus deseos de embarazo. Abstract in english 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 abnorm [...] ality 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.

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

    Science.gov (United States)

    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...

  4. Esquistosomiasis intestinal / Intestinal schistosomiasis

    Scientific Electronic Library Online (English)

    Jos Abel, Garca Acosta; Ariel Efrain, Delgado Rodrguez.

    2014-08-01

    Full Text Available Introduccin: la esquistosomiasis es una enfermedad parasitaria crnica causada por trematodos del gnero Schistosoma. La esquistosomiasis es prevalente en las regiones tropicales y subtropicales. Los sntomas de la esquistosomiasis son causados por la reaccin del organismo a los huevos del gusano. [...] Caso clnico: se presenta el caso de un paciente masculino de 21 aos, que ingresa en la Unidad de Cuidados Intensivos con cuadro de diarreas con sangre, deshidratacin y mal estado general, con empeoramiento clnico progresivo. Conclusiones: la esquistosomiasis intestinal es una enfermedad frecuente en Nampula, Mozambique; la enfermedad debe ser sospechada en pacientes con diarreas sanguinolentas y/o hematuria a fin de realizar el diagnstico oportuno e iniciar tratamiento con prazicuantel, con lo cual se obtiene curacin de la enfermedad en la mayora de los pacientes oportunamente tratados. Abstract in english Introduction: intestinal schistosomiasis is a chronic parasitic disease caused by trematodes and genus Schistosoma. Schistosomiasis prevails in tropical and subtropical regions. The symptoms are caused by the reaction of organism to the worm eggs. Case report: the case of a male aged 21 was admitted [...] to the Intensive Care Unit presenting bloody diarrhea, dehydration, and bad general status with progressive clinical worsening. Conclusions: intestinal schistosomiasis is a frequent disease in Nampula, Mozambique; the disease might be suspected in patients with bloody diarrhea and/or hematuria aimed at making the opportune diagnosis and starting the treatment with the specific and updated medication praziquantel, favoring the cure for the disease on the majority of patients properly treated.

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

    International Nuclear Information System (INIS)

    (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 ?g/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

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Characteristic hydrolyzing of megalosaccharide by human salivary ?-amylase and small intestinal enzymes, and its bioavailability in healthy subjects.

    Science.gov (United States)

    Nakamura, Sadako; Takami, Masayuki; Tanabe, Kenichi; Oku, Tsuneyuki

    2014-09-01

    The digestibility of Megalosaccharide (newly developed carbohydrate comprising ?-1,4-glucosaccharide) was investigated in vitro and in vivo. Isomaltosyl-megalosaccharide (IMS) and nigerosyl-megalosaccharide (NMS) contain 20% and 50% of the megalosaccharide fraction (degree of polymerization (DP) 10-35), respectively. IMS was hydrolyzed readily by ?-amylase to oligosaccharides (DP???7), and a small amount of glucose was produced from oligosaccharides by small intestinal enzymes (SIEs). NMS was partially hydrolyzed by ?-amylase to oligosaccharides, and a small amount of glucose produced by SIEs. When IMS and NMS were treated by SIEs after treatment with human saliva ?-amylase for a few minutes, IMS and NMS were hydrolyzed readily to glucose. Plasma levels of glucose and insulin upon ingestion of 50?g of IMS or NMS were elevated the same as those for 50?g of glucose, and breath hydrogen was not excreted. These results suggest that IMS and NMS are digestible carbohydrates. PMID:24725210

  8. Elevated levels of urinary hydrogen peroxide, advanced oxidative protein product (AOPP) and malondialdehyde in humans infected with intestinal parasites.

    Science.gov (United States)

    Chandramathi, S; Suresh, K; Anita, Z B; Kuppusamy, U R

    2009-03-01

    Oxidative stress has been implicated as an important pathogenic factor in the pathophysiology of various life-threatening diseases such as cancer, cardiovascular diseases and diabetes. It occurs when the production of free radicals (generated during aerobic metabolism, inflammation, and infections) overcome the antioxidant defences in the body. Although previous studies have implied that oxidative stress is present in serum of patients with parasitic infection there have been no studies confirming oxidative stress levels in the Malaysian population infected with intestinal parasites. Three biochemical assays namely hydrogen peroxide (H2O2), lipid peroxidation (LP) and advanced oxidative protein product (AOPP) assays were carried out to measure oxidative stress levels in the urine of human subjects whose stools were infected with parasites such as Blastocystis hominis, Ascaris, Trichuris, hookworm and microsporidia. The levels of H2O2, AOPP and LP were significantly higher (Pdrugs against parasitic infection and related diseases. PMID:19154644

  9. In vitro biotransformation of red ginseng extract by human intestinal microflora: metabolites identification and metabolic profile elucidation using LC-Q-TOF/MS.

    Science.gov (United States)

    Wang, Huai-You; Hua, Hai-Ying; Liu, Xing-Yan; Liu, Ji-Hua; Yu, Bo-Yang

    2014-09-01

    Ginseng is an important and widely used herbal medicine in Asia and has gained popularity in the western countries. Ginseng products are usually administered orally, after which their complicated components are brought into contact with intestinal microflora in the alimentary tract and metabolized. The metabolic investigation of ginseng in intestinal tract is necessary for elucidating its pharmacological activities. However, most of the reports about the metabolism of ginseng with intestinal microflora are focused on single ginseng saponin with the whole action of ginseng extract ignored. In the present paper, in vitro biotransformation of red ginseng extract by human intestinal microflora was conducted, and a rapid liquid chromatography with time-of-flight mass spectrometry (LC-Q-TOF/MS) method was used for rapid identification of the metabolites and metabolic profile of ginseng saponins. A total of 37 ginseng saponins in red ginseng extract were characterized, 17 of which were assessed to be metabolized by human intestinal microflora. Also, 30 metabolites, mostly deglycosylated, were detected and identified in the biotransformed red ginseng extract, including 4 original ingredients of red ginseng, 6 ginsenoside lactate esters, and 2 glycosylated metabolites. The metabolic profile of ginseng saponins biotransformed by human intestinal microflora was elucidated based on the metabolite information. The results indicated that deglycosylation was the major metabolic pathway of saponins in red ginseng. The esterification and glycosylation reaction also occurred during the biotransformation. Our study indicated that there was some differences in the biotransformation of single ginseng saponin and red ginseng extract. It must be noted that the ginsenoside lactate esters were firstly found in the metabolites of ginsenosides. PMID:24973593

  10. Tick-borne encephalitis virus replication, intracellular trafficking, and pathogenicity in human intestinal Caco-2 cell monolayers.

    Science.gov (United States)

    Yu, Chao; Achazi, Katharina; Mller, Lars; Schulzke, Joerg D; Niedrig, Matthias; Bcker, Roland

    2014-01-01

    Tick-borne encephalitis virus (TBEV) is one of the most important vector-borne viruses in Europe and Asia. Its transmission mainly occurs by the bite of an infected tick. However, consuming milk products from infected livestock animals caused TBEV cases. To better understand TBEV transmission via the alimentary route, we studied viral infection of human intestinal epithelial cells. Caco-2 cells were used to investigate pathological effects of TBEV infection. TBEV-infected Caco-2 monolayers showed morphological changes including cytoskeleton rearrangements and cytoplasmic vacuolization. Ultrastructural analysis revealed dilatation of the rough endoplasmic reticulum and further enlargement to TBEV containing caverns. Caco-2 monolayers maintained an intact epithelial barrier with stable transepithelial electrical resistance (TER) during early stage of infection. Concomitantly, viruses were detected in the basolateral medium, implying a transcytosis pathway. When Caco-2 cells were pre-treated with inhibitors of cellular pathways of endocytosis TBEV cell entry was efficiently blocked, suggesting that actin filaments (Cytochalasin) and microtubules (Nocodazole) are important for PI3K-dependent (LY294002) virus endocytosis. Moreover, experimental fluid uptake assay showed increased intracellular accumulation of FITC-dextran containing vesicles. Immunofluorescence microscopy revealed co-localization of TBEV with early endosome antigen-1 (EEA1) as well as with sorting nexin-5 (SNX5), pointing to macropinocytosis as trafficking mechanism. In the late phase of infection, further evidence was found for translocation of virus via the paracellular pathway. Five days after infection TER was slightly decreased. Epithelial barrier integrity was impaired due to increased epithelial apoptosis, leading to passive viral translocation. These findings illuminate pathomechanisms in TBEV infection of human intestinal epithelial cells and viral transmission via the alimentary route. PMID:24820351

  11. Testing of the Small Intestine (Intestinal Dysmotility)

    Science.gov (United States)

    ... Personal Stories Who We Are Contact Us Donate Testing of the Small Intestine Small Intestinal dysmotility Small ... Large Intestine Disorders of the Pelvic Floor Motility Testing Esophagus Stomach Small Intestine Large Intestine Anorectal and ...

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Transition between different search patterns in human online search behavior

    Science.gov (United States)

    Wang, Xiangwen; Pleimling, Michel

    2015-03-01

    We investigate the human online search behavior by analyzing data sets from different search engines. Based on the comparison of the results from several click-through data-sets collected in different years, we observe a transition of the search pattern from a Lvy-flight-like behavior to a Brownian-motion-type behavior as the search engine algorithms improve. This result is consistent with findings in animal foraging processes. A more detailed analysis shows that the human search patterns are more complex than simple Lvy flights or Brownian motions. Notable differences between the behaviors of different individuals can be observed in many quantities. We investigate the human online search behavior by analyzing data sets from different search engines. Based on the comparison of the results from several click-through data-sets collected in different years, we observe a transition of the search pattern from a Lvy-flight-like behavior to a Brownian-motion-type behavior as the search engine algorithms improve. This result is consistent with findings in animal foraging processes. A more detailed analysis shows that the human search patterns are more complex than simple Lvy flights or Brownian motions. Notable differences between the behaviors of different individuals can be observed in many quantities. This work is in part supported by the US National Science Foundation through Grant DMR-1205309.

  14. CHRFAM7A: a human-specific ?7-nicotinic acetylcholine receptor gene shows differential responsiveness of human intestinal epithelial cells to LPS.

    Science.gov (United States)

    Dang, Xitong; Eliceiri, Brian P; Baird, Andrew; Costantini, Todd W

    2015-06-01

    The human genome contains a unique, distinct, and human-specific ?7-nicotinic acetylcholine receptor (?7nAChR) gene [CHRNA7 (gene-encoding ?7-nicotinic acetylcholine receptor)] called CHRFAM7A (gene-encoding dup-?7-nicotinic acetylcholine receptor) on a locus of chromosome 15 associated with mental illness, including schizophrenia. Located 5' upstream from the "wild-type" CHRNA7 gene that is found in other vertebrates, we demonstrate CHRFAM7A expression in a broad range of epithelial cells and sequenced the CHRFAM7A transcript found in normal human fetal small intestine epithelial (FHs) cells to prove its identity. We then compared its expression to CHRNA7 in 11 gut epithelial cell lines, showed that there is a differential response to LPS when compared to CHRNA7, and characterized the CHRFAM7A promoter. We report that both CHRFAM7A and CHRNA7 gene expression are widely distributed in human epithelial cell lines but that the levels of CHRFAM7A gene expression vary up to 5000-fold between different gut epithelial cells. A 3-hour treatment of epithelial cells with 100 ng/ml LPS increased CHRFAM7A gene expression by almost 1000-fold but had little effect on CHRNA7 gene expression. Mapping the regulatory elements responsible for CHRFAM7A gene expression identifies a 1 kb sequence in the UTR of the CHRFAM7A gene that is modulated by LPS. Taken together, these data establish the presence, identity, and differential regulation of the human-specific CHRFAM7A gene in human gut epithelial cells. In light of the fact that CHRFAM7A expression is reported to modulate ligand binding to, and alter the activity of, the wild-type ?7nAChR ligand-gated pentameric ion channel, the findings point to the existence of a species-specific ?7nAChR response that might regulate gut epithelial function in a human-specific fashion.-Dang, X., Eliceiri, B. P., Baird, A., Costantini, T. W. CHRFAM7A: a human-specific ?7-nicotinic acetylcholine receptor gene shows differential responsiveness of human intestinal epithelial cells to LPS. PMID:25681457

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

    Directory of Open Access Journals (Sweden)

    Leo Lahti

    2013-02-01

    Full Text Available 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 lipids. We performed a comprehensive intestinal microbiota analysis using a phylogenetic microarray before and after Lactobacillus rhamnosus GG intervention. While a specific increase in the L. rhamnosus-related bacteria was observed during the intervention, no other changes in the composition or stability of the microbiota were detected. After the intervention, lactobacilli returned to their initial levels. As previously reported, also the serum lipid profiles remained unaltered during the intervention. Based on a high-resolution microbiota analysis, intake of L. rhamnosus GG did not modify the composition of the intestinal ecosystem in healthy adults, indicating that probiotics confer their health effects by other mechanisms. The most prevailing association between the gut microbiota and lipid profiles was a strong positive correlation between uncultured phylotypes of Ruminococcus gnavus-group and polyunsaturated serum triglycerides of dietary origin. Moreover, a positive correlation was detected between serum cholesterol and Collinsella (Coriobacteriaceae. These associations identified with the spectrometric lipidome profiling were corroborated by enzymatically determined cholesterol and triglyceride levels. Actinomycetaceae correlated negatively with triglycerides of highly unsaturated fatty acids while a set of Proteobacteria showed negative correlation with ether phosphatidylcholines. Our results suggest that several members of the Firmicutes, 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.

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

    DEFF Research Database (Denmark)

    Schr, Fabian; Inpankaew, Tawin

    2014-01-01

    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 weredetected 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.

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

    Science.gov (United States)

    Schr, 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

  18. Intestinal spirochetosis

    Scientific Electronic Library Online (English)

    Luis Roberto Manzione, Nadal; Sidney Roberto, Nadal.

    2011-12-01

    Full Text Available A espiroquetose intestinal est definida histologicamente como a presena de micro-organismos da famlia spirochetaceae ligadas ao pice das clulas do epitlio clico. A doena pode ser provocada por um grupo heterogneo de bactrias. Em humanos, a Brachyspira aalborgi e a Brachyspira pilosicoli pr [...] edominam. A incidncia varia desde 1%, nos pases desenvolvidos, at 34% nas reas mais pobres, atingindo taxas de colonizao de 62,5%, em homens que fazem sexo com homens (HSH) e vrus da imunodeficincia humana (HIV) positivo. O significado clnico dessa colonizao ainda incerto e a maioria dos infectados permanece assintomtica. Quando h sintomas gastrointestinais, o tratamento com metronidazol efetivo. Por razes desconhecidas, HSH positivos para o HIV, apresentam mais infestao sintomtica. A infeco pelo Treponema pallidum dever ser excluda, pois os tratamentos so diferentes e as complicaes por essa ltima so mais graves e definitivas. Abstract in english The intestinal spirochetosis (IS) is a histologically defined by the presence of spirochetal microorganisms connected to the apical cell membrane of the colorectal epithelium. The disease is caused by a heterogeneous group of bacteria. In humans, Brachyspira aalborgi and Brachyspira pilosicoli are p [...] revalent. The incidence ranges from 1% in developed countries to 34% in poorer areas. It affects 62.5% of colonized areas, as well as men who have intercourse with men (MSM) and those with the human immunodeficiency virus (HIV) infected. Clinical significance of such colonization is still not clear. Most infected people are asymptomatic. At the presence of gastrointestinal symptoms, treatment with metronidazole is effective. Due to unknown reasons, MSM and HIV-positive men are more likely to be symptomatic. Treponema pallidum infection must be excluded, since this agent may cause serious and permanent complications, and because the treatment is different.

  19. Impact of probiotic drugs, based on Enterobacter faecium autostrains, on human intestinal microflora in confined habitat

    Science.gov (United States)

    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 pronounced reduction of concentration of . hemolytic streptococcus, yeasts, S.aureus, hemolytic gramnegative nonfermentive rods. This results give an opportunity to use this drug to prevent the violations in intestine microflora in altered habitat conditions.

  20. Should an athlete eat straight after training?--A study of intestinal transit time and its relationship to prior exercise.

    OpenAIRE

    Scott, D.; Scott, B.

    1994-01-01

    The mouth-to-caecum transit time of food was measured using the rise in breath hydrogen after a standard breakfast of baked beans on two occasions in seven healthy volunteers. The first occasion was after resting and the second after moderate exercise on a bicycle ergometer. There was no significant difference between the transit times with or without prior exercise. It is concluded that moderate exercise taken before food does not interfere with transit time and therefore should not in that ...

  1. Similarity of hydrolyzing activity of human and rat small intestinal disaccharidases

    OpenAIRE

    Oku T; Tanabe K.; Ogawa S; Sadamori N; Nakamura S

    2011-01-01

    Tsuneyuki Oku, Kenichi Tanabe, Shigeharu Ogawa, Naoki Sadamori, Sadako NakamuraGraduate School of Human Health Science, University of Nagasaki, Siebold, Nagayo, Japan; Juzenkai Hospital, Kagomachi, Nagasaki, JapanBackground: The purpose of this study was to clarify whether it is possible to extrapolate results from studies of the hydrolyzing activity of disaccharidases from rats to humans.Materials and methods: We measured ...

  2. Determining the Long-term Effect of Antibiotic Administration on the Human Normal Intestinal Microbiota Using Culture and Pyrosequencing Methods.

    Science.gov (United States)

    Rashid, Mamun-Ur; Zaura, Egijia; Buijs, Mark J; Keijser, Bart J F; Crielaard, Wim; Nord, Carl Erik; Weintraub, Andrej

    2015-05-15

    The purpose of the study was to assess the effect of ciprofloxacin (500 mg twice daily for 10 days) or clindamycin (150 mg 4 times daily for 10 days) on the fecal microbiota of healthy humans for a period of 1 year as compared to placebo. Two different methods, culture and microbiome analysis, were used. Fecal samples were collected for analyses at 6 time-points. The interval needed for the normal microbiota to be normalized after ciprofloxacin or clindamycin treatment differed for various bacterial species. It took 1-12 months to normalize the human microbiota after antibiotic administration, with the most pronounced effect on day 11. Exposure to ciprofloxacin or clindamycin had a strong effect on the diversity of the microbiome, and changes in microbial composition were observed until the 12th month, with the most pronounced microbial shift at month 1. No Clostridium difficile colonization or C. difficile infections were reported. Based on the pyrosequencing results, it appears that clindamycin has more impact than ciprofloxacin on the intestinal microbiota. PMID:25922405

  3. A human strain of Oxalobacter (HC-1) promotes enteric oxalate secretion in the small intestine of mice and reduces urinary oxalate excretion.

    Science.gov (United States)

    Hatch, Marguerite; Freel, Robert W

    2013-10-01

    Enteric oxalate secretion that correlated with reductions in urinary oxalate excretion was previously reported in a mouse model of primary hyperoxaluria, and in wild type (WT) mice colonized with a wild rat strain (OXWR) of Oxalobacter (Am J Physiol 300:G461G469, 2010). Since a human strain of the bacterium is more likely to be clinically used as a probiotic therapeutic, we tested the effects of HC-1 in WT. Following artificial colonization of WT mice with HC-1, the bacteria were confirmed to be present in the large intestine and, unexpectedly, detected in the small intestine for varying periods of time. The main objective of the present study was to determine whether the presence of HC-1 promoted intestinal secretion in the more proximal segments of the gastrointestinal tract. In addition, we determined whether HC-1 colonization led to reductions in urinary oxalate excretion in these mice. The results show that the human Oxalobacter strain promotes a robust net secretion of oxalate in the distal ileum as well as in the caecum and distal colon and these changes in transport correlate with the beneficial effect of reducing renal excretion of oxalate. We conclude that OXWR effects on intestinal oxalate transport and oxalate homeostasis are not unique to the wild rat strain and that, mechanistically, HC-1 has significant potential for use as a probiotic treatment for hyperoxaluria especially if it is also targeted to the upper and lower gastrointestinal tract. PMID:23959075

  4. Small intestine CD4+ cell reduction and enteropathy in simian/human immunodeficiency virus KS661-infected rhesus macaques in the presence of low viral load.

    Science.gov (United States)

    Inaba, Katsuhisa; Fukazawa, Yoshinori; Matsuda, Kenta; Himeno, Ai; Matsuyama, Megumi; Ibuki, Kentaro; Miura, Yoshiharu; Koyanagi, Yoshio; Nakajima, Atsushi; Blumberg, Richard S; Takahashi, Hidemi; Hayami, Masanori; Igarashi, Tatsuhiko; Miura, Tomoyuki

    2010-03-01

    Human immunodeficiency virus type 1, simian immunodeficiency virus and simian/human immunodeficiency virus (SHIV) infection generally lead to death of the host accompanied by high viraemia and profound CD4(+) T-cell depletion. SHIV clone KS661-infected rhesus macaques with a high viral load set point (HVL) ultimately experience diarrhoea and wasting at 6-12 months after infection. In contrast, infected macaques with a low viral load set point (LVL) usually live asymptomatically throughout the observation period, and are therefore referred to as asymptomatic LVL (Asym LVL) macaques. Interestingly, some LVL macaques exhibit diarrhoea and wasting similar to the symptoms of HVL macaques and are termed symptomatic LVL (Sym LVL) macaques. This study tested the hypothesis that Sym LVL macaques have the same degree of intestinal abnormalities as HVL macaques. The proviral DNA loads in lymphoid tissue and the intestines of Sym LVL and Asym LVL macaques were comparable and all infected monkeys showed villous atrophy. Notably, the CD4(+) cell frequencies of lymphoid tissues and intestines in Sym LVL macaques were remarkably lower than those in Asym LVL and uninfected macaques. Furthermore, Sym LVL and HVL macaques exhibited an increased number of activated macrophages. In conclusion, intestinal disorders including CD4(+) cell reduction and abnormal immune activation can be observed in SHIV-KS661-infected macaques independent of virus replication levels. PMID:19889928

  5. Rapid and simple identification of human pathogenic heterophyid intestinal fluke metacercariae by PCR-RFLP.

    Science.gov (United States)

    Thaenkham, Urusa; Phuphisut, Orawan; Pakdee, Wallop; Homsuwan, Nirundorn; Sa-nguankiat, Surapol; Waikagul, Jitra; Nawa, Yukifumi; Dung, Do Trung

    2011-12-01

    Six species of heterophyid intestinal flukes (HIFs) constitute the major endemic zoonotic fish-borne pathogens in Asia: Haplorchis taichui, H. pumilio, H. yokogawai, Procerovum varium, Stellantchasmus falcatus, and Centrocestus formosanus. Several different species of these parasites are often found co-infecting the same second intermediate fish host. Because of their morphological similarities, differentiating between species of HIF metacercariae is difficult, time-consuming, and frequently results in misidentification. In this study, we aimed to develop an efficient and accurate method of identifying metacercariae of these 6 HIFs. Metacercariae were roughly grouped together, based on morphological characteristics seen under a stereomicroscope. Then, PCR-restriction fragment length polymorphism (PCR-RFLP) was used to identify the exact species of each metacercaria, using the 28S ribosomal RNA gene as the genetic marker and MboII as the restriction enzyme. Using a combination of morphological and molecular methods eliminates the need for DNA sequencing and infecting animal subjects to obtain adult worms, increases accuracy, and decreases the need for laborious morphological identification. Because the method is simple, rapid, and relatively cheap compared with PCR-sequencing, it may be an effective tool for epidemiological studies of HIFs in endemic areas. PMID:21946336

  6. Geometrical guidance and trapping transition of human sperm cells

    CERN Document Server

    Guidobaldi, A; Berdakin, I; Moshchalkov, V V; Condat, C A; Marconi, V I; Giojalas, L; Silhanek, A V

    2014-01-01

    The guidance of human sperm cells under confinement in quasi 2D microchambers is investigated using a purely physical method to control their distribution. Transport property measurements and simulations are performed with dilute sperm populations, for which effects of geometrical guidance and concentration are studied in detail. In particular, a trapping transition at convex angular wall features is identified and analyzed. We also show that highly efficient microratchets can be fabricated by using curved asymmetric obstacles to take advantage of the spermatozoa specific swimming strategy.

  7. Perfil epidemiolgico e morbimortalidade dos pacientes submetidos reconstruo de trnsito intestinal: experincia de um centro secundrio do Nordeste Brasileiro Epidemiologic profile and morbimortality of patients undergoing reconstruction intestinal transit: experience of a secundary health service in the Northeast of Brazil

    Directory of Open Access Journals (Sweden)

    Jeany Borges e Silva

    2010-09-01

    Full Text Available RACIONAL: A reconstruo do trnsito intestinal no est isenta de riscos cirrgicos e apresenta taxas considerveis de complicaes ps-operatrias, sendo que a infeco continua a ser um dos maiores desafios existentes neste procedimento. OBJETIVO: Perfil epidemiolgico e morbimortalidade dos pacientes submetidos reconstruo de trnsito intestinal. MTODOS: Foram analisados retrospectivamente 86 pronturios de pacientes com colostomia ou ileostomia, atravs de fatores que tivessem impacto sobre a morbimortalidade aps a reconstruo de trnsito intestinal, de janeiro de 2003 a abril de 2009. RESULTADOS: Houve 20 mulheres e 60 homens, com idade mdia de 43 anos. A colostomia em ala (n=34 e o trauma abdominal indicando colostomia ou ileostomia foram as condies mais frequentes. O intervalo mdio entre a confeco do estoma e a reconstruo de trnsito intestinal foi 15,7 meses. O ndice de morbidade foi 56,8%, sendo a infeco incisional a complicao mais comum (27.47%. A permanncia hospitalar mdia foi 7,6 dias. Houve regresso linear positiva entre permanncia hospitalar ps-operatria e a idade do paciente. Demonstrou-se associao estatisticamente significativa entre o prolongamento da permanncia hospitalar e a ocorrncia de complicaes (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 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 complication (27.47%. The mean inpatient length of stay was 7.6 days. There was positive linear regression between post-operative inpatient length of stay and inpatient's age. Inpatient length of stay prolongation is associated to occurrence of complications (p<0,001. CONCLUSION: It can be inferred that the occurrence of postoperative complications and age were associated with prolonged hospital stay.

  8. Perfil epidemiolgico e morbimortalidade dos pacientes submetidos reconstruo de trnsito intestinal: experincia de um centro secundrio do Nordeste Brasileiro / Epidemiologic profile and morbimortality of patients undergoing reconstruction intestinal transit: experience of a secundary health service in the Northeast of Brazil

    Scientific Electronic Library Online (English)

    Jeany Borges e, Silva; Djalma Ribeiro, Costa; Francisco Julimar Correia de, Menezes; Jos Marconi, Tavares; Adryano Gonalves, Marques; Rodrigo Dornfeld, Escalante.

    2010-09-01

    Full Text Available RACIONAL: A reconstruo do trnsito intestinal no est isenta de riscos cirrgicos e apresenta taxas considerveis de complicaes ps-operatrias, sendo que a infeco continua a ser um dos maiores desafios existentes neste procedimento. OBJETIVO: Perfil epidemiolgico e morbimortalidade dos paci [...] entes submetidos reconstruo de trnsito intestinal. MTODOS: Foram analisados retrospectivamente 86 pronturios de pacientes com colostomia ou ileostomia, atravs de fatores que tivessem impacto sobre a morbimortalidade aps a reconstruo de trnsito intestinal, de janeiro de 2003 a abril de 2009. RESULTADOS: Houve 20 mulheres e 60 homens, com idade mdia de 43 anos. A colostomia em ala (n=34) e o trauma abdominal indicando colostomia ou ileostomia foram as condies mais frequentes. O intervalo mdio entre a confeco do estoma e a reconstruo de trnsito intestinal foi 15,7 meses. O ndice de morbidade foi 56,8%, sendo a infeco incisional a complicao mais comum (27.47%). A permanncia hospitalar mdia foi 7,6 dias. Houve regresso linear positiva entre permanncia hospitalar ps-operatria e a idade do paciente. Demonstrou-se associao estatisticamente significativa entre o prolongamento da permanncia hospitalar e a ocorrncia de complicaes (p Abstract in english BACKGROUND: 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 und [...] ergoing 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 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 complication (27.47%). The mean inpatient length of stay was 7.6 days. There was positive linear regression between post-operative inpatient length of stay and inpatient's age. Inpatient length of stay prolongation is associated to occurrence of complications (p

  9. Arsenic Thiolation and the Role of Sulfate-Reducing Bacteria from the Human Intestinal Tract

    OpenAIRE

    DC.Rubin, Sergio S.C.; Alava, Pradeep; Zekker, Ivar; Du Laing, Gijs; de Wiele, Tom Van

    2014-01-01

    Background: Arsenic (As) toxicity is primarily based on its chemical speciation. Although inorganic and methylated As species are well characterized in terms of metabolism and formation in the human body, the origin of thiolated methylarsenicals is still unclear.

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

    OpenAIRE

    Jackson, R. S.; Creemers, J. W. M.; Farooqi, I. S.; O Rahilly, S.; Raffin-sanson, M-l; Bertagna, X.; Varro, A.; Dockray, G. J.; Holst, J. J.; Brubaker, P. L.; Corvol, P.; Polonsky, K. S.; Ostrega, D.; Becker, K. L.; Hutton, J. C.

    2003-01-01

    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 heterozygosity for novel missense and nonsense mutations. While both subjects shared the phenotypes of obesity, hypoadrenalism, reactive hypoglycemia, and elevated circulating levels of certain prohormones, the ...

  11. Enhanced uptake and transport of (+-catechin and (--epigallocatechin gallate in niosomal formulation by human intestinal Caco-2 cells

    Directory of Open Access Journals (Sweden)

    Song Q

    2014-05-01

    Full Text Available Qinxin Song,13 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, Peoples 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 1.220.16, 0.900.14, 3.250.37, and 1.920.22 g/mg protein, respectively (n=3. The apparent permeability coefficient values of catechin, EGCG, and their niosomes were 1.680.16, 0.880.09, 2.390.31, and 1.420.24 cm/second (n=3 at 37C, 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 significantly enhanced drug absorption. Additionally, drug-loaded niosomes exhibited stronger stability and lower toxicity. These findings showed that the oral absorption of tea flavonoids could be improved by using the novel drug delivery systems.Keywords: niosomes, formulation, bioavailability, stability

  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

    Directory of Open Access Journals (Sweden)

    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. In vitro adhesion of enterotoxigenic Escherichia coli to human intestinal epithelial cells from mucosal biopsies.

    OpenAIRE

    Knutton, S.; Lloyd, D. R.; Candy, D. C.; Mcneish, A. S.

    1984-01-01

    An adhesion assay with isolated human enterocytes prepared from duodenal biopsies has been developed and tested by using human enterotoxigenic Escherichia coli expressing colonization factor antigens I and II (CFA/I and CFA/II) and type 1 fimbriae. Enterotoxigenic E. coli strains H10407 (CFA/I) and B2C (CFA/II) bound to duodenal enterocytes to a much greater extent (mean of 4.6 and 4.0 bacteria per brush border) than did strain H10407P, a CFA/I- mutant of H10407 (mean of 0.1 bacteria per brus...

  14. Relationships between human intestinal absorption and polar interactions drug/phospholipids estimated by IAM-HPLC.

    Science.gov (United States)

    Grumetto, Lucia; Russo, Giacomo; Barbato, Francesco

    2015-07-15

    Phospholipid affinity indexes (logkW(IAM)) for 15 structurally non-related basic, acidic, ampholytic, and neutral drugs were measured by HPLC on two different phospholipid stationary phases (immobilized artificial membrane - IAM). According to a method we previously proposed, polar and electrostatic forces involved in drug/membrane interactions were quantified both as ?logkW(IAM) and as ?(')logkW(IAM). These values are the differences between the experimental logkW(IAM) and the values expected for a neutral compound having the lipophilicity value equal to either that of the neutral form of the analyte (logP(N)) or that of the mixture of charged and neutral forms of the analyte at jejunum pH 6.5 (logD(6.5)), respectively. Jejunum absorption values, logPeff, measured by the Loc-I-Gut technique, did not relate with logkW(IAM) values. A moderate linear relationship was observed with logP(N) values for all the analytes and a weak parabolic relationship was observed with logD(6.5) values, but only after the exclusion of two analytes. In contrast, a highly significant linear inverse relationship was observed with ?logkW(IAM) values. Therefore, differently from the results of our recent studies on blood-brain barrier passage, the intestinal absorption data for not only bases and zwitterions but also for acids relate significantly with ?logkW(IAM) and not with ?(')logkW(IAM) values. The results suggest that membrane passage at jejunum level can be described according to the "flip-flop" model; indeed, the lipophilicity of the neutral forms (logP(N)) appears related to the passage through the non-polar inner moieties of phospholipids whereas ?logkW(IAM) parameter appears related to the "trapping" forces at their polar surfaces. The method, easy to perform and at medium throughput, could be of use for preliminary screening of new drugs based on oral absorption potential. PMID:25917756

  15. Natural Mineral Waters Enhance the Intestinal Health and Stimulate Anti-inflammatory Immune Response in Functional Cell Model of a Non-cancerogenic Human Gut

    OpenAIRE

    Martin Trapecar; Ales Goropevsek; Lea Zbontar Zver; Avrelija Cencic

    2012-01-01

    Background Although mineral waters have been used extensively in human nutrition and have widely recognized health related properties; the availability of data on the mechanisms of their actions is limited. Methods and results We have therefore analyzed their ability to increase trans-epithelial resistance of small intestinal epithelia and cell renewal, the bioaccessibilityas well as evaluated their immunomodulatingpotentialin a 3D functional cell model of the gut. Results have showed that th...

  16. Mouse gastric tumor models with prostaglandin E2 pathway activation show similar gene expression profiles to intestinal-type human gastric cancer

    OpenAIRE

    Oshima Masanobu; Oshima Hiroko; Itadani Hiraku; Kotani Hidehito

    2009-01-01

    Abstract Background Gastric cancers are generally classified into better differentiated intestinal-type tumor and poorly differentiated diffuse-type one according to Lauren's histological categorization. Although induction of prostaglandin E2 pathway promotes gastric tumors in mice in cooperation with deregulated Wnt or BMP signalings, it has remained unresolved whether the gastric tumor mouse models recapitulate either of human gastric cancer type. This study assessed the similarity in expre...

  17. Moderate Ferulate and Diferulate Levels Do Not Impede Maize Cell Wall Degradation by Human Intestinal Microbiota

    Science.gov (United States)

    The degradation of plant fiber by human gut microbiota could be restricted by xylan substitution and cross-linking by ferulate and diferulates, for example by hindering the association of enzymes like xylanases with their substrates. To test the influence of feruloylation on cell wall degradability ...

  18. Selective growth-inhibiting effects of compounds identified in Tabebuia impetiginosa inner bark on human intestinal bacteria.

    Science.gov (United States)

    Park, Byeoung-Soo; Kim, Jun-Ran; Lee, Sung-Eun; Kim, Kyoung Soon; Takeoka, Gary R; Ahn, Young-Joon; Kim, Jeong-Han

    2005-02-23

    The growth-inhibiting activity of anthraquinone-2-carboxylic acid and lapachol identified in the inner bark of taheebo, Tabebuia impetiginosa, toward 10 human intestinal bacteria was evaluated by using a paper disk diffusion bioassay and compared to those of seven lapachol congeners (1,4-naphthoquinone, naphthazarin, menadione, lawsone, plumbagin, juglone, and dichlone) as well as two commercially available antibiotics, chloramphenicol and tetracycline. Anthraquinone-2-carboxylic acid exhibited very strong growth inhibition of Clostridium paraputrificum at 1 microg/disk while 100 microg/disk of lapachol was needed for moderate growth inhibition of the same organism. These two isolates exhibited weak inhibition of Clostridium perfringens and Escherichia coli at 100 microg/disk while no adverse effects were observed on the growth of Bifidobacterium adolescentis, Bifidobacterium bifidum, Bifidobacterium infantis, Lactobacillus acidophilus, and Lactobacillus casei at 1000 microg/disk. Structure-activity relationships indicate that a methyl group in the C-2 position of 1,4-naphthoquinone derivatives might play an important role in antibacterial activity. PMID:15713033

  19. Cytotoxic effect of linear alkylbenzene sulfonate on human intestinal Caco-2 cells: associated biomarkers for risk assessment.

    Science.gov (United States)

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

    2014-09-01

    Linear alkylbenzene sulfonate (LAS) is a synthetic anionic surfactant widely present in the environment due to its intensive production and use in the detergency field. Admitting that current procedure of risk assessment has limits in providing realistic risk assessment data and predicting the cumulative effect of the toxicant mixtures, the incorporation of information regarding the mode of action and cell response mechanism seems to be a potential solution to overcome these limits. In this regard, we investigated in this study the LAS cytotoxicity on human intestinal Caco-2 cells, trying to unveil the protein actors implicated in the cell response using proteomics approach in order to give a better understanding of the toxicological effect and allow the identification of appropriate biomarkers reflecting the mode of action associated with LAS. As results, we demonstrated that LAS induces a time- and dose-dependent cytotoxicity in Caco-2 cells accompanied by an induction of oxidative stress followed by an excessive increase of intracellular calcium level. Proteomics approach helped in discovering three informative biomarkers of effect associated with LAS cytotoxic effect, reported for the first time: calreticulin, thioredoxin, and heat shock cognate 71 (HSP7C), confirmed by real-time PCR and western blot analysis. These biomarkers could serve for more reliable future risk assessment studies that consider the toxicants mode of action in order to help in the prediction of potential cumulative effects of environmentally coexisting contaminants. PMID:24878558

  20. Effects of vasoactive intestinal polypeptide and substance P on human intramyometrial arteries and stem villous arteries in term pregnancy

    DEFF Research Database (Denmark)

    Hansen, V; Maigaard, S

    1988-01-01

    The effects of vasoactive intestinal polypeptide (VIP) and substance P on isolated human intramyometrial arteries and fetal stem villous arteries obtained from term pregnant women were compared. Ring preparations of small intramyometrial arteries and fetal stem villous arteries obtained at caesarean section were mounted in organ baths, and isometric tension was recorded. None of the peptides affected resting tension. In intramyometrial arteries precontracted by vasopressin (2.8 x 10(-9) M) both substance P (10(-12) to 10(-8) M) and VIP (10(-8) to 10(-6) M) caused relaxation. In fetal stem villous arteries precontracted by prostaglandin F2 alpha (10(-5) M) cumulative addition of substance P (10(-11) to 10(-6) M) did not produce significant changes in tension as compared with controls, while addition of single doses produced moderate relaxation. VIP (10(-8) to 10(-6) M) induced relaxation with similar effects for the addition of cumulative and single doses. The responses to VIP and substance P remained unaffected after pretreatment by atropine (10(-6) M), propranolol (10(-6) M), and indomethacin (10(-6) M). The results support a role for VIP and substance P in the regulation of uteroplacental blood flow in term pregnancy.

  1. Effects of phenol on barrier function of a human intestinal epithelial cell line correlate with altered tight junction protein localization.

    Science.gov (United States)

    McCall, Ingrid C; Betanzos, Abigail; Weber, Dominique A; Nava, Porfirio; Miller, Gary W; Parkos, Charles A

    2009-11-15

    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. PMID:19679145

  2. Effects of phenol on barrier function of a human intestinal epithelial cell line correlate with altered tight junction protein localization

    International Nuclear Information System (INIS)

    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 fluig 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.

  3. Modulation of pathogen-induced CCL20 secretion from HT-29 human intestinal epithelial cells by commensal bacteria.

    LENUS (Irish Health Repository)

    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.

  4. Measurement of gut hormonal peptides in biopsies from human stomach and proximal small intestine.

    OpenAIRE

    Bryant, M G; Bloom, S. R.; Polak, J.M.; Hobbs, S; Domschke, W; Domschke, S; Mitznegg, P; Ruppin, H; Demling, L

    1983-01-01

    Using sensitive and specific radioimmunoassays, concentrations of hormonal peptides have been measured in small biopsies taken from the human stomach, duodenum, and proximal jejunum. Comparison is made of these hormone concentrations and the number of respective endocrine cells present determined by quantitative immunocytochemistry. Immunoreactive somatostatin, VIP, motilin, and gastrin were detected in all regions examined, whereas secretin and GIP were undetectable in antral extracts. Enter...

  5. Glucose induces intestinal human UDP-glucuronosyltransferase (UGT) 1A1 to prevent neonatal hyperbilirubinemia

    OpenAIRE

    Naoya Aoshima; Yoshiko Fujie; Tomoo Itoh; Tukey, Robert H; Ryoichi Fujiwara

    2014-01-01

    Inadequate calorie intake or starvation has been suggested as a cause of neonatal jaundice, which can further cause permanent brain damage, kernicterus. This study experimentally investigated whether additional glucose treatments induce the bilirubin-metabolizing enzyme UDP-glucuronosyltransferase (UGT) 1A1 to prevent the onset of neonatal hyperbilirubinemia. Neonatal humanized UGT1 (hUGT1) mice physiologically develop jaundice. In this study, UGT1A1 expression levels were determined ...

  6. Inhibition of food intake in response to intestinal lipid is mediated by cholecystokinin in humans.

    Science.gov (United States)

    Matzinger, D; Gutzwiller, J P; Drewe, J; Orban, A; Engel, R; D'Amato, M; Rovati, L; Beglinger, C

    1999-12-01

    Intraduodenal fat inhibits gastric emptying and exerts early satiation in animals and humans, but it is not clear whether the effects are mediated by cholecystokinin (CCK) in humans. Here, we tested whether CCK-A receptors mediate the inhibition of fat on food intake. Two sequential, double-blind, crossover studies were performed in 24 male subjects. First, subjects received either intraduodenal fat or saline together with a preload of either water or banana shake. Second, 12 subjects received either intraduodenal fat or saline perfusion plus a concomitant infusion of saline or loxiglumide, a specific CCK-A receptor antagonist, together with a preload of banana shake. In both studies, subjects were free to eat and drink as much as they wished. Fat induced a reduction in calorie intake (P < 0.05) compared with controls. Furthermore, a decrease in hunger feelings was observed. Infusion of loxiglumide abolished the effects of fat. Duodenal fat interacts with an appetizer to modulate energy intake in humans. This effect is mediated by CCK-A receptors. PMID:10600919

  7. Toll-like receptor 2 activation by ?2?1-fructans protects barrier function of T84 human intestinal epithelial cells in a chain length-dependent manner.

    Science.gov (United States)

    Vogt, Leonie M; Meyer, Diederick; Pullens, Gerdie; Faas, Marijke M; Venema, Koen; Ramasamy, Uttara; Schols, Henk A; de Vos, Paul

    2014-07-01

    Dietary fiber intake is associated with lower incidence and mortality from disease, but the underlying mechanisms of these protective effects are unclear. We hypothesized that ?2?1-fructan dietary fibers confer protection on intestinal epithelial cell barrier function via Toll-like receptor 2 (TLR2), and we studied whether ?2?1-fructan chain-length differences affect this process. T84 human intestinal epithelial cell monolayers were incubated with 4 ?2?1-fructan formulations of different chain-length compositions and were stimulated with the proinflammatory phorbol 12-myristate 13-acetate (PMA). Transepithelial electrical resistance (TEER) was analyzed by electric cell substrate impedance sensing (ECIS) as a measure for tight junction-mediated barrier function. To confirm TLR2 involvement in barrier modulation by ?2?1-fructans, ECIS experiments were repeated using TLR2 blocking antibody. After preincubation of T84 cells with short-chain ?2?1-fructans, the decrease in TEER as induced by PMA (62.3 5.2%, P < 0.001) was strongly attenuated (15.2 8.8%, P < 0.01). However, when PMA was applied first, no effect on recovery was observed during addition of the fructans. By blocking TLR2 on the T84 cells, the protective effect of short-chain ?2?1-fructans was substantially inhibited. Stimulation of human embryonic kidney human TLR2 reporter cells with ?2?1-fructans induced activation of nuclear factor kappa-light-chain-enhancer of activated B cells, confirming that ?2?1-fructans are specific ligands for TLR2. To conclude, ?2?1-fructans exert time-dependent and chain length-dependent protective effects on the T84 intestinal epithelial cell barrier mediated via TLR2. These results suggest that TLR2 located on intestinal epithelial cells could be a target of ?2?1-fructan-mediated health effects. PMID:24790027

  8. Phase transitions in human IgG solutions

    Science.gov (United States)

    Wang, Ying; Lomakin, Aleksey; Latypov, Ramil F.; Laubach, Jacob P.; Hideshima, Teru; Richardson, Paul G.; Munshi, Nikhil C.; Anderson, Kenneth C.; Benedek, George B.

    2013-01-01

    Protein condensations, such as crystallization, liquid-liquid phase separation, aggregation, and gelation, have been observed in concentrated antibody solutions under various solution conditions. While most IgG antibodies are quite soluble, a few outliers can undergo condensation under physiological conditions. Condensation of IgGs can cause serious consequences in some human diseases and in biopharmaceutical formulations. The phase transitions underlying protein condensations in concentrated IgG solutions is also of fundamental interest for the understanding of the phase behavior of non-spherical protein molecules. Due to the high solubility of generic IgGs, the phase behavior of IgG solutions has not yet been well studied. In this work, we present an experimental approach to study IgG solutions in which the phase transitions are hidden below the freezing point of the solution. Using this method, we have investigated liquid-liquid phase separation of six human myeloma IgGs and two recombinant pharmaceutical human IgGs. We have also studied the relation between crystallization and liquid-liquid phase separation of two human cryoglobulin IgGs. Our experimental results reveal several important features of the generic phase behavior of IgG solutions: (1) the shape of the coexistence curve is similar for all IgGs but quite different from that of quasi-spherical proteins; (2) all IgGs have critical points located at roughly the same protein concentration at ?100 mg/ml while their critical temperatures vary significantly; and (3) the liquid-liquid phase separation in IgG solutions is metastable with respect to crystallization. These features of phase behavior of IgG solutions reflect the fact that all IgGs have nearly identical molecular geometry but quite diverse net inter-protein interaction energies. This work provides a foundation for further experimental and theoretical studies of the phase behavior of generic IgGs as well as outliers with large propensity to condense. The investigation of the phase diagram of IgG solutions is of great importance for the understanding of immunoglobulin deposition diseases as well as for the understanding of the colloidal stability of IgG pharmaceutical formulations. PMID:24089716

  9. Neuropilin-2 Mediated ?-Catenin Signaling and Survival in Human Gastro-Intestinal Cancer Cell Lines

    Science.gov (United States)

    Samuel, Shaija; Gaur, Puja; Fan, Fan; Xia, Ling; Gray, Michael J.; Dallas, Nikolaos A.; Bose, Debashish; Rodriguez-Aguayo, Cristian; Lopez-Berestein, Gabriel; Plowman, Greg; Bagri, Anil; Sood, Anil K.; Ellis, Lee M.

    2011-01-01

    NRP-2 is a high-affinity kinase-deficient receptor for ligands belonging to the class 3 semaphorin and vascular endothelial growth factor families. NRP-2 has been detected on the surface of several types of human cancer cells, but its expression and function in gastrointestinal (GI) cancer cells remains to be determined. We sought to determine the function of NRP-2 in mediating downstream signals regulating the growth and survival of human gastrointestinal cancer cells. In human gastric cancer specimens, NRP-2 expression was detected in tumor tissues but not in adjacent normal mucosa. In CNDT 2.5 cells, shRNA mediated knockdown NRP-2 expression led to decreased migration and invasion in vitro (p<0.01). Focused gene-array analysis demonstrated that loss of NRP-2 reduced the expression of a critical metastasis mediator gene, S100A4. Steady-state levels and function of ?-catenin, a known regulator of S100A4, were also decreased in the shNRP-2 clones. Furthermore, knockdown of NRP-2 sensitized CNDT 2.5 cells in vitro to 5FU toxicity. This effect was associated with activation of caspases 3 and 7, cleavage of PARP, and downregulation of Bcl-2. In vivo growth of CNDT 2.5 cells in the livers of nude mice was significantly decreased in the shNRP-2 group (p<0.05). Intraperitoneal administration of NRP-2 siRNA-DOPC decreased the tumor burden in mice (p?=?0.01). Collectively, our results demonstrate that tumor cellderived NRP-2 mediates critical survival signaling in gastrointestinal cancer cells. PMID:22028766

  10. El desarrollo de la microbiota intestinal humana, el concepto de probitico y su relacin con la salud humana / Development of the human intestinal microbiota, the concept probiotics and their relationships with human health

    Scientific Electronic Library Online (English)

    Oscar, Brunser T.

    2013-09-01

    Full Text Available Los probiticos son microorganismos vivos que al ser ingeridos en cantidades adecuadas confieren beneficios para la salud del husped. Provienen mayormente de la microbiota del colon de seres humanos aunque algunas cepas provienen del ambiente. El colon del recin nacido es colonizado durante el par [...] to por bacterias provenientes de las microbiotas fecal y vaginal maternas, del ambiente y por lactobacilos y bifidobacterias de la leche materna. Con el destete esta microbiota se hace compleja y desde los 2 aos de edad alberga unas 1500 especies y recuentos de 1014 bacterias. En la colonizacin del tubo digestivo de los prematuros el bajo peso de nacimiento, la inmadurez de las defensas y la alimentacin artificial cuando la madre es incapaz de amamantar, llevan en una proporcin de los casos a la enterocolitis necrosante, que puede afectar la pared ileal o colnica, con perforacin y peritonitis en algunos prematuros. La colonizacin microbiolgica anormal jugara un papel importante. Los probiticos disminuyen el riesgo de este cuadro y su morbilidad y mortalidad en los casos iniciales y de intensidad media. Estos efectos positivos son causados por diferentes probiticos. El riesgo de septicemia asociado con los probiticos ha sido ampliamente discutido. Estudios en Finlandia no han demostrado que durante 10 aos de su consumo masivo se produjeran aumentos de su incidencia ni cambios de su etiologa en comparacin con resultados previos a su introduccin. Las septicemias han sido detectadas principalmente en individuos con graves alteraciones de su salud, prdida de la funcin de barrera de su mucosa intestinal, trastornos congnitos graves de la inmunidad, lesiones valvulares cardacas o en estado de shock. Los pacientes con VIH y/o SIDA se benefician con el consumo de estos agentes. No se ha demostrado que el consumo de probiticos est asociado causalmente con la obesidad. Abstract in english Probiotics are live microorganisms which, when ingested in adequate numbers, confer health benefits to the host. They originate mostly from the colonic and vaginal microbiota of humans although a number of strains originate from the environment. The human fetus is colonized after birth by bacteria o [...] f maternal fecal and vaginal origin and by microorganisms from the environment. Maternal milk contains a varied microbiota, mainly lactobacilli and bifidobacteria. After weaning the resident microbiota becomes more complex and by 2 years of age it is composed of some 1500 species with 1014 microorganisms. During the colonization of the digestive tract of premature infants low birth weight, immaturity of the defenses and artificial feeding may lead to necrotizing enterocolitis. This inflammatory condition involves mainly the terminal ileum and the colon and may result in necrosis and perforation of the wall with subsequent peritonitis. Anoxia and abnormal colonization are important associated factors. Probiotic administration is associated with a decreased risk of this condition and decreases of its morbidity, mortality and sequelae if the treatment is started early. The positive effects are associated with more than one species of probiotics. The risk of septicemia associated with probiotics has been widely discussed. Studies in Helsinki, Finland, demonstrated that the results of comparing the frequency and etiology of septicemia during the 10 years after the introduction of probiotics with the results in the 10 years previous to their introduction were not different. Septicemia due to probiotics is infrequent and most cases are associated with extreme prematurity, failure of the intestinal barrier function, heart valve disease, severe shock and congenital immune deficiencies; patients with these conditions should be closely watched if they consume probiotics. However, patients with HIV and AIDS benefit from the consumption of these microorganisms. It has nor been demonstrated that probiotics play a role in the genesis of obesity.

  11. The importance of determining human leucocyte antigens in preventing intestinal lymphoma in patients with celiac disease

    OpenAIRE

    Doru Dejica; Ileana Constantinescu; Gabriel Samasca; Andreica Mariana; Angela Butnariu; Mihaela Iancu

    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, serologically nega...

  12. Curcumin affects cell survival and cell volume regulation in human renal and intestinal cells

    International Nuclear Information System (INIS)

    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 0.110 ?M curcumin modulates IClswell in a dose-dependent manner (0.1 ?M curcumin is ineffective, 0.55.0 ?M curcumin increase, while 10 ?M 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 can be ruled out. Furthermore, we show that curcumin exposure induces apoptosis in human kidney cells, and at a concentration of 5.010 ?M induces the appearance of a sub-population of cells with a dramatically increased volume. In these cells the regulation of the cell volume seems to be impaired, most likely as a consequence of the IClswell blockade. Similarly, 50 ?M curcumin induced apoptosis, caused cell cycle arrest in G1-phase and increased the volume of human colorectal adenocarcinoma HT-29 cells. The cell cycle arrest in G1 phase may be the mechanism underlying the volume increase observed in this cell line after exposure to curcumin.

  13. Breaking Human Cytomegalovirus Major Immediate-Early Gene Silence by Vasoactive Intestinal Peptide Stimulation of the Protein Kinase A-CREB-TORC2 Signaling Cascade in Human Pluripotent Embryonal NTera2 Cells?

    OpenAIRE

    Yuan, Jinxiang; Liu, Xiaoqiu; Wu, Allen W.; McGonagill, Patrick W.; Keller, Michael J.; Galle, Courtney S.; Meier, Jeffery L.

    2009-01-01

    The triggering mechanisms underlying reactivation of human cytomegalovirus (HCMV) in latently infected persons are unclear. During latency, HCMV major immediate-early (MIE) gene expression breaks silence to initiate viral reactivation. Using quiescently HCMV-infected human pluripotent embryonal NTera2 cells (NT2) to model HCMV reactivation, we show that vasoactive intestinal peptide (VIP), an immunomodulatory neuropeptide, immediately and dose-dependently (1 to 500 nM) activates HCMV MIE gene...

  14. Distribution of iodinated antibodies to the human organ-specific intestinal antigen in the body of nude mice with tumor geterografts

    International Nuclear Information System (INIS)

    131I labeled rabbit antibodies to the human epithelial intestinal antigen ?1MA was administered intravenously to nude mice together with human tumor grafts: colon cancer (CC), breast cancer, Ewing's sarcoma and hepatoma. Antibodies to ?1MA were selectively accumulated in CC only, excluding the other tumors. Iodinated nonspecific rabbit IgG in mice with CC were distributed like antibodies to ?1MA in the body of mice with control heterografts. A conclusion was made of the promising use of labeled antibodies to ?1MA in radioimmunoscintigraphy of CC and its metastases

  15. Structural insight into substrate specificity of human intestinal maltase-glucoamylase.

    Science.gov (United States)

    Ren, Limei; Qin, Xiaohong; Cao, Xiaofang; Wang, Lele; Bai, Fang; Bai, Gang; Shen, Yuequan

    2011-10-01

    Human maltase-glucoamylase (MGAM) hydrolyzes linear alpha-1,4-linked oligosaccharide substrates, playing a crucial role in the production of glucose in the human lumen and acting as an efficient drug target for type 2 diabetes and obesity. The amino- and carboxyl-terminal portions of MGAM (MGAM-N and MGAM-C) carry out the same catalytic reaction but have different substrate specificities. In this study, we report crystal structures of MGAM-C alone at a resolution of 3.1 , and in complex with its inhibitor acarbose at a resolution of 2.9 . Structural studies, combined with biochemical analysis, revealed that a segment of 21 amino acids in the active site of MGAM-C forms additional sugar subsites (+ 2 and + 3 subsites), accounting for the preference for longer substrates of MAGM-C compared with that of MGAM-N. Moreover, we discovered that a single mutation of Trp1251 to tyrosine in MGAM-C imparts a novel catalytic ability to digest branched alpha-1,6-linked oligosaccharides. These results provide important information for understanding the substrate specificity of alpha-glucosidases during the process of terminal starch digestion, and for designing more efficient drugs to control type 2 diabetes or obesity. PMID:22058037

  16. Anti-infective activities of lactobacillus strains in the human intestinal microbiota: from probiotics to gastrointestinal anti-infectious biotherapeutic agents.

    Science.gov (United States)

    Livin-Le Moal, Vanessa; Servin, Alain L

    2014-04-01

    A vast and diverse array of microbial species displaying great phylogenic, genomic, and metabolic diversity have colonized the gastrointestinal tract. Resident microbes play a beneficial role by regulating the intestinal immune system, stimulating the maturation of host tissues, and playing a variety of roles in nutrition and in host resistance to gastric and enteric bacterial pathogens. The mechanisms by which the resident microbial species combat gastrointestinal pathogens are complex and include competitive metabolic interactions and the production of antimicrobial molecules. The human intestinal microbiota is a source from which Lactobacillus probiotic strains have often been isolated. Only six probiotic Lactobacillus strains isolated from human intestinal microbiota, i.e., L. rhamnosus GG, L. casei Shirota YIT9029, L. casei DN-114 001, L. johnsonii NCC 533, L. acidophilus LB, and L. reuteri DSM 17938, have been well characterized with regard to their potential antimicrobial effects against the major gastric and enteric bacterial pathogens and rotavirus. In this review, we describe the current knowledge concerning the experimental antibacterial activities, including antibiotic-like and cell-regulating activities, and therapeutic effects demonstrated in well-conducted, placebo-controlled, randomized clinical trials of these probiotic Lactobacillus strains. What is known about the antimicrobial activities supported by the molecules secreted by such probiotic Lactobacillus strains suggests that they constitute a promising new source for the development of innovative anti-infectious agents that act luminally and intracellularly in the gastrointestinal tract. PMID:24696432

  17. Assessment of degradation and intestinal cell uptake of carotenoids and chlorophyll derivatives from spinach puree using an in vitro digestion and Caco-2 human cell model.

    Science.gov (United States)

    Ferruzzi, M G; Failla, M L; Schwartz, S J

    2001-04-01

    Although numerous studies have demonstrated the health benefits of chlorophyll derivatives, information regarding the digestion, absorption, and metabolism of these phytochemicals is quite limited. To better understand the digestion of these pigments, green vegetables including fresh spinach puree (FSP), heat- and acid-treated spinach puree (HASP), and ZnCl(2)-treated spinach puree (ZnSP) were subjected to an in vitro digestion method which simulates both the gastric and small intestinal phases of the process. Native chlorophylls were converted to Mg-free pheophytin derivatives during digestion. Conversely, Zn-pheophytins were completely stable during the digestive process. Transfer of lipophilic chlorophyll derivatives, as well as the carotenoids lutein and beta-carotene, into the aqueous micellar fraction from the food matrix was quantified. Micellarization of total chlorophyll derivatives differed significantly (p 0.05). Intestinal cell uptake of micellarized pigments was investigated using HTB-37 (parent) and clonal TC7 lines of human Caco-2 cells. Medium containing the pigment-enriched fraction generated during digestion was added to the apical surface of fully differentiated monolayers for 4 h. Pigments were then extracted from cells and analyzed by C18 HPLC with photodiode array detection. Both Caco-2 HTB-37 and TC7 clone cells accumulated 20-40% and 5-10% of micellarized carotenoid and chlorophyll derivatives, respectively. These results are the first to demonstrate uptake of chlorophyll derivatives by human intestinal cells and to support the potential importance of chlorophylls as health-promoting phytochemicals. PMID:11308371

  18. Cell surface glycopeptides from human intestinal epithelial cell lines derived from normal colon and colon adenocarcinomas

    International Nuclear Information System (INIS)

    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 gl, strong acid hydrolysis of the labeled glycopeptide fraction excluded from Bio-Gel P-6 produced 3H-labeled N-acetylglucosamine and N-acetylgalactosamine

  19. Aspectos funcionais, microbiolgicos e morfolgicos intestinais em crianas infectadas pelo vrus da imunodeficincia humana Functional, microbiological and morphological intestinal findings among human immunodeficiency virus infected children

    Directory of Open Access Journals (Sweden)

    Christiane Araujo Chaves Leite

    2006-12-01

    Full Text Available RACIONAL: O trato gastrointestinal freqentemente acometido nas crianas infectadas pelo vrus da imunodeficincia humana, com importantes repercusses no seu estado nutricional e sobrevida. A maioria dos estudos relacionados a esse tema foi desenvolvida com adultos, sendo menos investigado o problema nas crianas OBJETIVOS: Estudar aspectos digestivo-absortivos, microbiolgicos e morfolgicos intestinais em crianas infectadas pelo vrus da imunodeficincia humana MATERIAL E MTODOS: Onze crianas infectadas pelo vrus da imunodeficincia humana, menores de 13 anos, pertencentes s categorias clnicas A, B ou C, divididas em dois grupos: cinco pacientes com relato atual ou recente de diarria e seis pacientes sem diarria nos 30 dias que antecederam incluso no estudo. Investigao proposta: biopsia de intestino delgado e reto para anlise morfolgica e microbiolgica, coprocultura, protoparasitolgico de fezes, pesquisa de rotavrus, micobactrias e Cryptosporidium; teste da D-xilose RESULTADOS: Todos os pacientes testados (9/11 apresentavam m absoro da D-xilose (8,4-24,4 mg/dL. Os achados histopatolgicos de intestino delgado foram inespecficos, representados em sua maioria, por enteropatia grau I a II (6/10. Em todos os casos foi constatado aumento do infiltrado celular do crion. As alteraes histopatolgicas do reto tambm foram inespecficas, com presena de aumento do infiltrado celular do crion. A pesquisa de microorganismos enteropatognicos s foi positiva em dois casos, sendo identificado Mycobacterium avium intracellulare e Cryptosporidium nas fezes CONCLUSES: Demonstrou-se alta prevalncia (100% de m absoro intestinal em crianas infectadas pelo vrus da imunodeficincia humana, com ou sem diarria. No foi possvel estabelecer correlaes quanto presena de agentes enteropatognicos, m absoro intestinal, alteraes morfolgicas intestinais e ocorrncia ou no de diarria. No houve correlao entre os valores de D-xilose e os graus de atrofia vilositria.BACKGROUD: Gastrointestinal tract disorders are frequent among human immunodeficiency virus infected children, with important repercussions on nutrition and survival. Most studies related to this subject were restricted to adults, being less investigated the problem in the children. AIMS: To study intestinal digestion, absorption, microbiological and morphological findings among human immunodeficiency virus infected children. MATERIAL AND METHODS: Eleven human immunodeficiency virus infected children under 13 years old, belonging to clinical categories A, B or C, separated in two groups: five patients with current or recent episode of diarrhea and six patients without diarrhea in the last 30 days preceding entering in study. Investigation proposed: microbiological and morphological analysis of small intestine and rectum biopsy; stool exams for bacterium, parasite, rotavirus, Mycobacterium species and Cryptosporidium; D-xylose test RESULTS: All tested subjects (9/11 had low D-xylose absorption (8,4 _ 24,4 mg d/L. Small intestinal mucosa histology findings were nonspecific, represented, in majority, of grade I/II enteropathy (6/10. Increased cellular infiltration of the chorion was observed in all specimens. Rectum histology alterations were also nonspecific, with chorion increased cellular infiltration. Mycobacterim avium intracellulare and Cryptosporidium were the solely microorganisms founded, both in stool CONCLUSIONS: Our study demonstrated high prevalence (100% of intestinal malabsorption among human immunodeficiency virus infected children, despite the occurrence or not of diarrhea. It was not possible to establish relationships between the presence of microorganisms, intestinal malabsorption, intestinal morphologic findings and the occurrence or not of diarrhea. There was no correlation between D-xylose and intensity of villous atrophy.

  20. Intestinal stem cells.

    OpenAIRE

    Leedham, SJ; Brittan, M; Mcdonald, SA; Wright, NA

    2005-01-01

    The intestinal tract has a rapid epithelial cell turnover, which continues throughout life. The process is regulated and maintained by a population of stem cells, which give rise to all the intestinal epithelial cell lineages. Studies in both the mouse and the human show that these cells are capable of forming clonal crypt populations. Stem cells remain hard to identify, however it is thought that they reside in a 'niche' towards the base of the crypt and their activity is regulated by the pa...

  1. Genome sequences and comparative genomics of two Lactobacillus ruminis strains from the bovine and human intestinal tracts

    LENUS (Irish Health Repository)

    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 interactions of these motile intestinal lactobacilli.

  2. Cox2 and ?-Catenin/T-cell Factor Signaling Intestinalize Human Esophageal Keratinocytes When Cultured under Organotypic Conditions

    Directory of Open Access Journals (Sweden)

    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.

  3. Intestinal obstruction

    Science.gov (United States)

    ... intestine, it may cause infection and tissue death (gangrene). Risks for tissue death are related to the ... present. Hernias, volvulus, and intussusception carry a higher gangrene risk. In a newborn, paralytic ileus that destroys ...

  4. Cytotoxic activity of intestinal lamina propria lymphocytes on human immunodeficiency virus (HIV)-infected cells.

    Science.gov (United States)

    Di Massimo, A M; Placido, R; Bach, S; Anastasi, A M; Mastino, A; Capobianchi, M R; Colizzi, V

    1992-01-01

    The phenotype and cytotoxic activity of lamina propria lymphocytes (LPL) from the colorectal mucosa have been investigated primarily to analyse the role of LPL in human immunodeficiency virus (HIV) infection. The results reported here show that LPL strictly required a proliferative stimulus [either interleukin-2 (IL-2) or phytohaemaglutinin (PHA) to develop strong in vitro cytotoxicity, since freshly isolated LPL do not exhert cytotoxicity against either natural killer (NK)-sensitive or NK-resistant target cells. The cytotoxicity of activated LPL against a large panel of myeloid tumours or colorectal carcinoma target cells shows the irrelevance of the tissue origin of target cells. Moreover, activated LPL lysed HIV-infected H9 cells more efficiently than peripheral blood lymphocytes (PBL), and were susceptible to HIV infection. In contrast, unstimulated LPL failed to be cytotoxic and susceptible to HIV. Thus, we strongly suggest that for the lymphocytes of the colorectal mucosa expression of cytotoxic activity and susceptibility to HIV-infection show two faces of the same coin, and therefore may be relevant in understanding the mechanisms and paths of transmission of HIV infection. PMID:1628889

  5. Comparison study of oral iron preparations using a human intestinal model.

    Science.gov (United States)

    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

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

    International Nuclear Information System (INIS)

    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 ? 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 through a GLP-1-mediated pathway.

  7. 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

    OpenAIRE

    Tetens, Inge

    2011-01-01

    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 based on newly developed scientific evidence related to sugar beet fibre and decreasing intestinal transit time. The food constituent that is the subject of the health claim is sugar beet fibre. T...

  8. Aspectos funcionais, microbiolgicos e morfolgicos intestinais em crianas infectadas pelo vrus da imunodeficincia humana / Functional, microbiological and morphological intestinal findings among human immunodeficiency virus infected children

    Scientific Electronic Library Online (English)

    Christiane Araujo Chaves, Leite; Regina Clia de Menezes, Succi; Francy Reis da Silva, Patrcio; Ulysses, Fagundes-Neto.

    2006-12-01

    Full Text Available RACIONAL: O trato gastrointestinal freqentemente acometido nas crianas infectadas pelo vrus da imunodeficincia humana, com importantes repercusses no seu estado nutricional e sobrevida. A maioria dos estudos relacionados a esse tema foi desenvolvida com adultos, sendo menos investigado o prob [...] lema nas crianas OBJETIVOS: Estudar aspectos digestivo-absortivos, microbiolgicos e morfolgicos intestinais em crianas infectadas pelo vrus da imunodeficincia humana MATERIAL E MTODOS: Onze crianas infectadas pelo vrus da imunodeficincia humana, menores de 13 anos, pertencentes s categorias clnicas A, B ou C, divididas em dois grupos: cinco pacientes com relato atual ou recente de diarria e seis pacientes sem diarria nos 30 dias que antecederam incluso no estudo. Investigao proposta: biopsia de intestino delgado e reto para anlise morfolgica e microbiolgica, coprocultura, protoparasitolgico de fezes, pesquisa de rotavrus, micobactrias e Cryptosporidium; teste da D-xilose RESULTADOS: Todos os pacientes testados (9/11) apresentavam m absoro da D-xilose (8,4-24,4 mg/dL). Os achados histopatolgicos de intestino delgado foram inespecficos, representados em sua maioria, por enteropatia grau I a II (6/10). Em todos os casos foi constatado aumento do infiltrado celular do crion. As alteraes histopatolgicas do reto tambm foram inespecficas, com presena de aumento do infiltrado celular do crion. A pesquisa de microorganismos enteropatognicos s foi positiva em dois casos, sendo identificado Mycobacterium avium intracellulare e Cryptosporidium nas fezes CONCLUSES: Demonstrou-se alta prevalncia (100%) de m absoro intestinal em crianas infectadas pelo vrus da imunodeficincia humana, com ou sem diarria. No foi possvel estabelecer correlaes quanto presena de agentes enteropatognicos, m absoro intestinal, alteraes morfolgicas intestinais e ocorrncia ou no de diarria. No houve correlao entre os valores de D-xilose e os graus de atrofia vilositria. Abstract in english BACKGROUD: Gastrointestinal tract disorders are frequent among human immunodeficiency virus infected children, with important repercussions on nutrition and survival. Most studies related to this subject were restricted to adults, being less investigated the problem in the children. AIMS: To study i [...] ntestinal digestion, absorption, microbiological and morphological findings among human immunodeficiency virus infected children. MATERIAL AND METHODS: Eleven human immunodeficiency virus infected children under 13 years old, belonging to clinical categories A, B or C, separated in two groups: five patients with current or recent episode of diarrhea and six patients without diarrhea in the last 30 days preceding entering in study. Investigation proposed: microbiological and morphological analysis of small intestine and rectum biopsy; stool exams for bacterium, parasite, rotavirus, Mycobacterium species and Cryptosporidium; D-xylose test RESULTS: All tested subjects (9/11) had low D-xylose absorption (8,4 _ 24,4 mg d/L). Small intestinal mucosa histology findings were nonspecific, represented, in majority, of grade I/II enteropathy (6/10). Increased cellular infiltration of the chorion was observed in all specimens. Rectum histology alterations were also nonspecific, with chorion increased cellular infiltration. Mycobacterim avium intracellulare and Cryptosporidium were the solely microorganisms founded, both in stool CONCLUSIONS: Our study demonstrated high prevalence (100%) of intestinal malabsorption among human immunodeficiency virus infected children, despite the occurrence or not of diarrhea. It was not possible to establish relationships between the presence of microorganisms, intestinal malabsorption, intestinal morphologic findings and the occurrence or not of diarrhea. There was no correlation between D-xylose and intensity of villous atrophy.

  9. 1H Nuclear Magnetic Resonance Spectroscopy-Based Studies of the Metabolism of Food-Borne Carcinogen 2-Amino-3-Methylimidazo[4,5-f]Quinoline by Human Intestinal Microbiota

    OpenAIRE

    Humblot, Christle; Combourieu, Bruno; Visnen, Marja-Liisa; Furet, Jean-Pierre; Delort, Anne-Marie; Rabot, Sylvie

    2005-01-01

    2-Amino-3-methylimidazo[4,5-f]quinoline (IQ) is a mutagenic/carcinogenic compound formed from meat and fish during cooking. Following ingestion, IQ is metabolized mainly by liver xenobiotic-metabolizing enzymes, but intestinal bacteria may also contribute to its biotransformation. The aim of this study was to investigate the metabolism of IQ by the human intestinal microbiota. Following incubation of IQ (200 ?M) under anoxic conditions with 100-fold dilutions of stools freshly collected from ...

  10. Effects of oral adenosine 5'-triphosphate and adenosine in enteric-coated capsules on indomethacin-induced permeability changes in the human small intestine: a randomized cross-over study

    OpenAIRE

    Jl, Bours Martijn; Bos Hilde J; Meddings Jon B; Brummer Robert-Jan M; van den Brandt Piet A; Dagnelie Pieter C

    2007-01-01

    Abstract Background It is well-known that nonsteroidal anti-inflammatory drugs (NSAIDs) can cause damage to the small bowel associated with disruption of mucosal barrier function. In healthy human volunteers, we showed previously that topical administration of adenosine 5'-triphosphate (ATP) by naso-intestinal tube attenuated a rise in small intestinal permeability induced by short-term challenge with the NSAID indomethacin. This finding suggested that ATP may be involved in the preservation ...

  11. Characterization of In Vitro Glucuronidation Clearance of a Range of Drugs in Human Kidney Microsomes: Comparison with Liver and Intestinal Glucuronidation and Impact of Albumin

    Science.gov (United States)

    Gill, Katherine L.; Houston, J. Brian

    2012-01-01

    Previous studies have shown the importance of the addition of albumin for characterization of hepatic glucuronidation in vitro; however, no reports exist on the effects of albumin on renal or intestinal microsomal glucuronidation assays. This study characterized glucuronidation clearance (CLint, UGT) in human kidney, liver, and intestinal microsomes in the presence and absence of bovine serum albumin (BSA) for seven drugs with differential UDP-glucuronosyltransferase (UGT) 1A9 and UGT2B7 specificity, namely, diclofenac, ezetimibe, gemfibrozil, mycophenolic acid, naloxone, propofol, and telmisartan. The impact of renal CLint, UGT on accuracy of in vitro-in vivo extrapolation (IVIVE) of glucuronidation clearance was investigated. Inclusion of 1% BSA for acidic drugs and 2% for bases/neutral drugs in incubations was found to be suitable for characterization of CLint, UGT in different tissues. Although BSA increased CLint, UGT in all tissues, the extent was tissue- and drug-dependent. Scaled CLint, UGT in the presence of BSA ranged from 2.22 to 207, 0.439 to 24.4, and 0.292 to 23.8 ml min?1 g tissue?1 in liver, kidney, and intestinal microsomes. Renal CLint, UGT (per gram of tissue) was up to 2-fold higher in comparison with that for liver for UGT1A9 substrates; in contrast, CLint, UGT for UGT2B7 substrates represented approximately one-third of hepatic estimates. Scaled renal CLint, UGT (in the presence of BSA) was up to 30-fold higher than intestinal glucuronidation for the drugs investigated. Use of in vitro data obtained in the presence of BSA and inclusion of renal clearance improved the IVIVE of glucuronidation clearance, with 50% of drugs predicted within 2-fold of observed values. Characterization and consideration of kidney CLint, UGT is particularly important for UGT1A9 substrates. PMID:22275465

  12. Use of Glucuronidation Fingerprinting to Describe and Predict mono- and di-Hydroxyflavone Metabolism by Recombinant UGT Isoforms and Human Intestinal and Liver Microsomes

    Science.gov (United States)

    Tang, Lan; Ye, Ling; Singh, Rashim; Wu, Baojian; Lv, Chang; Zhao, Jie; Liu, Zhongqiu; Hu, Ming

    2010-01-01

    The present study aims to predict the regiospecific glucuronidation of three dihydroxyflavones and seven mono-hydroxyflavones in human liver and intestinal microsomes using recombinant UGT isoforms. Seven mono-hydroxyflavones (or HFs), 2?-, 3?-, 4?-, 3-, 5-, 6-, and 7-hydroxyflavone, and three di-hydroxyflavones (or diHFs), 3,7-dihydroxyflavone (3,7-diHF), 3,5-dihydroxyflavone (3,5-diHF) and 3,4?-dihydroxyflavone (3,4?-diHF) were chosen and rates were measured at 2.5, 10 and 35 ?M. The results indicated that the position of glucuronidation of three diHFs could be determined by using the UV spectra of relevant HFs. The results also indicated that UGT1A1, UGT1A7, UGT1A8, UGT1A9, UGT1A10 and UGT2B7 are the most important six UGT isoforms for metabolizing the chosen flavones. Regardless of isoforms used, 3-HF was always metabolized the fastest whereas 5-HF was usually metabolized the slowest, probably due to the formation of an intra-molecular hydrogen bond between 4-carbonyl and 5-OH group. Relevant UGT isoform-specific metabolism rates generally correlated well with the rates of glucuronidation in human intestinal and liver microsomes at each of the three tested concentrations. In conclusion, the glucuronidation fingerprint of seven selected mono-hydroxyflavones was affected by UGT isoforms used, positions of the ?OH group, and the substrate concentrations, and the rates of glucuronidation by important recombinant UGTs correlated well with those obtained using human liver and intestinal microsomes. PMID:20297805

  13. Methotrexate-induced intestinal mucositis delays gastric emptying and gastrointestinal transit of liquids in awake rats / Mucosite induzida pelo metotrexato retarda o esvaziamento gstrico e o trnsito gastrointestinal de lquidos em ratos acordados

    Scientific Electronic Library Online (English)

    Pedro M. G., Soares; Lorena O., Lopes; Jos Maurcio S. C., Mota; Jos Nelson, Belarmino-Filho; Ronaldo A., Ribeiro; Marcellus Henrique L. P. de, Souza.

    2011-03-01

    Full Text Available CONTEXTO: Metotrexato e outros agentes anticncer podem induzir uma mucosite intestinal, que um dos fatores de limitante mais comum que limitam o aumento escalonado da dose do metotrexato. OBJETIVOS: Avaliar o esvaziamento gstrico e o trnsito gastrointestinal de lquidos na mucosite intestinal i [...] nduzida por metotrexato. MTODOS: Ratos Wistar, receberam metotrexato (2.5 mg/kg/dia por 3 dias, subcutneo) ou salina. Aps 1, 3 ou 7 dias, seces do duodeno, jejuno e leo foram retirados para anlise morfomtrica e dosagem da atividade de mieloperoxidase (marcador bioqumico da infiltrao de neutrfilos). Outros ratos foram pr-tratados com metotrexato ou salina, aps 3 ou 7 dias, foram alimentados mediante gavagem com uma refeio teste e sacrificados aps 10, 20 e 30 minutos. As retenes fracionais do corante no estmago e em trs segmentos do intestino delgado foram determinados por espectrofotometria. RESULTADOS: Aps 3 dias do metotrexato, houve leso do epitlio intestinal em todos os segmentos, com aumento da atividade de mieloperoxidase, no duodeno e leo. Sete dias aps o metotrexato, foi observada completa reverso da leso intestinal. Observou-se ainda retardo no esvaziamento gstrico aps 10 min, 20 min e 30 min, aps 3 dias, mas no aps 7 dias do tratamento com metotrexato. A reteno fracional dos segmentos do intestino foi reduzida no primeiro e segundo segmentos aps 10 min, e no terceiro segmento aps 30 min da administrao da refeio, somente 3 dias aps o tratamento com metotrexato. CONCLUSO: A mucosite intestinal induzida por metotrexato retarda o esvaziamento gstrico e o trnsito gastrointestinal de lquidos em ratos acordados. Abstract in english CONTEXT: Methotrexate and other anticancer agents can induce intestinal mucositis, which is one of the most common limiting factor that prevent further dose escalation of the methotrexate. OBJECTIVES: To evaluate the gastric emptying and gastrointestinal transit of liquids in methotrexate-induced in [...] testinal mucositis. METHODS: Wistar rats received methotrexate (2.5 mg/kg/day for 3 days, subcutaneously) or saline. After 1, 3 and 7 days, sections of duodenum, jejunum and ileum were removed for assessment of epithelial damage and myeloperoxidase activity (biochemical marker of granulocyte infiltration). Others rats were pre-treated with methotrexate or saline, gavage-fed after 3 or 7 days with a standard test liquid meal, and sacrificed 10, 20 or 30-min later. Gastric and small intestine dye recoveries were measured by spectrophotometry. RESULTS: After 3 days of methotrexate, there was an epithelial intestinal damage in all segments, with myeloperoxidase activity increase in both in duodenum and ileum. Seven days after methotrexate, we observed a complete reversion of this intestinal damage. There was an increase in gastric dye recoveries after 10, 20, and 30-min post-prandial intervals after 3 days, but not after 7 days, of methotrexate. Intestine dye recoveries were decreased in the first and second segments at 10 min, in the third at 20 min, and in the second and third at 30 min, only after 3 days of methotrexate treatment. CONCLUSION: Methotrexate-induced intestinal mucositis delays gastric emptying and gastrointestinal transit of liquids in awake rats.

  14. Use of Glucuronidation Fingerprinting to Describe and Predict mono- and di-Hydroxyflavone Metabolism by Recombinant UGT Isoforms and Human Intestinal and Liver Microsomes

    OpenAIRE

    Tang, Lan; Ye, Ling; Singh, Rashim; Wu, Baojian; Lv, Chang; Zhao, Jie; Liu, Zhongqiu; Hu, Ming

    2010-01-01

    The present study aims to predict the regiospecific glucuronidation of three dihydroxyflavones and seven mono-hydroxyflavones in human liver and intestinal microsomes using recombinant UGT isoforms. Seven mono-hydroxyflavones (or HFs), 2?-, 3?-, 4?-, 3-, 5-, 6-, and 7-hydroxyflavone, and three di-hydroxyflavones (or diHFs), 3,7-dihydroxyflavone (3,7-diHF), 3,5-dihydroxyflavone (3,5-diHF) and 3,4?-dihydroxyflavone (3,4?-diHF) were chosen and rates were measured at 2.5, 10 and 35 ?M....

  15. Conjugated linoleic acid alters global gene expression in human intestinal-like Caco-2 cells in an isomer-specific manner

    OpenAIRE

    Calogero, Raffaele Adolfo

    2007-01-01

    Conjugated linoleic acid (CLA) exhibits isomer-specific effects on transepithelial calcium (Ca) transport as well as on cell growth in human intestinal-like Caco-2 cells. However, the molecular mechanisms of action are still unclear. Therefore, this study used a transcriptomic approach to help elucidate the molecular mechanisms underlying such isomer-specific effects. Caco-2 cells were treated with 80 micromol/L linoleic acid (control), 80 micromol/L trans-10, cis-12 CLA, or 80 micromol/L cis...

  16. The Genome Sequence of Methanosphaera stadtmanae Reveals Why This Human Intestinal Archaeon Is Restricted to Methanol and H2 for Methane Formation and ATP Synthesis

    OpenAIRE

    Fricke, Wolfgang F.; Seedorf, Henning; Henne, Anke; Krer, Markus; Liesegang, Heiko; Hedderich, Reiner; Gottschalk, Gerhard; Thauer, Rudolf K.

    2006-01-01

    Methanosphaera stadtmanae has the most restricted energy metabolism of all methanogenic archaea. This human intestinal inhabitant can generate methane only by reduction of methanol with H2 and is dependent on acetate as a carbon source. We report here the genome sequence of M. stadtmanae, which was found to be composed of 1,767,403 bp with an average G+C content of 28% and to harbor only 1,534 protein-encoding sequences (CDS). The genome lacks 37 CDS present in the genomes of all other methan...

  17. 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

    Science.gov (United States)

    Kumar, Veerendra; Mallika, Nagarajan; Sivaraman, J.

    2011-01-01

    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 withS-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?. Sequence analysis suggested that the two proteins are homologous small-molecule methyltransferases. PMID:22102231

  18. Improved, selective, human intestinal carboxylesterase inhibitors designed to modulate 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (irinotecan; CPT-11) toxicity

    OpenAIRE

    Hicks, Latorya D.; Hyatt, Janice L.; Stoddard, Shana; Tsurkan, Lyudmila; Edwards, Carol C.; Wadkins, Randy M.; Potter, Philip M.

    2009-01-01

    CPT-11 is an antitumor prodrug that is hydrolyzed by carboxylesterases (CE) to yield SN-38, a potent topoisomerase I poison. However, the dose limiting toxicity is delayed diarrhea that is thought to arise, in part, from activation of the prodrug by a human intestinal CE (hiCE). Therefore, we have sought to identify selective inhibitors of hiCE that may have utility in modulating drug toxicity. We have evaluated one such class of molecules (benzene sulfonamides), and developed QSAR models for...

  19. Natural Mineral Waters Enhance the Intestinal Health and Stimulate Anti-inflammatory Immune Response in Functional Cell Model of a Non-cancerogenic Human Gut

    Directory of Open Access Journals (Sweden)

    Martin Trapecar

    2012-04-01

    Full Text Available Background Although mineral waters have been used extensively in human nutrition and have widely recognized health related properties; the availability of data on the mechanisms of their actions is limited. Methods and results We have therefore analyzed their ability to increase trans-epithelial resistance of small intestinal epithelia and cell renewal, the bioaccessibilityas well as evaluated their immunomodulatingpotentialin a 3D functional cell model of the gut. Results have showed that the mineral content is highly accessible to the human body. Moreover, carbonated natural mineral water increases the trans-epithelial resistance and epithelial proliferation. In the same time they enhance the anti-inflammatory response by inhibiting activation of TNF- alpha and stimulating the TGF-beta cytokine in healthy epithelia as well as in macrophages. Conclusions We can conclude that by this action the mineral waters have the potential to increase the integrity of the small intestinal wall and its immune status. In addition to providing scientific grounds for a health-beneficial use of natural mineral water, this manuscript provides a novel methodology for the assessment of food derived bioactives in the human gut.

  20. Probing the active-site requirements of human intestinal N-terminal maltase-glucoamylase: Synthesis and enzyme inhibitory activities of a six-membered ring nitrogen analogue of kotalanol and its de-O-sulfonated derivative.

    Science.gov (United States)

    Mohan, Sankar; Sim, Lyann; Rose, David R; Pinto, B Mario

    2010-11-15

    In order to probe the active-site requirements of the human N-terminal subunit of maltase-glucoamylase (ntMGAM), one of the clinically relevant intestinal enzymes targeted for the treatment of type-2 diabetes, the syntheses of two new inhibitors are described. The target compounds are structural hybrids of kotalanol, a naturally occurring glucosidase inhibitor with a unique five-membered ring sulfonium-sulfate inner salt structure, and miglitol, a six-membered ring antidiabetic drug that is currently in clinical use. The compounds comprise the six-membered ring of miglitol and the side chain of kotalanol or its de-O-sulfonated derivative. Inhibition studies of these hybrid molecules with human ntMGAM indicated that they are inhibitors of this enzyme with comparable K(i) values to that of miglitol (kotalanol analogue: 2.30.6?M; corresponding de-O-sulfonated analogue: 1.40.5?M; miglitol: 1.00.1?M). However, they are less active compared to kotalanol (K(i)=0.190.03?M). These results suggest that the (3)T(2) enzyme-bound conformation of the five-membered thiocyclitol moiety of the kotalanol class of compounds more closely resembles the (4)H(3) conformation of the proposed transition state for the formation of an enzyme-substrate covalent intermediate in the glycosidase hydrolase family 31 (GH31)-catalyzed reaction. PMID:20970346

  1. Amebiasis and "nonpathogenic" intestinal protozoa.

    Science.gov (United States)

    Aucott, J N; Ravdin, J I

    1993-09-01

    Infection with single or multiple species of intestinal protozoa is common in humans and can result in either asymptomatic colonization or symptoms of intestinal disease. Entamoeba histolytica serves as a paradigm for invasive colonic protozoal infection. The key to diagnosis and treatment of amebiasis is knowledge of the epidemiologic risk factors and clinical manifestations, a rational approach to diagnosis, and an understanding of the sites of action and uses of anti-amebic drugs. This knowledge of treatment provides a context for consideration of intestinal infection with less common protozoan pathogens such as Dientamoeba fragilis and Balantidium coli and 'nonpathogenic' protozoa such as Blastocystis hominis and Entamoeba coli. PMID:8254155

  2. Disminucin de trnsito intestinal y ausencia de toxicologa aguda preclnicas de la decoccin de partes areas frescas de Phania matricarioides (Spreng. Griseb Reduction of the intestinal transit and lack of preclinical acute toxicology of decoction from Phania matricarioides (Spreng. Griseb fresh aerial parts

    Directory of Open Access Journals (Sweden)

    Ana Ibis Garca Hernndez

    2013-03-01

    Full Text Available Introduccin: la decoccin de partes areas frescas de Phania matricarioides (Spreng. Griseb (manzanilla, se emplea tradicionalmente en Cuba para afecciones digestivas como malas digestiones y diarrea aguda simple; no se encontraron estudios de validacin preclnica del efecto antidiarreico y su seguridad. Objetivos: evaluar la accin sobre el trnsito intestinal y la toxicologa aguda oral y tpica en modelos preclnicos de la decoccin de partes areas frescas de Phania matricarioides. Mtodos: se colectaron las partes areas frescas de Phania matricarioides y se realiz decoccin (30 y 50 %. Se aplic el modelo experimental: trnsito intestinal en ratones con una sola administracin de la decoccin al 30 % en dosis de 1,0, 5,0 y 10,0 g de material vegetal/kg de peso corporal por 1 da; y en dosis de 1,0 y 5,0 g de material vegetal/kg de peso corporal por 4 das. El estudio toxicolgico oral y tpico (decoccin 50 % se efectu en los modelos: clases txicas agudas y toxicidad drmica aguda en ratas con dosis de 2 000 mg/kg de peso corporal e irritabilidad drmica primaria en conejos. Resultados: la decoccin administrada por 1 da no modific de forma significativa el trnsito intestinal, la administracin por 4 das disminuy de forma significativa y dosis dependiente el trnsito intestinal (5,0 g/kg. en el estudio toxicolgico no se produjo ninguna muerte, no se evidenciaron signos de toxicidad ni lesiones macroscpicas en los rganos de las ratas, el aumento de peso fue el esperado. El ndice de irritacin primaria reflej 0. Conclusiones: los resultados permiten validar el efecto antidiarreico de la decoccin de partes areas frescas de Phania matricarioides para afecciones digestivas y no clasifica como txico.Introduction: Phania matricarioides (Spreng. Griseb (chamomile fresh aerial part decoction is traditionally used in Cuba to treat digestive disorders as upset stomach and simple acute diarrheas. However, there were no previous preclinical validation studies on the antidiarrheal effect and safety of this species. Objectives: to evaluate the action of decoction from Phania matricarioides fresh aerial parts on the intestinal transit and the oral and topical acute toxicology in preclinical models. Methods: the fresh aerial parts of this plant were harvested and decoction was obtained (30 and 50 %. The experimental model of intestinal transit in mice, with 30 % decoction being administrated once at doses of 1.0, 5.0 and 10.0 g of vegetal material/kg of bodyweight for one day, and at doses of 1.0 and 5.0 g/kg for 4 days, was applied. The oral and topical toxicological study (50 % decoction was conducted in the models acute-toxic and acute dermal toxic classes in rats at a dose of 2000 mg/kg of bodyweight and primary dermal irritability in rabbits. Results: the decoction administered for one day did not significantly change the intestinal transit, but the administration for 4 days did significantly change, depending on dose, the intestinal transit (5.0 g/kg. There was no death in the study, there were neither signs of toxicity nor macroscopic lesions in the rats' organs, whereas the weight gain behaved as expected. The index of primary irritation was null. Conclusions: the results allow validating the antidiarrheal effect of Phania matricarioides fresh aerial parts decoction on digestive disorders and it is not toxic.

  3. Disminucin de trnsito intestinal y ausencia de toxicologa aguda preclnicas de la decoccin de partes areas frescas de Phania matricarioides (Spreng.) Griseb / Reduction of the intestinal transit and lack of preclinical acute toxicology of decoction from Phania matricarioides (Spreng.) Griseb fresh aerial parts

    Scientific Electronic Library Online (English)

    Ana Ibis, Garca Hernndez; Mara del Carmen, Victoria Amador; Francisco, Morn Rodrguez; Marisol, Lpez Barreiro; Elisa, Boucourt Rodrguez; Mara J, Martnez Guerra; Zulema, Morejn Rodrguez.

    2013-03-01

    Full Text Available Introduccin: la decoccin de partes areas frescas de Phania matricarioides (Spreng.) Griseb (manzanilla), se emplea tradicionalmente en Cuba para afecciones digestivas como malas digestiones y diarrea aguda simple; no se encontraron estudios de validacin preclnica del efecto antidiarreico y su s [...] eguridad. Objetivos: evaluar la accin sobre el trnsito intestinal y la toxicologa aguda oral y tpica en modelos preclnicos de la decoccin de partes areas frescas de Phania matricarioides. Mtodos: se colectaron las partes areas frescas de Phania matricarioides y se realiz decoccin (30 y 50 %). Se aplic el modelo experimental: trnsito intestinal en ratones con una sola administracin de la decoccin al 30 % en dosis de 1,0, 5,0 y 10,0 g de material vegetal/kg de peso corporal por 1 da; y en dosis de 1,0 y 5,0 g de material vegetal/kg de peso corporal por 4 das. El estudio toxicolgico oral y tpico (decoccin 50 %) se efectu en los modelos: clases txicas agudas y toxicidad drmica aguda en ratas con dosis de 2 000 mg/kg de peso corporal e irritabilidad drmica primaria en conejos. Resultados: la decoccin administrada por 1 da no modific de forma significativa el trnsito intestinal, la administracin por 4 das disminuy de forma significativa y dosis dependiente el trnsito intestinal (5,0 g/kg). en el estudio toxicolgico no se produjo ninguna muerte, no se evidenciaron signos de toxicidad ni lesiones macroscpicas en los rganos de las ratas, el aumento de peso fue el esperado. El ndice de irritacin primaria reflej 0. Conclusiones: los resultados permiten validar el efecto antidiarreico de la decoccin de partes areas frescas de Phania matricarioides para afecciones digestivas y no clasifica como txico. Abstract in english Introduction: Phania matricarioides (Spreng.) Griseb (chamomile) fresh aerial part decoction is traditionally used in Cuba to treat digestive disorders as upset stomach and simple acute diarrheas. However, there were no previous preclinical validation studies on the antidiarrheal effect and safety o [...] f this species. Objectives: to evaluate the action of decoction from Phania matricarioides fresh aerial parts on the intestinal transit and the oral and topical acute toxicology in preclinical models. Methods: the fresh aerial parts of this plant were harvested and decoction was obtained (30 and 50 %). The experimental model of intestinal transit in mice, with 30 % decoction being administrated once at doses of 1.0, 5.0 and 10.0 g of vegetal material/kg of bodyweight for one day, and at doses of 1.0 and 5.0 g/kg for 4 days, was applied. The oral and topical toxicological study (50 % decoction) was conducted in the models acute-toxic and acute dermal toxic classes in rats at a dose of 2000 mg/kg of bodyweight and primary dermal irritability in rabbits. Results: the decoction administered for one day did not significantly change the intestinal transit, but the administration for 4 days did significantly change, depending on dose, the intestinal transit (5.0 g/kg). There was no death in the study, there were neither signs of toxicity nor macroscopic lesions in the rats' organs, whereas the weight gain behaved as expected. The index of primary irritation was null. Conclusions: the results allow validating the antidiarrheal effect of Phania matricarioides fresh aerial parts decoction on digestive disorders and it is not toxic.

  4. Human intestinal dendritic cells as controllers of mucosal immunity / Clulas dendrticas del intestino humano como controladoras de la inmunidad mucosa

    Scientific Electronic Library Online (English)

    David, Bernardo.

    2013-06-01

    Full Text Available Las clulas dendrticas son las clulas profesionales presentadoras de antgenos ms potentes que existen y, tras realizar la presentacin antignica, controlan el tipo de respuesta inmune que se establecer (proinflamatoria/reguladora), as como su localizacin. Debido a su gran plasticidad y capac [...] idad de maduracin en respuesta a seales de peligro locales derivadas de la inmunidad innata, las clulas dendrticas son un elemento clave en la conexin entre la inmunidad innata y las respuestas de la inmunidad adaptativa. En el intestino, las clulas dendrticas controlan los mecanismos de la tolerancia inmunolgica frente a los antgenos de la dieta y/o la flora comensal, a la vez que son capaces de iniciar una respuesta inmunolgica activa en presencia de un patgeno invasor. Las clulas dendrticas son pues muy eficientes en controlar el delicado balance entre tolerancia/inmunidad en un ambiente tan cargado de antgenos como es el intestino, y cualquier factor que las afecte puede tener repercusiones en su funcionalidad, pudiendo en ltima instancia desarrollarse patologas intestinales como la enfermedad celiaca o las enfermedades inflamatorias intestinales. En esta revisin sintetizaremos nuestro conocimiento de las clulas dendrticas del intestino humano, su capacidad para expresar e inducir marcadores de migracin, los diversos factores ambientales que modulan sus propiedades, los diferentes subtipos de clulas dendrticas que nos encontramos en el intestino y los problemas derivados de su estudio incluyendo sus diferentes estrategias de identificacin, las diferencias entre humanos y modelos murinos y sus variaciones fenotpicas a lo largo del tracto gastrointestinal. Abstract in english 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 t [...] o 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.

  5. INTESTINAL OBSTRUCTION

    Science.gov (United States)

    Whiffle, G. H.; Stone, H. B.; Bernheim, B. M.

    1913-01-01

    The blood of closed duodenal loop dogs is not toxic to normal dogs. The blood of dogs that have been fatally poisoned with duodenal loop fluid is likewise non-toxic to normal dogs. The mucosa of closed or drained duodenal loops contains a toxic substance quite similar to the toxic material found in the lumen of the closed loops. This toxic substance is absorbed from the mucosa itself and not from the lumen of the drained loops. The same is probably true of the closed loops which have an intact mucosa. It seems highly probable that the poison is formed by the mucosa and is in great part absorbed directly from it by the blood. Normal intestinal mucosa contains no toxic substance nor can it neutralize in vitro the toxic substance produced in the closed loops. There is no evidence that the toxic material when given intravenously is excreted by the intestine or held by the intestinal mucosa in any demonstrable form. The toxic substance is not absorbed from the normal intestinal tract. Destruction of the mucosa in a closed loop by means of sodium fluoride prevents the formation of the toxic substance. This fact furnishes the final proof that the mucosa is the essential factor in the elaboration of the poisonous material. PMID:19867645

  6. The colonization of a simulator of the human intestinal microbial ecosystem by a probiotic strain fed on a fermented oat bran product: effects on the gastrointestinal microbiota.

    Science.gov (United States)

    Kontula, P; Jaskari, J; Nollet, L; De Smet, I; von Wright, A; Poutanen, K; Mattila-Sandholm, T

    1998-08-01

    The effects of Lactobacillus-GG-fermented oat bran product on the microbiota and its metabolic activity in the human gut were investigated, using a simulator of the human intestinal microbial ecosystem (SHIME), by analysing the bacterial population, shortchain fatty acids and gas production. In addition, the effects of fermented oat bran supernatant and supernatant samples from reactors 4, 5 and 6 (large intestine) on the growth of Escherichia coli IHE 13047, Enterococcus faecalis VTT E-93203, Lactobacillus rhamnosus VTT E-94522 (Lactobacillus GG) and Lactococcus lactis subsp. lactis VTT E-90414 were monitored to ascertain possible stimulatory/inhibitory effects by an in vitro turbidometric method. Our experiments showed that Lactobacillus GG colonized the SHIME reactor and this colonization could be maintained for several weeks without extra supplementation. Oat bran feeding also favoured the growth of bifidobacteria and caused an increase in the production of acetic, propionic and butyric acid as well as CH4 and CO2. However, the effects of oat bran, either on bacterial populations or on their metabolic activity, were not directly dose-dependent. In turbidometric measurements, the supernatant of fermented oat bran exerted an inhibitory effect of Lactobacillus GG, but stimulated the growth of enterococci. PMID:9763692

  7. 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-1? effect and increase in the transepithelial passage of commensal bacteria

    International Nuclear Information System (INIS)

    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-1?), 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-1? 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 exancrease). 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

  8. Epidemiology and antimicrobial resistance of B. fragilis group organisms isolated from clinical specimen and human intestinal microbiota Epidemiologia e resistncia a antimicrobianos de microorganismos do grupo B. fragilis isolados de espcime clnico e microbiota intestinal humana

    Directory of Open Access Journals (Sweden)

    Cibele Barreto Mano de Carvalho

    1996-10-01

    Full Text Available Epidemiological aspects and the antimicrobial susceptibility profile of the Bacteroides fragilis group isolated from clinical and human intestinal specimens were examined in this study. B. fragilis group strains were isolated from 46 (37% of 124 clinical specimens and the source of the samples was: Blood culture (3, intraabdominal infection (27, brain abscess (2, soft tissue infection (17, respiratory sinus (3, pleural aspirate (9, breast abscess (3, surgical infected wound (22, pelvic inflammatory disease (22, chronic otitis media (9 and miscellaneous (7. Intraabdominal and soft tissue infections were responsible for more than half of the clinical isolates. Susceptibility to penicillin, cefoxitin, tetracycline, metronidazole, chloramphenicol and clindamycin was examined. All isolates were susceptible to metronidazole and chloramphenicol. For clindamycin and cefoxitin the resistance rates observed were 21.7% and 10.9% respectively. Susceptibility profiles varied among the different species tested. A total of 37 species of B. fragilis group isolated from intestinal microbiota of individuals who had no antimicrobial therapy for at least 1 month before the sampling was also examined. All strains were also susceptible to chloramphenicol and motronidazole and the resistance rates to clindamycin and cefoxitin were 19.4% and 5.4% respectively. A few institutions, in Brazil, have monitored the antimicrobial susceptibility of B. fragilis group strains isolated from anaerobic infections. The resistance rates to cefoxitin and clindamycin and the variation in susceptibility patterns among the species isolated in this study emphasize the need for monitoring of susceptibility patterns of B. fragilis group organisms isolated, especially at our University Hospitals.Alguns aspectos epidemiolgicos e o perfil de sensibilidade a antimicrobianos de amostras do grupo B. fragilis isoladas de espcime clnico e microbiota intestinal humana foram delineados neste estudo. As espcies do grupo B. fragilis foram isoladas de 46 (37% de 124 espcimes clnicos, como segue: hemocultura (3 infeco intra-abdominal (27, abscesso cerebral (2, infeco de tecido mole (17, seios da face (3, aspirado pleural (9, abscesso pulmonar (3, ferida cirrgica (22, doena inflamatria plvica (22, otite mdia crnica (9 e diversos (7. Mais da metade destes microorganismos foram isolados de infeco intra-abdominal e infeco de tecido mole. Os antimicrobianos testados foram Penicilina G, Cefoxitina, Cloranfenicol, Metronidazol, Tetraciclina e Clindamicina. Todas as amostras estudadas apresentaram-se sensveis ao Cloranfenicol e ao Metronidazol. Resistncia clindamicina e cefoxitina foi observada em 21.7 e 10.9% dos microrganismos para cada droga respectivamente. Variao na sensibilidade aos antimicrobianos entre as espcies do grupo foi detectada. O perfil de sensibilidade a antimicrobianos de amostras do grupo B. fragilis isoladas da microbiota intestinal de 37 indivduos que no faziam uso de antimicrobianos nos ltimos 30 dias antes do exame foi tambm estudado. Todas as amostras apresentaram-se sensveis ao cloranfenicol e metronidazol sendo de 19.4% e 5.4% os percentuais de resistncia clindamicina e cefoxitina respectivamente. Poucas Instituies no Brasil, realizam periodicamente teste de sensibilidade a antrimicrobianos para amostras do grupo B. fragilis isoladas de espcimes clnicos. A variao no perfil de sensibilidade entre as espcies do grupo e o alto percentual de resistncia clindamicina e cefoxitina encontrados neste trabalho, reforam a necessidade do isolamento, caracterizao e monitorao do perfil de sensibilidade a antimicrobianos destes microrganismos, pelo menos nos Hospitais Universitrios do pas.

  9. Identification of muscle synergies associated with gait transition in humans

    Science.gov (United States)

    Hagio, Shota; Fukuda, Mizuho; Kouzaki, Motoki

    2015-01-01

    There is no theoretical or empirical evidence to suggest how the central nervous system (CNS) controls a variety of muscles associated with gait transition between walking and running. Here, we examined the motor control during a gait transition based on muscle synergies, which modularly organize functionally similar muscles. To this end, the subjects walked or ran on a treadmill and performed a gait transition spontaneously as the treadmill speed increased or decreased (a changing speed condition) or voluntarily following an experimenters instruction at constant treadmill speed (a constant speed condition). Surface electromyograms (EMGs) were recorded from 11 lower limb muscles bilaterally. We then extracted the muscle weightings of synergies and their activation coefficients from the EMG data using non-negative matrix factorization. As a result, the gait transition was controlled by approximately 9 muscle synergies, which were common during a walking and running, and their activation profiles were changed before and after a gait transition. Near a gait transition, the peak activation phases of the synergies, which were composed of plantar flexor muscles, were shifted to an earlier phase at the walk-to-run transition, and vice versa. The shifts were gradual in the changing speed condition, but an abrupt change was observed in the constant speed condition. These results suggest that the CNS low-dimensionally regulate the activation profiles of the specific synergies based on afferent information (spontaneous gait transition) or by changing only the descending neural input to the muscle synergies (voluntary gait transition) to achieve a gait transition. PMID:25713525

  10. Specific interaction of food proteins with apical membranes of the human intestinal cell lines Caco-2 and T84.

    Science.gov (United States)

    Bolte, G; Wolburg, H; Beuermann, K; Stocker, S; Stern, M

    1998-02-23

    A comparison between the intestinal epithelial cell lines Caco-2 and T84 was made to assess the influence of enterocytic differentiation on food protein binding capacities of the brush border membrane. Cell morphology and expression of brush border-associated enzymes were studied as differentiation markers. Food protein binding to isolated brush border membranes was measured with a dot blot chemiluminescence assay. Early at confluence, Caco-2 cells exhibited a more differentiated state compared to T84 cells. Brush border membranes of both cell lines bound gliadin peptides, beta-lactoglobulin and ovalbumin specifically. Binding capacities increased from gliadin peptides to ovalbumin to beta-lactoglobulin. There was correlation of membrane binding capacity with degree of cell differentiation. Due to their similarity to small intestinal epithelial cells, the colon carcinoma cell lines Caco-2 and T84 represent models for studying food protein-enterocytic brush border membrane interactions in relation to varying degrees of cell differentiation. PMID:9544452

  11. Recipient NOD2/CARD15 status affects cellular infiltrates in human intestinal graft-versus-host disease

    OpenAIRE

    Landfried, K.; Bataille, F.; Rogler, G.; Brenmoehl, J.; Kosovac, K.; Wolff, D.; Hilgendorf, I.; Hahn, J.; Edinger, M.; Hoffmann, P.; Obermeier, F.; Schoelmerich, J.; Andreesen, R.; Holler, E.

    2010-01-01

    Nucleotide-binding oligomerization domain 2/caspase recruitment domain 15 (NOD2/CARD15) polymorphisms have been identified as risk factors of both Crohn's disease and graft-versus-host disease (GVHD) following allogeneic stem cell transplantation. However, the role of these receptors of innate immunity in the pathophysiology of gastrointestinal GVHD is still poorly defined. Immunohistological features of intestinal GVHD were analysed in gastrointestinal biopsies from 58 patients obtained at t...

  12. A four-organ-chip for interconnected long-term co-culture of human intestine, liver, skin and kidney equivalents.

    Science.gov (United States)

    Maschmeyer, Ilka; Lorenz, Alexandra K; Schimek, Katharina; Hasenberg, Tobias; Ramme, Anja P; Hbner, Juliane; Lindner, Marcus; Drewell, Christopher; Bauer, Sophie; Thomas, Alexander; Sambo, Naomia Sisoli; Sonntag, Frank; Lauster, Roland; Marx, Uwe

    2015-06-01

    Systemic absorption and metabolism of drugs in the small intestine, metabolism by the liver as well as excretion by the kidney are key determinants of efficacy and safety for therapeutic candidates. However, these systemic responses of applied substances lack in most in vitro assays. In this study, a microphysiological system maintaining the functionality of four organs over 28 days in co-culture has been established at a minute but standardized microsystem scale. Preformed human intestine and skin models have been integrated into the four-organ-chip on standard cell culture inserts at a size 100?000-fold smaller than their human counterpart organs. A 3D-based spheroid, equivalent to ten liver lobules, mimics liver function. Finally, a barrier segregating the media flow through the organs from fluids excreted by the kidney has been generated by a polymeric membrane covered by a monolayer of human proximal tubule epithelial cells. A peristaltic on-chip micropump ensures pulsatile media flow interconnecting the four tissue culture compartments through microfluidic channels. A second microfluidic circuit ensures drainage of the fluid excreted through the kidney epithelial cell layer. This four-organ-chip system assures near to physiological fluid-to-tissue ratios. In-depth metabolic and gene analysis revealed the establishment of reproducible homeostasis among the co-cultures within two to four days, sustainable over at least 28 days independent of the individual human cell line or tissue donor background used for each organ equivalent. Lastly, 3D imaging two-photon microscopy visualised details of spatiotemporal segregation of the two microfluidic flows by proximal tubule epithelia. To our knowledge, this study is the first approach to establish a system for in vitro microfluidic ADME profiling and repeated dose systemic toxicity testing of drug candidates over 28 days. PMID:25996126

  13. Campylobacter jejuni induces an anti-inflammatory response in human intestinal epithelial cells through activation of phosphatidylinositol 3-kinase/Akt pathway

    DEFF Research Database (Denmark)

    Li, Yiping; Vegge, Christina S.

    2011-01-01

    Campylobacterjejuni (C. jejuni) is the most common cause of human acute bacterial gastroenteritis. Poultry is a major reservoir of C. jejuni and considered an important source of human infections, thus, it is important to understand the host response to C. jejuni from chicken origin. In this study, we demonstrated firstly that a chicken isolate SC11 colonized chicks faster than clinical isolate NCTC11168. Using the SC11, we further studied the host respondsto C. jejuni in terms of inflammatory response and involvement of cellular signaling pathways. Infection of C. jejuni SC11 was able to activate phosphatidylinositol 3-kinase (PI3K)/Akt pathway and induce pro-inflammatory interleukin-8(IL-8) as well as anti-inflammatory cytokine IL-10 in human intestinal epithelial cell line Colo 205. The signalling pathways PI3K/Akt and mitogen-activated protein (MAP)kinases ERK and p38 were involved in C. jejuni-induced IL-8 and IL-10 expression. Inhibition of PI3K resulted in augmentation of C. jejuni-induced IL-8 production, concomitant with down-regulation of IL-10 mRNA, indicating an anti-inflammatory response was activated and associated with the activation of P13K/Akt. Similar effect was observed for cytolethal distending toxin (CDT) deficient mutants. Moreover, we demonstrated that heat-killed bacteria were able to induce IL-8 and IL-10 expression to a lower level than live bacteria. We therefore conclude that C. jejuni activate a PI3K/Akt-dependent anti-inflammatory pathway in human intestinal epithelial cells which may benefit the intracellular survival of C. jejuni during infection.

  14. Application of an LC-MS/MS method for the simultaneous quantification of human intestinal transporter proteins absolute abundance using a QconCAT technique.

    Science.gov (United States)

    Harwood, M D; Achour, B; Russell, M R; Carlson, G L; Warhurst, G; Rostami-Hodjegan, A

    2015-06-10

    Transporter proteins expressed in the gastrointestinal tract play a major role in the oral absorption of some drugs, and their involvement may lead to drug-drug interaction (DDI) susceptibility when given in combination with drugs known to inhibit gut wall transporters. Anticipating such liabilities and predicting the magnitude of the impact of transporter proteins on oral drug absorption and DDIs requires quantification of their expression in human intestine, and linking these to data obtained through in vitro experiments. A quantitative targeted absolute proteomic method employing liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) together with a quantitative concatenation (QconCAT) strategy to provide proteotypic peptide standards has been applied to quantify ATP1A1 (sodium/potassium-ATPase; Na/K-ATPase), CDH17 (human peptide transporter 1; HPT1), ABCB1 (P-glycoprotein; P-gp), ABCG2 (breast cancer resistance protein; BCRP), ABCC2 (multidrug resistance-associated protein 2; MRP2) and SLC51A (Organic Solute Transporter subunit alpha; OST-?), in human distal jejunum (n=3) and distal ileum (n=1) enterocyte membranes. Previously developed selected reaction monitoring (SRM) schedules were optimised to enable quantification of the proteotypic peptides for each transporter. After harvesting enterocytes by calcium chelation elution and generating a total membrane fraction, the proteins were subjected to proteolytic digestion. To account for losses of peptides during the digestion procedure, a gravimetric method is also presented. The linearity of quantifying the QconCAT from an internal standard (correlation coefficient, R(2)=0.998) and quantification of all target peptides in a pooled intestinal quality control sample (R(2)?0.980) was established. The assay was also assessed for within and between-day precision, demonstrating a 0.2fmol/?g membrane protein). MRP2 abundance could be quantified in distal jejunum but not in the distal ileum sample. OST-? was not detected in 2 out of 3 jejunum samples. This study highlights the utility of a QconCAT strategy to quantify absolute transporter abundances in human intestinal tissues. PMID:25796981

  15. Human neutrophil peptides induce interleukin-8 in intestinal epithelial cells through the P2receptor and ERK1/2 signaling pathways.

    Science.gov (United States)

    Ibusuki, Kazunari; Sakiyama, Toshio; Kanmura, Shuji; Maeda, Takuro; Iwashita, Yuji; Nasu, Yuichiro; Sasaki, Fumisato; Taguchi, Hiroki; Hashimoto, Shinichi; Numata, Masatsugu; Uto, Hirofumi; Tsubouchi, Hirohito; Ido, Akio

    2015-06-01

    Human neutrophil peptides (HNPs) are antimicrobial peptides produced predominantly by neutrophils. We have previously reported that HNP1-3 levels are increased in the sera and plasma of patients with active ulcerative colitis. The increased expression of interleukin-8 (IL-8) has also been demonstrated in the colonic mucosa of patients with active ulcerative colitis. HNPs induce IL-8 in lung epithelial cells and monocytes through the P2Y6 signaling pathway. However, the association between HNPs and IL-8 in the intestinal mucosa has not yet been investigated. In the present study, we investigated the effects of HNP-1 on the production of IL-8 by human intestinal epithelial cells and the underlying signaling mechanisms. We observed a significant increase in IL-8 expression in the human colon carcinoma cell line, Caco-2, following treatment with HNP-1. The non-selective P2receptor antagonists, suramin and pyridoxal phosphate-6-azo (benzene-2,4-disulfonic acid) tetrasodium salt hydrate (PPADS), significantly blocked the HNP-1-induced expression of IL-8 in the Caco-2 cells. The P2Y6-specific antagonist, MRS2578, led to a significant but partial decrease in IL-8 expression, suggesting that P2 receptors in addition to P2Y6 are involved in the HNP-1-induced production of IL-8 by Caco-2 cells. In agreement with this finding, HNP-1 also significantly increased IL-8 production in the P2Y6-negative human colon cancer cell line, HT-29, and this increase was blocked by treatment with suramin and PPADS. HNP-1 significantly increased the phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2) and p38mitogen-activated protein kinase (MAPK) in the HT-29 cells. However, the HNP-1-induced production of IL-8 was suppressed by the ERK1/2 inhibitor, U0126, but not by the p38MAPK inhibitor, SB203580. In conclusion, our data demonstrate that HNP-1 induces IL-8 production not only through P2Y6, but also through additional P2 receptors via an ERK1/2-dependent mechanism in intestinal epithelial cells. PMID:25816245

  16. Distortional binding of transition state analogs to human purine nucleoside phosphorylase probed by magic angle spinning solid-state NMR

    OpenAIRE

    Vetticatt, Mathew J.; Itin, Boris; Evans, Gary B.; Schramm, Vern L.

    2013-01-01

    Enzymes are efficient at bringing reactants to the transition state. Transition state analogs mimic the transition state but are chemically stable. What forces do enzymes apply to transition state analogs? Solid-state NMR is used to answer this question for human purine nucleoside phosphorylase. When imperfect and near-perfect transition state analogs are analysed on and off the enzyme, greater distortions are observed for the imperfect transition state analog. The distortion is energetically...

  17. The ecology of social transitions in human evolution

    OpenAIRE

    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...

  18. Inhibitiory properties of cytoplasmic extract of Lactobacilli isolated from common carp intestine on human chronic myelocytic leukemia K562 cell line: an in vitro study

    Directory of Open Access Journals (Sweden)

    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-proliferative effects on K562 cells. The cytoplasmic extractions of Lactobacillus paracasei and Lactobacillus casei inhibited K562 cell proliferation by 66.56% and 54.28% at 83.33 ?g/ml concentration, respectively. Nevertheless, the Lactobacillus cell wall could not inhibit the proliferations of K562 cells (p<0.05."n"nConclusion: In this study, the cytoplasmic extractions of the isolated Lactobacilli from the intestine of common carp had anti-proliferative effects on K562 cell line.

  19. Carrier-mediated -aminobutyric acid transport across the basolateral membrane of human intestinal Caco-2 cell monolayers

    DEFF Research Database (Denmark)

    Nielsen, Carsten Uhd; Carstensen, Mette

    2012-01-01

    The aim of the present study was to investigate the transport of -aminobutyric acid (GABA) across the basolateral membrane of intestinal cells. The proton-coupled amino acid transporter, hPAT1, mediates the influx of GABA and GABA mimetic drug substances such as vigabatrin and gaboxadol and the anticancer prodrug d-aminolevulinic acid across the apical membrane of small intestinal enterocytes. Little is however known about the basolateral transport of these substances. We investigated basolateral transport of GABA in mature Caco-2 cell monolayers using isotope studies. Here we report that, at least two transporters seem to be involved in the basolateral transport of GABA. The basolateral uptake consisted of a high-affinity system with a K(m) of 290M and V(max) of 75pmolcm(-2)min(-1) and a low affinity system with a K(m) of approximately 64mM and V(max) of 1.6nmolcm(-2)min(-1). The high-affinity transporter is Na(+) and Cl(-) dependent. The substrate specificity of the high-affinity transporter was further studied and Gly-Sar, Leucine, gaboxadol, sarcosine, lysine, betaine, 5-hydroxythryptophan, proline and glycine reduced the GABA uptake to approximately 44-70% of the GABA uptake in the absence of inhibitor. Other substances such as -alanine, GABA, 5-aminovaleric acid, taurine and d-aminolevulinic acid reduced the basolateral GABA uptake to 6-25% of the uptake in the absence of inhibitor. Our results indicate that the distance between the charged amino- and acid-groups is particular important for inhibition of basolateral GABA uptake. Thus, there seems to be a partial substrate overlap between the basolateral GABA transporter and hPAT1, which may prove important for understanding drug interactions at the level of intestinal transport.

  20. Inhibitory effect of O-glycosylation inhibition on human intestinal epithelial cells Mucin 2 expression and bacteria adherence

    Directory of Open Access Journals (Sweden)

    Li-li SONG

    2013-11-01

    Full Text Available Objective?To investigate the effect of O-glycosylation inhibition in intestinal epithelial cells on the expression of Mucin 2 (MUC2 and bacterial adherence. Methods?Intestinal epithelial cells HT-29 and differentiated HT-29 cells (HT-29-Gal were treated with an inhibitor of O-glycosylation (benzyl-?-GalNAc, and then named as HT-29-OBN and HT-29-Gal-OBN, respectively. The mRNA and protein expression of MUC2 in HT-29, HT29-Gal, HT-29-OBN and HT-29-Gal-OBN were detected by real-time PCR and Western blotting. Then the four kinds of above cells were incubated with enteropathogenic Escherichia coli (EPEC or enterohemorrhagic Escherichia coli serotype O157:H7 (EHEC O157:H7. The bacteria were quantified by determining the colony forming unit (CFU following the plating of serial dilutions of the bacteria to evaluate the effect of benzyl-?-GalNAc on bacteria adherence. Results?The results of real-time PCR and Western blotting showed that the mRNA and protein expression levels of MUC2 in HT-29-OBN and HT-29-Gal-OBN cells were significantly lower than those in the untreated cells HT-29 and HT-29-Gal (P<0.05. The bacterial adherence assay showed that the adherence of EPEC and EHEC O157:H7 to HT-29-OBN and HT-29-Gal-OBN cells significantly decreased compared with that to HT-29 and HT-29-Gal cells (P<0.05. Conclusion?Inhibition of O-glycosylation in intestinal epithelial cells may reduce the bacteria adherence and MUC2 expression. DOI: 10.11855/j.issn.0577-7402.2013.10.009

  1. Microbiota intestinal: sus repercusiones clnicas en el cuerpo humano / Gut microbiota: its clinical implications in the human body

    Scientific Electronic Library Online (English)

    Norberto D, Giglio; Fernando, Burgos; Brian M, Cavagnari.

    2013-12-01

    Full Text Available La comunidad de microbios que vive en el tracto gastrointestinal de una persona, denominada microbiota intestinal, cumple una importante funcin en la salud: estimula el sistema inmunitario, protege de la invasin por patgenos y obtiene energa de los nutrientes. Los cambios en la confguracin de l [...] a microbiota alteran la homeostasis husped-comunidad microbiana y repercuten en la salud. En el presente trabajo se comenta cmo se adquiere la microbiota, cul es su dinmica desde el nacimiento hasta la vejez, cmo es la relacin bidireccional que la microbiota establece con los seres humanos, y su repercusin en la salud, la enfermedad y la biodisponibilidad de los medicamentos.

  2. Metabolic Activities of Ginseng and Its Constituents, Ginsenoside Rb1 and Rg1, by Human Intestinal Microflora

    OpenAIRE

    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 ?-glucosidase activity for p-nitrophenyl- ?-D-glucopyranoside was 0 to 0.42 ?mol/min/mg and its average activity (meanSD) was 0.100.07 ?mol/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 ave...

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

    OpenAIRE

    Leo Lahti; Anne Salonen; Kekkonen, Riina A.; Jarkko Salojrvi; Jonna Jalanka-Tuovinen; Airi Palva; Matej Orei?; WillemM. deVos

    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...

  4. Bovine colostrum improves intestinal function following formula-induced gut inflammation in preterm pigs

    DEFF Research Database (Denmark)

    Sty, Ann Cathrine Findal; Heegaard, Peter M. H.

    2014-01-01

    Background & aims Only few hours of formula feeding may induce proinflammatory responses and predispose to necrotizing enterocolitis (NEC) in preterm pigs. We hypothesized that bovine colostrum, rich in bioactive factors, would improve intestinal function in preterm pigs following an initial 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, abundance and location of bacteria, and inflammation markers were investigated. Results NEC severity and interleukins (IL)-1? and -8 protein concentrations were lower, while villus height, galactose absorption, and brush-border enzyme activities were increased in the distal small intestine in COLOS and FCOLOS pigs, relative to FORM pigs. Intestinal gene expression of serum amyloid A, IL-1?, -6 and -8, and bacterial abundance, correlated positively with NEC severity of the distal small intestine. Conclusions Bovine colostrum restores intestinal function after initial formula-induced inflammation in 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. A Multicellular Approach Forms a Significant Amount of Tissue-Engineered Small Intestine in the Mouse

    Science.gov (United States)

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

    2011-01-01

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

  6. Calcium bioaccessibility and uptake by human intestinal like cells following in vitro digestion of casein phosphopeptide-calcium aggregates.

    Science.gov (United States)

    Perego, Silvia; Del Favero, Elena; De Luca, Paola; Dal Piaz, Fabrizio; Fiorilli, Amelia; Cantu', Laura; Ferraretto, Anita

    2015-06-10

    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

  7. Investigations on the method of in vitro accumulation measurements of 14C phenylalanine on human small intestine biopsies, illustrated by the example of Diabetes mellitus

    International Nuclear Information System (INIS)

    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)

  8. Transitions of Creatives? : Empirical Evidence on Occupation and Industry Specific Human Capital

    DEFF Research Database (Denmark)

    Fjllegaard, Cecilie Bryld

    The degree of transferability of skills and knowledge from an creative occupation in the creative industries to the wider economy is a great point of discussion within research in the arts and cultural and creative industries. By applying human capital theory on the labor market for creatives, this paper investigates the relationship between creative occupation and industry human capital and hourly wage after transitioning to a non-creative occupation and/ or industry. Further, it is investigated how the distance of the transition mediates the relationship between creative occupation and industry specific human capital and hourly wage. By making use of a matched employer-employee dataset from the Denmark from 1994 to 2007, wage equation are estimated. The results suggest that a transition from a creative occupation to a non-creative occupation results in an increase in the hourly wage. On the contrary, a transition from a creative industry to a non-creative industry is associated with a decrease in the hourlywage. These results are however completely mediated by the distance of the transition, meaning that the distance of the transition completely explains the effect on the hourly wage. The results have implication for the understanding of whether creative human capital is transferable to the wider economy.

  9. Retrospective analysis of patients undergoing bowel transit reconstruction in a tertiary referral hospital of So Paulo's east side / Anlise retrospectiva dos pacientes submetidos reconstruo de trnsito intestinal em hospital tercirio de referncia da zona leste de So Paulo

    Scientific Electronic Library Online (English)

    Isaac Jos Felippe, Corra Neto; Otvio Nunes, Si; Eduardo Augusto, Lopes; Rodrigo, Padilla; Katiucia Tereza Molezin, Portugal; Alexander S, Rolim; Rogrio Freitas Lino, Souza; Hugo Henriques, Watt; Larcio, Robles.

    2014-12-01

    Full Text Available Introduo: A morbi-mortalidade de pacientes submetidos reconstruo de trnsito intestinal alcana valores significativos e, por esse e outros fatores, talvez se explique o fato que de 30 a 60% dos portadores de ostomia intestinal terminal passam a possu-la de maneira definitiva, apesar de, na [...] maior parte das vezes, ela ser realizada como procedimento provisrio com o argumento de maior segurana do paciente. Objetivo: Analisar retrospectivamente os dados de pronturio de pacientes submetidos reconstruo de trnsito intestinal em um dos hospitais de referncia do SUS na cidade de So Paulo no perodo de outubro de 2008 a dezembro de 2011. Resultados: A mdia de idade dos pacientes foi de 53,9 anos e 54% dos 100 pacientes estudados no perodo de outubro de 2008 e dezembro de 2011 padeciam de alguma comorbidade. A indicao para confeco da ostomia inicial decorreu de doena maligna em 43% e o tempo mdio de permanncia com o estoma foi de 14,3 meses. A taxa de mortalidade foi de 6%. Concluso: Embora a reconstruo do trnsito intestinal seja um procedimento bastante desejado pelos pacientes, sua indicao deve ser bastante criteriosa, com consentimento adequado por parte do paciente. Abstract in english Introduction: The morbidity and mortality of patients undergoing bowel transit reconstruction reach significant values. Perhaps this and other factors could explain why 3060% of patients end up with definitive ostomies, even those with initially temporary ostomies, due to the procedure risks. Ob [...] jective: To analyze retrospectively the medical records of patients undergoing bowel transit reconstruction in one of the SUS referral hospitals in So Paulo from October 2008 to December 2011. Results: The mean age of our patients was 53.9 years and 54% of those 100 patients studied between October 2008 and December 2011 had significant comorbidity. The indication for creating an initial ostomy was malignancy in 43%, and the mean stoma duration 14.3 months. The mortality rate was 6%. Conclusion: Although the bowel transit reconstruction is a procedure quite desired by patients, its indication should be carefully evaluated, with an appropriate consent from the patient.

  10. Urban Transitions: On Urban Resilience and Human-Dominated Ecosystems

    OpenAIRE

    Ernstson, Henrik; Leeuw, Sander E.; Redman, Charles L.; Meffert, Douglas J.; Davis, George; Alfsen, Christine; Elmqvist, Thomas

    2010-01-01

    Urbanization is a global multidimensional process paired with increasing uncertainty due to climate change, migration of people, and changes in the capacity to sustain ecosystem services. This article lays a foundation for discussing transitions in urban governance, which enable cities to navigate change, build capacity to withstand shocks, and use experimentation and innovation in face of uncertainty. Using the three concrete case citiesNew Orleans, Cape Town, and Phoenixthe article an...

  11. Small intestinal bacterial overgrowth syndrome

    Directory of Open Access Journals (Sweden)

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

    2010-06-01

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

  12. Glutamatergic pre-ictal discharges emerge at the transition to seizure in human epilepsy.

    OpenAIRE

    Huberfeld, Gilles; Menendez La Prida, Liset; Pallud, Johan; Cohen, Ivan; Le Quyen, Michel; Adam, Claude; Clemenceau, Stephane; Baulac, Michel; Miles, Richard

    2011-01-01

    Abstract Mechanisms involved in the transition to an epileptic seizure remain unclear. We studied this question in tissue slices from human subjects with mesial temporal lobe epilepsies. Ictal-like discharges were induced in the subiculum by increasing excitability together with an alkalinization or low Mg2+. During the transition, distinct pre-ictal discharges emerged concurrently with interictal events. Intracranial recordings from the mesial temporal cortex of epileptic subjects...

  13. Influences of task concreteness upon transitive responding in humans

    OpenAIRE

    Siemann, Martina; Delius, Juan

    1996-01-01

    The derivation of the conclusion "Anna is bigger than Mary" from the premises "Anna is bigger than Paul" and "Mary is smaller than Paul" is considered an instance of transitive deduction. For a non-verbal presentation, the premise statements were here transformed into a multiple operant discrimination task. Adult subjects were trained with overlapping pairs of a six-member stimulus series (A+B, A+C, C+D, D+E, E+F; +: choice rewarded, choice penalized). A computer game-type pres...

  14. Sndrome de intestino corto: definicin, causas, adaptacin intestinal y sobrecrecimiento bacteriano / Short bowel syndrome: definition, causes, intestinal adaptation and bacterial overgrowth

    Scientific Electronic Library Online (English)

    M. D., Ballesteros Pomar; A., Vidal Casariego.

    2007-05-01

    Full Text Available El sndrome de intestino corto (SIC) es una entidad compleja debida a una prdida anatmica o funcional de una parte del intestino delgado que ocasiona un cuadro clnico de graves alteraciones metablicas y nutricionales debidas a la reduccin de la superficie absortiva intestinal efectiva. El SIC e [...] s una causa de la condicin ms amplia de "fallo intestinal". Actualmente, los accidentes vasculares mesentricos son la causa principal en adultos, seguidos de la enfermedad inflamatoria intestinal y la enteritis rdica, mientras que en nios las principales causas con las enfermedades congnitas y perinatales. La clnica asociada al SIC tambin est en funcin de la longitud y la zona de intestino delgado afectada, la presencia de enfermedad subyacente, la presencia o ausencia de colon y de vlvula ileocecal, y la naturaleza de la enfermedad de base. La adaptacin intestinal es el proceso que a lo largo de 1-2 aos trata de restablecer la absorcin intestinal a aquella previa a la reseccin intestinal y es un factor fundamental para determinar si un paciente con SIC progresar a fracaso intestinal y dependencia de NPD. La adaptacin intestinal puede ocurrir gracias a que el paciente haga una ingesta superior a la normal (hiperfagia); pero adems, el intestino tambin es capaz de adaptarse para asegurar una absorcin ms eficaz por unidad de superficie, bien aumentando su superficie absortiva (adaptacin estructural) y/o enlenteciendo el trnsito gastrointestinal (adaptacin estructural). An no estn bien establecidos estos cambios en humanos, aunque s en modelos animales. En el xito del proceso de adaptacin influye la presencia de nutrientes en la luz intestinal, as como algunas hormonas gastrointestinales, especialmente GLP-2. Los pacientes con SIC estn predispuestos a la aparicin de sobrecrecimiento bacteriano, que dificulta la adaptacin, empeora la sintomatologa y es un factor de dependencia de nutricin parenteral. Abstract in english The short bowel syndrome (SBS) is a complex entity due to anatomical or functional loss of part of the small bowel originating a clinical picture with severe metabolic and nutritional impairments due to reduction of the effective absorptive surface area of the gut. SBS is one of the causes of a larg [...] er entity known as "intestinal failure". Currently, mesenteric vascular accidents are the main cause in adults, followed by inflammatory bowel disease, and radiation enteritis, whereas in children, the main causes are congenital and perinatal diseases. The clinical picture associated with SBS varies according to the length and location of affected small bowel, the presence of underlying disease, the presence or absence of the large bowel and ileocecal valve, and the nature of the underlying disease. Intestinal adaptation is the process by which, throughout 1-2 years, intestinal absorption is reestablished to the situation prior to intestinal resection, and is a key factor determining whether a patient with SBS will progress to intestinal failure and depend on DPN. Intestinal adaptation may take place if the patient does oral intake higher than the usual one (hyperphagia); besides, the bowel may also adapt to secure a more effective absorption per surface area unit, either by increasing the absorptive surface area (structural adaptation) and/or slowing intestinal transit (functional adaptation). These changes are not still clearly established in humans, but there are so in animal models. The presence of nutrients within the intestinal lumen and certain gastrointestinal hormones, particularly GLP-2, have an influence on a successful adaptation process. Patients with SBS are prone to the occurrence of bacterial overgrowth that makes adaptation difficult and worsens the symptoms, besides being a factor for dependence on parenteral nutrition.

  15. Avaliao do nmero de clulas caliciformes nas criptas da mucosa colnica com e sem trnsito intestinal Evaluation of the number of goblet cells in crypts of the colonic mucosa with and without fecal transit

    Directory of Open Access Journals (Sweden)

    Rodrigo de Oliveira Mello

    2012-04-01

    Full Text Available OBJETIVO: Medir a espessura das criptas e quantificar o nmero de clulas caliciformes comparando a mucosa clica com e sem trnsito intestinal, relacionando-as ao tempo de excluso. MTODOS: Sessenta ratos Wistar, foram distribudos em trs grupos com 20 animais segundo a operao final para a retirada dos clons, realizadas em seis, 12 ou 18 semanas. Em cada grupo, 15 animais foram submetidos derivao do trnsito por colostomia proximal no clon esquerdo e fstula mucosa distal e cinco apenas laparotomia (controle. Os clons com e sem trnsito fecal foram removidos, processados, submetidos a cortes histolgicos corados pela hematoxilina-eosina. A altura das criptas colnicas e o nmero de clulas caliciformes foram mensurados por morfometria computadorizada. Foram utilizados os testes t de Student e Kruskal-Wallis para comparao e anlise de varincia, estabelecendo-se nvel de significncia de 5% (pOBJECTIVE: To measure the thickness of the crypts and quantify the number of goblet cells of the colonic mucosa with and without intestinal transit, relating them to exclusion time. METHODS: Sixty Wistar rats were divided into three groups of 20 animals each according to the time of the final operation for the removal of the colon, in six, 12 or 18 weeks. In each group 15 animals underwent colonic exclusion by left colon proximal colostomy and distal mucous fistula, and five underwent only laparotomy (control. The colons with and without fecal stream were removed, processed and submitted to histological sections stained with hematoxylin-eosin. The height of the colonic crypts and the number of goblet cells were measured by computerized morphometry. We used the Student t test and Kruskal-Wallis test for comparison and analysis of variance, using a significance level of 5% (p <0.05. RESULTS: The height of the crypts decreased in segments without fecal stream (p =0.0001, reducing from six to 12 weeks of exclusion (p = 0.0003, stabilizing thereafter. The number of goblet cells in the crypts was smaller in segments without transit after 12 and 18 weeks (p = 0.0001, but increased as the time of exclusion progressed (p = 0.04 CONCLUSION: The exclusion of intestinal transit decreases the thickness of the colonic crypts and the number of goblet cells in the segments without transit. There is an increased number of goblet cells in the course of time exclusion.

  16. Regional unemployment and human capital in transition economies

    OpenAIRE

    Jurajda, S?tepa?n; Terrell, Katherine

    2007-01-01

    Differences in regional unemployment in post-communist economies are large and persistent. We show that inherited variation in human-capital endowment across the regions of four such economies explains the bulk of regional unemployment variation there and we explore potential explanations for this outcome through related capital and labor mobility patterns. The evidence suggests that regions with high inherited skill endowments attract skilled workers as well as FDI. This mobility pattern, wh...

  17. Development of a high-specificity sandwich ELISA system for the quantification of human intestinal fatty acid-binding protein (I-FABP) concentrations.

    Science.gov (United States)

    Funaoka, Hiroyuki; Kanda, Tatsuo; Kajiura, Satoshi; Ohkaru, Yasuhiko; Fujii, Hiroshi

    2011-01-01

    Intestinal fatty acid-binding protein (I-FABP), a low molecular mass (approximately 15 kDa) cytoplasmic protein, is specifically located in epithelial cells of small bowel mucosal layer. This protein is rapidly released into the circulation after injury and/or destruction of these cells due to poor mesenteric blood flow and necrosis. Therefore, it can be used as a potential diagnostic biomarker for small bowel disease. In the present study, we have succeeded in developing a sandwich enzyme-linked immunosorbent assay (ELISA) system for quantification of human I-FABP. The range of sandwich ELISA system was 0.1-50 ng/mL of I-FABP in serum, and showed excellent quantitative characteristics such as reproducibility, dilution linearity, and recovery. No cross-reactivities were detected with other types of FABPs. As measured with this ELISA system, the serum I-FABP concentration was 1.1 0.9 ng/mL in 61 healthy individuals, indicating that the reference value was below 2.0 ng/mL regardless of gender and age. Furthermore, mild abdominal pain or diarrhea before blood sampling did not affect I-FABP levels. Thus, this ELISA system could be used to accurately quantify human I-FABP concentrations in serum samples. These results suggest that it could be used as a new biomarker for the diagnosis of small bowel disease. PMID:21204605

  18. Antagonism between two intestinal parasites in humans: the importance of co-infection for infection risk and recovery dynamics

    Science.gov (United States)

    Blackwell, Aaron D.; Martin, Melanie; Kaplan, Hillard; Gurven, Michael

    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 helminthgiardia co-infections in a panel study of foragerhorticulturalists in the Bolivian lowlands. Parasites were identified in faecal samples from 3275 participants, collected during 5235 medical exams over 6 years. Longitudinal co-infection patterns were examined using logistic mixed and multi-state Markov models. The most prevalent infections were hookworm (56%), Giardia lamblia (30%) and Ascaris lumbricoides (15%). Cross-sectionally, hookworm and A. lumbricoides were negatively associated with G. lamblia (OR = 0.60; OR = 0.65, respectively). Longitudinally, giardia infection was less likely in helminth-infected individuals (HR: 0.46). Infection with helminths was also less likely for individuals infected with giardia (HR: 0.71). Finally, treatment with mebendazole reduced subsequent hookworm infections, but resulted in a marginal increase in the odds of G. lamblia infection. Our results provide evidence for an antagonistic relationship between helminths and giardia, and suggest that co-infection should be considered in disease transmission models and treatment decisions. PMID:23986108

  19. Reversible monomer-oligomer transition in human prion protein

    OpenAIRE

    Sasaki, Ken; Gaikwad, Jyoti; Hashiguchi, Shuhei; Kubota, Toshiya; Sugimura, Kazuhisa; Kremer, Werner; Kalbitzer, Hans Robert; Akasaka, Kazuyuki

    2008-01-01

    The structure and the dissociation reaction of oligomers PrPoligo from reduced human prion huPrPC(23231) have been studied by 1H-NMR and tryptophan fluorescence spectroscopy at varying pressure, along with circular dichroism and atomic force microscopy. The 1H-NMR and fluorescence spectral feature of the oligomer is consistent with the notion that the N-terminal residues including all seven Trp residues, are free and mobile, while residues 105?210, comprising the AGAAAAGA motif and S1-Lo...

  20. Transition in the Human Exploration of Space at NASA

    Science.gov (United States)

    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.

  1. Distribution of vasoactive intestinal peptide, pituitary adenylate cyclase-activating peptide, nitric oxide synthase, and their receptors in human and rat sphenopalatine ganglion

    DEFF Research Database (Denmark)

    Csati, A; Tajti, J

    2012-01-01

    Cranial parasympathetic outflow is mediated through the sphenopalatine ganglion (SPG). The present study was performed to examine the expression of the parasympathetic signaling transmitters and their receptors in human and rat SPG. Indirect immunofluorescence technique was used for the demonstration of vasoactive intestinal peptide (VIP), pituitary adenylate cyclase-activating peptide (PACAP), nitric oxide synthase (NOS), glutamine synthetase (GS), glial fibrillary acidic protein (GFAP), VIP and PACAP common receptors (VPAC1, VPAC2), and PACAP receptor (PAC1). In addition, double labeling was carried out to reveal the co-localization of neurotransmitters. VIP-immunoreactive (-ir) neurons as well as fibers were frequently found in human SPG. Many, homogenously stained NOS-ir cells were found, but no positive fibers. In addition, PACAP-ir was observed in some of the neurons and in fibers. Co-localization was found between VIP and NOS. In rat VIP-, NOS-, and PACAP-ir were found in many neurons and fibers. Co-localization of PACAP and NOS was observed in neurons. PACAP and GS double staining revealed that the PACAP-ir was localized in/close to the cell membrane, but not in the satellite glial cells. PAC1 and VPAC1 immunoreactivity was found in the satellite glial cells of both human and rat. Western blot revealed protein expression of PAC1, VPAC1, and VPAC2 in rat SPG. The trigeminal-autonomic reflex may be active in migraine attacks. We hypothesized that VIP, PACAP, NOS, PAC1, VPAC1, and VPAC2 play a role in the activation of parasympathetic cranial outflow during migraine attacks.

  2. Intestinal adaptation after massive intestinal resection

    OpenAIRE

    Weale, A.; Edwards, A.; Bailey, M.; Lear, P.

    2005-01-01

    Patients with short bowel syndrome require long term parenteral nutrition support. However, after massive intestinal resection the intestine undergoes adaptation and nutritional autonomy may be obtained. Given that the complications of parenteral nutrition may be life threatening or result in treatment failure and the need for intestinal transplantation, a more attractive option is to wean patients off nutrition support by optimising the adaptive process. The article examines the evidence tha...

  3. Genistein-induced G2/M cell cycle arrest of human intestinal colon cancer Caco-2 cells is associated with Cyclin B1 and Chk2 down-regulation

    OpenAIRE

    Han, Junkyu; Kurita, Yui; Isoda, Hiroko

    2013-01-01

    Genistein is an isoflavonic phyto-oestrogen contained in soya beans. It is thought to display anti-cancer effects. This study was designed to investigate its effect on human intestinal colon cancer Caco-2 cells. MTT assay, flow cytometric analysis and western blotting were used to investigate the effect of genistein on cell proliferation, cell cycle progression and protein alterations of selected cell cycle-related proteins in Caco-2 cells. Our results showed that genistein and daidzein signi...

  4. Effects of phenol on barrier function of a human intestinal epithelial cell line correlate with altered tight junction protein localization

    OpenAIRE

    McCall, Ingrid C.; Betanzos, Abigail; Weber, Dominique A.; NAVA, PORFIRIO; Miller, Gary W.; PARKOS, CHARLES A.

    2009-01-01

    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.

  5. N-[5-nitro-2-furfurylidene]-3-amino-2-oxazolidinone activation by the human intestinal cell line Caco-2 monitored through noninvasive electron spin resonance spectroscopy.

    Science.gov (United States)

    Rossi, L; De Angelis, I; Pedersen, J Z; Marchese, E; Stammati, A; Rotilio, G; Zucco, F

    1996-03-01

    The pathways participating in the metabolism of the nitrofuran antimicrobial drug N-[5-nitro-2-furfurylidene]-3-amino-2-oxazolidinone (furazolidone) in intact cells were investigated in the human intestinal cell line Caco-2. One-electron reduction of furazolidone led to the formation of a free radical intermediate that could be monitored in dense cell suspensions by noninvasive electron spin resonance spectroscopy. The effects of enzyme inhibitors on the kinetics of radical production and decay were used to estimate the relative contribution of different enzymes to the reductive activation of the drug. Although many enzymes are known to reduce nitrofurans in vitro (e.g., xanthine oxidase, aldehyde oxidase, DT-diaphorase, mitochondrial redox chain components), their contributions were insignificant in living Caco-2 cells. The first reducing equivalent required for the formation of the nitroanion derivative of furazolidone appeared to be provided essentially by the microsomal cytochrome P450 reductase. This was confirmed through studies of the NADPH-dependent radical formation by microsomes. Differentiated Caco-2 cells, an established enterocyte model, showed only modestly increased radical formation and the same enzyme-specificity pattern as undifferentiated cells. Consistently, only a small increase in P450 reductase activity was found in differentiated cells, in contrast to the 10-fold increase seen in typical differentiation marker enzymes. With the electron spin resonance method that we describe, it is possible to distinguish between sites of bioactivation of redox active drugs in intact cells. PMID:8643095

  6. Vibrio cholerae non-O1: production of cell-associated hemagglutinins and in vitro adherence to mucus coat and epithelial surfaces of the villi and lymphoid follicles of human small intestines treated with formalin.

    Science.gov (United States)

    Yamamoto, T; Yokota, T

    1988-10-01

    Clinically isolated Vibrio cholerae non-O1 strains produced more cell-associated hemagglutinins (HAs) on colonization factor antigen agar after ca. 3 h than after ca. 20 h of incubation at 37 degrees C. A high cell-associated HA producer variant of strain TVN-318, grown for 3 h at 37 degrees C, was entrapped in a native mucus coat covering the human ileal mucosa and displayed a striking ability to adhere to the surface of a Formalin-treated mucus coat, in contrast to a poor cell-associated HA producer variant of TVN-318, grown for 20 h at 37 degrees C. Adherence to the Formalin-treated human mucus coat was confirmed with all of the strains tested. V. cholerae non-O1 strains also possessed the ability to adhere to the epithelial surfaces of Formalin-treated human and rabbit ileal or jejunal villi, as well as human lymphoid follicles, in proportion to cell-associated HA levels. The epithelial surface of the lymphoid follicles provided most of the adherence sites for V. cholerae non-O1 strains under the test conditions. We conclude that a mucus coat covering the human small intestinal mucosa is a primary adherence target for V. cholerae non-O1 strains in human intestinal infections and that cell-associated HAs have at least a partial role in the adherence of V. cholerae non-O1 strains to the human small intestine, suggesting a potential role for V. cholerae non-O1 strains in an oral live vaccine. PMID:2903173

  7. Enteral nutrients potentiate glucagon-like peptide-2 action and reduce dependence on parenteral nutrition in a rat model of human intestinal failure

    DEFF Research Database (Denmark)

    Brinkman, Adam S; Murali, Sangita G

    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 ?gkg(-1)day(-1)), PN + EN + GLP-2(7 days), PN + EN + GLP-2(18 days), and a nonsurgical oral reference group. Animals underwent massive distal bowel resection followed by jejunocolic anastomosis and placement of jugular catheters. Starting on postoperative day 4, rats in the EN groups were allowed ad libitum access to EN. Groups provided PN + EN + GLP-2 had their rate of PN reduced by 0.25 ml/day starting on postoperative day 6. Groups provided PN + EN + GLP-2 demonstrated significantly greater body weight gain with similar energy intake and a safe 80% reduction in PN compared with TPN GLP-2. Groups provided PN + EN + GLP-2 for 7 or 18 days showed similar body weight gain, residual jejunal length, and digestive capacity. Groups provided PN + EN + GLP-2 showed increased jejunal GLP-2 receptor (GLP-2R), insulin-like growth factor-I (IGF-I), and IGF-binding protein-5 (IGFBP-5) expression. Treatment with TPN + GLP-2 demonstrated increased jejunal expression of epidermal growth factor. Cessation of GLP-2 after 7 days with continued EN sustained the majority of intestinal adaption and significantly increased expression of colonic proglucagon compared with PN + EN + GLP-2 for 18 days, and increased plasma GLP-2 concentrations compared with TPN alone. In summary, EN potentiate the intestinotrophic actions of GLP-2 by improving body weight gain allowing for a safe 80% reduction in PN with increased jejunal expression of GLP-2R, IGF-I, and IGFBP-5 following distal bowel resection in the rat.

  8. Modulation of cellular phospholipid fatty acids and leukotriene B4 synthesis in the human intestinal cell (CaCo-2).

    OpenAIRE

    Dias, V. C.; Wallace, J. L.; Parsons, H. G.

    1992-01-01

    The ability of a human colonocyte epithelial cell line (CaCo-2) to synthesise leukotriene B4 was examined. In addition, the effects of stimulation with calcium ionophore, inhibition by a drug which specifically prevents activation of 5-lipoxygenase, and modification of the fatty acid composition of membrane phospholipids on leukotriene B4 synthesis were assessed. Incubation with calcium ionophore (A23187) resulted in a dose and time dependent increase in leukotriene B4 synthesis. After cell p...

  9. Neighboring Group Participation in the Transition State of Human Purine Nucleoside Phosphorylase

    Energy Technology Data Exchange (ETDEWEB)

    Murkin,A.; Birck, M.; Rinaldo-Matthis, A.; Shi, W.; Taylor, E.; Almo, S.; Schramm, V.

    2007-01-01

    The X-ray crystal structures of human purine nucleoside phosphorylase (PNP) with bound inosine or transition-state analogues show His{sup 257} within hydrogen bonding distance of the 5'-hydroxyl. The mutants His257Phe, His257Gly, and His257Asp exhibited greatly decreased affinity for Immucillin-H (ImmH), binding this mimic of an early transition state as much as 370-fold (K{sub m}/K{sub i}) less tightly than native PNP. In contrast, these mutants bound DADMe-ImmH, a mimic of a late transition state, nearly as well as the native enzyme. These results indicate that His{sup 257} serves an important role in the early stages of transition-state formation. Whereas mutation of His{sup 257} resulted in little variation in the PNP{center_dot}DADMe-ImmH{center_dot}SO{sub 4} structures, His257Phe{center_dot}ImmH{center_dot}PO{sub 4} showed distortion at the 5'-hydroxyl, indicating the importance of H-bonding in positioning this group during progression to the transition state. Binding isotope effect (BIE) and kinetic isotope effect (KIE) studies of the remote 5'-{sup 3}H for the arsenolysis of inosine with native PNP revealed a BIE of 1.5% and an unexpectedly large intrinsic KIE of 4.6%. This result is interpreted as a moderate electronic distortion toward the transition state in the Michaelis complex with continued development of a similar distortion at the transition state. The mutants His257Phe, His257Gly, and His257Asp altered the 5'-{sup 3}H intrinsic KIE to -3, -14, and 7%, respectively, while the BIEs contributed 2, 2, and -2%, respectively. These surprising results establish that forces in the Michaelis complex, reported by the BIEs, can be reversed or enhanced at the transition state.

  10. Assessing survival of dairy propionibacteria in gastrointestinal conditions and adherence to intestinal epithelia.

    Science.gov (United States)

    Zrate, Gabriela; Gonzlez, Silvia; Chaia, Adriana Prez

    2004-01-01

    The genus Propionibacterium consists of two principal groups, cutaneous and classical or dairy. Cutaneous species are predominant members of the microbial population of human skin and have also been isolated from the feces of humans and other vertebrate animals. They are often considered opportunistic organisms and have been occasionally associated with infections in humans. Dairy propionibacteria are microorganisms extensively used in the industry for manufacture of Swiss-type cheeses and biological production of propionic acid and vitamin B12. They can be isolated from soil, vegetables, silage, raw milk, and dairy products such as kefir and different cheeses with "eyes."In the last decade, several studies have demonstrated probiotic properties for members of the genus Propionibacterium. The effects claimed are based on the production of bacteriocins, vitamins, stimulation of growth of other colonic bacteria like bifidobacteria, beneficial modification of the composition and metabolic activities of the intestinal microflora, immunomodulation, and antimutagenic activity. It is thought that to produce many of these health benefits, the probiotic microorganisms must be able to survive the transit through the hostile conditions of the gastrointestinal tract (GIT) and remain at high levels in the intestine, avoiding removal by peristaltic contractions of the gut. In this sense, microorganisms with a short generation time or the ability to adhere to the intestinal mucosa will survive for prolonged periods in the body of the host. Therefore, two desirable properties for probiotic microorganisms are (1) resistance to gastric acidity, bile, and pancreatic enzymes; and (2) adhesion ability to mucosal surfaces. Dairy bacteria are traditionally not considered to persist as normal inhabitants of the human intestinal tract. Therefore, survival under GIT conditions and adherence are important properties to be considered, and tests to study them would be useful tools. In the present chapter we describe the methods used in our laboratory to assess survival, metabolic activity, and adhesion of dairy propionibacteria to intestinal epithelial cells after gastrointestinal digestion. PMID:15156053

  11. Radioimmunoimaging in human transitional cell carcinoma xenografted nude mice with monoclonal antibody L4B4

    International Nuclear Information System (INIS)

    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

  12. Regulation of taurine transport by Escherichia coli heat-stable enterotoxin and guanylin in human intestinal cell lines.

    OpenAIRE

    Brandsch, M; Ramamoorthy, S.; Marczin, N.; Catravas, J.D.; Leibach, J W; Ganapathy, V; Leibach, F H

    1995-01-01

    The human colon carcinoma cell lines Caco-2 and HT-29 take up taurine actively. Treatment of Caco-2 cells with Escherichia coli heat-stable enterotoxin (STa) or with guanylin inhibited taurine uptake by approximately 40%. In contrast, neither STa nor guanylin changed the uptake of taurine in HT-29 cells. The inhibition in Caco-2 cells was associated with a decrease in the maximal velocity as well as in the affinity of the transporter. STa caused a 21-fold increase in guanosine 3',5'-cyclic mo...

  13. Triclosan Potentiates Epithelial-To-Mesenchymal Transition in Anoikis-Resistant Human Lung Cancer Cells

    OpenAIRE

    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...

  14. Targeting canine bladder transitional cell carcinoma with a human bladder cancer-specific ligand

    OpenAIRE

    Li Bin; Xie Li; Wang Sisi; Zhang Hongyong; Lin Tzu-yin; Rodriguez Carlos O; de Vere White Ralph; Pan Chong-xian

    2011-01-01

    Abstract Objective To determine if a human bladder cancer-specific peptide named PLZ4 can target canine bladder cancer cells. Experimental Design The binding of PLZ4 to five established canine invasive transitional cell carcinoma (TCC) cell lines and to normal canine bladder urothelial cells was determined using the whole cell binding assay and an affinitofluorescence assay. The WST-8 assay was performed to determine whether PLZ4 affected cell viability. In vivo tumor-specific homing/targetin...

  15. Modulation of Mitochondrial Permeability Transition Pore Affects Multidrug Resistance in Human Hepatocellular Carcinoma Cells

    OpenAIRE

    Xianlong Ling, Yuan Zhou, Shi-Wei Li, Bin Yan, Lei Wen

    2010-01-01

    Multidrug resistance (MDR) is a critical problem in the chemotherapy of cancers. Human hepatocellular carcinoma (HCC) responds poorly to chemotherapy owing to its potent MDR. Chemotherapeutic drugs primarily act by inducing apoptosis of cancer cells, and defects in apoptosis may result in MDR. Mitochondrial permeability transition (mPT) is implicated as an important event in the control of cell death or survival and mPT represents a target for the development of cytotoxic drugs. This study ai...

  16. All in transition - Human resource management and labour relations in the Chinese industrial sector

    OpenAIRE

    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 ...

  17. The antifungal antibiotic, clotrimazole, inhibits chloride secretion by human intestinal T84 cells via blockade of distinct basolateral K+ conductances. Demonstration of efficacy in intact rabbit colon and in an in vivo mouse model of cholera.

    OpenAIRE

    Rufo, P. A.; Merlin, D.; Riegler, M.; Ferguson-maltzman, M. H.; Dickinson, B. L.; Brugnara, C.; Alper, S. L.; Lencer, W. I.

    1997-01-01

    The antifungal antibiotic clotrimazole (CLT) blocks directly and with high potency the Ca2+-activated K+ channels of human erythrocytes, erythroleukemia cells, and ferret vascular smooth muscle cells. We recently reported that CLT inhibits Cl- secretion in human intestinal T84 cells, likely by affecting K+ transport (Rufo, P.A., L. Jiang, S.J. Moe, C. Brugnara, S.L. Alper, and W.I. Lencer. 1996. J. Clin. Invest. 98:2066-2075). To determine if CLT had direct effects on K+ conductances in T84 c...

  18. Central Role of the Gut Epithelial Barrier in the Pathogenesis of Chronic Intestinal Inflammation : Lessons Learned from Animal Models and Human Genetics

    OpenAIRE

    Pastorelli, Luca; Vecchi, Maurizio

    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 intestin...

  19. The antifungal antibiotic, clotrimazole, inhibits chloride secretion by human intestinal T84 cells via blockade of distinct basolateral K+ conductances. Demonstration of efficacy in intact rabbit colon and in an in vivo mouse model of cholera.

    Science.gov (United States)

    Rufo, P A; Merlin, D; Riegler, M; Ferguson-Maltzman, M H; Dickinson, B L; Brugnara, C; Alper, S L; Lencer, W I

    1997-12-15

    The antifungal antibiotic clotrimazole (CLT) blocks directly and with high potency the Ca2+-activated K+ channels of human erythrocytes, erythroleukemia cells, and ferret vascular smooth muscle cells. We recently reported that CLT inhibits Cl- secretion in human intestinal T84 cells, likely by affecting K+ transport (Rufo, P.A., L. Jiang, S.J. Moe, C. Brugnara, S.L. Alper, and W.I. Lencer. 1996. J. Clin. Invest. 98:2066-2075). To determine if CLT had direct effects on K+ conductances in T84 cells, we selectively permeabilized apical membranes of confluent T84 cell monolayers using the ionophore amphotericin B. This technique permits direct measurement of basolateral K+ transport. We found that CLT and a stable des-imidazolyl derivative inhibited directly two pharmacologically distinct basolateral membrane K+conductances, but had no effect on apical membrane Cl- conductances. The effects of CLT on Cl- secretion were also examined in intact tissue. CLT inhibited forskolin-induced Cl- secretion in rabbit colonic mucosal sheets mounted in Ussing chambers by 91%. CLT also inhibited cholera toxin-induced intestinal Cl- secretion in intact mice by 94%. These data provide direct evidence that CLT blocks Cl- secretion in intestinal T84 cells by inhibition of basolateral K+ conductances, and show that CLT inhibits salt and water secretion from intact tissue in vitro and in vivo. The results further support the suggestion that CLT and its metabolites may show clinical efficacy in the treatment of secretory diarrheas of diverse etiologies. PMID:9399958

  20. Loss of HLTF function promotes intestinal carcinogenesis

    Directory of Open Access Journals (Sweden)

    Sandhu Sumit

    2012-03-01

    Full Text Available Abstract Background HLTF (Helicase-like Transcription Factor is a DNA helicase protein homologous to the SWI/SNF family involved in the maintenance of genomic stability and the regulation of gene expression. HLTF has also been found to be frequently inactivated by promoter hypermethylation in human colon cancers. Whether this epigenetic event is required for intestinal carcinogenesis is unknown. Results To address the role of loss of HLTF function in the development of intestinal cancer, we generated Hltf deficient mice. These mutant mice showed normal development, and did not develop intestinal tumors, indicating that loss of Hltf function by itself is insufficient to induce the formation of intestinal cancer. On the Apcmin/+ mutant background, Hltf- deficiency was found to significantly increase the formation of intestinal adenocarcinoma and colon cancers. Cytogenetic analysis of colon tumor cells from Hltf -/-/Apcmin/+ mice revealed a high incidence of gross chromosomal instabilities, including Robertsonian fusions, chromosomal fragments and aneuploidy. None of these genetic alterations were observed in the colon tumor cells derived from Apcmin/+ mice. Increased tumor growth and genomic instability was also demonstrated in HCT116 human colon cancer cells in which HLTF expression was significantly decreased. Conclusion Taken together, our results demonstrate that loss of HLTF function promotes the malignant transformation of intestinal or colonic adenomas to carcinomas by inducing genomic instability. Our findings highly suggest that epigenetic inactivation of HLTF, as found in most human colon cancers, could play an important role in the progression of colon tumors to malignant cancer.

  1. Surface-layer (S-layer) of human and animal Clostridium difficile strains and their behaviour in adherence to epithelial cells and intestinal colonization.

    Science.gov (United States)

    Spigaglia, Patrizia; Barketi-Klai, Amira; Collignon, Anne; Mastrantonio, Paola; Barbanti, Fabrizio; Rupnik, Maja; Janezic, Sandra; Kansau, Imad

    2013-09-01

    Clostridium difficile is a frequent cause of severe, recurrent post-antibiotic diarrhoea and pseudomembranous colitis. The surface layer (S-layer) is the predominant outer surface component of C. difficile which is involved in pathogen-host interactions critical to pathogenesis. In this study, we characterized the S-layer protein A (SlpA) of animal and human strains belonging to different PCR-ribotypes (PR) and compared the in vitro adherence and in vivo colonization properties of strains showing different SlpA variants. Since each SlpA variant has been recently associated with an S-layer cassette, we were able to deduce the cassette for each of our strains. In this study, an identity of 99-100 % was found among the SlpA of isolates belonging to PR 012, 014/020, 045 and 078. One exception was the SlpA of a poultry isolate, PR 014/020, which showed 99 % identity with that of strain 0160, another PR 014/020 which contains an S-layer cassette 6. Interestingly, this cassette has also been found in a PR 018 strain, an emerging virulent type currently predominant in Italy. Five other SlpA variants (v014/020a-e) were identified in strains PR 014/020. In vitro adherence assays and in vivo colonization experiments were performed on five PR 014/020 strains: human 1064 (v014/020e), human 4684/08 (v014/020b), human IT1106 (v078a), poultry P30 (v014/020d) and poultry PB90 (v014/020b) strains. Adhesion assays indicate that C. difficile strains vary in their capacity to adhere to cells in culture and that adhesion seems to be independent of the SlpA variant. Colonization properties were assessed in vivo using a dixenic mouse model of colonization. The kinetics of faecal shedding and caecal colonization were similar when human 4684/08 (v014/020b) strain was compared with human 1064 (v014/020e) and poultry PB90 (v014/020b) strain. In contrast, poultry P30 (v014/020d) strain outcompeted both human 4684/08 (v014/020b) and IT1106 (v078a) strains and its adherence to caeca at day 7 was significantly higher. The peculiar characteristics of C. difficile P30 seem to advantage it in colonizing the intestinal mice niche, increasing its ability to compete and adapt. The results obtained underline the need of an increased attention to the genetic evolution of C. difficile to prevent and limit the consequences of the emergence of increasingly virulent strains. PMID:23518658

  2. Avaliao do nmero de clulas caliciformes nas criptas da mucosa colnica com e sem trnsito intestinal / Evaluation of the number of goblet cells in crypts of the colonic mucosa with and without fecal transit

    Scientific Electronic Library Online (English)

    Rodrigo de Oliveira, Mello; Camila Morais Gonalves da, Silva; Fbio Piovezan, Fonte; Daniele Luchinitz Ferraz, Silva; Jos Aires, Pereira; Nelson Fontana, Margarido; Carlos Augusto Real, Martinez.

    2012-04-01

    Full Text Available OBJETIVO: Medir a espessura das criptas e quantificar o nmero de clulas caliciformes comparando a mucosa clica com e sem trnsito intestinal, relacionando-as ao tempo de excluso. MTODOS: Sessenta ratos Wistar, foram distribudos em trs grupos com 20 animais segundo a operao final para a reti [...] rada dos clons, realizadas em seis, 12 ou 18 semanas. Em cada grupo, 15 animais foram submetidos derivao do trnsito por colostomia proximal no clon esquerdo e fstula mucosa distal e cinco apenas laparotomia (controle). Os clons com e sem trnsito fecal foram removidos, processados, submetidos a cortes histolgicos corados pela hematoxilina-eosina. A altura das criptas colnicas e o nmero de clulas caliciformes foram mensurados por morfometria computadorizada. Foram utilizados os testes t de Student e Kruskal-Wallis para comparao e anlise de varincia, estabelecendo-se nvel de significncia de 5% (p Abstract in english OBJECTIVE: To measure the thickness of the crypts and quantify the number of goblet cells of the colonic mucosa with and without intestinal transit, relating them to exclusion time. METHODS: Sixty Wistar rats were divided into three groups of 20 animals each according to the time of the final operat [...] ion for the removal of the colon, in six, 12 or 18 weeks. In each group 15 animals underwent colonic exclusion by left colon proximal colostomy and distal mucous fistula, and five underwent only laparotomy (control). The colons with and without fecal stream were removed, processed and submitted to histological sections stained with hematoxylin-eosin. The height of the colonic crypts and the number of goblet cells were measured by computerized morphometry. We used the Student t test and Kruskal-Wallis test for comparison and analysis of variance, using a significance level of 5% (p

  3. Dietary whole-grain wheat increases intestinal levels of bifidobacteria in humans and bifidobacterial abundance is negatively correlated with the effect of fecal water on trans-epithelial resistance in vitro.

    DEFF Research Database (Denmark)

    Christensen, Ellen Gerd; Licht, Tine Rask

    Consumption of whole grain products are considered to have beneficial effects on human health including decreased risk of cardiovascular disease. However, effects on gut microbial composition have only been studied limitedly. We used quantitative PCR to determine changes in the gut bacterial composition in post-menopausal women following a 12-week energy restricted intervention with whole-grain wheat (WW, n=37) or refined wheat (RW, n=33). The WW intervention significantly increased the relative abundance of Bifidobacterium. Caco-2 cells were exposed to fecal water to determine effects of the bacterial community metabolites on the trans-epithelial resistance (TER). Fecal water increased TER independent of diet, indicating that commensal bacteria provide metabolites facilitating an increase in intestinal integrity. TER was unexpectedly found to be negatively correlated to the relative abundance of Bifidobacterium. The present study suggests that increase of specific bacterial groups, which are considered beneficial, may in some circumstances increase the permeability of the intestinal wall.

  4. Inducible gene knockouts in the small intestinal and colonic epithelium.

    Science.gov (United States)

    Saam, J R; Gordon, J I

    1999-12-31

    We have developed two systems for performing Cre-mediated recombination of target genes in the rapidly self-renewing mouse small intestinal and colonic epithelium. When expression of Cre recombinase is placed directly under the control of transcriptional regulatory elements from a fatty acid-binding protein gene (Fabp), deletion of loxP flanked (floxed) DNA sequences is initiated as early as embryonic day 13.5, well before completion of intestinal morphogenesis. By embryonic day 16.5, Fabp-Cre also directs recombination in all cell layers of the transitional epithelium that lines the renal calyces and pelvis, ureters, and bladder. Fabp-Cre expression and recombination are maintained in both epithelia throughout adulthood. The second system allows recombination to be induced only in the gut and at any period during adulthood. This system uses Fabp regulatory elements to direct expression of a reverse tetracycline-regulated transactivator (rtTA). Another transgene encodes Cre under the control of tet operator sequences and a minimal promoter from human cytomegalovirus (tetO-P(hCMV)-Cre). In the absence of a doxycycline inducer, no basal recombination is detectable in the gut of adult tri-transgenic mice containing Fabp-rtTA, tetO-P(hCMV)-Cre, plus a floxed reporter gene. After 4 days of oral administration of doxycycline, recombination of the reporter is apparent in the small intestinal, cecal, and colonic epithelium. After doxycycline is withdrawn, the recombined locus persists for at least 60 days, indicating that recombination has occurred in epithelial cell progenitors that have long residency times in the proliferative units of the intestine (crypts of Lieberkhn). This inducible system should have a number of applications for examining gene function at selected times in postnatal life, under selected physiologic or pathophysiologic conditions. PMID:10608876

  5. Human intestinal hydrolysis of phenol glycosides - a study with quercetin and p-nitrophenol glycosides using ileostomy fluid.

    Science.gov (United States)

    Knaup, Bastian; Kahle, Kathrin; Erk, Thomas; Valotis, Anagnostis; Scheppach, Wolfgang; Schreier, Peter; Richling, Elke

    2007-11-01

    In order to study the influence of sugar moiety, aglycon structure and microflora concentration on the human ileal hydrolysis of phenol glycosides, various quercetin and p-nitrophenol glycosides were incubated under anaerobic conditions (37 degrees C for 0, 0.5, 1, 2, 4, 6, 8, 10 and 24 h) with ileostomy fluids from three different donors. The glycosides, i.e. beta-D-glucopyranosides, beta-D-galactopyranosides, alpha-L-arabinofuranosides, beta-D-xylopyranosides and alpha-L-rhamnopyranosides as well as the liberated aglycones were identified by HPLC-DAD and HPLC-ESI-MS/MS. Among the quercetin glycosides under study, the 3-O-beta-D-glucopyranoside showed with 0.22 micromol/h the highest hydrolysis rate, followed by the 3-O-beta-D-galactopyranoside, the 3-O-beta-D-xylopyranoside and the 3-O-alpha-L-arabinofuranoside (0.04 and each 0.03 micromol/h, respectively). Quercetin 3-O-alpha-L-rhamnopyranoside was found to be stable for the entire incubation period. Using quercetin 3-O-beta-D-glucopyranoside as a representative example, linear hydrolysis rate was observed from 75 to 2500 microL ileostomy fluid corresponding to its microflora content (log 0.68 up to 21.9 colony forming units). Studies performed in the presence of antibiotics did not reveal any hydrolysis. The p-nitrophenol glycosides were hydrolyzed faster than the corresponding quercetin glycosides. The hydrolysis rate decreased from the beta-D-glucopyranoside (0.41 micromol/h), to the beta-D-galactopyranoside (0.21 micromol/h), the beta-D-xylopyranoside (0.12 micromol/h), the alpha-L-arabinofuranoside (0.09 micromol/h) to the alpha-L-rhamnopyranoside (0.06 micromol/h). These results demonstrate that the human ileal hydrolysis of phenol glycosides depends on the sugar and the aglycon structure as well as the microflora. PMID:17966139

  6. Nano-enhanced food contact materials and the in vitro toxicity to human intestinal cells of nano-ZnO at low dose

    Science.gov (United States)

    Claonadh, Niall .; Casey, Alan; Lyons, Sean; Higginbotham, Clement; Gupta Mukherjee, Sanchali; Chambers, Gordon

    2011-07-01

    Nano Zinc Oxide (nZnO) has been shown to display antimicrobial effects which have lead to its application in a number of areas such as antimicrobial surface coatings, anti bacterial wound dressings and more recently in polymer composite systems for use in food contact materials. Concerns have been raised due to the incorporation of nanoparticles in food packaging stemming from the possibility of repeated low dose direct exposure, through ingestion, primarily due to degradation and nanoparticle leaching from the polymer composite. To address these concerns, composites consisting of nZnO and polyethylene were formed using twin screw extrusion to mimic commercial methods of food contact material production. A leaching study was performed using Atomic Absorption Spectroscopy in order to determine the concentration of nZnO leached from the composite. Composite stability studies were performed and a leached nZnO concentration was evaluated. This concentration range was then utilised in a series of tests aimed at determining the toxicity response associated with nZnO when exposed to an intestinal model. In this study two human colorectal carcinoma cell lines, HT29 (ATCC No: HTB-38) and SW480 (ATTC No: CCL-228), were employed as a model to represent areas exposed by ingestion. These lines were exposed to a concentration range of nZnO which incorporated the concentration leached from the composites. The cytotoxic effects of nZnO were evaluated using four cytotoxic endpoints namely the Neutral Red, Alamar Blue, Coomassie Blue and MTT assays. The results of these studies are presented and their implications for the use on nano ZnO in direct food contact surfaces will be discussed.

  7. Nano-enhanced food contact materials and the in vitro toxicity to human intestinal cells of nano-ZnO at low dose

    International Nuclear Information System (INIS)

    Nano Zinc Oxide (nZnO) has been shown to display antimicrobial effects which have lead to its application in a number of areas such as antimicrobial surface coatings, anti bacterial wound dressings and more recently in polymer composite systems for use in food contact materials. Concerns have been raised due to the incorporation of nanoparticles in food packaging stemming from the possibility of repeated low dose direct exposure, through ingestion, primarily due to degradation and nanoparticle leaching from the polymer composite. To address these concerns, composites consisting of nZnO and polyethylene were formed using twin screw extrusion to mimic commercial methods of food contact material production. A leaching study was performed using Atomic Absorption Spectroscopy in order to determine the concentration of nZnO leached from the composite. Composite stability studies were performed and a leached nZnO concentration was evaluated. This concentration range was then utilised in a series of tests aimed at determining the toxicity response associated with nZnO when exposed to an intestinal model. In this study two human colorectal carcinoma cell lines, HT29 (ATCC No: HTB-38) and SW480 (ATTC No: CCL-228), were employed as a model to represent areas exposed by ingestion. These lines were exposed to a concentration range of nZnO which incorporated the concentration leached from the composites. The cytotoxic effects of nZnO were evaluated using four cytotoxic endpoints navaluated using four cytotoxic endpoints namely the Neutral Red, Alamar Blue, Coomassie Blue and MTT assays. The results of these studies are presented and their implications for the use on nano ZnO in direct food contact surfaces will be discussed.

  8. Estudio de un clculo intestinal en un paciente con adenocarcinoma de coln: es similar a los clculos renales? / Study of a intestinal enteroliths in human patient with colon adenocarcinome: Is it similar to renal calculi?

    Scientific Electronic Library Online (English)

    M.L., Traba Villameytide; J.A., Orts Costa; M., Morell.

    2006-02-01

    Full Text Available Este trabajo muestra el estudio realizado a enterolitos intestinales procedentes de un paciente de 91 aos que padeca una enterolitiasis mltiple confirmada por estudio radiolgico abdominal y TAC, mostrando clculos en el tracto intestinal, renal y biliar. Adems esta enterolitiasis estaba asociad [...] a a un adenocarcinoma de colon. Los enterolitos analizados proceden de una intervencin quirrgica en la que se practic una hemicolectoma derecha. Los enterolitos se sometieron a un anlisis por espectrometra de infrarrojos (IR) observndose un espectro de carbonato apatita no-estequiomtrica, tipo whitloquita, posiblemente con materia orgnica. Con el fin de estudiar el posible contenido de diversos elementos qumicos, se practic un anlisis por espectrometra de emisin atmica encontrndose, fundamentalmente, los iones Ca, Mg, K, Na y K (del orden de mg/100 mg de clculo) y Zn, Ba, Mn, Fe, Cu, Si, Ti y Br en menor proporcin (del orden de g/100 mg de clculo). Dada la morfologa del clculo y su espectro de IR (carbonato apatita no estequiomtrica) se determin la posible presencia de porfirinas por cromatografa lquida de alta resolucin (HPLC) encontrndose, fundamentalmente, coproporfirina (g/g de clculo) y en menor proporcin uroporfirina, protoporfirina y hepta-carboxi porfirina. El estudio se complet con el anlisis de los enterolitos mediante microscopa electrnica de barrido y EDX. El anlisis por difraccin de rayos X detect la presencia de CaP4O11. Los resultados obtenidos de los diferentes anlisis muestran que la composicin de los enterolitos es similar a la de los clculos renales, aunque su morfologa difiera de estos. Abstract in english This work shows the study performance to intestinal enterolithis from a 91 year old patient with multiple enterolithiasis confirmed by abdominal X-ray and TAC analyses showing the presence of intestinal, renal and bile stones. This enterolithis is associated with colon adenocarcinoma. The enterolith [...] s were obtained by hemicolectomia and were analyzed by infrared spectroscopy (IR), giving nonstoichiometry carbonate apatite whitloquite-like with, possibly, organic material. By atomic emission spectroscopy we found Ca, Mg, K, Na y K (mg/100 mg of calculi) and Zn, Ba, Mn, Fe, Cu, Si, Ti and Br in minor proportion (g/100 mg of calculi). Because of calculi morphology and the IR spectra (non-stoichiometry carbonate apatite) we carried out analysis by high performance liquid chromatography (HPLC) and found coproporphyrin (about g/g of calculi) and uroporphyrin, protoporphyrin and heptacarboxy-porphyrin in minor extent. Calculi were also studied by scanning electronic microscopy and EDX and X-ray diffraction giving crystals of CaP4O11. All these results show that intestinal enteroliths composition are similar to renal calculi although its morphology differs from renal calculi.

  9. Multiplex real-time PCR monitoring of intestinal helminths in humans reveals widespread polyparasitism in Northern Samar, the Philippines.

    Science.gov (United States)

    Gordon, Catherine A; McManus, Donald P; Acosta, Luz P; Olveda, Remigio M; Williams, Gail M; Ross, Allen G; Gray, Darren J; Gobert, Geoffrey N

    2015-06-01

    The global socioeconomic importance of helminth parasitic disease is underpinned by the considerable clinical impact on millions of people. While helminth polyparasitism is considered common in the Philippines, little has been done to survey its extent in endemic communities. High morphological similarity of eggs between related species complicates conventional microscopic diagnostic methods which are known to lack sensitivity, particularly in low intensity infections. Multiplex quantitative PCR diagnostic methods can provide rapid, simultaneous identification of multiple helminth species from a single stool sample. We describe a multiplex assay for the differentiation of Ascaris lumbricoides, Necator americanus, Ancylostoma, Taenia saginata and Taenia solium, building on our previously published findings for Schistosoma japonicum. Of 545 human faecal samples examined, 46.6% were positive for at least three different parasite species. High prevalences of S. japonicum (90.64%), A. lumbricoides (58.17%), T. saginata (42.57%) and A. duodenale (48.07%) were recorded. Neither T. solium nor N. americanus were found to be present. The utility of molecular diagnostic methods for monitoring helminth parasite prevalence provides new information on the extent of polyparasitism in the Philippines municipality of Palapag. These methods and findings have potential global implications for the monitoring of neglected tropical diseases and control measures. PMID:25858090

  10. Extraction of Antioxidant Components from Bidens pilosa Flowers and Their Uptake by Human Intestinal Caco-2 Cells

    Directory of Open Access Journals (Sweden)

    Charng-Cherng Chyau

    2013-01-01

    Full Text Available Bidens pilosa L. var. radiata (BPR, Asteraceae is a commonly used folk medicine for treating various disorders such as diabetes, inflammation and hypertension. Recent studies to determine its chemical composition have revealed three di-O-caffeoylquinic acids (DiCQAs and three polyacetylene glucosides (PGAs to be among the major bioactive markers. To obtain the major compounds of these two chemical classes, the ethyl acetate fraction (EM obtained using liquid-liquid partition from the methanol extract resulted in a fraction with the highest total phenolic and total flavonoid contents and antioxidant activities in radical scavenging and ferric reducing power assays. To assess the bioavailability of EM, we examined the in vitro uptake using the Caco-2 human colonic cell line. The apparent permeability coefficient (Papp for each of the compounds within PGAs measured in both apical (AP to basolateral (BL and BL to AP was found to preferentially appear BL to AP direction, indicated that a basolateral to apical efflux system was detected in the study. DiCQAs had a lower efflux ratio than those from PGAs (2.323.67 vs. 6.0378.36. Thus, it strongly implies that most of the DiCQAs are better absorbed than the PGAs.

  11. Gastrointestinal adaptation to enhanced small intestinal lipid exposure.

    OpenAIRE

    Brown, N. J.; Rumsey, R. D.; Read, N. W.

    1994-01-01

    Studies were performed on 20 male adult rats to investigate the effects of chronic intermittent infusion of lipid and physiological emulsifier into the distal small intestine on stomach to caecum transit time (SCTT) of the head of a test meal. SCTT was measured using environmental hydrogen analysis. Ileal lipid infusion normally delays gastric emptying and small intestinal transit (p < 0.001), but chronic intermittent infusion of lipid, given three times a week gradually reduced the delay in ...

  12. 1H Nuclear Magnetic Resonance Spectroscopy-Based Studies of the Metabolism of Food-Borne Carcinogen 2-Amino-3-Methylimidazo[4,5-f]Quinoline by Human Intestinal Microbiota

    Science.gov (United States)

    Humblot, Christle; Combourieu, Bruno; Visnen, Marja-Liisa; Furet, Jean-Pierre; Delort, Anne-Marie; Rabot, Sylvie

    2005-01-01

    2-Amino-3-methylimidazo[4,5-f]quinoline (IQ) is a mutagenic/carcinogenic compound formed from meat and fish during cooking. Following ingestion, IQ is metabolized mainly by liver xenobiotic-metabolizing enzymes, but intestinal bacteria may also contribute to its biotransformation. The aim of this study was to investigate the metabolism of IQ by the human intestinal microbiota. Following incubation of IQ (200 ?M) under anoxic conditions with 100-fold dilutions of stools freshly collected from three healthy volunteers, we quantified residual IQ by high-pressure liquid chromatography (HPLC) analysis and characterized the production of IQ metabolites by in situ 1H nuclear magnetic resonance (1H-NMR) spectroscopic analysis of crude incubation media. In addition, we looked for IQ-degrading bacteria by screening collection strains and by isolating new strains from the cecal contents of human-microbiota-associated rats gavaged with IQ on a regular basis. HPLC and 1H-NMR analyses showed that the three human microbiota degraded IQ with different efficiencies (range, 50 to 91% after 72 h of incubation) and converted it into a unique derivative, namely, 7-hydroxy-IQ. We found 10 bacterial strains that were able to perform this reaction: Bacteroides thetaiotaomicron (n = 2), Clostridium clostridiiforme (n = 3), Clostridium perfringens (n = 1), and Escherichia coli (n = 4). On the whole, our results indicate that bacteria belonging to the predominant communities of the human intestine are able to produce 7-hydroxy-IQ from IQ. They also suggest interindividual differences in the ability to perform this reaction. Whether it is a metabolic activation is still a matter of debate, since 7-hydroxy-IQ has been shown to be a direct-acting mutagen in the Ames assay but not carcinogenic in laboratory rodents. PMID:16151094

  13. Alistipes indistinctus sp. nov. and Odoribacter laneus sp. nov., common members of the human intestinal microbiota isolated from faeces.

    Science.gov (United States)

    Nagai, Fumiko; Morotomi, Masami; Watanabe, Yohei; Sakon, Hiroshi; Tanaka, Ryuichiro

    2010-06-01

    Two anaerobic, non-spore-forming, non-motile, Gram-negative-staining bacteria, strains YIT 12060(T) and YIT 12061(T), were isolated from human faeces. Cells of strain YIT 12060(T) were coccoid to rod-shaped with round ends, positive for catalase, negative for indole and oxidase production, produced succinic and acetic acids as end products of glucose metabolism in peptone/yeast extract/glucose medium and had a DNA G+C content of 55.2 mol%. The main respiratory quinones were MK-10 (40%) and MK-11 (57%). Fatty acid analysis demonstrated the presence of a high concentration of iso-C(15 : 0) (56%). Following 16S rRNA gene sequence analysis, this strain was found to be most closely related to species of the genus Alistipes, with 90.9-92.6% gene sequence similarities to type strains of this species. Phylogenetic analysis and biochemical data supported the affiliation of strain YIT 12060(T) to the genus Alistipes of the family 'Rikenellaceae'. Strain YIT 12060(T) therefore represents a novel species of the genus Alistipes for which the name Alistipes indistinctus sp. nov. is proposed; the type strain is YIT 12060(T) (=DSM 22520(T)=JCM 16068(T)). Cells of the other isolate, strain YIT 12061(T), were pleomorphic rods that were asaccharolytic, catalase- and oxidase-negative, positive for gelatin hydrolysis and indole production, produced small amounts of succinic, acetic and iso-valeric acids as end products of metabolism in peptone/yeast extract medium and had a DNA G+C content of approximately 42.4 mol%. On the basis of 16S rRNA gene sequence similarity values, this strain was shown to belong to the family 'Porphyromonadaceae' and related to the type strains of Odoribacter splanchnicus (89.6%) and Odoribacter denticanis (86.2%); similarity values with strains of recognized species within the family 'Porphyromonadaceae' were less than 84 %. Biochemical data supported the affiliation of strain YIT 12061(T) to the genus Odoribacter. Strain YIT 12061(T) therefore represents a novel species for which the name Odoribacter laneus sp. nov. is proposed; the type strain is YIT 12061(T) (=DSM 22474(T)=JCM 16069(T)). PMID:19667375

  14. Intestinal cytochromes P450 regulating the intestinal microbiota and its probiotic profile

    Directory of Open Access Journals (Sweden)

    Eugenia Elefterios Venizelos Bezirtzoglou

    2012-09-01

    Full Text Available Cytochromes P450 (CYPs enzymes metabolize a large variety of xenobiotic substances. In this vein, a plethora of studies were conducted to investigate their role, as cytochromes are located in both liver and intestinal tissues. The P450 profile of the human intestine has not been fully characterized. Human intestine serves primarily as an absorptive organ for nutrients, although it has also the ability to metabolize drugs. CYPs are responsible for the majority of phase I drug metabolism reactions. CYP3A represents the major intestinal CYP (80% followed by CYP2C9. CYP1A is expressed at high level in the duodenum, together with less abundant levels of CYP2C8-10 and CYP2D6. Cytochromes present a genetic polymorphism intra- or interindividual and intra- or interethnic. Changes in the pharmacokinetic profile of the drug are associated with increased toxicity due to reduced metabolism, altered efficacy of the drug, increased production of toxic metabolites, and adverse drug interaction. The high metabolic capacity of the intestinal flora is due to its enormous pool of enzymes, which catalyzes reactions in phase I and phase II drug metabolism. Compromised intestinal barrier conditions, when rupture of the intestinal integrity occurs, could increase passive paracellular absorption. It is clear that high microbial intestinal charge following intestinal disturbances, ageing, environment, or food-associated ailments leads to the microbial metabolism of a drug before absorption. The effect of certain bacteria having a benefic action on the intestinal ecosystem has been largely discussed during the past few years by many authors. The aim of the probiotic approach is to repair the deficiencies in the gut flora and establish a protective effect. There is a tentative multifactorial association of the CYP (P450 cytochrome role in the different diseases states, environmental toxic effects or chemical exposures and nutritional status.

  15. Evaluation of the use of Classical Nucleation Theory for predicting intestinal crystalline precipitation of two weakly basic BSC class II drugs.

    Science.gov (United States)

    Carlert, Sara; Lennerns, Hans; Abrahamsson, Bertil

    2014-03-12

    The aim of this work was to evaluate an in vitro-in silico approach for prediction of small intestinal crystalline precipitation and drug absorption of two weakly basic model BCS class II drugs, AZD0865 and mebendazole. The crystallization rates were investigated in an in vitro method using simulated gastric and intestinal media, and the result was modeled by using Classical Nucleation Theory (CNT). The effect of varying in vitro parameters (initial drug concentration, rate of mixing gastric and intestinal fluid, stirring and filtration) on the interfacial tension ?, being a key parameter in CNT, was investigated. The initial drug concentration had the most significant effect on ? for both substances tested, although ? is a fundamental parameter independent of concentration according to CNT. In the subsequent in silico prediction of drug absorption, by use of a Compartmental and Transit intestinal model, an empirical approach was used where ? was allowed to vary with simulated small intestinal concentrations. The in silico predictions were compared to published human in vivo plasma drug concentration data for different doses of AZD0865 and dog intestinal drug concentrations, amount precipitated in intestine and plasma concentrations for mebendazole. The results showed that lack of significant crystallization effects on absorption in man of the model drug AZD0865 up to doses of 4 mg/kg could be predicted which was in accordance with in vivo data. Mebendazole intestinal precipitation in canines was also well described by the model, where mean predicted amount precipitated was 136% (range 111-164%) of measured solid amount, and mean predicted intestinal concentration was 94% (range 59-147%) of measured concentration. In conclusion, the in vitro-in silico approach can be used for predictions of absorption effects of crystallization, but the model could benefit from further development work on the theoretical crystallization model and in vitro experimental design. PMID:24345794

  16. Small Intestinal Adenocarcinoma in Common Marmosets (Callithrix jacchus)

    OpenAIRE

    Miller, A.D.; Kramer, J.A.; Lin, K.C.; Knight, H.; Martinot, A.; Mansfield, K. G.

    2010-01-01

    Small intestinal adenocarcinomas are uncommon neoplasms that are rarely reported in non-human primates. These neoplasms are also rare in man, although they are thought to share a similar pathogenesis with the more common colorectal carcinoma. Herein we report the clinical, histologic, immunohistochemical, and molecular characteristics of small intestinal adenocarcinoma in 10 common marmosets (Callithrix jacchus). Retrospective analysis of necropsy records revealed small intestinal carcinoma t...

  17. INTESTINAL PARASITIC PREVALENCE IN HUMAN IMMUNO-DEFICIENT VIRUS (HIV INFECTED PATIENTS WITH AND WITHOUT DIARRHOEA AND ITS ASSOCIATION WITH CD4 T CELLS COUNTS

    Directory of Open Access Journals (Sweden)

    Namita A. Raytekar

    2012-12-01

    Full Text Available Background & objectives: Intestinal parasitic infections are major cause of diarrhoea in HIV infected individuals. The present study was undertaken to detect intestinal parasites in HIV infected patients with and without diarrhoea and to determine association between enteric parasites and CD4 T cell count. Methods: The study was carried out at Department of Microbiology, Rural Medical College, Loni, India, between September 2010 and August 2012 among consecutively enrolled 127 HIV infected patients presenting with and without diarrhoea. Stool samples were collected and examined for enteric parasites by microscopy and special staining methods. CD4 cell counts records of patients were taken from Antiretroviral Treatment Centre (ARTC of the hospital. Results: Out of total 127 cases intestinal parasites were detected in 27 cases. The incidence of intestinal parasitic infection was 21.25%. Of 27 cases where parasites detected in total, Entamoeba histolytica 13 (48.14 % was found to be most prevalent parasite followed by Cryptosporidium parvum 9 (33.33% followed by Giardia lamblia 3 (11.11 % followed by Taenia spp. 2 (7.40%. In HIV infected patients with CD4 count < 200 cells/?l, C. parvum was the most commonly observed (88.88% parasite. Whereas the proportion of intestinal parasites in patients with CD4 count 200 499 cells/?l was significantly higher as comparedwith other two groups of patients with CD4 count < 200 and ? 500 cells/?l

  18. Intestinal perfusion in the study of intestinal absorption

    International Nuclear Information System (INIS)

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

  19. Perfluorinated compounds: Levels, trophic web enrichments and human dietary intakes in transitional water ecosystems

    International Nuclear Information System (INIS)

    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

  20. A human breast cell model of pre-invasive to invasive transition

    Energy Technology Data Exchange (ETDEWEB)

    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. Primer reporte de pseudomiasis intestinal humana por Eristalis tenax (Diptera, Syrphidae) en zona semirida urbana del estado Falcn, Venezuela / First report of human intestinal pseudomiasis by Eristalis tenax (Diptera, Syrphidae) in urban semiarid area from Falcon state, Venezuela

    Scientific Electronic Library Online (English)

    Dalmiro J, Cazorla Perfetti; Pedro, Morales Moreno; Mara, Acosta; Sergio, Bermdez.

    2011-12-01

    Full Text Available Pseudomiasis es el trmino empleado cuando se considera que las larvas y/o huevos de moscas se adquieren accidentalmente per os y atraviesan con inmediatez a lo largo del tracto digestivo. Se documenta un caso de una pseudomiasis intestinal por larvas de Eristalis tenax (Diptera: Syrphidae) en una p [...] aciente femenina de 39 aos de edad, proveniente de un sector perifrico de la ciudad de Coro, estado Falcn, Venezuela. La paciente observ inmediatamente la presencia de la larva viva en sus heces. Aunque refiri sufrir eventualmente de clicos, al examen fsico se present normal. La paciente aparentemente no sufre de trastornos mentales, y posee un nivel socioeconmico bajo. El presente trabajo constituye el primer reporte documentado de una pseudomiasis entrica por E. tenax en la zona semirida del estado Falcn, en la regin nor-occidental de Venezuela. Abstract in english Pseudomyiasis is the term used for the accidental entrapment of swallowed fly maggots and/or eggs immediately passing through the digestive tract. We report a case of intestinal pseudomyasis caused by the larvae of the cosmopolitan drone fly Eristalis tenax (Diptera: Syrphidae) in a 39 year old woma [...] n, resident in a suburban sector from Coro city, Falcon state, Venezuela. The patient immediately noticed a living larva in her stool. Although patient referred eventually became colic, her physical examination was normal, with no mental disturbance. She was in a low socioeconomic level. This is the first report of an enteric pseudomyasis by E. tenax in the semiarid zone of Falcon state, in the northwestern region of Venezuela.

  2. Autologous intestinal reconstruction surgery as part of comprehensive management of intestinal failure.

    Science.gov (United States)

    Pakarinen, Mikko P

    2015-05-01

    Pediatric intestinal failure (IF) remains to be associated with significant morbidity and mortality, the most frequent underlying etiologies being short bowel syndrome (SBS), and primary motility disorders. Management aims to assure growth and development, while preventing complications and facilitating weaning off parenteral support (PS) by fully utilizing adaptation potential of the remaining gut. Probability of survival and weaning off PS is improved by coordinated multidisciplinary intestinal rehabilitation combining individualized physiological enteral and parenteral nutrition (PN), meticulous central line care and medical management with carefully planned surgical care. Increasing evidence suggests that autologous intestinal reconstruction (AIR) surgery is effective treatment for selected short bowel patients. Bowel lengthening procedures normalize pathological adaptation-associated short bowel dilatation with potential to support intestinal absorption and liver function by various mechanisms. Although reversed small intestinal segment, designed to prolong accelerated intestinal transit, improves absorption in adult SBS, its feasibility in children remains unclear. Controlled bowel obstruction to induce dilatation followed by bowel lengthening aims to gain extra length in patients with the shortest duodenojejunal remnant. Reduced PS requirement limits the extent of complications, improving prognosis and quality of life. The great majority of children with SBS can be weaned from PS while prognosis of intractable primary motility disorders remains poor without intestinal transplantation, which serves as a salvage therapy for life-threatening complications such as liver failure, central vein thrombosis or recurrent bloodstream infections. PMID:25820764

  3. Pulmonary artery and intestinal temperatures during heat stress and cooling

    DEFF Research Database (Denmark)

    Pearson, James; Ganio, Matthew S

    2012-01-01

    In humans, whole body heating and cooling are used to address physiological questions where core temperature is central to the investigated hypotheses. Core temperature can be measured in various locations throughout the human body. The measurement of intestinal temperature is increasingly used in laboratory settings as well as in athletics. However, it is unknown whether intestinal temperature accurately tracks pulmonary artery blood temperature, the gold standard, during thermal stimuli in resting humans, which is the investigated hypothesis.

  4. Modulation of Intestinal Dendritic Cells by Manipulation of Enteric Bacteria in Intestinal Inflammation

    OpenAIRE

    NG, Siew Chien

    2009-01-01

    Inflammatory bowel disease (IBD) involves dysregulated immune responses to intestinal microbiota. Intestinal dendritic cells (DC) play a pivotal role in bacterial recognition, tolerance induction, T cell homing and differentiation. We hypothesized that alterations in human colonic DC are central to the inflammatory process, lymphocyte homing, and therapeutic responses in patients with IBD. Colonic CD11c+ cells have been shown to be activated in IBD but CD11c- cells have not bee...

  5. HUMAN INTESTINAL PARASITIC INFECTIONS AND ENVIRONMENTAL HEALTH FACTORS IN RURAL EGYPTIAN COMMUNITIES. A REPORT OF THE U.S.-EGYPTIAN RIVER NILE AND LAKE NASSER RESEARCH PROJECT

    Science.gov (United States)

    A survey of common intestinal parasites was completed in three areas of the Egyptian Nile Valley: The Nile Delta, Upper Middle Egypt and Upper Egypt. The relocated Nubian population was also included. The total sampling included 15,664 persons in 41 villages. More than 95% attend...

  6. Intestinal permeability defects: is it time to treat?

    Science.gov (United States)

    Odenwald, Matthew A; Turner, Jerrold R

    2013-09-01

    An essential role of the intestinal epithelium is to separate luminal contents from the interstitium, a function primarily determined by the integrity of the epithelium and the tight junction that seals the paracellular space. Intestinal tight junctions are selectively permeable, and intestinal permeability can be increased physiologically in response to luminal nutrients or pathologically by mucosal immune cells and cytokines, the enteric nervous system, and pathogens. Compromised intestinal barrier function is associated with an array of clinical conditions, both intestinal and systemic. Although most available data are correlative, some studies support a model where cycles of increased intestinal permeability, intestinal immune activation, and subsequent immune-mediated barrier loss contribute to disease progression. This model is applicable to intestinal and systemic diseases. However, it has not been proven, and both mechanistic and therapeutic studies are ongoing. Nevertheless, the correlation between increased intestinal permeability and disease has caught the attention of the public, leading to a rise in popularity of the diagnosis of "leaky gut syndrome," which encompasses a range of systemic disorders. Proponents claim that barrier restoration will cure underlying disease, but this has not been demonstrated in clinical trials. Moreover, human and mouse studies show that intestinal barrier loss alone is insufficient to initiate disease. It is therefore uncertain whether increased permeability in these patients is a cause or effect of the underlying disorder. Although drug targets that may mediate barrier restoration have been proposed, none have been proven effective. As such, current treatments for barrier dysfunction should target the underlying disease. PMID:23851019

  7. Prevalence of intestinal microsporidiosis in Human Immunodeficiency Virus-infected patients with diarrhea in major United States cities Prevalncia de microsporidiose intestinal em pacientes infectados pelo HIV com diarria nas principais cidades dos Estados Unidos da Amrica do Norte

    Directory of Open Access Journals (Sweden)

    Mark S. Dworkin

    2007-12-01

    Full Text Available To determine the prevalence of intestinal microsporidiosis in HIV-infected patients, we performed a prospective study of HIV-infected patients with diarrheal illnesses in three US hospitals and examined an observational database of HIV-infected patients in 10 US cities. Among 737 specimens from the three hospitals, results were positive for 11 (prevalence 1.5%; seven (64% acquired HIV through male-to-male sexual contact, two (18% through male-to-male sexual contact and injection drug use, and one (9% through heterosexual contact; one (9% had an undetermined mode of transmission. Median CD4 count within six months of diagnosis of microsporidiosis was 33 cells/L (range 3 to 319 cells/L. For the national observational database (n = 24,098, the overall prevalence of microsporidiosis was 0.16%. Prevalence of microsporidiosis among HIV-infected patients with diarrheal disease is low, and microsporidiosis is most often diagnosed in patients with very low CD4+ cell counts. Testing for microsporidia appears to be indicated, especially for patients with very low CD4+ cell counts.Para determinar a prevalncia de microsporidiose intestinal em pacientes infectados pelo HIV foi realizado um estudo prospectivo em trs hospitais dos Estados Unidos da Amrica do Norte (EUA e analizada uma base de dados nacional composta de dados coletados de pacientes infectados pelo HIV em 10 cidades dos EUA. De um total de 737 amostras de fezes de pacientes infectados pelo HIV que apresentavam diarria, amostras de 11 pacientes (prevalncia de 1,5% foram positivas para microspordios. Todos os positivos eram do sexo masculino e, entre eles, sete (64% pacientes adquiriram a infeco pelo HIV atravs de relao homossexual, dois (18% atravs de relao sexual e drogas injetveis e um (9% atravs de contato heterosexual, enquanto que em um paciente o modo de transmisso do HIV no foi determinado. A contagem mdia de linfcitos CD4 realizada at seis meses do diagnstico de microsporidiose foi de 33 clulas/microlitro (3 a 319 clulas/microlitro. A anlise da base de dados nacional (n = 24.098 mostrou uma prevalncia de microsporidiose de 0,16%. A prevalncia de microsporidiose em pacientes HIV-positivos com diarria baixa. Entretando, como a microsporidiose mais frequentemente diagnosticada em pacientes com contagens de CD4 muito baixas, a indicao de pesquisa de microspordios justificada, especialmente para estes pacientes.

  8. Piracy of decay-accelerating factor (CD55) signal transduction by the diffusely adhering strain Escherichia coli C1845 promotes cytoskeletal F-actin rearrangements in cultured human intestinal INT407 cells.

    Science.gov (United States)

    Peiffer, I; Servin, A L; Bernet-Camard, M F

    1998-09-01

    Diffusely adhering Escherichia coli (DAEC) C1845 (clinical isolate) harboring the fimbrial adhesin F1845 can infect cultured human differentiated intestinal epithelial cells; this process is followed by the disassembly of the actin network in the apical domain. The aim of this study was to examine the mechanism by which DAEC C1845 promotes F-actin rearrangements. For this purpose, we used a human embryonic intestinal cell line (INT407) expressing the membrane-associated glycosylphosphatidylinositol (GPI) protein-anchored decay-accelerating factor (DAF), the receptor of the F1845 adhesin. We show here that infection of INT407 cells by DAEC C1845 can provoke dramatic F-actin rearrangements without cell entry. Clustering of phosphotyrosines was observed, revealing that the DAEC C1845-DAF interaction involves the recruitment of signal transduction molecules. A pharmacological approach with a subset of inhibitors of signal transduction molecules was used to identify the cascade of signal transduction molecules that are coupled to the DAF, that are activated upon infection, and that promote the F-actin rearrangements. DAEC C1845-induced F-actin rearrangements can be blocked dose dependently by protein tyrosine kinase, phospholipase Cgamma, phosphatidylinositol 3-kinase, protein kinase C, and Ca2+ inhibitors. F-actin rearrangements and blocking by inhibitors were observed after infection of the cells with two E. coli recombinants carrying the plasmids containing the fimbrial adhesin F1845 or the fimbrial hemagglutinin Dr, belonging to the same family of adhesins. These findings show that the DAEC Dr family of pathogens promotes alterations in the intestinal cell cytoskeleton by piracy of the DAF-GPI signal cascade without bacterial cell entry. PMID:9712744

  9. Congenital intestinal lymphangiectasia

    Directory of Open Access Journals (Sweden)

    Popovi? Duan ?.

    2011-01-01

    Full Text Available Background. Congenital intestinal lymphangiectasia is a disease which leads to protein losing enteropathy. Tortous, dilated lymphatic vessels in the intestinal wall and mesenterium are typical features of the disease. Clinical manifestations include malabsorption, diarrhea, steatorrhea, edema and effusions. Specific diet and medication are required for disease control. Case report. A 19-year old male patient was hospitalized due to diarrhea, abdominal swelling, weariness and fatigue. Physical examination revealed growth impairment, ascites, and lymphedema of the right hand and forearm. Laboratory assessment indicated iron deficiency anaemia, lymphopenia, malabsorption, inflammatory syndrome, and urinary infection. Enteroscopy and video capsule endoscopy demonstrated dilated lymphatic vessels in the small intestine. The diagnosis was confirmed by intestinal biopsy. The patient was put on high-protein diet containing medium-chain fatty acids, somatotropin and suportive therapy. Conclusion. Congenital intestinal lymphangiectasia is a rare disease, usually diagnosed in childhood. Early recognition of the disease and adequate treatment can prevent development of various complications.

  10. Nuclear Thermal Propulsion (NTP): A Proven, Growth Technology for Fast Transit Human Missions to Mars

    Science.gov (United States)

    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 to 120 day transit times, Copernicus' saddle truss/drop tank assembly is replaced by a "star truss" assembly with paired modular drop tanks to further increase the vehicle's propellant capacity. The HLV launch count increases (from approx. 5 to 7) and a fourth engine is needed to reduce total mission burn time and gravity losses. Using a "split mission" approach, the NTPS, in-line tank and the saddle truss/LH2 drop tank elements can be configured as a pre-deployed Earth Return Vehicle/propellant tanker supporting 90-day crewed mission transits. The split mission approach also eliminates the need for on-orbit assembly. Mission scenario descriptions, key features and operational characteristics for five different vehicle configurations are presented.

  11. Genistein-induced G2/M cell cycle arrest of human intestinal colon cancer Caco-2 cells is associated with Cyclin B1 and Chk2 down-regulation.

    Science.gov (United States)

    Han, Junkyu; Kurita, Yui; Isoda, Hiroko

    2013-12-01

    Genistein is an isoflavonic phyto-oestrogen contained in soya beans. It is thought to display anti-cancer effects. This study was designed to investigate its effect on human intestinal colon cancer Caco-2 cells. MTT assay, flow cytometric analysis and western blotting were used to investigate the effect of genistein on cell proliferation, cell cycle progression and protein alterations of selected cell cycle-related proteins in Caco-2 cells. Our results showed that genistein and daidzein significantly suppressed cell proliferation. Genistein treatment was demonstrated to modulate cell cycle distribution through accumulation of cells at G2/M phase, with a significant decreasing effect of Cyclin B1 and Serine/threonine-protein kinase 2 (Chk2) proteins expression. However, daidzein did not alter the cell cycle progression in Caco-2 cells. All these observation strongly indicate that genistein has anti-proliferative effect in human intestinal colon cancer Caco-2 cells through the down-regulation of cell cycle check point proteins, Cyclin B1 and Chk2. PMID:23794041

  12. Regulatory effect of heat shock protein 70 in stress-induced rat intestinal epithelial barrier dysfunction

    OpenAIRE

    Stevie Struiksma; Christine Oluwole; Perdue, Mary H.; Ya-Hong Tu; Ping-Chang Yang

    2009-01-01

    Background: Psychological stress is one of the factors associated with many human diseases; the mechanisms need to be further understood. Methods: Rats were subjected to chronic water avoid stress. Intestinal epithelial heat shock protein (HSP) 70 was evaluated. The intestinal epithelial permeability was examined with Ussing chamber technique. Results: HSP70 was detected in normal intestinal epithelial cells. Psychological stress decreased HSP70 in the intestinal epithelial cells that correla...

  13. Computer assisted human matching, a software tool for international transit matching

    International Nuclear Information System (INIS)

    One of the responsibilities of the IAEA is to confirm the receipt of international shipments of nuclear material by matching shipments reported by one member State against receipts reported by another Member State. When sufficient information is available, this matching of receipts against shipments is straight forward. However, because of non-uniform reporting practices in different countries a significant number of reports must be investigated manually. In these cases the matching reports are often hidden among a large number of other transactions. To identify matchings involves considerable work in studying lists of declarations and using expert judgment. An expert system, Computer Assisted Human Matching (CAHM) has been designed and implemented to reduce substantially the manpower required in the Human Transit Matching phase. This new system is completely integrated within the IAEA Safeguards Information System (ISIS) and since January 1989 has completely replaced the previous manual matching system. The current implementation of the system covers the area of international transfers and domestic transfers as well. The CAMH system: extracts data (un-matched records) from the accounting file, generates a new data structure, activates the automatic matching algorithm, displays the results for human acceptance, updates the matched records in the accounting file

  14. Human FcRn can mediate the transport across intestinal mucosal barrier and prolong the half-life of rabbit IgG in vivo

    Scientific Electronic Library Online (English)

    Guangchang, Pang; Yufang, Wang; Junbo, Xie; Qingsen, Chen; Zhihe, Hu.

    2015-06-01

    Full Text Available FcRn (neonatal Fc receptor) plays an important role in IgG transportation, antigen presentation and signal transmission. In this study, the complement fixation test and flow cytometry test were performed to verify whether the heterologous antibody could be transmitted to the serum or leukocyte with [...] Fc?R (Fc gamma receptor) across the intestinal mucosa. The results showed that rabbit anti-bovine IgG could be detected in both the serum and the leukocytes, which indicated that the heterologous antibody could transport across the intestinal mucosa to enter the blood and be effectively delivered to the leukocytes with Fc?R. In addition, the results also showed that the rabbit anti-bovine IgG still could be detected in the leukocyte group (P=0.044

  15. Accidental intestinal myiasis caused by genus Sarcophaga

    OpenAIRE

    Das A.; Pandey A; Madan M; Asthana A; Gautam A

    2010-01-01

    Myiasis of different organs has been reported off and on from various regions in the world. We report a human case of intestinal myiasis caused by larvae of Sarcophaga. A 25 - year - old male presented with symptom of passage of live worms in stool. Following diagnosis and treatment the patient improved completely with cessation of maggots in stool.

  16. New glucosidase inhibitors from an ayurvedic herbal treatment for type 2 diabetes: structures and inhibition of human intestinal maltase-glucoamylase with compounds from Salacia reticulata.

    Science.gov (United States)

    Sim, Lyann; Jayakanthan, Kumarasamy; Mohan, Sankar; Nasi, Ravindranath; Johnston, Blair D; Pinto, B Mario; Rose, David R

    2010-01-26

    An approach to controlling blood glucose levels in individuals with type 2 diabetes is to target alpha-amylases and intestinal glucosidases using alpha-glucosidase inhibitors acarbose and miglitol. One of the intestinal glucosidases targeted is the N-terminal catalytic domain of maltase-glucoamylase (ntMGAM), one of the four intestinal glycoside hydrolase 31 enzyme activities responsible for the hydrolysis of terminal starch products into glucose. Here we present the X-ray crystallographic studies of ntMGAM in complex with a new class of alpha-glucosidase inhibitors derived from natural extracts of Salacia reticulata, a plant used traditionally in Ayuverdic medicine for the treatment of type 2 diabetes. Included in these extracts are the active compounds salacinol, kotalanol, and de-O-sulfonated kotalanol. This study reveals that de-O-sulfonated kotalanol is the most potent ntMGAM inhibitor reported to date (K(i) = 0.03 microM), some 2000-fold better than the compounds currently used in the clinic, and highlights the potential of the salacinol class of inhibitors as future drug candidates. PMID:20039683

  17. ASBESTOS AND GASTRO-INTESTINAL CANCER: CELL CULTURE STUDIES

    Science.gov (United States)

    Three forms of asbestos: amosite, crocidolite, and chrysotile, were assayed for their cytotoxicity and mutagenicity in cell clture. Using embjryonic human intestine derived and adult rat liver derived epitelial cells, the order of toxicity was chrysotile > amosite = crocidolite. ...

  18. Deciphering the porcine intestinal microRNA transcriptome

    Directory of Open Access Journals (Sweden)

    Keller Andreas

    2010-04-01

    Full Text Available Abstract Background While more than 700 microRNAs (miRNAs are known in human, a comparably low number has been identified in swine. Because of the close phylogenetic distance to humans, pigs serve as a suitable model for studying e.g. intestinal development or disease. Recent studies indicate that miRNAs are key regulators of intestinal development and their aberrant expression leads to intestinal malignancy. Results Here, we present the identification of hundreds of apparently novel miRNAs in the porcine intestine. MiRNAs were first identified by means of deep sequencing followed by miRNA precursor prediction using the miRDeep algorithm as well as searching for conserved miRNAs. Second, the porcine miRNAome along the entire intestine (duodenum, proximal and distal jejunum, ileum, ascending and transverse colon was unraveled using customized miRNA microarrays based on the identified sequences as well as known porcine and human ones. In total, the expression of 332 intestinal miRNAs was discovered, of which 201 represented assumed novel porcine miRNAs. The identified hairpin forming precursors were in part organized in genomic clusters, and most of the precursors were located on chromosomes 3 and 1, respectively. Hierarchical clustering of the expression data revealed subsets of miRNAs that are specific to distinct parts of the intestine pointing to their impact on cellular signaling networks. Conclusions In this study, we have applied a straight forward approach to decipher the porcine intestinal miRNAome for the first time in mammals using a piglet model. The high number of identified novel miRNAs in the porcine intestine points out their crucial role in intestinal function as shown by pathway analysis. On the other hand, the reported miRNAs may share orthologs in other mammals such as human still to be discovered.

  19. Experimental evidence for phase synchronization transitions in human cardio-respiratory system

    CERN Document Server

    Bartsch, R; Kantelhardt, J W; Penzel, T; Bartsch, Ronny; Havlin, Shlomo; Kantelhardt, Jan W.; Penzel, Thomas

    2007-01-01

    Transitions in the dynamics of complex systems can be characterized by changes in the synchronization behavior of their components. Taking the human cardio-respiratory system as an example and using an automated procedure for screening the synchrograms of 112 healthy subjects we study the frequency and the distribution of synchronization episodes under different physiological conditions that occur during sleep. We find that phase synchronization between heartbeat and breathing is significantly enhanced during non-rapid-eye-movement (non-REM) sleep (deep sleep and light sleep) and reduced during REM sleep. Our results suggest that the synchronization is mainly due to a weak influence of the breathing oscillator upon the heartbeat oscillator, which is disturbed in the presence of long-term correlated noise, superimposed by the activity of higher brain regions during REM sleep.

  20. Modulation of Mitochondrial Permeability Transition Pore Affects Multidrug Resistance in Human Hepatocellular Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Xianlong Ling, Yuan Zhou, Shi-Wei Li, Bin Yan, Lei Wen

    2010-01-01

    Full Text Available Multidrug resistance (MDR is a critical problem in the chemotherapy of cancers. Human hepatocellular carcinoma (HCC responds poorly to chemotherapy owing to its potent MDR. Chemotherapeutic drugs primarily act by inducing apoptosis of cancer cells, and defects in apoptosis may result in MDR. Mitochondrial permeability transition (mPT is implicated as an important event in the control of cell death or survival and mPT represents a target for the development of cytotoxic drugs. This study aimed to investigate the effects of selective opener (Atractyloside glycoside, ATR and inhibitor (Cyclosporine A, CsA of mitochondrial permeability transition pore (mPTP on a CDDP-resistant HCC cell line (SK-Hep1 cells. In this study, a stable MDR phenotype characterization of SK-Hep1 cell line (SK-Hep1/CDDP cells was established and used to investigate the role of mPTP in MDR. Results suggested that ATR accelerated the decrease of mitochondrial membrane potential (??m, reduced the Bax activity, and increased the apoptosis of SK-Hep1/CDDP cells; while CsA inhibited mPTP opening, reduced and delayed the decline of mitochondrial membrane potential, and increased the Bax activity, leading to increased tolerance of SK-Hep1/CDDP cells to apoptosis induction. However, mPTP activity had no effect on the expression of MDR1 in cells,meanwhile the P-gp translocation to mitochondria was increased, and functionally activated. In conclusion, selective modulation of mPTP can affect MDR in human HCC cells. Therefore, activation of mPTP may provide a new strategy to sensitize cancer cells to chemotherapeutic drugs and to reverse the MDR in cancer cells.

  1. Issues for resolving adverse effects on the safety culture of human work underload and workload transitions in complex human-machine systems

    International Nuclear Information System (INIS)

    A workshop was conducted whose specific purpose was to build on earlier work of the US National Research Council, US federal government agencies, and the larger human factors community to: (1) clarify human factors issues pertaining to degraded safety 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. 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

  2. Dyslipidaemia--hepatic and intestinal cross-talk.

    LENUS (Irish Health Repository)

    Tomkin, Gerald H

    2010-06-01

    Cholesterol metabolism is tightly regulated with the majority of de novo cholesterol synthesis occurring in the liver and intestine. 3 Hydroxy-3-methylglutaryl coenzyme A reductase, a major enzyme involved in cholesterol synthesis, is raised in both liver and intestine in diabetic animals. Niemann PickC1-like1 protein regulates cholesterol absorption in the intestine and facilitates cholesterol transport through the liver. There is evidence to suggest that the effect of inhibition of Niemann PickC1-like1 lowers cholesterol through its effect not only in the intestine but also in the liver. ATP binding cassette proteins G5\\/G8 regulate cholesterol re-excretion in the intestine and in the liver, cholesterol excretion into the bile. Diabetes is associated with reduced ATP binding cassette protein G5\\/G8 expression in both the liver and intestine in animal models. Microsomal triglyceride transfer protein is central to the formation of the chylomicron in the intestine and VLDL in the liver. Microsomal triglyceride transfer protein mRNA is increased in diabetes in both the intestine and liver. Cross-talk between the intestine and liver is poorly documented in humans due to the difficulty in obtaining liver biopsies but animal studies are fairly consistent in showing relationships that explain in part mechanisms involved in cholesterol homeostasis.

  3. Small intestinal bacteria overgrowth decreases small intestinal motility in the NASH rats

    Directory of Open Access Journals (Sweden)

    Wan-Chun Wu, Wei Zhao, Sheng Li

    2008-01-01

    Full Text Available AIM: To explore the relationship between small intestinal motility and small intestinal bacteria overgrowth (SIBO in Nonalcoholic steatohepatitis (NASH, and to investigate the effect of SIBO on the pathogenesis of NASH in rats. The effect of cidomycin in alleviating severity of NASH is also studied.METHODS: Forty eight rats were randomly divided into NASH group (n = 16, cidomycin group (n = 16 and control group (n = 16. Then each group were subdivided into small intestinal motility group (n = 8, bacteria group (n = 8 respectively. A semi-solid colored marker was used for monitoring small intestinal transit. The proximal small intestine was harvested under sterile condition and processed for quantitation for aerobes (E. coli and anaerobes (Lactobacilli. Liver pathologic score was calculated to qualify the severity of hepatitis. Serum ALT, AST levels were detected to evaluate the severity of hepatitis.RESULTS: Small intestinal transit was inhibited in NASH group (P < 0.01. Rats treated with cidomycin had higher small intestine transit rate than rats in NASH group (P < 0.01. High fat diet resulted in quantitative alterations in the aerobes (E. coli but not in the anoerobics (Lactobacill. There was an increase in the number of E. coli in the proximal small intestinal flora in NASH group than in control group (1.70 0.12 log10 (CFU/g vs 1.28 0.07 log10 (CFU/g, P < 0.01. TNF-? concentration was significantly higher in NASH group than in control group (1.13 0.15 mmol/L vs 0.57 0.09 mmol/L, P < 0.01. TNF-?concentration was lower in cidomycin group than in NASH group (0.63 0.09 mmol/L vs 1.13 0.15 mmol/L, P < 0.01. Treatment with cidomycin showed its effect by significantly lowering serum ALT, AST and TNF-? levels of NASH rats.CONCLUSION: SIBO may decrease small intestinal movement in NASH rats. SIBO may be an important pathogenesis of Nash. And treatment with cidomycin by mouth can alleviate the severity of NASH.

  4. Small intestinal bacteria overgrowth decreases small intestinal motility in the NASH rats

    Science.gov (United States)

    Wu, Wan-Chun; Zhao, Wei; Li, Sheng

    2008-01-01

    AIM: To explore the relationship between small intestinal motility and small intestinal bacteria overgrowth (SIBO) in Nonalcoholic steatohepatitis (NASH), and to investigate the effect of SIBO on the pathogenesis of NASH in rats. The effect of cidomycin in alleviating severity of NASH is also studied. METHODS: Forty eight rats were randomly divided into NASH group (n = 16), cidomycin group (n = 16) and control group (n = 16). Then each group were subdivided into small intestinal motility group (n = 8), bacteria group (n = 8) respectively. A semi-solid colored marker was used for monitoring small intestinal transit. The proximal small intestine was harvested under sterile condition and processed for quantitation for aerobes (E. coli) and anaerobes (Lactobacilli). Liver pathologic score was calculated to qualify the severity of hepatitis. Serum ALT, AST levels were detected to evaluate the severity of hepatitis. RESULTS: Small intestinal transit was inhibited in NASH group (P < 0.01). Rats treated with cidomycin had higher small intestine transit rate than rats in NASH group (P < 0.01). High fat diet resulted in quantitative alterations in the aerobes (E. coli) but not in the anoerobics (Lactobacill). There was an increase in the number of E. coli in the proximal small intestinal flora in NASH group than in control group (1.70 0.12 log10 (CFU/g) vs 1.28 0.07 log10 (CFU/g), P < 0.01). TNF-? concentration was significantly higher in NASH group than in control group (1.13 0.15 mmol/L vs 0.57 0.09 mmol/L, P < 0.01). TNF-?concentration was lower in cidomycin group than in NASH group (0.63 0.09 mmol/L vs 1.13 0.15 mmol/L, P < 0.01). Treatment with cidomycin showed its effect by significantly lowering serum ALT, AST and TNF-? levels of NASH rats. CONCLUSION: SIBO may decrease small intestinal movement in NASH rats. SIBO may be an important pathogenesis of Nash. And treatment with cidomycin by mouth can alleviate the severity of NASH. PMID:18186574

  5. Cannabinoids cool the intestine

    OpenAIRE

    KUNOS, GEORGE; Pacher, Pl

    2004-01-01

    Cannabinoids inhibit motility and secretion in the intestine. They are now assigned the additional task of curbing excessive inflammation, suggesting that drugs targeting the endogenous cannabinoid system could be exploited for inflammatory bowel disease.

  6. Intestinal Pseudo-Obstruction

    Science.gov (United States)

    ... nutritional support to prevent malnutrition and weight loss. Enteral nutrition provides liquid food through a feeding tube inserted ... to care for the tube after returning home. Enteral nutrition is sufficient for most people with intestinal pseudo- ...

  7. Intestinal obstruction repair

    Science.gov (United States)

    ... contents of the intestines cannot pass through and exit the body. A complete obstruction is a surgical ... your bowel will be repaired or removed. This procedure is called bowel resection . If a section is ...

  8. Intestinal malrotation as a cause for abdominal pain in adults

    Directory of Open Access Journals (Sweden)

    Federico Guillermo Lubinus Badillo

    2006-08-01

    Full Text Available We show the case of a 63 year old woman complaining of chronicabdominal pain and bilious vomiting. The patient was admitted tothe hospital with a diagnosis of intestinal obstruction which got better by medical treatment. After performing an abdominal computarized tomography, a midgut volvulus was diagnosed and later confirmed by an intestinal transit time. The patient was discharged with out symptoms after medical treatment and an elective procedure was scheduled (Ladd procedure and to reduce the risk of volvulusand intestinal ischemia. We discuss the clinical presentation of thedisease, the diagnostic methods used and the treatment optionsavailable.

  9. The Intestinal Stem Cell

    OpenAIRE

    Barker, Nick; Wetering, Marc; Clevers, Hans

    2010-01-01

    The epithelium of the adult mammalian intestine is in a constant dialog with its underlying mesenchyme to direct progenitor proliferation, lineage commitment, terminal differentiation, and, ultimately, cell death. The epithelium is shaped into spatially distinct compartments that are dedicated to each of these events. While the intestinal epithelium represents the most vigorously renewing adult tissue in mammals, the stem cells that fuel this self-renewal process have been identified only rec...

  10. Role of mitochondrial permeability transition in human renal tubular epithelial cell death induced by aristolochic acid

    International Nuclear Information System (INIS)

    Aristolochic acid (AA), a natural nephrotoxin and carcinogen, can induce a progressive tubulointerstitial nephropathy. However, the mechanism by which AA causes renal injury remains largely unknown. Here we reported that the mitochondrial permeability transition (MPT) plays an important role in the renal injury induced by aristolochic acid I (AAI). We found that in the presence of Ca2+, AAI caused mitochondrial swelling, leakage of Ca2+, membrane depolarization, and release of cytochrome c in isolated kidney mitochondria. These alterations were suppressed by cyclosporin A (CsA), an agent known to inhibit MPT. Culture of HK-2 cell, a human renal tubular epithelial cell line for 24 h with AAI caused a decrease in cellular ATP, mitochondrial membrane depolarization, cytochrome c release, and increase of caspase 3 activity. These toxic effects of AAI were attenuated by CsA and bongkrekic acid (BA), another specific MPT inhibitor. Furthermore, AAI greatly inhibited the activity of mitochondrial adenine nucleotide translocator (ANT) in isolated mitochondria. We suggested that ANT may mediate, at least in part, the AAI-induced MPT. Taken together, these results suggested that MPT plays a critical role in the pathogenesis of HK-2 cell injury induced by AAI and implied that MPT might contribute to human nephrotoxicity of aristolochic acid

  11. Metabolism of ginsenoside Rb1 by human intestinal microflora and cloning of its metabolizing ?-D-glucosidase from Bifidobacterium longum H-1.

    Science.gov (United States)

    Jung, Il-Hoon; Lee, Jeong Hoon; Hyun, Yang-Jin; Kim, Dong-Hyun

    2012-01-01

    To understand the role of intestinal microflora in expressing the pharmacological effect of ginsenoside Rb1, the metabolic activity of ginsenoside Rb1 by 148 fecal specimens was measured and its metabolizing ?-glucosidase was cloned. The average activities for p-nitrophenyl-?-D-glucopyranoside and ginsenoside Rb1 were 0.0970.059 ?mol/min/mg and 0.3110.118 pmol/min/mg, respectively. These enzyme activities were not different between male and female, or between ages. A gene encoding ?-D-glucosidase (BglX) was cloned from Bifidobacterium longum H-1, which transformed ginsenoside Rb1 to compound K. The probe for cloning was synthesized from the genes encoding a ?-D-glucosidase of previously reported B. longum DJO10A. The sequences of the cloned gene revealed 2364 bp open reading frame (ORF) encoding a protein containing 787 amino acids (molecular weight of 95 kDa). The gene exhibited 99% homology (identities) to that of B. longum. The cloned gene was expressed under T7 promoter of the expression vector, pET-39b(+), in Escherichia coli BL21(DE3), and the expressed enzyme was purified by using HiTrap immobilized metal affinity chromatography (IMAC) HP. The enzyme potently biotransformed ginsenoside Rb1, loganin, arctiin and arbutin to ginsenoside Rd, loganetin, arctigenin and hydroquinone, respectively, but was not active in the case of hesperidin, and kakkalide. This is the first report on cloning and expression of ?-D-glucosidase from B. longum. Based on these findings, ginsenoside Rb1 may be metabolized to bioactive compound(s) by exo-?-D-glucosidase(s) produced from the intestinal bacteria and its pharmacological effects may be dependent on intestinal bacterial exo-?-D-glucosidase(s) activity. PMID:22466563

  12. Intestinal microbiota: its role in digestive diseases.

    Science.gov (United States)

    Bustos Fernandez, Luis M; Lasa, Juan S; Man, Fernando

    2014-09-01

    It is now well known that intestinal microbiota exerts not only several physiological functions, but has also been implied in the mechanisms of many conditions, both intestinal and extraintestinal. These advances, to the best of our knowledge, have been made possible by the development of new ways of studying gut flora. Metagenomics, the study of genetic material taken directly from environmental samples, avoiding individual culture, has become an excellent tool to study the human microbiota. Therefore, it has demonstrated an association between an altered intestinal microbiota and inflammatory bowel disease or irritable bowel syndrome, perhaps the most extensively studied conditions associated with this particular subject. However, microbiota has a potential role in the development of other diseases; their manifestations are not confined to the intestine only. In this article, an extensive updated review is conducted on the role intestinal microbiota has in health and in different diseases. Focus is made on the following conditions: inflammatory bowel disease, irritable bowel syndrome, celiac disease, hepatic encephalopathy, and obesity. PMID:24921207

  13. Regulatory effect of heat shock protein 70 in stress-induced rat intestinal epithelial barrier dysfunction

    Directory of Open Access Journals (Sweden)

    Stevie Struiksma

    2009-06-01

    Full Text Available Background: Psychological stress is one of the factors associated with many human diseases; the mechanisms need to be further understood. Methods: Rats were subjected to chronic water avoid stress. Intestinal epithelial heat shock protein (HSP 70 was evaluated. The intestinal epithelial permeability was examined with Ussing chamber technique. Results: HSP70 was detected in normal intestinal epithelial cells. Psychological stress decreased HSP70 in the intestinal epithelial cells that correlated with the stress-induced intestinal epithelial hyperpermeability. Pretreatment with HSP70 abrogated stress-induced intestinal barrier dysfunction. Conclusions: Chronic stress inhibits HSP70 activity in rat intestinal epithelial layer that is associated with intestinal epithelial barrier dysfunction, which can be prevented by pretreatment with HSP70 protein.

  14. Construction of stable cloning vectors that do not segregate from a human fecal Escherichia coli strain in the streptomycin-treated mouse large intestine.

    OpenAIRE

    Burghoff, R. L.; Laux, D. C.; Cohen, P. S.

    1990-01-01

    Escherichia coli F-18 Col- was previously shown to be a poor colonizer of the streptomycin-treated mouse large intestine, relative to its parent, E. coli F-18. Prior to attempting to clone genes responsible for the colonization phenotype of E. coli F-18 into E. coli F-18 Col-, a suitable cloning vector had to be found. In this investigation, we report that the commonly used cloning vectors pBR322, pHC79, and pBR329 all segregate from E. coli F-18 Col- both when grown in L broth under conditio...

  15. Reappraisal of the Immunophenotype of Pancreatic Intraductal Papillary Mucinous Neoplasms (IPMNs)Gastric Pyloric and Small Intestinal Immunophenotype Expression in Gastric and Intestinal Type IPMNs

    International Nuclear Information System (INIS)

    Pancreatic intraductal papillary mucinous neoplasms (IPMNs) are mucin-producing neoplasms of the main and/or branch pancreatic ducts. To assess differences between various IPMN subtypes, immunohistochemical markers of gastric surface mucous cells (MUC5AC), gastric gland mucous cells (MUC6 and GlcNAc?1?4Gal??R), gastric pyloric and duodenal epithelial cells (PDX1), intestinal cells (MUC2 and CDX2), small intestinal cells (CPS1) and large intestinal cells (SATB2) were evaluated in 33 surgically treated IPMNs. MUC2 expression classified IPMNs into gastric (n=17), intestinal (n=8) and mixed gastric and intestinal type (collision=7, composite=1). No differences in age or sex were observed among these types. MUC5AC and PDX1 were expressed in all IPMNs. MUC6 expression was higher in gastric and mixed types than in intestinal type. GlcNAc?1?4Gal??R was detected in gastric and mixed type, but not in intestinal type. MUC2 and CDX2 expression were higher in intestinal type than gastric and mixed type. CPS1 expression was higher in intestinal type than gastric type. SATB2 was not observed in any IPMNs. Frequent abrupt transition between the two IPMN types in mixed-type IPMNs was observed. Gastric pyloric and small intestinal differentiation are characteristic of gastric and intestinal type IPMN, respectively, and these two IPMN types may have distinct pathogenesis

  16. Intestinal lymphangiectasia in adults

    Directory of Open Access Journals (Sweden)

    Hugh James Freeman

    2011-02-01

    Full Text Available Intestinal lymphangiectasia in the adult may be characterized as a disorder with dilated intestinal lacteals causing loss of lymph into the lumen of the small intestine and resultant hypoproteinemia, hypogammaglobulinemia, hypoalbuminemia and reduced number of circulating lymphocytes or lymphopenia. Most often, intestinal lymphangiectasia has been recorded in children, often in neonates, usually with other congenital abnormalities but initial definition in adults including the elderly has become increasingly more common. Shared clinical features with the pediatric population such as bilateral lower limb edema, sometimes with lymphedema, pleural effusion and chylous ascites may occur but these reflect the severe end of the clinical spectrum. In some, diarrhea occurs with steatorrhea along with increased fecal loss of protein, reflected in increased fecal alpha-1-antitrypsin levels, while others may present with iron deficiency anemia, sometimes associated with occult small intestinal bleeding. Most lymphangiectasia in adults detected in recent years, however, appears to have few or no clinical features of malabsorption. Diagnosis remains dependent on endoscopic changes confirmed by small bowel biopsy showing histological evidence of intestinal lymphangiectasia. In some, video capsule endoscopy and enteroscopy have revealed more extensive changes along the length of the small intestine. A critical diagnostic element in adults with lymphangiectasia is the exclusion of entities (e.g. malignancies including lymphoma that might lead to obstruction of the lymphatic system and secondary changes in the small bowel biopsy. In addition, occult infectious (e.g. Whipples disease from Tropheryma whipplei or inflammatory disorders (e.g. Crohns disease may also present with profound changes in intestinal permeability and protein-losing enteropathy that also require exclusion. Conversely, rare B-cell type lymphomas have also been described even decades following initial diagnosis of intestinal lymphangiectasia. Treatment has been historically defined to include a low fat diet with medium-chain triglyceride supplementation that leads to portal venous rather than lacteal uptake. A number of other pharmacological measures have been reported or proposed but these are largely anecdotal. Finally, rare reports of localized surgical resection of involved areas of small intestine have been described but follow-up in these cases is often limited.

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

    Directory of Open Access Journals (Sweden)

    Shila Gilbert

    2015-02-01

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

  18. Intestinal carriage of Campylobacter jejuni and Campylobacter coli among cattle from South-western Norway and comparative genotyping of bovine and human isolates by amplified-fragment length polymorphism

    Directory of Open Access Journals (Sweden)

    Vardund T

    2006-06-01

    Full Text Available Abstract In a survey conducted in 19992001, the carriage of thermotolerant Campylobacters in cattle was investigated, and the genetic diversity of C. jejuni within one herd was examined and compared with human isolates. C. jejuni, C. coli and other thermotolerant Campylobacter spp. were isolated from intestinal contents from 26%, 3% and 2% of 804 cattle, respectively. The carriage rate was higher in calves (46% than in adults (29%. Twenty-nine C. jejuni isolates from one herd and 31 human isolates from the study area were genotyped with amplified-fragment length polymorphism (AFLP. Eighty-three % of the bovine isolates fell into three distinct clusters with 95100% similarity, persistent in the herd for 510 months. Among human isolates, 58% showed >90% similarity with bovine isolates. The results show that cattle are a significant and stable reservoir for C. jejuni in the study area. Transmission between individuals within the herd may be sufficient to maintain a steady C. jejuni population independent of environmental influx. The results of this study have provided new information on C. jejuni and C. coli transmission, and also on the carriage in cattle, genotypes stability and similarity between bovine and human isolates.

  19. Intestinal dendritic cells in the regulation of mucosal immunity.

    DEFF Research Database (Denmark)

    Bekiaris, Vasileios; Persson, Emma K.

    2014-01-01

    The intestine presents a huge surface area to the outside environment, a property that is of critical importance for its key functions in nutrient digestion, absorption, and waste disposal. As such, the intestine is constantly exposed to dietary and microbial-derived foreign antigens, to which immune cells within the mucosa must suitably respond to maintain intestinal integrity, while also providing the ability to mount effective immune responses to potential pathogens. Dendritic cells (DCs) are sentinel immune cells that play a central role in the initiation and differentiation of adaptive immune responses. In the intestinal mucosa, DCs are located diffusely throughout the intestinal lamina propria, within gut-associated lymphoid tissues, including Peyer's patches and smaller lymphoid aggregates, as well as in intestinal-draining lymph nodes, including mesenteric lymph nodes. The recognition that dietary nutrients and microbial communities in the intestine influence both mucosal and systemic immune cell development and function as well as immune-mediated disease has led to an explosion of literature in mucosal immunology in recent years and a growing interest in the functionality of intestinal DCs. In the current review, we discuss recent findings from our group and others that have provided important insights regarding murine and human intestinal lamina propria DCs and highlighted marked developmental and functional heterogeneity within this compartment. A thorough understanding of the role these subsets play in the regulation of intestinal immune homeostasis and inflammation will help to define novel strategies for the treatment of intestinal pathologies and contribute to improved rational design of mucosal vaccines.

  20. Transcriptome changes during intestinal cell differentiation

    DEFF Research Database (Denmark)

    Tadjali, Mehrdad; Seidelin, Jakob B

    2002-01-01

    The expression of 18149 genes have been analysed during the differentiation of the human intestinal cell line Caco-2. cDNA probes from undifferentiated and differentiated Caco-2 cells were separately hybridised to EST DNAs spotted in an array on a nylon membrane. A remarkable change in the transcriptome was observed during the differentiation of the Caco-2 cells. 8762 of the 18149 genes analysed were expressed above background level in the undifferentiated Caco-2 cells, whereas only 5767 genes were expressed above background in differentiated Caco-2 cells. This pattern of expression was caused by a general down-regulation of genes in the low abundance class. Similar results were found using mouse small intestinal crypt and villus cells, suggesting that the phenomenon also occurs in the intestine in vivo. The expression data were subsequently used in a search for markers for subsets of epithelial cells by performing reverse transcriptase-polymerase chain reaction on RNA extracted from laser dissected intestinal crypt and villi. In a screen of eight transcripts one - SART3 - was identified as a marker for human colonic crypts.

  1. Spinal motor outputs during step-to-step transitions of diverse human gaits

    Directory of Open Access Journals (Sweden)

    Francesco Lacquaniti

    2014-05-01

    Full Text Available Aspects of human motor control can be inferred from the coordination of muscles during movement. For instance, by combining multimuscle electromyographic (EMG recordings with human neuroanatomy, it is possible to estimate alpha-motoneuron (MN pool activations along the spinal cord. It has previously been shown that the spinal motor output fluctuates with the bodys center-of-mass motion, with bursts of activity around foot-strike and foot lift-off during walking. However, it is not known whether these MN bursts are generalizable to other ambulation tasks, nor is it clear if the spatial locus of the activity (along the rostrocaudal axis of the spinal cord is fixed or variable. Here we sought to address these questions by investigating the spatiotemporal characteristics of the spinal motor output during various tasks: walking forward, backward, tiptoe and uphill. We reconstructed spinal maps from 26 leg muscle EMGs, including some intrinsic foot muscles. We discovered that the various walking tasks shared qualitative similarities in their temporal spinal activation profiles, exhibiting peaks around foot-strike and foot-lift. However, we also observed differences in the segmental level and intensity of spinal activations, particularly following foot-strike. For example, forward level-ground walking exhibited a mean motor output roughly 2 times lower than the other gaits. Finally, we found that the reconstruction of the spinal motor output from multimuscle EMG recordings was relatively insensitive to the subset of muscles analyzed. In summary, our results suggested temporal similarities, but spatial differences in the segmental spinal motor outputs during the step-to-step transitions of disparate walking behaviors.

  2. Diagnosis of intestinal and extra intestinal amoebiasis

    International Nuclear Information System (INIS)

    The objective is to carry out a review of the national and international literature as of the XXth century in order to update the advances for the diagnosis of complex odd Entamoeba histolytic / Entamoeba dispar and that of intestinal and extra intestinal amoebiasis that may be of use to the scientific community. As well as to unify the diagnostic criteria of this parasitosis known as a public health problem, and as a consequence of that, optimize the quality of population care. Data source: there was a systematic search for the scientific literature Publisher in Spanish and English since 1960 until today, this selection started on the first semester of 2006 until 2007, in the development of the line on intestinal and extra-intestinal amoebiasis of the Medical School of the National University of Colombia. A retrospective search process was carried out, systematically reviewing the most relevant articles as well as the products of this research line. In deciding how to make this article, there was a continuous search in different data bases such as Medline, SciELO and other bases in the library of the National University of Colombia, as well as other classical books related to the subject. For that purpose the terms amoebiasis, odd Entamoeba histolytic, Entamoeba, diagnosis, epidemiology, dysentery, amoebic liver abscess, were used. Studies selection: titles and abstracts were reviewed to select the original publications and the most representative ones related to thihe most representative ones related to this article's subject. Data extraction: the articles were classified according to the subject, the chronology and the authors according to the scientific contribution to solve the problem. Synthesis of the data: in the fi rst instance, a chronological critical analysis was carried out to order and synthesize the progress made in the diagnosis until confirmation of the experts' agreements in the field of amoebiasis was obtained throughout the world. Conclusion: this article summarizes what has taken place during the XXth and the beginning of the XXIst century in updating the diagnosis of amoebiasis and accepting the hypothesis of the complex Entamoeba histolytic / Entamoeba dispar proposed by Brumpt in 1925. In Colombia, given the progress made in the diagnostic techniques, as well as the determination of Gal/GalNAc lectine in the feces, the prevalence of E. histolytic between 0.6%-1.4%. However, for the diagnosis of intestinal amoebiasis direct test without being able to define the species. On the other hand, the most important clinical picture of extra-intestinal amoebiasis is liver abscess; to make that diagnosis the clinical history the context is analyzed, including the clinical history, epidemiological aspects, imaging studies and IgG antibodies against histolytic. The histopathology of the colon lesions continues to be valid for the differential diagnosis with other etiologies. The advent of the new molecular biology tests, will be a helpful diagnosis tool in this pathology.

  3. Developmental regulation of intestinal angiogenesis by indigenous microbes via Paneth cells.

    Science.gov (United States)

    Stappenbeck, Thaddeus S; Hooper, Lora V; Gordon, Jeffrey I

    2002-11-26

    The adult mouse intestine contains an intricate vascular network. The factors that control development of this network are poorly understood. Quantitative three-dimensional imaging studies revealed that a plexus of branched interconnected vessels developed in small intestinal villi during the period of postnatal development that coincides with assembly of a complex society of indigenous gut microorganisms (microbiota). To investigate the impact of this environmental transition on vascular development, we compared the capillary networks of germ-free mice with those of ex-germ-free animals colonized during or after completion of postnatal gut development. Adult germ-free mice had arrested capillary network formation. The developmental program can be restarted and completed within 10 days after colonization with a complete microbiota harvested from conventionally raised mice, or with Bacteroides thetaiotaomicron, a prominent inhabitant of the normal mouse/human gut. Paneth cells in the intestinal epithelium secrete antibacterial peptides that affect luminal microbial ecology. Comparisons of germ-free and B. thetaiotaomicron-colonized transgenic mice lacking Paneth cells established that microbial regulation of angiogenesis depends on this lineage. These findings reveal a previously unappreciated mechanism of postnatal animal development, where microbes colonizing a mucosal surface are assigned responsibility for regulating elaboration of the underlying microvasculature by signaling through a bacteria-sensing epithelial cell. PMID:12432102

  4. Developmental regulation of intestinal angiogenesis by indigenous microbes via Paneth cells

    Science.gov (United States)

    Stappenbeck, Thaddeus S.; Hooper, Lora V.; Gordon, Jeffrey I.

    2002-01-01

    The adult mouse intestine contains an intricate vascular network. The factors that control development of this network are poorly understood. Quantitative three-dimensional imaging studies revealed that a plexus of branched interconnected vessels developed in small intestinal villi during the period of postnatal development that coincides with assembly of a complex society of indigenous gut microorganisms (microbiota). To investigate the impact of this environmental transition on vascular development, we compared the capillary networks of germ-free mice with those of ex-germ-free animals colonized during or after completion of postnatal gut development. Adult germ-free mice had arrested capillary network formation. The developmental program can be restarted and completed within 10 days after colonization with a complete microbiota harvested from conventionally raised mice, or with Bacteroides thetaiotaomicron, a prominent inhabitant of the normal mouse/human gut. Paneth cells in the intestinal epithelium secrete antibacterial peptides that affect luminal microbial ecology. Comparisons of germ-free and B. thetaiotaomicron-colonized transgenic mice lacking Paneth cells established that microbial regulation of angiogenesis depends on this lineage. These findings reveal a previously unappreciated mechanism of postnatal animal development, where microbes colonizing a mucosal surface are assigned responsibility for regulating elaboration of the underlying microvasculature by signaling through a bacteria-sensing epithelial cell. PMID:12432102

  5. Estudio de la fasciolosis heptica humana y parasitosis intestinales en el casero Mesa Arriba del municipio Carache, estado Trujillo,Venezuela / Study of human hepatic fasciolosis and intestinal parasitosis in the Mesa Arriba Village, Carache Municipality, Trujillo State, Venezuela

    Scientific Electronic Library Online (English)

    Salha, Abdul-Hadi; Ivonne, Figueira; Carlos, Madera; Carolina, Olaizola; Rosa, Contreras; Mara Antonia, Snchez; Cecilia, Colmenares; Mara Luisa, Safar.

    2009-12-01

    Full Text Available Se realiz un estudio clnico epidemiolgico para determinar la ocurrencia de fasciolosis heptica humana y parasitosis intestinales en el casero Mesa Arriba, municipio Carache. estado Trujillo, Venezuela, zona descrita como endmica para fasciolosis bovina, donde dos casos aislados, se han reporta [...] do en humanos. Se estudiaron 98 personas previo consentimiento informado, a quienes se les realiz una encuesta epidemiolgica, examen fsico, hematologa, aminotransferasas, estudio coproparasitolgico y serolgico: ELISA con antgeno de excrecin-secrecin de adultos de Fasciola hepatica (AFhES) y Western blot(WB). Con base en los datos obtenidos, se conoci que el 88,8% de los participantes haba consumido berro silvestre (Rorippa nasturtium aquaticum) y 59,2% tuvo contacto con ganado vacuno. En el estudio coproparasitolgico se encontr que el 47,9% present algn tipo de parsito intestinal, 20,4% correspondi a helmintos, 15,3% a protozoarios y 12,2% a infecciones mixtas. No se encontraron huevos de Fasciola hepatica. El 18,4% de las personas mostr eosinofilia. Se obtuvo un suero positivo por el mtodo de ELISA, con bandas inespecficas al WB-AFhES. Se administr tratamiento especfico para parsitos intestinales. No se demostr fasciolosis humana en este trabajo, a pesar de encontrar factores favorables a la infeccin, pero el mismo represent una aproximacin a su estudio epidemiolgico en el estado Trujillo. Abstract in english A clinical-epidemiological study to determine the occurrence of human hepatic fasciolosis and intestinal parasitosis was done at the Mesa Arriba Village, Carache Municipality, Trujillo State, Venezuela, area which has been described as endemic for bovine fasciolosis and where two isolated cases have [...] been reported in humans. The study included 98 persons who, after previously signing an informed consent form, answered an epidemiological survey and were physically examined and submitted to the following laboratory tests: complete hematology, aminotransferase, and coproparasitology and serology; ELISA using Fasciola hepatica adult excretion-secretion antigen (AFhES) and Western Blot (WB). Based on the results obtained, it was found that 88.8% of participants had consumed wild watercress (Rorippa nasturtium aquaticum) and 59.2% had contact with bovine cattle. The coproparasitological study showed that 47.9% had some type of intestinal parasite: 20.4% corresponded to helmints, 15.3% to protozoa, and 12.2% mixed infections. There were no Fasciola hepatica eggs; 18.4% of the individuals showed eosinophilia. The ELISA test gave one positive serum with non-specific WB-AFhES bands. Specific anti-intestinal parasite treatment was indicated. Human fasciolosis was not demonstrated in this study, in spite of finding favorable factors for this infection, but is represents and approximation to its epidemiological study at Trujillo State.

  6. Returns to Human Capital under the Communist Wage Grid and During the Transition to a Market Economy

    OpenAIRE

    Terrell, Katherine; Svejnar, Jan; Mnich, Daniel

    2000-01-01

    Under communism, workers had their wages set according to a centrally-determined wage grid. In this paper we use new micro data on men to estimate returns to human capital under the communist wage grid and during the transition to a market economy. We use data from the Czech Republic because it is a leading transition economy in which the communist grid remained intact until the very end of the communist regime. We demonstrate that for decades the communist wage grid maintained extremely low ...

  7. Targeting canine bladder transitional cell carcinoma with a human bladder cancer-specific ligand

    Directory of Open Access Journals (Sweden)

    Li Bin

    2011-01-01

    Full Text Available Abstract Objective To determine if a human bladder cancer-specific peptide named PLZ4 can target canine bladder cancer cells. Experimental Design The binding of PLZ4 to five established canine invasive transitional cell carcinoma (TCC cell lines and to normal canine bladder urothelial cells was determined using the whole cell binding assay and an affinitofluorescence assay. The WST-8 assay was performed to determine whether PLZ4 affected cell viability. In vivo tumor-specific homing/targeting property and biodistribution of PLZ4 was performed in a mouse xenograft model via tail vein injection and was confirmed with ex vivo imaging. Results PLZ4 exhibited high affinity and specific dose-dependent binding to canine bladder TCC cell lines, but not to normal canine urothelial cells. No significant changes in cell viability or proliferation were observed upon incubation with PLZ4. The in vivo and ex vivo optical imaging study showed that, when linked with the near-infrared fluorescent dye Cy5.5, PLZ4 substantially accumulated at the canine bladder cancer foci in the mouse xenograft model as compared to the control. Conclusions and Clinical Relevance PLZ4 can specifically bind to canine bladder cancer cells. This suggests that the preclinical studies of PLZ4 as a potential diagnostic and therapeutic agent can be performed in dogs with naturally occurring bladder cancer, and that PLZ4 can possibly be developed in the management of canine bladder cancer.

  8. Major transitions in human evolution revisited: a tribute to ancient DNA.

    Science.gov (United States)

    Ermini, Luca; Der Sarkissian, Clio; Willerslev, Eske; Orlando, Ludovic

    2015-02-01

    The origin and diversification of modern humans have been characterized by major evolutionary transitions and demographic changes. Patterns of genetic variation within modern populations can help with reconstructing this ?200 thousand year-long population history. However, by combining this information with genomic data from ancient remains, one can now directly access our evolutionary past and reveal our population history in much greater detail. This review outlines the main recent achievements in ancient DNA research and illustrates how the field recently moved from the polymerase chain reaction (PCR) amplification of short mitochondrial fragments to whole-genome sequencing and thereby revisited our own history. Ancient DNA research has revealed the routes that our ancestors took when colonizing the planet, whom they admixed with, how they domesticated plant and animal species, how they genetically responded to changes in lifestyle, and also, which pathogens decimated their populations. These approaches promise to soon solve many pending controversies about our own origins that are indecipherable from modern patterns of genetic variation alone, and therefore provide an extremely powerful toolkit for a new generation of molecular anthropologists. PMID:25532800

  9. Hispidulin prevents hypoxia-induced epithelial-mesenchymal transition in human colon carcinoma cells

    Science.gov (United States)

    Xie, Jing; Gao, Hui; Peng, Jianjun; Han, Yantao; Chen, Xuehong; Jiang, Qixiao; Wang, Chunbo

    2015-01-01

    Epithelial-mesenchymal transition (EMT) is considered as the most important mechanism that underlies the initiation of cancer metastasis. Here we report that the naturally existing flavonoid, hispidulin is capable of preventing human colorectal cancer cells from hypoxia-induced EMT. The treatment of the cells with hispidulin reversed the EMT-related phenotype that has the morphological changes, down-regulation of E-cadherin, and hypoxia-induced cell migration and invasion. The effect was mediated at least in part by inhibiting the mRNA and protein expressions of HIF-1? via modulation of PTEN/PI3K/Akt pathway. In addition, we found that hispidulin-mediated prevention of the E-cadherin down-regulation and cell motility involved blockade of the hypoxia-induced up-regulation of Snail, Slug and Twist. Hispidulin was also effective in increasing expression of E-cadherin mRNA in HT29 colorectal cancer xenografts implanted in the nude mice. In summary, this study showed that hispidulin can prevent EMT induced by hypoxia, the environment that commonly exists in the center of a solid tumor. Given the low toxicity of hispidulin to the healthy tissues, our study suggests that hispidulin can serve as a safe therapeutic agent for suppressing cancer metastasis. PMID:26045985

  10. The Influence of the Aspheric Profiles for Transition Zone on Optical Performance of Human Eye After Conventional Ablation

    Science.gov (United States)

    Fang, L.

    2014-12-01

    The analysis in the impact of transition zone on the optical performance of human eye after laser refractive surgery is important for improving visual correction technology. By designing the ablation profiles of aspheric transition zone and creating the ablation profile for conventional refractive surgery in optical zone, the influence of aspheric transition zone on residual aberrations was studied. The results indicated that the ablation profiles of transition zone had a significant influence on the residual wavefront aberrations. For a hyperopia correction, the profile #9 shows a larger induced coma and spherical aberration when the translation of the centre of pupil remains constant. However, for a myopia astigmatism correction, the induced coma and spherical aberration in profile #1 shows relatively larger RMS values than those in other profiles. Therefore, the residual higher order aberrations may be decreased by optimizing ablation profiles of transition zone, but they cannot be eliminated. In order to achieve the best visual performance, the design of ablation pattern of transition zone played a crucial role.