WorldWideScience

Sample records for human intestinal transit

  1. The Effect of Sex and Age on Small Intestinal Transit Times in Humans.

    Science.gov (United States)

    Fischer, Monika; Fadda, Hala M

    2016-02-01

    This study utilizes a novel approach of small bowel video capsule endoscopy for investigating the influence of sex and age on small intestinal transit times (SITT) in humans. A total of 81 outpatients undergoing investigations with the small bowel video capsule endoscope (SB-VCE) and meeting inclusion criteria were included in this study. Following an overnight fast, patients swallowed the SB-VCE with a glass of water. SITT were calculated from the first duodenal image to the first cecal image. This study showed that the SB-VCE provides accurate and reliable measurements of SITT under real-life conditions. A large inter-individual variability in SITT was observed, with times ranging from 50 to 460 min. This variability can have implications on drug absorption and bioavailability. The median SITT were 219 min for females and 191 min for males. Although SITT were 28 min longer in females than males, this difference was not found to be statistically significant (p = 0.66). No correlation was found between age and SITT (Pearson correlation coefficient 0.19). Therefore, any drug bioavailability differences of modified release dosage preparations that are observed between adult patient groups of different age or sex are unlikely to be attributable to SITT. PMID:26308649

  2. Shiga Toxin Interaction with Human Intestinal Epithelium

    OpenAIRE

    Stephanie Schüller

    2011-01-01

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

  3. Microbial functionality in the human intestinal tract

    NARCIS (Netherlands)

    Salonen, A.; Palva, A.; Vos, de W.M.

    2009-01-01

    The extent of metabolic interactions between symbiotic intestinal microbes and the human host, and their system-wide effects on the host physiology are beginning to be understood. The metabolic capacity encoded by the intestinal microbiome significantly extends that of the host, making many of man's

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

    OpenAIRE

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

    2007-01-01

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

  5. Human intestinal capillariasis in Thailand

    Institute of Scientific and Technical Information of China (English)

    Prasert Saichua; Choosak Nithikathkul; Natthawut Kaewpitoon

    2008-01-01

    Intestinal capillariasis caused by Capillaria philippinensis appeared first in the Philippines and subsequently in Thailand, Japan, Iran, Egypt and Taiwan; major outbreaks have occurred in the Philippines and Thailand. This article reviews the epidemiology, history and sources of C. philippinensis infection in Thailand. The annual epidemiological surveillance reports indicated that 82 accumulated cases of intestinal capillariasis were found in Thailand from 1994-2006. That made Thailand a Capillaria-prevalent area. Sisaket, in northeast Thailand, was the first province which has reported intestinal capillariasis. Moreover, Buri Ram presented a high prevalence of intestinal capillariasis, totaling 24 cases from 1994-2006. About half of all cases have consumed raw or undercooked fish. However, even if the numbers of the intestinal capillariasis cases in Thailand is reduced, C. philippinensis infection cases are still reported. The improvement of personal hygiene, specifically avoiding consumption of undercooked fish and promoting a health education campaign are required. These strategies may minimize or eliminate C. philippinensis infection in Thailand.

  6. A deconvolution technique for processing small intestinal transit data

    International Nuclear Information System (INIS)

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

  7. A deconvolution technique for processing small intestinal transit data

    Energy Technology Data Exchange (ETDEWEB)

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

    1999-03-01

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

  8. Tipping elements in the human intestinal ecosystem

    OpenAIRE

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

    2014-01-01

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

  9. Icariin Metabolism by Human Intestinal Microflora.

    Science.gov (United States)

    Wu, Hailong; Kim, Mihyang; Han, Jaehong

    2016-01-01

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

  10. Faecalibacterium prausnitzii and human intestinal health

    NARCIS (Netherlands)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    1984-12-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1984-12-01

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

  13. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Q.; Pantzar, N.; Jeppson, B.; Westroem, B.R.; Karlsson, B.W. [Univ. of Lund (Sweden)

    1994-11-01

    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 {sup 51}Cr-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 {sup 51}Cr-EDTA. In comparison with the sham-operated rats, septic rats had higher {sup 51}Cr-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.

  15. 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.

  16. Diversity of human small intestinal Streptococcus and Veillonella populations

    NARCIS (Netherlands)

    Bogert, B. van den; Erkus, O.; Boekhorst, J.; Goffau, M. de; Smid, E.J.; Zoetendal, E.G.; Kleerebezem, M.

    2013-01-01

    Molecular and cultivation approaches were employed to study the phylogenetic richness and temporal dynamics of Streptococcus and Veillonella populations in the small intestine. Microbial profiling of human small intestinal samples collected from four ileostomy subjects at four time points displayed

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

    Directory of Open Access Journals (Sweden)

    Nicholas Lahar

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

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

    Science.gov (United States)

    Vidal-Neira, L; León-Barúa, R

    1981-01-01

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

  19. Alternative Functional In Vitro Models of Human Intestinal Epithelia

    Directory of Open Access Journals (Sweden)

    Amanda L Kauffman

    2013-07-01

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

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

    Directory of Open Access Journals (Sweden)

    Tae Hyun Kang

    2016-06-01

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

  1. Human intestinal microbial metabolism of naringin.

    Science.gov (United States)

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

    2015-09-01

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

  2. The human intestinal B-cell response.

    Science.gov (United States)

    Spencer, J; Sollid, L M

    2016-09-01

    The intestinal immune system is chronically challenged by a huge plethora of antigens derived from the lumen. B-cell responses in organized gut-associated lymphoid tissues and regional lymph nodes that are driven chronically by gut antigens generate the largest population of antibody-producing cells in the body: the gut lamina propria plasma cells. Although animal studies have provided insights into mechanisms that underpin this dynamic process, some very fundamental differences in this system appear to exist between species. Importantly, this prevents extrapolation from mice to humans to inform translational research questions. Therefore, in this review we will describe the structures and mechanisms involved in the propagation, dissemination, and regulation of this immense plasma cell population in man. Uniquely, we will seek our evidence exclusively from studies of human cells and tissues. PMID:27461177

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

    Directory of Open Access Journals (Sweden)

    Camille Mayeur

    2016-03-01

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

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

    Science.gov (United States)

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

    2015-10-12

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

  5. 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.

  6. 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

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

    OpenAIRE

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

    1997-01-01

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

  8. 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.

  9. 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

  10. 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; Rumessen, Jüri J

    2006-01-01

    Although malabsorption of small amounts of fructose-sorbitol mixtures occurs frequently in healthy humans, insights into their effects on gastrointestinal motility are poor. The present study addresses the hypothesis that malabsorption of a fructose-sorbitol challenge changes the small intestinal...... than after ingestion of glucose (P = 0.0128). In healthy humans, malabsorption of small amounts of a fructose-sorbitol mixture accelerates small bowel transit....

  11. Intestinal and hepatic metabolism of glutamine and citrulline in humans.

    Science.gov (United States)

    van de Poll, Marcel C G; Ligthart-Melis, Gerdien C; Boelens, Petra G; Deutz, Nicolaas E P; van Leeuwen, Paul A M; Dejong, Cornelis H C

    2007-06-01

    Glutamine plays an important role in nitrogen homeostasis and intestinal substrate supply. It has been suggested that glutamine is a precursor for arginine through an intestinal-renal pathway involving inter-organ transport of citrulline. The importance of intestinal glutamine metabolism for endogenous arginine synthesis in humans, however, has remained unaddressed. The aim of this study was to investigate the intestinal conversion of glutamine to citrulline and the effect of the liver on splanchnic citrulline metabolism in humans. Eight patients undergoing upper gastrointestinal surgery received a primed continuous intravenous infusion of [2-(15)N]glutamine and [ureido-(13)C-(2)H(2)]citrulline. Arterial, portal venous and hepatic venous blood were sampled and portal and hepatic blood flows were measured. Organ specific amino acid uptake (disposal), production and net balance, as well as whole body rates of plasma appearance were calculated according to established methods. The intestines consumed glutamine at a rate that was dependent on glutamine supply. Approximately 13% of glutamine taken up by the intestines was converted to citrulline. Quantitatively glutamine was the only important precursor for intestinal citrulline release. Both glutamine and citrulline were consumed and produced by the liver, but net hepatic flux of both amino acids was not significantly different from zero. Plasma glutamine was the precursor of 80% of plasma citrulline and plasma citrulline in turn was the precursor of 10% of plasma arginine. In conclusion, glutamine is an important precursor for the synthesis of arginine after intestinal conversion to citrulline in humans.

  12. Major transitions in human evolution

    Science.gov (United States)

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

    2016-01-01

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

  13. Major transitions in human evolution.

    Science.gov (United States)

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

    2016-07-01

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

  14. Drug Transport and Metabolism in Rat and Human Intestine

    OpenAIRE

    Berggren, Sofia

    2006-01-01

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

  15. Understanding drug resistance in human intestinal protozoa.

    Science.gov (United States)

    El-Taweel, Hend Aly

    2015-05-01

    Infections with intestinal protozoa continue to be a major health problem in many areas of the world. The widespread use of a limited number of therapeutic agents for their management and control raises concerns about development of drug resistance. Generally, the use of any antimicrobial agent should be accompanied by meticulous monitoring of its efficacy and measures to minimize resistance formation. Evidence for the occurrence of drug resistance in different intestinal protozoa comes from case studies and clinical trials, sometimes with a limited number of patients. Large-scale field-based assessment of drug resistance and drug sensitivity testing of clinical isolates are needed. Furthermore, the association of drug resistance with certain geographic isolates or genotypes deserves consideration. Drug resistance has been triggered in vitro and has been linked to modification of pyruvate:ferredoxin oxidoreductase, nitroreductases, antioxidant defense, or cytoskeletal system. Further mechanistic studies will have important implications in the development of second generation therapeutic agents.

  16. Intestine.

    Science.gov (United States)

    Smith, J M; Skeans, M A; Horslen, S P; Edwards, E B; Harper, A M; Snyder, J J; Israni, A K; Kasiske, B L

    2016-01-01

    Intestine and intestine-liver transplant plays an important role in the treatment of intestinal failure, despite decreased morbidity associated with parenteral nutrition. In 2014, 210 new patients were added to the intestine transplant waiting list. Among prevalent patients on the list at the end of 2014, 65% were waiting for an intestine transplant and 35% were waiting for an intestine-liver transplant. The pretransplant mortality rate decreased dramatically over time for all age groups. Pretransplant mortality was highest for adult candidates, at 22.1 per 100 waitlist years compared with less than 3 per 100 waitlist years for pediatric candidates, and notably higher for candidates for intestine-liver transplant than for candidates for intestine transplant without a liver. Numbers of intestine transplants without a liver increased from a low of 51 in 2013 to 67 in 2014. Intestine-liver transplants increased from a low of 44 in 2012 to 72 in 2014. Short-gut syndrome (congenital and other) was the main cause of disease leading to both intestine and intestine-liver transplant. Graft survival improved over the past decade. Patient survival was lowest for adult intestine-liver recipients and highest for pediatric intestine recipients.

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

    NARCIS (Netherlands)

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

    2008-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    1996-06-01

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

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

    NARCIS (Netherlands)

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

    2007-01-01

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

  1. In silico modelling of the human intestinal microflora

    NARCIS (Netherlands)

    Kamerman, DJ; Wilkinson, MHF; Sloot, P; Tan, CJK; Dongarra, JJ; Hoekstra, AG

    2002-01-01

    The ecology of the human intestinal microflora and its interaction with the host are poorly understood. Though more and more data are being acquired, in part using modern molecular methods, development of a quantitative theory has not kept pace with this development. This is in part due to the compl

  2. In Silico Modelling of the Human Intestinal Microflora

    NARCIS (Netherlands)

    Kamerman, Derk Jan; Wilkinson, Michael H.F.

    2002-01-01

    The ecology of the human intestinal microflora and its interaction with the host are poorly understood. Though more and more data are being acquired, in part using modern molecular methods, development of a quantitative theory has not kept pace with this development. This is in part due to the compl

  3. Methane and hydrogen production by human intestinal anaerobic bacteria.

    Science.gov (United States)

    McKay, L F; Holbrook, W P; Eastwood, M A

    1982-06-01

    The gas above liquid cultures of a variety of human intestinal anaerobic bacteria was sampled and analysed by headspace gas chromatography. Hydrogen production was greatest with strains of the genus Clostridium, intermediate with anaerobic cocci and least with Bacteroides sp. Very few strains produced methane although small amounts were detected with one strain of B. thetaiotaomicron, C. perfringens and C. histolyticum. There may be a relationship between these anaerobic bacteria and several gastrointestinal disorders in which there is a build up of hydrogen or methane in the intestines.

  4. Molecular epidemiology of human intestinal amoebas in iran.

    Science.gov (United States)

    Hooshyar, H; Rostamkhani, P; Rezaian, M

    2012-01-01

    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.

  5. 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.

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

    Science.gov (United States)

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

    2008-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Alyssa D Flora

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2007-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

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

    OpenAIRE

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

    1997-01-01

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

  11. Development of the human infant intestinal microbiota.

    Directory of Open Access Journals (Sweden)

    Chana Palmer

    2007-07-01

    Full Text Available Almost immediately after a human being is born, so too is a new microbial ecosystem, one that resides in that person's gastrointestinal tract. Although it is a universal and integral part of human biology, the temporal progression of this process, the sources of the microbes that make up the ecosystem, how and why it varies from one infant to another, and how the composition of this ecosystem influences human physiology, development, and disease are still poorly understood. As a step toward systematically investigating these questions, we designed a microarray to detect and quantitate the small subunit ribosomal RNA (SSU rRNA gene sequences of most currently recognized species and taxonomic groups of bacteria. We used this microarray, along with sequencing of cloned libraries of PCR-amplified SSU rDNA, to profile the microbial communities in an average of 26 stool samples each from 14 healthy, full-term human infants, including a pair of dizygotic twins, beginning with the first stool after birth and continuing at defined intervals throughout the first year of life. To investigate possible origins of the infant microbiota, we also profiled vaginal and milk samples from most of the mothers, and stool samples from all of the mothers, most of the fathers, and two siblings. The composition and temporal patterns of the microbial communities varied widely from baby to baby. Despite considerable temporal variation, the distinct features of each baby's microbial community were recognizable for intervals of weeks to months. The strikingly parallel temporal patterns of the twins suggested that incidental environmental exposures play a major role in determining the distinctive characteristics of the microbial community in each baby. By the end of the first year of life, the idiosyncratic microbial ecosystems in each baby, although still distinct, had converged toward a profile characteristic of the adult gastrointestinal tract.

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

    OpenAIRE

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

    2015-01-01

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

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

    Science.gov (United States)

    Mulè, Flavia; Amato, Antonella; Serio, Rosa

    2010-01-01

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

  14. Survivability of Kudoa septempunctata in human intestinal conditions.

    Science.gov (United States)

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

    2016-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Paola Andrea Gómez Buitrago

    2015-10-01

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

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

    Science.gov (United States)

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

    2016-07-28

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

  17. Vasoactive intestinal peptide signaling axis in human leukemia

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Troncon L.E.A.

    2000-01-01

    Full Text Available The effects of a fraction (T1 of Tityus serrulatus scorpion venom prepared by gel filtration on gastric emptying and small intestinal transit were investigated in male Wistar rats. Fasted animals were anesthetized with urethane, submitted to tracheal intubation and right jugular vein cannulation. Scorpion toxin (250 µg/kg or saline was injected iv and 1 h later a bolus of saline (1.0 ml/100 g labeled with 99m technetium-phytate (10 MBq was administered by gavage. After 15 min, animals were sacrificed and the radioactivity remaining in the stomach was determined. Intestinal transit was evaluated by instillation of a technetium-labeled saline bolus (1.0 ml through a cannula previously implanted in the duodenum. After 60 min, the progression of the marker throughout 7 consecutive gut segments was estimated by the geometric center method. Gastric retention of the liquid test meal in rats injected with scorpion toxin (median: 88%; range: 52-95% was significantly higher (P<0.02 than in controls (54%; 21-76%, an effect which was not modified by gastric secretion blockade with ranitidine. The progression of the isotope marker throughout the small intestine was significantly slower (P<0.05 in rats treated with toxin (1.2; 1.0-2.5 than in control animals (2.3; 1.0-3.2. Inhibition of both gastric emptying and intestinal transit in rats injected with scorpion toxin suggests an increased resistance to aboral flow, which might be caused by abnormal neurotransmitter release or by the local effects of venom on smooth muscle cells.

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

    Directory of Open Access Journals (Sweden)

    Michihiro Yoshida

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

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

    DEFF Research Database (Denmark)

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

    2005-01-01

    The intestinal alkaline phosphatase gene (ALPI) encodes a digestive brush-border enzyme, which is highly upregulated during small intestinal epithelial cell differentiation. To identify new putative promoter motifs responsible for the regulation of ALPI expression during differentiation of the en......The intestinal alkaline phosphatase gene (ALPI) encodes a digestive brush-border enzyme, which is highly upregulated during small intestinal epithelial cell differentiation. To identify new putative promoter motifs responsible for the regulation of ALPI expression during differentiation...... of the enterocytes, we have conducted a computer-assisted cis-element search of the proximal human ALPI promoter sequence. A putative recognition site for the transcription factor hepatocyte nuclear factor (HNF)-4 was predicted at the positions from -94 to -82 in relation to the translational start site. The ability...

  1. 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

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

    DEFF Research Database (Denmark)

    Madsen, Jan Lysgård; Fuglsang, Stefan; Graff, J

    2006-01-01

    : 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...... 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....

  3. The predominant cholecystokinin in human plasma and intestine is cholecystokinin-33

    DEFF Research Database (Denmark)

    Rehfeld, J F; Sun, G; Christensen, T;

    2001-01-01

    Cholecystokinin (CCK) occurs in multiple molecular forms; the major ones are CCK-58, -33, -22, and -8. Their relative abundance in human plasma and intestine, however, is debated. To settle the issue, extracts of intestinal biopsies and plasma from 10 human subjects have been examined...... is the second most abundant ( approximately 34% and 30%, respectively). In contrast, CCK-58 is less abundant in human intestines ( approximately 18%) and plasma ( approximately 11%). Its predominance in feline intestines, however, was confirmed. Hence, the results show a significant species variation...

  4. Scintigraphic small intestinal transit time and defaecography in patients with J-pouch

    DEFF Research Database (Denmark)

    Kjær, Mie Dilling; Simonsen, Jane Angel; Hvidsten, Svend;

    2015-01-01

    Objective methods for examination of pouch function are warranted for a better understanding of the functional result and treatment of dysfunction. The objective of this study was to evaluate the results of scintigraphic intestinal transit time and defaecography compared to the results of pouch...... mucosal condition was evaluated by endoscopy and histology. Median transit time was 189 min (105–365). Median ejection fraction at defaecography (EF) was 49% (3–77) and 62% (17–98) after first and second defecation. Median pouch volume was 223 mL (100–360). A median daily stool frequency of nine (4......–25) was reported and three (14%) patients suffered from daytime incontinence. No patients had symptomatic or endoscopic pouchitis; however, the histology showed unspecific inflammation in 19 (90%) patients. There was no correlation between transit time, evacuation fraction (EF) and pouch function in univariate...

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

    Directory of Open Access Journals (Sweden)

    Bobyr V.V.

    2015-05-01

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

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

    OpenAIRE

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2015-04-15

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

  8. 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...... in respecting the rights of the accused arose. A group of paralegals known as the "Corps of Judicial Defenders" was thus relied upon as to provide legal assistance for genocide suspects, but also for civil parties. This paper describes the work of these paralegals relating to the transitional trials, and, more...

  9. Common occurrence of antibacterial agents in human intestinal microbiota

    Directory of Open Access Journals (Sweden)

    Fatima eDrissi

    2015-05-01

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

  10. Community and genomic analysis of the human small intestine microbiota

    NARCIS (Netherlands)

    Bogert, van den B.

    2013-01-01

      Our intestinal tract is densely populated by different microbes, collectively called microbiota, of which the majority are bacteria. Research focusing on the intestinal microbiota often use fecal samples as a representative of the bacteria that inhabit the end of the large intestine. These s

  11. 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 Κ- and δ-opioid receptor activity with a smaller µ-opioid receptor component. Both mouse and guinea pig tissue were sensitive to casoxin 4 antagonism of morphine inhibition of contraction. In contrast to naloxone, relatively high oral doses of the µ-opioid receptor antagonists

  12. Advanced approaches to characterize the human intestinal microbiota by computational meta-analysis

    NARCIS (Netherlands)

    Nikkilä, J.; Vos, de W.M.

    2010-01-01

    GOALS: We describe advanced approaches for the computational meta-analysis of a collection of independent studies, including over 1000 phylogenetic array datasets, as a means to characterize the variability of human intestinal microbiota. BACKGROUND: The human intestinal microbiota is a complex micr

  13. Ultrastructure of interstitial cells of Cajal in circular muscle of human small intestine

    DEFF Research Database (Denmark)

    Rumessen, J J; Mikkelsen, H B; Qvortrup, Klaus;

    1993-01-01

    Interstitial cells of Cajal (ICC) may be important regulatory cells in gut muscle layers. This study examined ICC within the circular muscle of human small intestine.......Interstitial cells of Cajal (ICC) may be important regulatory cells in gut muscle layers. This study examined ICC within the circular muscle of human small intestine....

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

    Directory of Open Access Journals (Sweden)

    Mie Dilling Kjaer

    2015-10-01

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

  15. 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; Rumessen, Jüri J

    2006-01-01

    Although malabsorption of small amounts of fructose-sorbitol mixtures occurs frequently in healthy humans, insights into their effects on gastrointestinal motility are poor. The present study addresses the hypothesis that malabsorption of a fructose-sorbitol challenge changes the small intestinal...... 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...

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

    Directory of Open Access Journals (Sweden)

    Z. Liu

    2010-05-01

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

  17. Functional Metagenomic Investigations of the Human Intestinal Microbiota

    DEFF Research Database (Denmark)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2009-07-01

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

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

    Science.gov (United States)

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

    2010-07-01

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

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

    Science.gov (United States)

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

    2015-09-01

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

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

    Science.gov (United States)

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

  2. 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.

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

    OpenAIRE

    Amor, Ben, K.

    2004-01-01

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

  4. Age-related human small intestine methylation: evidence for stem cell niches

    Directory of Open Access Journals (Sweden)

    Tavaré Simon

    2005-06-01

    Full Text Available Abstract Background The small intestine is constructed of many crypts and villi, and mouse studies suggest that each crypt contains multiple stem cells. Very little is known about human small intestines because mouse fate mapping strategies are impractical in humans. However, it is theoretically possible that stem cell histories are inherently written within their genomes. Genomes appear to record histories (as exemplified by use of molecular clocks, and therefore it may be possible to reconstruct somatic cell dynamics from somatic cell errors. Recent human colon studies suggest that random somatic epigenetic errors record stem cell histories (ancestry and total numbers of divisions. Potentially age-related methylation also occurs in human small intestines, which would allow characterization of their stem cells and comparisons with the colon. Methods Methylation patterns in individual crypts from 13 small intestines (17 to 78 years old were measured by bisulfite sequencing. The methylation patterns were analyzed by a quantitative model to distinguish between immortal or niche stem cell lineages. Results Age-related methylation was observed in the human small intestines. Crypt methylation patterns were more consistent with stem cell niches than immortal stem cell lineages. Human large and small intestine crypt niches appeared to have similar stem cell dynamics, but relatively less methylation accumulated with age in the small intestines. There were no apparent stem cell differences between the duodenum and ileum, and stem cell survival did not appear to decline with aging. Conclusion Crypt niches containing multiple stem cells appear to maintain human small intestines. Crypt niches appear similar in the colon and small intestine, and the small intestinal stem cell mitotic rate is the same as or perhaps slower than that of the colon. Although further studies are needed, age-related methylation appears to record somatic cell histories, and a

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

    NARCIS (Netherlands)

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

    2006-01-01

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

  6. Human and simulated intestinal fluids as solvent systems to explore food effects on intestinal solubility and permeability.

    Science.gov (United States)

    Stappaerts, Jef; Wuyts, Benjamin; Tack, Jan; Annaert, Pieter; Augustijns, Patrick

    2014-10-15

    The mixed micelles and vesicles present in the intraluminal environment of the postprandial state exhibit suitable solubilizing capacities for lipophilic drugs. This increase in solubility, however, is accompanied by a decrease in the free fraction caused by micellar entrapment of these lipophilic compounds. In this study, both simulated and aspirated human intestinal fluids of fasted and fed state conditions were used to evaluate the influence of food on the intestinal disposition of a series of structurally related β-blockers, with varying logP values. Using the in situ intestinal perfusion technique with mesenteric blood sampling in rats, it was demonstrated that fed state conditions significantly decreased the absorptive flux of the more lipophilic compounds metoprolol, propranolol and carvedilol, whereas the influence on the flux of the hydrophilic β-blocker atenolol was limited. The solubility of BCS class II compound carvedilol was found to increase significantly in simulated and aspirated media of the fed state. Intestinal perfusions using intestinal media saturated with carvedilol, revealed a higher flux in the fasted state compared to the fed state, despite the higher solubility in the fed state. This study underscores the importance of addressing the complex nature of the behavior of compounds in the intraluminal environment in fasted and fed state conditions. Moreover, our data point out the value of studying the effect of food on both solubility and permeability using biorelevant experimental conditions.

  7. Human intestinal dendritic cells as controllers of mucosal immunity

    Directory of Open Access Journals (Sweden)

    David Bernardo

    2013-06-01

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

  8. Human intestinal dendritic cells as controllers of mucosal immunity.

    Science.gov (United States)

    Bernardo, David

    2013-01-01

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

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

    OpenAIRE

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

    2003-01-01

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

  10. Microbial communities in the human small intestine: coupling diversity to metagenomics.

    Science.gov (United States)

    Booijink, Carien C G M; Zoetendal, Erwin G; Kleerebezem, Michiel; de Vos, Willem M

    2007-06-01

    The gastrointestinal tract is the main site where the conversion and absorption of food components takes place. The host-derived physiological processes and the residing microorganisms, especially in the small intestine, contribute to this nutrient supply. To circumvent sampling problems of the small intestine, several model systems have been developed to study microbial diversity and functionality in the small intestine. In addition, metagenomics offers novel possibilities to gain insight into the genetic potential and functional properties of these microbial communities. Here, an overview is presented of the most recent insights into the diversity and functionality of the microorganisms in the human gastrointestinal tract, with a focus on the small intestine.

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

    DEFF Research Database (Denmark)

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

    2003-01-01

    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...

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  13. 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.

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

    Directory of Open Access Journals (Sweden)

    Gondim F. de-A.A.

    1998-01-01

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

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

    Science.gov (United States)

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

    2015-09-01

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

  16. Involvement of Concentrative Nucleoside Transporter 1 in Intestinal Absorption of Trifluridine Using Human Small Intestinal Epithelial Cells.

    Science.gov (United States)

    Takahashi, Koichi; Yoshisue, Kunihiro; Chiba, Masato; Nakanishi, Takeo; Tamai, Ikumi

    2015-09-01

    TAS-102, which is effective for refractory metastatic colorectal cancer, is a combination drug of anticancer trifluridine (FTD; which is derived from pyrimidine nucleoside) and FTD-metabolizing enzyme inhibitor tipiracil hydrochloride (TPI) at a molecular ratio of 1:0.5. To evaluate the intestinal absorption mechanism of FTD, the uptake and transcellular transport of FTD by human small intestinal epithelial cell (HIEC) monolayer as a model of human intestinal epithelial cells was investigated. The uptake and membrane permeability of FTD by HIEC monolayers were saturable, Na(+) -dependent, and inhibited by nucleosides. These transport characteristics are mostly comparable with those of concentrative nucleoside transporters (CNTs). Moreover, the uptake of FTD by CNT1-expressing Xenopus oocytes was the highest among human CNT transporters. The obtained Km and Vmax values of FTD by CNT1 were 69.0 μM and 516 pmol/oocyte/30 min, respectively. The transcellular transport of FTD by Caco-2 cells, where CNT1 is heterologously expressed, from apical to basolateral side was greater than that by Mock cells. In conclusion, these results demonstrated that FTD exhibits high oral absorption by the contribution of human CNT1.

  17. Production of human intestinal trefoil factor in Pichia pastoris

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  18. Clinical features of human intestinal capillariasis in Taiwan

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2016-07-01

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

  1. Bile Salt Micelles and Phospholipid Vesicles Present in Simulated and Human Intestinal Fluids

    DEFF Research Database (Denmark)

    Elvang, Philipp A; Hinna, Askell H; Brouwers, Joachim;

    2016-01-01

    Knowledge about colloidal assemblies present in human intestinal fluids (HIFs), such as bile salt micelles and phospholipid vesicles, is regarded of importance for a better understanding of the in vivo dissolution and absorption behavior of poorly soluble drugs (Biopharmaceutics Classification...

  2. The metabolic profile of acteoside produced by human or rat intestinal bacteria or intestinal enzyme in vitro employed UPLC-Q-TOF-MS.

    Science.gov (United States)

    Cui, Qingling; Pan, Yingni; Xu, Xiaotong; Zhang, Wenjie; Wu, Xiao; Qu, Shouhe; Liu, Xiaoqiu

    2016-03-01

    Acteoside, the main and representative phenylethanoid glycosides of Herba Cistanches, possesses wide bioactivities but low oral bioavailability. It may serve as the prodrug and be converted into the active forms in gastrointestinal tract, which mainly occurred in intestinal tract composed of intestinal bacteria and intestinal enzyme. Intestinal bacteria, a new drug target, take a significant role on exerting pharmacological effects of drugs by oral administration. In this paper, acteoside was incubated with human or rat intestinal bacteria or rat intestinal enzyme for 36 h to seek metabolites responsible for pharmacodynamics. The samples were analyzed by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Besides the parent compound, 14 metabolites were detected and identified based on their retention times and fragmentation patterns in their MS spectra including 8 degradation metabolites, 2 isomers in intestinal bacteria and intestinal enzyme samples and 4 parent metabolites only found in intestinal enzymes. The metabolic pathway of acteoside was thus proposed. Identification of these metabolites of acteoside by the intestinal bacteria or intestinal enzyme gave an insight to clarify pharmacological mechanism of traditional Chinese medicines and identify the real active molecules.

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

    OpenAIRE

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

    2016-01-01

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

  4. SHP-2 Mediates Cryptosporidium parvum Infectivity in Human Intestinal Epithelial Cells

    OpenAIRE

    Varughese, Eunice A.; Susan Kasper; Anneken, Emily M.; Yadav, Jagjit S.

    2015-01-01

    The parasite, Cryptosporidium parvum, induces human gastroenteritis through infection of host epithelial cells in the small intestine. During the initial stage of infection, C. parvum is reported to engage host mechanisms at the host cell-parasite interface to form a parasitophorous vacuole. We determined that upon infection, the larger molecular weight proteins in human small intestinal epithelial host cells (FHs 74 Int) appeared to globally undergo tyrosine dephosphorylation. In parallel, e...

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

    OpenAIRE

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

    2015-01-01

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

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

    Science.gov (United States)

    Miguel-Aliaga, Irene

    2012-08-01

    The increasingly recognized role of gastrointestinal signals in the regulation of food intake, insulin production and peripheral nutrient storage has prompted a surge of interest in studying how the gastrointestinal tract senses and responds to nutritional information. Identification of metabolically important intestinal nutrient sensors could provide potential new drug targets for the treatment of diabetes, obesity and gastrointestinal disorders. From a more fundamental perspective, the study of intestinal chemosensation is revealing novel, non-neuronal modes of communication involving differentiated epithelial cells. It is also identifying signalling mechanisms downstream of not only canonical receptors but also nutrient transporters, thereby supporting a chemosensory role for "transceptors" in the intestine. This review describes known and proposed mechanisms of intestinal carbohydrate, protein and lipid sensing, best characterized in mammalian systems. It also highlights the potential of invertebrate model systems such as C. elegans and Drosophila melanogaster by summarizing known examples of molecular evolutionary conservation. Recently developed genetic tools in Drosophila, an emerging model system for the study of physiology and metabolism, allow the temporal, spatial and high-throughput manipulation of putative intestinal sensors. Hence, fruit flies may prove particularly suited to the study of the link between intestinal nutrient sensing and metabolic homeostasis. PMID:22248674

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

    Science.gov (United States)

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

    2016-06-01

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

  8. Vasoactive intestinal peptide (VIP) inhibits human renal cell carcinoma proliferation.

    Science.gov (United States)

    Vacas, Eva; Fernández-Martínez, Ana B; Bajo, Ana M; Sánchez-Chapado, Manuel; Schally, Andrew V; Prieto, Juan C; Carmena, María J

    2012-10-01

    Clear renal cell carcinoma (cRCC) is an aggressive and fatal neoplasm. The present work was undertaken to investigate the antiproliferative potential of vasoactive intestinal peptide (VIP) exposure on non-tumoral (HK2) and tumoral (A498, cRCC) human proximal tubular epithelial cell lines. Reverse transcription and semiquantitative PCR was used at the VIP mRNA level whereas enzyme immunoanalysis was performed at the protein level. Both renal cell lines expressed VIP as well as VIP/pituitary adenylate cyclase-activating peptide (VPAC) receptors whereas only HK2 cells expressed formyl peptide receptor-like 1 (FPRL-1). Receptors were functional, as shown by VIP stimulation of adenylyl cyclase activity. Treatment with 0.1μM VIP (24h) inhibited proliferation of A498 but not HK2 cells as based on a reduction in the incorporation of [(3)H]-thymidine and BrdU (5'-Br-2'-deoxyuridine), PCNA (proliferating-cell nuclear antigen) expression and STAT3 (signal transducer and activator of transcription 3) expression and activation. VPAC(1)-receptor participation was established using JV-1-53 antagonist and siRNA transfection. Growth-inhibitory response to VIP was related to the cyclic adenosine monophosphate (cAMP)/exchange protein directly activated by cAMP (EPAC)/phosphoinositide 3-kinase (PI3-K) signaling systems as shown by studies on adenylate cyclase stimulation, and using the EPAC-specific compound 8CPT-2Me-cAMP and specific kinase inhibitors such as H89, wortmannin and PD98059. The efficacy of VIP on the prevention of tumor progression was confirmed in vivo using xenografted athymic mouse. These actions support a potential role of this peptide and its agonists in new therapies for cRCC.

  9. Human intestine luminal ACE2 and amino acid transporter expression increased by ACE-inhibitors.

    Science.gov (United States)

    Vuille-dit-Bille, Raphael N; Camargo, Simone M; Emmenegger, Luca; Sasse, Tom; Kummer, Eva; Jando, Julia; Hamie, Qeumars M; Meier, Chantal F; Hunziker, Schirin; Forras-Kaufmann, Zsofia; Kuyumcu, Sena; Fox, Mark; Schwizer, Werner; Fried, Michael; Lindenmeyer, Maja; Götze, Oliver; Verrey, François

    2015-04-01

    Sodium-dependent neutral amino acid transporter B(0)AT1 (SLC6A19) and imino acid (proline) transporter SIT1 (SLC6A20) are expressed at the luminal membrane of small intestine enterocytes and proximal tubule kidney cells where they exert key functions for amino acid (re)absorption as documented by their role in Hartnup disorder and iminoglycinuria, respectively. Expression of B(0)AT1 was shown in rodent intestine to depend on the presence of the carboxypeptidase angiotensin-converting enzyme 2 (ACE2). This enzyme belongs to the renin-angiotensin system and its expression is induced by treatment with ACE-inhibitors (ACEIs) or angiotensin II AT1 receptor blockers (ARBs) in many rodent tissues. We show here in the Xenopus laevis oocyte expression system that human ACE2 also functionally interacts with SIT1. To investigate in human intestine the potential effect of ACEIs or ARBs on ACE2, we analysed intestinal biopsies taken during routine gastroduodenoscopy and ileocolonoscopy from 46 patients of which 9 were under ACEI and 13 ARB treatment. Analysis of transcript expression by real-time PCR and of proteins by immunofluorescence showed a co-localization of SIT1 and B(0)AT1 with ACE2 in the brush-border membrane of human small intestine enterocytes and a distinct axial expression pattern of the tested gene products along the intestine. Patients treated with ACEIs displayed in comparison with untreated controls increased intestinal mRNA levels of ACE2, peptide transporter PEPT1 (SLC15A1) and AA transporters B(0)AT1 and PAT1 (SLC36A1). This study unravels in human intestine the localization and distribution of intestinal transporters involved in amino acid absorption and suggests that ACEIs impact on their expression.

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

    Institute of Scientific and Technical Information of China (English)

    胡桂香; 商志才; 等

    2003-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Renes Johan

    2007-04-01

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

  12. A breakdown in communication? Understanding the effects of aging on the human small intestine epithelium.

    Science.gov (United States)

    Mabbott, Neil A

    2015-10-01

    In the intestine, a single layer of epithelial cells sealed together at their apical surfaces by tight junctions helps to prevent the luminal commensal and pathogenic micro-organisms and their toxins from entering host tissues. The intestinal epithelium also helps to maintain homoeostasis in the mucosal immune system by expressing anti-inflammatory cytokines in the steady state and inflammatory cytokines in response to pathogens. Although the function of the mucosal immune system is impaired in elderly humans, the molecular mechanisms which cause this dramatic functional decline are poorly understood. Our current understanding of the effects of aging on the physical and immunological properties of the intestinal epithelial barrier is also very limited. In this issue of Clinical Science, Man et al. provide further insight into the effects of aging on small intestinal barrier function in humans and the influence that gut luminal micro-organisms may have on it. Using human terminal ileal biopsy tissues they show that intestinal permeability to solutes, but not macromolecules, was significantly increased in the intestines of elderly humans. This was accompanied by elevated expression of the pro-inflammatory cytokine interleukin (IL)-6 which appeared to modulate claudin-2 expression and solute permeability in the epithelium. Conversely, IL-8 synthesis in response to flagellin stimulation was reduced in intestines of the elderly subjects, but was not associated with effects on Toll-like receptor 5 (TLR5) expression. These data provide an important advance in our understanding on the effects of aging on intestinal permeability and innate mucosal immune responsiveness in elderly humans.

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

    NARCIS (Netherlands)

    Veen, van der S.; Abee, T.

    2011-01-01

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

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    Several studies have shown associations between groups of intestinal bacterial or specific ratios between bacterial groups and various disease traits. Meanwhile, little is known about interactions and associations between eukaryotic and prokaryotic microorganisms in the human gut. In this work, we...... set out to investigate potential associations between common single-celled parasites such as Blastocystis spp. and Dientamoeba fragilis and intestinal bacteria. Stool DNA from patients with intestinal symptoms were selected based on being Blastocystis spp.-positive (B+)/negative (B-) and D. fragilis...

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

    DEFF Research Database (Denmark)

    Gassler, N; Newrzella, D; Böhm, C;

    2006-01-01

    BACKGROUND AND AIMS: Perturbation of differentiation of the crypt-villus axis of the human small intestine is associated with several intestinal disorders of clinical importance. At present, differentiation of small intestinal enterocytes in the crypt-villus axis is not well characterised. SUBJECTS...... the physiology of the crypt-villus architecture in human small intestine and provide new insights into pathophysiological phenomena, such as villus atrophy, which is clinically important....... genes, and vesicle/transport related genes was found. CONCLUSION: Two types of enterocytes were dissected at the molecular level, the non-absorptive enterocyte located in the upper part of crypts and the absorptive enterocyte found in the middle of villi. These data improve our knowledge about...

  16. Characterization of two cysteine proteases secreted by Blastocystis ST7, a human intestinal parasite.

    Science.gov (United States)

    Wawrzyniak, Ivan; Texier, Catherine; Poirier, Philippe; Viscogliosi, Eric; Tan, Kevin S W; Delbac, Frédéric; El Alaoui, Hicham

    2012-09-01

    Blastocystis spp. are unicellular anaerobic intestinal parasites of both humans and animals and the most prevalent ones found in human stool samples. Their association with various gastrointestinal disorders raises the questions of its pathogenicity and of the molecular mechanisms involved. Since secreted proteases are well-known to be implicated in intestinal parasite virulence, we intended to determine whether Blastocystis spp. possess such pathogenic factors. In silico analysis of the Blastocystis subtype 7 (ST7) genome sequence highlighted 22 genes coding proteases which were predicted to be secreted. We characterized the proteolytic activities in the secretory products of Blastocystis ST7 using specific protease inhibitors. Two cysteine proteases, a cathepsin B and a legumain, were identified in the parasite culture supernatant by gelatin zymographic SDS-PAGE gel and MS/MS analysis. These proteases might act on intestinal cells and disturb gut function. This work provides serious molecular candidates to link Blastocystis spp. and intestinal disorders.

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

    International Nuclear Information System (INIS)

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

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

    OpenAIRE

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

    2016-01-01

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

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

    OpenAIRE

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

    1985-01-01

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

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

    OpenAIRE

    Nord, C E; Edlund, C

    2011-01-01

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

  1. Impact of Diet on Human Intestinal Microbiota and Health

    NARCIS (Netherlands)

    Salonen, A.; Vos, de W.M.

    2014-01-01

    Our intestinal microbiota is involved in the breakdown and bioconversion of dietary and host components that are not degraded and taken up by our own digestive system. The end products generated by our microbiota fuel our enterocytes and support growth but also have signaling functions that generate

  2. Kinematics of transition during human accelerated sprinting

    Directory of Open Access Journals (Sweden)

    Ryu Nagahara

    2014-07-01

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

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

    Directory of Open Access Journals (Sweden)

    Joshua D Rouch

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

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

    Science.gov (United States)

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

    2016-05-01

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

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

    Science.gov (United States)

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

    2016-05-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2002-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Cui Zhu

    2016-08-01

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

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

    Science.gov (United States)

    Zhu, Cui; Chen, Zhuang; Jiang, Zongyong

    2016-01-01

    Stomach and intestines are involved in the secretion of gastrointestinal fluids and the absorption of nutrients and fluids, which ensure normal gut functions. Aquaporin water channels (AQPs) represent a major transcellular route for water transport in the gastrointestinal tract. Until now, at least 11 AQPs (AQP1–11) have been found to be present in the stomach, small and large intestines. These AQPs are distributed in different cell types in the stomach and intestines, including gastric epithelial cells, gastric glands cells, absorptive epithelial cells (enterocytes), goblet cells and Paneth cells. AQP1 is abundantly distributed in the endothelial cells of the gastrointestinal tract. AQP3 and AQP4 are mainly distributed in the basolateral membrane of epithelial cells in the stomach and intestines. AQP7, AQP8, AQP10 and AQP11 are distributed in the apical of enterocytes in the small and large intestines. Although AQP-null mice displayed almost no phenotypes in gastrointestinal tracts, the alterations of the expression and localization of these AQPs have been shown to be associated with the pathology of gastrointestinal disorders, which suggests that AQPs play important roles serving as potential therapeutic targets. Therefore, this review provides an overview of the expression, localization and distribution of AQPs in the stomach, small and large intestine of human and animals. Furthermore, this review emphasizes the potential roles of AQPs in the physiology and pathophysiology of stomach and intestines. PMID:27589719

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

    Science.gov (United States)

    Zhu, Cui; Chen, Zhuang; Jiang, Zongyong

    2016-08-29

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

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

    NARCIS (Netherlands)

    Gerritsen, J.; Smidt, H.; Rijkers, G.T.; Vos, de W.M.

    2011-01-01

    The complex communities of microorganisms that colonise the human gastrointestinal tract play an important role in human health. The development of culture-independent molecular techniques has provided new insights in the composition and diversity of the intestinal microbiota. Here, we summarise the

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

    OpenAIRE

    Miguel-Aliaga, Irene

    2012-01-01

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

  12. The human milk oligosaccharide 2'-fucosyllactose augments the adaptive response to extensive intestinal.

    Science.gov (United States)

    Mezoff, Ethan A; Hawkins, Jennifer A; Ollberding, Nicholas J; Karns, Rebekah; Morrow, Ardythe L; Helmrath, Michael A

    2016-03-15

    Intestinal resection resulting in short bowel syndrome (SBS) carries a heavy burden of long-term morbidity, mortality, and cost of care, which can be attenuated with strategies that improve intestinal adaptation. SBS infants fed human milk, compared with formula, have more rapid intestinal adaptation. We tested the hypothesis that the major noncaloric human milk oligosaccharide 2'-fucosyllactose (2'-FL) contributes to the adaptive response after intestinal resection. Using a previously described murine model of intestinal adaptation, we demonstrated increased weight gain from 21 to 56 days (P < 0.001) and crypt depth at 56 days (P < 0.0095) with 2'-FL supplementation after ileocecal resection. Furthermore, 2'-FL increased small bowel luminal content microbial alpha diversity following resection (P < 0.005) and stimulated a bloom in organisms of the genus Parabacteroides (log2-fold = 4.1, P = 0.035). Finally, transcriptional analysis of the intestine revealed enriched ontologies and pathways related to antimicrobial peptides, metabolism, and energy processing. We conclude that 2'-FL supplementation following ileocecal resection increases weight gain, energy availability through microbial community modulation, and histological changes consistent with improved adaptation.

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

    Science.gov (United States)

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

    2016-08-30

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

  14. Human Intestinal Tissue with Adult Stem Cell Properties Derived from Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Ryan Forster

    2014-06-01

    Full Text Available Genetically engineered human pluripotent stem cells (hPSCs have been proposed as a source for transplantation therapies and are rapidly becoming valuable tools for human disease modeling. However, many applications are limited due to the lack of robust differentiation paradigms that allow for the isolation of defined functional tissues. Here, using an endogenous LGR5-GFP reporter, we derived adult stem cells from hPSCs that gave rise to functional human intestinal tissue comprising all major cell types of the intestine. Histological and functional analyses revealed that such human organoid cultures could be derived with high purity and with a composition and morphology similar to those of cultures obtained from human biopsies. Importantly, hPSC-derived organoids responded to the canonical signaling pathways that control self-renewal and differentiation in the adult human intestinal stem cell compartment. This adult stem cell system provides a platform for studying human intestinal disease in vitro using genetically engineered hPSCs.

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

    Science.gov (United States)

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

    2007-09-01

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

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

    Science.gov (United States)

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

    2007-09-01

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

  17. Phase transitions in models of human cooperation

    Science.gov (United States)

    Perc, Matjaž

    2016-08-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Prokop, E.K.; Caride, V.J.; Marano, A.R.; McCallum, R.

    1984-01-01

    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 (pless than or equal toNS). 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.

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

    Science.gov (United States)

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

    2004-09-01

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

  20. Activation of AMPK inhibits cholera toxin stimulated chloride secretion in human and murine intestine.

    Directory of Open Access Journals (Sweden)

    Ailín C Rogers

    Full Text Available Increased intestinal chloride secretion through chloride channels, such as the cystic fibrosis transmembrane conductance regulator (CFTR, is one of the major molecular mechanisms underlying enterotoxigenic diarrhea. It has been demonstrated in the past that the intracellular energy sensing kinase, the AMP-activated protein kinase (AMPK, can inhibit CFTR opening. We hypothesized that pharmacological activation of AMPK can abrogate the increased chloride flux through CFTR occurring during cholera toxin (CTX mediated diarrhea. Chloride efflux was measured in isolated rat colonic crypts using real-time fluorescence imaging. AICAR and metformin were used to activate AMPK in the presence of the secretagogues CTX or forskolin (FSK. In order to substantiate our findings on the whole tissue level, short-circuit current (SCC was monitored in human and murine colonic mucosa using Ussing chambers. Furthermore, fluid accumulation was measured in excised intestinal loops. CTX and forskolin (FSK significantly increased chloride efflux in isolated colonic crypts. The increase in chloride efflux could be offset by using the AMPK activators AICAR and metformin. In human and mouse mucosal sheets, CTX and FSK increased SCC. AICAR and metformin inhibited the secretagogue induced rise in SCC, thereby confirming the findings made in isolated crypts. Moreover, AICAR decreased CTX stimulated fluid accumulation in excised intestinal segments. The present study suggests that pharmacological activation of AMPK effectively reduces CTX mediated increases in intestinal chloride secretion, which is a key factor for intestinal water accumulation. AMPK activators may therefore represent a supplemental treatment strategy for acute diarrheal illness.

  1. Human intestinal flora and the induction of chronic arthritis : studies in an animal model.

    NARCIS (Netherlands)

    A.J. Severijnen

    1990-01-01

    textabstractThe etiology of rheumatoid arthritis (RA), a chronic joint inflammation, is unknown. A microbial involvement is suspected, but no particular microorganism has been incriminated. The human intestinal microflora is an abundant and continuous source of bacterial antigens and may be involved

  2. Draft Genome Sequence of Enterococcus sp. Strain HSIEG1, Isolated from the Human Small Intestine

    NARCIS (Netherlands)

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

    2013-01-01

    Enterococcus sp. strain HSIEG1 was isolated from the human small intestine. Its draft genome predicts a broad carbohydrate fermentation capability, which matches well with the observed physiological characteristics of this strain. This metabolic flexibility is expected to be of importance for surviv

  3. The mucin degrader Akkermansia muciniphila is an abundant resident of the human intestinal tract

    NARCIS (Netherlands)

    Derrien, M.M.N.; Collado, M.C.; Ben-Amor, K.; Salminen, S.; Vos, de W.M.

    2008-01-01

    A 16S rRNA-targeted probe, MUC-1437, was designed and validated in order to determine the presence and numbers of cells of Akkermansia muciniphila, a mucin degrader, in the human intestinal tract. As determined by fluorescent in situ hybridization, A. muciniphila accounted more than 1% of the total

  4. Draft Genome Sequence of Veillonella parvula HSIVP1, Isolated from the Human Small Intestine

    NARCIS (Netherlands)

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

    2013-01-01

    Veillonella species are frequently encountered commensals in the human small intestine. Here, we report the draft genome sequence of the first cultured representative from this ecosystem, Veillonella parvula strain HSIVP1. The genome is predicted to encode all the necessary enzymes required for the

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

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

    Science.gov (United States)

    Moda, Tiago L; Andricopulo, Adriano D

    2012-04-15

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

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

    Science.gov (United States)

    Moda, Tiago L; Andricopulo, Adriano D

    2012-04-15

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

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

    DEFF Research Database (Denmark)

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

    1988-01-01

    The complete primary structure (967 amino acids) of an intestinal human aminopeptidase N (EC 3.4.11.2) was deduced from the sequence of a cDNA clone. Aminopeptidase N is anchored to the microvillar membrane via an uncleaved signal for membrane insertion. A domain constituting amino acid 250-555 p...

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    Intestinal epithelial cells (IECs) regulate the absorption and secretion of anions, such as HCO3(-) or Cl(-). Bestrophin genes represent a newly identified group of calcium-activated Cl(-) channels (CaCCs). Studies have suggested that, among the four human bestrophin-family genes, bestrophin-2 (B...

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

    NARCIS (Netherlands)

    Amor, Ben K.

    2004-01-01

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

  11. mir-35 is involved in intestine cell G1/S transition and germ cell proliferation in C.elegans

    Institute of Scientific and Technical Information of China (English)

    Min Liu; Pengpeng Liu; Li Zhang; Qingchun Cai; Ge Gao; Wenxia Zhang; Dong Liu; Qichang Fan; Zuoyan Zhu

    2011-01-01

    MicroRNA (miRNA) regulates gene expression in many cellular events,yet functions of only a few miRNAs are known in C.elegans.We analyzed the function of mir-35-41 unique to the worm,and show here that mir-35 regulates the G1/S transition of intestinal cells and germ cell proliferation.Loss of mir-35 leads to a decrease of nuclei numbers in intestine and distal mitotic gonad,while re-introduction of mir-35 rescues the mutant phenotypes.Genetic analysis indicates that mir-35 may act through Rb/E2F and SCF pathways.Further bioinformatic and functional analyses demonstrate that mir-35 targets evolutionaily conserved lin-23 and gld-1.Together,our study reveals a novel function of mir-35 family in cell division regulation.

  12. Isolation and characterization of cytotoxic effector cells and antibody producing cells from human intestine.

    Science.gov (United States)

    MacDermott, R P

    1985-01-01

    We have examined the ability of intestinal and peripheral blood mononuclear cells isolated from patients with inflammatory bowel disease to mediate killing against cell line targets in spontaneous, antibody-dependent, lectin-induced, and interferon-induced cell-mediated cytotoxicity assays, as well as responsiveness in the allogeneic mixed leukocyte reaction, and effector capabilities in cell-mediated lympholysis. IMC were poor mediators of spontaneous or antibody-dependent cellular cytotoxicity with cell line cells as targets (in comparison to normal PBMC, but were capable of killing antibody coated chicken red blood cells. Although IMC were capable of responding to allogeneic cell surface antigens in the mixed leukocyte reaction, they did not exhibit effector function in cell-mediated lympholysis. Mitogenic lectins induced cell-mediated cytotoxicity by isolated intestinal mononuclear cells from controls and patients. HFIF induces cytotoxicity by control but not inflammatory bowel disease intestinal cells. Pokeweed mitogen was the lectin which induced the greatest amount of killing against human cell line targets. We therefore speculate that exogenous agents, or endogenous factors released during viral infection, could play a role in inducing cell mediated cytotoxic damage to the intestine in inflammatory bowel disease patients. In addition, the functional differences between IMC and PBMC indicate that intestinal MNC may have unique cell capabilities which must be better understood prior to the delineation of immunopathologic events in solid organ tissues. We have also examined the secretion of IgA, IgM, and IgG by isolated human IMC, human bone marrow MNC from rib specimens, and PBMC from patients with CD, UC, SLE, or Henoch-Schoenlein purpura (HSP). Control IMC exhibited high spontaneous secretion of IgA, while intestinal MNC from UC and CD patients exhibited only modest increases in IgA secretion. PBMC from patients with CD, UC, SLE, or HSP exhibited markedly

  13. Chromosomal localization of the human apolipoprotein B gene and detection of homologous RNA in monkey intestine

    Energy Technology Data Exchange (ETDEWEB)

    Deeb, S.S.; Disteche, C.; Motulsky, A.G.; Lebo, R.V.; Kan, Y.W.

    1986-01-01

    A cDNA clone of the human apolipoprotein B-100 was used as a hybridization probe to detect homologous sequences in both flow-sorted and in situ metaphase chromosomes. The results indicate that the gene encoding this protein is on the distal end of the short arm of chromosome 2 (2p23-2p24). RNA isolated from monkey small intestine contained sequences (6.5 and 18 kilobases) homologous to the cDNA of apolipoprotein B-100. These results are consistent with the hypothesis that one gene codes for both the intestinal (B-48) and the hepatic (B-100) forms.

  14. 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......-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....

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

    OpenAIRE

    Lapaque, Nicolas; Doré, Joël; Blottière, Hervé

    2015-01-01

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

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

    DEFF Research Database (Denmark)

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

    2005-01-01

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

  17. Interaction of Campylobacter spp. and human probiotics in chicken intestinal mucus.

    Science.gov (United States)

    Ganan, M; Martinez-Rodriguez, A J; Carrascosa, A V; Vesterlund, S; Salminen, S; Satokari, R

    2013-03-01

    Campylobacter is the most common cause of bacterial food-borne diarrhoeal disease throughout the world. The principal risk of human contamination is handling and consumption of contaminated poultry meat. To colonize poultry, Campylobacter adheres to and persists in the mucus layer that covers the intestinal epithelium. Inhibiting adhesion to the mucus could prevent colonization of the intestine. The aim of this study was to investigate in vitro the protective effect of defined commercial human probiotic strains on the adhesion of Campylobacter spp. to chicken intestinal mucus, in a search for alternatives to antibiotics to control this food-borne pathogen. The probiotic strains Lactobacillus rhamnosus GG and Propionibacterium freudenreichii ssp. shermanii JS and a starter culture strain Lactococcus lactis ssp. lactis adhered well to chicken intestinal mucus and were able to reduce the binding of Campylobacter spp. when the mucus was colonized with the probiotic strain before contacting the pathogen. Human-intended probiotics could be useful as prophylactics in poultry feeding for controlling Campylobacter spp. colonization. PMID:22672405

  18. Reductive dechlorination of methoxychlor and DDT by human intestinal bacterium Eubacterium limosum under anaerobic conditions.

    Science.gov (United States)

    Yim, You-Jin; Seo, Jiyoung; Kang, Su-Il; Ahn, Joong-Hoon; Hur, Hor-Gil

    2008-04-01

    Methoxychlor [1,1,1-trichloro-2,2-bis(p-methoxyphenyl)ethane], a substitute for 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT), is a compound of environmental concern because of potential long-term health risks related to its endocrine-disrupting and carcinogenic potency. In order to determine the metabolic fate of methoxychlor and DDT in the human intestinal gut, Eubacterium limosum (ATCC 8486), a strict anaerobe isolated from the human intestine that is capable of O-demethylation toward O-methylated isoflavones, was used as a model intestinal microbial organism. Under anaerobic incubation conditions, E. limosum completely transformed methoxychlor and DDT in 16 days. Based on gas chromatography-mass chromatography analyses, the metabolites produced from methoxychlor and DDT by E. limosum were confirmed to be 1,1-dichloro-2,2-bis(p-methoxyphenyl)ethane (methoxydichlor) and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethane (DDD), respectively. This study suggests that E. limosum in the human intestinal gut might be a participant in the reductive dechlorination of methoxychlor to the more antiandrogenic active methoxydichlor.

  19. Interaction of Salmonella enterica Serovar Typhimurium with Intestinal Organoids Derived from Human Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Forbester, Jessica L; Goulding, David; Vallier, Ludovic; Hannan, Nicholas; Hale, Christine; Pickard, Derek; Mukhopadhyay, Subhankar; Dougan, Gordon

    2015-07-01

    The intestinal mucosa forms the first line of defense against infections mediated by enteric pathogens such as salmonellae. Here we exploited intestinal "organoids" (iHOs) generated from human induced pluripotent stem cells (hIPSCs) to explore the interaction of Salmonella enterica serovar Typhimurium with iHOs. Imaging and RNA sequencing were used to analyze these interactions, and clear changes in transcriptional signatures were detected, including altered patterns of cytokine expression after the exposure of iHOs to bacteria. S. Typhimurium microinjected into the lumen of iHOs was able to invade the epithelial barrier, with many bacteria residing within Salmonella-containing vacuoles. An S. Typhimurium invA mutant defective in the Salmonella pathogenicity island 1 invasion apparatus was less capable of invading the iHO epithelium. Hence, we provide evidence that hIPSC-derived organoids are a promising model of the intestinal epithelium for assessing interactions with enteric pathogens.

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

    DEFF Research Database (Denmark)

    Rumessen, J J

    1994-01-01

    electron microscopical studies emphasized similarities between ICC and fibroblasts. In our early studies of ICC in the external musculature of mouse small intestine, we identified ICC by their characteristic morphology and topography, and we analyzed the relation between ICC, autonomic nerves and smooth......Interstitial cells of Cajal (ICC) were described a century ago by Ramón y Cajal a.o. as primitive neurons in the intestines. In the period 1900-1960 a large number of light microscopical studies of ICC were published, in which ICC were identified by heir characteristic morphology. After 1960...... functions (mechanoreceptive, mediating inhibitory nervous input). In spite of this possible fundamental importance for G-I motility, ICC have not been adequately described or even identified in human intestine, and hence, never included in ultrastructural studies of G-I neuropathology. This survey presents...

  1. Protein abundance of clinically relevant multidrug transporters along the entire length of the human intestine.

    Science.gov (United States)

    Drozdzik, Marek; Gröer, Christian; Penski, Jette; Lapczuk, Joanna; Ostrowski, Marek; Lai, Yurong; Prasad, Bhagwat; Unadkat, Jashvant D; Siegmund, Werner; Oswald, Stefan

    2014-10-01

    Intestinal transporters are crucial determinants in the oral absorption of many drugs. We therefore studied the mRNA expression (N = 33) and absolute protein content (N = 10) of clinically relevant transporters in healthy epithelium of the duodenum, the proximal and distal jejunum and ileum, and the ascending, transversal, descending, and sigmoidal colon of six organ donors (24-54 years). In the small intestine, the abundance of nearly all studied proteins ranged between 0.2 and 1.6 pmol/mg with the exception of those of OCT3 (intestinal segment. ABCB1, ABCG2, PEPT1, and ASBT were significantly more abundant in jejunum and ileum than in colon. In contrast to this, the level of expression of ABCC2, ABCC3, and OCT3 was found to be highest in colon. Site-dependent differences in the levels of gene and protein expression were observed for ABCB1 and ASBT. Significant correlations between mRNA and protein levels have been found for ABCG2, ASBT, OCT3, and PEPT1 in the small intestine. Our data provide further physiological pieces of the puzzle required to predict intestinal drug absorption in humans.

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

  3. 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

    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......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...... 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...

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

    Science.gov (United States)

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

    2016-01-01

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

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

    OpenAIRE

    Corpet, D. E.

    1987-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Alistair eWalsham

    2016-03-01

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

  8. Effect of bisacodyl on the structure and function of rodent and human intestine.

    Science.gov (United States)

    Saunders, D R; Sillery, J; Rachmilewitz, D; Rubin, C E; Tytgat, G N

    1977-05-01

    The effect of bisacodyl on intestinal structure and function was investigated. Net water transport was measured under steady state conditions in vivo during single pass infusions of rodent and of human intestinal segments. Each segment served as its own control. Bisacodyl inhibited water absorption in rat jejunum, ileum, and colon. The degree of inhibition was linearly related to the logarithm of the bisacodyl concentration over the range of 0.05 to 2.0 mg per 100 ml. In human jejunal segments, bisacodyl, 1 mg per 100 ml, caused net water secretion. Bisacodyl, 5 mg every 6 hr, increased ileostomy output by 15% when it was fed to 5 patients with established ileostomies. By light microscopy, bisacodyl, 2 mg per 100 ml, erased cytoplasmic and nuclear detail within surface absorptive cells of rat intestine. By electron microscopy, the involved cells contained sparse and abnormal cytoplasmic organelles and nuclei which were deficient in chromatin. These results suggest that the laxative effect of bisacodyl is related to its ability to inhibit intestinal water absorption. Reduced absorption may be secondary to changes in surface absorptive cells.

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

    Science.gov (United States)

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

    2016-03-30

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

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

    NARCIS (Netherlands)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Zhimin Wang

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

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  13. Type I collagen as an extracellular matrix for the in vitro growth of human small intestinal epithelium.

    Directory of Open Access Journals (Sweden)

    Ziyad Jabaji

    Full Text Available We previously reported in vitro maintenance and proliferation of human small intestinal epithelium using Matrigel, a proprietary basement membrane product. There are concerns over the applicability of Matrigel-based methods for future human therapies. We investigated type I collagen as an alternative for the culture of human intestinal epithelial cells.Human small intestine was procured from fresh surgical pathology specimens. Small intestinal crypts were isolated using EDTA chelation. Intestinal subepithelial myofibroblasts were isolated from a pediatric sample and expanded in vitro. After suspension in Matrigel or type I collagen gel, crypts were co-cultured above a confluent layer of myofibroblasts. Crypts were also grown in monoculture with exposure to myofibroblast conditioned media; these were subsequently sub-cultured in vitro and expanded with a 1∶2 split ratio. Cultures were assessed with light microscopy, RT-PCR, histology, and immunohistochemistry.Collagen supported viable human epithelium in vitro for at least one month in primary culture. Sub-cultured epithelium expanded through 12 passages over 60 days. Histologic sections revealed polarized columnar cells, with apical brush borders and basolaterally located nuclei. Collagen-based cultures gave rise to monolayer epithelial sheets at the gel-liquid interface, which were not observed with Matrigel. Immunohistochemical staining identified markers of differentiated intestinal epithelium and myofibroblasts. RT-PCR demonstrated expression of α-smooth muscle actin and vimentin in myofibroblasts and E-Cadherin, CDX2, villin 1, intestinal alkaline phosphatase, chromogranin A, lysozyme, and Lgr5 in epithelial cells. These markers were maintained through several passages.Type I collagen gel supports long-term in vitro maintenance and expansion of fully elaborated human intestinal epithelium. Collagen-based methods yield familiar enteroid structures as well as a new pattern of sheet

  14. 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

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

    Directory of Open Access Journals (Sweden)

    Yoichi Shimoda

    2012-01-01

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

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

    Science.gov (United States)

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

    2015-05-01

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

  17. Localisation of hyaluronan in the human intestinal wall.

    OpenAIRE

    Gerdin, B; Hällgren, R

    1991-01-01

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

  18. 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...

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

    OpenAIRE

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

    2010-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    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 liverenriched 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 subjected to his...

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

    OpenAIRE

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

    2006-01-01

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

  2. Human amniotic membrane as an intestinal patch for neomucosal growth in the rabbit model.

    Science.gov (United States)

    Barlas, M; Gökçora, H; Erekul, S; Dindar, H; Yücesan, S

    1992-05-01

    This experiment was carried out as a preliminary study, an attempt to grow new intestinal mucosa on human amniotic membrane in the terminal ileum in 37 rabbits. After ketamin sulfate anesthesia at laparatomy, 5-cm ileal defects were patched with human amniotic membrane (5 x 2 cm). These patched intestines were investigated on the first postoperative day and the 2nd, 5th, 10th, and 20th weeks corresponding to 4, 5, 5, 10, and 10 rabbits, respectively. Only three rabbits died in the early postoperative period. There was no evidence of intestinal obstruction or dilatation with barium meal. Microscopically, the neomucosa consisted of a thin layer of columnar epithelial cells at 2 weeks with more maturity of the villi and less irregularity and branching by 20 weeks. All patches were covered with neomucosa commencing at 2 weeks and covering the whole patch area by 20 weeks. This technique's advantages are the large size and the ease of the availability of the human amniotic membrane for neonates at risk without jeopardizing the neonates tissues. It is hoped that this method might be considered when neonatal material is scarce.

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

    OpenAIRE

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

    2015-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    翁幸鐾; 糜祖煌

    2011-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  6. Hot spices influence permeability of human intestinal epithelial monolayers.

    Science.gov (United States)

    Jensen-Jarolim, E; Gajdzik, L; Haberl, I; Kraft, D; Scheiner, O; Graf, J

    1998-03-01

    Indirect evidence suggests that hot spices may interact with epithelial cells of the gastrointestinal tract to modulate their transport properties. Using HCT-8 cells, a cell line from a human ileocoecal carcinoma, we studied the effects of spices on transepithelial electrical resistance (TER), permeability for fluorescein isothiocyanate (FITC)-labeled dextrans with graded molecular weight, and morphological alterations of tight junctions by immunofluorescence using an anti-ZO-1 antibody, a marker for tight junction integrity. Two different reactivity patterns were observed: paprika and cayenne pepper significantly decreased the TER and increased permeability for 10-, 20- and 40-kDa dextrans but not for -70 kDa dextrans. Simultaneously, tight junctions exhibited a discontinuous pattern. Applying extracts from black or green pepper, bay leaf or nutmeg increased the TER and macromolecular permeability remained low. Immunofluorescence ZO-1 staining was preserved. In accordance with the above findings, capsaicin transiently reduced resistance and piperine increased resistance, making them candidates for causing the effects seen with crude spice extracts. The observation that Solanaceae spices (paprika, cayenne pepper) increase permeability for ions and macromolecules might be of pathophysiological importance, particularly with respect to food allergy and intolerance.

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

    Science.gov (United States)

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

    2010-11-01

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

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

    DEFF Research Database (Denmark)

    Tan, Hsih-Yin

    to enable real-time detection of cell responses, adjustment of cellular stimulation etc. leading to establishment of conditional experiments. In this project, microfluidic systems engineering was leveraged to develop an eight chamber multi-layer microchip for intestinal barrier studies. Sandwiched between...... the layers was a modified Teflon porous membrane for cell culture. The novelty lies in modifying the surface of the porous Teflon support membrane using thiol-ene ‘click’ chemistry, thus allowing the modified Teflon membrane to be bonded between the chip layers to form an enclosed microchip. Successful...... application of the multi-layer microchip was demonstrated by integrating the microchip to an existing cell culture fluidic system to culture the human intestinal epithelial cells, Caco-2, for long term studies. Under the continuous low flow conditions, the cells differentiated into columnar cells displaying...

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    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.......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 coli-stimulated secretion of proinflammatory immune factors (IL-8, IL-6, and TNF-α) and the anti-inflammatory cytokine IL-10. A murine model of dextran sodium sulfate-induced colitis was used...

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Benoît Couvigny

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

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

    Science.gov (United States)

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

    2015-01-01

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

  14. Human intestinal acyl-CoA synthetase 5 is sensitive to the inhibitor triacsin C

    Institute of Scientific and Technical Information of China (English)

    Elke Kaemmerer; Anne Peuscher; Andrea Reinartz; Christian Liedtke; Ralf Weiskirchen; Jürgen Kopitz; Nikolaus Gassler

    2011-01-01

    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 μL 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 pro-teins was found after incubation with isopropyl beta-D-1-thiogalactopyranoside and after ultracentrifugatio 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 μmol/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 μmol/L), total ACSL activity was dramatically diminished in

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

    Science.gov (United States)

    De Lisi, Stefania; Giovannini, Marc

    2016-02-01

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

  16. A novel method for the culture and polarized stimulation of human intestinal mucosa explants.

    Science.gov (United States)

    Tsilingiri, Katerina; Sonzogni, Angelica; Caprioli, Flavio; Rescigno, Maria

    2013-05-01

    Few models currently exist to realistically simulate the complex human intestine's micro-environment, where a variety of interactions take place. Proper homeostasis directly depends on these interactions, as they shape an entire immunological response inducing tolerance against food antigens while at the same time mounting effective immune responses against pathogenic microbes accidentally ingested with food. Intestinal homeostasis is preserved also through various complex interactions between the microbiota (including food-associated beneficial bacterial strains) and the host, that regulate the attachment/degradation of mucus, the production of antimicrobial peptides by the epithelial barrier, and the "education" of epithelial cells' that controls the tolerogenic or immunogenic phenotype of unique, gut-resident lymphoid cells' populations. These interactions have been so far very difficult to reproduce with in vitro assays using either cultured cell lines or peripheral blood mononuclear cells. In addition, mouse models differ substantially in components of the intestinal mucosa (mucus layer organization, commensal bacteria community) with respect to the human gut. Thus, studies of a variety of treatments to be brought in the clinics for important stress-related or pathological conditions such as irritable bowel syndrome, inflammatory bowel disease or colorectal cancer have been difficult to carry out. To address these issues, we developed a novel system that enables us to stimulate explants of human intestinal mucosa that retain their in situ conditioning by the host microbiota and immune response, in a polarized fashion. Polarized apical stimulation is of great importance for the outcome of the elicited immune response. It has been repeatedly shown that the same stimuli can produce completely different responses when they bypass the apical face of the intestinal epithelium, stimulating epithelial cells basolaterally or coming into direct contact with lamina

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

    Directory of Open Access Journals (Sweden)

    Go Ito

    Full Text Available 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.

  18. 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; Thuneberg, L;

    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...... 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...

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

    Science.gov (United States)

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

    2016-11-01

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

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

    Science.gov (United States)

    O'Brien Andersen, L; Karim, A B; Roager, H M; Vigsnæs, L K; Krogfelt, K A; Licht, T R; Stensvold, C R

    2016-09-01

    Several studies have shown associations between groups of intestinal bacterial or specific ratios between bacterial groups and various disease traits. Meanwhile, little is known about interactions and associations between eukaryotic and prokaryotic microorganisms in the human gut. In this work, we set out to investigate potential associations between common single-celled parasites such as Blastocystis spp. and Dientamoeba fragilis and intestinal bacteria. Stool DNA from patients with intestinal symptoms were selected based on being Blastocystis spp.-positive (B+)/negative (B-) and D. fragilis-positive (D+)/negative (D-), and split into four groups of 21 samples (B+ D+, B+ D-, B- D+, and B- D-). Quantitative PCR targeting the six bacterial taxa Bacteroides, Prevotella, the butyrate-producing clostridial clusters IV and XIVa, the mucin-degrading Akkermansia muciniphila, and the indigenous group of Bifidobacterium was subsequently performed, and the relative abundance of these bacteria across the four groups was compared. The relative abundance of Bacteroides in B- D- samples was significantly higher compared with B+ D- and B+ D+ samples (P Blastocystis alone or combined with D. fragilis is associated with gut microbiota characterized by low relative abundances of Bacteroides and Clostridial cluster XIVa and high levels of Prevotella. PMID:27230509

  1. Metabolism of the benzidine-based azo dye Direct Black 38 by human intestinal microbiota

    Energy Technology Data Exchange (ETDEWEB)

    Manning, B.W.; Cerniglia, C.E.; Federle, T.W.

    1985-07-01

    Benzidine-based azo dyes are proven mutagens and have been linked to bladder cancer. Previous studies have indicated that their initial reduction is the result of the azo reductase activity of the intestinal microbiota. Metabolism of the benzidine-based dye Direct Black 38 was examined by using a semicontinuous culture system that simulates the lumen of the human large intestine. The system was inoculated with freshly voided feces, and an active flora was maintained as evidenced by volatile fatty acid and gas production. Within 7 days after exposure to the dye, the following metabolites were isolated and identified by gas chromatography - mass spectrometry: benzidine, 4-aminobiphenyl, monoacetylbenzidine, and acetylaminobiphenyl. Benzidine reached its peak level after 24 h, accounting for 39.1% of the added dye. Its level began to decline, and by day 7 the predominant metabolite was acetylaminobiphenyl, which accounted for 51.1% of the parent compound. Formation of the deaminated and N-acetylated analogs of benzidine, which have enhanced mutagenicity and lipophilicity, previously has not been attributed to the intestinal microbiota.

  2. Infection with fully mature Corynosoma cf. validum causes ulcers in the human small intestine.

    Science.gov (United States)

    Takahashi, Keitaro; Ito, Takahiro; Sato, Tomonobu; Goto, Mitsuru; Kawamoto, Toru; Fujinaga, Akihiro; Yanagawa, Nobuyuki; Saito, Yoshinori; Nakao, Minoru; Hasegawa, Hideo; Fujiya, Mikihiro

    2016-06-01

    Corynosoma is a parasite that can normally be found in the intestinal tract of fish-eating mammals, particularly in seals and birds. The present case proposed that Corynosoma could attain full maturity in the human intestine. A 70-year-old female complained of abdominal pain. A computed tomography (CT) scan revealed a swelling of the intraperitoneal lymph nodes with no responsible lesion. Video capsule endoscopy and double-balloon endoscopy detected several ulcerations and one parasite in the ileum, which was tightly attached at the bottom of the ulcerations. The parasite was cylindrical and measured approximately 10 mm (long) x 3 mm (wide). Pathologically, the worm had a four-layered body wall and contained embryonated eggs. The sequences of the parasite-derived nuclear ribosomal DNA fragment and mitochondrial DNA fragment of cox1 were almost identical to those of Corynosoma validum. The patient's abdominal pain immediately improved after the administration of pyrantel pamoate (1,500 mg). Corynosoma was possibly the responsible disease in a patient who complained of abdominal pain and in whom no responsible lesion was detected by CT, gastroduodenoscopy or colonoscopy. Examinations of the small intestines should be aggressively performed in such cases.

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

    Science.gov (United States)

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

    2012-08-31

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

  4. Infection with fully mature Corynosoma cf. validum causes ulcers in the human small intestine.

    Science.gov (United States)

    Takahashi, Keitaro; Ito, Takahiro; Sato, Tomonobu; Goto, Mitsuru; Kawamoto, Toru; Fujinaga, Akihiro; Yanagawa, Nobuyuki; Saito, Yoshinori; Nakao, Minoru; Hasegawa, Hideo; Fujiya, Mikihiro

    2016-06-01

    Corynosoma is a parasite that can normally be found in the intestinal tract of fish-eating mammals, particularly in seals and birds. The present case proposed that Corynosoma could attain full maturity in the human intestine. A 70-year-old female complained of abdominal pain. A computed tomography (CT) scan revealed a swelling of the intraperitoneal lymph nodes with no responsible lesion. Video capsule endoscopy and double-balloon endoscopy detected several ulcerations and one parasite in the ileum, which was tightly attached at the bottom of the ulcerations. The parasite was cylindrical and measured approximately 10 mm (long) x 3 mm (wide). Pathologically, the worm had a four-layered body wall and contained embryonated eggs. The sequences of the parasite-derived nuclear ribosomal DNA fragment and mitochondrial DNA fragment of cox1 were almost identical to those of Corynosoma validum. The patient's abdominal pain immediately improved after the administration of pyrantel pamoate (1,500 mg). Corynosoma was possibly the responsible disease in a patient who complained of abdominal pain and in whom no responsible lesion was detected by CT, gastroduodenoscopy or colonoscopy. Examinations of the small intestines should be aggressively performed in such cases. PMID:27098251

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

    Directory of Open Access Journals (Sweden)

    Maria Giovanna Quaranta

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

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

    OpenAIRE

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

    2012-01-01

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

  7. 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

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

    Science.gov (United States)

    Lennernäs, 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.

  9. Evaluation of jojoba oil as a low-energy fat. 2. Intestinal transit time, stomach emptying and digestibility in short-term feeding studies in rats.

    Science.gov (United States)

    Verschuren, P M; Nugteren, D H

    1989-01-01

    The influence of jojoba oil (JO) incorporation in the diet on stomach emptying and intestinal transit time, and the digestion and absorption of JO were investigated in short-term feeding studies in rats. The animals were fed purified diets containing 18% (w/w) fat, of which half consisted of a mixture of lard and sunflower seed oil (SF) supplemented with an equivalent amount of JO. The control animals were fed a mixture of lard and SF (18%). No treatment-related differences were observed in the rate of stomach emptying or the intestinal transit time. Comparative lipid analysis of lymph, intestinal content, intestinal mucosa and faeces indicated that most of the ingested JO was degraded and absorbed. Part of the JO was present as wax ester in the lymph. Hydrolysis of JO was much slower than that of triacylglycerols and continued in the alimentary tract beyond the small intestine due to bacterial processes. JO did not influence the absorption of the conventional fat.

  10. Characterization of macrophage-like cells in the external layers of human small and large intestine

    DEFF Research Database (Denmark)

    Mikkelsen, H B; Rumessen, J J

    1992-01-01

    -DR-positive (expressing the MHC class-II antigen), in contrast to macrophage-like cells in the subserosa and submucosa. Macrophage-like cells in the external muscle layer were mostly acid phosphatase-negative, and at the electron-microscopic level they were found to have features of macrophages: primary lysosomes, coated...... vesicles and pits. However, very few secondary lysosomes were present. Birbeck granules were not observed. It is concluded that in the external muscle layer of human small and large intestine numerous macrophages of a special type are present. It is discussed whether this cell type plays a role...

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

    OpenAIRE

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

    2013-01-01

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

  12. Butyrate stimulates IL-32α expression in human intestinal epithelial cell lines

    Institute of Scientific and Technical Information of China (English)

    Ayako; Kobori; Shigeki; Bamba; Hirotsugu; Imaeda; Hiromitsu; Ban; Tomoyuki; Tsujikawa; Yasuharu; Saito; Yoshihide; Fujiyama; Akira; Andoh

    2010-01-01

    AIM: To investigate the effects of butyrate on interleukin (IL)-32α expression in epithelial cell lines. METHODS: The human intestinal epithelial cell lines HT-29, SW480, and T84 were used. Intracellular IL- 32α was determined by Western blotting analyses. IL- 32α mRNA expression was analyzed by real-time poly-merase chain reaction. RESULTS: Acetate and propionate had no effects on IL-32α mRNA expression. Butyrate significantly enhanced IL-32α expression in all cell lines. Butyrate also up-regulated IL-1β-i...

  13. Transepithelial transport of ambroxol hydrochloride across human intestinal Caco-2 cell monolayers.

    Science.gov (United States)

    Stetinová, Vera; Smetanová, Libuse; Kholová, Dagmar; Svoboda, Zbynek; Kvetina, Jaroslav

    2009-09-01

    This study aimed i) to characterize the transepithelial transport of the mucolytic agent ambroxol hydrochloride across the intestinal barrier, ii) to classify the ambroxol according to Biopharmaceutics Classification System (BCS) and iii) to predict ambroxol absorption in humans. Transport of ambroxol (100, 300 and 1000 micromol/l) was studied in a human colon carcinoma cell line Caco-2 in apical to basolateral and basolateral to apical direction, under iso-pH 7.4 and pH-gradient (6 vs. 7.4) conditions. The relative contribution of the paracellular route was estimated using Ca2+-free transport medium. Ambroxol samples from receiver compartments were analysed by HPLC with UV detection (242 nm). Results showed that ambroxol transport is linear with time, pH-dependent and direction-independent, displays non-saturable (first-order) kinetics. Thus, the transport seems to be transcellular mediated by passive diffusion. Estimated high solubility and high permeability (P(app) = 45 x 10(-6) cm/s) of ambroxol rank it among well absorbed compounds and class I of BCS. It can be expected that the oral dose fraction of ambroxol absorbed in human intestine is high.

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

    Directory of Open Access Journals (Sweden)

    Pierre-Jean Ferron

    2016-02-01

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

  15. 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

  16. Initiation of an inflammatory response in resident intestinal lamina propria cells -use of a human organ culture model.

    Directory of Open Access Journals (Sweden)

    Jutta Schröder-Braunstein

    Full Text Available Resident human lamina propria immune cells serve as powerful effectors in host defense. Molecular events associated with the initiation of an intestinal inflammatory response in these cells are largely unknown. Here, we aimed to characterize phenotypic and functional changes induced in these cells at the onset of intestinal inflammation using a human intestinal organ culture model. In this model, healthy human colonic mucosa was depleted of epithelial cells by EDTA treatment. Following loss of the epithelial layer, expression of the inflammatory mediators IL1B, IL6, IL8, IL23A, TNFA, CXCL2, and the surface receptors CD14, TLR2, CD86, CD54 was rapidly induced in resident lamina propria cells in situ as determined by qRT-PCR and immunohistology. Gene microarray analysis of lamina propria cells obtained by laser-capture microdissection provided an overview of global changes in gene expression occurring during the initiation of an intestinal inflammatory response in these cells. Bioinformatic analysis gave insight into signalling pathways mediating this inflammatory response. Furthermore, comparison with published microarray datasets of inflamed mucosa in vivo (ulcerative colitis revealed a significant overlap of differentially regulated genes underlining the in vivo relevance of the organ culture model. Furthermore, genes never been previously associated with intestinal inflammation were identified using this model. The organ culture model characterized may be useful to study molecular mechanisms underlying the initiation of an intestinal inflammatory response in normal mucosa as well as potential alterations of this response in inflammatory bowel disease.

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

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

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

  18. 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; Nielsen, Henrik Bjørn;

    2012-01-01

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

  19. Human capital, Demographic Transition and Economic Growth

    OpenAIRE

    Haitham Issa

    2003-01-01

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

  20. Intestinal microbiota and human diseases%肠道微生物与人类疾病

    Institute of Scientific and Technical Information of China (English)

    王子恺; 杨云生

    2012-01-01

    肠道内数以亿计的微生物及其代谢产物在人体能量代谢、营养物质吸收、先天和获得性免疫、胃肠道功能等方面发挥着重要作用,一旦宿主与肠道微生物之间共栖共生的稳态被打破,就会诱发多种人类疾病.目前已经认识到肠道微生物与人类健康和疾病的密切关系,仅仅从人类自身角度出发来研究人类疾病远远不够,必须考虑到与人类共栖共生的肠道微生物的作用.本文就近年来有关肠道微生物与人类疾病关系研究的进展进行综述.%The majority of human intestinal microbiota are harmless or even beneficial by performing functions essential for our survival. Changes in the microbial species that reside in our intestines have been associated with a long list of illness. The review provided an overview of the association between the microbiota and the occurrence of human diseases, and to stimulate future researches regarding infectious diseases and their consequences.

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

    Directory of Open Access Journals (Sweden)

    Tatiana Christides

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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    points (n¼192). Digestive transit time was estimated on d 29 using a chromic oxide marker; production variables and the extent of foot pad dermatitis were also recorded. 4. In the 3 h prior to a scotoperiod, feeding activity increased in chickens from DARK 8 but not DARK 4þ4. This increase was reflected...... in a higher relative content of the crop in DARK 8 at this time. 5. Immediately following the scotoperiod, feeding activity peaked and, although the chickens in DARK 4þ4 expressed more feeding behaviour in the first 20 min after the scotoperiod, the chickens in DARK 8 had overall higher feeding activity...

  3. Free fucose is a danger signal to human intestinal epithelial cells.

    Science.gov (United States)

    Chow, Wai Ling; Lee, Yuan Kun

    2008-03-01

    Fucose is present in foods, and it is a major component of human mucin glycoproteins and glycolipids. l-Fucose can also be found at the terminal position of many cell-surface oligosaccharide ligands that mediate cell-recognition and adhesion-signalling pathways. Mucin fucose can be released through the hydrolytic activity of pathogens and indigenous bacteria, leading to the release of free fucose into the intestinal lumen. The immunomodulating effects of free fucose on intestinal epithelial cells (enterocyte-like Caco-2) were investigated. It was found that the presence of l-fucose up regulated genes and secretion of their encoded proteins that are involved in both the innate and adaptive immune responses, possibly via the toll-like receptor-2 signalling pathway. These include TNFSF5, TNFSF7, TNF-alpha, IL12, IL17 and IL18. Besides modulating immune reactions in differentiated Caco-2 cells, fucose induced a set of cytokine genes that are involved in the development and proliferation of immune cells. These include the bone morphogenetic proteins (BMP) BMP2, BMP4, IL5, thrombopoietin and erythropoietin. In addition, the up regulated gene expression of fibroblast growth factor-2 may help to promote epithelial cell restitution in conjunction with the enhanced expression of transforming growth factor-beta mRNA. Since the exogenous fucose was not metabolised by the differentiated Caco-2 cells as a carbon source, the reactions elicited were suggested to be a result of the direct interaction of fucose and differentiated Caco-2 cells. The presence of free fucose may signal the invasion of mucin-hydrolysing microbial cells and breakage of the mucosal barrier. The intestinal epithelial cells respond by up regulation and secretion of cytokines, pre-empting the actual invasion of pathogens.

  4. Intestinal steroidogenesis.

    Science.gov (United States)

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

    2015-11-01

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

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

    NARCIS (Netherlands)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Marcelo Luiz Carvalho Gonçalves

    2003-01-01

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

  7. Evaluation of impact of exposure of Sudan azo dyes and their metabolites on human intestinal bacteria.

    Science.gov (United States)

    Pan, Hongmiao; Feng, Jinhui; He, Gui-Xin; Cerniglia, Carl E; Chen, Huizhong

    2012-08-01

    Sudan azo dyes are banned for food usage in most countries, but they are illegally used to maintain or enhance the color of food products due to low cost, bright staining, and wide availability of the dyes. In this report, we examined the toxic effects of these azo dyes and their potential reduction metabolites on 11 prevalent human intestinal bacterial strains. Among the tested bacteria, cell growth of 2, 3, 5, 5, and 1 strains was inhibited by Sudan I, II, III, IV, and Para Red, respectively. At the tested concentration of 100 μM, Sudan I and II inhibited growth of Clostridium perfringens and Lactobacillus rhamnosus with decrease of growth rates from 14 to 47%. Sudan II also affected growth of Enterococcus faecalis. Growth of Bifidobacterium catenulatum, C. perfringens, E. faecalis, Escherichia coli, and Peptostreptococcus magnus was affected by Sudan III and IV with decrease in growth rates from 11 to 67%. C. perfringens was the only strain in which growth was affected by Para Red with 47 and 26% growth decreases at 6 and 10 h, respectively. 1-Amino-2-naphthol, a common metabolite of the dyes, was capable of inhibiting growth of most of the tested bacteria with inhibition rates from 8 to 46%. However, the other metabolites of the dyes had no effect on growth of the bacterial strains. The dyes and their metabolites had less effect on cell viability than on cell growth of the tested bacterial strains. Clostridium indolis and Clostridium ramosum were the only two strains with about a 10 % decrease in cell viability in the presence of Sudan azo dyes. The present results suggested that Sudan azo dyes and their metabolites potentially affect the human intestinal bacterial ecology by selectively inhibiting some bacterial species, which may have an adverse effect on human health.

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

    Institute of Scientific and Technical Information of China (English)

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

    2007-01-01

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

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

    Science.gov (United States)

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

    2013-06-01

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

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

    OpenAIRE

    GAO, Jiang Jing; Hattori, Masao

    2005-01-01

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

  11. Transepithelial transport of putrescine across monolayers of the human intestinal epithelial cell line, Caco-2

    Institute of Scientific and Technical Information of China (English)

    Vladan Milovic; Lyudmila Turchanowa; Jurgen Stein; Wolfgang F. Caspary

    2001-01-01

    AIM To study the transepithelial transport characteristics of the polyamine putrescine in human intestinal Caco-2 cell monolayers to elucidate the mechanisms of the putrescine intestinal absorption.METHODS The transepithelial transport and the cellular accumulation of putrescine was measured using Caco 2 cell monolayers grown on permeable filters.RESULTS Transepithelial transport of putrescine in physiological concentrations (>0.5 mM)from the apical to basolateral side was linear. Intracellular accumulation of putrescine was higher in confluent than in fully differentiated Caco-2 cells, but still negligible (less than 0.5%) of the overall transport across the monolayers in apical-to-basolateral direction. EGF enhanced putrescine accumulation in Caco-2 cells by four-fold, as well as putrescine conversion to spermidine and spermine by enhancing the activity of Sadenosylmethionine decarboxylase. However,EGF did not have any significant influence on putrescine flux across the Caco-2 cell monolayers. Excretion of putrescine from Caco-2cells into the basolateral medium did not exceed 50 picomoles, while putrescine passive flux from the apical to the basolateral chamber,contributed hundreds of micromoles polyamines to the basolateral chamber.CONCLUSION Transepithelial transport of putrescine across Caco-2 cell monolayers occurs in passive diffusion, and is not influenced when epithelial cells are stimulated to proliferate by a potent mitogen such as EGF.

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    Jerzy Kaleczyc

    2010-11-01

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

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

    OpenAIRE

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

    2009-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Yan Bingfang

    2006-02-01

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

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

    DEFF Research Database (Denmark)

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

    1994-01-01

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

  17. Bifidobacteria Prevent Tunicamycin-Induced Endoplasmic Reticulum Stress and Subsequent Barrier Disruption in Human Intestinal Epithelial Caco-2 Monolayers.

    Science.gov (United States)

    Akiyama, Takuya; Oishi, Kenji; Wullaert, Andy

    2016-01-01

    Endoplasmic reticulum (ER) stress is caused by accumulation of unfolded and misfolded proteins in the ER, thereby compromising its vital cellular functions in protein production and secretion. Genome wide association studies in humans as well as experimental animal models linked ER stress in intestinal epithelial cells (IECs) with intestinal disorders including inflammatory bowel diseases. However, the mechanisms linking the outcomes of ER stress in IECs to intestinal disease have not been clarified. In this study, we investigated the impact of ER stress on intestinal epithelial barrier function using human colon carcinoma-derived Caco-2 monolayers. Tunicamycin-induced ER stress decreased the trans-epithelial electrical resistance of Caco-2 monolayers, concomitant with loss of cellular plasma membrane integrity. Epithelial barrier disruption in Caco-2 cells after ER stress was not caused by caspase- or RIPK1-dependent cell death but was accompanied by lysosomal rupture and up-regulation of the ER stress markers Grp78, sXBP1 and Chop. Interestingly, several bifidobacteria species inhibited tunicamycin-induced ER stress and thereby diminished barrier disruption in Caco-2 monolayers. Together, these results showed that ER stress compromises the epithelial barrier function of Caco-2 monolayers and demonstrate beneficial impacts of bifidobacteria on ER stress in IECs. Our results identify epithelial barrier loss as a potential link between ER stress and intestinal disease development, and suggest that bifidobacteria could exert beneficial effects on this phenomenon. PMID:27611782

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

    DEFF Research Database (Denmark)

    Rumessen, J J; Mikkelsen, H B; Thuneberg, L

    1992-01-01

    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......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...

  19. 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

  20. 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 Głogowska

    2015-02-01

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

  1. Innervation of enteric mast cells by primary spinal afferents in guinea pig and human small intestine.

    Science.gov (United States)

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

    2014-10-01

    Mast cells express the substance P (SP) neurokinin 1 receptor and the calcitonin gene-related peptide (CGRP) receptor in guinea pig and human small intestine. Enzyme-linked immunoassay showed that activation of intramural afferents by antidromic electrical stimulation or by capsaicin released SP and CGRP from human and guinea pig intestinal segments. Electrical stimulation of the afferents evoked slow excitatory postsynaptic potentials (EPSPs) in the enteric nervous system. The slow EPSPs were mediated by tachykinin neurokinin 1 and CGRP receptors. Capsaicin evoked slow EPSP-like responses that were suppressed by antagonists for protease-activated receptor 2. Afferent stimulation evoked slow EPSP-like excitation that was suppressed by mast cell-stabilizing drugs. Histamine and mast cell protease II were released by 1) exposure to SP or CGRP, 2) capsaicin, 3) compound 48/80, 4) elevation of mast cell Ca²⁺ by ionophore A23187, and 5) antidromic electrical stimulation of afferents. The mast cell stabilizers cromolyn and doxantrazole suppressed release of protease II and histamine when evoked by SP, CGRP, capsaicin, A23187, electrical stimulation of afferents, or compound 48/80. Neural blockade by tetrodotoxin prevented mast cell protease II release in response to antidromic electrical stimulation of mesenteric afferents. The results support a hypothesis that afferent innervation of enteric mast cells releases histamine and mast cell protease II, both of which are known to act in a diffuse paracrine manner to influence the behavior of enteric nervous system neurons and to elevate the sensitivity of spinal afferent terminals.

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

    Directory of Open Access Journals (Sweden)

    Francesca eCaloni

    2012-06-01

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

  3. SHP-2 Mediates Cryptosporidium parvum Infectivity in Human Intestinal Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Eunice A Varughese

    Full Text Available The parasite, Cryptosporidium parvum, induces human gastroenteritis through infection of host epithelial cells in the small intestine. During the initial stage of infection, C. parvum is reported to engage host mechanisms at the host cell-parasite interface to form a parasitophorous vacuole. We determined that upon infection, the larger molecular weight proteins in human small intestinal epithelial host cells (FHs 74 Int appeared to globally undergo tyrosine dephosphorylation. In parallel, expression of the cytoplasmic protein tyrosine phosphatase Src homology-2 domain-containing phosphatase 2 (SHP-2 increased in a time-dependent manner. SHP-2 co-localized with the C. parvum sporozoite and this interaction increased the rate of C. parvum infectivity through SH2-mediated SHP-2 activity. Furthermore, we show that one potential target that SHP-2 acts upon is the focal adhesion protein, paxillin, which undergoes moderate dephosphorylation following infection, with inhibition of SHP-2 rescuing paxillin phosphorylation. Importantly, treatment with an inhibitor to SHP-2 and with an inhibitor to paxillin and Src family kinases, effectively decreased the multiplicity of C. parvum infection in a dose-dependent manner. Thus, our study reveals an important role for SHP-2 in the pathogenesis of C. parvum. Furthermore, while host proteins can be recruited to participate in the development of the electron dense band at the host cell-parasite interface, our study implies for the first time that SHP-2 appears to be recruited by the C. parvum sporozoite to regulate infectivity. Taken together, these findings suggest that SHP-2 and its down-stream target paxillin could serve as targets for intervention.

  4. SHP-2 Mediates Cryptosporidium parvum Infectivity in Human Intestinal Epithelial Cells.

    Science.gov (United States)

    Varughese, Eunice A; Kasper, Susan; Anneken, Emily M; Yadav, Jagjit S

    2015-01-01

    The parasite, Cryptosporidium parvum, induces human gastroenteritis through infection of host epithelial cells in the small intestine. During the initial stage of infection, C. parvum is reported to engage host mechanisms at the host cell-parasite interface to form a parasitophorous vacuole. We determined that upon infection, the larger molecular weight proteins in human small intestinal epithelial host cells (FHs 74 Int) appeared to globally undergo tyrosine dephosphorylation. In parallel, expression of the cytoplasmic protein tyrosine phosphatase Src homology-2 domain-containing phosphatase 2 (SHP-2) increased in a time-dependent manner. SHP-2 co-localized with the C. parvum sporozoite and this interaction increased the rate of C. parvum infectivity through SH2-mediated SHP-2 activity. Furthermore, we show that one potential target that SHP-2 acts upon is the focal adhesion protein, paxillin, which undergoes moderate dephosphorylation following infection, with inhibition of SHP-2 rescuing paxillin phosphorylation. Importantly, treatment with an inhibitor to SHP-2 and with an inhibitor to paxillin and Src family kinases, effectively decreased the multiplicity of C. parvum infection in a dose-dependent manner. Thus, our study reveals an important role for SHP-2 in the pathogenesis of C. parvum. Furthermore, while host proteins can be recruited to participate in the development of the electron dense band at the host cell-parasite interface, our study implies for the first time that SHP-2 appears to be recruited by the C. parvum sporozoite to regulate infectivity. Taken together, these findings suggest that SHP-2 and its down-stream target paxillin could serve as targets for intervention. PMID:26556238

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

    Directory of Open Access Journals (Sweden)

    Lilach Golan

    2011-01-01

    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 tissue interactions. Fully developed, germ-free human and bovine small intestine and colon were established by subcutaneous transplantation of human and bovine fetal gut into SCID mice. Xenografts were allowed to develop for 3–4 months and thereafter were infected by direct intraluminal inoculation of Stx-negative derivatives of EHEC O157:H7, strain EDL933. The small intestine and colon xenografts closely mimicked the respective native tissues. Upon infection, EHEC induced formation of typical attaching and effacing lesions and tissue damage that resembled hemorrhagic colitis in colon xenografts. By contrast, xenografts infected with an EHEC mutant deficient in T3SS remained undamaged. Furthermore, EHEC did not attach to or damage the epithelium of small intestinal tissue, and these xenografts remained intact. EHEC damaged the colon in a T3SS-dependent manner, and this model is therefore useful for studying the molecular details of EHEC interactions with live human and bovine intestinal tissue. Furthermore, we demonstrate that Stx and gut microflora are not essential for EHEC virulence in the human gut.

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

    DEFF Research Database (Denmark)

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

    2004-01-01

    . Screening of antibodies from a hybridoma library led to the identification of an acyl-CoA synthetase 5-specific monoclonal antibody. Protein synthesis, mRNA expression, and the enzyme activity of acyl-CoA synthetase 5 were studied by several methods in human small intestinal tissues with Crohn's disease...

  7. 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; Leyer, G J;

    2010-01-01

    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...

  8. Noise-induced transition in human reaction times

    Science.gov (United States)

    Medina, José M.; Díaz, José A.

    2016-09-01

    The human reaction/response time can be defined as the time elapsed from the onset of stimulus presentation until a response occurs in many sensory and cognitive processes. A reaction time model based on Piéron’s law is investigated. The model shows a noise-induced transition in the moments of reaction time distributions due to the presence of strong additive noise. The model also demonstrates that reaction times do not follow fluctuation scaling between the mean and the variance but follow a generalized version between the skewness and the kurtosis. The results indicate that noise-induced transitions in the moments govern fluctuations in sensory-motor transformations and open an insight into the macroscopic effects of noise in human perception and action. The conditions that lead to extreme reaction times are discussed based on the transfer of information in neurons.

  9. Total Body Irradiation in the "Hematopoietic" Dose Range Induces Substantial Intestinal Injury in Non-Human Primates.

    Science.gov (United States)

    Wang, Junru; Shao, Lijian; Hendrickson, Howard P; Liu, Liya; Chang, Jianhui; Luo, Yi; Seng, John; Pouliot, Mylene; Authier, Simon; Zhou, Daohong; Allaben, William; Hauer-Jensen, Martin

    2015-11-01

    The non-human primate has been a useful model for studies of human acute radiation syndrome (ARS). However, to date structural changes in various parts of the intestine after total body irradiation (TBI) have not been systematically studied in this model. Here we report on our current study of TBI-induced intestinal structural injury in the non-human primate after doses typically associated with hematopoietic ARS. Twenty-four non-human primates were divided into three groups: sham-irradiated control group; and total body cobalt-60 (60Co) 6.7 Gy gamma-irradiated group; and total body 60Co 7.4 Gy gamma-irradiated group. After animals were euthanized at day 4, 7 and 12 postirradiation, sections of small intestine (duodenum, proximal jejunum, distal jejunum and ileum) were collected and fixed in 10% formalin. The intestinal mucosal surface length, villus height and crypt depths were assessed by computer-assisted image analysis. Plasma citrulline levels were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Total bone marrow cells were counted and hematopoietic stem/progenitor cells in bone marrow were analyzed by flow cytometer. Histopathologically, all segments exhibited conspicuous disappearance of plicae circulares and prominent atrophy of crypts and villi. Intestinal mucosal surface length was significantly decreased in all intestinal segments on day 4, 7 and 12 after irradiation (P 0.05). Crypt depth was also significantly reduced in all segments on day 4, 7 and 12 after irradiation (P irradiation, consistent with intestinal mucosal injury. Both 6.7 and 7.4 Gy TBI reduced total number of bone marrow cells. And further analysis showed that the number and function of CD45(+)CD34(+) hematopoietic stem/progenitors in bone marrow decreased significantly. In summary, TBI in the hematopoietic ARS dose range induces substantial intestinal injury in all segments of the small bowel. These findings underscore the importance of maintaining the

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

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

    Science.gov (United States)

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

    2016-08-01

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

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

    OpenAIRE

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

    2006-01-01

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

  13. Biotransformation of 1-nitropyrene to 1-aminopyrene and N-formyl-1-aminopyrene by the human intestinal microbiota

    Energy Technology Data Exchange (ETDEWEB)

    Manning, B.W.; Cerniglia, C.E.; Federle, T.W.

    1986-01-01

    The nitropolycyclic aromatic hydrocarbon 1-nitropyrene (1-NP) is an environmental pollutant, a potent bacterial and mammalian mutagen, and a carcinogen. The metabolism of 1-NP by the human intestinal microbiota was studied using a semicontinuous culture system that simulates the colonic lumen. (/sup 3/H)-1-Nitropyrene was metabolized by the intestinal microbiota to 1-aminopyrene (1-AP) and N-formyl-1-aminopyrene (FAP) as determined by high-performance liquid chromatography (HPLC) and mass spectrometry. Twenty-four hours after the addition of (/sup 3/H)-1-NP, the formylated compound and 1-AP accounted for 20 and 80% of the total metabolism respectively. This percentage increased to 66% for FAP after 24 h following 10 d of chronic exposure to unlabeled 1-NP, suggesting metabolic adaptation to 1-NP by the microbiota. Both 1-AP and FAP have been shown to be nonmutagenic towards Salmonella typhimurium TA98, which indicates that the intestinal microflora may potentially detoxify 1-NP.

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

    Directory of Open Access Journals (Sweden)

    Devendra Bansal

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

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

    Science.gov (United States)

    Bansal, Devendra; Ave, Patrick; Kerneis, Sophie; Frileux, Pascal; Boché, Olivier; Baglin, Anne Catherine; Dubost, Geneviève; Leguern, Anne-Sophie; Prevost, Marie-Christine; Bracha, Rivka; Mirelman, David; Guillén, Nancy; Labruyère, Elisabeth

    2009-11-17

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1997-04-15

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

  17. 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 μM. The choice of highest FB1 concentration considered the low toxicity previously reported on intestinal cell lines, whereas the lowest one corresponded to the lower FBs levels permitted by European Commission Regulation. Different functional parameters were tested such as cell proliferation, oxidative status, immunomodulatory effect and changes in membrane microviscosity. In addition FB1-FITC localization in this cell line was assessed by using confocal laser scanning microscopy. Lipid peroxidation induction was the main and early (12 h) effect induced by FB1 at concentrations ranging from 0.5 to 69 μM, followed by inhibition of cell proliferation (up to 8.6 μM), the immunomodulatory effect (up to 17.2 μM), by assessing IL-8 secretion, and increase in membrane microviscosity (up to 34.5 μM). The toxic effects observed in different functional parameters were not dose-dependent and could be the consequence of the FB1 intracytoplasmatic localization as confirmed by confocal microscopy results. The different timescales and concentrations active of different functional parameters could suggest different cellular targets of FB1. PMID:24549592

  18. Structural features of colloidal species in the human fasted upper small intestine

    DEFF Research Database (Denmark)

    Mullertz, Anette; Reppas, Christos; Psachoulias, Dimitrios;

    2015-01-01

    Objectives This paper aims to study the features of colloidal species in the lumen of the upper small intestine of two healthy adults at fasted state by means of electron microscopy. Methods Samples were aspirated from a location near the ligament of Treitz 30 min (volunteer no. 1, Aspirate30min...... with previously studied samples from the lower intestine in the fasted state. Micelles and unilamellar vesicles observed in both samples closely resemble morphological characteristics of those found in fluids simulating the colloidal species in fasted upper intestinal environment. Conclusions Features...... of colloidal species in contents of fasted small intestine have similarities with fluids simulating the contents in fasted upper small intestine and with contents of lower intestine in the fasted state....

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

    Science.gov (United States)

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

    2015-11-01

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

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

    Science.gov (United States)

    Mirazón Lahr, Marta

    2016-07-01

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

  1. Two-dimensional gel proteome reference map of human small intestine

    Directory of Open Access Journals (Sweden)

    Canzonieri Vincenzo

    2009-03-01

    Full Text Available Abstract Background The small intestine is an important human organ that plays a central role in many physiological functions including digestion, absorption, secretion and defense. Duodenal pathologies include, for instance, the ulcer associated to Helicobacter Pylori infection, adenoma and, in genetically predisposed individuals, celiac disease. Alterations in the bowel reduce its capability to absorb nutrients, minerals and fat-soluble vitamins. Anemia and osteopenia or osteoporosis may develop as a consequence of vitamins malabsorption. Adenoma is a benign tumor that has the potential to become cancerous. Adult celiac disease patients present an overall risk of cancer that is almost twice than that found in the general population. These disease processes are not completely known. To date, a two dimensional (2D reference map of proteins expressed in human duodenal tissue is not yet available: the aim of our study was to characterize the 2D protein map, and to identify proteins of duodenal mucosa of adult individuals without duodenal illness, to create a protein database. This approach, may be useful for comparing similar protein samples in different laboratories and for the molecular characterization of intestinal pathologies without recurring to the use of surgical material. Results The enrolled population comprised five selected samples (3 males and 2 females, aged 19 to 42, taken from 20 adult subjects, on their first visit at the gastroenterology unit for a suspected celiac disease, who did not turn to be affected by any duodenal pathology after gastrointestinal and histological evaluations. Proteins extracted from the five duodenal mucosal specimens were singly separated by 2D gel electrophoresis. After image analysis of each 2D gel, 179 protein spots, representing 145 unique proteins, from 218 spots tested, were successfully identified by MALDI-TOF ms analysis. Normalized volumes, for each protein, have been reported for every gel

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

    DEFF Research Database (Denmark)

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

    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 progl......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...

  3. Why do humans have two glucocorticoids: A question of intestinal fortitude.

    Science.gov (United States)

    Morris, David J

    2015-10-01

    The main purpose of this review article is threefold (a) to try to address the question "why are two adrenal glucocorticoids, cortisol and corticosterone, secreted by humans and other mammalian species?", (b) to outline a hypothesis that under certain physiological conditions, corticosterone has additional biochemical functions over and above those of cortisol, and (c) to emphasize the role of gastrointestinal bacteria in chemically transforming corticosterone into metabolites and that these re-cycled metabolites can be reabsorbed from the enterohepatic circuit. Cortisol and its metabolites are not secreted into the bile and thus are excluded from the enterohepatic circuit. Corticosterone was the first steroid hormone isolated from adrenal gland extracts. Many believe that corticosterone functions identically to cortisol. Yet, corticosterone causes significant sodium retention and potassium secretion in Addisonian patients, unlike cortisol. In humans, corticosterone and its metabolite, 3α,5α-TH-corticosterone, are excreted via the bile in humans where they are transformed in the intestine by anaerobic bacteria into 21-dehydroxylated products: 11β-OH-progesterone or 11β-OH-(allo)-5α-preganolones. These metabolites inhibit 11β-HSD2 and 11β-HSD1 dehydrogenase, being many-fold more potent than 3α,5α-TH-cortisol. Corticosterone has significantly lower Km's for both 11β-HSD2 and 11β-HSD1 enzymatic dehydrogenase activity, compared to cortisol. Patients diagnosed with 17α-hydroxylase deficiency have elevated blood pressure and high levels of circulating corticosterone, 3α,5α-TH-corticosterone, and their 21-dehydroxlated corticosterone derivatives. In humans, these 5α-corticosterone metabolites are likely to influence blood pressure regulation and Na(+) retention by inhibiting the rate of deactivation of cortisol by 11β-HSD isoforms.

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

    Directory of Open Access Journals (Sweden)

    Efstathia Papafragkou

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2003-01-01

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

  6. 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 naïve mast cell line HMC-1 cells or monocyte cell line THP-1 cells significantly upregulated the expression of CD23 and increased the antigen transport across the epithelium. Treatment with stem cell factor (SCF, nerve growth factor (NGF, retinoic acid (RA or dimethyl sulphoxide (DMSO enhanced CD23 expression in HT29 cells. Conditioned media from SCF, NGF or RA-treated HMC-1 cells, and SCF, NGF, DMSO or RA-treated THP-1 cells enhanced immune complex transport via enhancing the expression of the CD23 in HT29 cells and the release of inflammatory mediator TNF-α. Nuclear factor kappa B inhibitor, tryptase and TNF-α inhibited the increase in CD23 in HT29 cells and prevents the enhancement of epithelial barrier permeability. Conclusions: Mast cells play an important role in modulating the intestinal CD23 expression and the transport of antigen/IgE/CD23 complex across epithelial barrier.

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

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

    Science.gov (United States)

    Tamari, Farshad; Tychowski, Joanna; Lorentzen, Laura

    2013-01-01

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

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

    OpenAIRE

    Pasquale Tridico

    2007-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Stacy R. Finkbeiner

    2015-06-01

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

  11. Reduction of azo dyes and nitroaromatic compounds by bacterial enzymes from the human intestinal tract

    Energy Technology Data Exchange (ETDEWEB)

    Rafii, F.; Cerniglia, C.E. [Food and Drug Administration, Jefferson, AR (United States)

    1995-06-01

    Several anaerobic bacteria from the human intestinal tract are capable of reducing azo dyes and nitropolycyclic aromatic hydrocarbons to the corresponding aromatic amines with enzymes that have azoreductase and nitroreductase activities. The majority of bacteria with these activities belong to the genera Clostridium and Eubacterium. The azoreductases and nitroreductases from three Clostridium strains and one Eubacterium strain were studied. Both enzymes were produced constitutively in each of the bacteria; the enzymes from various bacteria had different electrophoretic mobilities. The azoreductases from all of the bacteria had immunological homology, as was evident from the cross-reactivity of an antibody raised against the azoreductase of C perfringens with azoreductases from other bacteria. Comparison of azoreductases and nitroreductases showed that they both had identical electrophoretic mobilities on polyacrylamide gels and reacted with the antibody against the azoreductase from C. perfringens. Furthermore, the nitroaromatic compounds competitively inhibited the azoreductase activity. The data indicate that the reduction of both nitroaromatic compounds and azo dyes may be carried out by the same enzyme, which is possibly a flavin adenine dinucleotide dehydrogenase that is synthesized throughout the cell and not associated with any organized subcellular structure. 15 refs., 1 fig., 2 tabs.

  12. Assessment and Molecular Characterization of Human Intestinal Parasites in Bivalves from Orchard Beach, NY, USA

    Directory of Open Access Journals (Sweden)

    Freda F. Tei

    2016-03-01

    Full Text Available Bivalves have been shown to be carriers of the human intestinal parasites Cryptosporidium parvum and Toxoplasma gondii. The goal of this study is to determine the prevalence of protozoan parasites in mollusks of New York City using a polymerase chain reaction (PCR-based assay. Four species of mollusks, Mya arenaria, Geukensia demissa, Crassostrea virginica, and Mytilis edulis, were collected from Orchard Beach, NY in the fall of 2014, totaling 159 specimens. Each individual mollusk was dissected to harvest the digestive gland, the mantle, the gills, the foot and the siphon. The tissues were assayed for the presence of Cryptosporidium parvum, Giardia lamblia, and Toxoplasma gondii DNA by using primers that target parasite-specific genes. C. parvum was found at a prevalence of 50%, 11.3%, and 1%, respectively, in Mya arenaria, G. demissa, and Mytilis edulis. C. parvum DNA was detected in all the tissues of these bivalve species, except the gills. Furthermore, G. lamblia was detected in Mya arenaria, G. demissa, Crassostrea virginica and Mytilis edulis at a prevalence of 37.5%, 4.5%, 60%, and 20.6%, respectively, while T. gondii DNA was not detected.

  13. Investigation of intestinal parasites in pig feces that are also human pathogens.

    Science.gov (United States)

    Uysal, Hayriye Kirkoyun; Boral, Ozden; Metiner, Kemal; Ilgaz, Atilla

    2009-01-01

    A total of 238 pig fecal specimens were collected from pig farms in Corlu (Tekirdağ), Ayazma, and Arnavutköy (Istanbul) during the summer. Out of the 238 pig specimens, 105 were from pigs younger than 6 months and 133 from pigs older than 6 months. These were investigated for intestine parasites in particular the ones that are human pathogens. Cryptosporidium spp. was detected In 21 fecal specimens (8.8%), Giardia spp. in 9 (3.7%), Balantidium coli cysts in 4 (1.6%) and Ascaris suum eggs in 9 (4.1%). Giardia lamblia were found in 8 (7.6%) of 105 pigs younger than 6 months, Cryptosporidium spp. in 12 (11.4%), Balantidium coli cysts in 2 (1.5%). In the pigs older than 6 months Giardia lamblia were found in 1 (0.7%), Cryptosporidium spp. in 9 (6.7%), Balantidium coli cysts in 2 (1.5%). and Ascaris suum eggs in 9 (6.7%). The difference in the rate of G. lamblia (p=0.01) in pigs less than 6 months and of A. suum in those over 6 months was found to be statistically significant (p=0.005). Our results revealed that pigs are important sources of these parasites. PMID:19851968

  14. Influence of Phenol-Enriched Olive Oils on Human Intestinal Immune Function.

    Science.gov (United States)

    Martín-Peláez, Sandra; Castañer, Olga; Solà, Rosa; Motilva, María José; Castell, Margarida; Pérez-Cano, Francisco José; Fitó, Montserrat

    2016-01-01

    Olive oil (OO) phenolic compounds (PC) are able to influence gut microbial populations and metabolic output. Our aim was to investigate whether these compounds and changes affect the mucosal immune system. In a randomized, controlled, double blind cross-over human trial, for three weeks, preceded by two-week washout periods, 10 hypercholesterolemic participants ingested 25 mL/day of three raw virgin OO differing in their PC concentration and origin: (1) an OO containing 80 mg PC/kg (VOO); (2) a PC-enriched OO containing 500 mg PC/kg from OO (FVOO); and (3) a PC-enriched OO containing a mixture of 500 mg PC/kg from OO and thyme (1:1, FVOOT). Intestinal immunity (fecal immunoglobulin A (IgA) and IgA-coated bacteria) and inflammation markers (C-reactive protein (CRP) and fecal interleukin 6 (IL-6), tumor necrosis factor α (TNFα) and calprotectin) was analyzed. The ingestion of high amounts of OO PC, as contained in FVOO, tended to increase the proportions of IgA-coated bacteria and increased plasma levels of CRP. However, lower amounts of OO PC (VOO) and the combination of two PC sources (FVOOT) did not show significant effects on the variables investigated. Results indicate a potential stimulation of the immune system with very high doses of OO PC, which should be further investigated. PMID:27077879

  15. Influence of Phenol-Enriched Olive Oils on Human Intestinal Immune Function

    Directory of Open Access Journals (Sweden)

    Sandra Martín-Peláez

    2016-04-01

    Full Text Available Olive oil (OO phenolic compounds (PC are able to influence gut microbial populations and metabolic output. Our aim was to investigate whether these compounds and changes affect the mucosal immune system. In a randomized, controlled, double blind cross-over human trial, for three weeks, preceded by two-week washout periods, 10 hypercholesterolemic participants ingested 25 mL/day of three raw virgin OO differing in their PC concentration and origin: (1 an OO containing 80 mg PC/kg (VOO; (2 a PC-enriched OO containing 500 mg PC/kg from OO (FVOO; and (3 a PC-enriched OO containing a mixture of 500 mg PC/kg from OO and thyme (1:1, FVOOT. Intestinal immunity (fecal immunoglobulin A (IgA and IgA-coated bacteria and inflammation markers (C-reactive protein (CRP and fecal interleukin 6 (IL-6, tumor necrosis factor α (TNFα and calprotectin was analyzed. The ingestion of high amounts of OO PC, as contained in FVOO, tended to increase the proportions of IgA-coated bacteria and increased plasma levels of CRP. However, lower amounts of OO PC (VOO and the combination of two PC sources (FVOOT did not show significant effects on the variables investigated. Results indicate a potential stimulation of the immune system with very high doses of OO PC, which should be further investigated.

  16. Assessment and Molecular Characterization of Human Intestinal Parasites in Bivalves from Orchard Beach, NY, USA.

    Science.gov (United States)

    Tei, Freda F; Kowalyk, Steven; Reid, Jhenelle A; Presta, Matthew A; Yesudas, Rekha; Mayer, D C Ghislaine

    2016-04-01

    Bivalves have been shown to be carriers of the human intestinal parasites Cryptosporidium parvum and Toxoplasma gondii. The goal of this study is to determine the prevalence of protozoan parasites in mollusks of New York City using a polymerase chain reaction (PCR)-based assay. Four species of mollusks, Mya arenaria, Geukensia demissa, Crassostrea virginica, and Mytilis edulis, were collected from Orchard Beach, NY in the fall of 2014, totaling 159 specimens. Each individual mollusk was dissected to harvest the digestive gland, the mantle, the gills, the foot and the siphon. The tissues were assayed for the presence of Cryptosporidium parvum, Giardia lamblia, and Toxoplasma gondii DNA by using primers that target parasite-specific genes. C. parvum was found at a prevalence of 50%, 11.3%, and 1%, respectively, in Mya arenaria, G. demissa, and Mytilis edulis. C. parvum DNA was detected in all the tissues of these bivalve species, except the gills. Furthermore, G. lamblia was detected in Mya arenaria, G. demissa, Crassostrea virginica and Mytilis edulis at a prevalence of 37.5%, 4.5%, 60%, and 20.6%, respectively, while T. gondii DNA was not detected. PMID:27043590

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

    Science.gov (United States)

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

    2016-08-01

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

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

    DEFF Research Database (Denmark)

    Rumessen, J J; Thuneberg, L

    1991-01-01

    with elastin fibers. The organization shown in this study strongly supports the concept of interstitial cells of Cajal as important regulatory cells also in the human small intestine. The characteristic cytology and organization of interstitial cells of Cajal may provide a basis for future morphological......Previous morphological and electrophysiological studies have supported the hypothesis that interstitial cells of Cajal have important regulatory (pacemaker) functions in the gut. In the current study, interstitial cells of Cajal associated with Auerbach's plexus in human small intestine were...... of bundles containing processes of two to seven cells with fibroblastlike cells interspersed in the bundles. The bundles were innervated by nerve elements of Auerbach's plexus and extended into both layers of smooth muscle, between muscle cells, and into septa. The bundles were closely associated...

  19. 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

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

    OpenAIRE

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

    1999-01-01

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

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

    OpenAIRE

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

    2013-01-01

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

  2. Lipopolysaccharide binding protein and serum amyloid A secretion by human intestinal epithelial cells during the acute phase response.

    Science.gov (United States)

    Vreugdenhil, A C; Dentener, M A; Snoek, A M; Greve, J W; Buurman, W A

    1999-09-01

    The acute phase proteins LPS binding protein (LBP) and serum amyloid A (SAA) are produced by the liver and are present in the circulation. Both proteins have been shown to participate in the immune response to endotoxins. The intestinal mucosa forms a large surface that is continuously exposed to these microbial products. By secretion of antimicrobial and immunomodulating agents, the intestinal epithelium contributes to the defense against bacteria and their products. The aim of this study was to explore the influence of the inflammatory mediators TNF-alpha, IL-6, and IL-1beta on the release of LBP and SAA by intestinal epithelial cells (IEC). In addition, the induction of LBP and SAA release by cell lines of intestinal epithelial cells and hepatic cells was compared. The data obtained show that in addition to liver cells, IEC also expressed LBP mRNA and released bioactive LBP and SAA upon stimulation. Regulation of LBP and SAA release by IEC and hepatocytes was typical for class 1 acute phase proteins, although differences in regulation between the cell types were observed. Endotoxin did not induce LBP and SAA release. Glucocorticoids were demonstrated to strongly enhance the cytokine-induced release of LBP and SAA by IEC, corresponding to hepatocytes. The data from this study, which imply that human IEC can produce LBP and SAA, suggest a role for these proteins in the local defense mechanism of the gut to endotoxin. Furthermore, the results demonstrate that tissues other than the liver are involved in the acute phase response.

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

    International Nuclear Information System (INIS)

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

  4. Lactic acid bacteria protect human intestinal epithelial cells from Staphylococcus aureus and Pseudomonas aeruginosa infections.

    Science.gov (United States)

    Affhan, S; Dachang, W; Xin, Y; Shang, D

    2015-01-01

    Staphylococcus aureus and Pseudomonas aeruginosa are opportunistic pathogens that cause nosocomial and food-borne infections. They promote intestinal diseases. Gastrointestinal colonization by S. aureus and P. aeruginosa has rarely been researched. These organisms spread to extra gastrointestinal niches, resulting in increasingly progressive infections. Lactic acid bacteria are Gram-positive bacteria that produce lactic acid as the major end-product of carbohydrate fermentation. These bacteria inhibit pathogen colonization and modulate the host immune response. This study aimed to investigate the effects of Lactobacillus acidophilus and Lactobacillus rhamnosus on enteric infections caused by the paradigmatic human pathogens S. aureus ATCC25923 and P. aeruginosa ATCC27853. The effect of whole cells and neutralized cell-free supernatant (CFS) of the lactobacilli on LoVo human carcinoma enterocyte (ATCC CCL-229) infection was analyzed by co-exposure, pre-exposure, and post-exposure studies. Simultaneous application of whole cells and CFS of the lactobacilli significantly eradicated enterocyte infection (P 0.05). This result could be attributed to interference by extracellular polymeric substances and cell surface hydrophobicity, which resulted in the development of a pathogen that did not form colonies. Furthermore, results of the plate count and LIVE/ DEAD BacLight bacterial viability staining attributed this inhibition to a non-bacteriocin-like substance, which acted independently of organic acid and H2O2 production. Based on these results, the cell-free supernatant derived from lactobacilli was concluded to restrain the development of S. aureus and P. aeruginosa enteric infections. PMID:26681052

  5. Impact of Different Fecal Processing Methods on Assessments of Bacterial Diversity in the Human Intestine

    Science.gov (United States)

    Hsieh, Yu-Hsin; Peterson, Courtney M.; Raggio, Anne; Keenan, Michael J.; Martin, Roy J.; Ravussin, Eric; Marco, Maria L.

    2016-01-01

    The intestinal microbiota are integral to understanding the relationships between nutrition and health. Therefore, fecal sampling and processing protocols for metagenomic surveys should be sufficiently robust, accurate, and reliable to identify the microorganisms present. We investigated the use of different fecal preparation methods on the bacterial community structures identified in human stools. Complete stools were collected from six healthy individuals and processed according to the following methods: (i) randomly sampled fresh stool, (ii) fresh stool homogenized in a blender for 2 min, (iii) randomly sampled frozen stool, and (iv) frozen stool homogenized in a blender for 2 min, or (v) homogenized in a pneumatic mixer for either 10, 20, or 30 min. High-throughput DNA sequencing of the 16S rRNA V4 regions of bacterial community DNA extracted from the stools showed that the fecal microbiota remained distinct between individuals, independent of processing method. Moreover, the different stool preparation approaches did not alter intra-individual bacterial diversity. Distinctions were found at the level of individual taxa, however. Stools that were frozen and then homogenized tended to have higher proportions of Faecalibacterium, Streptococcus, and Bifidobacterium and decreased quantities of Oscillospira, Bacteroides, and Parabacteroides compared to stools that were collected in small quantities and not mixed prior to DNA extraction. These findings indicate that certain taxa are at particular risk for under or over sampling due to protocol differences. Importantly, homogenization by any method significantly reduced the intra-individual variation in bacteria detected per stool. Our results confirm the robustness of fecal homogenization for microbial analyses and underscore the value of collecting and mixing large stool sample quantities in human nutrition intervention studies.

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    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...... 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...

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

    Science.gov (United States)

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

    2015-02-01

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

  8. The rule of unity for human intestinal absorption 2: application to pharmaceutical drugs that are marketed as salts.

    Science.gov (United States)

    Patel, Raj B; Admire, Brittany; Yalkowsky, Samuel H

    2015-01-01

    The efficiency of the human intestinal absorption (HIA) of the 59 drugs which are marketed as salts is predicted using the rule of unity. Intrinsic aqueous solubilities and partition coefficients along with the drug dose are used to calculate modified absorption potential (MAP) values. These values are shown to be related to the fraction of the dose that is absorbed upon oral administration in humans (FA). It is shown that the MAP value can distinguish between drugs that are poorly absorbed (FA unity based solely on in vitro data for predicting whether or not a drug will be well absorbed at a given dose.

  9. 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

    -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

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

    Science.gov (United States)

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

    2011-11-01

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

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

    Directory of Open Access Journals (Sweden)

    Ekaette Godwin Edelduok

    2013-01-01

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

  12. Antioxidant activity of vasoactive intestinal peptide in HK2 human renal cells.

    Science.gov (United States)

    Vacas, Eva; Bajo, Ana M; Schally, Andrew V; Sánchez-Chapado, Manuel; Prieto, Juan C; Carmena, María J

    2012-12-01

    Oxidative stress is a major mediator of tissue and cell injuries. The injury in chronic nephrotic syndrome, acute renal failure, myeloma kidney injury and other kidney diseases is initiated by oxidative stress. We have previously demonstrated that vasoactive intestinal peptide (VIP) acts as an antiproliferative agent in renal cancer cells. This study was designed to evaluate the renoprotective activity of VIP against H(2)O(2)-induced oxidative damage in a proximal tubule kidney cell line (human, non-tumor, HK2 cells) in order to investigate the potential usefulness of this peptide in the treatment of oxidative-stress related kidney diseases. HK2 cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Propidium iodide was used to identify cells undergoing apoptosis. Western blotting was performed with anti-Bcl-2, anti-Bax and anti-formyl peptide receptor (low-affinity variant FPRL-1) monoclonal antibodies whereas 2,7-dichlorofluorescein diacetate was used for measurement of levels of intracellular reactive oxygen species (ROS). HK2 cells were injured with H(2)O(2) in order to induce apoptosis: the effect was time- and dose-dependent. VIP increased the levels of the antiapoptotic protein Bcl-2 and decreased those of the proapoptotic protein Bax. VIP decreased the intracellular ROS levels reached by H(2)O(2)-induced oxidative stress. VIP effect on ROS levels involved FPLR-1 but not VPAC(1,2) receptors as evidenced by the use of the respective antagonists WRW4 and JV-1-53. Thus, VIP protects HK2 cells from apoptosis by increasing Bcl-2 levels and this effect is initiated through FPLR1 receptor. In conclusion, VIP might exert a renoprotective effect by the suppression of oxidative stress.

  13. 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

  14. Gelatin tannate reduces the proinflammatory effects of lipopolysaccharide in human intestinal epithelial cells

    Directory of Open Access Journals (Sweden)

    Frasca G

    2012-05-01

    Full Text Available Giuseppina Frasca1, Venera Cardile1, Carmelo Puglia2, Claudia Bonina2, Francesco Bonina21Department of Biomedical Sciences, (Physiology, 2Department of Drug Sciences, University of Catania, Catania, ItalyBackground: Gelatin tannate is a mixture of tannic acid and gelatin. Tannic acid has astringent properties, due to its capacity to form protein–macromolecular complexes, as well as antibacterial and antioxidant properties. However, little is known about its anti-inflammatory properties. Purpose: To evaluate the anti-inflammatory activity of gelatin tannate by quantifying the suppression of key molecules produced during inflammatory events in lipopolysaccharide (LPS-stimulated human intestinal cells. Methods: Intercellular adhesion molecule-1 (ICAM-1 expression was determined by Western blot analysis; interleukin-8 (IL-8 and tumor necrosis factor-α (TNF-α concentrations were measured by enzyme-linked immunosorbent assays in Caco-2 cells 24 hours after treatment with LPS (1 μg/mL in presence of different concentrations of gelatin tannate. Results: ICAM-1 is induced on a wide variety of cells by inflammatory stimuli such as LPS. Our results have shown gelatin tannate as a potent inhibitor of ICAM-1 expression in LPS-stimulated Caco-2 cells. IL-8 and TNF-α are important inflammatory mediators, recruiting neutrophils and T-lymphocytes. Together with LPS, adding gelatin tannate at different concentrations induced a dose-dependent inhibition of IL-8 and TNF-α released by Caco-2 cells. Conclusion: These results suggest that gelatin tannate exerts anti-inflammatory effects by inhibiting the specific cytokines and adhesion molecules involved in several inflammatory disorders.Keywords: Caco-2, ICAM-1, IL-8, TNF-α

  15. 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

  16. Understanding the human dimensions of a sustainable energy transition

    Directory of Open Access Journals (Sweden)

    Linda eSteg

    2015-06-01

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

  17. Understanding the human dimensions of a sustainable energy transition.

    Science.gov (United States)

    Steg, Linda; Perlaviciute, Goda; van der Werff, Ellen

    2015-01-01

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

  18. THE EPIDEMIOLOGICAL SURVEY OF HUMAN INTESTINAL PARASITES IN RURAL AREAS OF LARIJAN

    Directory of Open Access Journals (Sweden)

    M. Rezaian

    1992-06-01

    Full Text Available This Survey was carried out from June to October 1990, in order to evaluate the prevalence of intestinal parasites in the residents. A total of 2227 persons were selected from 44 Villages by using linear Systematic Sampling Method. The Samples of stool from these people were examined by formalin - ether concentration procedure. The collected data were analyzed by spss package. The result showed that 69.2% of the specimens were infected with intestinal parasites, which 58.4% of them were pathogenic (33.8% 16.9%, and 7.7% were infected with 1,2 and 3 species intestinal pathogen parasites respectively. Infection rates with intestinal pathogen parasites was higher in mountains (71.4% than plain areas (49.6%. and also higher in age groups 5-14 years (68.0% than other age groups. The difference of the infection rates was nonsignificant between males and females. Prevalence of different intestinal parasites was as follows: Protozoa; E.Coli 27.9% G. lamblia 17.2% I.butschlii 7/0% E.histolytica 5.9% E. hartmann 2.9% E. nana 2. 1% D. fragilis. 6% and C.. mesnili 0.4% Helminths; T. trichiura 26. 8% A. lumbricoides 17.8% Hook worm 8.9% S. stercoralis 8.5% E. vermicularis 3. 6% T.saginata 1. 4%, H.nana %1.0 and Trichostrongylus sp. 0.7%

  19. Transcriptional response of HT-29 intestinal epithelial cells to human and bovine milk oligosaccharides.

    Science.gov (United States)

    Lane, Jonathan A; O'Callaghan, John; Carrington, Stephen D; Hickey, Rita M

    2013-12-01

    Human milk oligosaccharides (HMO) have been shown to interact directly with immune cells. However, large quantities of HMO are required for intervention or clinical studies, but these are unavailable in most cases. In this respect, bovine milk is potentially an excellent source of commercially viable analogues of these unique molecules. In the present study, we compared the transcriptional response of colonic epithelial cells (HT-29) to the entire pool of HMO and bovine colostrum oligosaccharides (BCO) to determine whether the oligosaccharides from bovine milk had effects on gene expression that were similar to those of their human counterparts. Gene set enrichment analysis of the transcriptional data revealed that there were a number of similar biological processes that may be influenced by both treatments including a response to stimulus, signalling, locomotion, and multicellular, developmental and immune system processes. For a more detailed insight into the effects of milk oligosaccharides, the effect on the expression of immune system-associated glycogenes was chosen as a case study when performing validation studies. Glycogenes in the current context are genes that are directly or indirectly regulated in the presence of glycans and/or glycoconjugates. RT-PCR analysis revealed that HMO and BCO influenced the expression of cytokines (IL-1β, IL-8, colony-stimulating factor 2 (granulocyte-macrophage) (GM-CSF2), IL-17C and platelet factor 4 (PF4)), chemokines (chemokine (C-X-C motif) ligand 1 (CXCL1), chemokine (C-X-C motif) ligand 3 (CXCL3), chemokine (C-C motif) ligand 20 (CCL20), chemokine (C-X-C motif) ligand 2 (CXCL2), chemokine (C-X-C motif) ligand 6 (CXCL6), chemokine (C-C motif) ligand 5 (CCL5), chemokine (C-X3-C motif) ligand 1 (CX3CL1) and CXCL2) and cell surface receptors (interferon γ receptor 1 (IFNGR1), intercellular adhesion molecule-1 (ICAM-1), intercellular adhesion molecule-2 (ICAM-2) and IL-10 receptor α (IL10RA)). The present study suggests

  20. Drug transport and transport-metabolism interplay in the human and rat intestine : ex vivo studies with precision-cut intestinal slices

    NARCIS (Netherlands)

    Li, Ming

    2016-01-01

    The intestine plays an important role in uptake and metabolism of physiological, but also xenobiotic compounds, such as medical drugs. This function is supported by specialized transporters and metabolic enzymes. Together these proteins determine the concentration of compounds in intestinal cells an

  1. Epidermal growth factor inhibits glycyl sarcosine transport and hPepT1 expression in a human intestinal cell line

    DEFF Research Database (Denmark)

    Nielsen, Carsten Uhd; Amstrup, Jan; Steffansen, Bente;

    2001-01-01

    Intestinal oligopeptide transporter, growth factor, immunocytochemistry, laser scanning confocal microscopy......Intestinal oligopeptide transporter, growth factor, immunocytochemistry, laser scanning confocal microscopy...

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Luca ePastorelli

    2013-09-01

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

  4. The intestine is a blender

    Science.gov (United States)

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

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

  5. SURVEY OF HOUSE RAT INTESTINAL PARASITES FROM SURABAYA DISTRICT, EAST JAVA, INDONESIA THAT CAN CAUSE OPPORTUNISTIC INFECTIONS IN HUMANS.

    Science.gov (United States)

    Prasetyo, R H

    2016-03-01

    The purpose of this study was to investigate the prevalence of house rat zoonotic intestinal parasites from Surabaya District, East Java, Indonesia that have the potential to cause opportunistic infection in humans. House rat fecal samples were collected from an area of Surabaya District with a dense rat population during May 2015. Intestinal parasites were detected microscopically using direct smear of feces stained with Lugol's iodine and modified Ziehl-Neelsen stains. The fecal samples were also cultured for Strongyloides stercoralis. Ninety-eight house rat fecal samples were examined. The potential opportunistic infection parasite densities found in those samples were Strongyloides stercoralis in 53%, Hymenolepis nana in 42%, Cryptosporidium spp in 33%, and Blastocystis spp in 6%. This is the first report of this kind in Surabaya District. Measures need to be taken to control the house rat population in the study area to reduce the risk of the public health problem. Keywords: zoonotic intestinal parasites, opportunistic infection, house rat, densely populated area, Indonesia PMID:27244955

  6. SURVEY OF HOUSE RAT INTESTINAL PARASITES FROM SURABAYA DISTRICT, EAST JAVA, INDONESIA THAT CAN CAUSE OPPORTUNISTIC INFECTIONS IN HUMANS.

    Science.gov (United States)

    Prasetyo, R H

    2016-03-01

    The purpose of this study was to investigate the prevalence of house rat zoonotic intestinal parasites from Surabaya District, East Java, Indonesia that have the potential to cause opportunistic infection in humans. House rat fecal samples were collected from an area of Surabaya District with a dense rat population during May 2015. Intestinal parasites were detected microscopically using direct smear of feces stained with Lugol's iodine and modified Ziehl-Neelsen stains. The fecal samples were also cultured for Strongyloides stercoralis. Ninety-eight house rat fecal samples were examined. The potential opportunistic infection parasite densities found in those samples were Strongyloides stercoralis in 53%, Hymenolepis nana in 42%, Cryptosporidium spp in 33%, and Blastocystis spp in 6%. This is the first report of this kind in Surabaya District. Measures need to be taken to control the house rat population in the study area to reduce the risk of the public health problem. Keywords: zoonotic intestinal parasites, opportunistic infection, house rat, densely populated area, Indonesia

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2002-01-01

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

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

    Science.gov (United States)

    Traber, M G; Kayden, H J; Rindler, M J

    1987-11-01

    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 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. Secretion of lipoproteins was dependent on the lipid content of the medium; prior incubation with lipoprotein-depleted serum specifically reduced the secretion of lipoproteins, while addition of both LDL and oleic acid to the medium maintained the level of apoB-100, B-48, and A-IV secretion to that observed in the control

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

    Science.gov (United States)

    Pampiglione, S; Visconti, S; Pezzino, G

    1987-04-01

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

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

    OpenAIRE

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

    2002-01-01

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

  12. Digestion of so-called resistant starch sources in the human small intestine

    NARCIS (Netherlands)

    Vonk, RJ; Hagedoorn, RE; de Graaff, R; Elzinga, H; Tabak, S; Yang, YX; Stellaard, F

    2000-01-01

    Background: Resistant starch sources, which are only partially digested in the small intestine, can be used to increase colonic availability of short-chain fatty acids. Objective: To study the characteristics of the fermentation of resistant starch, the digestion of resistant starch in the small int

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

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

    DEFF Research Database (Denmark)

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

    2005-01-01

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

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

    NARCIS (Netherlands)

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

    2007-01-01

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

  16. 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 ...

  17. Intestinal leiomyoma

    Science.gov (United States)

    Leiomyoma - intestine ... McLaughlin P, Maher MM. The duodenum and small intestine. In: Adam A, Dixon AK, Gillard JH, Schaefer- ... Roline CE, Reardon RF. Disorders of the small intestine. In: Marx JA, Hockberger RS, Walls RM, et ...

  18. Among plant lignans, pinoresinol has the strongest antiinflammatory properties in human intestinal Caco-2 cells.

    Science.gov (United States)

    During, Alexandrine; Debouche, Céline; Raas, Thomas; Larondelle, Yvan

    2012-10-01

    Dietary lignans show some promising health benefits, but little is known about their fate and activities in the small intestine. The purpose of this study was thus to investigate whether plant lignans are taken up by intestinal cells and modulate the intestinal inflammatory response using the Caco-2 cell model. Six lignan standards [secoisolariciresinol diglucoside (SDG), secoisolariciresinol (SECO), pinoresinol (PINO), lariciresinol, matairesinol (MAT), and hydroxymatairesinol] and their colonic metabolites [enterolactone (ENL) and enterodiol] were studied. First, differentiated cells were exposed to SDG, SECO, PINO, or ENL at increasing concentrations for 4 h, and their cellular contents (before and after deconjugation) were determined by HPLC. Second, in IL-1β-stimulated confluent and/or differentiated cells, lignan effects were tested on different soluble proinflammatory mediators quantified by enzyme immunoassays and on the NF-κB activation pathway by using cells transiently transfected. SECO, PINO, and ENL, but not SDG, were taken up and partly conjugated by cells, which is a saturable conjugation process. PINO was the most efficiently conjugated (75% of total in cells). In inflamed cells, PINO significantly reduced IL-6 by 65% and 30% in confluent and differentiated cells, respectively, and cyclooxygenase (COX)-2-derived prostaglandin E(2) by 62% in confluent cells. In contrast, MAT increased significantly COX-2-derived prostaglandin E(2) in confluent cells. Moreover, PINO dose-dependently decreased IL-6 and macrophage chemoattractant protein-1 secretions and NF-κB activity. Our findings suggest that plant lignans can be absorbed and metabolized in the small intestine and, among the plant lignans tested, PINO exhibited the strongest antiinflammatory properties by acting on the NF-κB signaling pathway, possibly in relation to its furofuran structure and/or its intestinal metabolism.

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

    Science.gov (United States)

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

    2011-01-01

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

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

    DEFF Research Database (Denmark)

    Schär, Fabian; Inpankaew, Tawin; Traub, Rebecca J.;

    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......., 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...

  1. 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

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

    Directory of Open Access Journals (Sweden)

    Frederique Respondek

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

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

    Directory of Open Access Journals (Sweden)

    Carolin A Kolmeder

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

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

    Institute of Scientific and Technical Information of China (English)

    RoelJ.Vonk; Yue-XinYang; 等

    2001-01-01

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

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

    OpenAIRE

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

    2013-01-01

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

  6. 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.

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

    Science.gov (United States)

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

    2015-11-01

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

  8. 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.

  9. 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

  10. 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; Hendriksen, Niels Bohse;

    2006-01-01

    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......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...... 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....

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

    OpenAIRE

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

    2007-01-01

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

  12. Intestinal microbiota and ulcerative colitis.

    Science.gov (United States)

    Ohkusa, Toshifumi; Koido, Shigeo

    2015-11-01

    There is a close relationship between the human host and the intestinal microbiota, which is an assortment of microorganisms, protecting the intestine against colonization by exogenous pathogens. Moreover, the intestinal microbiota play a critical role in providing nutrition and the modulation of host immune homeostasis. Recent reports indicate that some strains of intestinal bacteria are responsible for intestinal ulceration and chronic inflammation in inflammatory bowel diseases (IBD) such as ulcerative colitis (UC) and Crohn's disease (CD). Understanding the interaction of the intestinal microbiota with pathogens and the human host might provide new strategies treating patients with IBD. This review focuses on the important role that the intestinal microbiota plays in maintaining innate immunity in the pathogenesis and etiology of UC and discusses new antibiotic therapies targeting the intestinal microbiota.

  13. 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 μmol/L. Micronuclei assay measurement indicates that CpG-ODN can protect HIEC from radiation damage by reducing the micronucleus frequency (MNF) and the micronucleus cell frequency (MNCF). The experiment results reveal that CpG-ODN is safe and may have radioprotection effect on some non-immune human cell types. (authors)

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

    Science.gov (United States)

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

    2015-01-01

    Polyphenolic compounds (anthocyanins, flavonoid glycosides) in berries prevent the initiation, promotion, and progression of carcinogenesis in rat's digestive tract and esophagus, in part, via anti-inflammatory pathways. Angiogenesis has been implicated in the pathogenesis of chronic inflammation and tumorigenesis. In this study, we investigated the anti-inflammatory and anti-angiogenic effects of black raspberry extract (BRE) on two organ specific primary human intestinal microvascular endothelial cells, (HIMEC) and human esophageal microvascular endothelial cells (HEMEC), isolated from surgically resected human intestinal and donor discarded esophagus, respectively. HEMEC and HIMEC were stimulated with TNF-α/IL-1β with or without BRE. The anti-inflammatory effects of BRE were assessed based upon COX-2, ICAM-1 and VCAM-1 gene and protein expression, PGE2 production, NFκB p65 subunit nuclear translocation as well as endothelial cell-leukocyte adhesion. The anti-angiogenic effects of BRE were assessed on cell migration, proliferation and tube formation following VEGF stimulation as well as on activation of Akt, MAPK and JNK signaling pathways. BRE inhibited TNF-α/IL-1β-induced NFκB p65 nuclear translocation, PGE2 production, up-regulation of COX-2, ICAM-1 and VCAM-1 gene and protein expression and leukocyte binding in HEMEC but not in HIMEC. BRE attenuated VEGF-induced cell migration, proliferation and tube formation in both HEMEC and HIMEC. The anti-angiogenic effect of BRE is mediated by inhibition of Akt, MAPK and JNK phosphorylations. BRE exerted differential anti-inflammatory effects between HEMEC and HIMEC following TNF-α/IL-1β activation whereas demonstrated similar anti-angiogenic effects following VEGF stimulation in both cell lines. These findings may provide more insight into the anti-tumorigenic capacities of BRE in human disease and cancer.

  15. Small intestinal bacterial overgrowth syndrome

    Institute of Scientific and Technical Information of China (English)

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

    2010-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Shota eHagio

    2015-02-01

    Full Text Available 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 experimenter’s 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.

  17. A galectin-specific signature in the gut delineates Crohn's disease and ulcerative colitis from other human inflammatory intestinal disorders.

    Science.gov (United States)

    Papa Gobbi, Rodrigo; De Francesco, Nicolás; Bondar, Constanza; Muglia, Cecilia; Chirdo, Fernando; Rumbo, Martín; Rocca, Andrés; Toscano, Marta A; Sambuelli, Alicia; Rabinovich, Gabriel A; Docena, Guillermo H

    2016-01-01

    Inflammatory bowel diseases (IBD) are chronic and relapsing inflammatory conditions of the gastrointestinal tract including Crohn's disease (CD) and ulcerative colitis (UC). Galectins, defined by shared consensus amino acid sequence and affinity for β-galactosides, are critical modulators of the inflammatory response. However, the relevance of the galectin network in the pathogenesis of human IBD has not yet been explored. Here, we analyzed the expression of relevant members of the galectin family in intestinal biopsies, and identified their contribution as novel mucosal markers in IBD. Colonic biopsies were obtained from 59 IBD patients (22 CD and 37 UC), 9 patients with gut rejection after transplantation, 8 adult celiac patients, and 32 non-IBD donors. Galectin mRNA expression was analyzed by RT-PCR and qPCR using specific primers for individual galectins. A linear discriminant analysis (LDA) was used to analyze galectin expression in individual intestinal samples. Expression of common mucosal-associated galectins (Gal-1, -3, -4, -9) is dysregulated in inflamed tissues of IBD patients compared with non-inflamed IBD or control samples. LDA discriminated between different inflammation grades in active IBD and showed that remission IBD samples were clusterized with control samples. Galectin profiling could not distinguish CD and UC. Furthermore, inflamed IBD was discriminated from inflamed tissue of rejected gut in transplanted patients and duodenum of celiac patients, which could not be distinguished from control duodenum samples. The integrative analysis of galectins discriminated IBD from other intestinal inflammatory conditions and could be used as potential mucosal biomarker.

  18. Anti-Human Tissue Factor Antibody Ameliorated Intestinal Ischemia Reperfusion-Induced Acute Lung Injury in Human Tissue Factor Knock-In Mice

    Science.gov (United States)

    Mura, Marco; Li, Li; Cypel, Marcelo; Soderman, Avery; Picha, Kristen; Yang, Jing; Liu, Mingyao

    2008-01-01

    Background Interaction between the coagulation and inflammation systems plays an important role in the development of acute respiratory distress syndrome (ARDS). Anti-coagulation is an attractive option for ARDS treatment, and this has promoted development of new antibodies. However, preclinical trials for these antibodies are often limited by the high cost and availability of non-human primates. In the present study, we developed a novel alternative method to test the role of a humanized anti-tissue factor mAb in acute lung injury with transgenic mice. Methodology/Principal Findings Human tissue factor knock-in (hTF-KI) transgenic mice and a novel humanized anti-human tissue factor mAb (anti-hTF mAb, CNTO859) were developed. The hTF-KI mice showed a normal and functional expression of hTF. The anti-hTF mAb specifically blocked the pro-coagulation activity of brain extracts from the hTF-KI mice and human, but not from wild type mice. An extrapulmonary ARDS model was used by intestinal ischemia-reperfusion. Significant lung tissue damage in hTF-KI mice was observed after 2 h reperfusion. Administration of CNTO859 (5 mg/kg, i.v.) attenuated the severity of lung tissue injury, decreased the total cell counts and protein concentration in bronchoalveolar lavage fluid, and reduced Evans blue leakage. In addition, the treatment significantly reduced alveolar fibrin deposition, and decreased tissue factor and plasminogen activator inhibitor-1 activity in the serum. This treatment also down-regulated cytokine expression and reduced cell death in the lung. Conclusions This novel anti-hTF antibody showed beneficial effects on intestinal ischemia-reperfusion induced acute lung injury, which merits further investigation for clinical usage. In addition, the use of knock-in transgenic mice to test the efficacy of antibodies against human-specific proteins is a novel strategy for preclinical studies. PMID:18231608

  19. A modular organization of the human intestinal mucosal microbiota and its association with inflammatory bowel disease.

    Directory of Open Access Journals (Sweden)

    Maomeng Tong

    Full Text Available Abnormalities of the intestinal microbiota are implicated in the pathogenesis of Crohn's disease (CD and ulcerative colitis (UC, two spectra of inflammatory bowel disease (IBD. However, the high complexity and low inter-individual overlap of intestinal microbial composition are formidable barriers to identifying microbial taxa representing this dysbiosis. These difficulties might be overcome by an ecologic analytic strategy to identify modules of interacting bacteria (rather than individual bacteria as quantitative reproducible features of microbial composition in normal and IBD mucosa. We sequenced 16S ribosomal RNA genes from 179 endoscopic lavage samples from different intestinal regions in 64 subjects (32 controls, 16 CD and 16 UC patients in clinical remission. CD and UC patients showed a reduction in phylogenetic diversity and shifts in microbial composition, comparable to previous studies using conventional mucosal biopsies. Analysis of weighted co-occurrence network revealed 5 microbial modules. These modules were unprecedented, as they were detectable in all individuals, and their composition and abundance was recapitulated in an independent, biopsy-based mucosal dataset 2 modules were associated with healthy, CD, or UC disease states. Imputed metagenome analysis indicated that these modules displayed distinct metabolic functionality, specifically the enrichment of oxidative response and glycan metabolism pathways relevant to host-pathogen interaction in the disease-associated modules. The highly preserved microbial modules accurately classified IBD status of individual patients during disease quiescence, suggesting that microbial dysbiosis in IBD may be an underlying disorder independent of disease activity. Microbial modules thus provide an integrative view of microbial ecology relevant to IBD.

  20. Analysis of the human intestinal microbiota from 92 volunteers after ingestion of identical meals.

    Science.gov (United States)

    Jin, J S; Touyama, M; Kibe, R; Tanaka, Y; Benno, Y; Kobayashi, T; Shimakawa, M; Maruo, T; Toda, T; Matsuda, I; Tagami, H; Matsumoto, M; Seo, G; Chonan, O; Benno, Y

    2013-06-01

    The intestinal microbiota composition of 92 volunteers living in Japan was identified following the consumption of 'identical meals' (1,879 kcal/day) for 3 days. When faecal samples were analysed by terminal restriction fragment length polymorphism with several primer-restriction enzyme systems and then clustered, the patterns could be divided into 2 clusters. Contribution tests and partition modelling showed that OTU211 of the 35f-MspI system and OTU237 of the 35f-AluI system were key factors in the distribution of these groups. However, significant differences among these groups in terms of body mass index and age were not observed.

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

    Science.gov (United States)

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

    1987-12-01

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

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

    Science.gov (United States)

    Barrera, Girolamo J; Sánchez, Gabriela

    2016-08-01

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

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

    Science.gov (United States)

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

    2016-02-01

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

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

    International Nuclear Information System (INIS)

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

  5. 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 γ-secretase inhibitor significantly down-regulated the induction of those genes in IECs, resulting in a markedly poor response to IL-22. Our present findings identify a new role for the molecular function of Hes1 in which the protein can interact with cytokine signals and regulate the immune response of IECs.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-02-01

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

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2007-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Ulrike Lodemann

    2015-01-01

    Full Text Available 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.

  11. 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 λ light chains. The real time polymerase chain reaction (QRT-PCR) method detected many copies from the genome of type 8 human herpesvirus (VHH-8) (133 copies/μL of DNA) in biopsy of intestinal nodule DNA. VHH-8 infection may to be a significant factor in pathogenesis of lymphoproliferative disorders in patients presenting with CVID

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Malgorzata Nepelska

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

  14. Intestinal absorption and biomagnification of organic contaminants in fish, wildlife, and humans.

    Science.gov (United States)

    Kelly, Barry C; Gobas, Frank A P C; McLachlan, Michael S

    2004-10-01

    Methods for the regulatory assessment of the bioaccumulation potential of organic chemicals are founded on empirical measurements and mechanistic models of dietary absorption and biomagnification. This study includes a review of the current state of knowledge regarding mechanisms and models of intestinal absorption and biomagnification of organic chemicals in organisms of aquatic and terrestrial food chains and also includes a discussion of the implications of these models for assessing the bioaccumulation potential of organic chemicals. Four mechanistic models, including biomass conversion, digestion or gastrointestinal magnification, micelle-mediated diffusion, and fat-flush diffusion, are evaluated. The models contain many similarities and represent an evolution in understanding of chemical bioaccumulation processes. An important difference between the biomagnification models is whether intestinal absorption of an ingested contaminant occurs solely via passive molecular diffusion through serial resistances or via facilitated diffusion that incorporates an additional advective transport mechanism in parallel (i.e., molecular ferrying within gastrointestinal micelles). This difference has an effect on the selection of physicochemical properties that best anticipate the bioaccumulative potential of commercial chemicals in aquatic and terrestrial food chains. Current regulatory initiatives utilizing Kow threshold criteria to assess chemical bioaccumulation potential are shown to be unable to identify certain bioaccumulative substances in air-breathing animals. We urge further research on dietary absorption and biomagnification of organic chemicals to develop better models for assessing the bioaccumulative nature of organic chemicals. PMID:15511095

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

    International Nuclear Information System (INIS)

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

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

  17. Small intestinal ischemia and infarction

    Science.gov (United States)

    Intestinal necrosis; Ischemic bowel - small intestine; Dead bowel - small intestine; Dead gut - small intestine; Infarcted bowel - small intestine; Atherosclerosis - small intestine; Hardening of the arteries - small intestine

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

    Science.gov (United States)

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

    2016-05-01

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

  19. The prenylflavonoid isoxanthohumol from hops (Humulus lupulus L.) is activated into the potent phytoestrogen 8-prenylnaringenin in vitro and in the human intestine.

    Science.gov (United States)

    Possemiers, Sam; Bolca, Selin; Grootaert, Charlotte; Heyerick, Arne; Decroos, Karel; Dhooge, Willem; De Keukeleire, Denis; Rabot, Sylvie; Verstraete, Willy; Van de Wiele, Tom

    2006-07-01

    Hops, an essential beer ingredient, are a source of prenylflavonoids, including 8-prenylnaringenin (8-PN), one of the most potent phytoestrogens. Because 8-PN concentrations in beers are generally low, its health effects after moderate beer consumption were considered negligible. However, human intestinal microbiota may activate up to 4 mg/L isoxanthohumol (IX) in beer into 8-PN. Depending on interindividual differences in the intestinal transformation potential, this conversion could easily increase the 8-PN exposure 10-fold upon beer consumption. Here, we present a further investigation of the process both in vitro and in vivo. In vitro experiments with the dynamic SHIME model showed that hop prenylflavonoids pass unaltered through the stomach and small intestine and that activation of IX into 8-PN (up to 80% conversion) occurs only in the distal colon. In vitro incubations of 51 fecal samples from female volunteers with IX enabled us to separate the fecal microbiota into high (8 of 51), moderate (11 of 51) and slow (32 of 51) 8-PN producers, clearly illustrating an interindividual variability. Three women, selected from the respective groups, received a daily dose of 5.59 mg IX for 4 d. Intestinal IX activation and urinary 8-PN excretion were correlated (R(2) = 0.6417, P < 0.01). These data show that intestinal conversion of IX upon moderate beer consumption can lead to 8-PN exposure values that might fall within the range of human biological activity.

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

    Science.gov (United States)

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

    2016-01-01

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

  1. Gastro-intestinal effects of Indian spice mixture (Garam Masala).

    Science.gov (United States)

    Kochhar, K P; Bijlani, R L; Sachdeva, U; Mahapatra, S C; Padhy, A K; Tandon, R K

    1999-01-01

    Spices are a part of diet all over the world but the variety and quantity consumed in tropical countries is particularly significant. The intestinal transit time of Indians is shorter, and their stool weight larger than that of Europeans on a comparable fibre intake. Ingestion of chilli is associated with a faster whole gut transit time. There is hardly any human work on the effects of spices on intestinal transit or gastric emptying. To explore the effects of spices on gastro intestinal transit this study was conducted on 18 well nourished healthy human adult volunteers using Radiolabelled Idli with or without Garam Masala. On gastric scintigraphy the gastric emptying time was much faster in subjects when spicy meal was given. The t1/2 of the spicy meal, 40.09 +/- (p < 0.05) thus implying a faster transit through the stomach. In 17 out of the 18 subjects t1/2 of the spicy meal was consistently lower than that of spicefree meal. The lag phase of gastric emptying showed no significant difference. There was a tendency towards slower gastrocolic transit with Spicefree meal but more subjects need to be done to confirm this. PMID:10769605

  2. Dipeptide transport: an active process with energy- and proton-dependence in the human intestinal cell line, Caco-2

    Institute of Scientific and Technical Information of China (English)

    SUN Bing-wei; SHI Lei; CHEN Xi; CHEN Zhao-yong; TAI Ning-zheng; ZHAO Xiao-chen; LI Ning

    2007-01-01

    Objective: To determine the active process on dipeptide transport with proton- and energydependence in Caco-2 cells. Methods: A human intestinal cell monolayer (Caco-2) was used as the in vitro model of human small intestine and cephalexin as the model substrate for dipeptide transporter (PepT1). Caco-2 cells grown on multiwell dishes (24 wells) and Transwell membrane filters were incubated in the culture medium. The transport and uptake experiments of cephalexin across apical membranes were then conducted with different temperature and different pH values. Uptake of cephalexin in Caco-2 cells grown on multiple well dishes with addition of energy inhibitors( sodium azide, SA and 2,4-dinitrophenol, DNP) were then measured. Results: The accumulation of cephalexin into Caco-2 monolayers increased with the duration of culture. The uptake from the apical surface was markedly influenced by the pH of the apical medium, and the maximal uptake was achieved at pH 5.5; further acidification of the incubation medium may decrease transport of cephalexin despite an increase inward H + gradient.Cephalexin uptake was linear over the concentration range when the cells were incubated at 4 ℃ while the uptake rate was enhanced and tended to be saturated as the cephalexin concentration increased when the cells were incubated at 37 ℃. The kinetic parameters for the cephalexin transport carrier were determined to be: Vmax of (22. 173 ±1.9) nmol/min per mg protein, Km of (2.069 ±0.9) mol/L, the Kd was estimated to be (0.07 ± 0.02) nmol/min per mg protein per mmol/L. Uptake of cephalexin was markedly inhibited by sodium azide (SA) and 2,4-dinitrophenol (DNP). Conclusion: Cephalexin was transported actively across Caco-2 cells, and the transport process was proton- and energy-dependent. In addition, Caco-2 cells taked up cephalexin by dipeptide transporters that closely resembled the transporters present in the intestine. Caco-2 cells represented an ideal cellular model for future

  3. Development of a Multicellular Three-dimensional Organotypic Model of the Human Intestinal Mucosa Grown Under Microgravity.

    Science.gov (United States)

    Salerno-Goncalves, Rosangela; Fasano, Alessio; Sztein, Marcelo B

    2016-01-01

    Because cells growing in a three-dimensional (3-D) environment have the potential to bridge many gaps of cell cultivation in 2-D environments (e.g., flasks or dishes). In fact, it is widely recognized that cells grown in flasks or dishes tend to de-differentiate and lose specialized features of the tissues from which they were derived. Currently, there are mainly two types of 3-D culture systems where the cells are seeded into scaffolds mimicking the native extracellular matrix (ECM): (a) static models and (b) models using bioreactors. The first breakthrough was the static 3-D models. 3-D models using bioreactors such as the rotating-wall-vessel (RWV) bioreactors are a more recent development. The original concept of the RWV bioreactors was developed at NASA's Johnson Space Center in the early 1990s and is believed to overcome the limitations of static models such as the development of hypoxic, necrotic cores. The RWV bioreactors might circumvent this problem by providing fluid dynamics that allow the efficient diffusion of nutrients and oxygen. These bioreactors consist of a rotator base that serves to support and rotate two different formats of culture vessels that differ by their aeration source type: (1) Slow Turning Lateral Vessels (STLVs) with a co-axial oxygenator in the center, or (2) High Aspect Ratio Vessels (HARVs) with oxygenation via a flat, silicone rubber gas transfer membrane. These vessels allow efficient gas transfer while avoiding bubble formation and consequent turbulence. These conditions result in laminar flow and minimal shear force that models reduced gravity (microgravity) inside the culture vessel. Here we describe the development of a multicellular 3-D organotypic model of the human intestinal mucosa composed of an intestinal epithelial cell line and primary human lymphocytes, endothelial cells and fibroblasts cultured under microgravity provided by the RWV bioreactor. PMID:27500889

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

    Directory of Open Access Journals (Sweden)

    Alip Borthakur

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-01-01

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

  6. 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.; Brøndsted, Lone;

    2011-01-01

    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...

  7. Carboxypeptidase-B-like processing of the C-terminus of glucagon-like peptide-2 in pig and human small intestine

    DEFF Research Database (Denmark)

    Orskov, C; Buhl, T; Rabenhøj, L;

    1989-01-01

    no mutual cross-reactivity. By gel filtration of extracts of pig and human small intestine, the immunoreactivity eluting at the position of GLP-2 was identified by the radioimmunoassays for glucagon-like peptide-2 (PG 126-159) and for PG 151-158, whereas the assay for PG 151-160 was completely negative. We...

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

    OpenAIRE

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

    2006-01-01

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

  9. The effect of consumption of milk fermented by Lactobacillus casei strain Shirota on the intestinal microflora and immune parameters in humans

    NARCIS (Netherlands)

    Spanhaak, S.; Havenaar, R.; Schaafsma, G.

    1998-01-01

    Objective: To determine the effect of consumption of milk fermented by Lactobacillus casei strain Shirota (L. casei Shirota) on the composition and metabolic activities of the intestinal microflora, and immune parameters in humans. Subjects: Twenty healthy male subjects aged 40-65 years were selecte

  10. 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...

  11. The Juvenile Transition: A Developmental Switch Point in Human Life History

    Science.gov (United States)

    Del Giudice, Marco; Angeleri, Romina; Manera, Valeria

    2009-01-01

    This paper presents a new perspective on the transition from early to middle childhood (i.e., human juvenility), investigated in an integrative evolutionary framework. Juvenility is a crucial life history stage, when social learning and interaction with peers become central developmental functions; here it is argued that the "juvenile transition"…

  12. Intestinal obstruction

    Science.gov (United States)

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

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

    Science.gov (United States)

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

    2015-09-01

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

  14. Understanding the human dimensions of a sustainable energy transition

    NARCIS (Netherlands)

    Steg, Linda; Perlaviciute, Goda; van der Werff, Ellen

    2015-01-01

    Global climate change threatens the health, economic prospects, and basic food and water sources of people. A wide range of changes in household energy behavior is needed to realize a sustainable energy transition. We propose a general framework to understand and encourage sustainable energy behavio

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

    Science.gov (United States)

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

    2014-08-01

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

  16. 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.

  17. 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

    , 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.

  18. 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

  19. 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...

  20. Microbial diversity in the human intestine and novel insights from metagenomics

    OpenAIRE

    Ventura, Marco; Turroni, Francesca; Canchaya, Carlos; Vaughan, Elaine E.; O'Toole, Paul W.; Van Sinderen, Douwe

    2009-01-01

    Bacterial communities reside in very different ecological niches on and within the human host, such as those associated with the alimentary tract. The human gastrointestinal tract is populated with as many as 100 trillion bacterial cells, whose collective genome likely reflects the co-evolution between the microbial community and its host. Recent progress has highlighted the intriguing diversity of these bacterial populations and their important contributions to human physiology. Thus, a thor...

  1. Endometriosis intestinal Intestinal endometriosis

    OpenAIRE

    C.I. González; M. Cires; F. J. Jiménez; Rubio, T.

    2008-01-01

    La endometriosis es un trastorno ginecológico crónico, benigno y frecuente entre las mujeres en edad fértil, estimándose que existe algún grado de endometriosis hasta en el 15% de las mujeres premenopáusicas, asociándose a historia de infertilidad, antecedente de cesárea, dismenorrea y anormalidad en el sangrado uterino. Se cree que es debida al ascenso por las trompas de Falopio de contenido menstrual (menstruación retrógrada). En la afectación intestinal, el colon es el segmento más frecuen...

  2. Endometriosis intestinal Intestinal endometriosis

    Directory of Open Access Journals (Sweden)

    C.I. González

    2008-08-01

    Full Text Available La endometriosis es un trastorno ginecológico crónico, benigno y frecuente entre las mujeres en edad fértil, estimándose que existe algún grado de endometriosis hasta en el 15% de las mujeres premenopáusicas, asociándose a historia de infertilidad, antecedente de cesárea, dismenorrea y anormalidad en el sangrado uterino. Se cree que es debida al ascenso por las trompas de Falopio de contenido menstrual (menstruación retrógrada. En la afectación intestinal, el colon es el segmento más frecuentemente afectado, sobre todo a nivel rectosigmodeo. La clínica de presentación es inespecífica, siendo lo más frecuente el dolor abdominal y/o pélvico de tipo cólico que coincide o se exacerba con la menstruación. El diagnóstico diferencial incluye la enfermedad inflamatoria intestinal, diverticulitis, colitis isquémica y procesos neoplásicos, siendo el diagnóstico definitivo anatomopatológico. En cuanto al tratamiento, éste dependerá de la clínica y de la edad de la paciente, así como de sus deseos de embarazo.Endometriosis is a chronic, benign gynaecological disorder that is frequent in women of a child-bearing age. It is estimated that there is some degree of endometriosis in as many as 15% of pre-menopausal women, associated with a history of infertility, caesarean antecedents, dysmenorrhoea and abnormality in uterine bleeding. It is believed to be due to the rise of menstrual contents through the Fallopian tubes (retrograde menstruation. In the intestinal affectation, the colon is the segment most frequently affected, above all at the rectosigmoidal level. The clinical features are unspecific, with abdominal pain the most frequent and/or pelvic pain of a cholic type that coincides with, or is exacerbated by, menstruation. Differential diagnosis includes intestinal inflammatory disease, diverticulitis, ischemic colitis and neoplastic processes, with the definitive diagnosis being anatomopathological. With respect to treatment

  3. New small-intestine modeling method for surface-based computational human phantoms.

    Science.gov (United States)

    Yeom, Yeon Soo; Kim, Han Sung; Nguyen, Thang Tat; Choi, Chansoo; Han, Min Cheol; Kim, Chan Hyeong; Lee, Jai Ki; Zankl, Maria; Petoussi-Henss, Nina; Bolch, Wesley E; Lee, Choonsik; Chung, Beom Sun

    2016-06-01

    When converting voxel phantoms to a surface format, the small intestine (SI), which is usually not accurately represented in a voxel phantom due to its complex and irregular shape on one hand and the limited voxel resolutions on the other, cannot be directly converted to a high-quality surface model. Currently, stylized pipe models are used instead, but they are strongly influenced by developer's subjectivity, resulting in unacceptable geometric and dosimetric inconsistencies. In this paper, we propose a new method for the construction of SI models based on the Monte Carlo approach. In the present study, the proposed method was tested by constructing the SI model for the polygon-mesh version of the ICRP reference male phantom currently under development. We believe that the new SI model is anatomically more realistic than the stylized SI models. Furthermore, our simulation results show that the new SI model, for both external and internal photon exposures, leads to dose values that are more similar to those of the original ICRP male voxel phantom than does the previously constructed stylized SI model. PMID:27007802

  4. Human intestinal tissue with adult stem cell properties derived from pluripotent stem cells

    NARCIS (Netherlands)

    Forster, Ryan; Chiba, Kunitoshi; Schaeffer, Lorian; Regalado, Samuel G; Lai, Christine S; Gao, Qing; Kiani, Samira; Farin, Henner F; Clevers, Hans; Cost, Gregory J; Chan, Andy; Rebar, Edward J; Urnov, Fyodor D; Gregory, Philip D; Pachter, Lior; Jaenisch, Rudolf; Hockemeyer, Dirk

    2014-01-01

    Genetically engineered human pluripotent stem cells (hPSCs) have been proposed as a source for transplantation therapies and are rapidly becoming valuable tools for human disease modeling. However, many applications are limited due to the lack of robust differentiation paradigms that allow for the i

  5. Intestinal microbiology in early life: Specific prebiotics can have similar functionalities as human-milk oligosaccharides

    NARCIS (Netherlands)

    R. Oozeer (Raish); K. van Limpt (Kees); T. Ludwig (Thomas); K.B. Amor (Kaouther); R. Martin (Rocio); R.D. Wind (Richèle); G. Boehm (Günther); J. Knol (Jan)

    2013-01-01

    textabstractHuman milk is generally accepted as the best nutrition for newborns and has been shown to support the optimal growth and development of infants. On the basis of scientific insights from human-milk research, a specific mixture of nondigestible oligosaccharides has been developed, with the

  6. Colonic transit time relates to bacterial metabolism and mucosal turnover in the human gut

    DEFF Research Database (Denmark)

    Roager, Henrik Munch; Hansen, Lea Benedicte Skov; Bahl, Martin Iain;

    Little is known about how colonic transit time relates to human colonic metabolism, and its importance for host health, although stool consistency, a proxy for colonic transit time, has recently been negatively associated with gut microbial richness. To address the relationships between colonic...... transit time and the gut microbial composition and metabolism, we assessed the colonic transit time of 98 subjects using radiopaque markers, and profiled their gut microbiota by16S rRNA gene sequencingand their urine metabolome by ultra performance liquid chromatography mass spectrometry. Based...... on correlation analyses,we show that colonic transit time is associated with overall gutmicrobial composition, diversity and metabolism. A relatively prolonged colonic transit time associates with high microbial species richness and a shift in colonic metabolismfrom carbohydrate fermentation to protein...

  7. Chip-based human liver-intestine and liver-skin co-cultures--A first step toward systemic repeated dose substance testing in vitro.

    Science.gov (United States)

    Maschmeyer, Ilka; Hasenberg, Tobias; Jaenicke, Annika; Lindner, Marcus; Lorenz, Alexandra Katharina; Zech, Julie; Garbe, Leif-Alexander; Sonntag, Frank; Hayden, Patrick; Ayehunie, Seyoum; Lauster, Roland; Marx, Uwe; Materne, Eva-Maria

    2015-09-01

    Systemic repeated dose safety assessment and systemic efficacy evaluation of substances are currently carried out on laboratory animals and in humans due to the lack of predictive alternatives. Relevant international regulations, such as OECD and ICH guidelines, demand long-term testing and oral, dermal, inhalation, and systemic exposure routes for such evaluations. So-called "human-on-a-chip" concepts are aiming to replace respective animals and humans in substance evaluation with miniaturized functional human organisms. The major technical hurdle toward success in this field is the life-like combination of human barrier organ models, such as intestine, lung or skin, with parenchymal organ equivalents, such as liver, at the smallest biologically acceptable scale. Here, we report on a reproducible homeostatic long-term co-culture of human liver equivalents with either a reconstructed human intestinal barrier model or a human skin biopsy applying a microphysiological system. We used a multi-organ chip (MOC) platform, which provides pulsatile fluid flow within physiological ranges at low media-to-tissue ratios. The MOC supports submerse cultivation of an intact intestinal barrier model and an air-liquid interface for the skin model during their co-culture with the liver equivalents respectively at (1)/100.000 the scale of their human counterparts in vivo. To increase the degree of organismal emulation, microfluidic channels of the liver-skin co-culture could be successfully covered with human endothelial cells, thus mimicking human vasculature, for the first time. Finally, exposure routes emulating oral and systemic administration in humans have been qualified by applying a repeated dose administration of a model substance - troglitazone - to the chip-based co-cultures. PMID:25857839

  8. Identification of TRPM7 channels in human intestinal interstitial cells of Cajal

    Institute of Scientific and Technical Information of China (English)

    Byung Joo Kim; Kyu Joo Park; Hyung Woo Kim; Seok Choi; Jae Yeoul Jun; In Youb Chang; Ju-Hong Jeon; Insuk So; Seon Jeong Kim

    2009-01-01

    AIM: To investigate the characteristics of slow electrical waves and the presence of transient receptor potential melastatin-type 7 (TRPM7) in the human gastrointestinal (GI) tract. METHODS: Conventional microelectrode techniques were used to record intracellular electrical responses from human GI smooth muscle tissue. Immunohistochemistry was used to identify TRPM7 channels in interstitial cells of Cajal (ICCs). RESULTS: The human GI tract generated slow electrical waves and had ICCs which functioned as pacemaker cells. Flufenamic acid, a nonselective cation channel blocker, and 2-APB (2-aminoethoxydiphenyl borate) and La3~+, TRPM7 channel blockers, inhibited the slow waves. Also, TRPM7 channels were expressed in ICCs in human tissue. CONCLUSION: These results suggest that the human GI tract generates slow waves and that TRPM7 channels expressed in the ICCs may be involved in the generation of the slow waves.

  9. Anti-human tissue factor antibody ameliorated intestinal ischemia reperfusion-induced acute lung injury in human tissue factor knock-in mice.

    Directory of Open Access Journals (Sweden)

    Xiaolin He

    Full Text Available BACKGROUND: Interaction between the coagulation and inflammation systems plays an important role in the development of acute respiratory distress syndrome (ARDS. Anti-coagulation is an attractive option for ARDS treatment, and this has promoted development of new antibodies. However, preclinical trials for these antibodies are often limited by the high cost and availability of non-human primates. In the present study, we developed a novel alternative method to test the role of a humanized anti-tissue factor mAb in acute lung injury with transgenic mice. METHODOLOGY/PRINCIPAL FINDINGS: Human tissue factor knock-in (hTF-KI transgenic mice and a novel humanized anti-human tissue factor mAb (anti-hTF mAb, CNTO859 were developed. The hTF-KI mice showed a normal and functional expression of hTF. The anti-hTF mAb specifically blocked the pro-coagulation activity of brain extracts from the hTF-KI mice and human, but not from wild type mice. An extrapulmonary ARDS model was used by intestinal ischemia-reperfusion. Significant lung tissue damage in hTF-KI mice was observed after 2 h reperfusion. Administration of CNTO859 (5 mg/kg, i.v. attenuated the severity of lung tissue injury, decreased the total cell counts and protein concentration in bronchoalveolar lavage fluid, and reduced Evans blue leakage. In addition, the treatment significantly reduced alveolar fibrin deposition, and decreased tissue factor and plasminogen activator inhibitor-1 activity in the serum. This treatment also down-regulated cytokine expression and reduced cell death in the lung. CONCLUSIONS: This novel anti-hTF antibody showed beneficial effects on intestinal ischemia-reperfusion induced acute lung injury, which merits further investigation for clinical usage. In addition, the use of knock-in transgenic mice to test the efficacy of antibodies against human-specific proteins is a novel strategy for preclinical studies.

  10. Brucella invasion of human intestinal epithelial cells elicits a weak proinflammatory response but a significant CCL20 secretion.

    Science.gov (United States)

    Ferrero, Mariana C; Fossati, Carlos A; Rumbo, Martín; Baldi, Pablo C

    2012-10-01

    In spite of the frequent acquisition of Brucella infection by the oral route in humans, the interaction of the bacterium with cells of the intestinal mucosa has been poorly studied. Here, we show that different Brucella species can invade human colonic epithelial cell lines (Caco-2 and HT-29), in which only smooth species can replicate efficiently. Infection with smooth strains did not produce a significant cytotoxicity, while the rough strain RB51 was more cytotoxic. Infection of Caco-2 cells or HT-29 cells with either smooth or rough strains of Brucella did not result in an increased secretion of TNF-α, IL-1β, MCP-1, IL-10 or TGF-β as compared with uninfected controls, whereas all the infections induced the secretion of IL-8 and CCL20 by both cell types. The MCP-1 response to flagellin from Salmonella typhimurium was similar in Brucella-infected or uninfected cells, ruling out a bacterial inhibitory mechanism as a reason for the weak proinflammatory response. Infection did not modify ICAM-1 expression levels in Caco-2 cells, but increased them in HT-29 cells. These results suggest that Brucella induces only a weak proinflammatory response in gut epithelial cells, but produces a significant CCL20 secretion. The latter may be important for bacterial dissemination given the known ability of Brucella to survive in dendritic cells.

  11. Differential Regulation of TLR Signaling on the Induction of Antiviral Interferons in Human Intestinal Epithelial Cells Infected with Enterovirus 71.

    Science.gov (United States)

    Wang, Chunyang; Ji, Lianfu; Yuan, Xinhui; Jin, Yu; Cardona, Carol J; Xing, Zheng

    2016-01-01

    Enterovirus 71 (EV71) causes hand-foot-and-mouth disease, which can lead to fatal neurological complications in young children and infants. Few gastrointestinal symptoms are observed clinically, suggesting the presence of a unique immunity to EV71 in the gut. We reported a robust induction of interferons (IFNs) in human intestinal epithelial cells (HT-29), which was suppressed in other types such as RD and HeLa cells. The underlying mechanism for the apparent difference remains obscure. In this study we report that in EV71-infected HT-29 cells, TLR/TRIF signaling was essential to IFN induction; viral replication increased and the induction of IFN-α, -β, -ω, -κ, and -ε decreased markedly in TRIF-silenced HT-29 cells. Importantly, TRIF was degraded by viral 3Cpro in RD cells, but resisted cleavage, and IRF3 was activated and translocated into the nucleus in HT-29 cells. Taken together, our data suggest that IFNs were induced differentially in human HT-29 cells through an intact TLR/TRIF signaling, which differs from other cell types and may be implicated in viral pathogenesis in EV71 infection. PMID:27007979

  12. Differential Regulation of TLR Signaling on the Induction of Antiviral Interferons in Human Intestinal Epithelial Cells Infected with Enterovirus 71

    Science.gov (United States)

    Wang, Chunyang; Ji, Lianfu; Yuan, Xinhui; Jin, Yu; Cardona, Carol J.; Xing, Zheng

    2016-01-01

    Enterovirus 71 (EV71) causes hand-foot-and-mouth disease, which can lead to fatal neurological complications in young children and infants. Few gastrointestinal symptoms are observed clinically, suggesting the presence of a unique immunity to EV71 in the gut. We reported a robust induction of interferons (IFNs) in human intestinal epithelial cells (HT-29), which was suppressed in other types such as RD and HeLa cells. The underlying mechanism for the apparent difference remains obscure. In this study we report that in EV71-infected HT-29 cells, TLR/TRIF signaling was essential to IFN induction; viral replication increased and the induction of IFN-α, -β, -ω, -κ, and -ε decreased markedly in TRIF-silenced HT-29 cells. Importantly, TRIF was degraded by viral 3Cpro in RD cells, but resisted cleavage, and IRF3 was activated and translocated into the nucleus in HT-29 cells. Taken together, our data suggest that IFNs were induced differentially in human HT-29 cells through an intact TLR/TRIF signaling, which differs from other cell types and may be implicated in viral pathogenesis in EV71 infection. PMID:27007979

  13. Motor response of the human isolated small intestine and urinary bladder to porcine neuromedin U-8.

    OpenAIRE

    Maggi, C. A.; Patacchini, R.; S. Giuliani; Turini, D; Barbanti, G.; ROVERO P; Meli, A.

    1990-01-01

    1. Porcine neuromedin U-8 produced a concentration (0.3 nM-1 microM)-dependent contraction of the longitudinal muscle of the human isolated ileum, which was unaffected by either atropine (1 microM) or tetrodotoxin (1 microM). 2. By contrast, neuromedin U-8 had only a weak effect on the circular muscle of the human isolated ileum. 3. Neuromedin U-8 also produced a concentration-dependent contraction of mucosa-free muscle strips from the dome of the human isolated urinary bladder, its action be...

  14. 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:G461–G469, 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.

  15. Effect of Exogenous Glial Cell Line-derived Neurotrophic Factor on Intestinal Transit Function in Slow Transit Constipation Rats%外源性胶质细胞源性神经营养因子对慢传输型便秘大鼠肠道传输功能的影响

    Institute of Scientific and Technical Information of China (English)

    张兴; 范一宏; 李延玲; 吕宾; 张璐

    2013-01-01

    Background: Slow transit constipation ( STC) is mainly characterized by colonic motility disorder and has a close relationship with enteric nervous system alterations. Aims: To investigate the effect of exogenous glial cell line-derived neurotrophic factor ( GDNF) on expression of GDNF in colonic tissue and intestinal transit function in STC rats. Methods: STC model was established by gastric infusion of rhubarb in rats. Rats were randomly divided into normal control group, GDNF control group, STC model group and model GDNF group. Rats in GDNF control group and model GDNF group were injected with recombinant human GDNF into caudal vein. Normal control group and STC model group were injected with same amount of 0.9% NaCl solution. One week later, the colonic transit function was measured by ink propulsion test, and the expression of GDNF in colonic tissue was determined by immunohistochemistry. Results: The intestinal propulsion rate in STC model group was significantly lower than that in normal control group and GDNF control group (P 0. 05 ). The positive area and integrated optical density (IOD) value of GDNF in colonic tissue in STC model group were significantly lower than those in normal control group and GDNF control group ( P 0.05). Conclusions; Long term use of rhubarb can down-regulate the expression of GDNF in colonic tissue of rats. Exogenous GDNF may enhance the expression of GDNF and improve the intestinal transit function.%背景:慢传输型便秘(STC)是一种以结肠动力障碍为主要特点的顽固性便秘,与肠神经系统功能紊乱密切相关.目的:探讨外源性胶质细胞源性神经营养因子(GDNF)对STC大鼠结肠组织中的GDNF表达及其肠道传输功能的影响.方法:以大黄灌胃建立STC大鼠模型.将大鼠随机分为正常对照组、GDNF对照组、STC模型组和模型GDNF组.GDNF对照组和模型GDNF组经尾静脉注射重组人GDNF,正常对照组和STC模型组经尾静脉注射0.9% NaCl溶液.1周后,

  16. 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,1–3 Danhui Li,3 Yongzhi Zhou,3 Jie Yang,1 Wanqi Yang,1 Guohua Zhou,2 Jingyuan Wen31Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, School of Pharmacy, China Pharmaceutical University, 2Department of Pharmacology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, People’s Republic of China; 3School of Pharmacy, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New ZealandAbstract: The aim of this study was to evaluate (+-catechin and (−-epigallocatechin gallate (EGCG cellular uptake and transport across human intestinal Caco-2 cell monolayer in both the absence and presence of niosomal carrier in variable conditions. The effect of free drugs and drug-loaded niosomes on the growth of Caco-2 cells was studied. The effects of time, temperature, and concentration on drug cellular uptake in the absence or presence of its niosomal delivery systems were investigated. The intestinal epithelial membrane transport of the drug-loaded niosomes was examined using the monolayer of the human Caco-2 cells. The kinetics of transport, and the effect of temperature, adenosine triphosphate inhibitor, permeability glycoprotein inhibitor, multidrug resistance-associated protein 2 inhibitor, and the absorption enhancer on transport mechanism were investigated. It was found that the uptake of catechin, EGCG, and their niosomes by Caco-2 cells was 1.22±0.16, 0.90±0.14, 3.25±0.37, and 1.92±0.22 µg/mg protein, respectively (n=3. The apparent permeability coefficient values of catechin, EGCG, and their niosomes were 1.68±0.16, 0.88±0.09, 2.39±0.31, and 1.42±0.24 cm/second (n=3 at 37°C, respectively. The transport was temperature- and energy-dependent. The inhibitors of permeability glycoprotein and multidrug resistance-associated protein 2 and the absorption enhancer significantly enhanced the uptake amount. Compared with the free drugs, niosomal formulation

  17. Regulation of VDR expression in rat and human intestine and liver - Consequences for CYP3A expression

    NARCIS (Netherlands)

    Khan, Ansar A.; Dragt, Bieuwke S.; Porte, Robert J.; Groothuis, Geny M. M.

    2010-01-01

    The vitamin D receptor (VDR) regulates the expression of drug metabolizing enzymes and transporters in intestine and liver, but the regulation of VDR expression in intestine and liver is incompletely understood. We studied the regulation of VDR mRNA expression by ligands for VDR, farnesoid X recepto

  18. Altered Enthalpy-Entropy Compensation in Picomolar Transition State Analogues of Human Purine Nucleoside Phosphorylase†

    OpenAIRE

    Edwards, Achelle A.; Mason, Jennifer M.; Clinch, Keith; Tyler, Peter C.; Evans, Gary B.; Schramm, Vern L.

    2009-01-01

    Human purine nucleoside phosphorylase (PNP) belongs to the trimeric class of PNPs and is essential for catabolism of deoxyguanosine. Genetic deficiency of PNP in humans causes a specific T-cell immune deficiency and transition state analogue inhibitors of PNP are in development for treatment of T-cell cancers and autoimmune disorders. Four generations of Immucillins have been developed, each of which contains inhibitors binding with picomolar affinity to human PNP. Full inhibition of PNP occu...

  19. Human intestinal dendritic cells decrease cytokine release against Salmonella infection in the presence of Lactobacillus paracasei upon TLR activation.

    Directory of Open Access Journals (Sweden)

    Miriam Bermudez-Brito

    Full Text Available Probiotic bacteria have been shown to modulate immune responses and could have therapeutic effects in allergic and inflammatory disorders. However, little is known about the signalling pathways that are engaged by probiotics. Dendritic cells (DCs are antigen-presenting cells that are involved in immunity and tolerance. Monocyte-derived dendritic cells (MoDCs and murine DCs are different from human gut DCs; therefore, in this study, we used human DCs generated from CD34+ progenitor cells (hematopoietic stem cells harvested from umbilical cord blood; those DCs exhibited surface antigens of dendritic Langerhans cells, similar to the lamina propria DCs in the gut. We report that both a novel probiotic strain isolated from faeces of exclusively breast-fed newborn infants, Lactobacillus paracasei CNCM I-4034, and its cell-free culture supernatant (CFS decreased pro-inflammatory cytokines and chemokines in human intestinal DCs challenged with Salmonella. Interestingly, the supernatant was as effective as the bacteria in reducing pro-inflammatory cytokine expression. In contrast, the bacterium was a potent inducer of TGF-β2 secretion, whereas the supernatant increased the secretion of TGF-β1 in response to Salmonella. We also showed that both the bacteria and its supernatant enhanced innate immunity through the activation of Toll-like receptor (TLR signalling. These treatments strongly induced the transcription of the TLR9 gene. In addition, upregulation of the CASP8 and TOLLIP genes was observed. This work demonstrates that L. paracasei CNCM I-4034 enhanced innate immune responses, as evidenced by the activation of TLR signalling and the downregulation of a broad array of pro-inflammatory cytokines. The use of supernatants like the one described in this paper could be an effective and safe alternative to using live bacteria in functional foods.

  20. Intestinal fermentation of lactose and prebiotic lactose derivatives, including human milk oligosaccharides

    NARCIS (Netherlands)

    Venema, K.

    2012-01-01

    This review describes the recent advances in technology to study fermentation of lactose and its prebiotic derivatives, including human milk oligosaccharides. Novel molecular tools to identify members of the microbiota that ferment these substrates are highlighted, as well as the use of stable isoto

  1. Adaptive function of soil consumption: An in vitro study modeling the human stomach and small intestine

    NARCIS (Netherlands)

    Dominy, N.J.; Davoust, E.; Minekus, M.

    2004-01-01

    Despite occurring in a wide variety of taxa, deliberate soil consumption (geophagy) is a poorly understood behavior. In humans, geophagy is sometimes considered aberrant or a sign of metabolic dysfunction. However, geophagy is normally assigned an adaptive function in nonhuman primates and various o

  2. An experimental platform using human intestinal epithelial cell lines to differentiate between hazardous and non-hazardous proteins.

    Science.gov (United States)

    Hurley, Bryan P; Pirzai, Waheed; Eaton, Alex D; Harper, Marc; Roper, Jason; Zimmermann, Cindi; Ladics, Gregory S; Layton, Raymond J; Delaney, Bryan

    2016-06-01

    Human intestinal epithelial cell lines (T84, Caco-2, and HCT-8) grown on permeable Transwell™ filters serve as models of the gastrointestinal barrier. In this study, this in vitro model system was evaluated for effectiveness at distinguishing between hazardous and non-hazardous proteins. Indicators of cytotoxicity (LDH release, MTT conversion), monolayer barrier integrity ([(3)H]-inulin flux, horseradish peroxidase flux, trans-epithelial electrical resistance [TEER]), and inflammation (IL-8, IL-6 release) were monitored following exposure to hazardous or non-hazardous proteins. The hazardous proteins examined include streptolysin O (from Streptococcus pyogenes), Clostridium difficile Toxins A and B, heat-labile toxin from enterotoxigenic Escherichia coli, listeriolysin O (from Listeria monocytogenes), melittin (from bee venom), and mastoparan (from wasp venom). Non-hazardous proteins included bovine and porcine serum albumin, bovine fibronectin, and ribulose bisphosphate carboxylase/oxygenase (RuBisco) from spinach. Food allergenic proteins bovine milk β-lactoglobulin and peanut Ara h 2 were also tested as was the anti-nutritive food protein wheat germ agglutinin. Results demonstrated that this model system effectively distinguished between hazardous and non-hazardous proteins through combined analysis of multiple cells lines and assays. This experimental strategy may represent a useful adjunct to multi-component analysis of proteins with unknown hazard profiles. PMID:27060235

  3. Distinct regulation of vasoactive intestinal peptide (VIP) expression at mRNA and peptide levels in human neuroblastoma cells.

    Science.gov (United States)

    Agoston, D V; Colburn, S; Krajniak, K G; Waschek, J A

    1992-05-25

    Neuronal differentiation was induced in cultures of the human neuroblastoma cell line subclone SH-SY5Y by 14-day treatment with dibutyryl cAMP (dBcAMP), retinoic acid, and phorbol 12-myristate 13-acetate (PMA). An approximate 4-fold increase in vasoactive intestinal peptide (VIP) mRNA concentration was observed after differentiation with retinoic acid, whereas no change in VIP mRNA concentration was observed after differentiation with dBcAMP or PMA. A short-term treatment of cells with PMA did however result in a 5-fold transient increase in VIP mRNA; prior differentiation with retinoic acid or dBcAMP diminished this effect. Observed increases in VIP mRNA were in all cases accompanied by increases in VIP immunoreactivity. Remarkably, however, long-term treatment of cells with dBcAMP, which caused no change in mRNA levels, resulted in a six-fold increase in VIP immunoreactivity. Acute (36-h) treatment with carbachol also caused an increase in VIP immunoreactivity (about 2-fold, and blocked by atropine) without an increase in VIP mRNA level. Thus, a quantitative change in gene transcription or mRNA stability appears not to be a prerequisite for increased VIP expression, indicating that regulation can occur at translational or post-translational steps.

  4. The influence of protein fractions from bovine colostrum digested in vivo and in vitro on human intestinal epithelial cell proliferation.

    Science.gov (United States)

    Morgan, Alison J; Riley, Lisa G; Sheehy, Paul A; Wynn, Peter C

    2014-02-01

    Colostrum consists of a number of biologically active proteins and peptides that influence physiological function and development of a neonate. The present study investigated the biological activity of peptides released from first day bovine colostrum through in vitro and in vivo enzymatic digestion. This was assessed for proliferative activity using a human intestinal epithelial cell line, T84. Digestion of the protein fraction of bovine colostrum in vitro was conducted with the enzymes pepsin, chymosin and trypsin. Pepsin and chymosin digests yielded protein fractions with proliferative activity similar to that observed with undigested colostrum and the positive control foetal calf serum (FCS). In contrast trypsin digestion significantly (P<0·05) decreased colostral proliferative activity when co-cultured with cells when compared with undigested colostrum. The proliferative activity of undigested colostrum protein and abomasal whey protein digesta significantly increased (P<0·05) epithelial cell proliferation in comparison to a synthetic peptide mix. Bovine colostrum protein digested in vivo was collected from different regions of the gastrointestinal tract (GIT) in newborn calves fed either once (n=3 calves) or three times at 12-h intervals (n=3 calves). Digesta collected from the distal duodenum, jejunum and colon of calves fed once, significantly (P<0·05) stimulated cell proliferation in comparison with comparable samples collected from calves fed multiple times. These peptide enriched fractions are likely to yield candidate peptides with potential application for gastrointestinal repair in mammalian species. PMID:24433585

  5. Epidermal growth factor inhibits glycylsarcosine transport and hPepT1 expression in a human intestinal cell line

    DEFF Research Database (Denmark)

    Nielsen, C U; Amstrup, J; Steffansen, B;

    2001-01-01

    The human intestinal cell line Caco-2 was used as a model system to study the effects of epidermal growth factor (EGF) on peptide transport. EGF decreased apical-to-basolateral fluxes of [(14)C]glycylsarcosine ([(14)C]Gly-Sar) up to 50.2 +/- 3.6% (n = 6) of control values. Kinetic analysis...... of the fluxes showed that maximal flux (V(max)) of transepithelial transport decreased from 3.00 +/- 0.17 nmol x cm(-2) x min(-1) in control cells to 0.50 +/- 0.07 nmol x cm(-2) x min(-1) in cells treated with 5 ng/ml EGF (n = 6, P ... = 6) in control cells and 1.89 +/- 0.28 mM (n = 6, not significantly different from control) in EGF-treated cells. Similarly, apical uptake of [(14)C]Gly-Sar decreased in cells treated with EGF, with an ED(50) value of 0.36 +/- 0.06 ng/ml (n = 6) EGF and a maximal inhibition of 80 +/- 0.02% (n = 6). V...

  6. Demonstration of Brachyspira aalborgi lineages 2 and 3 in human colonic biopsies with intestinal spirochaetosis by specific fluorescent in situ hybridization

    DEFF Research Database (Denmark)

    Jensen, Tim Kåre; Teglbjærg, Peter S.; Lindboe, Christian F.;

    2004-01-01

    organisms in human intestinal spirochaetosis. Seventeen human colonic biopsies from Norway and Denmark with intestinal spirochaetosis caused by Brachyspira-like organisms different from the type strain of B. aalborgi (lineage 1) were examined. Application of the probe gave a positive signal in two Norwegian......Sequences of known 16S rRNA genes, derived from sequence analysis of cloned 16S rDNA, were used to design a specific oligonucleotide probe targeting spirochaetes of Brachyspira aalborgi lineages 2 and 3. The probe was used with fluorescent in situ hybridization to study the involvement of these...... biopsies, whereas the 15 other biopsies were hybridization-negative. The positive reaction visualized the spirochaetes as a fluorescent, 3-5 mum-high fringe on the surface epithelium, extending into the crypts. The study verified the presence of B. aalborgi lineages 2 and 3 and identified the bacteria as...

  7. The genome of Bifidobacterium pseudocatenulatum IPLA 36007, a human intestinal strain with isoflavone-activation activity

    OpenAIRE

    Alegría, Ángel; Delgado, Susana; Guadamuro, Lucía; Flórez García, Ana Belén; Felis, Giovanna E.; Torriani, Sandra; Mayo Pérez, Baltasar

    2014-01-01

    Background Bifidobacterium species, including Bifidobacterium pseudocatenulatum, are among the dominant microbial populations of the human gastrointestinal tract. They are also major components of many commercial probiotic products. Resident and transient bifidobacteria are thought to have several beneficial health effects. However, our knowledge of how these bacteria interact and communicate with host cells remains poor. This knowledge is essential for scientific support of their purported h...

  8. Identification of a novel human deoxynivalenol metabolite enhancing proliferation of intestinal and urinary bladder cells

    Science.gov (United States)

    Warth, Benedikt; Del Favero, Giorgia; Wiesenberger, Gerlinde; Puntscher, Hannes; Woelflingseder, Lydia; Fruhmann, Philipp; Sarkanj, Bojan; Krska, Rudolf; Schuhmacher, Rainer; Adam, Gerhard; Marko, Doris

    2016-01-01

    The mycotoxin deoxynivalenol (DON) is an abundant contaminant of cereal based food and a severe issue for global food safety. We report the discovery of DON-3-sulfate as a novel human metabolite and potential new biomarker of DON exposure. The conjugate was detectable in 70% of urine samples obtained from pregnant women in Croatia. For the measurement of urinary metabolites, a highly sensitive and selective LC-MS/MS method was developed and validated. The method was also used to investigate samples from a duplicate diet survey for studying the toxicokinetics of DON-3-sulfate. To get a preliminary insight into the biological relevance of the newly discovered DON-sulfates, in vitroexperiments were performed. In contrast to DON, sulfate conjugates lacked potency to suppress protein translation. However, surprisingly we found that DON-sulfates enhanced proliferation of human HT-29 colon carcinoma cells, primary human colon epithelial cells (HCEC-1CT) and, to some extent, also T24 bladder cancer cells. A proliferative stimulus, especially in tumorigenic cells raises concern on the potential impact of DON-sulfates on consumer health. Thus, a further characterization of their toxicological relevance should be of high priority. PMID:27659167

  9. 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.

  10. Recombinant human MFG-E8 attenuates intestinal injury and mortality in severe whole body irradiation in rats.

    Directory of Open Access Journals (Sweden)

    Michael A Ajakaiye

    Full Text Available The gastrointestinal (GI syndrome component of acute radiation syndrome (ARS results from depletion of immature parenchymal stem cells after high dose irradiation and contributes significantly to early mortality. It is associated with severe, irreparable damage in the GI tract and extremely low survival. There is a need for the development of viable mitigators of whole body irradiation (WBI due to the possibility of unexpected high level radiation exposure from nuclear accidents or attacks. We therefore examined the effect of recombinant human milk fat globule-EGF factor 8 (rhMFG-E8 in mitigating damage after WBI. Male Sprague-Dawley rats were exposed to 10 Gy WBI using Cesium-137 as the radiation source. The animals in the treatment group received rhMFG-E8 (166 µg/kg BW subcutaneously once a day with the first dose given 6 h after WBI. Blood and tissue samples from the ileum were collected after 3 days of treatment. A separate cohort of animals was treated for 7 days and the 21 day mortality rate was determined. Treatment with rhMFG-E8 significantly improved the survival from 31% to 75% over 21 days. Furthermore, rhMFG-E8 treatment resulted in a 36% reduction in the radiation injury intestinal mucosal damage score, corresponding to visible histological changes. MFG-E8 gene expression was significantly decreased in WBI-induced animals as compared to sham controls. Treatment with rhMFG-E8 increased p53 and p21 expression by 207% and 84% compared to untreated controls. This was accompanied by an 80% increase in the expression of anti-apoptotic cell regulator Bcl-2. p53 and p21 levels correlate with improved survival after radiation injury. These cell regulators arrest the cell after DNA damage and enable DNA repair as well as optimize cell survival. Taken together, these results indicate that rhMFG-E8 ameliorates the GI syndrome and improves survival after WBI by minimizing intestinal cell damage and optimizing recovery.

  11. Phase transition of the microvascular network architecture in human pathologies.

    Science.gov (United States)

    Bianciardi, Giorgio; Traversi, Claudio; Cattaneo, Ruggero; De Felice, Claudia; Monaco, Annalisa; Tosi, Gianmarco; Parrini, Stefano; Latini, Giuseppe

    2012-01-01

    We have investigated the microvascular pattern in acquired or genetic diseases in humans. The lower gingival and vestibular oral mucosa, as well as the optic nerve head, was chosen to characterize the vascular pattern complexity due to the simple accessibility and visibility Local fractal dimensions, fractal dimension of the minimum path and Lempel-Ziv complexity have been used as operational numerical tools to characterize the microvascular networks. In the normal healthy subjects microvascular networks show nonlinear values corresponding to the complexity of a diffusion limited aggregation (DLA) model, while in several acquired or genetic diseases they are approaching the ones of an invasion percolation model. PMID:23193796

  12. 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.

  13. Anti-Inflammatory Effects of the Nicotinergic Peptides SLURP-1 and SLURP-2 on Human Intestinal Epithelial Cells and Immunocytes

    Directory of Open Access Journals (Sweden)

    Alex I. Chernyavsky

    2014-01-01

    Full Text Available A search for novel and more efficient therapeutic modalities of inflammatory bowel disease (IBD is one of the most important tasks of contemporary medicine. The anti-inflammatory action of nicotine in IBD might be therapeutic, but its toxicity due to off-target and nonreceptor effects limited its use and prompted a search for nontoxic nicotinergic drugs. We tested the hypothesis that SLURP-1 and -2—the physiological nicotinergic substances produced by the human intestinal epithelial cells (IEC and immunocytes—can mimic the anti-inflammatory effects of nicotine. We used human CCL-241 enterocytes, CCL-248 colonocytes, CCRF-CEM T-cells, and U937 macrophages. SLURP-1 diminished the TLR9-dependent secretion of IL-8 by CCL-241, and IFNγ-induced upregulation of ICAM-1 in both IEC types. rSLURP-2 inhibited IL-1β-induced secretion of IL-6 and TLR4- and TLR9-dependent induction of CXCL10 and IL-8, respectively, in CCL-241. rSLURP-1 decreased production of TNFα by T-cells, downregulated IL-1β and IL-6 secretion by macrophages, and moderately upregulated IL-10 production by both types of immunocytes. SLURP-2 downregulated TNFα and IFNγR in T-cells and reduced IL-6 production by macrophages. Combining both SLURPs amplified their anti-inflammatory effects. Learning the pharmacology of SLURP-1 and -2 actions on enterocytes, colonocytes, T cells, and macrophages may help develop novel effective treatments of IBD.

  14. GUTSS: An Alignment-Free Sequence Comparison Method for Use in Human Intestinal Microbiome and Fecal Microbiota Transplantation Analysis

    Science.gov (United States)

    Heltshe, Sonya L.; Hayden, Hillary S.; Radey, Matthew C.; Weiss, Eli J.; Damman, Christopher J.; Zisman, Timothy L.; Suskind, David L.; Miller, Samuel I.

    2016-01-01

    Background Comparative analysis of gut microbiomes in clinical studies of human diseases typically rely on identification and quantification of species or genes. In addition to exploring specific functional characteristics of the microbiome and potential significance of species diversity or expansion, microbiome similarity is also calculated to study change in response to therapies directed at altering the microbiome. Established ecological measures of similarity can be constructed from species abundances, however methods for calculating these commonly used ecological measures of similarity directly from whole genome shotgun (WGS) metagenomic sequence are lacking. Results We present an alignment-free method for calculating similarity of WGS metagenomic sequences that is analogous to the Bray–Curtis index for species, implemented by the General Utility for Testing Sequence Similarity (GUTSS) software application. This method was applied to intestinal microbiomes of healthy young children to measure developmental changes toward an adult microbiome during the first 3 years of life. We also calculate similarity of donor and recipient microbiomes to measure establishment, or engraftment, of donor microbiota in fecal microbiota transplantation (FMT) studies focused on mild to moderate Crohn's disease. We show how a relative index of similarity to donor can be calculated as a measure of change in a patient's microbiome toward that of the donor in response to FMT. Conclusion Because clinical efficacy of the transplant procedure cannot be fully evaluated without analysis methods to quantify actual FMT engraftment, we developed a method for detecting change in the gut microbiome that is independent of species identification and database bias, sensitive to changes in relative abundance of the microbial constituents, and can be formulated as an index for correlating engraftment success with clinical measures of disease. More generally, this method may be applied to clinical

  15. Antitumoral effects of vasoactive intestinal peptide in human renal cell carcinoma xenografts in athymic nude mice.

    Science.gov (United States)

    Vacas, Eva; Arenas, M Isabel; Muñoz-Moreno, Laura; Bajo, Ana M; Sánchez-Chapado, Manuel; Prieto, Juan C; Carmena, María J

    2013-08-01

    We studied antitumor effect of VIP in human renal cell carcinoma (RCC) (A498 cells xenografted in immunosuppressed mice). VIP-treated cells gave resulted in p53 upregulation and decreased nuclear β-catenin translocation and NFκB expression, MMP-2 and MMP-9 activities, VEGF levels and CD-34 expression. VIP led to a more differentiated tubular organization in tumours and less metastatic areas. Thus, VIP inhibits growth of A498-cell tumours acting on the major issues involved in RCC progression such as cell proliferation, microenvironment remodelling, tumour invasion, angiogenesis and metastatic ability. These antitumoral effects of VIP offer new therapeutical possibilities in RCC treatment.

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

    OpenAIRE

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

    2010-01-01

    Identification of celiac disease, by determining human leucocyte antigens DQ2/DQ8, is important since recent long-term studies have shown that the mortality of celiac disease is increased, if it is unrecognized and untreated. In this sense, we wanted to see the usefulness of genetic tests in celiac disease diagnosis and screening. Material and methods. During 2010 we determined by PCR, DQ2/DQ8 haplotype, in a group of 27 children with celiac disease and 9 of their brothers, serolo...

  17. Transitions in pathways of human development and carbon emissions

    International Nuclear Information System (INIS)

    Countries are known to follow diverse pathways of life expectancy and carbon emissions, but little is known about factors driving these dynamics. In this letter we estimate the cross-sectional economic, demographic and geographic drivers of consumption-based carbon emissions. Using clustering techniques, countries are grouped according to their drivers, and analysed with respect to a criteria of one tonne of carbon emissions per capita and a life expectancy over 70 years (Goldemberg’s Corner). Five clusters of countries are identified with distinct drivers and highly differentiated outcomes of life expectancy and carbon emissions. Representatives from four clusters intersect within Goldemberg’s Corner, suggesting diverse combinations of drivers may still lead to sustainable outcomes, presenting many countries with an opportunity to follow a pathway towards low-carbon human development. By contrast, within Goldemberg’s Corner, there are no countries from the core, wealthy consuming nations. These results reaffirm the need to address economic inequalities within international agreements for climate mitigation, but acknowledge plausible and accessible examples of low-carbon human development for countries that share similar underlying drivers of carbon emissions. In addition, we note differences in drivers between models of territorial and consumption-based carbon emissions, and discuss interesting exceptions to the drivers-based cluster analysis. (paper)

  18. Interaction of graphene-related materials with human intestinal cells: an in vitro approach

    Science.gov (United States)

    Kucki, M.; Rupper, P.; Sarrieu, C.; Melucci, M.; Treossi, E.; Schwarz, A.; León, V.; Kraegeloh, A.; Flahaut, E.; Vázquez, E.; Palermo, V.; Wick, P.

    2016-04-01

    Graphene-related materials (GRM) inherit unique combinations of physicochemical properties which offer a high potential for technological as well as biomedical applications. It is not clear which physicochemical properties are the most relevant factors influencing the behavior of GRM in complex biological environments. In this study we have focused on the interaction of GRM, especially graphene oxide (GO), and Caco-2 cells in vitro. We mimiked stomach transition by acid-treatment of two representative GRM followed by analysis of their physicochemical properties. No significant changes in the material properties or cell viability of exposed Caco-2 cells in respect to untreated GRM could be detected. Furthermore, we explored the interaction of four different GO and Caco-2 cells to identify relevant physicochemical properties for the establishment of a material property-biological response relationship. Despite close interaction with the cell surface and the formation of reactive oxygen species (ROS), no acute toxicity was found for any of the applied GO (concentration range 0-80 μg ml-1) after 24 h and 48 h exposure. Graphene nanoplatelet aggregates led to low acute toxicity at high concentrations, indicating that aggregation, the number of layers or the C/O ratio have a more pronounced effect on the cell viability than the lateral size alone.Graphene-related materials (GRM) inherit unique combinations of physicochemical properties which offer a high potential for technological as well as biomedical applications. It is not clear which physicochemical properties are the most relevant factors influencing the behavior of GRM in complex biological environments. In this study we have focused on the interaction of GRM, especially graphene oxide (GO), and Caco-2 cells in vitro. We mimiked stomach transition by acid-treatment of two representative GRM followed by analysis of their physicochemical properties. No significant changes in the material properties or cell

  19. Structural Transformation of 8-5-Coupled Dehydrodiferulates by Human Intestinal Microbiota.

    Science.gov (United States)

    Schendel, Rachel R; Karrer, Cecile; Bunzel, Diana; Huch, Melanie; Hildebrand, Andreas A; Kulling, Sabine E; Bunzel, Mirko

    2015-09-16

    Ingested dehydrodiferulates (DFAs) are partially released from cereal dietary fiber by human colonic microbiota, but little research has explored the further microbial metabolism of 8-5-coupled DFAs. This study investigated the in vitro microbial metabolism and elucidated major metabolites of free 8-5-DFAs (benzofuran and open forms) and an esterified analogue, 8-5-DFA diethyl ester (benzofuran). Synthesized standard compounds were incubated with fresh human fecal suspensions. Metabolites were isolated and structurally elucidated using high-resolution-LC-time-of-flight-(ToF)-MS, GC-MS, and NMR. Nine metabolite structures were unambiguously characterized with NMR, and four additional metabolites were tentatively identified to reveal structural conversion motifs: propenyl side chain hydrogenation (all substrates), O-demethylation and reductive ring-opening (8-5-DFA diethyl ester and free 8-5-DFA [benzofuran]), and de-esterification (8-5-DFA diethyl ester). A pathway of microbial 8-5-DFA metabolism was proposed based on metabolite formation kinetics. Importantly, de-esterification of the 8-5-DFA diethyl ester occurred primarily after and/or concurrently with other metabolism steps. Cleavage to monomers was not observed. PMID:26287944

  20. Prebiotic effect of fructooligosaccharide in the simulator of the human intestinal microbial ecosystem (SHIME® model).

    Science.gov (United States)

    Sivieri, Katia; Morales, Martha L Villarreal; Saad, Susana M I; Adorno, Maria A Tallarico; Sakamoto, Isabel Kimiko; Rossi, Elizeu A

    2014-08-01

    Maintaining "gut health" is a goal for scientists throughout the world. Therefore, microbiota management models for testing probiotics, prebiotics, and synbiotics have been developed. The SHIME(®) model was used to study the effect of fructooligosaccharide (FOS) on the fermentation pattern of the colon microbiota. Initially, an inoculum prepared from human feces was introduced into the reactor vessels and stabilized over 2 weeks using a culture medium. This stabilization period was followed by a 2-week control period during which the microbiota was monitored. The microbiota was then subjected to a 4-week treatment period by adding 5 g/day-1 FOS to vessel one (the "stomach" compartment). Plate counts, Denaturing Gradient Gel Electrophoresis (DGGE), short-chain fatty acid (SCFA), and ammonium analyses were used to observe the influence of FOS treatment in simulated colon compartments. A significant increase (P<.01) in the Lactobacillus spp. and Bifidobacterium spp. populations was observed during the treatment period. The DGGE obtained showed the overall microbial community was changed in the ascending colon compartment of the SHIME reactor. FOS induced increase of the SCFA concentration (P<.05) during the treatment period, mainly due to significant increased levels of acetic and butyric acids. However, ammonium concentrations increased during the same period (P<.01). This study indicates the usefulness of in vitro methods that simulate the colon region as part of research towards the improvement of human health.

  1. Prebiotic effect of fructooligosaccharide in the simulator of the human intestinal microbial ecosystem (SHIME® model).

    Science.gov (United States)

    Sivieri, Katia; Morales, Martha L Villarreal; Saad, Susana M I; Adorno, Maria A Tallarico; Sakamoto, Isabel Kimiko; Rossi, Elizeu A

    2014-08-01

    Maintaining "gut health" is a goal for scientists throughout the world. Therefore, microbiota management models for testing probiotics, prebiotics, and synbiotics have been developed. The SHIME(®) model was used to study the effect of fructooligosaccharide (FOS) on the fermentation pattern of the colon microbiota. Initially, an inoculum prepared from human feces was introduced into the reactor vessels and stabilized over 2 weeks using a culture medium. This stabilization period was followed by a 2-week control period during which the microbiota was monitored. The microbiota was then subjected to a 4-week treatment period by adding 5 g/day-1 FOS to vessel one (the "stomach" compartment). Plate counts, Denaturing Gradient Gel Electrophoresis (DGGE), short-chain fatty acid (SCFA), and ammonium analyses were used to observe the influence of FOS treatment in simulated colon compartments. A significant increase (PFOS induced increase of the SCFA concentration (P<.05) during the treatment period, mainly due to significant increased levels of acetic and butyric acids. However, ammonium concentrations increased during the same period (P<.01). This study indicates the usefulness of in vitro methods that simulate the colon region as part of research towards the improvement of human health. PMID:24654949

  2. Perfil epidemiológico e morbimortalidade dos pacientes submetidos à reconstrução de trânsito intestinal: experiência de um centro secundário do Nordeste Brasileiro Epidemiologic profile and morbimortality of patients undergoing reconstruction intestinal transit: experience of a secundary health service in the Northeast of Brazil

    Directory of Open Access Journals (Sweden)

    Jeany Borges e Silva

    2010-09-01

    Full Text Available RACIONAL: A reconstrução do trânsito intestinal não está isenta de riscos cirúrgicos e apresenta taxas consideráveis de complicações pós-operatórias, sendo que a infecção continua a ser um dos maiores desafios existentes neste procedimento. OBJETIVO: Perfil epidemiológico e morbimortalidade dos pacientes submetidos à reconstrução de trânsito intestinal. MÉTODOS: Foram analisados retrospectivamente 86 prontuários de pacientes com colostomia ou ileostomia, através de fatores que tivessem impacto sobre a morbimortalidade após a reconstrução de trânsito intestinal, de janeiro de 2003 a abril de 2009. RESULTADOS: Houve 20 mulheres e 60 homens, com idade média de 43 anos. A colostomia em alça (n=34 e o trauma abdominal indicando colostomia ou ileostomia foram as condições mais frequentes. O intervalo médio entre a confecção do estoma e a reconstrução de trânsito intestinal foi 15,7 meses. O índice de morbidade foi 56,8%, sendo a infecção incisional a complicação mais comum (27.47%. A permanência hospitalar média foi 7,6 dias. Houve regressão linear positiva entre permanência hospitalar pós-operatória e a idade do paciente. Demonstrou-se associação estatisticamente significativa entre o prolongamento da permanência hospitalar e a ocorrência de complicações (pBACKGROUND: The reconstruction of the intestinal tract is not surgical complications risk-free and is associated to postoperative complications high rates; furthermore, infection remains the hardest challenge in this procedure. AIM: Epidemiological profile and mortality and morbidity in patients undergoing reconstruction of intestinal transit. METHODS: Retrospectively, 86 patients with intestinal stomas were analyzed through factors that impact on the morbimortality afterwards intestinal transit reconstruction, since January 2003 to April 2009. RESULTS: Loop colostomy (n=34 and abdominal trauma implicating 38.2% of indications to colostomy or

  3. Bridging the bonding gap: the transition from primates to humans

    Science.gov (United States)

    Dunbar, R. I. M.

    2012-01-01

    Primate societies are characterized by bonded social relationships of a kind that are rare in other mammal taxa. These bonded relationships, which provide the basis for coalitions, are underpinned by an endorphin mechanism mediated by social grooming. However, bonded relationships of this kind impose constraints on the size of social groups that are possible. When ecological pressures have demanded larger groups, primates have had to evolve new mechanisms to facilitate bonding. This has involved increasing the size of vocal and visual communication repertoires, increasing the time devoted to social interaction and developing a capacity to manage two-tier social relationships (strong and weak ties). I consider the implications of these constraints for the evolution of human social communities and argue that laughter was an early evolutionary innovation that helped bridge the bonding gap between the group sizes characteristic of chimpanzees and australopithecines and those in later hominins. PMID:22641822

  4. Sequence of an intestinal cDNA encoding human gastric inhibitory polypeptide precursor

    International Nuclear Information System (INIS)

    Gastric inhibitory polypeptide (GIP) is a 42-amino acid hormone that stimulates insulin secretion in the presence of glucose. Complementary DNA clones encoding human GIP were isolated from a library prepared with RNA from duodenum. The predicted amino acid sequence indicates that GIP is derived by proteolytic processing of a 153-residue precursor, preproGIP. The GIP moiety is flanked by polypeptide segments of 51 and 60 amino acids at its NH2 and COOH termini, respectively. The former includes a signal peptide of about 21 residues and an NH2-terminal propeptide of 30 amino acids. GIP is released from the precursor by processing at single arginine residues. There is a region of nine amino acids in the COOH-terminal propeptide of the GIP precursor that has partial homology with a portion of chromogranin A as well as pancreastatin

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    , 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...

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

    DEFF Research Database (Denmark)

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

    , 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...

  7. The Vibrio cholerae cytolysin promotes chloride secretion from intact human intestinal mucosa.

    Directory of Open Access Journals (Sweden)

    Lucantonio Debellis

    Full Text Available BACKGROUND: The pathogenicity of the Vibrio cholerae strains belonging to serogroup O1 and O139 is due to the production of virulence factors such as cholera toxin (CT and the toxin-coregulated pilus (TCP. The remaining serogroups, which mostly lack CT and TCP, are more frequently isolated from aquatic environmental sources than from clinical samples; nevertheless, these strains have been reported to cause human disease, such as sporadic outbreaks of watery diarrhoea and inflammatory enterocolitis. This evidence suggested the possibility that other virulence factor(s than cholera toxin might be crucial in the pathogenesis of Vibrio cholerae-induced diarrhoea, but their nature remains unknown. VCC, the hemolysin produced by virtually all Vibrio cholerae strains, has been proposed as a possible candidate, though a clear-cut demonstration attesting VCC as crucial in the pathogenesis of Vibrio cholerae-induced diarrhoea is still lacking. METHODOLOGY/PRINCIPAL FINDINGS: Electrophysiological parameters and paracellular permeability of stripped human healthy colon tissues, obtained at subtotal colectomy, mounted in Ussing chamber were studied in the presence or absence of VCC purified from culture supernatants of V. cholerae O1 El Tor strain. Short circuit current (I(SC and transepithelial resistance (R(T were measured by a computerized voltage clamp system. The exposure of sigmoid colon specimens to 1 nM VCC resulted in an increase of I(SC by 20.7%, with respect to the basal values, while R(T was reduced by 12.3%. Moreover, increase in I(SC was abolished by bilateral Cl(- reduction. CONCLUSION/SIGNIFICANCE: Our results demonstrate that VCC, by forming anion channels on the apical membrane of enterocytes, triggers an outward transcellular flux of chloride. Such an ion movement, associated with the outward movement of Na(+ and water, might be responsible for the diarrhoea caused by the non-toxigenic strains of Vibrio cholerae.

  8. 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 glycopeptide fraction excluded from Bio-Gel P-6 produced 3H-labeled N-acetylglucosamine and N-acetylgalactosamine

  9. Human oral isolate Lactobacillus fermentum AGR1487 reduces intestinal barrier integrity by increasing the turnover of microtubules in Caco-2 cells.

    Directory of Open Access Journals (Sweden)

    Rachel C Anderson

    Full Text Available Lactobacillus fermentum is found in fermented foods and thought to be harmless. In vivo and clinical studies indicate that some L. fermentum strains have beneficial properties, particularly for gastrointestinal health. However, L. fermentum AGR1487 decreases trans-epithelial electrical resistance (TEER, a measure of intestinal barrier integrity. The hypothesis was that L. fermentum AGR1487 decreases the expression of intestinal cell tight junction genes and proteins, thereby reducing barrier integrity. Transcriptomic and proteomic analyses of Caco-2 cells (model of human intestinal epithelial cells treated with L. fermentum AGR1487 were used to obtain a global view of the effect of the bacterium on intestinal epithelial cells. Specific functional characteristics by which L. fermentum AGR1487 reduces intestinal barrier integrity were examined using confocal microscopy, cell cycle progression and adherence bioassays. The effects of TEER-enhancing L. fermentum AGR1485 were investigated for comparison. L. fermentum AGR1487 did not alter the expression of Caco-2 cell tight junction genes (compared to L. fermentum AGR1485 and tight junction proteins were not able to be detected. However, L. fermentum AGR1487 increased the expression levels of seven tubulin genes and the abundance of three microtubule-associated proteins, which have been linked to tight junction disassembly. Additionally, Caco-2 cells treated with L. fermentum AGR1487 did not have defined and uniform borders of zona occludens 2 around each cell, unlike control or AGR1485 treated cells. L. fermentum AGR1487 cells were required for the negative effect on barrier integrity (bacterial supernatant did not cause a decrease in TEER, suggesting that a physical interaction may be necessary. Increased adherence of L. fermentum AGR1487 to Caco-2 cells (compared to L. fermentum AGR1485 was likely to facilitate this cell-to-cell interaction. These findings illustrate that bacterial strains of the

  10. Biotransformation and metabolic profile of buddleoside with human intestinal microflora by ultrahigh-performance liquid chromatography coupled to hybrid linear ion trap/orbitrap mass spectrometer.

    Science.gov (United States)

    Tao, Jin-Hua; Duan, Jin-Ao; Jiang, Shu; Qian, Yi-Yun; Qian, Da-Wei

    2016-07-01

    Buddleoside (also known as linarin) as the major flavonoid in Chrysanthemum morifolium Ramat., has been reported to possess a wide range of pharmacological activities. The human intestinal microbiota might have an important impact on drug metabolism and ultimately on the drug oral bioavailability. However, the interaction of the buddleoside with human intestinal bacteria remains unknown. In this study, the conversion of buddleoside by different bacteria from human feces was firstly investigated. A reliable, sensitive and rapid analytical method, ultra performance liquid chromatography was established and successfully applied to investigate the metabolites and metabolic profile of buddleoside by human intestinal bacteria. Among the isolated bacteria, four strains including Escherichia sp. 4, Escherichia sp. 34, Enterococcus sp. 45 and Bacillus sp. 46 showed more powerful conversion capability. Based on the accurate mass data and the characteristic MS(n) product ions, the parent and six metabolites were detected and tentatively identified compared with blank samples. The metabolites were produced by four main metabolic pathways including deglycosylation, acetylation, methylation and hydroxylation. Buddleoside could be firstly converted to its aglycon acacetin (M2) by the majority of the isolated intestinal bacteria. Subsequently, M2 was further metabolize to its methylated (M3), acetylated (M4), hydroxylated (M5) and hydrogenated product (M6). However, acacetin-7-glucosid (M1) was obtained only from the minor bacterial samples like Bacillus sp. 46. To further explain the metabolism of buddleoside, the β-d-glucosidase and α-l-rhamnosidase activities of four strains were analyzed. Bacillus sp. 46 could only produce α-l-rhamnosidase, while the other three strains showed two kinds of enzyme activities. Furthermore, the activities of α-l-rhamnosidase and β-d-glucosidase reached the highest level at 12-18h and 10-12h, respectively. The metabolic routes and metabolites

  11. Insider ownership, human resource strategies and performance in a transition economy

    OpenAIRE

    Buck, T.; Filatotchev, I.; N Demina; Wright, M

    2003-01-01

    Researchers and potential investors in transition economies need to understand the Human Resource Management (HRM) strategies of target firms, since human resources are arguably their most valuable assets. Understanding is difficult, however, because HRM strategies help to determine firms' performance, but are in turn influenced by corporate governance, particularly insider ownership. This paper employs a structural equation modeling methodology to examine the relations between governance, HR...

  12. Does human resource management matter in a transitional economy? China as an example

    OpenAIRE

    Law, K. S.; D K Tse; Zhou, N.

    2003-01-01

    This paper investigates the significance of how firms manage their human resources (HRs) within the confines of powerful social institutions in a transitional economy, the People's Republic of China (China). We propose that two dimensions, the role of human resource management (RHR) and followers' perception of the leader (TOP), are important contributors to firm performance as are the influences of the regional economy and firm ownership. We tested our hypotheses with a survey of 180 firms f...

  13. Interaction between oblongifolin C and UDP-glucuronosyltransferase isoforms in human liver and intestine microsomes.

    Science.gov (United States)

    Gao, Cui; Shi, Rong; Wang, Tianming; Tan, Hongsheng; Xu, Hongxi; Ma, Yueming

    2015-01-01

    1. Oblongifolin C (OC) is a potential natural anticancer candidate, and its metabolic profile has not yet been established. 2. One major OC glucuronidation metabolite (OCG) has been identified in a pool of human liver microsomes (HLMs). Chemical inhibition experiments suggested that OCG was mainly formed by UGT1A. A screen of recombinant UDP-glucuronosyltransferase isoforms (UGTs) indicated that UGT1A1 primarily mediates OC conjugation, with minor contributions from UGT1A3 and UGT1A8. Enzyme kinetic studies showed that UGT1A1 was the main UGT isoform involved in OCG in HLMs. 3. Further investigation suggested that OC is a broad inhibitor of UGTs. Additionally, OC competitively inhibited UGT1A6 with a Ki value of 3.49 ± 0.57 μM, whereas non-competitively inhibited UGT1A10 with a Ki value of 2.12 ± 0.18 μM. 4. Understanding the interaction between OC and UGTs will greatly contribute to future investigations regarding the inter-individual differences in OC metabolism in clinical trials and potential drug-drug interactions. PMID:25714435

  14. The pyrohealth transition: how combustion emissions have shaped health through human history.

    Science.gov (United States)

    Johnston, Fay H; Melody, Shannon; Bowman, David M J S

    2016-06-01

    Air pollution from landscape fires, domestic fires and fossil fuel combustion is recognized as the single most important global environmental risk factor for human mortality and is associated with a global burden of disease almost as large as that of tobacco smoking. The shift from a reliance on biomass to fossil fuels for powering economies, broadly described as the pyric transition, frames key patterns in human fire usage and landscape fire activity. These have produced distinct patters of human exposure to air pollution associated with the Agricultural and Industrial Revolutions and post-industrial the Earth global system-wide changes increasingly known as the Anthropocene. Changes in patterns of human fertility, mortality and morbidity associated with economic development have been previously described in terms of demographic, epidemiological and nutrition transitions, yet these frameworks have not explicitly considered the direct consequences of combustion emissions for human health. To address this gap, we propose a pyrohealth transition and use data from the Global Burden of Disease (GBD) collaboration to compare direct mortality impacts of emissions from landscape fires, domestic fires, fossil fuel combustion and the global epidemic of tobacco smoking. Improving human health and reducing the environmental impacts on the Earth system will require a considerable reduction in biomass and fossil fuel combustion.This article is part of the themed issue 'The interaction of fire and mankind'. PMID:27216506

  15. A Novel Tightly Regulated Gene Expression System for the Human Intestinal Symbiont Bacteroides thetaiotaomicron

    Science.gov (United States)

    Horn, Nikki; Carvalho, Ana L.; Overweg, Karin; Wegmann, Udo; Carding, Simon R.; Stentz, Régis

    2016-01-01

    There is considerable interest in studying the function of Bacteroides species resident in the human gastrointestinal (GI)-tract and the contribution they make to host health. Reverse genetics and protein expression techniques, such as those developed for well-characterized Escherichia coli cannot be applied to Bacteroides species as they and other members of the Bacteriodetes phylum have unique promoter structures. The availability of useful Bacteroides-specific genetic tools is therefore limited. Here we describe the development of an effective mannan-controlled gene expression system for Bacteroides thetaiotaomicron containing the mannan-inducible promoter–region of an α-1,2-mannosidase gene (BT_3784), a ribosomal binding site designed to modulate expression, a multiple cloning site to facilitate the cloning of genes of interest, and a transcriptional terminator. Using the Lactobacillus pepI as a reporter gene, mannan induction resulted in an increase of reporter activity in a time- and concentration-dependent manner with a wide range of activity. The endogenous BtcepA cephalosporinase gene was used to demonstrate the suitability of this novel expression system, enabling the isolation of a His-tagged version of BtCepA. We have also shown with experiments performed in mice that the system can be induced in vivo in the presence of an exogenous source of mannan. By enabling the controlled expression of endogenous and exogenous genes in B. thetaiotaomicron this novel inducer-dependent expression system will aid in defining the physiological role of individual genes and the functional analyses of their products. PMID:27468280

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

    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

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

    Science.gov (United States)

    Liévin-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.

  18. 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

  19. Cox2 and β-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.

  20. Screening in a Lactobacillus delbrueckii subsp. bulgaricus Collection to select a strain able to survive to the human intestinal tract

    Directory of Open Access Journals (Sweden)

    Clotilde Vázquez

    2013-08-01

    Full Text Available Objectives: Genetic diversity and resistance of Lactobacillus bulgaricus sbsp. delbrueckii collection with 100 isolates from different home-made yogurt in rural Bulgarian areas were determined. Methods: The strain K98 was the most resistant to bile salts and low pH. Survival and effects on short chain fatty acids production were tested in 20 healthy volunteers. High genetic diversity was observed in the L. bulgaricus collection by RAPD, whereas the ability of tolerate high deoxycholic acid concentrations, and different acid pHs was variable. The strain K98 was selected and used to prepare a homemade yogurt which was administered to 20 healthy volunteers (500 ml/day during 15d. A basal faecal sample and another after yogurt intake were recovered. Results: DGGE experiments, using both universal and Lactic Acid Bacteria (LAB primers, demonstrated no significant changes in the qualitative composition of gut microbiota. A band corresponding to L. bulgaricus was observed in all 20 samples. Viable L. bulgaricus K98 strain was only recovered in one volunteer. After yogurt intake we found an increase of LAB and Clostridium perfringens, and a decrease of Bacteroides-Prevotella-Porphyromonas. In addition, increases of acetic, butyric and 2-hydroxybutyric acids in faeces were detected. Conclusions: Genetic diversity of L. delbrueckii subsp. bulgaricus especie is high We have isolated a probiotic resistant strain to bile and high acidity, L. delbrueckii subsp. bulgaricus-K98. Qualitative and quantitative changes in the intestinal microbiota are found after ingestion of a homemade yogurt containing this strain, with a concomitant increase in faecal SCFA. Our findings support the interest in developing further studies providing different amounts of L. delbrueckii subsp. bulgaricus-K98, and should evaluate its clinical effects in human disease.

  1. Concord and Niagara Grape Juice and Their Phenolics Modify Intestinal Glucose Transport in a Coupled in Vitro Digestion/Caco-2 Human Intestinal Model

    Science.gov (United States)

    Moser, Sydney; Lim, Jongbin; Chegeni, Mohammad; Wightman, JoLynne D.; Hamaker, Bruce R.; Ferruzzi, Mario G.

    2016-01-01

    While the potential of dietary phenolics to mitigate glycemic response has been proposed, the translation of these effects to phenolic rich foods such as 100% grape juice (GJ) remains unclear. Initial in vitro screening of GJ phenolic extracts from American grape varieties (V. labrusca; Niagara and Concord) suggested limited inhibitory capacity for amylase and α-glucosidase (6.2%–11.5% inhibition; p < 0.05). Separately, all GJ extracts (10–100 µM total phenolics) did reduce intestinal trans-epithelial transport of deuterated glucose (d7-glu) and fructose (d7-fru) by Caco-2 monolayers in a dose-dependent fashion, with 60 min d7-glu/d7-fru transport reduced 10%–38% by GJ extracts compared to control. To expand on these findings by assessing the ability of 100% GJ to modify starch digestion and glucose transport from a model starch-rich meal, 100% Niagara and Concord GJ samples were combined with a starch rich model meal (1:1 and 1:2 wt:wt) and glucose release and transport were assessed in a coupled in vitro digestion/Caco-2 cell model. Digestive release of glucose from the starch model meal was decreased when digested in the presence of GJs (5.9%–15% relative to sugar matched control). Furthermore, transport of d7-glu was reduced 10%–38% by digesta containing bioaccessible phenolics from Concord and Niagara GJ compared to control. These data suggest that phenolics present in 100% GJ may alter absorption of monosaccharides naturally present in 100% GJ and may potentially alter glycemic response if consumed with a starch rich meal. PMID:27399765

  2. Biomechanics of the human walk-to-run gait transition in persons with unilateral transtibial amputation.

    Science.gov (United States)

    Giest, Tracy N; Chang, Young-Hui

    2016-06-14

    Propulsive force production (indicative of intrinsic force-length-velocity characteristics of the plantar flexor muscles) has been shown to be a major determinant of the human walk-to-run transition. The purpose of this work was to determine the gait transition speed of persons with unilateral transtibial amputation donning a passive-elastic prosthesis and assess whether a mechanical limit of their intact side plantar flexor muscles is a major determinant of their walk-to-run transition. We determined each individual׳s gait transition speed (GTS) via an incremental protocol and assessed kinetics and kinematics during walking at speeds 50%, 60%, 70%, 80%, 90%, 100%, 120%, and 130% of that gait transition speed (100%:GTS). Unilateral transtibial amputees transitioned between gaits at significantly slower absolute speeds than matched able-bodied controls (1.73±0.13 and 2.09±0.05m/s respectively, p120%: 0.23±0.05BW, p<0.05). In contrast, amputee subjects' intact side generated significantly higher peak anterior-posterior propulsive forces while walking at speeds above their preferred gait transition speed (100%: 0.28±0.04<110%: 0.30±0.04BW, p<0.05). Changes in propulsive force production were found to be a function of changes in absolute speed, rather than relative to the walk-to-run transition speed. Therefore, the walk-to-run transition in unilateral transtibial amputees is not likely dictated by propulsive force production or the force-length-velocity characteristics of the intact side plantar flexor muscles. PMID:27087677

  3. Hydrolytic Fate of 3/15-Acetyldeoxynivalenol in Humans: Specific Deacetylation by the Small Intestine and Liver Revealed Using in Vitro and ex Vivo Approaches.

    Science.gov (United States)

    Ajandouz, El Hassan; Berdah, Stéphane; Moutardier, Vincent; Bege, Thierry; Birnbaum, David Jérémie; Perrier, Josette; Di Pasquale, Eric; Maresca, Marc

    2016-01-01

    In addition to deoxynivalenol (DON), acetylated derivatives, i.e., 3-acetyl and 15-acetyldexynivalenol (or 3/15ADON), are present in cereals leading to exposure to these mycotoxins. Animal and human studies suggest that 3/15ADON are converted into DON after their ingestion through hydrolysis of the acetyl moiety, the site(s) of such deacetylation being still uncharacterized. We used in vitro and ex vivo approaches to study the deacetylation of 3/15ADON by enzymes and cells/tissues present on their way from the food matrix to the blood in humans. We found that luminal deacetylation by digestive enzymes and bacteria is limited. Using human cells, tissues and S9 fractions, we were able to demonstrate that small intestine and liver possess strong deacetylation capacity compared to colon and kidneys. Interestingly, in most cases, deacetylation was more efficient for 3ADON than 15ADON. Although we initially thought that carboxylesterases (CES) could be responsible for the deacetylation of 3/15ADON, the use of pure human CES1/2 and of CES inhibitor demonstrated that CES are not involved. Taken together, our original model system allowed us to identify the small intestine and the liver as the main site of deacetylation of ingested 3/15ADON in humans. PMID:27483321

  4. Hydrolytic Fate of 3/15-Acetyldeoxynivalenol in Humans: Specific Deacetylation by the Small Intestine and Liver Revealed Using in Vitro and ex Vivo Approaches

    Science.gov (United States)

    Ajandouz, El Hassan; Berdah, Stéphane; Moutardier, Vincent; Bege, Thierry; Birnbaum, David Jérémie; Perrier, Josette; Di Pasquale, Eric; Maresca, Marc

    2016-01-01

    In addition to deoxynivalenol (DON), acetylated derivatives, i.e., 3-acetyl and 15-acetyldexynivalenol (or 3/15ADON), are present in cereals leading to exposure to these mycotoxins. Animal and human studies suggest that 3/15ADON are converted into DON after their ingestion through hydrolysis of the acetyl moiety, the site(s) of such deacetylation being still uncharacterized. We used in vitro and ex vivo approaches to study the deacetylation of 3/15ADON by enzymes and cells/tissues present on their way from the food matrix to the blood in humans. We found that luminal deacetylation by digestive enzymes and bacteria is limited. Using human cells, tissues and S9 fractions, we were able to demonstrate that small intestine and liver possess strong deacetylation capacity compared to colon and kidneys. Interestingly, in most cases, deacetylation was more efficient for 3ADON than 15ADON. Although we initially thought that carboxylesterases (CES) could be responsible for the deacetylation of 3/15ADON, the use of pure human CES1/2 and of CES inhibitor demonstrated that CES are not involved. Taken together, our original model system allowed us to identify the small intestine and the liver as the main site of deacetylation of ingested 3/15ADON in humans. PMID:27483321

  5. The origins of the Acheulean: past and present perspectives on a major transition in human evolution.

    Science.gov (United States)

    de la Torre, Ignacio

    2016-07-01

    The emergence of the Acheulean from the earlier Oldowan constitutes a major transition in human evolution, the theme of this special issue. This paper discusses the evidence for the origins of the Acheulean, a cornerstone in the history of human technology, from two perspectives; firstly, a review of the history of investigations on Acheulean research is presented. This approach introduces the evolution of theories throughout the development of the discipline, and reviews the way in which cumulative knowledge led to the prevalent explanatory framework for the emergence of the Acheulean. The second part presents the current state of the art in Acheulean origins research, and reviews the hard evidence for the appearance of this technology in Africa around 1.7 Ma, and its significance for the evolutionary history of Homo erectusThis article is part of the themed issue 'Major transitions in human evolution'. PMID:27298475

  6. The origins of the Acheulean: past and present perspectives on a major transition in human evolution.

    Science.gov (United States)

    de la Torre, Ignacio

    2016-07-01

    The emergence of the Acheulean from the earlier Oldowan constitutes a major transition in human evolution, the theme of this special issue. This paper discusses the evidence for the origins of the Acheulean, a cornerstone in the history of human technology, from two perspectives; firstly, a review of the history of investigations on Acheulean research is presented. This approach introduces the evolution of theories throughout the development of the discipline, and reviews the way in which cumulative knowledge led to the prevalent explanatory framework for the emergence of the Acheulean. The second part presents the current state of the art in Acheulean origins research, and reviews the hard evidence for the appearance of this technology in Africa around 1.7 Ma, and its significance for the evolutionary history of Homo erectusThis article is part of the themed issue 'Major transitions in human evolution'.

  7. INTERRELATIONSHIPS BETWEEN HUMAN CAPITAL AND SOCIAL CAPITAL: IMPLICATIONS FOR ECONOMIC DEVELOPMENT IN TRANSITION ECONOMIES

    OpenAIRE

    Eve Parts

    2003-01-01

    One of the main tasks of the transition economies is to catch up with the advanced levels of highly developed economies. The lack of social capital is a major impediment to this process, as it does not allow taking advantage of the comparatively high level of human capital in these countries. The purpose of the current paper is to study the interrelationships between human capital and social capital, with the main emphasis on how social capital affects the accumulation of human capital. In ge...

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-01-07

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

  10. Intestinal Malrotation

    Science.gov (United States)

    ... to maintain adequate nutrition (a condition known as short bowel syndrome). They may be dependent on intravenous nutrition for a time after surgery (or even permanently if too little intestine remains) ...

  11. Growth-Inhibiting and morphostructural effects of constituents identified in Asarum heterotropoides root on human intestinal bacteria

    Science.gov (United States)

    2013-01-01

    the antimicrobial susceptibility of the harmful Gram-positive bacteria and the harmful and nonpathogenic Gram-negative bacteria was not observed. Scanning electron microscopy observations showed different degrees of physical damage and morphological alteration to both Gram-positive and Gram-negative bacteria treated with α-asarone, δ-3-carene, pellitorine, or ciprofloxacin, indicating that they do not share a common mode of action. Conclusion A. heterotropoides root-derived materials described merit further study as potential antibacterial products or lead molecules for the prevention or eradication from humans from diseases caused by harmful intestinal bacteria. PMID:24083511

  12. Human intestinal parasites in Karakuak, West Flores, Indonesia and the effect of treatment with mebendazole and pyrantel pamoate.

    Science.gov (United States)

    Purnomo; Partono, F; Soewarta, A

    1980-09-01

    A survey for intestinal parasites and mass-treatment with a combination of mebendazole and pyrantel pamoate were conducted in Karakuak, West Flores in 1977. A total of 198 stool specimens from 104 males and 94 females ranging in age from less than 1 to 70 years were examined and 72% harbored one or more intestinal parasites. Ascaris lumbricoides (43%) and Entamoeba histolytica (21%) were the most common, followed by Entamoeba coli (19%), hookworm (18%), Iodamoeba bütschlii (8%), Giardia lamblia (5%) and Trichuris trichiura (4%). Other intestinal parasites infrequently found were: Entamoeba hartmanni (2%), Chilomastix mesnili (2%), Endolimax nana (1%), Enterobius vermicularis (1%) and a heterophyid sp. (1%). A combination of mebendazole base at 200 mg/day and pyrantel pamoate salt at 60 mg/day for three consecutive days was 100% effective. PMID:7444573

  13. Marmoset cytochrome P450 2J2 mainly expressed in small intestines and livers effectively metabolizes human P450 2J2 probe substrates, astemizole and terfenadine.

    Science.gov (United States)

    Uehara, Shotaro; Uno, Yasuhiro; Inoue, Takashi; Okamoto, Eriko; Sasaki, Erika; Yamazaki, Hiroshi

    2016-11-01

    1. Common marmoset (Callithrix jacchus), a New World Monkey, has potential to be a useful animal model in preclinical studies. However, drug metabolizing properties have not been fully understood due to insufficient information on cytochrome P450 (P450), major drug metabolizing enzymes. 2. Marmoset P450 2J2 cDNA was isolated from marmoset livers. The deduced amino acid sequence showed a high-sequence identity (91%) with cynomolgus monkey and human P450 2J2 enzymes. A phylogenetic tree revealed that marmoset P450 2J2 was evolutionarily closer to cynomolgus monkey and human P450 2J2 enzymes, than P450 2J forms in pigs, rabbits, rats or mice. 3. Marmoset P450 2J2 mRNA was abundantly expressed in the small intestine and liver, and to a lesser extent in the brain, lung and kidney. Immunoblot analysis also showed expression of marmoset P450 2J2 protein in the small intestine and liver. 4. Enzyme assays using marmoset P450 2J2 protein heterologously expressed in Escherichia coli indicated that marmoset P450 2J2 effectively catalyzed astemizole O-demethylation and terfenadine t-butyl hydroxylation, similar to human and cynomolgus monkey P450 2J2 enzymes. 5. These results suggest the functional characteristics of P450 2J2 enzymes are similar among marmosets, cynomolgus monkeys and humans. PMID:26899760

  14. Marmoset cytochrome P450 2J2 mainly expressed in small intestines and livers effectively metabolizes human P450 2J2 probe substrates, astemizole and terfenadine.

    Science.gov (United States)

    Uehara, Shotaro; Uno, Yasuhiro; Inoue, Takashi; Okamoto, Eriko; Sasaki, Erika; Yamazaki, Hiroshi

    2016-11-01

    1. Common marmoset (Callithrix jacchus), a New World Monkey, has potential to be a useful animal model in preclinical studies. However, drug metabolizing properties have not been fully understood due to insufficient information on cytochrome P450 (P450), major drug metabolizing enzymes. 2. Marmoset P450 2J2 cDNA was isolated from marmoset livers. The deduced amino acid sequence showed a high-sequence identity (91%) with cynomolgus monkey and human P450 2J2 enzymes. A phylogenetic tree revealed that marmoset P450 2J2 was evolutionarily closer to cynomolgus monkey and human P450 2J2 enzymes, than P450 2J forms in pigs, rabbits, rats or mice. 3. Marmoset P450 2J2 mRNA was abundantly expressed in the small intestine and liver, and to a lesser extent in the brain, lung and kidney. Immunoblot analysis also showed expression of marmoset P450 2J2 protein in the small intestine and liver. 4. Enzyme assays using marmoset P450 2J2 protein heterologously expressed in Escherichia coli indicated that marmoset P450 2J2 effectively catalyzed astemizole O-demethylation and terfenadine t-butyl hydroxylation, similar to human and cynomolgus monkey P450 2J2 enzymes. 5. These results suggest the functional characteristics of P450 2J2 enzymes are similar among marmosets, cynomolgus monkeys and humans.

  15. Relationship between human intestinal symbiotic microbes and health and disease%肠道共生微生物与健康和疾病

    Institute of Scientific and Technical Information of China (English)

    胡旭; 王涛; 王沥; 金锋

    2012-01-01

    Human body is a natural habitat for large and dynamic microbial communities. The microbiota are widely distributed on the surface of human skin, mouth, digestive tract, respiratory and reproductive tract. These organisms and human body form a symbiotic complex. Comparing with micriobiota colonized on other parts of human body, the relevance and the effect of intestinal microbiota on the physiological and pathological status in host have been well illuminated. The functions of intestinal microbiota are promoting metabolization, which results in better energy harvest and nutrients aborption, providing nut-ritients for epithelium and enhancing immune system in order to protect the host from pathogen invitation. Futhermore, the imbalance of the intestinal microbiota is the symptom of some diseases or inductive causes, such as obesity, diabetes and intestinal inflammation. Further study of the relationship between symbiotic microbes and human health will provide new methods to prevent and treat some diseases.%人体是个庞大的动态的微生物群落的天然寄居场所,人体的皮肤、口腔、消化道、呼吸道和生殖道等部位都寄生着大量的微生物.这些微生物与人体互惠互利,形成共生复合体.其中,肠道共生微生物与宿主的相关性及对宿主生理和病理状态的影响已经得到了很好的阐释.肠道共生微生物的主要功能是帮助宿主代谢,使得能量和可吸收的营养物质更好的被利用,为肠道上皮细胞提供营养,增强免疫功能,帮助寄主抵抗外来微生物的入侵.肠道菌群紊乱也是一些疾病的症状或诱发原因,比如肥胖、糖尿病和肠道炎症等.深入研究人类共生微生物与健康和疾病的关系,将为一些疾病的预防和治疗提供新的手段.

  16. Effect of Spore-bearing Lactic Acid-forming Bacteria (Bacillus coagulans SANK 70258) Administration on the Intestinal Environment, Defecation Frequency, Fecal Characteristics and Dermal Characteristics in Humans and Rats

    OpenAIRE

    Ara, Katsutoshi; Meguro, Shinichi; Hase, Tadasi; Tokimitsu, Ichirou; OTSUJI, Kazuya; Kawai, Shuji; Ito, Susumu; Iino, Hisakazu

    2011-01-01

    The effects of spore-bearing lactic acid-forming bacteria (Bacillus coagulans SANK 70258) on intestinal flora and decomposition products in the intestine, as well as on various dermal characteristics were determined in healthy humans and rats. Improvement of fecal shape, change of fecal color from dark brown to yellowish brown, decrease of fecal odor and fecal pH and an increase in defecation frequency in persons whose defecation frequency was relatively low were observed after administration...

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

    NARCIS (Netherlands)

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

    2013-01-01

    Background: Vitamin B6 is present in various forms (vitamers) in the diet that need to be metabolized to pyridoxal phosphate (PLP), the active cofactor form of vitamin B6. In literature, the liver has been reported to be the major site for this conversion, whereas the exact role of the intestine rem

  18. Intra-urban human mobility and activity transition: evidence from social media check-in data.

    Directory of Open Access Journals (Sweden)

    Lun Wu

    Full Text Available Most existing human mobility literature focuses on exterior characteristics of movements but neglects activities, the driving force that underlies human movements. In this research, we combine activity-based analysis with a movement-based approach to model the intra-urban human mobility observed from about 15 million check-in records during a yearlong period in Shanghai, China. The proposed model is activity-based and includes two parts: the transition of travel demands during a specific time period and the movement between locations. For the first part, we find the transition probability between activities varies over time, and then we construct a temporal transition probability matrix to represent the transition probability of travel demands during a time interval. For the second part, we suggest that the travel demands can be divided into two classes, locationally mandatory activity (LMA and locationally stochastic activity (LSA, according to whether the demand is associated with fixed location or not. By judging the combination of predecessor activity type and successor activity type we determine three trip patterns, each associated with a different decay parameter. To validate the model, we adopt the mechanism of an agent-based model and compare the simulated results with the observed pattern from the displacement distance distribution, the spatio-temporal distribution of activities, and the temporal distribution of travel demand transitions. The results show that the simulated patterns fit the observed data well, indicating that these findings open new directions for combining activity-based analysis with a movement-based approach using social media check-in data.

  19. Colonization of the streptomycin-treated mouse large intestine by a human fecal Escherichia coli strain: role of growth in mucus.

    OpenAIRE

    Wadolkowski, E A; Laux, D C; Cohen, P S

    1988-01-01

    The relative colonizing abilities of Escherichia coli F-18, isolated from the feces of a healthy human, and E. coli F-18col-, a strain derived from it which does not make the E. coli F-18 colicin, were studied. In a previous report, it was shown that when each strain was fed individually to streptomycin-treated mice, at approximately 10(10) CFU per mouse, each colonized the large intestine at between 10(7) and 10(8) CFU/g of feces indefinitely. However, when simultaneously fed to mice, althou...

  20. The Effect of Lactulose on the Survival of Lactobacillus rhamnosus in the Simulator of the Human Intestinal Microbial Ecosystem (SHIME) and in vivo

    OpenAIRE

    Kontula, Pia; Nollet, Lode; Saarela, Maria; Vilpponen-Salmela, Terttu; Verstraete, Willy; Mattila-Sandholm, Tiina; von Wright, Atte

    2011-01-01

    The effect of lactulose on the survival of Lactobacillus rhamnosus VTT E-97800 and on the colon microbiota and its metabolic activity was studied using the Simulator of the Human Intestinal Microbial Ecosystem (SHIME) model. L. rhamnosus VTT E-97800 and lactulose together enhanced the production of butyric acid and decreased ammonium concentration in the model. The numbers of Bacteroides were observed to decrease 2.5–2.0 log10 cfu:ml during the SHIME experiment. In the subsequent in viv...

  1. 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; Hitt, Stacy;

    2012-01-01

    Glucagon-like peptide-2 (GLP-2) is a nutrient-dependent, proglucagon-derived gut hormone that shows promise for the treatment of short bowel syndrome (SBS). Our objective was to investigate how combination GLP-2 + enteral nutrients (EN) affects intestinal adaption in a rat model that mimics severe...... human SBS and requires parenteral nutrition (PN). Male Sprague-Dawley rats were assigned to one of five groups and maintained with PN for 18 days: total parenteral nutrition (TPN) alone, TPN + GLP-2 (100 μg·kg(-1)·day(-1)), PN + EN + GLP-2(7 days), PN + EN + GLP-2(18 days), and a nonsurgical oral...

  2. Spontaneous quaternary and tertiary T-R transitions of human hemoglobin in molecular dynamics simulation.

    Directory of Open Access Journals (Sweden)

    Jochen S Hub

    2010-05-01

    Full Text Available We present molecular dynamics simulations of unliganded human hemoglobin (Hb A under physiological conditions, starting from the R, R2, and T state. The simulations were carried out with protonated and deprotonated HC3 histidines His(beta146, and they sum up to a total length of 5.6 micros. We observe spontaneous and reproducible T-->R quaternary transitions of the Hb tetramer and tertiary transitions of the alpha and beta subunits, as detected from principal component projections, from an RMSD measure, and from rigid body rotation analysis. The simulations reveal a marked asymmetry between the alpha and beta subunits. Using the mutual information as correlation measure, we find that the beta subunits are substantially more strongly linked to the quaternary transition than the alpha subunits. In addition, the tertiary populations of the alpha and beta subunits differ substantially, with the beta subunits showing a tendency towards R, and the alpha subunits showing a tendency towards T. Based on the simulation results, we present a transition pathway for coupled quaternary and tertiary transitions between the R and T conformations of Hb.

  3. Transitions between dynamical states of differing stability in the human brain

    OpenAIRE

    Meyer-Lindenberg, Andreas; Ziemann, Ulf; Hajak, Göran; Cohen, Leonardo; Berman, Karen Faith

    2002-01-01

    What mechanisms underlie the flexible formation, adaptation, synchronization, and dissolution of large-scale neural assemblies from the 1010 densely interconnected, continuously active neurons of the human brain? Nonlinear dynamics provides a unifying perspective on self-organization. It shows that the emergence of patterns in open, nonequilibrium systems is governed by their stability in response to small disturbances and predicts macroscopic transitions between patterns of differing stabili...

  4. 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 ...

  5. Cyclophilin D-Sensitive Mitochondrial Permeability Transition in Adult Human Brain and Liver Mitochondria

    OpenAIRE

    Hansson, Magnus; Morota, Saori; Li CHEN; Matsuyama, Nagahisa; SUZUKI, YOSHIAKI; Nakajima, Satoshi; Tanoue, Tadashi; Omi, Akibumi; Shibasaki, Futoshi; Shimazu, Motohide; IKEDA, Yukio; Uchino, Hiroyuki; Elmér, Eskil

    2011-01-01

    The mitochondrial permeability transition (mPT) is considered to be a major cause of cell death under a variety of pathophysiological conditions of the central nervous system (CNS) and other organs. Pharmacological inhibition or genetic knockout of the matrix protein cyclophilin D (CypD) prevents mPT and cell degeneration in several models of brain injury. If these findings in animal models are translatable to human disease, pharmacological inhibition of mPT offers a promising therapeutic tar...

  6. Ultra-High Field MRI: Transition to Human 7 T in Finland - Workshop Memorandum

    OpenAIRE

    Auranen, Toni; Carlson, Synnöve; Hämäläinen, Matti; Jousmäki, Veikko; Renvall, Ville; Salmelin, Riitta

    2016-01-01

    A workshop “Ultra-High Field MRI: Transition to Human 7 T in Finland” was organized at Aalto University on October 8–9, 2015. The organizers included Aalto University School of Science, Finnish Infrastructures for Functional Imaging (FIFI), Aalto NeuroImaging (ANI), Aalto Brain Centre (ABC), and Department of Neuroscience and Biomedical Engineering (NBE). The purpose of the workshop was to demonstrate scientific achievements and possibilities enabled by ultra-high field (UHF) magnetic resonan...

  7. How institutions shaped the last major evolutionary transition to large-scale human societies.

    Science.gov (United States)

    Powers, Simon T; van Schaik, Carel P; Lehmann, Laurent

    2016-02-01

    What drove the transition from small-scale human societies centred on kinship and personal exchange, to large-scale societies comprising cooperation and division of labour among untold numbers of unrelated individuals? We propose that the unique human capacity to negotiate institutional rules that coordinate social actions was a key driver of this transition. By creating institutions, humans have been able to move from the default 'Hobbesian' rules of the 'game of life', determined by physical/environmental constraints, into self-created rules of social organization where cooperation can be individually advantageous even in large groups of unrelated individuals. Examples include rules of food sharing in hunter-gatherers, rules for the usage of irrigation systems in agriculturalists, property rights and systems for sharing reputation between mediaeval traders. Successful institutions create rules of interaction that are self-enforcing, providing direct benefits both to individuals that follow them, and to individuals that sanction rule breakers. Forming institutions requires shared intentionality, language and other cognitive abilities largely absent in other primates. We explain how cooperative breeding likely selected for these abilities early in the Homo lineage. This allowed anatomically modern humans to create institutions that transformed the self-reliance of our primate ancestors into the division of labour of large-scale human social organization. PMID:26729937

  8. Small & Large Intestine

    Science.gov (United States)

    ... the large intestine produces no digestive enzymes. Chemical digestion is completed in the small intestine before the chyme reaches the large intestine. Functions of the large intestine include the absorption of water and electrolytes and the elimination of ...

  9. Perfil epidemiológico e morbimortalidade dos pacientes submetidos à reconstrução de trânsito intestinal: experiência de um centro secundário do nordeste Brasileiro Epidemiologic profile and morbimortality of patients undergoing to intestinal transit reconstruction: experience of a secundary health service in Brazil northeast

    Directory of Open Access Journals (Sweden)

    Jeany Borges e Silva

    2010-09-01

    Full Text Available Racional- A reconstrução do trânsito intestinal não está isenta de riscos cirúrgicos e apresenta taxas consideráveis de complicações pós-operatórias, sendo que a infecção continua a ser um dos maiores desafios existentes neste procedimento. Métodos- Foram analisados retrospectivamente 86 prontuários de pacientes com colostomia ou ileostomia, através de fatores que tivessem impacto sobre a morbimortalidade após a reconstrução de trânsito intestinal, de janeiro de 2003 a abril de 2009. Resultados- Houve 20 mulheres e 60 homens, com idade média de 43 anos. A colostomia em alça (n: 34 e o trauma abdominal indicando colostomia ou ileostomia foram as condições mais frequentes. O intervalo médio entre a confecção do estoma e a reconstrução de trânsito intestinal foi 15,7 meses. O índice de morbidade foi 56,8%, sendo a infecção incisional a complicação mais comum (27.47%. A permanência hospitalar média foi 7,6 dias. Houve regressão linear positiva entre permanência hospitalar pós-operatória e a idade do paciente. Demonstrou-se associação estatisticamente significativa entre o prolongamento da permanência hospitalar e a ocorrência de complicações (pBackground - The reconstruction of the intestinal tract is not surgical complications risk-free and is associated to postoperative complications high rates; furthermore, infection remains the hardest challenge in this procedure. Methods - Retrospectively, eighty-six patients with intestinal stomas were analyzed through factors that impact on the morbimortality afterwards intestinal transit reconstruction, since January 2003 to April 2009. Results - Loop colostomy (n=34 and abdominal trauma implicating 38.2% of indications to colostomy or ileostomy were the most frequent conditions. The mean interval between stoma confection and intestinal transit reconstruction was 15.7 months. The morbidity frequency was 56.8% and incisional infection was its commonest

  10. Inhibition of the NF-kappaB pathway in human intestinal epithelial cells by commensal Streptococcus salivarius.

    Science.gov (United States)

    Kaci, Ghalia; Lakhdari, Omar; Doré, Joël; Ehrlich, S Dusko; Renault, Pierre; Blottière, Hervé M; Delorme, Christine

    2011-07-01

    Streptococcus salivarius exhibited an anti-inflammatory effect on intestinal epithelial cells (IECs) and monocytes. Strains were screened using a reporter clone, HT-29/kB-luc-E, induced by tumor necrosis factor alpha (TNF-α). Supernatant from each strain downregulated NF-κB activation. The two most efficient strains produced an active metabolite (<3 kDa) which was able to downregulate the secretion of the proinflammatory chemokine interleukin-8 (IL-8). PMID:21602373

  11. Inhibition of the NF-κB Pathway in Human Intestinal Epithelial Cells by Commensal Streptococcus salivarius ▿ †

    Science.gov (United States)

    Kaci, Ghalia; Lakhdari, Omar; Doré, Joël; Ehrlich, S. Dusko; Renault, Pierre; Blottière, Hervé M.; Delorme, Christine

    2011-01-01

    Streptococcus salivarius exhibited an anti-inflammatory effect on intestinal epithelial cells (IECs) and monocytes. Strains were screened using a reporter clone, HT-29/kB-luc-E, induced by tumor necrosis factor alpha (TNF-α). Supernatant from each strain downregulated NF-κB activation. The two most efficient strains produced an active metabolite (<3 kDa) which was able to downregulate the secretion of the proinflammatory chemokine interleukin-8 (IL-8). PMID:21602373

  12. Pancreatoduodenectomy as a source of human small intestine for Ussing Chamber Investigations and comparative studies with rat tissue

    OpenAIRE

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

    2011-01-01

    Abstract A clear understanding of oral drug absorption is an important aspect of the drug development process. The permeability of drug compounds across intact sections of small intestine from numerous species, including man, has often been investigated using modified Ussing Chambers. The maintenance of viable, intact tissue is critical to the success of this technique. This study therefore aimed to assess the viability and integrity of tissue from patients undergoing pancreatod...

  13. Modulators of intestinal alkaline phosphatase.

    Science.gov (United States)

    Bobkova, Ekaterina V; Kiffer-Moreira, Tina; Sergienko, Eduard A

    2013-01-01

    Small molecule modulators of phosphatases can lead to clinically useful drugs and serve as invaluable tools to study functional roles of various phosphatases in vivo. Here, we describe lead discovery strategies for identification of inhibitors and activators of intestinal alkaline phosphatases. To identify isozyme-selective inhibitors and activators of the human and mouse intestinal alkaline phosphatases, ultrahigh throughput chemiluminescent assays, utilizing CDP-Star as a substrate, were developed for murine intestinal alkaline phosphatase (mIAP), human intestinal alkaline phosphatase (hIAP), human placental alkaline phosphatase (PLAP), and human tissue-nonspecific alkaline phosphatase (TNAP) isozymes. Using these 1,536-well assays, concurrent HTS screens of the MLSMR library of 323,000 compounds were conducted for human and mouse IAP isozymes monitoring both inhibition and activation. This parallel screening approach led to identification of a novel inhibitory scaffold selective for murine intestinal alkaline phosphatase. SAR efforts based on parallel testing of analogs against different AP isozymes generated a potent inhibitor of the murine IAP with IC50 of 540 nM, at least 65-fold selectivity against human TNAP, and >185 selectivity against human PLAP. PMID:23860652

  14. Identification and Characterization of a Novel Nontranslated Sequence Variant of the Human Intestinal Di-/Tripeptide Transporter, hPEPT1

    Directory of Open Access Journals (Sweden)

    Helle Bach Søndergaard

    2012-01-01

    Full Text Available The human H+-coupled di-/tripeptide transporter (hPEPT1 mediates intestinal absorption of dietary di- and tripeptides, as well as several peptidomimetic drug compounds. The aim of the present study was to investigate the possible role of the hPEPT1 variant hPEPT1-RF in hPEPT1 regulation. However, the proposed hPEPT1-RF mRNA sequence could not be detected in Caco-2 cells or in human intestinal samples. Instead, a new sequence variant, hPEPT1-RFI, was found, which is almost identical to the proposed hPEPT1-RF, except for two nucleotide insertions and one deletion that resulted in a changed open reading frame as compared to hPEPT1-RF. In vitro translation analysis showed that hPEPT1-RFI was not translated. In conclusion, the existence of hPEPT1-RF could not be confirmed; furthermore, the identified sequence variant, hPEPT1-RFI, does not appear to be translated and is therefore unlikely to have a regulatory effect on hPEPT1 transport activity.

  15. Both direct and indirect effects account for the pro-inflammatory activity of enteropathogenic mycotoxins on the human intestinal epithelium: Stimulation of interleukin-8 secretion, potentiation of interleukin-1β effect and increase in the transepithelial passage of commensal bacteria

    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-1β), and/or (ii) an increase in the transepithelial passage of non-invasive commensal Escherichia coli. We found that deoxynivalenol, ochratoxin A and patulin all potentiated the effect of IL-1β on IL-8 secretion (ranging from 35% to 138% increase) and increased the transepithelial passage of commensal bacteria (ranging from 12- to 1544-fold increase). In addition to potentially exacerbate established intestinal inflammation, these mycotoxins may thus participate in the induction of sepsis and intestinal inflammation in vivo. Taken together, our results suggest that the pro-inflammatory activity of enteropathogenic mycotoxins is mediated by both direct and indirect effects

  16. Noise-induced phase transition in the model of human virtual stick balancing

    CERN Document Server

    Zgonnikov, Arkady

    2016-01-01

    Humans face the task of balancing dynamic systems near an unstable equilibrium repeatedly throughout their lives. Much research has been aimed at understanding the mechanisms of intermittent control in the context of human balance control. The present paper deals with one of the recent developments in the theory of human intermittent control, namely, the double-well model of noise-driven control activation. We demonstrate that the double-well model can reproduce the whole range of experimentally observed distributions under different conditions. Moreover, we show that a slight change in the noise intensity parameter leads to a sudden shift of the action point distribution shape, that is, a phase transition is observed.

  17. Changes in vasoactive intestinal peptide, pituitary adenylate cyclase-activating polypeptide and neuropeptide Y-ergic structures of the enteric nervous system in the carcinoma of the human large intestine.

    Directory of Open Access Journals (Sweden)

    Ireneusz Mirosław Łakomy

    2010-08-01

    Full Text Available This investigation was aimed at immunohistochemical analysis of potential changes in the enteric nervous system caused by cancer of the large intestine. In this purpose, neurons and nerve fibers of intestinal plexuses containing neuropeptides: vasoactive intestinal peptide (VIP, pituitary adenylate cyclase-activating polypeptide (PACAP and neuropeptide Y (NPY, in pathologically changed part of the large intestine were microscpically observed and compared. Samples were taken from patients operated due to cancer of the sigmoid colon and rectum. The number of neurons and density of nerve fibres containing neuropeptides found in sections with cancer tissues were compared to those observed in sections from the uninvolved intestinal wall. Changes relating to reductions in the number of NPY-ergic neurons and density of nerve fibres in submucous and myenteric plexuses in the sections with cancer tissues (pathological sections were statistically significant. A statistically similar presence of VIP-ergic and PACAP-ergic neurons in the submucosal and myenteric plexuses was observed in both the pathological and control sections. On the other hand, in the pathological sections, VIP-ergic nerve fibres in the myenteric plexuses and PACAP-ergic nerve fibres in the submucosal and myenteric plexuses were found to be less dense. Analysis revealed changes in pathologically affected part of the large intestine may caused disruption of proper intestinal function. Observed changes in the neural elements which are responsible for relaxation of the intestine may suggest dysfunction in the innervation of this part of the colon.

  18. The gene encoding human intestinal trefoil factor (TFF3) is located on chromosome 21q22.3 clustered with other members of the trefoil peptide family

    Energy Technology Data Exchange (ETDEWEB)

    Chinery, R. [Royal College of Surgeons of England, London (United Kingdom); Williamson, J.; Poulsom, R. [Imperial Cancer Research Fund, London (United Kingdom)

    1996-03-01

    The gene coding for human intestinal trefoil factor (hITF), a recently described cellular motogen produced by gastrointestinal goblet cells and epithelia elsewhere, is a member of the rapidly growing trefoil peptide family. In a rodent-human somatic cell hybrid panel, the hITF (HGMW-approved symbol TFF3) genomic locus segregated with human chromosome 21q. Fluorescence in situ hybridization with a 2.1-kb genomic probe of the hITF gene mapped this locus more precisely to the q22.3 region. Triple fluorescence in situ hybridization, together with physical mapping of human genomic DNA using pulsed-field gel electrophoresis, revealed that the hITF gene is tightly linked to those encoding the other known human trefoil peptides, namely the breast cancer estrogen-inducable gene pS2 (BCEI) and human spasmolytic polypeptide (hSP/SML1). This gene family could become a useful marker for the genetic and physical mapping of chromosome 21 and for a better definition of the region involved in the clinical phenotype of several genetic diseases. 17 refs., 2 figs.

  19. Src-mediated cross-talk between farnesoid X and epidermal growth factor receptors inhibits human intestinal cell proliferation and tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Zhongsheng Peng

    Full Text Available Besides its essential role in controlling bile acid and lipid metabolism, the farnesoid X receptor (FXR protects against intestinal tumorigenesis by promoting apoptosis and inhibiting cell proliferation. However, the mechanisms underlying these anti-proliferative actions of FXR remain to be elucidated. In the present study, we examined the effects of FXR activation (FXR overexpression and treatment with an FXR agonist GW4064 and inactivation (treatment with FXR siRNA and an FXR antagonist guggulsterone on colon cancer cell proliferation in vitro using human colon cancer cell lines (H508, SNU-C4 and HT-29 and in vivo using xenografts in nude mice. Blocking FXR activity with guggulsterone stimulated time- and dose-dependent EGFR (Tyr845 phosphorylation and ERK activation. In contrast, FXR overexpression and activation with GW4064 attenuated cell proliferation by down-regulating EGFR (Tyr845 phosphorylation and ERK activation. Treatment with guggulsterone and GW4064 also caused dose-dependent changes in Src (Tyr416 phosphorylation. In stably-transfected human colon cancer cells, overexpression of FXR reduced EGFR, ERK, Src phosphorylation and cell proliferation, and in nude mice attenuated the growth of human colon cancer xenografts (64% reduction in tumor volume; 47% reduction in tumor weight; both P<0.01. Moreover, guggulsterone-induced EGFR and ERK phosphorylation and cell proliferation were abolished by inhibiting activation of Src, EGFR and MEK. Collectively these data support the novel conclusion that in human colon cancer cells Src-mediated cross-talk between FXR and EGFR modulates ERK phosphorylation, thereby regulating intestinal cell proliferation and tumorigenesis.

  20. 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; Hübner, Juliane; Lindner, Marcus; Drewell, Christopher; Bauer, Sophie; Thomas, Alexander; Sambo, Naomia Sisoli; Sonntag, Frank; Lauster, Roland; Marx, Uwe

    2015-06-21

    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.

  1. Evaluation by computerized morphometry of histopathological alterations of the colon wall in segments with and without intestinal transit in rats Avaliação por morfometria computadorizada das alterações histopatológicas da parede cólica em segmentos com e sem trânsito intestinal em ratos

    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

  2. Numerical Simulations on Injury to Human Intestinal Walls Produced by Spiral Micro-robots%螺旋微型机器人对人体肠道壁损伤的数值仿真

    Institute of Scientific and Technical Information of China (English)

    梁亮; 彭辉; 胡冠昱; 侯海良

    2011-01-01

    提出了一种无损伤螺旋式肠道微型机器人,建立了机器人运行时,肠道粘液的动力学控制方程,运用计算流体力学方法数值分析了在机体的正转和反转两种情况下,不同机器人转速、肠道粘液密度、粘度和机器人直径与肠道壁所受压力的关系:随着机器人转速、粘液密度、粘液粘度、机器人直径的增加,机器人运行时对肠道壁产生的压力基本也随着增大,并且机器人直径的影响最大,粘液密度影响最小,所产生的对肠道壁的压力都是人体能够承受的,而肠道的扭曲程度对肠道壁所受压力的影响并不大.上述理论分析结果将为高速旋转的螺旋式医用微型机器人应用于人体肠道的无创或微创手术提供了必要的理论依据.%A non-invasive spiral intestinal micro-robot was introduced. When it drove in the human intestine, dynamic control equations of intestinal fluid were established. By computational fluid dynamics metbod the relations between different robotic rotating speeds, intestine fluid densities, intestine fluid dynamic viscosities, robotic diameters and impact pressures of human intestinal wall produced by the micro-robot were calculated and analyzed in the circumstances of cylindrical forward and reverse rotation. It was obtained that when the robotic rotating speed, intestinal fluid density,intestinal fluid dynamic viscosity, robotic diameter were increased. the impact pressures of human intestinal wall produced by the running micro-robot were basically enlarged, and the most influence factor was the robotic diameter, and the least influence factor was the intestinal fluid density. The impact pressures of human intestinal wall produced by the micro-robot could be endured by people. While the influence of distorting extent of intestine on impact pressures of human intestinal wall produced by the micro-robot was not large. The above theoretical analysis results provide an essential

  3. Intestinal volvulus in cetaceans.

    Science.gov (United States)

    Begeman, L; St Leger, J A; Blyde, D J; Jauniaux, T P; Lair, S; Lovewell, G; Raverty, S; Seibel, H; Siebert, U; Staggs, S L; Martelli, P; Keesler, R I

    2013-07-01

    Intestinal volvulus was recognized as the cause of death in 18 cetaceans, including 8 species of toothed whales (suborder Odontoceti). Cases originated from 11 institutions from around the world and included both captive (n = 9) and free-ranging (n = 9) animals. When the clinical history was available (n = 9), animals consistently demonstrated acute dullness 1 to 5 days prior to death. In 3 of these animals (33%), there was a history of chronic gastrointestinal illness. The pathological findings were similar to those described in other animal species and humans, and consisted of intestinal volvulus and a well-demarcated segment of distended, congested, and edematous intestine with gas and bloody fluid contents. Associated lesions included congested and edematous mesentery and mesenteric lymph nodes, and often serofibrinous or hemorrhagic abdominal effusion. The volvulus involved the cranial part of the intestines in 85% (11 of 13). Potential predisposing causes were recognized in most cases (13 of 18, 72%) but were variable. Further studies investigating predisposing factors are necessary to help prevent occurrence and enhance early clinical diagnosis and management of the condition. PMID:23150643

  4. 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-α-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-α-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

  5. 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.

  6. [Intestinal endometriosis].

    Science.gov (United States)

    González Rodríguez, C I; Cires, M; Jiménez, F J; Rubio, T

    2008-01-01

    Endometriosis is a chronic, benign gynaecological disorder that is frequent in women of a child-bearing age. It is estimated that there is some degree of endometriosis in as many as 15% of pre-menopausal women, associated with a history of infertility, caesarean antecedents, dysmenorrhoea and abnormality in uterine bleeding. It is believed to be due to the rise of menstrual contents through the Fallopian tubes (retrograde menstruation). In the intestinal affectation, the colon is the segment most frequently affected, above all at the rectosigmoidal level. The clinical features are unspecific, with abdominal pain the most frequent and/or pelvic pain of a cholic type that coincides with, or is exacerbated by, menstruation. Differential diagnosis includes intestinal inflammatory disease, diverticulitis, ischemic colitis and neoplastic processes, with the definitive diagnosis being anatomopathological. With respect to treatment, this will depend on the clinical features and the age of the patient, as well as her wishes with regard to pregnancy. PMID:18953367

  7. Intestinal steroidogenesis

    OpenAIRE

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

    2015-01-01

    Steroids are fundamental hormones that control a wide variety of physiological processes such as metabolism, immune functions, and sexual characteristics. Historically, steroid synthesis was considered a function restricted to the adrenals and the gonads. In the past 20 years, a significant number of studies have demonstrated that steroids could also be synthesized or metabolized by other organs. According to these studies, the intestine appears to be a major source of de novo produced glucoc...

  8. Characterization of tight junction disruption and immune response modulation in a miniaturized Caco-2/U937 coculture-based in vitro model of the human intestinal barrier.

    Science.gov (United States)

    Ramadan, Qasem; Jing, Lin

    2016-02-01

    A microfluidic-based dynamic in vitro model of the human intestinal barrier has been constructed and characterized. The intestinal epithelial monolayer was mimicked by culturing caco-2 cells on a porous membrane in a double-layered microfluidic chip and interfaced with a co-culture of U937 as a model of immune responsive cells. The physiological flow was also mimicked by a continuous perfusion of culture media from the apical and basolateral side of the porous membrane. This dynamic "in vivo-like" environment maintains a continuous supply of cell nutrient and waste removal and create mechanical shear stress within the physiological ranges which promotes uniform cell growth and tight junction formation. The monolayer permeability to soluble ion changes after treating with LPS, and TNF α as indicated by the reduction of the TEER value. In addition, the immune competent caco-2/U937-based model allowed the investigating the role of the epithelial layer as a protection barrier to biological hazards as indicated by the suppressing of the pro-inflammatory cytokine expression. PMID:26809386

  9. Arabinogalactan and fructo-oligosaccharides have a different fermentation profile in the Simulator of the Human Intestinal Microbial Ecosystem (SHIME ®).

    Science.gov (United States)

    Terpend, Kathleen; Possemiers, Sam; Daguet, David; Marzorati, Massimo

    2013-08-01

    Current prebiotics, such as fructo-oligosaccharides (FOS), are limited in their persistence in the distal colon and are predominantly fermented in the proximal colon. In order to identify a potential alternative, the differences in the fermentation profile of arabinogalactan (AG) and FOS have been assessed in the Simulator of the Human Intestinal Microbial Ecosystem. The effect of each product on the composition and activity of the microbial community was analysed during a 3-week treatment period at a dose of 5 g day(-1). While FOS indeed was mainly fermented in the simulated proximal colon, AG was still available for fermentation in the simulated distal colon as shown by pH profiles, size exclusion chromatography and analyses of specific enzymatic activities. As a consequence, the main effect of the products (increase in propionate and butyrate and decrease in ammonium production) occurred in different intestinal areas. DGGE and qPCR analyses confirmed that the main modulation of the microbiota by the two products occurred in different areas of the gut. AG was associated with a statistically significant increase in the concentration of total bacteria, Bacteroidetes, Faecalibacterium prausnitzii, a delayed bifidogenic effect and a decrease of the pathogenic Clostridium perfringens. FOS led to a strong lactobacillogenic effect. PMID:23864575

  10. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to chitosan and reduction in body weight (ID 679, 1499), maintenance of normal blood LDL-cholesterol concentrations (ID 4663), reduction of intestinal transit time (ID

    DEFF Research Database (Denmark)

    Tetens, Inge

    claims in relation to chitosan and reduction in body weight, maintenance of normal blood LDL-cholesterol concentrations, reduction of intestinal transit time and reduction of inflammation. The scientific substantiation is based on the information provided by the Member States in the consolidated list...

  11. 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

  12. Effects of lactulose on intestinal endotoxin and bacterial translocation in cirrhotic rats

    Institute of Scientific and Technical Information of China (English)

    张顺财; 王唯; 任卫英; 戴茜; 贺伯明; 周康

    2003-01-01

    Objective To investigate the effects of lactulose on intestinal bacterial overgrowth (IBO), bacterial translocation (BT), intestinal transit and permeability in cirrhotic rats. Methods BT in all animals was assessed by bacterial culture of mesenteric lymph node (MLN), liver and spleen, and IBO was assessed by a jejunal bacterial count of the specific organism. Intestinal permeability was determined by the 24-hour urinary 99mTc-diethylenetriaminepentaacetate (99mTc-DTPA) excretion, and intestinal transit was determined by measuring the distribution of 51 Cr in the intestine. Results BT and IBO were found in 48% and 80% of the cirrhotic rats, respectively, while not in the control rats. Cirrhotic rats with IBO had significantly higher levels of intestinal endotoxin higher rates of bacterial translocation, shorter intestinal transit time and higher intestinal permeability than those without IBO. It was also found that BT was closely associated with IBO and injury of the intestinal barrier. Compared with the placebo group, lactulose-treated rats had lower rates of BT and IBO, which was closely associated with increased intestinal transit and improved intestinal permeability by lactulose. Conclusions Our study indicate that endotoxin and bacterial translocation in cirrhotic rats may attribute to IBO and increased intestinal permeability. Lactulose that accelerates intestinal transit and improves intestinal permeability might be helpful in preventing intestinal bacterial and endotoxin translocation.

  13. Intestinal acariasis in Anhui Province

    Institute of Scientific and Technical Information of China (English)

    Chao-Pin Li; Jian Wang

    2000-01-01

    The mites found in stored food and house comprise a large group of subclass Acari, belonging to the suborder Acardida of the order Acarifornes. They can be found in dust and vacuum samples from floors, furniture, mattresses, Chinese herbal medicine, dry fruit, grain, flour, sugar, and bedding. These mites are nidicolous and feed on organic debris, including sloughed human skin, fungi, spilled food, pollen, etc. These mites are particularly prevalent in Chinese herbal medicine, dry fruit, grain, flour, sugar, beds, though carpeted floors near beds or couches may also have large numbers. The most common species are Acarus siro, Tyrophagus putrescentiae , Dermatophagoides farinae , D . pteronyssinus, Glycyphagus domesticus, G. Ornatus, Carpoglyphus lactis and Tarsonemus granarius, etc. The viability of mites in storage is quite strong and they can invade and parasitize the intestines of humans[1 -15]. They can cause pulmonary acariasis[16-25] , urinary acariasis[26-33] and so on. The dejecta of mites is a quite strong allergen and can cause different allergic diseases[34-44]. Intestinal acariasis can be caused by some mites related to the way of diet intake and invading against intestinal mucosa, intestinal muscle[45-5a]. The first report of intestinal acariasis caused by these mites was made by Hinman et al (1934)[45]. From then on, all kinds of studies on the disease have been reported gradually. In order to make an epidemiological survey of intestinal acariasis the investigation of the disease was taken in some areas of Anhui Province from 1989 to 1996.

  14. Nonequilibrium arrhythmic states and transitions in a mathematical model for diffuse fibrosis in human cardiac tissue.

    Directory of Open Access Journals (Sweden)

    Rupamanjari Majumder

    Full Text Available We present a comprehensive numerical study of spiral- and scroll-wave dynamics in a state-of-the-art mathematical model for human ventricular tissue with fiber rotation, transmural heterogeneity, myocytes, and fibroblasts. Our mathematical model introduces fibroblasts randomly, to mimic diffuse fibrosis, in the ten Tusscher-Noble-Noble-Panfilov (TNNP model for human ventricular tissue; the passive fibroblasts in our model do not exhibit an action potential in the absence of coupling with myocytes; and we allow for a coupling between nearby myocytes and fibroblasts. Our study of a single myocyte-fibroblast (MF composite, with a single myocyte coupled to N(f fibroblasts via a gap-junctional conductance G(gap, reveals five qualitatively different responses for this composite. Our investigations of two-dimensional domains with a random distribution of fibroblasts in a myocyte background reveal that, as the percentage P(f of fibroblasts increases, the conduction velocity of a plane wave decreases until there is conduction failure. If we consider spiral-wave dynamics in such a medium we find, in two dimensions, a variety of nonequilibrium states, temporally periodic, quasiperiodic, chaotic, and quiescent, and an intricate sequence of transitions between them; we also study the analogous sequence of transitions for three-dimensional scroll waves in a three-dimensional version of our mathematical model that includes both fiber rotation and transmural heterogeneity. We thus elucidate random-fibrosis-induced nonequilibrium transitions, which lead to conduction block for spiral waves in two dimensions and scroll waves in three dimensions. We explore possible experimental implications of our mathematical and numerical studies for plane-, spiral-, and scroll-wave dynamics in cardiac tissue with fibrosis.

  15. Pretreatment with Bone Morphogenetic Protein-7 (BMP-7) Mimics Ischemia Preconditioning Following Intestinal Ischemia/Reperfusion Injury in The Intestine and Liver

    OpenAIRE

    Radhakrishnan, Ravi S.; Radhakrishnan, Geetha L.; Radhakrishnan, Hari R.; Xue, Hasen; Adams, Sasha D.; Moore-Olufemi, Stacey D.; Harting, Matthew T.; Cox, Charles S.; Kone, Bruce C.

    2008-01-01

    Intestinal ischemia/reperfusion (I/R) injury has been shown to cause intestinal mucosal injury and adversely affect function. Ischemic preconditioning (IPC) has been shown to protect against intestinal I/R injury by reducing polymorphonuclear leukocyte infiltration, intestinal mucosal injury, and liver injury, and preserve intestinal transit. Bone morphogenetic protein 7 (BMP-7) has been shown to protect against I/R injury in the kidney and brain. Recently, microarray analysis has been used t...

  16. 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

  17. 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)

  18. Anti-inflammatory properties of fruit juices enriched with pine bark extract in an in vitro model of inflamed human intestinal epithelium: the effect of gastrointestinal digestion.

    Science.gov (United States)

    Frontela-Saseta, Carmen; López-Nicolás, Rubén; González-Bermúdez, Carlos A; Martínez-Graciá, Carmen; Ros-Berruezo, Gaspar

    2013-03-01

    Enrichment of fruit juices with pine bark extract (PBE) could be a strategy to compensate for phenolic losses during the gastrointestinal digestion. A coculture system with Caco-2 cells and RAW 264.7 macrophages was established as an in vitro model of inflamed human intestinal epithelium for evaluating the anti-inflammatory capacity of fruit juices enriched with PBE (0.5 g L(-1)) before and after in vitro digestion. The digestion of both PBE-enriched pineapple and red fruit juice led to significant changes in most of the analysed phenolic compounds. The in vitro inflammatory state showed cell barrier dysfunction and overproduction of IL-8, nitric oxide (NO) and reactive oxygen species (ROS). In the inflamed cells, incubation with nondigested samples reduced (Pproperties of PBE-enriched fruit juices decreased after digestion; further research on the bioavailability of the assayed compounds is needed to properly assess their usefulness for the treatment of gut inflammation.

  19. In vitro evaluation of N-methyl amide tripeptidomimetics as substrates for the human intestinal di-/tri-peptide transporter hPEPT1

    DEFF Research Database (Denmark)

    Andersen, Rikke; Nielsen, Carsten Uhd; Begtrup, Mikael;

    2006-01-01

    of structural properties of 6859 N-methyl amide tripeptidomimetics. In vitro extracellular degradation of the selected tripeptidomimetics as well as affinity for and transepithelial transport via hPEPT1 were investigated in Caco-2 cells. Decreased apparent degradation was observed for all tripeptidomimetics......Oral absorption of tripeptides is generally mediated by the human intestinal di-/tri-peptide transporter, hPEPT1. However, the bioavailability of tripeptides is often limited due to degradation in the GI-tract by various peptidases. The aim of the present study was to evaluate the general...... application of N-methyl amide bioisosteres as peptide bond replacements in tripeptides in order to decrease degradation by peptidases and yet retain affinity for and transport via hPEPT1. Seven structurally diverse N-methyl amide tripeptidomimetics were selected based on a principal component analysis...

  20. Inhibitory effect of oatmeal extract oligomer on vasoactive intestinal peptide-induced inflammation in surviving human skin.

    Science.gov (United States)

    Boisnic, S; Branchet-Gumila, M C; Coutanceau, C

    2003-01-01

    The aim of this study was to evaluate the antiinflammatory effect of oatmeal extract oligomer on skin fragments stimulated by a neuromediator, vasoactive intestinal peptide (VIP). Skin fragments (from plastic surgery) were maintained in survival conditions for 6 h. To induce inflammation, VIP was placed in contact with dermis by culture medium. Histological analysis was then performed on hematoxylin- and eosin-stained slides. Edema was evaluated with semiquantitative scores. Vasodilation was studied by quantifying the percentage of dilated vessels according to scores and by measuring their surface by morphometrical image analysis. TNF-alpha dosage was made on culture supernatants. Vasodilation was significantly increased after application of VIP. After treatment with oatmeal extract oligomer, the mean surface of dilated vessels and edema were significantly decreased compared with VIP-treated skin. Moreover, treatment with this extract decreased TNF-alpha.