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Sample records for human large intestine

  1. The fate of epithelial cells in the human large intestine.

    Science.gov (United States)

    Barkla, D H; Gibson, P R

    1999-08-01

    One hundred and forty biopsies of the colon and rectum, collected during routine colonoscopies of 51 patients aged 19 to 74 years, were examined using light microscopy and transmission and scanning electron microscopy. The results indicated that surface epithelial cells undergo apoptosis, passing through fenestrations in the basement membrane to where they enter the lamina propria and are taken up by macrophages; and it is hypothesized that apoptotic cells are carried through the fenestrations on a current of fluid. The study also found that epithelial cells positioned over the crypts are better attached and more robust than those more distant from the crypt opening; and it is further hypothesized that, after reaching the top of the crypts, some goblet cells cease secreting mucus and pass onto the surface compartment of absorptive cells. An unexpected finding was that the lower regions of the crypts commonly contain isolated necrotic colonocytes. Apoptotic cells were rarely observed in the crypt epithelium. The findings of this study support the "recycling" model of epithelial cell death in the surface compartment of the human colon.

  2. Metabolism of sinigrin (2-propenyl glucosinolate) by the human colonic microflora in a dynamic in vitro large-intestinal model.

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    Krul, Cyrille; Humblot, Christèle; Philippe, Catherine; Vermeulen, Martijn; van Nuenen, Marleen; Havenaar, Robert; Rabot, Sylvie

    2002-06-01

    Cruciferous vegetables, such as Brassica, which contain substantial quantities of glucosinolates, have been suggested to possess anticarcinogenic activity. Cutting and chewing of cruciferous vegetables releases the thioglucosidase enzyme myrosinase, which degrades glucosinolates to isothiocyanates and other minor metabolites. Cooking of cruciferous vegetables inactivates the myrosinase enzyme, allowing intact glucosinolates to reach the large intestine, where they can be degraded by the indigenous microflora into isothiocyanates. This local release of isothiocyanates may explain the protective effect of cruciferous vegetables on the colon epithelium. However, little is known about the amounts and identities of glucosinolate metabolites produced by the human microflora. The production of allyl isothiocyanate from sinigrin was investigated in a dynamic in vitro large-intestinal model, after inoculation with a complex microflora of human origin. Sinigrin and allyl isothiocyanate concentrations were analysed in the lumen and dialysis fluid of the model. Peak levels of allyl isothiocyanate were observed between 9 and 12 h after the addition of sinigrin. The model was first set up with a pooled and cultured human microflora, in which 1 and 4% of, respectively, 1 and 15 mM sinigrin, was converted into AITC. However, the conversion rate was remarkably higher if different individual human microflora were used. Between 10% and 30% (mean 19%) of the sinigrin was converted into allyl isothiocyanate. The results of this study suggest that allyl isothiocyanate is converted further into other, yet unknown, metabolites.

  3. Human Intestinal Spirochaetosis

    NARCIS (Netherlands)

    Westerman, L.J.

    2013-01-01

    Human intestinal spirochaetosis is a condition of the colon that is characterized by the presence of spirochaetes attached to the mucosal cells of the colon. These spirochaetes belong to the family Brachyspiraceae and two species are known to occur in humans: Brachyspira aalborgi and Brachyspira

  4. Diversity, metabolism and microbial ecology of butyrate-producing bacteria from the human large intestine.

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    Louis, Petra; Flint, Harry J

    2009-05-01

    Butyrate-producing bacteria play a key role in colonic health in humans. This review provides an overview of the current knowledge of the diversity, metabolism and microbial ecology of this functionally important group of bacteria. Human colonic butyrate producers are Gram-positive firmicutes, but are phylogenetically diverse, with the two most abundant groups related to Eubacterium rectale/Roseburia spp. and to Faecalibacterium prausnitzii. Five different arrangements have been identified for the genes of the central pathway involved in butyrate synthesis, while in most cases butyryl-CoA : acetate CoA-transferase, rather than butyrate kinase, appears to perform the final step in butyrate synthesis. Mechanisms have been proposed recently in non-gut Clostridium spp. whereby butyrate synthesis can result in energy generation via both substrate-level phosphorylation and proton gradients. Here we suggest that these mechanisms also apply to the majority of butyrate producers from the human colon. The roles of these bacteria in the gut community and their influence on health are now being uncovered, taking advantage of the availability of cultured isolates and molecular methodologies. Populations of F. prausnitzii are reported to be decreased in Crohn's disease, for example, while populations of Roseburia relatives appear to be particularly sensitive to the diet composition in human volunteer studies.

  5. Rice Bran and Probiotics Alter the Porcine Large Intestine and Serum Metabolomes for Protection against Human Rotavirus Diarrhea

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    Elizabeth P. Ryan

    2017-04-01

    Full Text Available Human rotavirus (HRV is a leading cause of severe childhood diarrhea, and there is limited vaccine efficacy in the developing world. Neonatal gnotobiotic pigs consuming a prophylactic synbiotic combination of probiotics and rice bran (Pro+RB did not exhibit HRV diarrhea after challenge. Multiple immune, gut barrier protective, and anti-diarrheal mechanisms contributed to the prophylactic efficacy of Pro+RB when compared to probiotics (Pro alone. In order to understand the molecular signature associated with diarrheal protection by Pro+RB, a global non-targeted metabolomics approach was applied to investigate the large intestinal contents and serum of neonatal gnotobiotic pigs. The ultra-high performance liquid chromatography-tandem mass spectrometry platform revealed significantly different metabolites (293 in LIC and 84 in serum in the pigs fed Pro+RB compared to Pro, and many of these metabolites were lipids and amino acid/peptides. Lipid metabolites included 2-oleoylglycerol (increased 293.40-fold in LIC of Pro+RB, p = 3.04E-10, which can modulate gastric emptying, andhyodeoxycholate (decreased 0.054-fold in the LIC of Pro+RB, p = 0.0040 that can increase colonic mucus production to improve intestinal barrier function. Amino acid metabolites included cysteine (decreased 0.40-fold in LIC, p = 0.033, and 0.62-fold in serum, p = 0.014 of Pro+RB, which has been found to reduce inflammation, lower oxidative stress and modulate mucosal immunity, and histamine (decreased 0.18-fold in LIC, p = 0.00030, of Pro+RB and 1.57-fold in serum, p = 0.043, which modulates local and systemic inflammatory responses as well as influences the enteric nervous system. Alterations to entire LIC and serum metabolic pathways further contributed to the anti-diarrheal and anti-viral activities of Pro+RB such as sphingolipid, mono/diacylglycerol, fatty acid, secondary bile acid, and polyamine metabolism. Sphingolipid and long chain fatty acid profiles influenced the

  6. Evaluating the microbial diversity of an in vitro model of the human large intestine by phylogenetic microarray analysis

    NARCIS (Netherlands)

    Rajilic-Stojanovic, M.; Maathuis, A.; Heilig, G.H.J.; Venema, K.; Vos, de W.M.; Smidt, H.

    2010-01-01

    A high-density phylogenetic microarray targeting small subunit rRNA (SSU rRNA) sequences of over 1000 microbial phylotypes of the human gastrointestinal tract, the HITChip, was used to assess the impact of faecal inoculum preparation and operation conditions on an in vitro model of the human large

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

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    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

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

    International Nuclear Information System (INIS)

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

    2005-01-01

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

  9. 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.

  10. Compartmentalization of Aquaporins in the Human Intestine

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    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.

  11. Biomagnetic Signals of the Large Intestine

    International Nuclear Information System (INIS)

    Cordova, T.; Sosa, M.; Bradshaw, L. A.; Adilton, A.

    2008-01-01

    Large intestine is part of the gastrointestinal tract with an average length, in adults, of 1.5 m. The gold standard technique in clinical medicine is the colonoscopy. Nevertheless, other techniques are capable of presenting information on physiological processes which take place in this part of the gastrointestinal system. Three recent studies are discussed in this paper in order to make this information more widely available. The authors consider that the biomagnetic technique could be easily implemented in hospitals around the world. Options will be available for research and clinical medicine

  12. Enterohemorrhagic Escherichia coli senses low biotin status in the large intestine for colonization and infection

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    Yang, Bin; Feng, Lu; Wang, Fang; Wang, Lei

    2015-01-01

    Enterohemorrhagic Escherichia coli (EHEC) is an important foodborne pathogen that infects humans by colonizing the large intestine. Here we identify a virulence-regulating pathway in which the biotin protein ligase BirA signals to the global regulator Fur, which in turn activates LEE (locus of enterocyte effacement) genes to promote EHEC adherence in the low-biotin large intestine. LEE genes are repressed in the high-biotin small intestine, thus preventing adherence and ensuring selective colonization of the large intestine. The presence of this pathway in all nine EHEC serotypes tested indicates that it is an important evolutionary strategy for EHEC. The pathway is incomplete in closely related small-intestinal enteropathogenic E. coli due to the lack of the Fur response to BirA. Mice fed with a biotin-rich diet show significantly reduced EHEC adherence, indicating that biotin might be useful to prevent EHEC infection in humans. PMID:25791315

  13. The Contributions of Human Mini-Intestines to the Study of Intestinal Physiology and Pathophysiology.

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    Yu, Huimin; Hasan, Nesrin M; In, Julie G; Estes, Mary K; Kovbasnjuk, Olga; Zachos, Nicholas C; Donowitz, Mark

    2017-02-10

    The lack of accessibility to normal and diseased human intestine and the inability to separate the different functional compartments of the intestine even when tissue could be obtained have held back the understanding of human intestinal physiology. Clevers and his associates identified intestinal stem cells and established conditions to grow "mini-intestines" ex vivo in differentiated and undifferentiated conditions. This pioneering work has made a new model of the human intestine available and has begun making contributions to the understanding of human intestinal transport in normal physiologic conditions and the pathophysiology of intestinal diseases. However, this model is reductionist and lacks many of the complexities of normal intestine. Consequently, it is not yet possible to predict how great the advances using this model will be for understanding human physiology and pathophysiology, nor how the model will be modified to include multiple other intestinal cell types and physical forces necessary to more closely approximate normal intestine. This review describes recent studies using mini-intestines, which have readdressed previously established models of normal intestinal transport physiology and newly examined intestinal pathophysiology. The emphasis is on studies with human enteroids grown either as three-dimensional spheroids or two-dimensional monolayers. In addition, comments are provided on mouse studies in cases when human studies have not yet been described.

  14. Impact of palm date consumption on microbiota growth and large intestinal health: a randomised, controlled, cross-over, human intervention study.

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    Eid, Noura; Osmanova, Hristina; Natchez, Cecile; Walton, Gemma; Costabile, Adele; Gibson, Glenn; Rowland, Ian; Spencer, Jeremy P E

    2015-10-28

    The reported inverse association between the intake of plant-based foods and a reduction in the prevalence of colorectal cancer may be partly mediated by interactions between insoluble fibre and (poly)phenols and the intestinal microbiota. In the present study, we assessed the impact of palm date consumption, rich in both polyphenols and fibre, on the growth of colonic microbiota and markers of colon cancer risk in a randomised, controlled, cross-over human intervention study. A total of twenty-two healthy human volunteers were randomly assigned to either a control group (maltodextrin-dextrose, 37·1 g) or an intervention group (seven dates, approximately 50 g). Each arm was of 21 d duration and was separated by a 14-d washout period in a cross-over manner. Changes in the growth of microbiota were assessed by fluorescence in situ hybridisation analysis, whereas SCFA levels were assessed using HPLC. Further, ammonia concentrations, faecal water genotoxicity and anti-proliferation ability were also assessed using different assays, which included cell work and the Comet assay. Accordingly, dietary intakes, anthropometric measurements and bowel movement assessment were also carried out. Although the consumption of dates did not induce significant changes in the growth of select bacterial groups or SCFA, there were significant increases in bowel movements and stool frequency (Pfruit intake significantly reduced genotoxicity in human faecal water relative to control (Pfruit may reduce colon cancer risk without inducing changes in the microbiota.

  15. 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

  16. Understanding how commensal obligate anaerobic bacteria regulate immune functions in the large intestine.

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    Maier, Eva; Anderson, Rachel C; Roy, Nicole C

    2014-12-24

    The human gastrointestinal tract is colonised by trillions of commensal bacteria, most of which are obligate anaerobes residing in the large intestine. Appropriate bacterial colonisation is generally known to be critical for human health. In particular, the development and function of the immune system depends on microbial colonisation, and a regulated cross-talk between commensal bacteria, intestinal epithelial cells and immune cells is required to maintain mucosal immune homeostasis. This homeostasis is disturbed in various inflammatory disorders, such as inflammatory bowel diseases. Several in vitro and in vivo studies indicate a role for Faecalibacterium prausnitzii, Bacteroides thetaiotaomicron, Bacteroides fragilis, Akkermansia muciniphila and segmented filamentous bacteria in maintaining intestinal immune homeostasis. These obligate anaerobes are abundant in the healthy intestine but reduced in several inflammatory diseases, suggesting an association with protective effects on human health. However, knowledge of the mechanisms underlying the effects of obligate anaerobic intestinal bacteria remains limited, in part due to the difficulty of co-culturing obligate anaerobes together with oxygen-requiring human epithelial cells. By using novel dual-environment co-culture models, it will be possible to investigate the effects of the unstudied majority of intestinal microorganisms on the human epithelia. This knowledge will provide opportunities for improving human health and reducing the risk of inflammatory diseases.

  17. Understanding How Commensal Obligate Anaerobic Bacteria Regulate Immune Functions in the Large Intestine

    Science.gov (United States)

    Maier, Eva; Anderson, Rachel C.; Roy, Nicole C.

    2014-01-01

    The human gastrointestinal tract is colonised by trillions of commensal bacteria, most of which are obligate anaerobes residing in the large intestine. Appropriate bacterial colonisation is generally known to be critical for human health. In particular, the development and function of the immune system depends on microbial colonisation, and a regulated cross-talk between commensal bacteria, intestinal epithelial cells and immune cells is required to maintain mucosal immune homeostasis. This homeostasis is disturbed in various inflammatory disorders, such as inflammatory bowel diseases. Several in vitro and in vivo studies indicate a role for Faecalibacterium prausnitzii, Bacteroides thetaiotaomicron, Bacteroides fragilis, Akkermansia muciniphila and segmented filamentous bacteria in maintaining intestinal immune homeostasis. These obligate anaerobes are abundant in the healthy intestine but reduced in several inflammatory diseases, suggesting an association with protective effects on human health. However, knowledge of the mechanisms underlying the effects of obligate anaerobic intestinal bacteria remains limited, in part due to the difficulty of co-culturing obligate anaerobes together with oxygen-requiring human epithelial cells. By using novel dual-environment co-culture models, it will be possible to investigate the effects of the unstudied majority of intestinal microorganisms on the human epithelia. This knowledge will provide opportunities for improving human health and reducing the risk of inflammatory diseases. PMID:25545102

  18. Neural influences on human intestinal epithelium in vitro.

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    Krueger, Dagmar; Michel, Klaus; Zeller, Florian; Demir, Ihsan E; Ceyhan, Güralp O; Slotta-Huspenina, Julia; Schemann, Michael

    2016-01-15

    We present the first systematic and, up to now, most comprehensive evaluation of the basic features of epithelial functions, such as basal and nerve-evoked secretion, as well as tissue resistance, in over 2200 surgical specimens of human small and large intestine. We found no evidence for impaired nerve-evoked epithelial secretion or tissue resistance with age or disease pathologies (stomach, pancreas or colon cancer, polyps, diverticulitis, stoma reversal). This indicates the validity of future studies on epithelial secretion or resistance that are based on data from a variety of surgical specimens. ACh mainly mediated nerve-evoked and basal secretion in the small intestine, whereas vasoactive intestinal peptide and nitric oxide were the primary pro-secretory transmitters in the large intestine. The results of the present study revealed novel insights into regional differences in nerve-mediated secretion in the human intestine and comprise the basis by which to more specifically target impaired epithelial functions in the diseased gut. Knowledge on basic features of epithelial functions in the human intestine is scarce. We used Ussing chamber techniques to record basal tissue resistance (R-basal) and short circuit currents (ISC; secretion) under basal conditions (ISC-basal) and after electrical field stimulation (ISC-EFS) of nerves in 2221 resectates from 435 patients. ISC-EFS was TTX-sensitive and of comparable magnitude in the small and large intestine. ISC-EFS or R-basal were not influenced by the patients' age, sex or disease pathologies (cancer, polyps, diverticulitis). Ion substitution, bumetanide or adenylate cyclase inhibition studies suggested that ISC-EFS depended on epithelial cAMP-driven chloride and bicarbonate secretion but not on amiloride-sensitive sodium absorption. Although atropine-sensitive cholinergic components prevailed for ISC-EFS of the duodenum, jejunum and ileum, PG97-269-sensitive [vasoactive intestinal peptide (VIP) receptor 1

  19. Cholesterol esterase activity of human intestinal mucosa

    International Nuclear Information System (INIS)

    Ponz de Leon, M.; Carubbi, F.; Di Donato, P.; Carulli, N.

    1985-01-01

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

  20. Effects of probiotics and antibiotics on the intestinal homeostasis in a computer controlled model of the large intestine

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    Rehman Ateequr

    2012-03-01

    Full Text Available Abstract Background Antibiotic associated diarrhea and Clostridium difficile infection are frequent complications of broad spectrum antibiotic therapy. Probiotic bacteria are used as therapeutic and preventive agents in these disorders, but the exact functional mechanisms and the mode of action are poorly understood. The effects of clindamycin and the probiotic mixture VSL#3 (containing the 8 bacterial strains Streptococcus thermophilus, Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus paracasei and Lactobacillus delbrueckii subsp. Bulgaricus consecutively or in combination were investigated and compared to controls without therapy using a standardized human fecal microbiota in a computer-controlled in vitro model of large intestine. Microbial metabolites (short chain fatty acids, lactate, branched chain fatty acids, and ammonia and the intestinal microbiota were analyzed. Results Compared to controls and combination therapy, short chain fatty acids and lactate, but also ammonia and branched chain fatty acids, were increased under probiotic therapy. The metabolic pattern under combined therapy with antibiotics and probiotics had the most beneficial and consistent effect on intestinal metabolic profiles. The intestinal microbiota showed a decrease in several indigenous bacterial groups under antibiotic therapy, there was no significant recovery of these groups when the antibiotic therapy was followed by administration of probiotics. Simultaneous application of anti- and probiotics had a stabilizing effect on the intestinal microbiota with increased bifidobacteria and lactobacilli. Conclusions Administration of VSL#3 parallel with the clindamycin therapy had a beneficial and stabilizing effect on the intestinal metabolic homeostasis by decreasing toxic metabolites and protecting the endogenic microbiota from destruction. Probiotics could be a reasonable

  1. Diversity of human small intestinal Streptococcus and Veillonella populations

    NARCIS (Netherlands)

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

    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

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

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    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.

  3. Alternative Functional In Vitro Models of Human Intestinal Epithelia

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    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.

  4. 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.

  5. A new approach to predict human intestinal absorption using porcine intestinal tissue and biorelevant matrices

    NARCIS (Netherlands)

    Westerhout, J.; Steeg, E. van de; Grossouw, D.; Zeijdner, E.E.; Krul, C.A.M.; Verwei, M.; Wortelboer, H.M.

    2014-01-01

    A reliable prediction of the oral bioavailability in humans is crucial and of high interest for pharmaceutical and food industry. The predictive value of currently used in silico methods, in vitro cell lines, ex vivo intestinal tissue and/or in vivo animal studies for human intestinal absorption,

  6. The Gut-Associated Lymphoid Tissues in the Small Intestine, Not the Large Intestine, Play a Major Role in Oral Prion Disease Pathogenesis

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    Donaldson, David S.; Else, Kathryn J.

    2015-01-01

    ABSTRACT Prion diseases are infectious neurodegenerative disorders characterized by accumulations of abnormally folded cellular prion protein in affected tissues. Many natural prion diseases are acquired orally, and following exposure, the early replication of some prion isolates upon follicular dendritic cells (FDC) within gut-associated lymphoid tissues (GALT) is important for the efficient spread of disease to the brain (neuroinvasion). Prion detection within large intestinal GALT biopsy specimens has been used to estimate human and animal disease prevalence. However, the relative contributions of the small and large intestinal GALT to oral prion pathogenesis were unknown. To address this issue, we created mice that specifically lacked FDC-containing GALT only in the small intestine. Our data show that oral prion disease susceptibility was dramatically reduced in mice lacking small intestinal GALT. Although these mice had FDC-containing GALT throughout their large intestines, these tissues were not early sites of prion accumulation or neuroinvasion. We also determined whether pathology specifically within the large intestine might influence prion pathogenesis. Congruent infection with the nematode parasite Trichuris muris in the large intestine around the time of oral prion exposure did not affect disease pathogenesis. Together, these data demonstrate that the small intestinal GALT are the major early sites of prion accumulation and neuroinvasion after oral exposure. This has important implications for our understanding of the factors that influence the risk of infection and the preclinical diagnosis of disease. IMPORTANCE Many natural prion diseases are acquired orally. After exposure, the accumulation of some prion diseases in the gut-associated lymphoid tissues (GALT) is important for efficient spread of disease to the brain. However, the relative contributions of GALT in the small and large intestines to oral prion pathogenesis were unknown. We show that the

  7. The Gut-Associated Lymphoid Tissues in the Small Intestine, Not the Large Intestine, Play a Major Role in Oral Prion Disease Pathogenesis.

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    Donaldson, David S; Else, Kathryn J; Mabbott, Neil A

    2015-09-01

    Prion diseases are infectious neurodegenerative disorders characterized by accumulations of abnormally folded cellular prion protein in affected tissues. Many natural prion diseases are acquired orally, and following exposure, the early replication of some prion isolates upon follicular dendritic cells (FDC) within gut-associated lymphoid tissues (GALT) is important for the efficient spread of disease to the brain (neuroinvasion). Prion detection within large intestinal GALT biopsy specimens has been used to estimate human and animal disease prevalence. However, the relative contributions of the small and large intestinal GALT to oral prion pathogenesis were unknown. To address this issue, we created mice that specifically lacked FDC-containing GALT only in the small intestine. Our data show that oral prion disease susceptibility was dramatically reduced in mice lacking small intestinal GALT. Although these mice had FDC-containing GALT throughout their large intestines, these tissues were not early sites of prion accumulation or neuroinvasion. We also determined whether pathology specifically within the large intestine might influence prion pathogenesis. Congruent infection with the nematode parasite Trichuris muris in the large intestine around the time of oral prion exposure did not affect disease pathogenesis. Together, these data demonstrate that the small intestinal GALT are the major early sites of prion accumulation and neuroinvasion after oral exposure. This has important implications for our understanding of the factors that influence the risk of infection and the preclinical diagnosis of disease. Many natural prion diseases are acquired orally. After exposure, the accumulation of some prion diseases in the gut-associated lymphoid tissues (GALT) is important for efficient spread of disease to the brain. However, the relative contributions of GALT in the small and large intestines to oral prion pathogenesis were unknown. We show that the small intestinal

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

    OpenAIRE

    Levitt, David G

    2013-01-01

    Background Understanding the quantitative relationship between a drug?s physical chemical properties and its rate of intestinal absorption (QSAR) is critical for selecting candidate drugs. Because of limited experimental human small intestinal permeability data, approximate surrogates such as the fraction absorbed or Caco-2 permeability are used, both of which have limitations. Methods Given the blood concentration following an oral and intravenous dose, the time course of intestinal absorpti...

  9. Development and Characterization of a Human and Mouse Intestinal Epithelial Cell Monolayer Platform

    Directory of Open Access Journals (Sweden)

    Kenji Kozuka

    2017-12-01

    Full Text Available Summary: We describe the development and characterization of a mouse and human epithelial cell monolayer platform of the small and large intestines, with a broad range of potential applications including the discovery and development of minimally systemic drug candidates. Culture conditions for each intestinal segment were optimized by correlating monolayer global gene expression with the corresponding tissue segment. The monolayers polarized, formed tight junctions, and contained a diversity of intestinal epithelial cell lineages. Ion transport phenotypes of monolayers from the proximal and distal colon and small intestine matched the known and unique physiology of these intestinal segments. The cultures secreted serotonin, GLP-1, and FGF19 and upregulated the epithelial sodium channel in response to known biologically active agents, suggesting intact secretory and absorptive functions. A screen of over 2,000 pharmacologically active compounds for inhibition of potassium ion transport in the mouse distal colon cultures led to the identification of a tool compound. : Siegel and colleagues describe their development of a human and mouse intestinal epithelial cell monolayer platform that maintains the cellular, molecular, and functional characteristics of tissue for each intestinal segment. They demonstrate the platform's application to drug discovery by screening a library of over 2,000 compounds to identify an inhibitor of potassium ion transport in the mouse distal colon. Keywords: intestinal epithelium, organoids, monolayer, colon, small intestine, phenotype screening assays, enteroid, colonoid

  10. Virtual CT-colonoscopy resources in large intestine neoplasia

    Directory of Open Access Journals (Sweden)

    Chalyk Yu.V.

    2011-12-01

    Full Text Available The research goal is to state possibility of virtual colonoscopy and to determine the localization and nature of neoplasms in the large intestine. Materials and methods: 38 patients have been examined by the method of virtual colonoscopy. The preceding stage of diagnosis by total fibrocolonoscopy has not been a success. Results: Virtual colonoscopy has been performed in 94.7% of patients. The same tumors have been identified in the proximal colon, direct examination of which has not been possible. Conclusion: Virtual colonoscopy is the method of choice for topical diagnosis of tumors of the colon

  11. Intestinal Stem Cell Dynamics: A Story of Mice and Humans.

    Science.gov (United States)

    Hodder, Michael C; Flanagan, Dustin J; Sansom, Owen J

    2018-06-01

    Stem cell dynamics define the probability of accumulating mutations within the intestinal epithelium. In this issue of Cell Stem Cell, Nicholson et al. (2018) report that human intestinal stem cell dynamics differ significantly from those of mice and establish that oncogenic mutations are more likely to expand; therefore, "normal" epithelium may carry multiple mutations. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. Sequential cancer mutations in cultured human intestinal stem cells

    NARCIS (Netherlands)

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

    2015-01-01

    Crypt stem cells represent the cells of origin for intestinal neoplasia. Both mouse and human intestinal stem cells can be cultured in medium containing the stem-cell-niche factors WNT, R-spondin, epidermal growth factor (EGF) and noggin over long time periods as epithelial organoids that remain

  13. Effect of the Novel Polysaccharide PolyGlycopleX® on Short-Chain Fatty Acid Production in a Computer-Controlled in Vitro Model of the Human Large Intestine

    Directory of Open Access Journals (Sweden)

    Raylene A. Reimer

    2014-03-01

    Full Text Available Many of the health benefits associated with dietary fiber are attributed to their fermentation by microbiota and production of short chain fatty acids (SCFA. The aim of this study was to investigate the fermentability of the functional fiber PolyGlyopleX® (PGX® in vitro. A validated dynamic, computer-controlled in vitro system simulating the conditions in the proximal large intestine (TIM-2 was used. Sodium hydroxide (NaOH consumption in the system was used as an indicator of fermentability and SCFA and branched chain fatty acids (BCFA production was determined. NaOH consumption was significantly higher for Fructooligosaccharide (FOS than PGX, which was higher than cellulose (p = 0.002. At 32, 48 and 72 h, acetate and butyrate production were higher for FOS and PGX versus cellulose. Propionate production was higher for PGX than cellulose at 32, 48, 56 and 72 h and higher than FOS at 72 h (p = 0.014. Total BCFA production was lower for FOS compared to cellulose, whereas production with PGX was lower than for cellulose at 72 h. In conclusion, PGX is fermented by the colonic microbiota which appeared to adapt to the substrate over time. The greater propionate production for PGX may explain part of the cholesterol-lowering properties of PGX seen in rodents and humans.

  14. D-tagatose has low small intestinal digestibility but high large intestinal fermentability in pigs.

    Science.gov (United States)

    Laerke, H N; Jensen, B B

    1999-05-01

    The digestibility of D-tagatose, its effect on the digestibility of macronutrients and the metabolic response of the microbiota of the gastrointestinal tract to the ingestion of this carbohydrate were studied in pigs. Eight pigs were fed a low fiber diet comprising 15% sucrose (control group). Another eight pigs were fed a similar diet except that 100 g sucrose per kg diet was replaced by D-tagatose (test group). After 18 d, the pigs were killed and the gastrointestinal contents removed for analysis. The digestibility of D-tagatose was 25.8 +/- 5.6% in the distal third of the small intestine. The small intestinal digestibilities of dry matter (86.9 +/- 1.3 vs. 92.9 +/- 0.9%), gross energy (74.4 +/- 1.6 vs. 80.7 +/- 1.8%) and sucrose (90.4 +/- 2.5 vs. 98.0 +/- 0.5%) were lower (P D-tagatose. Digestibilities of starch, protein and fat did not differ between groups. D-Tagatose, sucrose and starch were fully digested in the large intestine. The fecal digestibilities of energy, dry matter and fat did not differ between the two groups, whereas D-tagatose reduced the fecal digestibility of protein (91.1 +/- 0.6 vs. 93.5 +/- 0.7%, P D-Tagatose served as a substrate for the microbiota in the cecum and proximal colon as indicated by a reduced pH, and a greater ATP concentration, adenylate energy charge (AEC) ratio and concentration of short-chain fatty acids. In particular, the increase in the concentrations of propionate, butyrate and valerate suggests possible health benefits of this monosaccharide.

  15. Transcriptome Analysis of Three Sheep Intestinal Regions reveals Key Pathways and Hub Regulatory Genes of Large Intestinal Lipid Metabolism.

    Science.gov (United States)

    Chao, Tianle; Wang, Guizhi; Ji, Zhibin; Liu, Zhaohua; Hou, Lei; Wang, Jin; Wang, Jianmin

    2017-07-13

    The large intestine, also known as the hindgut, is an important part of the animal digestive system. Recent studies on digestive system development in ruminants have focused on the rumen and the small intestine, but the molecular mechanisms underlying sheep large intestine metabolism remain poorly understood. To identify genes related to intestinal metabolism and to reveal molecular regulation mechanisms, we sequenced and compared the transcriptomes of mucosal epithelial tissues among the cecum, proximal colon and duodenum. A total of 4,221 transcripts from 3,254 genes were identified as differentially expressed transcripts. Between the large intestine and duodenum, differentially expressed transcripts were found to be significantly enriched in 6 metabolism-related pathways, among which PPAR signaling was identified as a key pathway. Three genes, CPT1A, LPL and PCK1, were identified as higher expression hub genes in the large intestine. Between the cecum and colon, differentially expressed transcripts were significantly enriched in 5 lipid metabolism related pathways, and CEPT1 and MBOAT1 were identified as hub genes. This study provides important information regarding the molecular mechanisms of intestinal metabolism in sheep and may provide a basis for further study.

  16. 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

  17. 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.

  18. 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.

  19. Absorption of l-methionine from the human small intestine

    Science.gov (United States)

    Schedl, Harold P.; Pierce, Charles E.; Rider, Alan; Clifton, James A.

    1968-01-01

    Absorption of L-methionine was measured in all parts of the human small intestine using transintestinal intubation and perfusion. In four normal subjects, adsorption was higher in the proximal than in the distal intestine. In two patients with nontropical sprue in relapse, there was a proximal zone of low absorption with higher absorption distally. In all parts of the small intestine, absorption showed rate-limiting kinetics as methionine concentration was increased. In normal subjects, the proximal Km (Michaelis constant) was more than 3 times higher than the distal, which suggests a difference in transport mechanisms between the two segments. PMID:12066784

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

    NARCIS (Netherlands)

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

    2014-01-01

    The human small intestine is a key site for interactions between the intestinal microbiota and the mucosal immune system. Here we investigated the immunomodulatory properties of representative species of commonly dominant small-intestinal microbial communities, including six streptococcal strains

  1. 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

  2. Human zonulin, a potential modulator of intestinal tight junctions.

    Science.gov (United States)

    Wang, W; Uzzau, S; Goldblum, S E; Fasano, A

    2000-12-01

    Intercellular tight junctions are dynamic structures involved in vectorial transport of water and electrolytes across the intestinal epithelium. Zonula occludens toxin derived from Vibrio cholerae interacts with a specific intestinal epithelial surface receptor, with subsequent activation of a complex intracellular cascade of events that regulate tight junction permeability. We postulated that this toxin may mimic the effect of a functionally and immunologically related endogenous modulator of intestinal tight junctions. Affinity-purified anti-zonula occludens toxin antibodies and the Ussing chamber assay were used to screen for one or more mammalian zonula occludens toxin analogues in both fetal and adult human intestine. A novel protein, zonulin, was identified that induces tight junction disassembly in non-human primate intestinal epithelia mounted in Ussing chambers. Comparison of amino acids in the active zonula occludens toxin fragment and zonulin permitted the identification of the putative receptor binding domain within the N-terminal region of the two proteins. Zonulin likely plays a pivotal role in tight junction regulation during developmental, physiological, and pathological processes, including tissue morphogenesis, movement of fluid, macromolecules and leukocytes between the intestinal lumen and the interstitium, and inflammatory/autoimmune disorders.

  3. Human intervention study to investigate the intestinal accessibility and bioavailability of anthocyanins from bilberries.

    Science.gov (United States)

    Mueller, Dolores; Jung, Kathrin; Winter, Manuel; Rogoll, Dorothee; Melcher, Ralph; Richling, Elke

    2017-09-15

    We investigated the importance of the large intestine on the bioavailability of anthocyanins from bilberries in humans with/without a colon. Low bioavailability of anthocyanins in plasma and urine was observed in the frame of this study. Anthocyanins reached the circulation mainly as glucuronides. Analysis of ileal effluents (at end of small intestine) demonstrated that 30% of ingested anthocyanins were stable during 8h passage through the upper intestine. Only 20% degradants were formed and mostly intact anthocyanins were absorbed from the small intestine. Higher amounts of degradants than anthocyanins reached the circulation after bilberry extract consumption in both groups of subjects. Comparison of the bioavailability of anthocyanins in healthy subjects versus ileostomists revealed substantially higher amounts of anthocyanins and degradants in the plasma/urine of subjects with an intact gut. The results suggested that the colon is a significant site for absorption of bioactive components such as anthocyanins and their degradation products. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Flow and active mixing have a strong impact on bacterial growth dynamics in the proximal large intestine

    Science.gov (United States)

    Cremer, Jonas; Segota, Igor; Yang, Chih-Yu; Arnoldini, Markus; Groisman, Alex; Hwa, Terence

    2016-11-01

    More than half of fecal dry weight is bacterial mass with bacterial densities reaching up to 1012 cells per gram. Mostly, these bacteria grow in the proximal large intestine where lateral flow along the intestine is strong: flow can in principal lead to a washout of bacteria from the proximal large intestine. Active mixing by contractions of the intestinal wall together with bacterial growth might counteract such a washout and allow high bacterial densities to occur. As a step towards understanding bacterial growth in the presence of mixing and flow, we constructed an in-vitro setup where controlled wall-deformations of a channel emulate contractions. We investigate growth along the channel under a steady nutrient inflow. Depending on mixing and flow, we observe varying spatial gradients in bacterial density along the channel. Active mixing by deformations of the channel wall is shown to be crucial in maintaining a steady-state bacterial population in the presence of flow. The growth-dynamics is quantitatively captured by a simple mathematical model, with the effect of mixing described by an effective diffusion term. Based on this model, we discuss bacterial growth dynamics in the human large intestine using flow- and mixing-behavior having been observed for humans.

  5. 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

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

    Science.gov (United States)

    Denton, P W; Nochi, T; Lim, A; Krisko, J F; Martinez-Torres, F; Choudhary, S K; Wahl, A; Olesen, R; Zou, W; Di Santo, J P; Margolis, D M; Garcia, J V

    2012-09-01

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

  7. Transepithelial Transport of PAMAM Dendrimers Across Isolated Human Intestinal Tissue.

    Science.gov (United States)

    Hubbard, Dallin; Enda, Michael; Bond, Tanner; Moghaddam, Seyyed Pouya Hadipour; Conarton, Josh; Scaife, Courtney; Volckmann, Eric; Ghandehari, Hamidreza

    2015-11-02

    Poly(amido amine) (PAMAM) dendrimers have shown transepithelial transport across intestinal epithelial barrier in rats and across Caco-2 cell monolayers. Caco-2 models innately lack mucous barriers, and rat isolated intestinal tissue has been shown to overestimate human permeability. This study is the first report of transport of PAMAM dendrimers across isolated human intestinal epithelium. It was observed that FITC labeled G4-NH2 and G3.5-COOH PAMAM dendrimers at 1 mM concentration do not have a statistically higher permeability compared to free FITC controls in isolated human jejunum and colonic tissues. Mannitol permeability was increased at 10 mM concentrations of G3.5-COOH and G4-NH2 dendrimers. Significant histological changes in human colonic and jejunal tissues were observed at G3.5-COOH and G4-NH2 concentrations of 10 mM implying that dose limiting toxicity may occur at similar concentrations in vivo. The permeability through human isolated intestinal tissue in this study was compared to previous rat and Caco-2 permeability data. This study implicates that PAMAM dendrimer oral drug delivery may be feasible, but it may be limited to highly potent drugs.

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

    Directory of Open Access Journals (Sweden)

    Paola Andrea Gómez Buitrago

    2014-10-01

    Full Text Available Human intestinal mucus essentially consists of a network of Mucin2 glycoproteins embedded in many lower molecular weight proteins. This paper contributes to the proteomic study of human intestinal mucus by comparing two sample collection methods (transanal irrigation and brush cytology during proctosigmoidoscopy and analysis techniques (electrophoresis and digestion in solution. The entire sample collection and treatment process is explained, including protein extraction, digestion and desalination and peptide characterisation using a nanoAcquity UPLC chromatograph coupled to an HDMS spectrometer equipped with a nanoESI source. Collecting mucus via transanal irrigation provided a larger sample volume and protein concentration from a single patient. The proctosigmoidoscopy sample could be analysed via digestion in solution after depleting albumin. The analysis indicates that a simple mucus lysis method can evaluate the electrophoresis and digestion in solution techniques. Studying human intestinal mucus complexes is important because they perform two essential survival functions for humans as the first biochemical and physical defences for the gastrointestinal tract and a habitat for intestinal microbiota, which are primarily hosted in the colon and exceeds the human genetic information and cell number 100- and 10-fold (1.

  9. Delayed radiation effects at the small and large intestine

    International Nuclear Information System (INIS)

    Wunder, S.

    1982-01-01

    The work deals with 56 patients treated within a period of 15 years for delayed radiation damage to the intestine. Gynecologic carcinomas were most frequently the basic disease. By the time the complaints occurred, which mostly took the form of an ileus, the radiation therapy dated back 4 months to 38 years. The mean age of the patients was 60 years. The report points out the diagnostical problem as well as clinical, radiographic and histological findings. Especially hydronephrosis and renal failure were observed as additional radiation sequelae. Whenever possible, resection of the intestinal segment concerned should be carried through. The portion of radiological patients who attracted the disorder was of 72 per cent, with a lethal result in 37 per cent. Half the patients died from an imperfect anastomosis followed by peritonitis. In 16 per cent of the patients recidivations of the malignant basic disease occurred. Whether treatment of radiation damage of the intestine is successful depends on the care taken to give a diagnosis and on the assessment of the intestinal segment damaged. As the actinic injury tends to aggravate early surgical intervention is recommended. Because the treatment of malignant tumours by irradiation is partly quite successful, injuries to the intestine must to some extent be put up with. (orig./MG) [de

  10. Comprehensive postmortem analyses of intestinal microbiota changes and bacterial translocation in human flora associated mice.

    Directory of Open Access Journals (Sweden)

    Markus M Heimesaat

    Full Text Available BACKGROUND: Postmortem microbiological examinations are performed in forensic and medical pathology for defining uncertain causes of deaths and for screening of deceased tissue donors. Interpretation of bacteriological data, however, is hampered by false-positive results due to agonal spread of microorganisms, postmortem bacterial translocation, and environmental contamination. METHODOLOGY/PRINCIPAL FINDINGS: We performed a kinetic survey of naturally occurring postmortem gut flora changes in the small and large intestines of conventional and gnotobiotic mice associated with a human microbiota (hfa applying cultural and molecular methods. Sacrificed mice were kept under ambient conditions for up to 72 hours postmortem. Intestinal microbiota changes were most pronounced in the ileal lumen where enterobacteria and enterococci increased by 3-5 orders of magnitude in conventional and hfa mice. Interestingly, comparable intestinal overgrowth was shown in acute and chronic intestinal inflammation in mice and men. In hfa mice, ileal overgrowth with enterococci and enterobacteria started 3 and 24 hours postmortem, respectively. Strikingly, intestinal bacteria translocated to extra-intestinal compartments such as mesenteric lymphnodes, spleen, liver, kidney, and cardiac blood as early as 5 min after death. Furthermore, intestinal tissue destruction was characterized by increased numbers of apoptotic cells and neutrophils within 3 hours postmortem, whereas counts of proliferative cells as well as T- and B-lymphocytes and regulatory T-cells decreased between 3 and 12 hours postmortem. CONCLUSIONS/SIGNIFICANCE: We conclude that kinetics of ileal overgrowth with enterobacteria and enterococci in hfa mice can be used as an indicator for compromized intestinal functionality and for more precisely defining the time point of death under defined ambient conditions. The rapid translocation of intestinal bacteria starting within a few minutes after death will help

  11. Comparison of Surgically Treated Large Versus Small Intestinal Volvulus (2009-2014).

    Science.gov (United States)

    Davis, Elizabeth; Townsend, Forrest I; Bennett, Julie W; Takacs, Joel; Bloch, Christopher P

    2016-01-01

    The purpose of this retrospective study was to compare the outcome for dogs with surgically treated large versus small intestinal volvulus between October 2009 and February 2014. A total of 15 dogs met the inclusion criteria and underwent an abdominal exploratory. Nine dogs were diagnosed with large intestinal volvulus during the study period, and all nine had surgical correction for large intestinal volvulus. All dogs were discharged from the hospital. Of the seven dogs available for phone follow-up (74 to 955 days postoperatively), all seven were alive and doing well. Six dogs were diagnosed with small intestinal volvulus during the study period. One of the six survived to hospital discharge. Three of the six were euthanized at the time of surgery due to an extensive amount of necrotic bowel. Of the three who were not, one died postoperatively the same day, one died 3 days later, and one dog survived for greater than 730 days. Results concluded that the outcome in dogs with surgically corrected large intestinal volvulus is excellent, compared with a poor outcome in dogs with small intestinal volvulus. The overall survival to discharge for large intestinal volvulus was 100%, versus 16% for small intestinal volvulus.

  12. The growth pattern of the human intestine and its mesentery

    NARCIS (Netherlands)

    Soffers, Jelly H. M.; Hikspoors, Jill P. J. M.; Mekonen, Hayelom K.; Koehler, S. Eleonore; Lamers, Wouter H.

    2015-01-01

    It remains unclear to what extent midgut rotation determines human intestinal topography and pathology. We reinvestigated the midgut during its looping and herniation phases of development, using novel 3D visualization techniques. We distinguished 3 generations of midgut loops. The topography of

  13. Long-term monitoring of the human intestinal microbiota composition

    NARCIS (Netherlands)

    Rajilic-Stojanovic, M.; Heilig, G.H.J.; Tims, S.; Zoetendal, E.G.; Vos, de W.M.

    2013-01-01

    The microbiota that colonizes the human intestinal tract is complex and its structure is specific for each of us. In this study we expand the knowledge about the stability of the subject-specific microbiota and show that this ecosystem is stable in short-term intervals (¿10 years). The faecal

  14. 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

  15. Biotransformation of Food Dyes by Human Intestinal Bacteria ...

    African Journals Online (AJOL)

    Biotransformation of food dyes (Tartrazine and Quinoline yellow) by Streptococcus faecalis and Escherichia coli isolated from human intestinal microflora was investigated. Decolourisation of the media containing the dyes was used as an index of biotransformation. Biotransformation was higher under aerobic than under ...

  16. Metabolism of gentiopicroside (gentiopicrin) by human intestinal bacteria.

    Science.gov (United States)

    el-Sedawy, A I; Hattori, M; Kobashi, K; Namba, T

    1989-09-01

    As a part of our studies on the metabolism of crude drug components by intestinal bacteria, gentiopicroside (a secoiridoid glucoside isolated from Gentiana lutea), was anaerobically incubated with various defined strains of human intestinal bacteria. Many species had ability to transform it to a series of metabolites. Among them, Veillonella parvula ss parvula produced five metabolites, which were identified as erythrocentaurin, gentiopicral, 5-hydroxymethylisochroman-1-one,5-hydroxymethylisochromen-1- one and trans-5,6-dihydro-5-hydroxymethyl-6-methyl-1H,3H-pyrano[3,4-c]pyra n-1-one.

  17. Zebrafish Axenic Larvae Colonization with Human Intestinal Microbiota.

    Science.gov (United States)

    Arias-Jayo, Nerea; Alonso-Saez, Laura; Ramirez-Garcia, Andoni; Pardo, Miguel A

    2018-04-01

    The human intestine hosts a vast and complex microbial community that is vital for maintaining several functions related with host health. The processes that determine the gut microbiome composition are poorly understood, being the interaction between species, the external environment, and the relationship with the host the most feasible. Animal models offer the opportunity to understand the interactions between the host and the microbiota. There are different gnotobiotic mice or rat models colonized with the human microbiota, however, to our knowledge, there are no reports on the colonization of germ-free zebrafish with a complex human intestinal microbiota. In the present study, we have successfully colonized 5 days postfertilization germ-free zebrafish larvae with the human intestinal microbiota previously extracted from a donor and analyzed by high-throughput sequencing the composition of the transferred microbial communities that established inside the zebrafish gut. Thus, we describe for first time which human bacteria phylotypes are able to colonize the zebrafish digestive tract. Species with relevant interest because of their linkage to dysbiosis in different human diseases, such as Akkermansia muciniphila, Eubacterium rectale, Faecalibacterium prausnitzii, Prevotella spp., or Roseburia spp. have been successfully transferred inside the zebrafish digestive tract.

  18. Species and prevalence determination of Human Intestinal ...

    African Journals Online (AJOL)

    ADOWIE PERE

    harm to some extent by the association or may cause death. Human ... Center and Specialist Hospital Yola, Adamawa state. MATERIALS ..... of animal dungs as manure could aid in transfer of cysts. .... American Journal of Tropical. Medicine ...

  19. Functional Metagenomic Investigations of the Human Intestinal Microbiota

    DEFF Research Database (Denmark)

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

    2011-01-01

    The human intestinal microbiota encode multiple critical functions impacting human health, including metabolism of dietary substrate, prevention of pathogen invasion, immune system modulation, and provision of a reservoir of antibiotic resistance genes accessible to pathogens. The complexity...... 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...

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

    Science.gov (United States)

    Van den Bogert, Bartholomeus; Boekhorst, Jos; Herrmann, Ruth; Smid, Eddy J.; Zoetendal, Erwin G.; Kleerebezem, Michiel

    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 strains in public databases. The Streptococcus pangenome consists of 12,403 orthologous groups of which 574 are shared among all sequenced streptococci and are defined as the Streptococcus core genome. Genome mining of the small-intestinal streptococci focused on functions playing an important role in the interaction of these streptococci in the small-intestinal ecosystem, including natural competence and nutrient-transport and metabolism. Analysis of the small-intestinal Streptococcus genomes predicts a high capacity to synthesize amino acids and various vitamins as well as substantial divergence in their carbohydrate transport and metabolic capacities, which is in agreement with observed physiological differences between these Streptococcus strains. Gene-specific PCR-strategies enabled evaluation of conservation of Streptococcus populations in intestinal samples from different human individuals, revealing that the S. salivarius strains were frequently detected in the small-intestine microbiota, supporting the representative value of the genomes provided in this study. Finally, the Streptococcus genomes allow prediction of the effect of dietary substances on Streptococcus population dynamics in the human small-intestine. PMID:24386196

  1. THE CHANGES OF LARGE INTESTINE CAVITY’S MICROBIOTA IN PATIENTS WITH HIV INFECTION

    Directory of Open Access Journals (Sweden)

    Savinova O.M.

    2015-12-01

    features of obligate microfloras’ functions (bifidus bacteria, lactobacillus, E.coli, its lack has a negative impact on microecological system of the human body and reduces immunomodulatory effect on humoral and cellular immunity. So one of the issues which will have a positive impact on the health of patients with HIV infection is a normalization of obligate microflora deficit and reducing of opportunistic microflora. The conducted researches point to the need of microbiological analysis of fecal on dysbiosis for the patients with HIV infection and depending on the revealed dysbiotic changes making correction of microflora by biological agents. To correct the number of anaerobic bacteria (bifidus bacteria, lactobacillus use of bacterial preparations is not enough for only one month. It is necessary to continue taking of medicine for at least one month under the control of microbiological studies. The positive dynamics of the microflora of the large intestine points to changes that may be found in the immune system of the person that takes biological preparations. The close interaction between the microbiota of intestinal canal and the immune system leads to the formation of non–specific resistance of the organism. In this regard, the big importance has a modulating effect of intestinal microflora on products of cytokines, which are characterized by a wide range of biological effects. Conclusion. 1. Patients with HIV infection irrespective of the clinical stage of the disease have deficit both anaerobic (bifidobacteria and lactobacilli and facultative anaerobic microorganisms. 2. E.coli is the leading microorganism among the facultative anaerobic intestinal microflora, its amount of has been reduced to levels <106 CFU / mL at 56% at the patients. 3. Correction of patients' microflora by bacterial agents showed that the number of E.coli already in a month have reached the normal level in 100% of cases.

  2. Are Human Intestinal Eukaryotes Beneficial or Commensals?

    Czech Academy of Sciences Publication Activity Database

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

    2015-01-01

    Roč. 11, č. 8 (2015), e1005039 E-ISSN 1553-7374 R&D Projects: GA ČR GAP305/12/2261 EU Projects: European Commission(XE) 316304 Institutional support: RVO:60077344 Keywords : human gut microbiota * Blastocystis * infection * diversity * parasites * impact Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.003, year: 2015

  3. Development of the human infant intestinal microbiota.

    Science.gov (United States)

    Palmer, Chana; Bik, Elisabeth M; DiGiulio, Daniel B; Relman, David A; Brown, Patrick O

    2007-07-01

    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.

  4. 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.

  5. In Silico Prediction for Intestinal Absorption and Brain Penetration of Chemical Pesticides in Humans.

    Science.gov (United States)

    Chedik, Lisa; Mias-Lucquin, Dominique; Bruyere, Arnaud; Fardel, Olivier

    2017-06-30

    Intestinal absorption and brain permeation constitute key parameters of toxicokinetics for pesticides, conditioning their toxicity, including neurotoxicity. However, they remain poorly characterized in humans. The present study was therefore designed to evaluate human intestine and brain permeation for a large set of pesticides ( n = 338) belonging to various chemical classes, using an in silico graphical BOILED-Egg/SwissADME online method based on lipophilicity and polarity that was initially developed for drugs. A high percentage of the pesticides (81.4%) was predicted to exhibit high intestinal absorption, with a high accuracy (96%), whereas a lower, but substantial, percentage (38.5%) displayed brain permeation. Among the pesticide classes, organochlorines ( n = 30) constitute the class with the lowest percentage of intestine-permeant members (40%), whereas that of the organophosphorus compounds ( n = 99) has the lowest percentage of brain-permeant chemicals (9%). The predictions of the permeations for the pesticides were additionally shown to be significantly associated with various molecular descriptors well-known to discriminate between permeant and non-permeant drugs. Overall, our in silico data suggest that human exposure to pesticides through the oral way is likely to result in an intake of these dietary contaminants for most of them and brain permeation for some of them, thus supporting the idea that they have toxic effects on human health, including neurotoxic effects.

  6. Human Enteroids as a Model of Upper Small Intestinal Ion Transport Physiology and Pathophysiology

    NARCIS (Netherlands)

    J. Foulke-Abel (Jennifer); J. In (Julie); Yin, J. (Jianyi); N.C. Zachos (Nicholas C.); O. Kovbasnjuk (Olga); M.K. Estes (Mary K.); H.R. de Jonge (Hugo); M. Donowitz (Mark)

    2016-01-01

    textabstractBackground & Aims Human intestinal crypt-derived enteroids are a model of intestinal ion transport that require validation by comparison with cell culture and animal models. We used human small intestinal enteroids to study neutral Na+ absorption and stimulated fluid and anion secretion

  7. The growth pattern of the human intestine and its mesentery.

    Science.gov (United States)

    Soffers, Jelly H M; Hikspoors, Jill P J M; Mekonen, Hayelom K; Koehler, S Eleonore; Lamers, Wouter H

    2015-08-22

    It remains unclear to what extent midgut rotation determines human intestinal topography and pathology. We reinvestigated the midgut during its looping and herniation phases of development, using novel 3D visualization techniques. We distinguished 3 generations of midgut loops. The topography of primary and secondary loops was constant, but that of tertiary loops not. The orientation of the primary loop changed from sagittal to transverse due to the descent of ventral structures in a body with a still helical body axis. The 1st secondary loop (duodenum, proximal jejunum) developed intraabdominally towards a left-sided position. The 2nd secondary loop (distal jejunum) assumed a left-sided position inside the hernia before returning, while the 3rd and 4th secondary loops retained near-midline positions. Intestinal return into the abdomen resembled a backward sliding movement. Only after return, the 4th secondary loop (distal ileum, cecum) rapidly "slid" into the right lower abdomen. The seemingly random position of the tertiary small-intestinal loops may have a biomechanical origin. The interpretation of "intestinal rotation" as a mechanistic rather than a descriptive concept underlies much of the confusion accompanying the physiological herniation. We argue, instead, that the concept of "en-bloc rotation" of the developing midgut is a fallacy of schematic drawings. Primary, secondary and tertiary loops arise in a hierarchical fashion. The predictable position and growth of secondary loops is pre-patterned and determines adult intestinal topography. We hypothesize based on published accounts that malrotations result from stunted development of secondary loops.

  8. Esterification of xanthophylls by human intestinal Caco-2 cells.

    Science.gov (United States)

    Sugawara, Tatsuya; Yamashita, Kyoko; Asai, Akira; Nagao, Akihiko; Shiraishi, Tomotaka; Imai, Ichiro; Hirata, Takashi

    2009-03-15

    We recently found that peridinin, which is uniquely present in dinoflagellates, reduced cell viability by inducing apoptosis in human colon cancer cells. Peridinin is also found in edible clams and oysters because the major food sources of those shellfish are phytoplanktons such as dinoflagellates. Little is known, however, about the fate of dietary peridinin and its biological activities in mammals. The aim of the present study was to investigate the enzymatic esterification of xanthophylls, especially peridinin which is uniquely present in dinoflagellates, using differentiated cultures of Caco-2 human intestinal cells. We found that peridinin is converted to peridininol and its fatty acid esters in differentiated Caco-2 cells treated with 5mumol/L peridinin solubilized with mixed micelles. The cell homogenate was also able to deacetylate peridinin and to esterify peridininol. Other xanthophylls, such as fucoxanthin, astaxanthin and zeaxanthin, were also esterified, but at relatively lower rates than peridinin. In this study, we found the enzymatic esterification of xanthophylls in mammalian intestinal cells for the first time. Our results suggest that the esterification of xanthophylls in intestinal cells is dependent on their polarity.

  9. Large intestine bacterial flora of nonhibernating and hibernating leopard frogs (Rana pipiens).

    OpenAIRE

    Gossling, J; Loesche, W J; Nace, G W

    1982-01-01

    The bacteria in the large intestines of 10 northern leopard frogs (Rana pipiens) were enumerated and partially characterized. Four nonhibernating frogs were collected in the summer, four hibernating frogs were collected in the winter, and two frogs just emerged from hibernation were collected in the spring. All frogs had about 10(10) bacteria per g (wet weight) of intestinal contents and about 10(9) bacteria per g (wet weight) of mucosal scraping, although the counts from the winter frogs wer...

  10. Functional Metagenomic Investigations of the Human Intestinal Microbiota

    Directory of Open Access Journals (Sweden)

    Aimee Marguerite Moore

    2011-10-01

    Full Text Available The human intestinal microbiota encode multiple critical functions impacting human health, including, metabolism of dietary substrate, prevention of pathogen invasion, immune system modulation, and provision of a reservoir of antibiotic resistance genes accessible to pathogens. The complexity 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 community and its human host.

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

    Science.gov (United States)

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

    2013-08-01

    Molecular and cultivation approaches were employed to study the phylogenetic richness and temporal dynamics of Streptococcus and Veillonella populations in the small intestine. Microbial profiling of human small intestinal samples collected from four ileostomy subjects at four time points displayed abundant populations of Streptococcus spp. most affiliated with S. salivarius, S. thermophilus, and S. parasanguinis, as well as Veillonella spp. affiliated with V. atypica, V. parvula, V. dispar, and V. rogosae. Relative abundances varied per subject and time of sampling. Streptococcus and Veillonella isolates were cultured using selective media from ileostoma effluent samples collected at two time points from a single subject. The richness of the Streptococcus and Veillonella isolates was assessed at species and strain level by 16S rRNA gene sequencing and genetic fingerprinting, respectively. A total of 160 Streptococcus and 37 Veillonella isolates were obtained. Genetic fingerprinting differentiated seven Streptococcus lineages from ileostoma effluent, illustrating the strain richness within this ecosystem. The Veillonella isolates were represented by a single phylotype. Our study demonstrated that the small intestinal Streptococcus populations displayed considerable changes over time at the genetic lineage level because only representative strains of a single Streptococcus lineage could be cultivated from ileostoma effluent at both time points. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  12. Human Milk Hyaluronan Enhances Innate Defense of the Intestinal Epithelium*

    Science.gov (United States)

    Hill, David R.; Rho, Hyunjin K.; Kessler, Sean P.; Amin, Ripal; Homer, Craig R.; McDonald, Christine; Cowman, Mary K.; de la Motte, Carol A.

    2013-01-01

    Breast-feeding is associated with enhanced protection from gastrointestinal disease in infants, mediated in part by an array of bioactive glycan components in milk that act through molecular mechanisms to inhibit enteric pathogen infection. Human milk contains hyaluronan (HA), a glycosaminoglycan polymer found in virtually all mammalian tissues. We have shown that synthetic HA of a specific size range promotes expression of antimicrobial peptides in intestinal epithelium. We hypothesize that hyaluronan from human milk also enhances innate antimicrobial defense. Here we define the concentration of HA in human milk during the first 6 months postpartum. Importantly, HA isolated from milk has a biological function. Treatment of HT-29 colonic epithelial cells with human milk HA at physiologic concentrations results in time- and dose-dependent induction of the antimicrobial peptide human β-defensin 2 and is abrogated by digestion of milk HA with a specific hyaluronidase. Milk HA induction of human β-defensin 2 expression is also reduced in the presence of a CD44-blocking antibody and is associated with a specific increase in ERK1/2 phosphorylation, suggesting a role for the HA receptor CD44. Furthermore, oral administration of human milk-derived HA to adult, wild-type mice results in induction of the murine Hβ D2 ortholog in intestinal mucosa and is dependent upon both TLR4 and CD44 in vivo. Finally, treatment of cultured colonic epithelial cells with human milk HA enhances resistance to infection by the enteric pathogen Salmonella typhimurium. Together, our observations suggest that maternally provided HA stimulates protective antimicrobial defense in the newborn. PMID:23950179

  13. The effects of Strongylus vulgaris parasitism on eosinophil distribution and accumulation in equine large intestinal mucosa.

    Science.gov (United States)

    Rötting, A K; Freeman, D E; Constable, P D; Moore, R M; Eurell, J C; Wallig, M A; Hubert, J D

    2008-06-01

    Eosinophilic granulocytes have been associated with parasite or immune-mediated diseases, but their functions in other disease processes remain unclear. Cause and timing of eosinophil migration into the equine gastrointestinal mucosa are also unknown. To determine the effects of intestinal parasitism on eosinophils in equine large intestinal mucosa. Large intestinal mucosal samples were collected from horses and ponies (n = 16) from the general veterinary hospital population, ponies (n = 3) raised in a parasite-free environment, ponies experimentally infected with 500 infective Strongylus vulgaris larvae and treated with a proprietary anthelmintic drug (n = 14), and a similar group of ponies (n = 7) that received no anthelmintic treatment. Total eosinophil counts and eosinophil distribution in the mucosa were determined by histological examination. A mixed model analysis was performed and appropriate Bonferroni adjusted P values used for each family of comparisons. Pvulgaris and those raised in a parasite-free environment. Experimental infection with S. vulgaris, with or without subsequent anthelmintic treatment, did not change eosinophil counts, and counts were similar to those for horses from the general population. Migration of eosinophils to the equine large intestinal mucosa appears to be independent of exposure to parasites. Large intestinal mucosal eosinophils may have more functions in addition to their role in defence against parasites.

  14. Concentrations of cadmium and selected essential elements in malignant large intestine tissue

    Science.gov (United States)

    Dziki, Adam; Kilanowicz, Anna; Sapota, Andrzej; Duda-Szymańska, Joanna; Daragó, Adam

    2015-01-01

    Introduction Colorectal cancer is one of the most common cancers worldwide. Incidence rates of large intestine cancer indicate a role of environmental and occupational factors. The role of essential elements and their interaction with toxic metals can contribute to the explanation of a complex mechanism by which large intestine cancer develops. Bearing this in mind, determining the levels of essential and toxic elements in tissues (organs), as well as in body fluids, seems to shed light on their role in the mode of action in malignant disease. Aim Determination of the levels of cadmium, zinc, copper, selenium, calcium, magnesium, and iron in large intestine malignant tissue. Material and methods Two intraoperative intestine sections were investigated: one from the malignant tissue and the other one from the normal tissue, collected from each person with diagnosed large intestine cancer. Cadmium, zinc, copper, calcium, magnesium, and iron levels were determined with atomic absorption spectrometry, and selenium levels by spectrofluorimetric method. Results The levels of copper, selenium, and magnesium were higher in the malignant than in normal tissues. In addition, the zinc/copper and calcium/magnesium relationship was altered in malignant tissue, where correlations were lower compared to non-malignant tissue. Conclusions The results seems to demonstrate disturbed homeostasis of some essential elements. However, it is hard to confirm their involvement in the aetiology of colorectal cancer. PMID:27110307

  15. Microbial production of volatile sulphur compounds in the large intestine of pigs fed two different diets.

    Science.gov (United States)

    Poulsen, H V; Jensen, B B; Finster, K; Spence, C; Whitehead, T R; Cotta, M A; Canibe, N

    2012-07-01

      To investigate the production of volatile sulphur compounds (VSC) in the segments of the large intestine of pigs and to assess the impact of diet on this production.   Pigs were fed two diets based on either wheat and barley (STD) or wheat and dried distillers grains with solubles (DDGS). Net production of VSC and potential sulphate reduction rate (SRR) (sulphate saturated) along the large intestine were determined by means of in vitro incubations. The net production rate of hydrogen sulphide and potential SRR increased from caecum towards distal colon and were significantly higher in the STD group. Conversely, the net methanethiol production rate was significantly higher in the DDGS group, while no difference was observed for dimethyl sulphide. The number of sulphate-reducing bacteria and total bacteria were determined by quantitative PCR and showed a significant increase along the large intestine, whereas no diet-related differences were observed.   VSC net production varies widely throughout the large intestine of pigs and the microbial processes involved in this production can be affected by diet.   This first report on intestinal production of all VSC shows both spatial and dietary effects, which are relevant to both bowel disease- and odour mitigation research. © 2012 The Authors. Journal of Applied Microbiology © 2012 The Society for Applied Microbiology.

  16. The human intestinal IgA response; burning questions.

    Directory of Open Access Journals (Sweden)

    Jo eSpencer

    2012-05-01

    Full Text Available Understanding the cellular and molecular mechanisms that generate the human intestinal IgA response is fundamentally important if effective mucosal vaccination is to be successful and broadly applied. There have been several major advances in this field recently that have allowed us to feel optimistic that this will be achieved. However, there are still many unanswered questions. These questions have been used as a scaffold for this review that considers findings at the current leading edge alongside the many uncertainties in this field.

  17. Methylation of mercuric chloride by human intestinal bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Rowland, I R; Grasso, P; Davies, M J

    1975-01-01

    There is now evidence that ingested mercuric chloride (HgCl/sub 2/) may be methylated, in vivo, in the rat intestine and, in vitro, by human feces. However, one cannot infer from these experiments that the microbial flora of the intestine is responsible for the methylation reaction, since the gut contents contain several sources of metabolic activity other than bacteria. Data are presented on the ability of pure cultures of bacteria and yeasts, isolated from human feces, to convert HgCl/sub 2/ to methylmercury. Strains of Escherichia coli, streptococci, staphylococci, bacteriodes and bifidobacteria were inoculated into a medium containing 0.1 M potassium phosphate buffer, pH 7.0, Bacto-tryptone, yeast extract and D-glucose, each at 0.5% (w/v). Results indicate that most strains of staphylococci, streptococci, yeasts and E. coli isolated from human feces, could synthesize methylmercury compounds. In contrast, few strains of obligate anaerobes could do so. Up to 6 ng methylmercury/ml were formed in 44 h from 2 ..mu..g mercuric chloride.

  18. Intestinal mucus protects Giardia lamblia from killing by human milk.

    Science.gov (United States)

    Zenian, A J; Gillin, F D

    1987-02-01

    We have previously shown that nonimmune human milk kills Giardia lamblia trophozoites in vitro. Killing requires a bile salt and the activity of the milk bile salt-stimulated lipase. We now show that human small-intestinal mucus protects trophozoites from killing by milk. Parasite survival increased with mucus concentration, but protection was overcome during longer incubation times or with greater milk concentrations. Trophozoites preincubated with mucus and then washed were not protected. Protective activity was associated with non-mucin CsCl density gradient fractions. Moreover, it was heat-stable, non-dialyzable, and non-lipid. Whereas whole mucus inhibited milk lipolytic activity, protective mucus fractions did not inhibit the enzyme. Furthermore, mucus partially protected G. lamblia trophozoites against the toxicity of oleic acid, a fatty acid which is released from milk triglycerides by lipase. These studies show that mucus protects G. lamblia both by inhibiting lipase activity and by decreasing the toxicity of products of lipolysis. The ability of mucus to protect G. lamblia from toxic lipolytic products may help to promote intestinal colonization by this parasite.

  19. First report of human intestinal sarcocystosis in Cambodia.

    Science.gov (United States)

    Khieu, Virak; Marti, Hanspeter; Chhay, Saomony; Char, Meng Chuor; Muth, Sinuon; Odermatt, Peter

    2017-10-01

    Human intestinal sarcocystosis (HIS), caused by Sarcocystis species, is acquired by eating undercooked meat from sarcocyst-containing cattle (S. hominis, S. heydorni) and pigs (S. suihominis). We report on the detection of human intestinal Sarcocystis infections in a cross-sectional survey of Strongyloides stercoralis in early 2014, in Rovieng District, Preah Vihear Province, northern Cambodia. Among 1081 participants, 108 (10.0%) were diagnosed with Sarcocystis spp. oocysts in stool samples. Males had a significantly higher risk of infection than females (OR: 1.9, 95% CI: 1.3-2.9, p=0.001). None of the reported symptoms (abdominal discomfort, diarrhea, muscle pain and itching skin) occurring in the two weeks preceding the examinations were associated with a Sarcocystis infection. Many Sarcocystis cases were found among those who had participated in a wedding celebration and Chinese New Year festivities, where they had consumed raw or insufficiently cooked beef (83.3%) and pork (38.9%) based dishes. This report documents the first HIS cases in Cambodia. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. 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 ...

  1. Microfluidic Organ-on-a-Chip Models of Human IntestineSummary

    Directory of Open Access Journals (Sweden)

    Amir Bein

    Full Text Available Microfluidic organ-on-a-chip models of human intestine have been developed and used to study intestinal physiology and pathophysiology. In this article, we review this field and describe how microfluidic Intestine Chips offer new capabilities not possible with conventional culture systems or organoid cultures, including the ability to analyze contributions of individual cellular, chemical, and physical control parameters one-at-a-time; to coculture human intestinal cells with commensal microbiome for extended times; and to create human-relevant disease models. We also discuss potential future applications of human Intestine Chips, including how they might be used for drug development and personalized medicine. Keywords: Organs-on-Chips, Gut-on-a-Chip, Intestine-on-a-Chip, Microfluidic

  2. Metabolism of aspartame by human and pig intestinal microvillar peptidases.

    Science.gov (United States)

    Hooper, N M; Hesp, R J; Tieku, S

    1994-01-01

    The artificial sweetener aspartame (N-L-alpha-aspartyl-L-phenyl-alanine-1-methyl ester; Nutrasweet), its decomposition product alpha Asp-Phe and the related peptide alpha Asp-PheNH2 were rapidly hydrolysed by microvillar membranes prepared from human duodenum, jejunum and ileum, and from pig duodenum and kidney. The metabolism of aspartame by the human and pig intestinal microvillar membrane preparations was inhibited significantly (> 78%) by amastatin or 1,10-phenanthroline, and partially (> 38%) by actinonin or bestatin, and was activated 2.9-4.5-fold by CaCl2. The inhibition by amastatin and 1,10-phenanthroline, and the activation by CaCl2 are characteristic of the cell-surface ectoenzyme aminopeptidase A (EC 3.4.11.7) and a purified preparation of this enzyme hydrolysed aspartame with a Km of 0.25 mM and a Vmax of 126 mumol/min per mg. A purified preparation of aminopeptidase W (EC 3.4.11.16) also hydrolysed aspartame but with a Km of 4.96 mM and a Vmax of 110 mumol/min per mg. However, rentiapril, an inhibitor of aminopeptidase W, caused only slight inhibition (maximally 19%) of the hydrolysis of aspartame by the microvillar membrane preparations. Similar patterns of inhibition and kinetic parameters were observed for alpha Asp-Phe and alpha Asp-PheNH2. Two other decomposition products of aspartame, beta Asp-PheMe and cyclo-Asp-Phe, were essentially resistant to hydrolysis by both the human and pig intestinal microvillar membrane preparations and the purified preparations of aminopeptidases A and W. Although the relatively selective inhibitor of aminopeptidase N (EC 3.4.11.2), actinonin, partially inhibited the metabolism of aspartame, alpha Asp-Phe and alpha Asp-PheNH2 by the human and pig intestinal microvillar membrane preparations, these peptides were not hydrolysed by a purified preparation of aminopeptidase N. Membrane dipeptidase (EC 3.4.13.19) only hydrolysed the unblocked dipeptide, alpha Asp-Phe, but the selective inhibitor of this enzyme, cilastatin

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

    OpenAIRE

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

    2010-01-01

    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 epithel...

  4. [Microbial "friend-foe" identification in human intestine microsymbiocenosis].

    Science.gov (United States)

    Bukharin, O V; Petrunova, N B

    2011-01-01

    Development of methodical approach of evaluation of microbial "friend-foe" identification in human intestine microsymbiocenosis. 9 bifidobacteria cultures (dominants) and 18 opportunistic microorganism strains (associants) isolated from patients during examination for intestine dysbiosis and identified by conventional methods were used. Evaluation of microbial "friend-foe" identification in microsymbiocenosis was performed by author developed technique that is based on determination of growth factors (GF), anti-lysozyme activity (ALA) and formation of biofilms (BFF) of associants co-incubated with exometabolites of dominants. GF, ALA, BFF were studied photometrically (Bukharin O.V., 1999, 2009; O'Toole G.A., 2000). The data were statistically analyzed by Fisher-Student criteria. The detected opposite (increase/reduction) phenomenon of the "dominant-associant" pair allowed realization of the "friend-foe" identification in microsymbiocenosis. Associants (E. coli and Enterococcus faecium) were "friend" species, in which bifidobacteria exometabolites did not change growth properties and stimulated ALA (by 17,5--32%) and BFF (by 25 - 39%). Associants (Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Candida albicans) were "foe" microsymbiont species, in which bifidoflora exometabolites decreased GF (by 20,7--68%), ALA (by 22,7--54%) and BFF (by 22,5 --39%). Indigenous microflora during microsymbiocenosis formation can participate in "friend-foe" identification, the basis of which is determined by microsymbiont exometabolites. The data obtained open a perspective of understanding mechanisms of intramicrobial interactions and can be used for both diagnostics and optimal selection of "candidates" during creation of new probiotics and synbiotics.

  5. 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.

  6. 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

  7. 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.

  8. Human Primary Intestinal Epithelial Cells as an Improved In Vitro Model for Cryptosporidium parvum Infection

    Science.gov (United States)

    Cabada, Miguel M.; Nichols, Joan; Gomez, Guillermo; White, A. Clinton

    2013-01-01

    The study of human intestinal pathogens has been limited by the lack of methods for the long-term culture of primary human intestinal epithelial cells (PECs). The development of infection models with PECs would allow a better understanding of host-parasite interactions. The objective of this study was to develop a novel method for prolonged in vitro cultivation of PECs that can be used to study Cryptosporidium infection. We isolated intact crypts from human intestines removed during weight loss surgery. The fragments of intestinal layers were cultivated with culture medium supplemented with growth factors and antiapoptotic molecules. After 7 days, the PECs formed self-regenerating cell clusters, forming villi that resemble intestinal epithelium. The PECs proliferated and remained viable for at least 60 days. The cells expressed markers for intestinal stem cells, epithelial cells, and mature enterocytes. The PECs were infected with Cryptosporidium. In contrast to older models in which parasite numbers decay, the burden of parasites increased for >120 h. In summary, we describe here a novel method for the cultivation of self-regenerating human epithelial cells from small intestinal crypts, which contain both intestinal stem cells and mature villus cells. We present data that suggest these cells support Cryptosporidium better than existing cell lines. PECs should provide an improved tool for studying host-parasite interactions involving Cryptosporidium and other intestinal pathogens. PMID:23509153

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

    International Nuclear Information System (INIS)

    Escaffit, Fabrice; Pare, Frederic; Gauthier, Remy; Rivard, Nathalie; Boudreau, Francois; Beaulieu, Jean-Francois

    2006-01-01

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

  10. Characterization of acyl-coenzyme A:diacylglycerol acyltransferase (DGAT) enzyme of human small intestine.

    Science.gov (United States)

    Hiramine, Yasushi; Tanabe, Toshizumi

    2011-06-01

    Acyl-coenzyme A:diacylglycerol acyltransferase (DGAT) enzyme plays a significant role in dietary triacylglycerol (TAG) absorption in the small intestine. However, the characteristics of human intestinal DGAT enzyme have not been examined in detail. The aim of our study was to characterize the human intestinal DGAT enzyme by examining acyl-CoA specificity, temperature dependency, and selectivity for 1,2-diacylglycerol (DAG) or 1,3-DAG. We detected DGAT activity of human intestinal microsome and found that the acyl-CoA specificity and temperature dependency of intestinal DGAT coincided with those of recombinant human DGAT1. To elucidate the selectivity of human intestinal DGAT to 1,2-DAG or 1,3-DAG, we conducted acyl-coenzyme A:monoacylglycerol acyltransferase assays using 1- or 2-monoacylglycerol (MAG) as substrates. When 2-MAG was used as acyl acceptor, both 1,2-DAG and TAG were generated; however, when 1-MAG was used, 1,3-DAG was predominantly observed and little TAG was detected. These findings suggest that human small intestinal DGAT, which is mainly encoded by DGAT1, utilizes 1,2-DAG as the substrate to form TAG. This study will contribute to understand the lipid absorption profile in the small intestine.

  11. WRN conditioned media is sufficient for in vitro propagation of intestinal organoids from large farm and small companion animals.

    Science.gov (United States)

    Powell, Robin H; Behnke, Michael S

    2017-05-15

    Recent years have seen significant developments in the ability to continuously propagate organoids derived from intestinal crypts. These advancements have been applied to mouse and human samples providing models for gastrointestinal tissue development and disease. We adapt these methods for the propagation of intestinal organoids (enteroids) from various large farm and small companion (LF/SC) animals, including cat, dog, cow, horse, pig, sheep and chicken. We show that LF/SC enteroids propagate and expand in L-WRN conditioned media containing signaling factors Wnt3a, R-spondin-3, and Noggin (WRN). Multiple successful isolations were achieved for each species, and the growth of LF/SC enteroids was maintained to high passage number. LF/SC enteroids expressed crypt stem cell marker LGR5 and low levels of mesenchymal marker VIM. Labeling with EdU also showed distinct regions of cell proliferation within the enteroids marking crypt-like regions. The ability to grow and maintain LF/SC enteroid cell lines provides additional models for the study of gastrointestinal developmental biology as well as platforms for the study of host-pathogen interactions between intestinal cells and zoonotic enteric pathogens of medical importance. © 2017. Published by The Company of Biologists Ltd.

  12. WRN conditioned media is sufficient for in vitro propagation of intestinal organoids from large farm and small companion animals

    Directory of Open Access Journals (Sweden)

    Robin H. Powell

    2017-05-01

    Full Text Available Recent years have seen significant developments in the ability to continuously propagate organoids derived from intestinal crypts. These advancements have been applied to mouse and human samples providing models for gastrointestinal tissue development and disease. We adapt these methods for the propagation of intestinal organoids (enteroids from various large farm and small companion (LF/SC animals, including cat, dog, cow, horse, pig, sheep and chicken. We show that LF/SC enteroids propagate and expand in L-WRN conditioned media containing signaling factors Wnt3a, R-spondin-3, and Noggin (WRN. Multiple successful isolations were achieved for each species, and the growth of LF/SC enteroids was maintained to high passage number. LF/SC enteroids expressed crypt stem cell marker LGR5 and low levels of mesenchymal marker VIM. Labeling with EdU also showed distinct regions of cell proliferation within the enteroids marking crypt-like regions. The ability to grow and maintain LF/SC enteroid cell lines provides additional models for the study of gastrointestinal developmental biology as well as platforms for the study of host-pathogen interactions between intestinal cells and zoonotic enteric pathogens of medical importance.

  13. 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

  14. Gross morphology and anatomy of the large intestine of the paca (Cuniculus paca Linnaeus, 1766

    Directory of Open Access Journals (Sweden)

    Camila Paes Bürger

    2012-06-01

    Full Text Available Exploring the potential of using the paca as livestock involves understanding the morphophysiology of its digestive tract so its nutrition can be properly managed. The morphological and anatomical aspects of the large intestine of this species were investigated by inspecting material that was fresh and fixed in an aqueous solution of 10% formaldehyde. The material was provided by the Setor de Animais Selvagens do Departamento de Zootecnia da Faculdade de Ciências Agrárias e Veterinárias de Jaboticabal – UNESP (FCAV – UNESP. The large intestine of the paca is formed by cecum, colon and rectum, and is located in the abdominal and pelvic cavity near the third or fourth lumbar vertebrae. It was found, in the 10 samples analyzed, that there was no change in the pattern of this arrangement and that this pattern resembles that of mammals in general.

  15. Intestinal diffuse large B-cell lymphoma: an evaluation of different staging systems.

    Science.gov (United States)

    Hwang, Hee Sang; Yoon, Dok Hyun; Suh, Cheolwon; Park, Chan-Sik; Huh, Jooryung

    2014-01-01

    The gastrointestinal tract is the most common primary extranodal site for diffuse large B-cell lymphoma (DLBCL). However, there is no consensus on the most appropriate staging system for intestinal DLBCL. We evaluated the utility of the modified Ann Arbor system, the Lugano system, and the Paris staging system (a modification of the Tumor, Node, Metastases [TNM] staging for epithelial tumors) in 66 cases of resected intestinal DLBCL. The cases were treated with surgery, plus either cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) chemotherapy alone (n=26) or with the addition of rituximab immunotherapy (n=40). Median follow-up time was 40.4 months (range, 2.1-171.6 months). Fifty-six patients (84.8%) achieved complete remission. The overall 5-yr survival rate was 86.4% (57/66). Of the stage categories defined for each staging system, only the T stage of the Paris classification showed prognostic significance for overall survival by univariate analysis. However, none of the stage parameters was significantly correlated with patient survival on multivariate analysis. In conclusion, the results suggest that the T stage of the Paris classification system may be a prognostic indicator in intestinal DLBCL. The results also imply that in surgically resected intestinal DLBCL, the addition of rituximab to the CHOP regimen does not confer significant survival advantage.

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

    International Nuclear Information System (INIS)

    Labadie, Karine; Pelletier, Isabelle; Saulnier, Aure; Martin, Javier; Colbere-Garapin, Florence

    2004-01-01

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

  17. Prediction of Human Intestinal Absorption of Compounds Using Artificial Intelligence Techniques.

    Science.gov (United States)

    Kumar, Rajnish; Sharma, Anju; Siddiqui, Mohammed Haris; Tiwari, Rajesh Kumar

    2017-01-01

    Information about Pharmacokinetics of compounds is an essential component of drug design and development. Modeling the pharmacokinetic properties require identification of the factors effecting absorption, distribution, metabolism and excretion of compounds. There have been continuous attempts in the prediction of intestinal absorption of compounds using various Artificial intelligence methods in the effort to reduce the attrition rate of drug candidates entering to preclinical and clinical trials. Currently, there are large numbers of individual predictive models available for absorption using machine learning approaches. Six Artificial intelligence methods namely, Support vector machine, k- nearest neighbor, Probabilistic neural network, Artificial neural network, Partial least square and Linear discriminant analysis were used for prediction of absorption of compounds. Prediction accuracy of Support vector machine, k- nearest neighbor, Probabilistic neural network, Artificial neural network, Partial least square and Linear discriminant analysis for prediction of intestinal absorption of compounds was found to be 91.54%, 88.33%, 84.30%, 86.51%, 79.07% and 80.08% respectively. Comparative analysis of all the six prediction models suggested that Support vector machine with Radial basis function based kernel is comparatively better for binary classification of compounds using human intestinal absorption and may be useful at preliminary stages of drug design and development. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. 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.

  19. Vasoactive intestinal polypeptide (VIP) innervation of the human eyelid glands.

    Science.gov (United States)

    Seifert, P; Spitznas, M

    1999-06-01

    This study was conducted to obtain morphological proof of innervating nerve fibres in the glands of the human eyelid (accessory lacrimal glands of Wolfring, meibomian glands, goblet cells, glands of Zeis, glands of Moll, sweat glands, glands of lanugo hair follicles) and identification of the secretomotorically active neuropeptide vasoactive intestinal polypeptide (VIP) as a common transmitter. Epoxy-embedded ultrathin sections of tissue samples from human eyelids were studied using electron microscopy. Paraffin sections fixed in Bouin-Hollande solution were immunostained with rabbit antiserum against VIP. With the electron microscope we were able to identify nerves in the glandular stroma of all the glands examined with the exception of goblet cells. Intraepithelial single axons were only seen in the parenchyma of Wolfring glands. The morphological findings corresponded with the immunological finding of VIP-positive, nerve-like structures in the same locations, with the exception of lanugo hair follicle glands, and goblet cells. Our findings indicate that the glands of the eyelids and main lacrimal gland represent a functional unit with VIP as a possible common stimulating factor. Copyright 1999 Academic Press.

  20. Maternal Obesity Induces Sustained Inflammation in Both Fetal and Offspring Large Intestine of Sheep

    Science.gov (United States)

    Yan, Xu; Huang, Yan; Wang, Hui; Du, Min; Hess, Bret W.; Ford, Stephen P.; Nathanielsz, Peter W.; Zhu, Mei-Jun

    2010-01-01

    Background Both maternal obesity and inflammatory bowel diseases (IBDs) are increasing. It was hypothesized that maternal obesity induces an inflammatory response in the fetal large intestine, predisposing offspring to IBDs. Methods Nonpregnant ewes were assigned to a control (Con, 100% of National Research Council [NRC] recommendations) or obesogenic (OB, 150% of NRC) diet from 60 days before conception. The large intestine was sampled from fetuses at 135 days (term 150 days) after conception and from offspring lambs at 22.5 ± 0.5 months of age. Results Maternal obesity enhanced mRNA expression tumor necrosis factor (TNF)α, interleukin (IL)1α, IL1β, IL6, IL8, and monocyte/macrophage chemotactic protein-1 (MCP1), as well as macrophage markers, CD11b, CD14, and CD68 in fetal gut. mRNA expression of Toll-like receptor (TLR) 2 and TLR4 was increased in OB versus Con fetuses; correspondingly, inflammatory NF-κB and JNK signaling pathways were also upregulated. Both mRNA expression and protein content of transforming growth factor (TGF) β was increased. The IL-17A mRNA expression and protein content was higher in OB compared to Con samples, which was associated with fibrosis in the large intestine of OB fetuses. Similar inflammatory responses and enhanced fibrosis were detected in OB compared to Con offspring. Conclusions Maternal obesity induced inflammation and enhanced expression of proinflammatory cytokines in fetal and offspring large intestine, which correlated with increased TGFβ and IL17 expression. These data show that maternal obesity may predispose offspring gut to IBDs. PMID:21674707

  1. FEATURES OF THE LARGE INTESTINE MICROFLORA OF CHILDREN – DONOR LIVER TRANSPLANT RECIPIENTS

    Directory of Open Access Journals (Sweden)

    N. I. Gabrielyan

    2013-01-01

    Full Text Available Aim. The study microecology of the large intestine of children with cirrhosis before transplantation of the share liver. Materials and methods. Studied the flora of the colon 157 children of 1 to 17 years admitted to hospital for liver transplantation fragment from a related donor. Identification was carried out using microbial panels BD Crystal and databases BBL Crystal MIND. Methicillin-resistant staphylococci were determined by their sensiti- vity to oxacillin and cefoxitin. Beta-lactamase activity was tested using discs with ceftazidime and ceftazidime/ clavulanic acid. Results. Microecological revealed deep irregularities in the large intestine transplantation in children up lobe of the liver on a spectrum and composition of the microflora. Among the resident microflora decreased levels of bifidobacteria, lactobacilli and coliform bacteria, especially in children under one year. A sig- nificant portion of the children surveyed (over 60–70% had an increase of frequency of finding stateally bacteria, especially Klebsiella and enterobacteria in third children – non-fermenting bacteria – Pseudomonas and Acine- tobacter spp. Revealed the spread of strains of gram-negative bacteria with extended-spectrum betalaktamaz.Conclusion. Expressed microecological violations in the large intestine in children with higher levels of bac- teria are conditionally risk factor reeks of infectious complications in the postoperative period and require are complex tools to assist in eliminatsii.s given antibiotic resistance of bacteria. 

  2. Calcium absorption in rat large intestine in vivo: availability of dietary calcium

    International Nuclear Information System (INIS)

    Ammann, P.; Rizzoli, R.; Fleisch, H.

    1986-01-01

    Calcium absorption in the large intestine of the rat was investigated in vivo. After a single injection of 45 CaCl 2 into the cecum, 26.0 +/- 2.5% (mean +/- SE, n = 9) of the 45 CaCl 2 injected disappeared. This absorption was modulated by 1,25-dihydroxyvitamin D3, increased to 64.0 +/- 4.2% under a low-Ca diet, and increased under low-Pi diet. In contrast, when the difference of nonradioactive Ca in the cecal content and the feces was measured, only 4.1 +/- 4.6% (not significant) was absorbed. Secretion of intravenously injected 45 Ca into the lumen was small and not altered by any of the conditions tested. When cecum contents were placed into duodenal tied loops, 14 +/- 6.2% were absorbed in situ when 45 Ca was given orally, whereas when 45 Ca was directly added to the content 35.6 +/- 4.6% were absorbed (P less than 0.02). These results indicate that the large intestine has an important vitamin D-dependent Ca absorptive system detectable if 45 Ca is injected into the cecum. However, it is not effective in vivo because the Ca arriving in the large intestine appears to be no longer in an absorbable form

  3. Why did humans develop a large brain?

    OpenAIRE

    Muscat Baron, Yves

    2012-01-01

    "Of all animals, man has the largest brain in proportion to his size"- Aristotle. Dr Yves Muscat Baron shares his theory on how humans evolved large brains. The theory outlines how gravity could have helped humans develop a large brain- the author has named the theory 'The Gravitational Vascular Theory'. http://www.um.edu.mt/think/why-did-humans-develop-a-large-brain/

  4. Analysis of 16S libraries of mouse gastrointestinal microflora reveals a large new group of mouse intestinal bacteria

    NARCIS (Netherlands)

    Salzman, NH; de Jong, H; Paterson, Y; Harmsen, HJM; Welling, GW; Bos, NA

    2002-01-01

    Total genomic DNA from samples of intact mouse small intestine, large intestine, caecum and faeces was used as template for PCR amplification of 16S rRNA gene sequences with conserved bacterial primers. Phylogenetic analysis of the amplification products revealed 40 unique 16S rDNA sequences. Of

  5. Comparison of three contrast radiographic techniques in the dog large intestine

    International Nuclear Information System (INIS)

    Vargas, L.; Thibaut, J.; Olhaberry, E.; Born, R.; Deppe, R.

    1994-01-01

    In order to compare three radiographic techniques -pneumocolon, barium enema and double contrast- in the large intestine of the dog, three radiographic series in ventrodorsal and right lateral projections were taken. Six healthy adult dogs of both sexes with an approximate weight between 5 to 10 kg were used. Three enemas were administered 24, 12 and 2 hrs. before the series of radiographs were taken. Then dogs were anaesthetized with sodium tiopental (20 mg/kg iv) and the contrast media were introduced. Pneumocolon was carried out in the first series introducing air (20 cc/kg) in the large intestine through a Foley rectal catheter. Radiographs were taken in both projections, after 5 and 15min. respectively. Barium enema was performed in the second series introducing barium sulfate (18%) in the large intestine through a Foley rectal catheter (25 cc/kg); 5 and 15 min. later, the radiographs were taken. In the third series -double contrast- the barium sulfate, which was obtained from each dog using a catheter, was substituted by a volume of air equal to that obtained from the contrast medium. Later the radiographs were taken in both projections. The radiographic plates of each series were analized comparing the characteristics of: radiographic density, outline and volume. With the pneumocolon barium enema and double contrast, the radiographic density was, in most cases, low, high and inter-mediate respectively. The radiographic outline was, in most cases, regular for the three techniques. Thee radiographic volume was similar in all of the series. From the results obtained, it is concluded that double contrast best outlines the intestinal mucosa and more information can be obtained from it [es

  6. Human mini-guts: new insights into intestinal physiology and host-pathogen interactions.

    Science.gov (United States)

    In, Julie G; Foulke-Abel, Jennifer; Estes, Mary K; Zachos, Nicholas C; Kovbasnjuk, Olga; Donowitz, Mark

    2016-11-01

    The development of indefinitely propagating human 'mini-guts' has led to a rapid advance in gastrointestinal research related to transport physiology, developmental biology, pharmacology, and pathophysiology. These mini-guts, also called enteroids or colonoids, are derived from LGR5 + intestinal stem cells isolated from the small intestine or colon. Addition of WNT3A and other growth factors promotes stemness and results in viable, physiologically functional human intestinal or colonic cultures that develop a crypt-villus axis and can be differentiated into all intestinal epithelial cell types. The success of research using human enteroids has highlighted the limitations of using animals or in vitro, cancer-derived cell lines to model transport physiology and pathophysiology. For example, curative or preventive therapies for acute enteric infections have been limited, mostly due to the lack of a physiological human intestinal model. However, the human enteroid model enables specific functional studies of secretion and absorption in each intestinal segment as well as observations of the earliest molecular events that occur during enteric infections. This Review describes studies characterizing these human mini-guts as a physiological model to investigate intestinal transport and host-pathogen interactions.

  7. The role of metabolism in diclofenac-induced intestinal toxicity in rat and human in vitro

    NARCIS (Netherlands)

    Niu, Xiaoyu; Makkinje, Miriam; de Graaf, Inge; Groothuis, Genoveva

    The use of Diclofenac (DCF), a non-steroidal anti-inflammatory drug is associated with severe gastro-intestinal side-effects. The mechanisms of drug-induced intestinal toxicity are largely unknown due to the lack of in vitro models. In vivo rat studies suggested that reactive metabolites of DCF

  8. Klebsiella pneumoniae capsule expression is necessary for colonization of large intestines of streptomycin-treated mice

    DEFF Research Database (Denmark)

    Favre-Bonte, S.; Licht, Tine Rask; Forestier, C.

    1999-01-01

    The role of the Klebsiella pneumoniae capsular polysaccharide (K antigen) during colonization of the mouse large intestine was assessed with mild-type K. pneumoniae LM21 and its isogenic capsule-defective mutant. When bacterial strains were fed alone to mice, the capsulated bacteria persisted...... in the intestinal tract at levels of 10(8) CFU/g of feces while the capsule-defective strain colonized at low levels, 10(4) CFU/g of feces. In mixed-infection experiments, the mutant was rapidly outcompeted by the wild type. In situ hybridization on colonic sections revealed that bacterial cells of both strains...... were evenly distributed in the mucus layer at day 1 after infection, while at day 20 the wild type remained dispersed and the capsule-defective strain was seen in clusters in the mucus layer. These results suggest that capsular polysaccharide plays an important role in the gut colonization ability of K...

  9. Diclofenac toxicity in human intestine ex vivo is not related to the formation of intestinal metabolites

    NARCIS (Netherlands)

    Niu, Xiaoyu; de Graaf, Inge A. M.; Langelaar-Makkinje, Miriam; Horvatovich, Peter; Groothuis, Geny M. M.

    The use of diclofenac (DCF), a nonsteroidal anti-inflammatory drug, is associated with a high prevalence of gastrointestinal side effects. In vivo studies in rodents suggested that reactive metabolites of DCF produced by the liver or the intestine might be responsible for this toxicity. In the

  10. Human organoids: a model system for intestinal diseases

    OpenAIRE

    Wiegerinck, C.L.

    2015-01-01

    You are what you eat. A common saying that indicates that your physical or mental state can be influenced by your choice of food. Unfortunately, not all people have the luxury to choose what to eat; this can be related to place of birth, social, economic state, or the physical inability of the diseased intestine to take up certain food. A cell layer, the epithelium, covers the intestine, and harbors the main functions of the intestine: uptake, digestion of food, and a barrier against unwanted...

  11. Congruent strain specific intestinal persistence of Lactobacillus plantarum in an intestine-mimicking in vitro system and in human volunteers.

    Directory of Open Access Journals (Sweden)

    Hermien van Bokhorst-van de Veen

    Full Text Available BACKGROUND: An important trait of probiotics is their capability to reach their intestinal target sites alive to optimally exert their beneficial effects. Assessment of this trait in intestine-mimicking in vitro model systems has revealed differential survival of individual strains of a species. However, data on the in situ persistence characteristics of individual or mixtures of strains of the same species in the gastrointestinal tract of healthy human volunteers have not been reported to date. METHODOLOGY/PRINCIPAL FINDINGS: The GI-tract survival of individual L. plantarum strains was determined using an intestine mimicking model system, revealing substantial inter-strain differences. The obtained data were correlated to genomic diversity of the strains using comparative genome hybridization (CGH datasets, but this approach failed to discover specific genetic loci that explain the observed differences between the strains. Moreover, we developed a next-generation sequencing-based method that targets a variable intergenic region, and employed this method to assess the in vivo GI-tract persistence of different L. plantarum strains when administered in mixtures to healthy human volunteers. Remarkable consistency of the strain-specific persistence curves were observed between individual volunteers, which also correlated significantly with the GI-tract survival predicted on basis of the in vitro assay. CONCLUSION: The survival of individual L. plantarum strains in the GI-tract could not be correlated to the absence or presence of specific genes compared to the reference strain L. plantarum WCFS1. Nevertheless, in vivo persistence analysis in the human GI-tract confirmed the strain-specific persistence, which appeared to be remarkably similar in different healthy volunteers. Moreover, the relative strain-specific persistence in vivo appeared to be accurately and significantly predicted by their relative survival in the intestine-mimicking in vitro

  12. Increased chromogranin A cell density in the large intestine of patients with irritable bowel syndrome after receiving dietary guidance

    OpenAIRE

    Mazzawi, Tarek; Gundersen, Doris Irene; Hausken, Trygve; El-Salhy, Magdy

    2015-01-01

    The large intestine contains five types of endocrine cells that regulate its functions by sensing its luminal contents and releasing specific hormones. Chromogranin A (CgA) is a common marker for the gastrointestinal endocrine cells, and it is abnormal in irritable bowel syndrome (IBS) patients. Most IBS patients relate their symptoms to certain food elements. The present study investigated the effect of dietary guidance on the total endocrine cells of the large intestine as detected by CgA i...

  13. Early establishment of epithelial apoptosis in the developing human small intestine.

    Science.gov (United States)

    Vachon, P H; Cardin, E; Harnois, C; Reed, J C; Vézina, A

    2000-12-01

    In the adult small intestine, the dynamic renewal of the epithelium is characterized by a sequence of cell production in the crypts, cell maturation and cell migration to the tip of villi, where apoptosis is undertaken. Little is known about enterocytic apoptosis during development. In man, intestinal architectural features and functions are acquired largely by mid-gestation (18-20 wks); the question whether the establishment of enterocytic apoptotic processes parallels or not the acquisition of other intestinal functional features remains open. In the present study, we approached this question by examining enterocytic apoptosis during development of the human jejunum (9-20 wks gestation), using the ISEL (in situ terminal uridine deoxynucleotidyl nick-end labelling) method. Between 9 and 17 wks, apoptotic enterocytes were not evidenced. However, beginning at the 18 wks stage, ISEL-positive enterocytes were regularly observed at the tip of villi. Since the Bcl-2 family of proteins constitutes a critical checkpoint in apoptosis, acting upstream of the apoptotic machinery, we investigated the expression of six Bcl-2 homologs (Bcl-2, Bcl-X(L), Mcl-1, Bax, Bak, Bad) and one non-homologous associated molecule (Bag-1). By immunofluorescence, we found that all homologs analyzed were expressed by enterocytes between 9 and 20 wks. However, Bcl-2 homologs underwent a gradual compartmentalization of epithelial expression along the maturing crypt-villus axis, to establish gradients of expression by 18-20 wks. Western blot analyses indicated that the expression levels of Bcl-2 homologs were modulated during morphogenesis of the crypt-villus axis, in parallel to their gradual compartmentalization of expression. Altogether, these data suggest that regulatory mechanisms of human enterocytic apoptosis become established by mid-gestation (18-20 wks) and coincide with the maturation of the crypt-villus axis of cell proliferation, differentiation and renewal.

  14. 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.

  15. Eosinophils may play regionally disparate roles in influencing IgA(+) plasma cell numbers during large and small intestinal inflammation.

    Science.gov (United States)

    Forman, Ruth; Bramhall, Michael; Logunova, Larisa; Svensson-Frej, Marcus; Cruickshank, Sheena M; Else, Kathryn J

    2016-05-31

    Eosinophils are innate immune cells present in the intestine during steady state conditions. An intestinal eosinophilia is a hallmark of many infections and an accumulation of eosinophils is also observed in the intestine during inflammatory disorders. Classically the function of eosinophils has been associated with tissue destruction, due to the release of cytotoxic granule contents. However, recent evidence has demonstrated that the eosinophil plays a more diverse role in the immune system than previously acknowledged, including shaping adaptive immune responses and providing plasma cell survival factors during the steady state. Importantly, it is known that there are regional differences in the underlying immunology of the small and large intestine, but whether there are differences in context of the intestinal eosinophil in the steady state or inflammation is not known. Our data demonstrates that there are fewer IgA(+) plasma cells in the small intestine of eosinophil-deficient ΔdblGATA-1 mice compared to eosinophil-sufficient wild-type mice, with the difference becoming significant post-infection with Toxoplasma gondii. Remarkably, and in complete contrast, the absence of eosinophils in the inflamed large intestine does not impact on IgA(+) cell numbers during steady state, and is associated with a significant increase in IgA(+) cells post-infection with Trichuris muris compared to wild-type mice. Thus, the intestinal eosinophil appears to be less important in sustaining the IgA(+) cell pool in the large intestine compared to the small intestine, and in fact, our data suggests eosinophils play an inhibitory role. The dichotomy in the influence of the eosinophil over small and large intestinal IgA(+) cells did not depend on differences in plasma cell growth factors, recruitment potential or proliferation within the different regions of the gastrointestinal tract (GIT). We demonstrate for the first time that there are regional differences in the requirement of

  16. Intestinal Obstruction

    Science.gov (United States)

    ... Colostomy ) is required to relieve an obstruction. Understanding Colostomy In a colostomy, the large intestine (colon) is cut. The part ... 1 What Causes Intestinal Strangulation? Figure 2 Understanding Colostomy Gastrointestinal Emergencies Overview of Gastrointestinal Emergencies Abdominal Abscesses ...

  17. Biomechanical testing and material characterization for the rat large intestine: regional dependence of material parameters.

    Science.gov (United States)

    Sokolis, Dimitrios P; Orfanidis, Ioannis K; Peroulis, Michalis

    2011-12-01

    The function of the large bowel is to absorb water from the remaining indigestible food matter and subsequently pass useless waste material from the body, but there has been only a small amount of data in the literature on its biomechanical characteristics that would facilitate our understanding of its transport function. Our study aims to fill this gap by affording comprehensive inflation/extension data of intestinal segments from distinct areas, spanning a physiologically relevant deformation range (100-130% axial stretches and 0-15 mmHg lumen pressures). These data were characterized by the Fung-type exponential model in the thick-walled setting, showing reasonable agreement, i.e. root-mean-square error ~30%. Based on optimized material parameters, i.e. a(1)testing and material characterization results for the large intestine of healthy young animals are expected to aid in comprehending the adaptation/remodeling that occurs with ageing, pathological conditions and surgical procedures, as well as for the development of suitable biomaterials for replacement.

  18. 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

  19. Intestinal short chain fatty acids and their link with diet and human health

    Directory of Open Access Journals (Sweden)

    David eRios-Covian

    2016-02-01

    Full Text Available The colon is inhabited by a dense population of microorganisms, the so-called gut microbiota, able to ferment carbohydrates and proteins that escape absorption in the small intestine during digestion. This microbiota produces a wide range of metabolites, including short chain fatty acids (SCFA. These compounds are absorbed in the large bowel and are defined as 1-6 carbon volatile fatty acids which can present straight or branched-chain conformation. Their production is influenced by the pattern of food intake and diet-mediated changes in the gut microbiota. SCFA have distinct physiological effects: they contribute to shaping the gut environment, influence the physiology of the colon, they can be used as energy sources by host cells and the intestinal microbiota and they also participate in different host-signalling mechanisms. We summarize the current knowledge about the production of SCFA, including bacterial cross-feedings interactions, and the biological properties of these metabolites with impact on the human health

  20. 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

    Background and objective: The present project is part of the large ISAFRUIT project, where one of the objectives is to identify effects of apple and apple product on parameters related to gut health. In a previous rat study we observed changes in the intestinal microbiota of rats fed whole apples......, pomace or apple pectin ([1], and we were interested in finding out if the same effect can be observed in humans. Method: The study was conducted as a randomized, controlled 5 x 28 days cross-over study with 24 healthy persons of both genders. The persons were following a pectin- and polyphenol free......-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...

  1. Expressions of tight junction proteins Occludin and Claudin-1 are under the circadian control in the mouse large intestine: implications in intestinal permeability and susceptibility to colitis.

    Directory of Open Access Journals (Sweden)

    Oh-oka Kyoko

    Full Text Available BACKGROUND & AIMS: The circadian clock drives daily rhythms in behavior and physiology. A recent study suggests that intestinal permeability is also under control of the circadian clock. However, the precise mechanisms remain largely unknown. Because intestinal permeability depends on tight junction (TJ that regulates the epithelial paracellular pathway, this study investigated whether the circadian clock regulates the expression levels of TJ proteins in the intestine. METHODS: The expression levels of TJ proteins in the large intestinal epithelium and colonic permeability were analyzed every 4, 6, or 12 hours between wild-type mice and mice with a mutation of a key clock gene Period2 (Per2; mPer2(m/m. In addition, the susceptibility to dextran sodium sulfate (DSS-induced colitis was compared between wild-type mice and mPer2(m/m mice. RESULTS: The mRNA and protein expression levels of Occludin and Claudin-1 exhibited daily variations in the colonic epithelium in wild-type mice, whereas they were constitutively high in mPer2(m/m mice. Colonic permeability in wild-type mice exhibited daily variations, which was inversely associated with the expression levels of Occludin and Claudin-1 proteins, whereas it was constitutively low in mPer2(m/m mice. mPer2(m/m mice were more resistant to the colonic injury induced by DSS than wild-type mice. CONCLUSIONS: Occludin and Claudin-1 expressions in the large intestine are under the circadian control, which is associated with temporal regulation of colonic permeability and also susceptibility to colitis.

  2. 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

    in parallel. Comparative functional analysis with fecal metagenomes identified functions that are overrepresented in the small intestine, including simple carbohydrate transport phosphotransferase systems (PTS), central metabolism and biotin production. Moreover, metatranscriptome analysis supported high...... level in-situ expression of PTS and carbohydrate metabolic genes, especially those belonging to Streptococcus sp. Overall, our findings suggest that rapid uptake and fermentation of available carbohydrates contribute to maintaining the microbiota in the human small intestine....

  3. Diversity of human intestinal helminthiasis in Lao PDR.

    Science.gov (United States)

    Sayasone, Somphou; Vonghajack, Youthanavane; Vanmany, Monely; Rasphone, Oroth; Tesana, Smarn; Utzinger, Jürg; Akkhavong, Kongsap; Odermatt, Peter

    2009-03-01

    Food-borne trematodiasis is an emerging public health problem, including in Lao PDR. We investigated the diversity of intestinal helminthes and polyparasitism in patients with hepatobiliary or intestinal symptoms in hospital and community-based surveys. Stool samples from 232 individuals aged >or=15 years were examined by the Kato-Katz method (three samples) and a formalin ethyl-acetate concentration technique (one sample). Opisthorchis viverrini and minute intestinal flukes (MIF) were common, with prevalences of 86.2% and 62.9%, respectively. Hookworm was the predominant soil-transmitted helminth (65.9%). The prevalences of Taenia spp., Strongyloides stercoralis and Trichuris trichiura were 22.8%, 10.3% and 8.6%, respectively. Additionally, 97 individuals were purged; O. viverrini and Haplorchis taichui were found in 95 and 76 participants, respectively. Other trematodes included Phaneropsolus bonnei (22.7%), Prosthodendrium molenkampi (14.4%), Haplorchis pumilio (5.2%), Haplorchis yokogawai (3.1%) and Echinochasmus japonicus (3.1%). Co-infection with O. viverrini and MIFs was rampant (81.4%). Polytrematode infection is highly prevalent in Lao PDR and hence requires urgent attention.

  4. Metagenomic Characterization of the Human Intestinal Microbiota in Fecal Samples from STEC-Infected Patients

    NARCIS (Netherlands)

    Gigliucci, Federica; von Meijenfeldt, F A Bastiaan; Knijn, Arnold; Michelacci, Valeria; Scavia, Gaia; Minelli, Fabio; Dutilh, Bas E|info:eu-repo/dai/nl/304546313; Ahmad, Hamideh M; Raangs, Gerwin C; Friedrich, Alex W; Rossen, John W A; Morabito, Stefano

    2018-01-01

    The human intestinal microbiota is a homeostatic ecosystem with a remarkable impact on human health and the disruption of this equilibrium leads to an increased susceptibility to infection by numerous pathogens. In this study, we used shotgun metagenomic sequencing and two different bioinformatic

  5. 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

  6. Analyzing the functionality of the human intestinal microbiota by stable isotope probing

    NARCIS (Netherlands)

    Kovatcheva, P.P.

    2010-01-01

    Key words: gut bacteria, dietary carbohydrates, digestion, RNA-SIP, TIM-2, HITChip, human trial

    The human gastro-intestinal (GI) tract comprises a series of complex and dynamic organs ranging from the stomach to the distal colon, which harbor immense microbial assemblages, with

  7. [Antibacterial prevention of suppurative complications after operations on the large intestine].

    Science.gov (United States)

    Kuzin, M I; Pomelov, V S; Vandiaev, G K; Ialgashev, T Ia; Blatun, L A

    1983-05-01

    The data on comparative study of complications after operations on the large intestine are presented. During the preoperative period, 62 patients of the control group were treated with phthalylsulfathiazole, nevigramon and nystatin. Thirty-nine patients of the test group were treated with metronidazole and kanamycin monosulfate. Kanamycin monosulfate was used 3 days before the operation in a dose of 0.5 g orally 4 times a day whereas metronidazole in a dose of 0.5 g 3 times a day. The last doses of the drugs were administered 4-5 hours before the operation. After the operations the patients were treated with kanamycin sulfate for 3-5 days in a daily dose of 2 g intramuscularly. The number of the postoperative suppurative complications decreased from 22 to 5 per cent. No lethal outcomes were registered in the test group. The number of lethal outcomes in the control group amounted to 8 per cent.

  8. Quantitation of the late effects of x radiation on the large intestine

    International Nuclear Information System (INIS)

    Black, W.C.; Gomez, L.S.; Yuhas, J.M.; Kligerman, M.M.

    1980-01-01

    A model for quantitating late effects of x radiation on the large intestine utilizing the rectum of the Sprague-Dawley rat is reported. This model was constructed prefatory to establishing relative biological effectiveness for negative pions as a component of preclinical trials at the Clinton P. Anderson Meson Physics Facility. The endpoint involves microscopic evaluation of the severity of the experimental lesion, compared with surgically resected bowel lesions we have studied following clinical radiation exposure of the bowel. Individual components of the overall lesion include mucosal ulceration, a typical epithelial regeneration, colitis cystica profunda, fibrosis, and vascular sclerosis. Dose response curves were established for animals receiving 1, 2, 5 and 10 fractions with groups sacrificed at both four and 12 months after completion of radiation exposures

  9. Study of the usefulness of large intestine screening inspections using multi-slice CT (MSCT)

    International Nuclear Information System (INIS)

    Yamasaki, Michihiro; Nonogaki, Hidehiko; Hara, Koji; Naruse, Yutaka; Hara, Hiroto; Suematsu, Seiji; Yanase, Tadahiko; Otou, Taiji

    2005-01-01

    CT-colonography (CT-C), a new diagnostic imaging technique for cancer of the large intestine-which is increasing rapidly owing to westernized eating habits-has advanced from the developmental stage to the stage of practical application, thanks to progress in MSCT and workstation development. Therefore, based on the results of CT-C application using 16 lines of MSCT to a screening test, we reviewed the usefulness of CT-C in our clinic. We supplemented defective depiction, and found that change of position was effective for virtual image exclusion. We consider that CT-C can support diagnosis if the target of screening tests is a polypoid lesion of more than 6 mm. In addition, it is expected that the number of examinations performed during office visits will increase because of the decreased invasiveness of the procedure, its lack of pain, and its ability to provide early lesion detection. (author)

  10. Studies on the nitrogen metabolism of the large intestine of ruminants. 2

    International Nuclear Information System (INIS)

    Sommer, A.; Ceresnakova, Z.; Szakacs, J.; Chrastinova, L.; Bergner, H.; Simon, O.

    1986-01-01

    3 bulls with body weights of 201, 168 and 190 kg, were equipped with a ileo-cecal re-entrant cannula and with catheters in the jugular veins on both sides. The pelleted ration was composed of straw 70-72%, cereals 10%, molasses 12-41% ammoniumhydrogencarbonate 3%, urea 2% and mineral mixture 1%. During a preliminary period ileal digesta were collected, deep-freezed and stored. During the main experiment 15 N-urea was infused intravenously for 24 hours. In this period and during the following 6 hours outflowing ileal digesta were collected quantitatively. At the same time precollected, unlabelled digesta together with a supplement of partly hydrolyzed straw meal were reintroduced into the cecal part of the cannula. Plasma urea N, urinary N as well as several N fractions of feces and digesta were analyzed for 15 N abundance. A urea flux rate of 27.9 +- 3.4 μmol per minute per kg/sup 0.75/ was estimated. It was calculated that 52% of this amount of urea was transfered into the digestive tract. In both, digesta and feces NH 3 nitrogen was highest 15 N-labelled indicating a direct urea entry and degradation in both segments of the digestive tract. The amounts of 15 N excess found during the period of digesta replacement were in feces 0.25 and in ileal digesta 4.02% of the infused 15 N. Although the microbial utilization of endogenous urea N was generally low in the large intestine there was a clear stimulation of this process due to the additional supply of the large intestine with a fermentable source. (author)

  11. The use of large databases to inform the development of an intestinal scoring system for the poultry industry.

    Science.gov (United States)

    Kasab-Bachi, H; Arruda, A G; Roberts, T E; Wilson, J B

    2017-10-01

    There is increasing interest among the poultry industry to develop a comprehensive index that can be used to evaluate overall intestinal health and impact on production performance. The Intestinal Integrity (I 2 ) index is a quantitative measurement tool used to assess the intestinal health of flocks that use the Health Tracking System (HTSi), a global surveillance system developed by Elanco Animal Health that captures flock-level information on health and performance. To generate an I 2 index score for a flock, the presence of 23 intestinal health conditions is assessed and recorded, then entered into a mathematical equation. The objective of this study was to use data from the HTSi dataset to investigate the association between health conditions contained within the I 2 index and five performance outcomes: average daily gain (ADG), mortality during the first week, feed conversion ratio (FCR), European Production Efficiency Factor (EPEF), and percent livability. At the time of analysis, the HTSi dataset contained information from the years 2006-2015 on 921,646 individual bird necropsy records from over 153,576 flocks at 1,570 broiler production flows across 53 countries. Flock-level production data used for this study were available for a subset of this population, 33,212 total flocks representing 6 US and 4 UK production flows. A separate multivariable linear or logistic regression model, with farm as a random effect, was built for each of the five outcomes mentioned above. All models controlled for clustering of flocks within production flows. Significant associations were found between key performance indicators and ten intestinal conditions (gross E. acervulina, gross E. maxima, microscopic E. maxima, gizzard erosions, roundworms, excessive intestinal fluid, thin intestines, excessive intestinal mucus, feed passage, and necrotic enteritis) and two management parameters (production flow and down time). Results from this study demonstrate that large databases

  12. Analysis of 16S libraries of mouse gastrointestinal microflora reveals a large new group of mouse intestinal bacteria.

    Science.gov (United States)

    Salzman, Nita H; de Jong, Hendrik; Paterson, Yvonne; Harmsen, Hermie J M; Welling, Gjalt W; Bos, Nicolaas A

    2002-11-01

    Total genomic DNA from samples of intact mouse small intestine, large intestine, caecum and faeces was used as template for PCR amplification of 16S rRNA gene sequences with conserved bacterial primers. Phylogenetic analysis of the amplification products revealed 40 unique 16S rDNA sequences. Of these sequences, 25% (10/40) corresponded to described intestinal organisms of the mouse, including Lactobacillus spp., Helicobacter spp., segmented filamentous bacteria and members of the altered Schaedler flora (ASF360, ASF361, ASF502 and ASF519); 75% (30/40) represented novel sequences. A large number (11/40) of the novel sequences revealed a new operational taxonomic unit (OTU) belonging to the Cytophaga-Flavobacter-Bacteroides phylum, which the authors named 'mouse intestinal bacteria'. 16S rRNA probes were developed for this new OTU. Upon analysis of the novel sequences, eight were found to cluster within the Eubacterium rectale-Clostridium coccoides group and three clustered within the Bacteroides group. One of the novel sequences was distantly related to Verrucomicrobium spinosum and one was distantly related to Bacillus mycoides. Oligonucleotide probes specific for the 16S rRNA of these novel clones were generated. Using a combination of four previously described and four newly designed probes, approximately 80% of bacteria recovered from the murine large intestine and 71% of bacteria recovered from the murine caecum could be identified by fluorescence in situ hybridization (FISH).

  13. A Refined Culture System for Human Induced Pluripotent Stem Cell-Derived Intestinal Epithelial Organoids

    Directory of Open Access Journals (Sweden)

    Yu Takahashi

    2018-01-01

    Full Text Available Gut epithelial organoids are routinely used to investigate intestinal biology; however, current culture methods are not amenable to genetic manipulation, and it is difficult to generate sufficient numbers for high-throughput studies. Here, we present an improved culture system of human induced pluripotent stem cell (iPSC-derived intestinal organoids involving four methodological advances. (1 We adopted a lentiviral vector to readily establish and optimize conditioned medium for human intestinal organoid culture. (2 We obtained intestinal organoids from human iPSCs more efficiently by supplementing WNT3A and fibroblast growth factor 2 to induce differentiation into definitive endoderm. (3 Using 2D culture, followed by re-establishment of organoids, we achieved an efficient transduction of exogenous genes in organoids. (4 We investigated suspension organoid culture without scaffolds for easier harvesting and assays. These techniques enable us to develop, maintain, and expand intestinal organoids readily and quickly at low cost, facilitating high-throughput screening of pathogenic factors and candidate treatments for gastrointestinal diseases.

  14. Smoking cessation alters intestinal microbiota: insights from quantitative investigations on human fecal samples using FISH.

    Science.gov (United States)

    Biedermann, Luc; Brülisauer, Karin; Zeitz, Jonas; Frei, Pascal; Scharl, Michael; Vavricka, Stephan R; Fried, Michael; Loessner, Martin J; Rogler, Gerhard; Schuppler, Markus

    2014-09-01

    There has been a dramatic increase in investigations on the potential mechanistic role of the intestinal microbiota in various diseases and factors modulating intestinal microbial composition. We recently reported on intestinal microbial shifts after smoking cessation in humans. In this study, we aimed to conduct further microbial analyses and verify our previous results obtained by pyrosequencing using a direct quantitative microbial approach. Stool samples of healthy smoking human subjects undergoing controlled smoking cessation during a 9-week observational period were analyzed and compared with 2 control groups, ongoing smoking and nonsmoking subjects. Fluorescence in situ hybridization was applied to quantify specific bacterial groups. Intestinal microbiota composition was substantially altered after smoking cessation as characterized by an increase in key representatives from the phyla of Firmicutes (Clostridium coccoides, Eubacterium rectale, and Clostridium leptum subgroup) and Actinobacteria (HGC bacteria and Bifidobacteria) as well as a decrease in Bacteroidetes (Prevotella spp. and Bacteroides spp.) and Proteobacteria (β- and γ-subgroup of Proteobacteria). As determined by fluorescence in situ hybridization, an independent direct quantitative microbial approach, we could confirm that intestinal microbiota composition in humans is influenced by smoking. The characteristics of observed microbial shifts suggest a potential mechanistic association to alterations in body weight subsequent to smoking cessation. More importantly, regarding previously described microbial hallmarks of dysbiosis in inflammatory bowel diseases, a variety of observed microbial alterations after smoking cessation deserve further consideration in view of the divergent effect of smoking on the clinical course of Crohn's disease and ulcerative colitis.

  15. Intestinal Microbiota Distinguish Gout Patients from Healthy Humans

    Science.gov (United States)

    Guo, Zhuang; Zhang, Jiachao; Wang, Zhanli; Ang, Kay Ying; Huang, Shi; Hou, Qiangchuan; Su, Xiaoquan; Qiao, Jianmin; Zheng, Yi; Wang, Lifeng; Koh, Eileen; Danliang, Ho; Xu, Jian; Lee, Yuan Kun; Zhang, Heping

    2016-01-01

    Current blood-based approach for gout diagnosis can be of low sensitivity and hysteretic. Here via a 68-member cohort of 33 healthy and 35 diseased individuals, we reported that the intestinal microbiota of gout patients are highly distinct from healthy individuals in both organismal and functional structures. In gout, Bacteroides caccae and Bacteroides xylanisolvens are enriched yet Faecalibacterium prausnitzii and Bifidobacterium pseudocatenulatum depleted. The established reference microbial gene catalogue for gout revealed disorder in purine degradation and butyric acid biosynthesis in gout patients. In an additional 15-member validation-group, a diagnosis model via 17 gout-associated bacteria reached 88.9% accuracy, higher than the blood-uric-acid based approach. Intestinal microbiota of gout are more similar to those of type-2 diabetes than to liver cirrhosis, whereas depletion of Faecalibacterium prausnitzii and reduced butyrate biosynthesis are shared in each of the metabolic syndromes. Thus the Microbial Index of Gout was proposed as a novel, sensitive and non-invasive strategy for diagnosing gout via fecal microbiota. PMID:26852926

  16. 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...... System class II/IV drugs) because of their drug-solubilizing ability. The characterization of these potential drug-solubilizing compartments is a prerequisite for further studies of the mechanistic interplays between drug molecules and colloidal structures within HIFs. The aim of the present study...... and HIF indicate that the simulated intestinal fluids (FaSSIF-V1 and FeSSIF-V1) represent rather simplified models of the real human intestinal environment in terms of coexisting colloidal particles. It is hypothesized that the different supramolecular assemblies detected differ in their lipid composition...

  17. The Effects of Deoxynivalenol and Zearalenone on the Pig Large Intestine. A Light and Electron Microscopy Study

    Directory of Open Access Journals (Sweden)

    Barbara Przybylska-Gornowicz

    2018-04-01

    Full Text Available The contamination of feed with mycotoxins results in reduced growth, feed refusal, immunosuppression, and health problems. Deoxynivalenol (DON and zearalenone (ZEN are among the most important mycotoxins. The aim of the study was to examine the effects of low doses of these mycotoxins on the histological structure and ultrastructure of the large intestine in the pig. The study was performed on 36 immature gilts of mixed breed (White Polish Big × Polish White Earhanging, which were divided into four groups administrated per os with ZEN at 40 µg/kg BW, DON at 12 µg/kg BW, a mixture of ZEN (40 µg/kg BW and DON (12 µg/kg BW or a placebo. The pigs were killed by intravenous overdose of pentobarbital after one, three, and six weeks of treatment. The cecum, ascending and descending colon samples were prepared for light and electron microscopy. Administration of toxins did not influence the architecture of the mucosa and submucosa in the large intestine. ZEN and ZEN + DON significantly decreased the number of goblet cells in the cecum and descending colon. The mycotoxins changed the number of lymphocytes and plasma cells in the large intestine, which usually increased in number. However, this effect differed between the intestine segments and toxins. Mycotoxins induced some changes in the ultrastructure of the mucosal epithelium. They did not affect the expression of proliferative cell nuclear antigen and the intestinal barrier permeability. The obtained results indicate that mycotoxins especially ZEN may influence the defense mechanisms of the large intestine.

  18. 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.

  19. gamma-Aminobutyric acid production in small and large intestine of normal and germ-free Wistar rats. Influence of food intake and intestinal flora.

    Science.gov (United States)

    van Berlo, C L; de Jonge, H R; van den Bogaard, A E; van Eijk, H M; Janssen, M A; Soeters, P B

    1987-09-01

    In recent hypotheses concerning the pathogenesis of hepatic encephalopathy, gamma-aminobutyric acid (GABA) is claimed to be produced by the colonic flora, although enzymes necessary to generate GABA have been reported to be present in intestinal mucosa. In this study, using normal and germ-free Wistar rats, we determined GABA levels and amino-grams of arterial blood and of venous effluent from small and large bowel. The data indicate that large and small intestinal mucosa significantly contribute to GABA production. In the fasted state GABA concentrations are greater in the venous effluent of the small bowel than in the venous effluent of the large bowel. Feeding increases the arterioportal differences, and uptake in the small bowel is still significantly higher than in the large bowel. This process is not, or can only be to a minor degree, bacterially mediated, because GABA production in the gut both in the fed and fasted state is of similar magnitude in germ-free and normal animals. gamma-Aminobutyric acid release correlates significantly with glutamine uptake in the small bowel of fasted rats. Only a small fraction of the glutamine taken up is needed to account for GABA release, so that conclusions concerning which amino acids may serve as precursors of GABA cannot be drawn. Further studies are needed to delineate the metabolic pathways leading to GABA synthesis.

  20. 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...

  1. 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

  2. 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...

  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 by chromato......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...... by chromatography, enzyme cleavages, and measurements using a library of sequence-specific RIAs. Plasma samples were drawn in the fasting state and at intervals after a meal. The abundance of the larger forms varied with the 8 C-terminal assays in the library, as 2 assays overestimated and 3 underestimated...... the amounts present. One assay, however, measured carboxyamidated and O:-sulfated CCKs with equimolar potency before and after tryptic cleavage. This assay showed that the predominant plasma form is CCK-33, both in the fasting state ( approximately 51%) and postprandially ( approximately 57%), whereas CCK-22...

  4. Complete sequences of glucagon-like peptide-1 from human and pig small intestine

    DEFF Research Database (Denmark)

    Orskov, C; Bersani, M; Johnsen, A H

    1989-01-01

    intestine of the proglucagon precursor were determined by pairs of basic amino acid residues flanking the two peptides. Earlier studies have shown that synthetic glucagon-like peptide-1 (GLP-1) synthesized according to the proposed structure (proglucagon 71-108 or because residue 108 is Gly, 72-107 amide......) had no physiological effects, whereas a truncated from of GLP-1, corresponding to proglucagon 78-107 amide, strongly stimulated insulin secretion and depressed glucagon secretion. To determine the amino acid sequence of the naturally occurring peptide we isolated GLP-1 from human small intestine...

  5. 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

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

    DEFF Research Database (Denmark)

    Machado, Ana Manuel; Sommer, Morten

    2014-01-01

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

  7. Transformation of trollioside and isoquercetin by human intestinal flora in vitro.

    Science.gov (United States)

    Yuan, Ming; Shi, Duo-Zhi; Wang, Teng-Yu; Zheng, Shi-Qi; Liu, Li-Jia; Sun, Zhen-Xiao; Wang, Ru-Feng; Ding, Yi

    2016-03-01

    The present study was designed to determine the intestinal bacterial metabolites of trollioside and isoquercetin and their antibacterial activities. A systematic in vitro biotransformation investigation on trollioside and isoquercetin, including metabolite identification, metabolic pathway deduction, and time course, was accomplished using a human intestinal bacterial model. The metabolites were analyzed and identified by HPLC and HPLC-MS. The antibacterial activities of trollioside, isoquercetin, and their metabolites were evaluated using the broth microdilution method with berberine as a positive control, and their potency was measured as minimal inhibitory concentration (MIC). Our results indicated that trollioside and isoquercetin were metabolized by human intestinal flora through O-deglycosylation, yielding aglycones proglobeflowery acid and quercetin, respectively The antibacterial activities of both metabolites were more potent than that of their parent compounds. In conclusion, trollioside and isoquercetin are totally and rapidly transformed by human intestinal bacteria in vitro and the transformation favors the improvement of the antibacterial activities of the parent compounds. Copyright © 2016 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2012-01-21

    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. 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. 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. 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.

  9. Studies on the nitrogen metabolism of the large intestine of ruminants. 3

    International Nuclear Information System (INIS)

    Kijora, C.; Simon, O.; Bergner, H.; Goersch, R.; Jacobi, U.; Rossow, N.

    1986-01-01

    Two experiments were performed on sheep, receiving on maintenance level a pelleted straw ration high in crude fibre (straw 70.5%; dried sugar beet pulp 12%; cereals 10%; urea 2%; ammonium hydrogen carbonate 3%; minerals 2.5%). The animals were fitted with ileo-cecal re-entrant cannulas. The effects of the introduction of partly hydrolyzed straw meal into the digesta of the large intestine on the digestion processes in that segment were studied. Under these conditions the metabolism of 14 C and 15 N-labelled urea, which was given into the cecum, was estimated. In experiment 1 (E1; 2 animals) unlabelled, precollected digesta were hourly reintroduced together with 14 C and 15 N-labelled urea via the cecal cannula. In experiment 2 (E2; 3 animals) the digesta were supplemented with partly hydrolyzed straw meal (10% of the mean daily dry matter intake with the ration). The supplement of partly hydrolyzed straw meal caused an increase of the 15 N excretion with feces from 13.4% (E1) to 19.8% (E2) of the dose. The 15 N was mainly incorporated in the bacterial fraction (98% E1; 96% E2). As a reason for the increased 15 N incorporation into the bacterial fraction of 106.4 mg 15 N' in E2 vs. 67.3 mg 15 N' in the experiment without straw meal supplement the higher supply of energy as fermentable carbohydrates was assumed. (author)

  10. Methods for the cultivation of ciliated protozoa from the large intestine of horses.

    Science.gov (United States)

    Bełżecki, Grzegorz; Miltko, Renata; Michałowski, Tadeusz; McEwan, Neil R

    2016-01-01

    This paper describes cultivation methods for ciliates from the digestive tract of horses. Members of three different genera were successfully grown in vitro for short periods of time. However, only cells belonging to the genus Blepharocorys, which resides in the horse's large intestine, were maintained for longer periods. This Blepharocorys culture was successfully grown in vitro after inoculation of freshly excreted horse faeces in culture medium containing a population of bacteria. The ciliates survived for over six months, and the density of their population varied between 1.7 × 10(3) and 2.4 × 10(3) cells mL(-1). Favourable conditions for the prolonged cultivation of this ciliate were observed when the medium was prepared by mixing horse faeces and 'caudatum' salt solution in a 1:1 V/V ratio together with food (60% powdered meadow hay, 16% wheat gluten, 12% barley flour and 12% microcrystalline cellulose) supplied as 0.20 mg mL(-1) culture per day. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. Oral absorption of peptides and nanoparticles across the human intestine: Opportunities, limitations and studies in human tissues.

    Science.gov (United States)

    Lundquist, P; Artursson, P

    2016-11-15

    In this contribution, we review the molecular and physiological barriers to oral delivery of peptides and nanoparticles. We discuss the opportunities and predictivity of various in vitro systems with special emphasis on human intestine in Ussing chambers. First, the molecular constraints to peptide absorption are discussed. Then the physiological barriers to peptide delivery are examined. These include the gastric and intestinal environment, the mucus barrier, tight junctions between epithelial cells, the enterocytes of the intestinal epithelium, and the subepithelial tissue. Recent data from human proteome studies are used to provide information about the protein expression profiles of the different physiological barriers to peptide and nanoparticle absorption. Strategies that have been employed to increase peptide absorption across each of the barriers are discussed. Special consideration is given to attempts at utilizing endogenous transcytotic pathways. To reliably translate in vitro data on peptide or nanoparticle permeability to the in vivo situation in a human subject, the in vitro experimental system needs to realistically capture the central aspects of the mentioned barriers. Therefore, characteristics of common in vitro cell culture systems are discussed and compared to those of human intestinal tissues. Attempts to use the cell and tissue models for in vitro-in vivo extrapolation are reviewed. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  12. CORRECTION OF LARGE INTESTINE DYSBIOSIS IN PATIENTS WITH ACUTE HEPATITIS B

    Directory of Open Access Journals (Sweden)

    Sklyar, А.I.

    2018-04-01

    Full Text Available Introduction. Viral hepatitis is one of the global challenges for modern medicine. Among them, hepatitis B (GB remains one of the most widespread viral diseases of the present day. According to the WHO estimates, more than 1/3 of the world's population (2 billion people has serological evidence of current or transmitted HBV infection, of which 350 million are chronically infected. Separate studies have identified the state of the colon biocenosis in patients with acute hepatitis and found that dysbiotic lesions of varying degrees are found in patients with viral hepatitis in 73.3% - 96% of cases [6-8]. Disturbances of the quantitative and qualitative composition of the microflora reduce the detoxification function of the intestine and increase the toxic load on the liver, which, in turn, negatively affects the development of the basic pathological process. The aim of the work was to determine the degree of dysbiotic changes in the microflora of the large intestine and to evaluate the effectiveness of their correction with a symbiotic drug in patients with acute hepatitis B. Materials and methods. To perform the task, 108 patients with acute hepatitis B, aged 18-69 being on hospital treatment at Kharkiv Regional Clinical Hospital of Infectious Diseases, have been examined. The diagnosis has been set on the basis of clinical anamnestic, epidemiological, laboratory and instrumental data. The etiological verification of the diagnosis has been performed by detecting specific serological markers of hepatitis B (HBsAg, HBeAg, anti-HBc IgM, by the ELISA method. The diagnosis of GHB and its clinical and pathogenetic variants of the course, form and degree of severity have been determined according to the International Statistical Classification of Diseases and Related Security Problems Health (ICD-10, version 2006. According to the purpose of study the patients have been divided into groups as follows: group A - the main one, where patients have

  13. Microstructure-based constitutive modeling for the large intestine validated by histological observations.

    Science.gov (United States)

    Sokolis, Dimitrios P; Sassani, Sofia G

    2013-05-01

    Other than its transport role, the large bowel performs numerous sophisticated functions, e.g. water, electrolyte, and vitamin absorption, optimized by its contractile properties and passive recoil capacity, but these properties have attracted limited attention than has been the case for other parts of the gastrointestinal tract. Accordingly, we investigated in vitro the pseudo-elastic properties of tubular specimens from the ascending, mid, and descending colon, and the rectum of healthy Wistar rats under passive quasi-static conditions and a physiologic range of pressures/axial stretches. A neo-Hookean and five-fiber family model was chosen as a microstructure-based material model for its efficiency in producing accurate representations of the three-dimensional inflation/extension data in relation to the underlying microstructure. Guided by our optical microscopy observations, this model took account of isotropic elastin properties and multi-directional collagen organization, but suffered from parameter covariance. Moreover, the contributions to the total model of the neo-Hookean and circumferential-fiber family were negligible, given the tiny amounts of elastin and circumferentially-arranged collagen fibers that were disclosed histologically, and the contributions of the diagonal and radial-fiber families to data representation were similar. The multiaxial response of the intestinal wall was fit equally accurately but without over-parameterization problems by the neo-Hookean and three-fiber (diagonal and axial) family model. The preferred alignment of collagen fibers towards the axial direction bestowed increased axial stiffness to the tissue. The mid colon was the stiffest region by virtue of its greatest material parameters, as validated by its higher collagen content than that of the distal regions. The present findings generate a more cohesive understanding of the large bowel in histomechanical terms, with potential for clinical and biomedical applications

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

    Science.gov (United States)

    Lee, Han-Seung

    2013-12-01

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

  15. Human Intestinal Fluid Layer Separation: The Effect On Colloidal Structures & Solubility Of Lipophilic Compounds.

    Science.gov (United States)

    Danny, Riethorst; Amitava, Mitra; Filippos, Kesisoglou; Wei, Xu; Jan, Tack; Joachim, Brouwers; Patrick, Augustijns

    2018-05-23

    In addition to individual intestinal fluid components, colloidal structures are responsible for enhancing the solubility of lipophilic compounds. The present study investigated the link between as well as the variability in the ultrastructure of fed state human intestinal fluids (FeHIF) and their solubilizing capacity for lipophilic compounds. For this purpose, FeHIF samples from 10 healthy volunteers with known composition and ultrastructure were used to determine the solubility of four lipophilic compounds. In light of the focus on solubility and ultrastructure, the study carefully considered the methodology of solubility determination in relation to colloid composition and solubilizing capacity of FeHIF. To determine the solubilizing capacity of human and simulated intestinal fluids, the samples were saturated with the compound of interest, shaken for 24 h, and centrifuged. When using FeHIF, solubilities were determined in the micellar layer of FeHIF, i.e. after removing the upper (lipid) layer (standard procedure), as well as in 'full' FeHIF (without removal of the upper layer). Compound concentrations were determined using HPLC-UV/fluorescence. To link the solubilizing capacity with the ultrastructure, all human and simulated fluids were imaged using transmission electron microscopy (TEM) before and after centrifugation and top layer (lipid) removal. Comparing the ultrastructure and solubilizing capacity of individual FeHIF samples demonstrated a high intersubject variability in postprandial intestinal conditions. Imaging of FeHIF after removal of the upper layer clearly showed that only micellar structures remain in the lower layer. This observation suggests that larger colloids such as vesicles and lipid droplets are contained in the upper, lipid layer. The solubilizing capacity of most FeHIF samples substantially increased with inclusion of this lipid layer. The relative increase in solubilizing capacity upon inclusion of the lipid layer was most pronounced

  16. 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.

  17. 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.

  18. Naturally occurring glucagon-like peptide-2 (GLP-2) receptors in human intestinal cell lines.

    Science.gov (United States)

    Sams, Anette; Hastrup, Sven; Andersen, Marie; Thim, Lars

    2006-02-17

    Although clinical trials with GLP-2 receptor agonists are currently ongoing, the mechanisms behind GLP-2-induced intestinal epithelial growth remain to be understood. To approach the GLP-2 mechanism of action this study aimed to identify intestinal cell lines endogenously expressing the GLP-2 receptor. Here we report the first identification of a cell line endogenously expressing functional GLP-2 receptors. The human intestinal epithelial cell line, FHC, expressed GLP-2 receptor encoding mRNA (RT-PCR) and GLP-2 receptor protein (Western blot). In cultured FHC cells, GLP-2 induced concentration dependent cAMP accumulation (pEC(50)=9.7+/-0.04 (mean+/-S.E.M., n=4)). In addition, a naturally occurring human intestinal fibroblast cell line, 18Co, endogenously expressing GLP-2 receptor encoding mRNA (RT-PCR) and protein (Western blot) was identified. No receptor functionality (binding or G-protein signalling) could be demonstrated in 18Co cells. The identified gut-relevant cell lines provide tools for future clarification of the mechanisms underlying GLP-2-induced epithelial growth.

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

    NARCIS (Netherlands)

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

    2012-01-01

    BACKGROUND: An important trait of probiotics is their capability to reach their intestinal target sites alive to optimally exert their beneficial effects. Assessment of this trait in intestine-mimicking in vitro model systems has revealed differential survival of individual strains of a species.

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

    NARCIS (Netherlands)

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

    2012-01-01

    BACKGROUND: An important trait of probiotics is their capability to reach their intestinal target sites alive to optimally exert their beneficial effects. Assessment of this trait in intestine-mimicking in vitro model systems has revealed differential survival of individual strains of a species.

  1. 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...

  2. 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

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

  3. Epidemiology of infections with intestinal parasites and human immunodeficiency virus (HIV) among sugar-estate residents in Ethiopia

    NARCIS (Netherlands)

    Fontanet, A. L.; Sahlu, T.; Rinke de Wit, T.; Messele, T.; Masho, W.; Woldemichael, T.; Yeneneh, H.; Coutinho, R. A.

    2000-01-01

    Intestinal parasitic infections could play an important role in the progression of infection with human immunodeficiency virus (HIV), by further disturbing the immune system whilst it is already engaged in the fight against HIV. HIV and intestinal parasitic infections were investigated in 1239,

  4. A paradox of transcriptional and functional innate interferon responses of human intestinal enteroids to enteric virus infection

    OpenAIRE

    Saxena, Kapil; Simon, Lukas M.; Zeng, Xi-Lei; Blutt, Sarah E.; Crawford, Sue E.; Sastri, Narayan P.; Karandikar, Umesh C.; Ajami, Nadim J.; Zachos, Nicholas C.; Kovbasnjuk, Olga; Donowitz, Mark; Conner, Margaret E.; Shaw, Chad A.; Estes, Mary K.

    2017-01-01

    Understanding host?enteric virus interactions has been limited by the inability to culture nontransformed small intestinal epithelial cells and to infect animal models with human viruses. We report epithelial responses in human small intestinal enteroid cultures from different individuals following infection with human rotavirus (HRV), a model enteric pathogen. RNA-sequencing and functional assays revealed type III IFN as the dominant transcriptional response that activates interferon-stimula...

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

    Czech Academy of Sciences Publication Activity Database

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

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Oku T

    2011-06-01

    Full Text Available Tsuneyuki Oku¹, Kenichi Tanabe¹, Shigeharu Ogawa², Naoki Sadamori¹, Sadako Nakamura¹¹Graduate School of Human Health Science, University of Nagasaki, Siebold, Nagayo, Japan; ²Juzenkai Hospital, Kagomachi, Nagasaki, JapanBackground: The purpose of this study was to clarify whether it is possible to extrapolate results from studies of the hydrolyzing activity of disaccharidases from rats to humans.Materials and methods: We measured disaccharidase activity in humans and rats using identical preparation and assay methods, and investigated the similarity in hydrolyzing activity. Small intestinal samples without malignancy were donated by five patients who had undergone bladder tumor surgery, and homogenates were prepared to measure disaccharidase activity. Adult rat homogenates were prepared using small intestine.Results: Maltase activity was the highest among the five disaccharidases, followed by sucrase and then palatinase in humans and rats. Trehalase activity was slightly lower than that of palatinase in humans and was similar to that of sucrase in rats. Lactase activity was the lowest in humans, but was similar to that of palatinase in rats. Thus, the hydrolyzing activity of five disaccharidases was generally similar in humans and rats. The relative activity of sucrose and palatinase versus maltase was generally similar between humans and rats. The ratio of rat to human hydrolyzing activity of maltase, sucrase, and palatinase was 1.9–3.1, but this was not a significant difference. Leaf extract from Morus alba strongly inhibited the activity of maltase, sucrase, and palatinase, but not trehalase and lactase, and the degree of inhibition was similar in humans and rats. L-arabinose mildly inhibited sucrase activity, but hardly inhibited the activity of maltase, palatinase, trehalase and lactase in humans and rats. The digestibility of 1-kestose, galactosylsucrose, and panose by small intestinal enzymes was very similar between humans and

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

    International Nuclear Information System (INIS)

    Crow, J. Allen; Borazjani, Abdolsamad; Potter, Philip M.; Ross, Matthew K.

    2007-01-01

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

  8. The small intestine microbiota, nutritional modulation and relevance for health

    NARCIS (Netherlands)

    El Aidy, Sahar; van den Bogert, Bartholomeus; Kleerebezem, Michiel

    The intestinal microbiota plays a profound role in human health and extensive research has been dedicated to identify microbiota aberrations that are associated with disease. Most of this work has been targeting the large intestine and fecal microbiota, while the small intestine microbiota may also

  9. Biorelevant media resistant co-culture model mimicking permeability of human intestine.

    Science.gov (United States)

    Antoine, Delphine; Pellequer, Yann; Tempesta, Camille; Lorscheidt, Stefan; Kettel, Bernadette; Tamaddon, Lana; Jannin, Vincent; Demarne, Frédéric; Lamprecht, Alf; Béduneau, Arnaud

    2015-03-15

    Cell culture models are currently used to predict absorption pattern of new compounds and formulations in the human gastro-intestinal tract (GIT). One major drawback is the lack of relevant apical incubation fluids allowing mimicking luminal conditions in the GIT. Here, we suggest a culture model compatible with biorelevant media, namely Fasted State Simulated Intestinal Fluid (FaSSIF) and Fed State Simulated Intestinal Fluid (FeSSIF). Co-culture was set up from Caco-2 and mucus-secreting HT29-MTX cells using an original seeding procedure. Viability and cytotoxicity assays were performed following incubation of FeSSIF and FaSSIF with co-culture. Influence of biorelevant fluids on paracellular permeability or transporter proteins were also evaluated. Results were compared with Caco-2 and HT29-MTX monocultures. While Caco-2 viability was strongly affected with FeSSIF, no toxic effect was detected for the co-cultures in terms of viability and lactate dehydrogenase release. The addition of FeSSIF to the basolateral compartment of the co-culture induced cytotoxic effects which suggested the apical mucus barrier being cell protective. In contrast to FeSSIF, FaSSIF induced a slight increase of the paracellular transport and both tested media inhibited partially the P-gp-mediated efflux in the co-culture. Additionally, the absorptive transport of propranolol hydrochloride, a lipophilic β-blocker, was strongly affected by biorelevant fluids. This study demonstrated the compatibility of the Caco-2/HT29-MTX model with some of the current biorelevant media. Combining biorelevant intestinal fluids with features such as mucus secretion, adjustable paracellular and P-gp mediated transports, is a step forward to more realistic in-vitro models of the human intestine. Copyright © 2015. Published by Elsevier B.V.

  10. PVA gel as a potential adhesion barrier: a safety study in a large animal model of intestinal surgery.

    Science.gov (United States)

    Renz, Bernhard W; Leitner, Kurt; Odermatt, Erich; Worthley, Daniel L; Angele, Martin K; Jauch, Karl-Walter; Lang, Reinhold A

    2014-03-01

    Intra-abdominal adhesions following surgery are a major source of morbidity and mortality including abdominal pain and small bowel obstruction. This study evaluated the safety of PVA gel (polyvinyl alcohol and carboxymethylated cellulose gel) on intestinal anastomoses and its potential effectiveness in preventing adhesions in a clinically relevant large animal model. Experiments were performed in a pig model with median laparotomy and intestinal anastomosis following small bowel resection. The primary endpoint was the safety of PVA on small intestinal anastomoses. We also measured the incidence of postoperative adhesions in PVA vs. control groups: group A (eight pigs): stapled anastomosis with PVA gel compared to group B (eight pigs), which had no PVA gel; group C (eight pigs): hand-sewn anastomosis with PVA gel compared to group B (eight pigs), which had no anti-adhesive barrier. Animals were sacrificed 14 days after surgery and analyzed. All anastomoses had a patent lumen without any stenosis. No anastomoses leaked at an intraluminal pressure of 40 cmH2O. Thus, anastomoses healed very well in both groups, regardless of whether PVA was administered. PVA-treated animals, however, had significantly fewer adhesions in the area of stapled anastomoses. The hand-sewn PVA group also had weaker adhesions and trended towards fewer adhesions to adjacent organs. These results suggest that PVA gel does not jeopardize the integrity of intestinal anastomoses. However, larger trials are needed to investigate the potential of PVA gel to prevent adhesions in gastrointestinal surgery.

  11. 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.

  12. 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

    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...... 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......, and only few gap junctions with other interstitial cells of Cajal or with the musculature were observed. Compared with interstitial cells of Cajal from other mammals, those associated with the deep muscular plexus in the human small intestine more closely resemble smooth muscle cells...

  13. Soluble arabinoxylan enhances large intestinal microbial health biomarkers in pigs fed a red meat-containing diet.

    Science.gov (United States)

    Williams, Barbara A; Zhang, Dagong; Lisle, Allan T; Mikkelsen, Deirdre; McSweeney, Christopher S; Kang, Seungha; Bryden, Wayne L; Gidley, Michael J

    2016-04-01

    The aim of this study was to investigate how moderately increased dietary red meat combined with a soluble fiber (wheat arabinoxylan [AX]) alters the large intestinal microbiota in terms of fermentative end products and microbial community profiles in pigs. Four groups of 10 pigs were fed Western-type diets containing two amounts of red meat, with or without a solubilized wheat AX-rich fraction for 4 wk. After euthanasia, fermentative end products (short-chain fatty acids, ammonia) of digesta from four sections of large intestine were measured. Di-amino-pimelic acid was a measure of total microbial biomass, and bacterial profiles were determined using a phylogenetic microarray. A factorial model determined effects of AX and meat content. Arabinoxylan was highly fermentable in the cecum, as indicated by increased concentrations of short-chain fatty acids (particularly propionate). Protein fermentation end products were decreased, as indicated by the reduced ammonia and branched-chain ratio although this effect was less prominent distally. Microbial profiles in the distal large intestine differed in the presence of AX (including promotion of Faecalibacterium prausnitzii), consistent with an increase in carbohydrate versus protein fermentation. Increased di-amino-pimelic acid (P < 0.0001) suggested increased microbial biomass for animals fed AX. Solubilized wheat AX has the potential to counteract the effects of dietary red meat by reducing protein fermentation and its resultant toxic end products such as ammonia, as well as leading to a positive shift in fermentation end products and microbial profiles in the large intestine. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  14. A single point acupuncture treatment at large intestine meridian: a randomized controlled trial in acute tonsillitis and pharyngitis.

    Science.gov (United States)

    Fleckenstein, Johannes; Lill, Christian; Lüdtke, Rainer; Gleditsch, Jochen; Rasp, Gerd; Irnich, Dominik

    2009-09-01

    One out of 4 patients visiting a general practitioner reports of a sore throat associated with pain on swallowing. This study was established to examine the immediate pain alleviating effect of a single point acupuncture treatment applied to the large intestine meridian of patients with sore throat. Sixty patients with acute tonsillitis and pharyngitis were enrolled in this randomized placebo-controlled trial. They either received acupuncture, or sham laser acupuncture, directed to the large intestine meridian section between acupuncture points LI 8 and LI 10. The main outcome measure was the change of pain intensity on swallowing a sip of water evaluated by a visual analog scale 15 minutes after treatment. A credibility assessment regarding the respective treatment was performed. The pain intensity for the acupuncture group before and immediately after therapy was 5.6+/-2.8 and 3.0+/-3.0, and for the sham group 5.6+/-2.5 and 3.8+/-2.5, respectively. Despite the articulation of a more pronounced improvement among the acupuncture group, there was no significant difference between groups (Delta=0.9, confidence interval: -0.2-2.0; P=0.12; analysis of covariance). Patients' satisfaction was high in both treatment groups. The study was prematurely terminated due to a subsequent lack of suitable patients. A single acupuncture treatment applied to a selected area of the large intestine meridian was no more effective in the alleviation of pain associated with clinical sore throat than sham laser acupuncture applied to the same area. Hence, clinically relevant improvement could be achieved. Pain alleviation might partly be due to the intense palpation of the large intestine meridian. The benefit of a comprehensive acupuncture treatment protocol in this condition should be subject to further trials.

  15. Autoradiographic quantification of vasoactive intestinal peptide binding sites in sections from human blood mononuclear cell pellets

    Energy Technology Data Exchange (ETDEWEB)

    Gutkind, J.S.; Kurihara, M.; Castren, E.; Saavedra, J.M.

    1988-09-01

    Quantitative autoradiographic methods were utilized to characterize specific, high-affinity vasoactive intestinal peptide binding sites (Kd = 310 +/- 60 pmol/L; Bmax = 93 +/- 11 fmol/mg protein) in frozen sections obtained from a mononuclear cell pellet derived from 20 ml of human blood. The method is at least one order of magnitude more sensitive than conventional membrane binding techniques, and it has the potential for wide applications in studies of neuropeptide, biogenic amine, and drug binding in clinical samples.

  16. Autoradiographic quantification of vasoactive intestinal peptide binding sites in sections from human blood mononuclear cell pellets

    International Nuclear Information System (INIS)

    Gutkind, J.S.; Kurihara, M.; Castren, E.; Saavedra, J.M.

    1988-01-01

    Quantitative autoradiographic methods were utilized to characterize specific, high-affinity vasoactive intestinal peptide binding sites (Kd = 310 +/- 60 pmol/L; Bmax = 93 +/- 11 fmol/mg protein) in frozen sections obtained from a mononuclear cell pellet derived from 20 ml of human blood. The method is at least one order of magnitude more sensitive than conventional membrane binding techniques, and it has the potential for wide applications in studies of neuropeptide, biogenic amine, and drug binding in clinical samples

  17. 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. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Increased Chromogranin A Cell Density in the Large Intestine of Patients with Irritable Bowel Syndrome after Receiving Dietary Guidance

    Directory of Open Access Journals (Sweden)

    Tarek Mazzawi

    2015-01-01

    Full Text Available The large intestine contains five types of endocrine cells that regulate its functions by sensing its luminal contents and releasing specific hormones. Chromogranin A (CgA is a common marker for the gastrointestinal endocrine cells, and it is abnormal in irritable bowel syndrome (IBS patients. Most IBS patients relate their symptoms to certain food elements. The present study investigated the effect of dietary guidance on the total endocrine cells of the large intestine as detected by CgA in 13 IBS patients. Thirteen control subjects were also included. Each patient received three sessions of dietary guidance. Colonoscopies were performed on controls and patients (at baseline and at 3–9 months after receiving guidance. Biopsy samples from the colon and rectum were immunostained for CgA and quantified by computerized image analysis. The densities of CgA cells in the total colon (mean ± SEM among the controls and the IBS patients before and after receiving dietary guidance were 83.3±10.1, 38.6±3.7, and 64.7±4.2 cells/mm2, respectively (P=0.0004, and were unchanged in the rectum. In conclusion, the increase in CgA cell density after receiving dietary guidance may reflect a change in the densities of the large intestinal endocrine cells causing an improvement in the IBS symptoms.

  19. Primary human polarized small intestinal epithelial barriers respond differently to a hazardous and an innocuous protein.

    Science.gov (United States)

    Eaton, A D; Zimmermann, C; Delaney, B; Hurley, B P

    2017-08-01

    An experimental platform employing human derived intestinal epithelial cell (IEC) line monolayers grown on permeable Transwell ® filters was previously investigated to differentiate between hazardous and innocuous proteins. This approach was effective at distinguishing these types of proteins and perturbation of monolayer integrity, particularly transepithelial electrical resistance (TEER), was the most sensitive indicator. In the current report, in vitro indicators of monolayer integrity, cytotoxicity, and inflammation were evaluated using primary (non-transformed) human polarized small intestinal epithelial barriers cultured on Transwell ® filters to compare effects of a hazardous protein (Clostridium difficile Toxin A [ToxA]) and an innocuous protein (bovine serum albumin [BSA]). ToxA exerted a reproducible decrease on barrier integrity at doses comparable to those producing effects observed from cell line-derived IEC monolayers, with TEER being the most sensitive indicator. In contrast, BSA, tested at concentrations substantially higher than ToxA, did not cause changes in any of the tested variables. These results demonstrate a similarity in response to certain proteins between cell line-derived polarized IEC models and a primary human polarized small intestinal epithelial barrier model, thereby reinforcing the potential usefulness of cell line-derived polarized IECs as a valid experimental platform to differentiate between hazardous and non-hazardous proteins. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. A role for the epidermal growth factor receptor signaling in development of intestinal serrated polyps in mice and humans.

    Science.gov (United States)

    Bongers, Gerold; Muniz, Luciana R; Pacer, Michelle E; Iuga, Alina C; Thirunarayanan, Nanthakumar; Slinger, Erik; Smit, Martine J; Reddy, E Premkumar; Mayer, Lloyd; Furtado, Glaucia C; Harpaz, Noam; Lira, Sergio A

    2012-09-01

    Epithelial cancers can be initiated by activating mutations in components of the mitogen-activated protein kinase signaling pathway such as v-raf murine sarcoma viral oncogene homolog B1 (BRAF), v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), or epidermal growth factor receptor (EGFR). Human intestinal serrated polyps are a heterogeneous group of benign lesions, but some progress to colorectal cancer. Tumors that arise from these polyps frequently contain activating mutations in BRAF or KRAS, but little is known about the role of EGFR activation in their development. Polyp samples were obtained from adults during screening colonoscopies at Mount Sinai Hospital in New York. We measured levels of EGFR protein and phosphorylation in human serrated polyps by immunohistochemical and immunoblot analyses. We generated transgenic mice that express the ligand for EGFR, Heparin-binding EGF-like growth factor (HB-EGF), in the intestine. EGFR and the extracellular-regulated kinases (ERK)1/2 were phosphorylated in serrated areas of human hyperplastic polyps (HPPs), sessile serrated adenomas, and traditional serrated adenomas. EGFR and ERK1/2 were phosphorylated in the absence of KRAS or BRAF activating mutations in a subset of HPP. Transgenic expression of the EGFR ligand HB-EGF in the intestines of mice promoted development of small cecal serrated polyps. Mice that expressed a combination of HB-EGF and US28 (a constitutively active, G-protein-coupled receptor that increases processing of HB-EGF from the membrane) rapidly developed large cecal serrated polyps. These polyps were similar to HPPs and had increased phosphorylation of EGFR and ERK1/2 within the serrated epithelium. Administration of pharmacologic inhibitors of EGFR or MAPK to these transgenic mice significantly reduced polyp development. Activation of EGFR signaling in the intestine of mice promotes development of serrated polyps. EGFR signaling also is activated in human HPPs, sessile serrated adenomas

  1. Comparative analysis of pyrosequencing and a phylogenetic microarray for exploring microbial community structures in the human distal intestine

    NARCIS (Netherlands)

    Claesson, M.J.; O'Sullivan, O.; Wang, Q.; Nikkilä, J.; Marchesi, J.R.; Smidt, H.; Vos, de W.M.; Ross, R.P.; O'Toole, P.W.

    2009-01-01

    BACKGROUND: Variations in the composition of the human intestinal microbiota are linked to diverse health conditions. High-throughput molecular technologies have recently elucidated microbial community structure at much higher resolution than was previously possible. Here we compare two such

  2. The effect of storage time of human red cells on intestinal microcirculatory oxygenation in a rat isovolemic exchange model

    NARCIS (Netherlands)

    Raat, N. J.; Verhoeven, A. J.; Mik, E. G.; Gouwerok, C. W.; Verhaar, R.; Goedhart, P. T.; de Korte, D.; Ince, C.

    2005-01-01

    Objective: To determine whether the storage time of human leukodepleted red blood cell concentrates compromises intestinal microvascular oxygen concentration oxygen (muPo(2)) during isovolemic exchange transfusion at low hematocrit. Design: Prospective, randomized, controlled study. Setting:

  3. A probiotic strain of L. acidophilus reduces DMH-induced large intestinal tumors in male Sprague-Dawley rats.

    Science.gov (United States)

    McIntosh, G H; Royle, P J; Playne, M J

    1999-01-01

    Probiotic bacteria strains were examined for their influence on 1,2-dimethylhydrazine (DMH)-induced intestinal tumors in 100 male Sprague-Dawley rats. Lactobacillus acidophilus (Delvo Pro LA-1), Lactobacillus rhamnosus (GG), Bifidobacterium animalis (CSCC1941), and Streptococcus thermophilus (DD145) strains were examined for their influence when added as freeze-dried bacteria to an experimental diet based on a high-fat semipurified (AIN-93) rodent diet. Four bacterial treatments were compared: L. acidophilus, L. acidophilus + B. animalis, L. rhamnosus, and S. thermophilus, the bacteria being added daily at 1% freeze-dried weight (10(10) colony-forming units/g) to the diet. Trends were observed in the incidence of rats with large intestinal tumors for three treatments: 25% lower than control for L. acidophilus, 20% lower for L. acidophilus + B. animalis and L. rhamnosus treatments, and 10% lower for S. thermophilus. Large intestinal tumor burden was significantly lower for treated rats with L. acidophilus than for the control group (10 and 3 tumors/treatment group, respectively, p = 0.05). Large intestinal tumor mass index was also lower for the L. acidophilus treatment than for control (1.70 and 0.10, respectively, p L. acidophilus, no adenocarcinomas were present in the colons. Pulsed-field gel electrophoresis of bacterial chromosomal DNA fragments was used to differentiate introduced (exogenous) bacterial strains from indigenous bacteria of the same genera present in the feces. Survival during gut passage and displacement of indigenous lactobacilli occurred with introduced L. acidophilus and L. rhamnosus GG during the probiotic treatment period. However, introduced strains of B. animalis and S. thermophilus were not able to be isolated from feces. It is concluded that this strain of L. acidophilus supplied as freeze-dried bacteria in the diet was protective, as seen by a small but significant inhibition of tumors within the rat colon.

  4. Distribution and characterisation of CCK containing enteroendocrine cells of the mouse small and large intestine

    DEFF Research Database (Denmark)

    Fakhry, Josiane; Wang, Joyce; Martins, Patricia

    2017-01-01

    but positive cells were rare in the rectum. Immunoreactive EEC were as common in the caecum and proximal colon as they were in the duodenum and jejunum. CCK gene transcripts were found in the mucosa throughout the intestine but mRNA for gastrin, a hormone that can bind some anti-CCK antibodies, was only found...

  5. Azoreductase activity of anaerobic bacteria isolated from human intestinal microflora.

    Science.gov (United States)

    Rafii, F; Franklin, W; Cerniglia, C E

    1990-01-01

    A plate assay was developed for the detection of anaerobic bacteria that produce azoreductases. With this plate assay, 10 strains of anaerobic bacteria capable of reducing azo dyes were isolated from human feces and identified as Eubacterium hadrum (2 strains), Eubacterium spp. (2 species), Clostridium clostridiiforme, a Butyrivibrio sp., a Bacteroides sp., Clostridium paraputrificum, Clostridium nexile, and a Clostridium sp. The average rate of reduction of Direct Blue 15 dye (a dimethoxybenzidine-based dye) in these strains ranged from 16 to 135 nmol of dye per min per mg of protein. The enzymes were inactivated by oxygen. In seven isolates, a flavin compound (riboflavin, flavin adenine dinucleotide, or flavin mononucleotide) was required for azoreductase activity. In the other three isolates and in Clostridium perfringens, no added flavin was required for activity. Nondenaturing polyacrylamide gel electrophoresis showed that each bacterium expressed only one azoreductase isozyme. At least three types of azoreductase enzyme were produced by the different isolates. All of the azoreductases were produced constitutively and released extracellularly. Images PMID:2202258

  6. Azoreductase activity of anaerobic bacteria isolated from human intestinal microflora.

    Science.gov (United States)

    Rafii, F; Franklin, W; Cerniglia, C E

    1990-07-01

    A plate assay was developed for the detection of anaerobic bacteria that produce azoreductases. With this plate assay, 10 strains of anaerobic bacteria capable of reducing azo dyes were isolated from human feces and identified as Eubacterium hadrum (2 strains), Eubacterium spp. (2 species), Clostridium clostridiiforme, a Butyrivibrio sp., a Bacteroides sp., Clostridium paraputrificum, Clostridium nexile, and a Clostridium sp. The average rate of reduction of Direct Blue 15 dye (a dimethoxybenzidine-based dye) in these strains ranged from 16 to 135 nmol of dye per min per mg of protein. The enzymes were inactivated by oxygen. In seven isolates, a flavin compound (riboflavin, flavin adenine dinucleotide, or flavin mononucleotide) was required for azoreductase activity. In the other three isolates and in Clostridium perfringens, no added flavin was required for activity. Nondenaturing polyacrylamide gel electrophoresis showed that each bacterium expressed only one azoreductase isozyme. At least three types of azoreductase enzyme were produced by the different isolates. All of the azoreductases were produced constitutively and released extracellularly.

  7. Long chain poly-unsaturated fatty acids attenuate the IL-1?-induced pro-inflammatory response in human fetal intestinal epithelial cells

    OpenAIRE

    Wijendran, Vasuki; Brenna, JT; Wang, Dong Hao; Zhu, Weishu; Meng, Di; Ganguli, Kriston; Kothapalli, Kumar SD; Requena, Pilar; Innis, Sheila; Walker, WA

    2015-01-01

    Background Evidence suggests that excessive inflammation of the immature intestine may predispose premature infants to necrotizing enterocolitis (NEC). We investigated the anti-inflammatory effects of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and arachidonic acid (ARA) in human fetal and adult intestinal epithelial cells (IEC) in primary culture. Methods Human fetal IEC in culture were derived from a healthy fetal small intestine (H4) or resected small intestine of a neonate wit...

  8. Studies of the nitrogen metabolism in the large intestine of ruminants. 5

    International Nuclear Information System (INIS)

    Bergner, H.; Goetz, K.P.; Simon, O.

    1989-01-01

    Six heifers of a live weight of 215, 227 and 238 kg (experiment 1) and 220, 227 and 233 kg resp. (experiment 2) were supplied with ileocaecal re-entrance cannulae, jugular venal catheters and bladder catheters. The ration consisted of 4 kg maize silage and 4 kg wheat straw pellets per animal and day. Up to 3.5 kg of the straw pellets consisting of 73% wheat straw, 10% barley, 12% molasses, NPN salts and a mineral mixture were consumed per animal and day. In a preliminary period 50% of the digesta flow was collected over 12 h/d on 5 consecutive days and stored in a deep-freeze. During the main trial the re-entrance cannula was disrupted and the flowing digesta was quantitatively collected at the end of the ileum; previously collected digesta was supplemented with 15 N-urea and every hour over 24 h infused into the caecal part of the re-entrance cannula. Between the 24th and 30th hours the digesta was infused without 15 N-urea supplement. In trial 2 the digesta was also supplemented with partly hydrolysed straw meal between the 1st and 30th hours. The 15 N labelling decrease of the plasma urea N shows that the half life is 7.9 h in trial 1 and 7.0 h in trial 2. The NH 3 nitrogen in faeces was distinctly higher labelled in trial 2 after the supplement of straw meal than in trial 1. The total N in faeces was also twice as highly labelled as in trial 1. Atom-% 15 N' in urine was significantly higher in trial 2 than in trial 1 between the 6th and 16th hours after the beginning of 15 N-urea supplementation. In the decrease curve of atom-% 15 N' (after the 26th hour of trial) the values in trial 1 were generally higher than in trial 2. The higher bacterial protein synthesis in the large intestine in trial 2 had the effect that 13.6% of the supplemented 15 N' were excreted in faeces by the 30th hour of trial, in contrast to this only 4.7% in group 1. (author)

  9. The Ussing Chamber Assay to Study Drug Metabolism and Transport in the Human Intestine.

    Science.gov (United States)

    Kisser, Beatrice; Mangelsen, Eva; Wingolf, Caroline; Partecke, Lars Ivo; Heidecke, Claus-Dieter; Tannergren, Christer; Oswald, Stefan; Keiser, Markus

    2017-06-22

    The Ussing chamber is an old but still powerful technique originally designed to study the vectorial transport of ions through frog skin. This technique is also used to investigate the transport of chemical agents through the intestinal barrier as well as drug metabolism in enterocytes, both of which are key determinants for the bioavailability of orally administered drugs. More contemporary model systems, such as Caco-2 cell monolayers or stably transfected cells, are more limited in their use compared to the Ussing chamber because of differences in expression rates of transporter proteins and/or metabolizing enzymes. While there are limitations to the Ussing chamber assay, the use of human intestinal tissue remains the best laboratory test for characterizing the transport and metabolism of compounds following oral administration. Detailed in this unit is a step-by-step protocol for preparing human intestinal tissue, for designing Ussing chamber experiments, and for analyzing and interpreting the findings. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

  10. Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco-2) cells

    International Nuclear Information System (INIS)

    Artursson, P.; Karlsson, J.

    1991-01-01

    Monolayers of a well differentiated human intestinal epithelial cell line, Caco-2, were used as a model to study passive drug absorption across the intestinal epithelium. Absorption rate constants (expressed as apparent permeability coefficients) were determined for 20 drugs and peptides with different structural properties. The permeability coefficients ranged from approximately 5 x 10 - 8 to 5 x 10 - 5 cm/s. A good correlation was obtained between data on oral absorption in humans and the results in the Caco-2 model. Drugs that are completely absorbed in humans had permeability coefficients greater than 1 x 10 - 6 cm/s. Drugs that are absorbed to greater than 1% but less than 100% had permeability coefficients of 0.1-1.0 x 10 - 6 cm/s while drugs and peptides that are absorbed to less than 1% had permeability coefficients of less than or equal to 1 x 10 - 7 cm/s. The results indicate that Caco-2 monolayers can be used as a model for studies on intestinal drug absorption

  11. Exploring Human Cognition Using Large Image Databases.

    Science.gov (United States)

    Griffiths, Thomas L; Abbott, Joshua T; Hsu, Anne S

    2016-07-01

    Most cognitive psychology experiments evaluate models of human cognition using a relatively small, well-controlled set of stimuli. This approach stands in contrast to current work in neuroscience, perception, and computer vision, which have begun to focus on using large databases of natural images. We argue that natural images provide a powerful tool for characterizing the statistical environment in which people operate, for better evaluating psychological theories, and for bringing the insights of cognitive science closer to real applications. We discuss how some of the challenges of using natural images as stimuli in experiments can be addressed through increased sample sizes, using representations from computer vision, and developing new experimental methods. Finally, we illustrate these points by summarizing recent work using large image databases to explore questions about human cognition in four different domains: modeling subjective randomness, defining a quantitative measure of representativeness, identifying prior knowledge used in word learning, and determining the structure of natural categories. Copyright © 2016 Cognitive Science Society, Inc.

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

    International Nuclear Information System (INIS)

    Wu, S.G.; Miyamoto, T.

    1990-01-01

    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

  13. 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...

  14. Optimization of micro-fabricated porous membranes for intestinal epithelial cell culture and in vitro modeling of the human intestinal barrier

    Science.gov (United States)

    Nair Gourikutty Sajay, Bhuvanendran; Yin, Chiam Su; Ramadan, Qasem

    2017-12-01

    In vitro modeling of organs could provide a controlled platform for studying physiological events and has great potential in the field of pharmaceutical development. Here, we describe the characterization of in vitro modeling of the human intestinal barrier mimicked using silicon porous membranes as a substrate. To mimic an intestinal in vivo setup as closely as possible, a porous substrate is required in a dynamic environment for the cells to grow rather than a static setup with an impermeable surface such as a petri dish. In this study, we focus on the detailed characterization of Caco-2 cells cultured on a silicon membrane with different pore sizes as well as the effect of dynamic fluid flow on the model. The porous silicon membrane together with continuous perfusion of liquid applying shear stress on the cells enhances the differentiation of polarized cells by providing access to the both their basal and apical surfaces. Membranes with pore sizes of 0.5-3 µm were used and a shear stress of ~0.03 dyne cm-2 was created by applying a low flow rate of 20 nl s-1. By providing these optimized conditions, cells were able to differentiate with columnar morphology, which developed microvilli structures on their apical side and tight junctions between adjacent cells like those in a healthy human intestinal barrier. In this setup, it is possible to study the important cellular functions of the intestine such as transport, absorption and secretion, and thus this model has great potential in drug screening.

  15. 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.

  16. 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

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

  17. Intestinal parasites isolated in a large teaching hospital, Italy, 1 May 2006 to 31 December 2008.

    Science.gov (United States)

    Masucci, L; Graffeo, R; Bani, S; Bugli, F; Boccia, S; Nicolotti, N; Fiori, B; Fadda, G; Spanu, T

    2011-06-16

    Intestinal parasites account for the majority of parasitic diseases, particularly in endemic areas. Most are transmitted via contaminated food. Because of increased immigration and travel, enteric parasitoses are now distributed worldwide. Between May 2006 and December 2008, we examined stool specimens from 5,351 patients (4,695 Italians, 656 non-Italians) for ova and parasites using microscopy, culture techniques, and molecular methods. Stools from 594 patients (11.1%) were contaminated and for all patients samples combined, a total of 700 intestinal parasites were counted. Ninety of the 594 infected patients had more than one parasite in their stools. Parasites causing intestinal disease occurred in 8.8% of patients. The prevalence was over twice as high among non-Italians (26.8% vs 8.9% in Italians, p003). Most isolates were pathogenic protozoa, including in decreasing order of frequency: Blastocystis hominis, Giardia intestinalis, Entamoeba histolytica, and Cyclospora cayetanensis. The latter two species tended to be more common in Italians, although not at significant level (3.6% (15/418) vs 1.7% (3/176) in non-Italians, OR: 2.15; 95%CI: 0.60–11.70, p=0.22). Helminthes were found in 28 patients, mainly non-Italians (5.7% (10/176) vs 4.3% (18/418), OR: 1.34; 95%CI: 0.54–3.13, p=0.47). Ascaris lumbricoides and Hymenolepis nana were the most common. Strongyloides stercoralis, Enterobius vermicularis, Taenia spp. and Trichuris trichiura were also found. Intestinal parasites are a serious problem in developing countries, but should not be underestimated in industrialised countries.

  18. Intestinal Parasitic Infections in Human Immunodeficiency Virus-Infected and Noninfected Persons in a High Human Immunodeficiency Virus Prevalence Region of Cameroon.

    Science.gov (United States)

    Nkenfou, Céline Nguefeu; Tchameni, Sandrine Mboula; Nkenfou, Carine Nguefeu; Djataou, Patrice; Simo, Ulrich Florian; Nkoum, Alexandre Benjamin; Estrin, William

    2017-09-01

    The problem of intestinal parasitic infection in human immunodeficiency virus (HIV)-infected people requires careful consideration in the developing world where poor nutrition is associated with poor hygiene and several coinfecting diseases. Studies have addressed this issue in Cameroon, especially in the low HIV prevalence area. The current study was conducted to determine the prevalence of intestinal parasitosis in people living with HIV (PLHIV) in Adamaoua and to identify associated risk factors. Stool and blood specimens from study participants were screened for intestinal parasites and anti-HIV antibodies, respectively. Of 235 participants, 68 (28.9%) were HIV positive, 38 of them on antiretroviral treatment (ART). The overall prevalence of intestinal parasites was 32.3%. Of 68 PLHIV, 32.3% (22/68) were infected with intestinal parasites, compared with 32.3% (54/167) of the HIV-negative patients. Univariate analysis showed no difference between the prevalence of intestinal parasites among PLHIV and HIV-negative patients ( P = 0.69). ART was not associated with the prevalence of intestinal parasites. Multivariate analysis showed that the quality of water and the personal hygiene were the major risk factors associated to intestinal parasitosis. The level of education was associated with HIV serostatus: the higher the level of education, the lower the risk of being infected with HIV ( P = 0.00). PLHIV and the general population should be screened routinely for intestinal parasites and treated if infected.

  19. Functional modulation of human intestinal epithelial cell responses by Bifidobacterium infantis and Lactobacillus salivarius

    Science.gov (United States)

    O'Hara, Ann M; O'Regan, Padraig; Fanning, Áine; O'Mahony, Caitlin; MacSharry, John; Lyons, Anne; Bienenstock, John; O'Mahony, Liam; Shanahan, Fergus

    2006-01-01

    Intestinal epithelial cells (IECs) and dendritic cells (DCs) play a pivotal role in antigen sampling and the maintenance of gut homeostasis. However, the interaction of commensal bacteria with the intestinal surface remains incompletely understood. Here we investigated immune cell responses to commensal and pathogenic bacteria. HT-29 human IECs were incubated with Bifidobacterium infantis 35624, Lactobacillus salivarius UCC118 or Salmonella typhimurium UK1 for varying times, or were pretreated with a probiotic for 2 hr prior to stimulation with S. typhimurium or flagellin. Gene arrays were used to examine inflammatory gene expression. Nuclear factor (NF)-κB activation, interleukin (IL)-8 secretion, pathogen adherence to IECs, and mucin-3 (MUC3) and E-cadherin gene expression were assayed by TransAM assay, enzyme-linked immunosorbent assay (ELISA), fluorescence, and real-time reverse transcriptase–polymerase chain reaction (RT-PCR), respectively. IL-10 and tumour necrosis factor (TNF)-α secretion by bacteria-treated peripheral blood-derived DCs were measured using ELISA. S. typhimurium increased expression of 36 of the 847 immune-related genes assayed, including NF-κB and IL-8. The commensal bacteria did not alter expression levels of any of the 847 genes. However, B. infantis and L. salivarius attenuated both IL-8 secretion at baseline and S. typhimurium-induced pro-inflammatory responses. B. infantis also limited flagellin-induced IL-8 protein secretion. The commensal bacteria did not increase MUC3 or E-cadherin expression, or interfere with pathogen binding to HT-29 cells, but they did stimulate IL-10 and TNF-α secretion by DCs. The data demonstrate that, although the intestinal epithelium is immunologically quiescent when it encounters B. infantis or L. salivarius, these commensal bacteria exert immunomodulatory effects on intestinal immune cells that mediate host responses to flagellin and enteric pathogens. PMID:16771855

  20. 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 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.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.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.

  1. Morphologic observation of mucosa-associated lymphoid tissue in the large intestine of Bactrian camels (Camelus bactrianus).

    Science.gov (United States)

    ZhaXi, Yingpai; Wang, Wenhui; Zhang, Wangdong; Gao, Qiang; Guo, Minggang; Jia, Shuai

    2014-07-01

    The structure and distribution of the mucosa-associated lymphoid tissue (MALT) throughout the large intestine of 10 Bactrian camels were comparatively studied by anatomical and histological methods. The results showed that Peyer's patches (PPs) were mainly located on the mucosal surfaces of the entire ileocecal orifice, the beginning of the cecum and the first third of the colon. The shape of PPs gradually changed from "scrotiform" to "faviform" along the large intestine with the scrotiform PP as the major type in the ileocecal orifice. The distribution density also gradually decreased from the ileocecal orifice to the colon. The histological observations further revealed that the MALT in the form of PPs or isolated lymphoid follicles (ILF) and lamina propria lymphocytes was mainly present in the lamina propria and submucosa from the entire ileocecal orifice, where the muscularis mucosa is usually incomplete, to the colonic forepart. In addition, lymphoid tissue was much more abundant in the lamina propria and submucosa of the ileocecal orifice as compared to the cecum and colon. Statistically, the MALT of the ileocecal orifice contained a higher number of lymphoid follicles (37.7/10 mm(2) ) than that of the cecum, colon, or rectum (P lymphoid follicles were clearly visible. Together, our data suggest that the ileocecal orifice constitutes the main inductive site for the mucosal immunity in the large intestine of the Bactrian camel; and that scrotiform PPs are likely to the result of long-term adaptation of the Bactrian camel to the harsh living environment. © 2014 Wiley Periodicals, Inc.

  2. Gut bacteria in health and disease: a survey on the interface between intestinal microbiology and colorectal cancer

    NARCIS (Netherlands)

    Boleij, A.; Tjalsma, H.

    2012-01-01

    A healthy human body contains at least tenfold more bacterial cells than human cells and the most abundant and diverse microbial community resides in the intestinal tract. Intestinal health is not only maintained by the human intestine itself and by dietary factors, but is also largely supported by

  3. Impact of enrofloxacin on the human intestinal microbiota revealed by comparative molecular analysis.

    Science.gov (United States)

    Kim, Bong-Soo; Kim, Jong Nam; Yoon, Seok-Hwan; Chun, Jongsik; Cerniglia, Carl E

    2012-06-01

    The indigenous human intestinal microbiota could be disrupted by residues of antibiotics in foods as well as therapeutically administered antibiotics to humans. These disruptions may lead to adverse health outcomes. To observe the possible impact of residues of antibiotics at concentrations below therapeutic levels on human intestinal microbiota, we performed studies using in vitro cultures of fecal suspensions from three individuals with 10 different concentrations (0, 0.1, 0.5, 1, 5, 10, 15, 25, 50 and 150 μg/ml) of the fluoroquinolone, enrofloxacin. The bacterial communities of the control and enrofloxacin dosed fecal samples were analyzed by denaturing gradient gel electrophoresis (DGGE) and pyrosequencing. In addition, changes of functional gene expression were analyzed by a pyrosequencing-based random whole-community mRNA sequencing method. Although each individual had a unique microbial composition, the communities of all individuals were affected by enrofloxacin. The proportions of two phyla, namely, Bacteroidetes and Proteobacteria, were significantly reduced with increasing concentrations of enrofloxacin exposure, while the proportion of Firmicutes increased. Principal Coordinate Analysis (PCoA) using the Fast UniFrac indicated that the community structures of intestinal microbiota were shifted by enrofloxacin. Most of the mRNA transcripts and the anti-microbial drug resistance genes increased with increasing concentrations of enrofloxacin. 16S rRNA gene pyrosequencing of control and enrofloxacin treated fecal suspensions provided valuable information of affected bacterial taxa down to the species level, and the community transcriptomic analyses using mRNA revealed the functional gene expression responses of the changed bacterial communities by enrofloxacin. Published by Elsevier Ltd.

  4. In vitro and in vivo imaging and tracking of intestinal organoids from human induced pluripotent stem cells.

    Science.gov (United States)

    Jung, Kwang Bo; Lee, Hana; Son, Ye Seul; Lee, Ji Hye; Cho, Hyun-Soo; Lee, Mi-Ok; Oh, Jung-Hwa; Lee, Jaemin; Kim, Seokho; Jung, Cho-Rok; Kim, Janghwan; Son, Mi-Young

    2018-01-01

    Human intestinal organoids (hIOs) derived from human pluripotent stem cells (hPSCs) have immense potential as a source of intestines. Therefore, an efficient system is needed for visualizing the stage of intestinal differentiation and further identifying hIOs derived from hPSCs. Here, 2 fluorescent biosensors were developed based on human induced pluripotent stem cell (hiPSC) lines that stably expressed fluorescent reporters driven by intestine-specific gene promoters Krüppel-like factor 5 monomeric Cherry (KLF5 mCherry ) and intestine-specific homeobox enhanced green fluorescence protein (ISX eGFP ). Then hIOs were efficiently induced from those transgenic hiPSC lines in which mCherry- or eGFP-expressing cells, which appeared during differentiation, could be identified in intact living cells in real time. Reporter gene expression had no adverse effects on differentiation into hIOs and proliferation. Using our reporter system to screen for hIO differentiation factors, we identified DMH1 as an efficient substitute for Noggin. Transplanted hIOs under the kidney capsule were tracked with fluorescence imaging (FLI) and confirmed histologically. After orthotopic transplantation, the localization of the hIOs in the small intestine could be accurately visualized using FLI. Our study establishes a selective system for monitoring the in vitro differentiation and for tracking the in vivo localization of hIOs and contributes to further improvement of cell-based therapies and preclinical screenings in the intestinal field.-Jung, K. B., Lee, H., Son, Y. S., Lee, J. H., Cho, H.-S., Lee, M.-O., Oh, J.-H., Lee, J., Kim, S., Jung, C.-R., Kim, J., Son, M.-Y. In vitro and in vivo imaging and tracking of intestinal organoids from human induced pluripotent stem cells. © FASEB.

  5. Conformational restrictions in ligand binding to the human intestinal di-/tripeptide transporter

    DEFF Research Database (Denmark)

    Våbenø, Jon; Nielsen, Carsten Uhd; Steffansen, Bente

    2005-01-01

    The aim of the present study was to develop a computational method aiding the design of dipeptidomimetic pro-moieties targeting the human intestinal di-/tripeptide transporter hPEPT1. First, the conformation in which substrates bind to hPEPT1 (the bioactive conformation) was identified...... to change the peptide backbone conformation (DeltaE(bbone)) from the global energy minimum conformation to the identified bioactive conformation was calculated for 20 hPEPT1 targeted model prodrugs with known K(i) values. Quantitatively, an inverse linear relationship (r(2)=0.81, q(2)=0.80) was obtained...

  6. Smoking cessation induces profound changes in the composition of the intestinal microbiota in humans.

    Directory of Open Access Journals (Sweden)

    Luc Biedermann

    Full Text Available BACKGROUND: The human intestinal microbiota is a crucial factor in the pathogenesis of various diseases, such as metabolic syndrome or inflammatory bowel disease (IBD. Yet, knowledge about the role of environmental factors such as smoking (which is known to influence theses aforementioned disease states on the complex microbial composition is sparse. We aimed to investigate the role of smoking cessation on intestinal microbial composition in 10 healthy smoking subjects undergoing controlled smoking cessation. METHODS: During the observational period of 9 weeks repetitive stool samples were collected. Based on abundance of 16S rRNA genes bacterial composition was analysed and compared to 10 control subjects (5 continuing smokers and 5 non-smokers by means of Terminal Restriction Fragment Length Polymorphism analysis and high-throughput sequencing. RESULTS: Profound shifts in the microbial composition after smoking cessation were observed with an increase of Firmicutes and Actinobacteria and a lower proportion of Bacteroidetes and Proteobacteria on the phylum level. In addition, after smoking cessation there was an increase in microbial diversity. CONCLUSIONS: These results indicate that smoking is an environmental factor modulating the composition of human gut microbiota. The observed changes after smoking cessation revealed to be similar to the previously reported differences in obese compared to lean humans and mice respectively, suggesting a potential pathogenetic link between weight gain and smoking cessation. In addition they give rise to a potential association of smoking status and the course of IBD.

  7. Culture media from hypoxia conditioned endothelial cells protect human intestinal cells from hypoxia/reoxygenation injury.

    Science.gov (United States)

    Hummitzsch, Lars; Zitta, Karina; Bein, Berthold; Steinfath, Markus; Albrecht, Martin

    2014-03-10

    Remote ischemic preconditioning (RIPC) is a phenomenon, whereby short episodes of non-lethal ischemia to an organ or tissue exert protection against ischemia/reperfusion injury in a distant organ. However, there is still an apparent lack of knowledge concerning the RIPC-mediated mechanisms within the target organ and the released factors. Here we established a human cell culture model to investigate cellular and molecular effects of RIPC and to identify factors responsible for RIPC-mediated intestinal protection. Human umbilical vein cells (HUVEC) were exposed to repeated episodes of hypoxia (3 × 15 min) and conditioned culture media (CM) were collected after 24h. Human intestinal cells (CaCo-2) were cultured with or without CM and subjected to 90 min of hypoxia/reoxygenation injury. Reverse transcription-polymerase chain reaction, Western blotting, gelatin zymography, hydrogen peroxide measurements and lactate dehydrogenase (LDH) assays were performed. In HUVEC cultures hypoxic conditioning did not influence the profile of secreted proteins but led to an increased gelatinase activity (Pcultures 90 min of hypoxia/reoxygenation resulted in morphological signs of cell damage, increased LDH levels (Pculture model may help to unravel RIPC-mediated cellular events and to identify molecules released by RIPC. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Plasma endocannabinoid levels in lean, overweight and obese humans: relationships with intestinal permeability markers, inflammation and incretin secretion.

    Science.gov (United States)

    Little, Tanya J; Cvijanovic, Nada; DiPatrizio, Nicholas V; Argueta, Donovan A; Rayner, Christopher K; Feinle-Bisset, Christine; Young, Richard L

    2018-02-13

    Intestinal production of endocannabinoid and oleoylethanolamide (OEA) is impaired in high-fat diet/obese rodents, leading to reduced satiety. Such diets also alter the intestinal microbiome in association with enhanced intestinal permeability and inflammation, however little is known of these effects in humans. This study aimed to: (i) evaluate effects of lipid on plasma anandamide (AEA), 2-arachidonyl-sn-glycerol (2-AG) and OEA in humans, and (ii) examine relationships with intestinal permeability, inflammation markers and incretin hormone secretion. 20 lean, 18 overweight and 19 obese participants underwent intraduodenal Intralipid® infusion (2 kcal/min) with collection of endoscopic duodenal biopsies and blood. Plasma AEA, 2-AG, and OEA (HPLC/tandem mass spectrometry), tumour necrosis factor-α (TNF-α), glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) (multiplex), and duodenal expression of occludin, zona-occludin-1 (ZO-1), intestinal-alkaline-phosphatase (IAP), and toll-like receptor-4 (TLR4) (RT-PCR), were assessed. Fasting plasma AEA was increased in obese, compared with lean and overweight (Plean (Plean and overweight. The relationships between plasma AEA with duodenal ZO-1 and IAP, and GIP, suggest that altered endocannabinoid signalling may contribute to changes in intestinal permeability, inflammation and incretin release in human obesity.

  9. Staphylococcus aureus induces IL-8 expression through its lipoproteins in the human intestinal epithelial cell, Caco-2.

    Science.gov (United States)

    Kang, Seok-Seong; Noh, Su Young; Park, Ok-Jin; Yun, Cheol-Heui; Han, Seung Hyun

    2015-09-01

    Staphylococcus aureus can cause the intestinal inflammatory diseases. However, little is known about the molecular mechanism of S. aureus infection in the intestine. In the present study, we investigated whether S. aureus could stimulate human intestinal epithelial cells triggering inflammation. When the human intestinal epithelial cell-line, Caco-2, and the primary colon cells were stimulated with ethanol-inactivated S. aureus, IL-8 expression was induced in a dose-dependent manner. The inactivated S. aureus preferentially stimulated Toll-like receptor (TLR) 2 rather than TLR4. Lipoproteins, lipoteichoic acid (LTA), and peptidoglycan (PGN) are considered as potential TLR2 ligands of S. aureus. Interestingly, S aureus lipoproteins and Pam2CSK4 mimicking Gram-positive bacterial lipoproteins, but not LTA and PGN of S. aureus, significantly induced IL-8 expression in Caco-2 cells. Furthermore, lipoprotein-deficient S. aureus mutant strain failed to induce IL-8 production. Collectively, these results suggest that S. aureus stimulates the human intestinal epithelial cells to induce the chemokine IL-8 production through its lipoproteins, potentially contributing the development of intestinal inflammation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Metagenomic Characterization of the Human Intestinal Microbiota in Fecal Samples from STEC-Infected Patients

    Directory of Open Access Journals (Sweden)

    Federica Gigliucci

    2018-02-01

    Full Text Available The human intestinal microbiota is a homeostatic ecosystem with a remarkable impact on human health and the disruption of this equilibrium leads to an increased susceptibility to infection by numerous pathogens. In this study, we used shotgun metagenomic sequencing and two different bioinformatic approaches, based on mapping of the reads onto databases and on the reconstruction of putative draft genomes, to investigate possible changes in the composition of the intestinal microbiota in samples from patients with Shiga Toxin-producing E. coli (STEC infection compared to healthy and healed controls, collected during an outbreak caused by a STEC O26:H11 infection. Both the bioinformatic procedures used, produced similar result with a good resolution of the taxonomic profiles of the specimens. The stool samples collected from the STEC infected patients showed a lower abundance of the members of Bifidobacteriales and Clostridiales orders in comparison to controls where those microorganisms predominated. These differences seemed to correlate with the STEC infection although a flexion in the relative abundance of the Bifidobacterium genus, part of the Bifidobacteriales order, was observed also in samples from Crohn's disease patients, displaying a STEC-unrelated dysbiosis. The metagenomics also allowed to identify in the STEC positive samples, all the virulence traits present in the genomes of the STEC O26 that caused the outbreak as assessed through isolation of the epidemic strain and whole genome sequencing. The results shown represent a first evidence of the changes occurring in the intestinal microbiota of children in the course of STEC infection and indicate that metagenomics may be a promising tool for the culture-independent clinical diagnosis of the infection.

  11. Metagenomic Characterization of the Human Intestinal Microbiota in Fecal Samples from STEC-Infected Patients

    Science.gov (United States)

    Gigliucci, Federica; von Meijenfeldt, F. A. Bastiaan; Knijn, Arnold; Michelacci, Valeria; Scavia, Gaia; Minelli, Fabio; Dutilh, Bas E.; Ahmad, Hamideh M.; Raangs, Gerwin C.; Friedrich, Alex W.; Rossen, John W. A.; Morabito, Stefano

    2018-01-01

    The human intestinal microbiota is a homeostatic ecosystem with a remarkable impact on human health and the disruption of this equilibrium leads to an increased susceptibility to infection by numerous pathogens. In this study, we used shotgun metagenomic sequencing and two different bioinformatic approaches, based on mapping of the reads onto databases and on the reconstruction of putative draft genomes, to investigate possible changes in the composition of the intestinal microbiota in samples from patients with Shiga Toxin-producing E. coli (STEC) infection compared to healthy and healed controls, collected during an outbreak caused by a STEC O26:H11 infection. Both the bioinformatic procedures used, produced similar result with a good resolution of the taxonomic profiles of the specimens. The stool samples collected from the STEC infected patients showed a lower abundance of the members of Bifidobacteriales and Clostridiales orders in comparison to controls where those microorganisms predominated. These differences seemed to correlate with the STEC infection although a flexion in the relative abundance of the Bifidobacterium genus, part of the Bifidobacteriales order, was observed also in samples from Crohn's disease patients, displaying a STEC-unrelated dysbiosis. The metagenomics also allowed to identify in the STEC positive samples, all the virulence traits present in the genomes of the STEC O26 that caused the outbreak as assessed through isolation of the epidemic strain and whole genome sequencing. The results shown represent a first evidence of the changes occurring in the intestinal microbiota of children in the course of STEC infection and indicate that metagenomics may be a promising tool for the culture-independent clinical diagnosis of the infection. PMID:29468143

  12. Clinical picture and treatment of complications of lower part of large intestine resulting from radiotherapy for intra-pelvic cancer

    International Nuclear Information System (INIS)

    Ikeda, Yoshihito; Sunagawa, Keishin; Matsumura, Shigejiro; Watanabe, Kenji; Masaoka, Yoshio

    1976-01-01

    The authors described clinical pictures and those treatments of 40 patients with complications of the lower part of the large intestine resulting from radiotherapy for cancer of the uterus, ovarium or the penis. As the radiotherapy, 60 Co-telecobalt (6,000-16,000R) and 60 Co-needle (1,000-8,568 mch) intracavitary irradiation were used alone or in combination. Findings in the complications of the lower part of the large intestine were classified into Grade I (13 cases), II (14), III (14), and IV (4) according to Sherman. The prodromal symptoms of the complications appeared in 2-6 months following the irradiation in more than a half of the patients, and it appeared within a year in most of the patients. Most of the patients complained about melena, anemia, proctagra, tenesmus and diarrhea. In the cases of Grade III, the symptoms of ileus such as constipation, abdominal distention, and abdominal pain appeared. Internal treatment was given principally, and preternal anus was made when frequent blood transfusion was required. Fourteen cases of those in Grade I and II recovered within 1-3 years. The cases which received proctostomy, including those who had bleeding, stricture and fistulation, had favorable prognosis. This result suggested that the radiotherapy for intra-pelvic cancer should be controlled to prevent further development of the complications in the rectum beyond Grade I. (Serizawa, K.)

  13. 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 vi...

  14. Examinations on cases of surgery for radiation-induced disorders of large intestine

    Energy Technology Data Exchange (ETDEWEB)

    Shiba, Tadaaki [Toho Univ., Tokyo (Japan). School of Medicine

    1996-11-01

    Author`s experience of surgery for radiation colitis was examined and discussed on the primary disease, radiation dose, major symptoms, surgical techniques, results and post-operative complication. Patients were 1 male and 21 females of the average age of 59.5 y. The primary diseases were bladder cancer for the male and uterine cancer for the females. The radiation dose ranged from 35-120 Gy and was 63.4 Gy in a mean. The symptoms for surgery were 14 ileuses, 4 intestinal hemorrhages, 1 perforation and 3 burrows. Colostomy was performed for 18 cases; enterostomy, 2; anastomosis, 1; and enterectomy, 1, which resulted in improvement of symptoms in 5 cases, 0, 1 and 1, respectively. The author concluded that radiation colitis should be treated preventively. (K.H.)

  15. Cockroaches as carriers of human intestinal parasites in two localities in Ethiopia.

    Science.gov (United States)

    Kinfu, Addisu; Erko, Berhanu

    2008-11-01

    A study was undertaken to assess the role of cockroaches as potential carriers of human intestinal parasites in Addis Ababa and Ziway, Ethiopia. A total of 6480 cockroaches were trapped from the two localities from October 2006 to March 2007. All the cockroaches trapped in Addis Ababa (n=2240) and almost 50% (2100/4240) of those trapped in Ziway were identified as Blattella germanica. The rest of the cockroaches trapped in Ziway were identified as Periplaneta brunnea (24.52%), Pycnoscelus surinamensis (16.03%) and Supella longipalpa (9.90%). Microscopic examination of the external body washes of pooled cockroaches and individual gut contents revealed that cockroaches are carriers of Entamoeba coli and Entamoeba histolytica/dispar cysts as well as Enterobius vermicularis, Trichuris trichiura, Taenia spp. and Ascaris lumbricoides ova. Besides their role as a nuisance, the present study further confirms that cockroaches serve as carriers of human intestinal parasites. The possible association of cockroaches with allergic conditions such as asthma is also discussed. Hence, appropriate control measures should be taken particularly to make hotels and residential areas free of cockroaches as they represent a health risk.

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

    International Nuclear Information System (INIS)

    Zeller, P.; Clement, M.; Fessard, V.

    2011-01-01

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

  17. The effect of reducing numbers of Campylobacter in broiler intestines on human health risk

    DEFF Research Database (Denmark)

    Nauta, Maarten; Johannessen, Gro; Laureano Adame, Laura

    2016-01-01

    in concentration on the meat and a reduction in the human health risk of campylobacteriosis. In this study, two methods are presented and compared. The first is a linear regression model, based on count data from caecal contents and skin sample data, obtained after processing from the same flocks. Alternatively....... However, it is not possible to derive a generic rule that can be used to relate a reduction in concentration in broiler intestines into a reduction in human health risk. Regression models based on different data sets predict different relationships between bacterial count data from caeca and skins......, a previously published risk assessment model is used, that describes the dynamics of transfer and survival of Campylobacter during broiler processing at the slaughterhouse. Data from five European countries are used as inputs for the models. For both approaches the analyses show that a one to two log reduction...

  18. Influence of resistant starch on the SCFA production and cell counts of butyrate-producing Eubacterium spp. in the human intestine.

    Science.gov (United States)

    Schwiertz, A; Lehmann, U; Jacobasch, G; Blaut, M

    2002-01-01

    The genus Eubacterium, which is the second most common genus in the human intestine, includes several known butyrate producers. We hypothesized that Eubacterium species play a role in the intestinal butyrate production and are inducible by resistant starch. In a human pilot study species-specific and group-specific 16S rRNA-targeted, Cy3 (indocarbocyanine)-labelled oligonucleotide probes were used to quantify butyrogenic species of the genera Eubacterium, Clostridium and Ruminococcus. Following the intake of RS type III a significant increase in faecal butyrate but not in total SCFA was observed. However, increase in butyrate was not accompanied by a proliferation in the targeted bacteria. The tested Eubacterium species have the capacity to produce butyrate but do not appear to play a major role for butyric acid production in the human intestine. In view of the fact that the bacteria responsible for butyrate production are largely unknown, it is still difficult to devise a dietary intervention to stimulate butyrogenic bacteria in a targeted way.

  19. Dysfunctions at human intestinal barrier by water-borne protozoan parasites: lessons from cultured human fully differentiated colon cancer cell lines.

    Science.gov (United States)

    Liévin-Le Moal, Vanessa

    2013-06-01

    Some water-borne protozoan parasites induce diseases through their membrane-associated functional structures and virulence factors that hijack the host cellular molecules and signalling pathways leading to structural and functional lesions in the intestinal barrier. In this Microreview we analyse the insights on the mechanisms of pathogenesis of Entamoeba intestinalis, Giardia and Cryptosporidium observed in the human colon carcinoma fully differentiated colon cancer cell lines, cell subpopulations and clones expressing the structural and functional characteristics of highly specialized fully differentiated epithelial cells lining the intestinal epithelium and mimicking structurally and functionally an intestinal barrier. © 2013 John Wiley & Sons Ltd.

  20. Evaluation of Fetal Intestinal Cell Growth and Antimicrobial Biofunctionalities of Donor Human Milk After Preparative Processes.

    Science.gov (United States)

    Kanaprach, Pasinee; Pongsakul, Nutkridta; Apiwattanakul, Nopporn; Muanprasat, Chatchai; Supapannachart, Sarayut; Nuntnarumit, Pracha; Chutipongtanate, Somchai

    2018-04-01

    Donor human milk is considered the next best nutrition following mother's own milk to prevent neonatal infection and necrotizing enterocolitis in preterm infants who are admitted at neonatal intensive care unit. However, donor milk biofunctionalities after preparative processes have rarely been documented. To evaluate biofunctionalities preserved in donor milk after preparative processes by cell-based assays. Ten pools of donor milk were produced from 40 independent specimens. After preparative processes, including bacterial elimination methods (holder pasteurization and cold-sterilization microfiltration) and storage conditions (-20°C freezing storage and lyophilization) with varied duration of storage (0, 3, and 6, months), donor milk biofunctionalities were examined by fetal intestinal cell growth and antimicrobial assays. At baseline, raw donor milk exhibited 193.1% ± 12.3% of fetal intestinal cell growth and 42.4% ± 11.8% of antimicrobial activities against Escherichia coli. After bacteria eliminating processes, growth promoting activity was better preserved in pasteurized donor milk than microfiltrated donor milk (169.5% ± 14.3% versus 146.0% ± 11.8%, respectively; p pasteurized donor milk was further examined for the effects of storage conditions at 3 and 6 months. Freezing storage, but not lyophilization, could preserve higher growth-promoting activity during 6 months of storage (163.0% ± 9.4% versus 72.8% ± 6.2%, respectively; p < 0.005). Nonetheless, antimicrobial activity was lost at 6 months, regardless of the storage methods. This study revealed that fetal intestinal cell growth and antimicrobial assays could be applied to measure donor milk biofunctionalities and support the utilization of donor milk within 3 months after preparative processes.

  1. Characterization of an exo-chitinase from a Citrobacter strain isolated from the intestine content of large yellow croakers.

    Science.gov (United States)

    Xu, Jie; Yang, Yalin; Liu, Yang; Ran, Chao; Li, Juan; He, Suxu; Xu, Li; Ai, Xhunxiang; Zhou, Zhigang

    2016-07-04

    We isolated bacterial strains with chitin-degrading activity from the digesta of large yellow croakers (Pseudosciaena crocea) fed with chitin-enriched trash fish, and characterized potential chitinases thereof. Chitin-degrading strains were screened with colloidal chitin agar from the digesta of P. crocea fed with trash fish. The chitinase gene (chi-X) was cloned and expressed in Escherichia coli, and the enzymatic properties of the chitinase (CHI-X) were characterized. A Citrobacter freundii strain with chitin-degrading activity was isolated. The chitinase gene encodes a protein containing 493 amino acid residues, with a proposed glycoside hydrolase family-18 catalytic domain. CHI-X could hydrolyze colloidal chitin. The optimal pH for CHI-X was 4.0 at optimal temperature (60 ℃). CHI-X was active over a broad pH range, with around 90% of the activity maintained after incubation at pH between 3.0 and 11 for 1 h. The enzymatic activity of CHI-X was stimulated by Mn2+, Li+, and K+, but inhibited by Ag+. The enzyme was stable after treatment by proteases and grouper intestinal juice. CHI-X hydrolyzes colloidal chitin into GlcNAc and (GlcNAc)2. Furthermore, an synergic effect was observed between CHIX and ChiB565 (a chitinase from Aeromonas veronii B565) on colloidal chitin. CHI-X from intestinal bacterium may be potentially used as feed additive enzyme for warm water marine fish.

  2. Studies on the nitrogen metabolism of the large intestine of ruminants. 4

    International Nuclear Information System (INIS)

    Bergner, H.; Kijora, C.; Simon, O.; Goersch, R.

    1986-01-01

    Two experiments were performed with wethers (body weight 34 to 44 kg) receiving a ration rich in crude fiber at maintenance level. The animals were fitted with ileo-cecal cannulas into which 14 C-, 15 N-labelled urea together with digesta was introduced hourly for a 24 hours period (V 1 ; 2 animals). In experiment two (V 2 ; 3 animals) in addition HCl-partly hydrolyzed straw meal was introduced. After ureolytic degradation the intracecal applied urea entered mainly the intermediary metabolism. The resulting ammonia was resynthesized to urea without any time lag. The rate constant for the increase in 15 N labelling of urea was 3.2 d -1 in both experiments. Urea leaves the plasma with half-lives of 10.6 (V 1 ) and 5.2 (V 2 ) hours. More than 60% of the applied urea were excreted with urine. Formed 14 CO 2 appeared at proportions of 66% (V 2 ) and 71% (V 1 ) in the respiration gases. Both, the decline of the 14 C activity in blood plasma and the specific 14 C activity of CO 2 in the respiration gases after the end of the labelling period do not follow a kinetic of first order. The 15 N labelling of the NH 3 nitrogen in ileal digesta was very high and reached plateau values similar with those of plasma urea (2.54 vs. 2.56 atom-% 15 N excess). A direct entry of plasma urea into the small intestine was concluded. (author)

  3. Glucuronidation of trans-resveratrol by human liver and intestinal microsomes and UGT isoforms.

    Science.gov (United States)

    Brill, Shirley S; Furimsky, Anna M; Ho, Mark N; Furniss, Michael J; Li, Yi; Green, Adam G; Bradford, Wallace W; Green, Carol E; Kapetanovic, Izet M; Iyer, Lalitha V

    2006-04-01

    Resveratrol (trans-resveratrol, trans-3,5,4'-trihydroxystilbene) is a naturally occurring stilbene analogue found in high concentrations in red wine. There is considerable research interest to determine the therapeutic potential of resveratrol, as it has been shown to have tumour inhibitory and antioxidant properties. This study was performed to investigate the glucuronidation of resveratrol and possible drug interactions via glucuronidation. Two glucuronide conjugates, resveratrol 3-O-glucuronide and resveratrol 4'-O-glucuronide, were formed by human liver and intestinal microsomes. UGT1A1 and UGT1A9 were predominantly responsible for the formation of the 3-O-glucuronide (Km = 149 microM) and 4'-O-glucuronide (Km = 365 microM), respectively. The glucuronide conjugates were formed at higher levels (up to 10-fold) by intestinal rather than liver microsomes. Resveratrol was co-incubated with substrates of UGT1A1 (bilirubin and 7-ethyl-10-hydroxycamptothecin (SN-38)) and UGT1A9 (7-hydroxytrifluoromethyl coumarin (7-HFC)). No major changes were noted in bilirubin glucuronidation in the presence of resveratrol. Resveratrol significantly inhibited the glucuronidation of SN-38 (Ki = 6.2 +/- 2.1 microM) and 7-HFC (Ki = 0.6 +/- 0.2 microM). Hence, resveratrol has the potential to inhibit the glucuronidation of concomitantly administered therapeutic drugs or dietary components that are substrates of UGT1A1 and UGT1A9.

  4. Role of intestinal microbiota and metabolites on gut homeostasis and human diseases.

    Science.gov (United States)

    Lin, Lan; Zhang, Jianqiong

    2017-01-06

    A vast diversity of microbes colonizes in the human gastrointestinal tract, referred to intestinal microbiota. Microbiota and products thereof are indispensable for shaping the development and function of host innate immune system, thereby exerting multifaceted impacts in gut health. This paper reviews the effects on immunity of gut microbe-derived nucleic acids, and gut microbial metabolites, as well as the involvement of commensals in the gut homeostasis. We focus on the recent findings with an intention to illuminate the mechanisms by which the microbiota and products thereof are interacting with host immunity, as well as to scrutinize imbalanced gut microbiota (dysbiosis) which lead to autoimmune disorders including inflammatory bowel disease (IBD), Type 1 diabetes (T1D) and systemic immune syndromes such as rheumatoid arthritis (RA). In addition to their well-recognized benefits in the gut such as occupation of ecological niches and competition with pathogens, commensal bacteria have been shown to strengthen the gut barrier and to exert immunomodulatory actions within the gut and beyond. It has been realized that impaired intestinal microbiota not only contribute to gut diseases but also are inextricably linked to metabolic disorders and even brain dysfunction. A better understanding of the mutual interactions of the microbiota and host immune system, would shed light on our endeavors of disease prevention and broaden the path to our discovery of immune intervention targets for disease treatment.

  5. 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.

  6. Use of micro-lightguide spectrophotometry for evaluation of microcirculation in the small and large intestines of horses without gastrointestinal disease.

    Science.gov (United States)

    Reichert, Christof; Kästner, Sabine B R; Hopster, Klaus; Rohn, Karl; Rötting, Anna K

    2014-11-01

    To evaluate the use of a micro-lightguide tissue spectrophotometer for measurement of tissue oxygenation and blood flow in the small and large intestines of horses under anesthesia. 13 adult horses without gastrointestinal disease. Horses were anesthetized and placed in dorsal recumbency. Ventral midline laparotomy was performed. Intestinal segments were exteriorized to obtain measurements. Spectrophotometric measurements of tissue oxygenation and regional blood flow of the jejunum and pelvic flexure were obtained under various conditions that were considered to have a potential effect on measurement accuracy. In addition, arterial oxygen saturation at the measuring sites was determined by use of pulse oximetry. 12,791 single measurements of oxygen saturation, relative amount of hemoglobin, and blood flow were obtained. Errors occurred in 381 of 12,791 (2.98%) measurements. Most measurement errors occurred when surgical lights were directed at the measuring site; covering the probe with the surgeon's hand did not eliminate this error source. No measurement errors were observed when the probe was positioned on the intestinal wall with room light, at the mesenteric side, or between the mesenteric and antimesenteric side. Values for blood flow had higher variability, and this was most likely caused by motion artifacts of the intestines. The micro-lightguide spectrophotometry system was easy to use on the small and large intestines of horses and provided rapid evaluation of the microcirculation. Results indicated that measurements should be performed with room light only and intestinal motion should be minimized.

  7. Localization and role of NPC1L1 in cholesterol absorption in human intestine.

    Science.gov (United States)

    Sané, Alain Théophile; Sinnett, Daniel; Delvin, Edgard; Bendayan, Moise; Marcil, Valérie; Ménard, Daniel; Beaulieu, Jean-François; Levy, Emile

    2006-10-01

    Recent studies have documented the presence of Niemann-Pick C1-Like 1 (NPC1L1) in the small intestine and its capacity to transport cholesterol in mice and rats. The current investigation was undertaken to explore the localization and function of NPC1L1 in human enterocytes. Cell fractionation experiments revealed an NPC1L1 association with apical membrane of the enterocyte in human jejunum. Signal was also detected in lysosomes, endosomes, and mitochondria. Confirmation of cellular NPC1L1 distribution was obtained by immunocytochemistry. Knockdown of NPC1L1 caused a decline in the ability of Caco-2 cells to capture micellar [(14)C]free cholesterol. Furthermore, this NPC1L1 suppression resulted in increased and decreased mRNA levels and activity of HMG-CoA reductase, the rate-limiting step in cholesterol synthesis, and of ACAT, the key enzyme in cholesterol esterification, respectively. An increase was also noted in the transcriptional factor sterol-regulatory element binding protein that modulates cholesterol homeostasis. Efforts were devoted to define the impact of NPC1L1 knockdown on other mediators of cholesterol uptake. RT-PCR evidence is presented to show the significant decrease in the levels of scavenger receptor class B type I (SR-BI) with no changes in ABCA1, ABCG5, and cluster determinant 36 in NPC1L1-deficient Caco-2 cells. Together, our data suggest that NPC1L1 contributes to intestinal cholesterol homeostasis and possibly cooperates with SR-BI to mediate cholesterol absorption in humans.

  8. Intestinal pseudo-obstruction

    Science.gov (United States)

    ... Staying in bed for long periods of time (bedridden). Taking drugs that slow intestinal movements. These include ... be tried: Colonoscopy may be used to remove air from the large intestine. Fluids can be given ...

  9. 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...... studied. Freshly resected intestine was examined by light and electron microscopy. The interstitial cells of Cajal resembled modified smooth muscle cells. They had caveolae and dense bodies, an incomplete basal lamina, a very well-developed smooth endoplasmic reticulum, and abundant intermediate (10 nm...

  10. A paradox of transcriptional and functional innate interferon responses of human intestinal enteroids to enteric virus infection

    Science.gov (United States)

    Saxena, Kapil; Simon, Lukas M.; Zeng, Xi-Lei; Blutt, Sarah E.; Crawford, Sue E.; Sastri, Narayan P.; Karandikar, Umesh C.; Ajami, Nadim J.; Zachos, Nicholas C.; Kovbasnjuk, Olga; Donowitz, Mark; Conner, Margaret E.; Shaw, Chad A.; Estes, Mary K.

    2017-01-01

    The intestinal epithelium can limit enteric pathogens by producing antiviral cytokines, such as IFNs. Type I IFN (IFN-α/β) and type III IFN (IFN-λ) function at the epithelial level, and their respective efficacies depend on the specific pathogen and site of infection. However, the roles of type I and type III IFN in restricting human enteric viruses are poorly characterized as a result of the difficulties in cultivating these viruses in vitro and directly obtaining control and infected small intestinal human tissue. We infected nontransformed human intestinal enteroid cultures from multiple individuals with human rotavirus (HRV) and assessed the host epithelial response by using RNA-sequencing and functional assays. The dominant transcriptional pathway induced by HRV infection is a type III IFN-regulated response. Early after HRV infection, low levels of type III IFN protein activate IFN-stimulated genes. However, this endogenous response does not restrict HRV replication because replication-competent HRV antagonizes the type III IFN response at pre- and posttranscriptional levels. In contrast, exogenous IFN treatment restricts HRV replication, with type I IFN being more potent than type III IFN, suggesting that extraepithelial sources of type I IFN may be the critical IFN for limiting enteric virus replication in the human intestine. PMID:28069942

  11. Gastric intestinal metaplasia with basal gland atypia: a morphological and biologic evaluation in a large Chinese cohort.

    Science.gov (United States)

    Li, Yuan; Chang, Xiaoyan; Zhou, Weixun; Xiao, Yu; Nakatsuka, Laura N; Chen, Jie; Lauwers, Gregory Y

    2013-04-01

    Gastric intestinal metaplasia can display cytoarchitectural atypia that falls short of qualifying for dysplasia but can be classified as indefinite for dysplasia. Yet few studies have evaluated the prevalence, the morphologic, and biologic characteristics of this variant. Out of a cohort of 554 biopsies with chronic atrophic gastritis and/or dysplasia, we categorized the cases as either (1) simple intestinal metaplasia; (2) intestinal metaplasia with hyperplasia; (3) intestinal metaplasia with basal gland atypia; and (4) gastric dysplasia. The relationship between the subtypes and various clinicopathologic features, mucin immunophenotypes, and biologic characteristics was evaluated. The final cohort consisted of 424 cases of simple intestinal metaplasia, 93 intestinal metaplasia with hyperplasia, 16 intestinal metaplasia with basal gland atypia, and 21 gastric dysplasia. Intestinal metaplasia with basal gland atypia had a prevalence of 2.8% and similar to gastric dysplasia, 3.7%. Both of these lesions were similar in body/fundus distribution (12.5%) and paucity of goblet cells (68.8%). Intestinal metaplasia with basal gland atypia and gastric dysplasia seem to share some biologic similarities but with a lower frequency of alpha-methylacyl-CoA racemase expression (25% versus 62%), p53 expression (6.3% versus 47.6%), and increased Ki-67 index on surface/pit and isthmus in intestinal metaplasia with basal gland atypia. Alternatively, simple intestinal metaplasia and intestinal metaplasia with hyperplasia did not differ statistically with regard to the various characteristics evaluated. We concluded that gastric intestinal metaplasia can be divided into 2 broad categories that are readily defined by cytoarchitectural and biologic characteristics. Based on the characteristics of intestinal metaplasia with basal gland atypia and in keeping with others, we confirm that this subtype could represent a preneoplastic lesion that needs further evaluation. Copyright © 2013

  12. [Megas and cancer. Cancer of the large intestine in chagasic patients with megacolon].

    Science.gov (United States)

    Meneses, A C; Lopes, M A; Rocha, A; Fatureto, M C; Lopes, G P; Lopes, E R; Chapadeiro, E

    1989-01-01

    This is a review of 4.690 necropsies and 24.209 surgical pathology specimens describing the association between megacolon chagasic and malignant tumors of the large bowel. The prevalence of malignant tumors of the large bowel was not higher in megacolon.

  13. Identification of glucose-fermenting bacteria present in an in vitro model of the human intestine by RNA-stable isotope probing

    NARCIS (Netherlands)

    Egert, M.; Graaf, A.A. de; Maathuis, A.; Waard, P. de; Plugge, C.M.; Smidt, H.; Deutz, N.E.P.; Dijkema, C.; Vos, W.M. de; Venema, K.

    2007-01-01

    16S rRNA-based stable isotope probing (SIP) and nuclear magnetic resonance (NMR) spectroscopy-based metabolic profiling were used to identify bacteria fermenting glucose under conditions simulating the human intestine. The TIM-2 in vitro model of the human intestine was inoculated with a GI tract

  14. Nutrient Fortification of Human Donor Milk Affects Intestinal Function and Protein Metabolism in Preterm Pigs

    DEFF Research Database (Denmark)

    Sun, Jing; Li, Yanqi; Nguyen, Duc Ninh

    2018-01-01

    (BC) may be an alternative nutrient fortifier, considering its high content of protein and milk bioactive factors. Objective: We investigated whether BC was superior to an FF product based on processed bovine milk and vegetable oil to fortify donor human milk (DHM) for preterm pigs, used as a model......) and DHM with or without FF or BC fortification (+4.6 g protein ⋅ kg-1 ⋅ d-1). Results: DPM-fed pigs showed higher growth (10-fold), protein synthesis (+15-30%), villus heights, lactase and peptidase activities (+30%), and reduced intestinal cytokines (-50%) relative to DHM pigs (all P ....05). Fortification increased protein synthesis (+20-30%), but with higher weight gain and lower urea and cortisol concentrations for DHM+BC compared with DHM+FF pigs (2- to 3-fold differences, all P ≤ 0.06). DHM+FF pigs showed more diarrhea and reduced lactase and peptidase activities, hexose uptake, and villus...

  15. 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, Per Glud; 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. Follicula...

  16. The Nucleotide Synthesis Enzyme CAD Inhibits NOD2 Antibacterial Function in Human Intestinal Epithelial Cells

    Science.gov (United States)

    Richmond, Amy L.; Kabi, Amrita; Homer, Craig R.; García, Noemí Marina; Nickerson, Kourtney P.; NesvizhskiI, Alexey I.; Sreekumar, Arun; Chinnaiyan, Arul M.; Nuñez, Gabriel; McDonald, Christine

    2013-01-01

    BACKGROUND & AIMS Polymorphisms that reduce the function of nucleotide-binding oligomerization domain (NOD)2, a bacterial sensor, have been associated with Crohn’s disease (CD). No proteins that regulate NOD2 activity have been identified as selective pharmacologic targets. We sought to discover regulators of NOD2 that might be pharmacologic targets for CD therapies. METHODS Carbamoyl phosphate synthetase/ aspartate transcarbamylase/dihydroorotase (CAD) is an enzyme required for de novo pyrimidine nucleotide synthesis; it was identified as a NOD2-interacting protein by immunoprecipitation-coupled mass spectrometry. CAD expression was assessed in colon tissues from individuals with and without inflammatory bowel disease by immunohistochemistry. The interaction between CAD and NOD2 was assessed in human HCT116 intestinal epithelial cells by immunoprecipitation, immunoblot, reporter gene, and gentamicin protection assays. We also analyzed human cell lines that express variants of NOD2 and the effects of RNA interference, overexpression and CAD inhibitors. RESULTS CAD was identified as a NOD2-interacting protein expressed at increased levels in the intestinal epithelium of patients with CD compared with controls. Overexpression of CAD inhibited NOD2-dependent activation of nuclear factor κB and p38 mitogen-activated protein kinase, as well as intracellular killing of Salmonella. Reduction of CAD expression or administration of CAD inhibitors increased NOD2-dependent signaling and antibacterial functions of NOD2 variants that are and are not associated with CD. CONCLUSIONS The nucleotide synthesis enzyme CAD is a negative regulator of NOD2. The antibacterial function of NOD2 variants that have been associated with CD increased in response to pharmacologic inhibition of CAD. CAD is a potential therapeutic target for CD. PMID:22387394

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

    International Nuclear Information System (INIS)

    Naidu, S.S.; Erdei, J.; Forsgren, A.; Naidu, A.S.; Czirok, E.; Gado, I.; Kalfas, S.; Thoren, A.

    1991-01-01

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

  18. Effects of nonpathogenic bacteria on cytokine secretion by human intestinal mucosa.

    Science.gov (United States)

    Borruel, Natalia; Casellas, Francesc; Antolín, María; Llopis, Marta; Carol, Monica; Espíin, Eloy; Naval, Javier; Guarner, Francisco; Malagelada, Juan R

    2003-04-01

    The human intestine harbors a complex microbial ecosystem, and the mucosa is the interface between the immune system and the luminal environment. The aim of this study was to elucidate whether host-bacteria interactions influence mucosal cytokine production. Macroscopically normal colonic specimens were obtained at surgery from eight patients with neoplasm, and inflamed ileal specimens were obtained from two patients with Crohn's disease. Mucosal explants were cultured for 24 h with either nonpathogenic Escherichia coli ECOR-26, Lactobacillus casei DN-114 001, L. casei DN-114 056, L. casei ATCC-334, or Lactobacillus bulgaricus LB-10. Each study included blank wells with no bacteria. Tissue and bacteria viability were confirmed by LDH release and culture. Concentration of tumor necrosis factor (TNF)alpha, transforming growth factor beta1, interleukin (IL)-8, and IL-10 was measured in supernatants. In parallel experiments, neutralizing anti-TNFalpha antibody was added to the culture. Co-culture of mucosa with bacteria did not modify LDH release. Co-culture with L. casei strains significantly reduced TNFalpha release, whereas E. coli increased it. These effects were observed both in normal and inflamed mucosa. In combination studies, L. casei DN-114 001 prevented TNFalpha stimulation by E. coli. L. casei DN-114 001 also reduced IL-8 release via a TNFalpha-independent pathway. L. casei DN-114 056 or E. coli increased IL-10 release in the presence of neutralizing anti-TNFalpha. Nonpathogenic bacteria interact with human intestinal mucosa and can induce changes in cytokine production that are strain specific.

  19. Impact of food grade and nano-TiO2 particles on a human intestinal community.

    Science.gov (United States)

    Dudefoi, William; Moniz, Kristy; Allen-Vercoe, Emma; Ropers, Marie-Hélène; Walker, Virginia K

    2017-08-01

    Titanium dioxide (TiO 2 ) nanoparticles (NPs) are used as an additive (E171 or INS171) in foods such as gum, candy and puddings. To address concerns about the potential hazardous effects of ingested NPs, the toxicity of these food-grade NPs was investigated with a defined model intestinal bacterial community. Each titania preparation (food-grade TiO 2 formulations, E171-1 and E171-6a) was tested at concentrations equivalent to those found in the human intestine after sampling 1-2 pieces of gum or candy (100-250 ppm). At the low concentrations used, neither the TiO 2 food additives nor control TiO 2 NPs had an impact on gas production and only a minor effect on fatty acids profiles (C16:00, C18:00, 15:1 w5c, 18:1 w9c and 18:1 w9c, p < 0.05). DNA profiles and phylogenetic distributions confirmed limited effects on the bacterial community, with a modest decrease in the relative abundance of the dominant Bacteroides ovatus in favor of Clostridium cocleatum (-13% and +14% respectively, p < 0.05). Such minor shifts in the treated consortia suggest that food grade and nano-TiO 2 particles do not have a major effect on human gut microbiota when tested in vitro at relevant low concentrations. However, the cumulative effects of chronic TiO 2 NP ingestion remain to be tested. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. 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 th...

  1. 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...

  2. Rapid reversal of human intestinal ischemia-reperfusion induced damage by shedding of injured enterocytes and reepithelialisation.

    Directory of Open Access Journals (Sweden)

    Joep P M Derikx

    Full Text Available BACKGROUND: Intestinal ischemia-reperfusion (IR is a phenomenon related to physiological conditions (e.g. exercise, stress and to pathophysiological events (e.g. acute mesenteric ischemia, aortic surgery. Although intestinal IR has been studied extensively in animals, results remain inconclusive and data on human intestinal IR are scarce. Therefore, an experimental harmless model for human intestinal IR was developed, enabling us to clarify the sequelae of human intestinal IR for the first time. METHODS AND FINDINGS: In 30 patients undergoing pancreatico-duodenectomy we took advantage of the fact that in this procedure a variable length of jejunum is removed. Isolated jejunum (5 cm was subjected to 30 minutes ischemia followed by reperfusion. Intestinal Fatty Acid Binding Protein (I-FABP arteriovenous concentration differences across the bowel segment were measured before and after ischemia to assess epithelial cell damage. Tissue sections were collected after ischemia and at 25, 60 and 120 minutes reperfusion and stained with H&E, and for I-FABP and the apoptosis marker M30. Bonferroni's test was used to compare I-FABP differences. Mean (SEM arteriovenous concentration gradients of I-FABP across the jejunum revealed rapidly developing epithelial cell damage. I-FABP release significantly increased from 290 (46 pg/ml before ischemia towards 3,997 (554 pg/ml immediately after ischemia (p<0.001 and declined gradually to 1,143 (237 pg/ml within 1 hour reperfusion (p<0.001. Directly after ischemia the intestinal epithelial lining was microscopically normal, while subepithelial spaces appeared at the villus tip. However, after 25 minutes reperfusion, enterocyte M30 immunostaining was observed at the villus tip accompanied by shedding of mature enterocytes into the lumen and loss of I-FABP staining. Interestingly, within 60 minutes reperfusion the epithelial barrier resealed, while debris of apoptotic, shedded epithelial cells was observed in the lumen

  3. Carboxylated nanodiamonds are neither cytotoxic nor genotoxic on liver, kidney, intestine and lung human cell lines.

    Science.gov (United States)

    Paget, V; Sergent, J A; Grall, R; Altmeyer-Morel, S; Girard, H A; Petit, T; Gesset, C; Mermoux, M; Bergonzo, P; Arnault, J C; Chevillard, S

    2014-08-01

    Although nanodiamonds (NDs) appear as one of the most promising nanocarbon materials available so far for biomedical applications, their risk for human health remains unknown. Our work was aimed at defining the cytotoxicity and genotoxicity of two sets of commercial carboxylated NDs with diameters below 20 and 100 nm, on six human cell lines chosen as representative of potential target organs: HepG2 and Hep3B (liver), Caki-1 and Hek-293 (kidney), HT29 (intestine) and A549 (lung). Cytotoxicity of NDs was assessed by measuring cell impedance (xCELLigence® system) and cell survival/death by flow cytometry while genotoxicity was assessed by γ-H2Ax foci detection, which is considered the most sensitive technique for studying DNA double-strand breaks. To validate and check the sensitivity of the techniques, aminated polystyrene nanobeads were used as positive control in all assays. Cell incorporation of NDs was also studied by flow cytometry and luminescent N-V center photoluminescence (confirmed by Raman microscopy), to ensure that nanoparticles entered the cells. Overall, we show that NDs effectively entered the cells but NDs do not induce any significant cytotoxic or genotoxic effects on the six cell lines up to an exposure dose of 250 µg/mL. Taken together these results strongly support the huge potential of NDs for human nanomedicine but also their potential as negative control in nanotoxicology studies.

  4. Role of commercial probiotic strains against human pathogen adhesion to intestinal mucus.

    Science.gov (United States)

    Collado, M C; Meriluoto, J; Salminen, S

    2007-10-01

    The aims of this study present were to assess and to evaluate in vitro the abilities of commercial probiotic strains derived from fermented milk products and related sources currently marketed in European countries, to inhibit, compete and displace the adhesion of selected potential pathogens to immobilized human mucus. The adhesion was assessed by measuring the radioactivity of bacteria adhered to the human mucus. We tested 12 probiotic strains against eight selected pathogens. All strains tested were able to adhere to mucus. All probiotic strains tested were able to inhibit and displace (P<0.05) the adhesion of Bacteroides, Clostridium, Staphylococcus and Enterobacter. In addition, the abilities to inhibit and to displace adhered pathogens depended on both the probiotic and the pathogen strains tested suggesting that several complementary mechanisms are implied in the processes. Our results indicate the need for a case-by-case assessment in order to select strains with the ability to inhibit or displace a specific pathogen. Probiotics could be useful to correct deviations observed in intestinal microbiota associated with specific diseases and also, to prevent pathogen infections. The competitive exclusion properties of probiotics as well as their ability to displace and inhibit pathogens are the most importance for therapeutic manipulation of the enteric microbiota. The application of such strategies could contribute to expand the beneficial properties on human health against pathogen infection.

  5. Alteration of a human intestinal microbiota under extreme life environment in the Antarctica.

    Science.gov (United States)

    Jin, Jong-Sik; Touyama, Mutsumi; Yamada, Shin; Yamazaki, Takashi; Benno, Yoshimi

    2014-01-01

    The human intestinal microbiota (HIM) settles from birth and continues to change phenotype by some factors (e.g. host's diet) throughout life. However, the effect of extreme life environment on human HIM composition is not well known. To understand HIM fluctuation under extreme life environment in humans, fecal samples were collected from six Japanese men on a long Antarctic expedition. They explored Antarctica for 3 months and collected their fecal samples at once-monthly intervals. Using terminal restriction fragment length polymorphism (T-RFLP) and real time polymerase chain reaction (PCR) analysis, the composition of HIM in six subjects was investigated. Three subjects presented restoration of HIM after the expedition compared versus before and during the expedition. Two thirds samples collected during the expedition belonged to the same cluster in dendrogram. However, all through the expedition, T-RFLP patterns showed interindividual variability. Especially, Bifidobacterium spp. showed a tendency to decrease during and restore after the expedition. A reduction of Bifidobacterium spp. was observed in five subjects the first 1 month of the expedition. Bacteroides thetaiotaomicron, which is thought to proliferate during emotional stress, significantly decreased in one subject, indicating that other factors in addition to emotional stress may affect the composition of HIM in this study. These findings could be helpful to understand the effect of extreme life environment on HIM.

  6. Chromogranin A cell density in the large intestine of Asian and European patients with irritable bowel syndrome.

    Science.gov (United States)

    El-Salhy, Magdy; Patcharatrakul, Tanisa; Hatlebakk, Jan Gunnar; Hausken, Trygve; Gilja, Odd Helge; Gonlachanvit, Sutep

    Patients with irritable bowel syndrome (IBS) in Asia show distinctive differences from those in the western world. The gastrointestinal endocrine cells appear to play an important role in the pathophysiology of IBS. The present study aimed at studying the density of chromogranin A (CgA) cells in the large intestine of Thai and Norwegian IBS patients. Thirty Thai IBS patients and 20 control subjects, and 47 Norwegian IBS patients and 20 control subjects were included. A standard colonoscopy was performed in both the patients and controls, and biopsy samples were taken from the colon and the rectum. The biopsy samples were stained with hematoxylin-eosin and immunostained for CgA. The density of CgA cells was determined by computerized image analysis. In the colon and rectum, the CgA cell densities were far higher in both IBS and healthy Thai subjects than in Norwegians. The colonic CgA cell density was lower in Norwegian IBS patients than in controls, but did not differ between Thai IBS patients and controls. In the rectum, the CgA cell densities in both Thai and Norwegian patients did not differ from those of controls. The higher densities of CgA cells in Thai subjects than Norwegians may be explained by a higher exposure to infections at childhood and the development of a broad immune tolerance, by differences in the intestinal microbiota, and/or differing diet habits. The normal CgA cell density in Thai IBS patients in contrast to that of Norwegians may be due to differences in pathophysiology.

  7. Large-scale determinants of intestinal schistosomiasis and intermediate host snail distribution across Africa

    DEFF Research Database (Denmark)

    Stensgaard, Anna-Sofie; Utzinger, Jürg; Vounatsou, Penelope

    2013-01-01

    The geographical ranges of most species, including many infectious disease agents and their vectors and intermediate hosts, are assumed to be constrained by climatic tolerances, mainly temperature. It has been suggested that global warming will cause an expansion of the areas potentially suitable...... impacts of climatic changes. Snail species distribution models included several combinations of climatic and habitat-related predictors; the latter divided into "natural" and "human-impacted" habitat variables to measure anthropogenic influence. The predictive performance of the combined snail...... are more likely to contract and/or move into cooler areas in the south and east. Importantly, we also note that even though climate per se matters, the impact of humans on habitat play a crucial role in determining the distribution of the intermediate host snails in Africa. Thus, a future contraction...

  8. 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

    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......BACKGROUND: Glyceryl trinitrate is a donor of nitric oxide that relaxes smooth muscle cells of the gastrointestinal tract. Little is known about the effect of glyceryl trinitrate on gastric emptying and no data exist on the possible effect of glyceryl trinitrate on small intestinal transit. AIM......: To examine the effect of intravenous infusion of glyceryl trinitrate on gastric and small intestinal motor function after a meal in healthy humans. METHODS: Nine healthy volunteers participated in a placebo-controlled, double-blind, crossover study. Each volunteer was examined during intravenous infusion...

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

    International Nuclear Information System (INIS)

    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. [ 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 [ 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

  10. 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...... emptying time, gastric half emptying time, gastric retention at 15 min or small intestinal mean transit time. Glyceryl trinitrate did not influence the frequency of duodenal contractions, the amplitude of duodenal contractions or the duodenal motility index. CONCLUSIONS: Intravenous infusion of glyceryl...

  11. The Escherichia coli K-12 gntP gene allows E. coli F-18 to occupy a distinct nutritional niche in the streptomycin-treated mouse large intestine

    DEFF Research Database (Denmark)

    Sweeney, N.J.; Klemm, Per; McCormick, Beth A.

    1996-01-01

    Escherichia coli F-18 is a human fecal isolate that makes type 1 fimbriae, encoded by the fim gene cluster, and is an excellent colonizer of the streptomycin-treated mouse intestine. E. coli F-18 fimA::tet, lacking type 1 fimbriae, was constructed by bacteriophage P1 transduction of the fim regio...

  12. Epidemiology of human fascioliasis and intestinal parasitosis among schoolchildren in Lake Tana Basin, northwest Ethiopia.

    Science.gov (United States)

    Fentie, Tsegaw; Erqou, Sebhat; Gedefaw, Molla; Desta, Almaw

    2013-08-01

    Parasitic diseases are the second most frequent cause of outpatient morbidity in Ethiopia. A cross-sectional study was conducted in Lake Tana Basin, northwest Ethiopia, from November 2007 to February 2008, to assess the magnitude and associated risk factors for parasitic diseases, including human fascioliasis. We examined 520 stool samples from randomly selected schoolchildren in six schools by microscopy. Rapid sedimentation and Kato-Katz techniques were used to detect and count Fasciola and Schistosoma eggs. The formol-ether concentration method was used for the identification of other helminth eggs, larvae and cysts of protozoan parasites. The overall prevalence of intestinal parasitic infections was 71.3% (95% CI 67.3-75.1%). Hookworm was the predominant intestinal parasite (23.5%, 95% CI 19.8-27.1%), followed by Ascaris lumbricoides (18.5%, 95% CI 15.2-21.9%) and Schistosoma mansoni (16.7%, 95% CI 13.5-19.9%). One hundred and sixty-three (31.4%) children had multiple parasitic infections. The most relevant finding was a prevalence of Fasciola spp. of 3.3% in an area where only sporadic cases have been reported previously. The risk of Fasciola spp. infection was significantly associated with raw vegetable consumption, use of unsafe drinking water sources, irrigation practices and sheep and/or cattle ownership. Irrigation practices, male gender, raw vegetable consumption and use of unsafe drinking water sources were risk factors for S. mansoni infection. A high prevalence of parasitic infections among children in the region was found, including a relatively high prevalence of Fasciola spp. infection. Epidemiological studies on the magnitude of parasitic infections in different regions will enable high-risk communities to be identified and allow for planning of appropriate interventions.

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

    International Nuclear Information System (INIS)

    Zhang Fengli; Luecke, Christian; Baier, Leslie J.; Sacchettini, James C.; Hamilton, James A.

    1997-01-01

    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 β-strands which form two nearly orthogonal β-sheets of five strands each, and two short α-helices that connect the β-strands A and B. The interior of the protein consists of a water-filled cavity between the two β-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

  14. 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.

  15. Endurance Exercise Increases Intestinal Uptake of the Peanut Allergen Ara h 6 after Peanut Consumption in Humans

    Directory of Open Access Journals (Sweden)

    Lonneke M. JanssenDuijghuijsen

    2017-01-01

    Full Text Available Controlled studies on the effect of exercise on intestinal uptake of protein are scarce and underlying mechanisms largely unclear. We studied the uptake of the major allergen Ara h 6 following peanut consumption in an exercise model and compared this with changes in markers of intestinal permeability and integrity. Ten overnight-fasted healthy non-allergic men (n = 4 and women (n = 6 (23 ± 4 years ingested 100 g of peanuts together with a lactulose/rhamnose (L/R solution, followed by rest or by 60 min cycling at 70% of their maximal workload. Significantly higher, though variable, levels of Ara h 6 in serum were found during exercise compared to rest (Peak p = 0.03; area under the curve p = 0.006, with individual fold changes ranging from no increase to an increase of over 150-fold in the uptake of Ara h 6. Similarly, uptake of lactulose (2–18 fold change, p = 0.0009 and L/R ratios (0.4–7.9 fold change, p = 0.04 were significantly increased which indicates an increase in intestinal permeability. Intestinal permeability and uptake of Ara h 6 were strongly correlated (r = 0.77, p < 0.0001 for lactulose and Ara h 6. Endurance exercise after consumption may lead to increased paracellular intestinal uptake of food proteins.

  16. 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

  17. Intestinal transplantation: The anesthesia perspective.

    Science.gov (United States)

    Dalal, Aparna

    2016-04-01

    Intestinal transplantation is a complex and challenging surgery. It is very effective for treating intestinal failure, especially for those patients who cannot tolerate parenteral nutrition nor have extensive abdominal disease. Chronic parental nutrition can induce intestinal failure associated liver disease (IFALD). According to United Network for Organ Sharing (UNOS) data, children with intestinal failure affected by liver disease secondary to parenteral nutrition have the highest mortality on a waiting list when compared with all candidates for solid organ transplantation. Intestinal transplant grafts can be isolated or combined with the liver/duodenum/pancreas. Organ Procurement and Transplantation Network (OPTN) has defined intestinal donor criteria. Living donor intestinal transplant (LDIT) has the advantages of optimal timing, short ischemia time and good human leukocyte antigen matching contributing to lower postoperative complications in the recipient. Thoracic epidurals provide excellent analgesia for the donors, as well as recipients. Recipient management can be challenging. Thrombosis and obstruction of venous access maybe common due to prolonged parenteral nutrition and/or hypercoaguability. Thromboelastography (TEG) is helpful for managing intraoperative product therapy or thrombosis. Large fluid shifts and electrolyte disturbances may occur due to massive blood loss, dehydration, third spacing etc. Intestinal grafts are susceptible to warm and cold ischemia and ischemia-reperfusion injury (IRI). Post-reperfusion syndrome is common. Cardiac or pulmonary clots can be monitored with transesophageal echocardiography (TEE) and treated with recombinant tissue plasminogen activator. Vasopressors maybe used to ensure stable hemodynamics. Post-intestinal transplant patients may need anesthesia for procedures such as biopsies for surveillance of rejection, bronchoscopy, endoscopy, postoperative hemorrhage, anastomotic leaks, thrombosis of grafts etc. Asepsis

  18. Gastrointestinal Simulation Model TWIN-SHIME Shows Differences between Human Urolithin-Metabotypes in Gut Microbiota Composition, Pomegranate Polyphenol Metabolism, and Transport along the Intestinal Tract.

    Science.gov (United States)

    García-Villalba, Rocío; Vissenaekens, Hanne; Pitart, Judit; Romo-Vaquero, María; Espín, Juan C; Grootaert, Charlotte; Selma, María V; Raes, Katleen; Smagghe, Guy; Possemiers, Sam; Van Camp, John; Tomas-Barberan, Francisco A

    2017-07-12

    A TWIN-SHIME system was used to compare the metabolism of pomegranate polyphenols by the gut microbiota from two individuals with different urolithin metabotypes. Gut microbiota, ellagitannin metabolism, short-chain fatty acids (SCFA), transport of metabolites, and phase II metabolism using Caco-2 cells were explored. The simulation reproduced the in vivo metabolic profiles for each metabotype. The study shows for the first time that microbial composition, metabolism of ellagitannins, and SCFA differ between metabotypes and along the large intestine. The assay also showed that pomegranate phenolics preserved intestinal cell integrity. Pomegranate polyphenols enhanced urolithin and propionate production, as well as Akkermansia and Gordonibacter prevalence with the highest effect in the descending colon. The system provides an insight into the mechanisms of pomegranate polyphenol gut microbiota metabolism and absorption through intestinal cells. The results obtained by the combined SHIME/Caco-2 cell system are consistent with previous human and animal studies and show that although urolithin metabolites are present along the gastrointestinal tract due to enterohepatic circulation, they are predominantly produced in the distal colon region.

  19. Lactococcus lactis subsp. cremoris strain JFR1 attenuates Salmonella adhesion to human intestinal cells in vitro.

    Science.gov (United States)

    Zhang, Justina Su; Guri, Anilda; Corredig, Milena; Morales-Rayas, Rocio; Hassan, Ashraf; Griffiths, Mansel; LaPointe, Gisèle

    2016-12-01

    Lactococcus lactis subsp. cremoris JFR1 has been studied in reduced fat cheese due to its ability to produce exopolysaccharides (EPS) in situ, contributing to improved textural and organoleptic properties. In this study, the effect of strain JFR1 on virulence gene expression and attachment of Salmonella to HT-29 human colon carcinoma cells was investigated. Overnight cultures of L. lactis subsp. cremoris JFR1 containing EPS, grown in M17 media with 0.5% glucose supplementation, decreased attachment as well as down regulated virulence gene expression in Salmonella enterica subsp. enterica when tested on HT-29 cells. However, EPS isolated from milk fermented with L. lactis subsp. cremoris JFR1 did not affect Salmonella virulence gene expression or attachment to HT-29 cells. These results suggest that EPS does not contribute to the attachment of Salmonella to human intestinal cells. However, the possibility that the isolation process may have affected the structural features of EPS cannot be ruled out. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Using human intestinal biopsies to study the pathogenesis of irritable bowel syndrome.

    Science.gov (United States)

    Nasser, Y; Boeckxstaens, G E; Wouters, M M; Schemann, M; Vanner, S

    2014-04-01

    Although animal models of the irritable bowel syndrome (IBS) have provided important insights, there are no models that fully express the features of this complex condition. One alternative approach is the use of human intestinal biopsies obtained during endoscopic procedures to examine peripheral mechanisms in this disorder. These studies have served to confirm the existence of peripheral pathways in humans with IBS and have provided many new mechanistic insights. Two general approaches have been employed; one approach has been to examine the biological activity of mediators within the mucosal tissue of IBS patients and the other has been to examine changes in the structural properties of key signaling pathways contained within the biopsies. Using these approaches, important changes have been discovered involving the enteric nervous system and the extrinsic sensory pathway (dorsal root ganglia neurons), the immune system, and epithelial signaling in IBS patients compared to healthy subjects. This review will systematically explore these mechanistic pathways, highlight the implications of these novel findings and discuss some of the important limitations of this approach. © 2014 John Wiley & Sons Ltd.

  1. The effect of dietary prebiotics and probiotics on body weight, large intestine indices, and fecal bile acid profile in wild type and IL10-/- mice.

    Directory of Open Access Journals (Sweden)

    Shiu-Ming Kuo

    Full Text Available Previous studies have suggested roles of probiotics and prebiotics on body weight management and intestinal function. Here, the effects of a dietary prebiotic, inulin (50 mg/g diet, and probiotic, Bfidobacterium animalis subsp. lactis (Bb12 (final dose verified at 10(5 colony forming unit (cfu/g diet, comparable to human consumption, were determined separately and in combination in mice using cellulose-based AIN-93G diets under conditions allowed for the growth of commensal bacteria. Continuous consumption of Bb12 and/or inulin did not affect food intake or body, liver, and spleen weights of young and adult mice. Fecal bile acid profiles were determined by nanoESI-MS/MS tandem mass spectrometry. In the presence of inulin, more bacterial deconjugation of taurine from primary bile acids was observed along with an increased cecal weight. Consumption of inulin in the absence or presence of Bb12 also increased the villus cell height in the proximal colon along with a trend of higher bile acid sulfation by intestinal cells. Feeding Bb12 alone at the physiological dose did not affect bile acid deconjugation and had little effect on other intestinal indices. Although interleukin (IL10-null mice are susceptible to enterocolitis, they maintained the same body weight as the wild type mice under our specific pathogen-free housing condition and showed no signs of inflammation. Nevertheless, they had smaller cecum suggesting a mildly compromised intestinal development even before the disease manifestation. Our results are consistent with the notion that dietary factors such as prebiotics play important roles in the growth of intestinal microbiota and may impact on the intestinal health. In addition, fecal bile acid profiling could potentially be a non-invasive tool in monitoring the intestinal environment.

  2. Human Breast Milk and Infant Formulas Differentially Modify the Intestinal Microbiota in Human Infants and Host Physiology in Rats.

    Science.gov (United States)

    Liu, Zhenmin; Roy, Nicole C; Guo, Yanhong; Jia, Hongxin; Ryan, Leigh; Samuelsson, Linda; Thomas, Ancy; Plowman, Jeff; Clerens, Stefan; Day, Li; Young, Wayne

    2016-02-01

    In the absence of human breast milk, infant and follow-on formulas can still promote efficient growth and development. However, infant formulas can differ in their nutritional value. The objective of this study was to compare the effects of human milk (HM) and infant formulas in human infants and a weanling rat model. In a 3 wk clinical randomized controlled trial, babies (7- to 90-d-old, male-to-female ratio 1:1) were exclusively breastfed (BF), exclusively fed Synlait Pure Canterbury Stage 1 infant formula (SPCF), or fed assorted standard formulas (SFs) purchased by their parents. We also compared feeding HM or SPCF in weanling male Sprague-Dawley rats for 28 d. We examined the effects of HM and infant formulas on fecal short chain fatty acids (SCFAs) and bacterial composition in human infants, and intestinal SCFAs, the microbiota, and host physiology in weanling rats. Fecal Bifidobacterium concentrations (mean log copy number ± SEM) were higher (P = 0.003) in BF (8.17 ± 0.3) and SPCF-fed infants (8.29 ± 0.3) compared with those fed the SFs (6.94 ± 0.3). Fecal acetic acid (mean ± SEM) was also higher (P = 0.007) in the BF (5.5 ± 0.2 mg/g) and SPCF (5.3 ± 2.4 mg/g) groups compared with SF-fed babies (4.3 ± 0.2 mg/g). Colonic SCFAs did not differ between HM- and SPCF-fed rats. However, cecal acetic acid concentrations were higher (P = 0.001) in rats fed HM (42.6 ± 2.6 mg/g) than in those fed SPCF (30.6 ± 0.8 mg/g). Cecal transcriptome, proteome, and plasma metabolite analyses indicated that the growth and maturation of intestinal tissue was more highly promoted by HM than SPCF. Fecal bacterial composition and SCFA concentrations were similar in babies fed SPCF or HM. However, results from the rat study showed substantial differences in host physiology between rats fed HM and SPCF. This trial was registered at Shanghai Jiào tong University School of Medicine as XHEC-C-2012-024. © 2016 American Society for Nutrition.

  3. Determination of carcinoembryonic antigen in patients with tumors of the large intestine

    International Nuclear Information System (INIS)

    Lamerz, R.; Ruider, H.

    1976-01-01

    Specimens from 93 patients with histologically confirmed tumors of the large bowel (53 single, 40 sequential determinations) were investigated by a new CEA radioimmunoassay (double antibody method, direct serum determination). Of the single and preoperative sequential determinations 37-40% were normal (below 2.5 ng/ml), one third was intermediately elevated (2.6 ng/ml) and 26-28% were highly pathological leveled (over 15 ng/ml). Following operation, cases with local or regionally confined tumor showed significantly more normal or normalizing CEA levels within 1-6 weeks (17/27), whereas patients with overt metastases developed more pathological or increasingly pathological levels (8/11). (orig.) [de

  4. Gluten-degrading bacteria are present in the human small intestine of healthy volunteers and celiac patients.

    Science.gov (United States)

    Herrán, Alexandra R; Pérez-Andrés, Jénifer; Caminero, Alberto; Nistal, Esther; Vivas, Santiago; Ruiz de Morales, José María; Casqueiro, Javier

    2017-09-01

    Gluten is the only known environmental factor that triggers celiac disease. Several studies have described an imbalance between the intestinal microbiota of different individuals based on diagnoses. Moreover, recent studies have suggested that human bacteria may play an important role in gluten hydrolysis. However, there has been no research focusing on the small intestine. This study aimed to characterize the adult small intestine microbiota possibly implicated in gluten hydrolysis. Duodenal biopsies from different diagnosed individuals were cultured in a gluten-containing medium, and the grown microbiota was analyzed by culture dependent/independent methods. Results showed that gluten-degrading bacteria can be found in the human small intestine. Indeed, 114 bacterial strains belonging to 32 species were isolated; 85 strains were able to grow in a medium containing gluten as the sole nitrogen source, 31 strains showed extracellular proteolytic activity against gluten protein and 27 strains showed peptidolytic activity towards the 33 mer peptide, an immunogenic peptide for celiac disease patients. We found that there are no differences based on the diagnosis, but each individual has its own population of gluten-hydrolyzing bacteria. These bacteria or their gluten-degrading enzymes could help to improve the quality of life of celiac disease patients'. Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  5. Compartment-specific distribution of human intestinal innate lymphoid cells is altered in HIV patients under effective therapy.

    Directory of Open Access Journals (Sweden)

    Benjamin Krämer

    2017-05-01

    Full Text Available Innate lymphocyte cells (ILCs, a novel family of innate immune cells are considered to function as key orchestrators of immune defences at mucosal surfaces and to be crucial for maintaining an intact intestinal barrier. Accordingly, first data suggest depletion of ILCs to be involved in human immunodeficiency virus (HIV-associated damage of the intestinal mucosa and subsequent microbial translocation. However, although ILCs are preferentially localized at mucosal surfaces, only little is known regarding distribution and function of ILCs in the human gastrointestinal tract. Here, we show that in HIV(- individuals composition and functional capacity of intestinal ILCs is compartment-specific with group 1 ILCs representing the major fraction in the upper gastrointestinal (GI tract, whereas ILC3 are the predominant population in ileum and colon, respectively. In addition, we present first data indicating that local cytokine concentrations, especially that of IL-7, might modulate composition of gut ILCs. Distribution of intestinal ILCs was significantly altered in HIV patients, who displayed decreased frequency of total ILCs in ileum and colon owing to reduced numbers of both CD127(+ILC1 and ILC3. Of note, frequency of colonic ILC3 was inversely correlated with serum levels of I-FABP and sCD14, surrogate markers for loss of gut barrier integrity and microbial translocation, respectively. Both expression of the IL-7 receptor CD127 on ILCs as well as mucosal IL-7 mRNA levels were decreased in HIV(+ patients, especially in those parts of the GI tract with reduced ILC frequencies, suggesting that impaired IL-7 responses of ILCs might contribute to incomplete reconstitution of ILCs under effective anti-retroviral therapy. This is the first report comparing distribution and function of ILCs along the intestinal mucosa of the entire human gastrointestinal tract in HIV(+ and HIV(- individuals.

  6. The role of metabolism in Diclofenac-induced intestinal toxicity in human ex vivo

    NARCIS (Netherlands)

    Niu, Xiaoyu; Makkinje, Miriam; de Graaf, Inge; Groothuis, Genoveva

    2012-01-01

    The use of Diclofenac (DCF: 2-(2,6-dichloranilino) phenyl acetic acid ), a non-steroidal anti-inflammatory drug is associated with severe gastro-intestinal side-effects. In vivo rat studies suggest that reactive metabolites of DCF, produced by the liver, play an important role in the intestinal

  7. Assessment of the mode of action underlying development of rodent small intestinal tumors following oral exposure to hexavalent chromium and relevance to humans

    Science.gov (United States)

    Proctor, Deborah M.; Suh, Mina; Haws, Laurie C.; Kirman, Christopher R.; Harris, Mark A.

    2013-01-01

    Chronic exposure to high concentrations of hexavalent chromium (Cr(VI)) in drinking water causes intestinal adenomas and carcinomas in mice, but not in rats. Cr(VI) causes damage to intestinal villi and crypt hyperplasia in mice after only one week of exposure. After two years of exposure, intestinal damage and crypt hyperplasia are evident in mice (but not rats), as are intestinal tumors. Although Cr(VI) has genotoxic properties, these findings suggest that intestinal tumors in mice arise as a result of chronic mucosal injury. To better understand the mode of action (MOA) of Cr(VI) in the intestine, a 90-day drinking water study was conducted to collect histological, biochemical, toxicogenomic and pharmacokinetic data in intestinal tissues. Using MOA analyses and human relevance frameworks proposed by national and international regulatory agencies, the weight of evidence supports a cytotoxic MOA with the following key events: (a) absorption of Cr(VI) from the intestinal lumen, (b) toxicity to intestinal villi, (c) crypt regenerative hyperplasia and (d) clonal expansion of mutations within the crypt stem cells, resulting in late onset tumorigenesis. This article summarizes the data supporting each key event in the MOA, as well as data that argue against a mutagenic MOA for Cr(VI)-induced intestinal tumors. PMID:23445218

  8. Present status and future view on virtual endoscopy. Depiction of minute lesions in the large intestine with CT colonography

    International Nuclear Information System (INIS)

    Sugino, Yoshinori

    2002-01-01

    CT colonography is a new imaging technique using helical CT. We studied the efficacy of CT colonoscopy in the detection of small polyps and depiction of superficial lesions. Concerning the detection of small polyps, we studied 54 patients with abnormality checked by barium enema. Conventional colonoscopy revealed 79 lesions (5 advanced carcinomas, 4 superficial-type adenomas and 70 polyps). CT colonography identified all 5 carcinomas, 3 of the 4 superficial lesions and 43 of the 45 polyps that were 0.5 cm or smaller in diameter, 18 of 22 polyps that were 0.6 to 0.9 cm, and all 3 polyps that were 1.0 cm or more in diameter. There were 92 false positive polyps that were 0.5 cm or smaller in diameter. On a superficial lesion, we could depict a superficial depressive type early colonic carcinoma 1.0 cm in diameter, using very thin-slice CT equipment. In conclusion, CT colonography has a high sensitivity for detection of small polyps and sufficient capability for depiction of superficial lesions. CT colonography may be suitable for screening examinations of the large intestine. (author)

  9. Epidemiology of large intestinal cancer in Nagasaki city with reference to atomic bomb exposure, 1973∼1982

    International Nuclear Information System (INIS)

    Kinoshita, Shingo; Shimokawa, Isao; Iwasaki, Keisuke; Sakai, Hidetaka; Matsuo, Takeshi; Ikeda, Takayoshi; Mori, Hiroyuki; Mine, Mariko

    1988-01-01

    Epidemiological studies were conducted on 1098 cases of large intestinal cancer (615 cases of colon cancer and 483 cases of rectum cancer) registered at the Nagasaki Tumor Registry from 1973 to 1982, with emphasis on the relation to radiation exposure. The incidence in atomic bomb survivors was not significantly different from that in non-exposed persons, but the incidence in persons exposed at a young age tends to be higher, particularly the incidence of colon cancer in females. By site, about 56% of all colorectal cases investigated were shown to originate in the colon. In the colon, sigmoid cancer was the most frequent in both males and females, but there was no difference with regard to exposure status. In a comparison of the incidence during the first and second halves of the period examined, colorectal cancer revealed a general increasing trend, particularly for colon cancer in males and rectum cancer in females. Histologically, over 90% was differentiated adenocarcinoma and showed no difference by age, sex or exposure status. Nevertheless, it is noteworthy that musinous carcinoma was more frequent in atomic bomb survivors than in non-exposed people. Further analysis of the incidence, site and histologic type of colorectal cancer, especially in the group exposed at a young age, is necessary. (author)

  10. Enteroendocrine, Musashi 1 and neurogenin 3 cells in the large intestine of Thai and Norwegian patients with irritable bowel syndrome.

    Science.gov (United States)

    El-Salhy, Magdy; Patcharatrakul, Tanisa; Hatlebakk, Jan Gunnar; Hausken, Trygve; Gilja, Odd Helge; Gonlachanvit, Sutep

    2017-12-01

    The prevalence, gender distribution and clinical presentation of IBS differ between Asian and Western countries. This study aimed at studying and comparing enteroendocrine, Musashi 1 (Msi 1) and neurogenin 3 (neurog 3) cells in Thai and Norwegian IBS patients. Thirty Thai and 61 Norwegian IBS patients as well as 20 Thai and 24 Norwegian controls were included. Biopsy samples were taken from each of the sigmoid colon and the rectum during a standard colonoscopy. The samples were immunostained for serotonin, peptide YY, oxyntomodulin, pancreatic polypeptide, somatostatin, Msi 1 and neurog 3. The densities of immunoreactive cells were determined with computerized image analysis. The densities of several enteroendocrine cell types were altered in both the colon and rectum of both Thai and Norwegian IBS patients. Some of these changes were similar in Thai and Norwegian IBS patients, while others differed. The findings of abnormal densities of the enteroendocrine cells in Thai patients support the notion that enteroendocrine cells are involved in the pathophysiology of IBS. The present observations highlight that IBS differs in Asian and Western countries, and show that the changes in large-intestine enteroendocrine cells in Thai and Norwegian IBS patients might be caused by different mechanisms.

  11. Towards a defined ECM and small molecule based monolayer culture system for the expansion of mouse and human intestinal stem cells.

    Science.gov (United States)

    Tong, Zhixiang; Martyn, Keir; Yang, Andy; Yin, Xiaolei; Mead, Benjamin E; Joshi, Nitin; Sherman, Nicholas E; Langer, Robert S; Karp, Jeffrey M

    2018-02-01

    Current ISC culture systems face significant challenges such as animal-derived or undefined matrix compositions, batch-to-batch variability (e.g. Matrigel-based organoid culture), and complexity of assaying cell aggregates such as organoids which renders the research and clinical translation of ISCs challenging. Here, through screening for suitable ECM components, we report a defined, collagen based monolayer culture system that supports the growth of mouse and human intestinal epithelial cells (IECs) enriched for an Lgr5 + population comparable or higher to the levels found in a standard Matrigel-based organoid culture. The system, referred to as the Bolstering Lgr5 Transformational (BLT) Sandwich culture, comprises a collagen IV-coated porous substrate and a collagen I gel overlay which sandwich an IEC monolayer in between. The distinct collagen cues synergistically regulate IEC attachment, proliferation, and Lgr5 expression through maximizing the engagement of distinct cell surface adhesion receptors (i.e. integrin α2β1, integrin β4) and cell polarity. Further, we apply our BLT Sandwich system to identify that the addition of a bone morphogenetic protein (BMP) receptor inhibitor (LDN-193189) improves the expansion of Lgr5-GFP + cells from mouse small intestinal crypts by nearly 2.5-fold. Notably, the BLT Sandwich culture is capable of expanding human-derived IECs with higher LGR5 mRNA levels than conventional Matrigel culture, providing superior expansion of human LGR5 + ISCs. Considering the key roles Lgr5 + ISCs play in intestinal epithelial homeostasis and regeneration, we envision that our BLT Sandwich culture system holds great potential for understanding and manipulating ISC biology in vitro (e.g. for modeling ISC-mediated gut diseases) or for expanding a large number of ISCs for clinical utility (e.g. for stem cell therapy). Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Antoine Huguet

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

  13. Human intestinal parasites in crusader Acre: Evidence for migration with disease in the medieval period.

    Science.gov (United States)

    Mitchell, Piers D; Anastasiou, Evilena; Syon, Danny

    2011-12-01

    The aim of this research is to highlight the role of ancient parasites as evidence for human migration in past populations. The material analysed was soil sediment from the excavation of a medieval cesspool in the city of Acre, in Israel. Archaeological stratigraphy and radiocarbon dating of a fragment of animal bone from the cesspool confirm its use in the 13th century CE, during the crusader period. At that time Acre was located in the Frankish Kingdom of Jerusalem. Soil samples from the cesspool were analysed and eggs of the roundworm (Ascaris lumbricoides) and fish tapeworm (Diphyllobothrium latum) were identified. The fish tapeworm has only been found in the mainland Near East once before, in a latrine of the crusader Order of St. John (Knights Hospitaller). It has been absent in all earlier cesspools, latrines and coprolites so far studied in the region. In contrast to its rarity in the Levant, the fish tapeworm was common in northern Europe during the medieval period. The presence of fish tapeworm eggs in a crusader period cesspool in Acre suggests its use by crusaders or pilgrims from northern Europe who travelled to the Levant carrying these parasites in their intestines. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Assessment of adhesion properties of novel probiotic strains to human intestinal mucus.

    Science.gov (United States)

    Ouwehand, A C; Tuomola, E M; Tölkkö, S; Salminen, S

    2001-02-28

    Potential new probiotic strains Lactobacillus brevis PELI, L. reuteri ING1, L. rhamnosus VTT E-800 and L. rhamnosus LC-705 were assessed for their adhesion properties using the human intestinal mucus model. The effect on the adhesion of exposure to acid and pepsin and to milk were tested to simulate gastric and food processing conditions, and the effect of different growth media on adhesion was tested. The properties of the four strains were compared to the well-investigated probiotic L. rhamnosus strain GG. Three of the tested strains showed significant adhesion properties in the mucus model, while L. brevis PELI had intermediate adhesion and L. rhamnosus LC-705 adhered poorly. Pretreatment with different milks decreased the adhesion and low pH and pepsin treatment reduced the adhesion of all tested strains except L. rhamnosus LC-705. No competitive exclusion of pathogenic Salmonella typhimurium or Escherichia coli SfaII was observed. The results indicate that major differences exist between tested proposed probiotic strains. The growth media and the food matrix significantly affect the adhesive ability of the tested strains. This has previously not been taken into account when selecting novel probiotic strains.

  15. Assessment of the prebiotic effect of quinoa and amaranth in the human intestinal ecosystem.

    Science.gov (United States)

    Gullón, Beatriz; Gullón, Patricia; Tavaria, Freni K; Yáñez, Remedios

    2016-09-14

    Quinoa and amaranth belong to the group of the so called "superfoods" and have a nutritional composition that confers multiple benefits. In this work, we explored the possibility of these foods exhibiting a prebiotic effect. These pseudocereals were subjected to an in vitro digestion and used as carbon sources in batch cultures with faecal human inocula. The effects on the microbiota composition and their metabolic products were determined by assessment of variations in pH, short-chain fatty acid (SCFA) production and changes in the dynamic bacterial populations by fluorescence in situ hybridization (FISH). After 48 h of incubation, the total SCFAs were 106.5 mM for quinoa and 108.83 mM for amaranth, in line with the decrease in pH. Considerable differences (p spp., Lactobacillus-Enterococcus, Atopobium, Bacteroides-Prevotella, Clostridium coccoides-Eubacterium rectale, Faecalibacterium prausnitzii and Roseburia intestinalis. Our research suggests that these pseudocereals can have the prebiotic potential and that their intake may improve dysbiosis or maintain the gastrointestinal health through a balanced intestinal microbiota, although additional studies are necessary.

  16. Human behaviour can trigger large carnivore attacks in developed countries.

    Science.gov (United States)

    Penteriani, Vincenzo; Delgado, María del Mar; Pinchera, Francesco; Naves, Javier; Fernández-Gil, Alberto; Kojola, Ilpo; Härkönen, Sauli; Norberg, Harri; Frank, Jens; Fedriani, José María; Sahlén, Veronica; Støen, Ole-Gunnar; Swenson, Jon E; Wabakken, Petter; Pellegrini, Mario; Herrero, Stephen; López-Bao, José Vicente

    2016-02-03

    The media and scientific literature are increasingly reporting an escalation of large carnivore attacks on humans in North America and Europe. Although rare compared to human fatalities by other wildlife, the media often overplay large carnivore attacks on humans, causing increased fear and negative attitudes towards coexisting with and conserving these species. Although large carnivore populations are generally increasing in developed countries, increased numbers are not solely responsible for the observed rise in the number of attacks by large carnivores. Here we show that an increasing number of people are involved in outdoor activities and, when doing so, some people engage in risk-enhancing behaviour that can increase the probability of a risky encounter and a potential attack. About half of the well-documented reported attacks have involved risk-enhancing human behaviours, the most common of which is leaving children unattended. Our study provides unique insight into the causes, and as a result the prevention, of large carnivore attacks on people. Prevention and information that can encourage appropriate human behaviour when sharing the landscape with large carnivores are of paramount importance to reduce both potentially fatal human-carnivore encounters and their consequences to large carnivores.

  17. Evaluation of an FDA approved library against laboratory models of human intestinal nematode infections.

    Science.gov (United States)

    Keiser, Jennifer; Panic, Gordana; Adelfio, Roberto; Cowan, Noemi; Vargas, Mireille; Scandale, Ivan

    2016-07-01

    Treatment options for infections with soil-transmitted helminths (STH) - Ascaris lumbricoides, Trichuris trichiura and the two hookworm species, Ancylostoma duodenale and Necator americanus - are limited despite their considerable global health burden. The aim of the present study was to test the activity of an openly available FDA library against laboratory models of human intestinal nematode infections. All 1,600 drugs were first screened against Ancylostoma ceylanicum third-stage larvae (L3). Active compounds were scrutinized and toxic compounds, drugs indicated solely for topical use, and already well-studied anthelmintics were excluded. The remaining hit compounds were tested in parallel against Trichuris muris first-stage larvae (L1), Heligmosomoides polygyrus third-stage larvae (L3), and adult stages of the three species in vitro. In vivo studies were performed in the H. polygyrus and T. muris mice models. Fifty-four of the 1,600 compounds tested revealed an activity of > 60 % against A. ceylanicum L3 (hit rate of 3.4 %), following incubation at 200 μM for 72 h. Twelve compounds progressed into further screens. Adult A. ceylanicum were the least affected (1/12 compounds active at 50 μM), while eight of the 12 test compounds revealed activity against T. muris L1 (100 μM) and adults (50 μM), and H. polygyrus L3 (200 μM). Trichlorfon was the only compound active against all stages of A. ceylanicum, H. polygyrus and T. muris. In addition, trichlorfon achieved high worm burden reductions of 80.1 and 98.9 %, following a single oral dose of 200 mg/kg in the T. muris and H. polygyrus mouse model, respectively. Drug screening on the larval stages of intestinal parasitic nematodes is feasible using small libraries and important given the empty drug discovery and development pipeline for STH infections. Differences and commonalities in drug activities across the different STH species and stages were confirmed. Hits identified might serve as a

  18. Alterations in human milk leptin and insulin are associated with early changes in the infant intestinal microbiome.

    Science.gov (United States)

    Lemas, Dominick J; Young, Bridget E; Baker, Peter R; Tomczik, Angela C; Soderborg, Taylor K; Hernandez, Teri L; de la Houssaye, Becky A; Robertson, Charles E; Rudolph, Michael C; Ir, Diana; Patinkin, Zachary W; Krebs, Nancy F; Santorico, Stephanie A; Weir, Tiffany; Barbour, Linda A; Frank, Daniel N; Friedman, Jacob E

    2016-05-01

    Increased maternal body mass index (BMI) is a robust risk factor for later pediatric obesity. Accumulating evidence suggests that human milk (HM) may attenuate the transfer of obesity from mother to offspring, potentially through its effects on early development of the infant microbiome. Our objective was to identify early differences in intestinal microbiota in a cohort of breastfeeding infants born to obese compared with normal-weight (NW) mothers. We also investigated relations between HM hormones (leptin and insulin) and both the taxonomic and functional potentials of the infant microbiome. Clinical data and infant stool and fasting HM samples were collected from 18 NW [prepregnancy BMI (in kg/m(2)) obese (prepregnancy BMI >30.0) mothers and their exclusively breastfed infants at 2 wk postpartum. Infant body composition at 2 wk was determined by air-displacement plethysmography. Infant gastrointestinal microbes were estimated by using 16S amplicon and whole-genome sequencing. HM insulin and leptin were determined by ELISA; short-chain fatty acids (SCFAs) were measured in stool samples by using gas chromatography. Power was set at 80%. Infants born to obese mothers were exposed to 2-fold higher HM insulin and leptin concentrations (P obesity may adversely affect the early infant intestinal microbiome, HM insulin and leptin are independently associated with beneficial microbial metabolic pathways predicted to increase intestinal barrier function and reduce intestinal inflammation. This trial was registered at clinicaltrials.gov as NCT01693406. © 2016 American Society for Nutrition.

  19. Calcium Imaging of Nerve-Mast Cell Signaling in the Human Intestine

    Directory of Open Access Journals (Sweden)

    Sabine Buhner

    2017-11-01

    Full Text Available Introduction: It is suggested that an altered microenvironment in the gut wall alters communication along a mast cell nerve axis. We aimed to record for the first time signaling between mast cells and neurons in intact human submucous preparations.Methods: We used the Ca2+ sensitive dye Fluo-4 AM to simultaneously image changes in intracellular calcium [Ca+2]i (%ΔF/F in neurons and mast cells. Data are presented as median with interquartile ranges (25/75%.Results: We recorded nerve responses in 29 samples upon selective activation of 223 mast cells by IgE receptor cross linking with the antibody mAb22E7. Mast cells responded to mAb22E7 with a median [Ca+2]i increase of 20% (11/39 peaking 90 s (64/144 after the application. Only very few neurons responded and the median percentage of responding neuronal area was 0% (0/5.9. Mast cell activation remained in the presence of the fast sodium channel blocker tetrodotoxin. Specific neuronal activation by transmural electrical field stimulation (EFS in 34 samples evoked instantaneously [Ca+2]i signals in submucous neurons. This was followed by a [Ca+2]i peak response of 8%ΔF/F (4/15 in 33% of 168 mast cells in the field of view. The mast cell response was abolished by the nerve blocker tetrododoxin, reduced by the Calcitonin Gene-Related Peptide receptor 1 antagonist BIBN-4096 and the Vasoactive Intestinal Peptide receptor antagonist PG97-269, but not by blockade of the neurokinin receptors 1–3.Conclusion: The findings revealed bidirectional signaling between mast cells and submucous neurons in human gut. In our macroscopically normal preparations a nerve to mast cell signaling was very prominent whereas a mast cell to nerve signaling was rather rare.

  20. Linking Spatial Structure and Community-Level Biotic Interactions through Cooccurrence and Time Series Modeling of the Human Intestinal Microbiota.

    Science.gov (United States)

    de Muinck, Eric J; Lundin, Knut E A; Trosvik, Pål

    2017-01-01

    The gastrointestinal (GI) microbiome is a densely populated ecosystem where dynamics are determined by interactions between microbial community members, as well as host factors. The spatial organization of this system is thought to be important in human health, yet this aspect of our resident microbiome is still poorly understood. In this study, we report significant spatial structure of the GI microbiota, and we identify general categories of spatial patterning in the distribution of microbial taxa along a healthy human GI tract. We further estimate the biotic interaction structure in the GI microbiota, both through time series and cooccurrence modeling of microbial community data derived from a large number of sequentially collected fecal samples. Comparison of these two approaches showed that species pairs involved in significant negative interactions had strong positive contemporaneous correlations and vice versa, while for species pairs without significant interactions, contemporaneous correlations were distributed around zero. We observed similar patterns when comparing these models to the spatial correlations between taxa identified in the adherent microbiota. This suggests that colocalization of microbial taxon pairs, and thus the spatial organization of the GI microbiota, is driven, at least in part, by direct or indirect biotic interactions. Thus, our study can provide a basis for an ecological interpretation of the biogeography of the human gut. IMPORTANCE The human gut microbiome is the subject of intense study due to its importance in health and disease. The majority of these studies have been based on the analysis of feces. However, little is known about how the microbial composition in fecal samples relates to the spatial distribution of microbial taxa along the gastrointestinal tract. By characterizing the microbial content both in intestinal tissue samples and in fecal samples obtained daily, we provide a conceptual framework for how the spatial

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

    OpenAIRE

    Mabbott, Neil A.

    2015-01-01

    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 ...

  2. Changes of Locoregional Skin Temperature in Neonates Undergoing Laser Needle Acupuncture at the Acupuncture Point Large Intestine 4

    Directory of Open Access Journals (Sweden)

    Stefan Kurath-Koller

    2015-01-01

    Full Text Available Laser acupuncture bears a potential risk for the skin surface, especially in neonates whose skin has histological and physiological peculiarities. We evaluated thermal changes of skin temperature in neonates during laser acupuncture by using a thermal camera (Flir i5, Flir Systems Inc., Portland, USA. Laserneedles (Laserneedle GmbH, Glienicke/Nordbahn, Germany were fixed to the skin at Large Intestine 4 (LI 4, Hegu, bilaterally. Before application of laser acupuncture (685 nm, 15 mW, 500 μm, as well as after 1, 5, and 10 min, thermographic pictures of both hands were taken. The measuring was carried out on the 23rd day after birth (20 neonates, mean postmenstrual gestational age 38 + 2, mean weight 2604 g. Compared to the initial temperature of 34.2°C on the right hand, the skin temperature had increased to 35.3°C (P<0.05 after 5 min and up to 36.1°C (P<0.05 after 10 min of stimulation. Equally, on the left hand, an increase of the skin temperature from 34.5°C to 35.9°C (P<0.05 and 35.9°C (P<0.05 was measured. The highest measured skin temperature after 10 min of stimulation amounted to 38.7°C, without any clinically visible changes on the skin surface.

  3. 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

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

    International Nuclear Information System (INIS)

    Brunet, Jean-Luc; Maresca, Marc; Fantini, Jacques; Belzunces, Luc P.

    2004-01-01

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

  5. 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.

  6. 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

  7. Suppressive effect of nobiletin and epicatechin gallate on fructose uptake in human intestinal epithelial Caco-2 cells.

    Science.gov (United States)

    Satsu, Hideo; Awara, Sohei; Unno, Tomonori; Shimizu, Makoto

    2018-04-01

    Inhibition of excessive fructose intake in the small intestine could alleviate fructose-induced diseases such as hypertension and non-alcoholic fatty liver disease. We examined the effect of phytochemicals on fructose uptake using human intestinal epithelial-like Caco-2 cells which express the fructose transporter, GLUT5. Among 35 phytochemicals tested, five, including nobiletin and epicatechin gallate (ECg), markedly inhibited fructose uptake. Nobiletin and ECg also inhibited the uptake of glucose but not of L-leucine or Gly-Sar, suggesting an inhibitory effect specific to monosaccharide transporters. Kinetic analysis further suggested that this reduction in fructose uptake was associated with a decrease in the apparent number of cell-surface GLUT5 molecules, and not with a change in the affinity of GLUT5 for fructose. Lastly, nobiletin and ECg suppressed the permeation of fructose across Caco-2 cell monolayers. These findings suggest that nobiletin and ECg are good candidates for preventing diseases caused by excessive fructose intake.

  8. Di-tri-octahedral smectite for the prevention of post-operative diarrhea in equids with surgical disease of the large intestine: results of a randomized clinical trial.

    Science.gov (United States)

    Hassel, Diana M; Smith, Phoebe A; Nieto, Jorge E; Beldomenico, Pablo; Spier, Sharon J

    2009-11-01

    The aim of this study was to evaluate the effects of a commercially available di-tri-octahedral (DTO) smectite product on clinical signs and prevalence of post-operative diarrhea in horses with colic associated with disease of the large intestine. Sixty-seven horses with surgical disease of the large intestine were randomly assigned to be treated with DTO smectite (n=37; 0.5 kg via nasogastric intubation every 24 h for 3 days post-operatively) or a placebo (n=30). The effect of treatment on fecal scores and clinical and hematological parameters, including heart rate, mucous membrane color, temperature, total white blood cell count, total neutrophil count and total plasma protein values, were determined. Horses treated with DTO smectite had a significant reduction in the prevalence of post-operative diarrhea (10.8%), compared with controls (41.4%). A significant improvement in mucous membrane color was observed 72 h post-operatively in horses receiving treatment, compared with placebo. Administration of DTO smectite to colic patients with disease of the large intestine reduced the occurrence of diarrhea in the early post-operative period.

  9. Intestinal Bacterial Communities of Trypanosome-Infected and Uninfected Glossina palpalis palpalis from Three Human African Trypanomiasis Foci in Cameroon

    Directory of Open Access Journals (Sweden)

    Franck Jacob

    2017-08-01

    Full Text Available Glossina sp. the tsetse fly that transmits trypanosomes causing the Human or the Animal African Trypanosomiasis (HAT or AAT can harbor symbiotic bacteria that are known to play a crucial role in the fly's vector competence. We hypothesized that other bacteria could be present, and that some of them could also influence the fly's vector competence. In this context the objectives of our work were: (a to characterize the bacteria that compose the G. palpalis palpalis midgut bacteriome, (b to evidence possible bacterial community differences between trypanosome-infected and non-infected fly individuals from a given AAT and HAT focus or from different foci using barcoded Illumina sequencing of the hypervariable V3-V4 region of the 16S rRNA gene. Forty G. p. palpalis flies, either infected by Trypanosoma congolense or uninfected were sampled from three trypanosomiasis foci in Cameroon. A total of 143 OTUs were detected in the midgut samples. Most taxa were identified at the genus level, nearly 50% at the species level; they belonged to 83 genera principally within the phyla Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria. Prominent representatives included Wigglesworthia (the fly's obligate symbiont, Serratia, and Enterobacter hormaechei. Wolbachia was identified for the first time in G. p. palpalis. The average number of bacterial species per tsetse sample was not significantly different regarding the fly infection status, and the hierarchical analysis based on the differences in bacterial community structure did not provide a clear clustering between infected and non-infected flies. Finally, the most important result was the evidence of the overall very large diversity of intestinal bacteria which, except for Wigglesworthia, were unevenly distributed over the sampled flies regardless of their geographic origin and their trypanosome infection status.

  10. 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

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

    DEFF Research Database (Denmark)

    Rumessen, Jüri Johannes; Thuneberg, Lars

    1991-01-01

    Anatomy, interstitial cells of Cajal, small intestine, gut motility, pacemaker cells, smooth muscle......Anatomy, interstitial cells of Cajal, small intestine, gut motility, pacemaker cells, smooth muscle...

  12. 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...

  13. Intestinal cytochromes P450 regulating the intestinal microbiota and its probiotic profile

    Directory of Open Access Journals (Sweden)

    Eugenia Elefterios Venizelos Bezirtzoglou

    2012-09-01

    Full Text Available Cytochromes P450 (CYPs enzymes metabolize a large variety of xenobiotic substances. In this vein, a plethora of studies were conducted to investigate their role, as cytochromes are located in both liver and intestinal tissues. The P450 profile of the human intestine has not been fully characterized. Human intestine serves primarily as an absorptive organ for nutrients, although it has also the ability to metabolize drugs. CYPs are responsible for the majority of phase I drug metabolism reactions. CYP3A represents the major intestinal CYP (80% followed by CYP2C9. CYP1A is expressed at high level in the duodenum, together with less abundant levels of CYP2C8-10 and CYP2D6. Cytochromes present a genetic polymorphism intra- or interindividual and intra- or interethnic. Changes in the pharmacokinetic profile of the drug are associated with increased toxicity due to reduced metabolism, altered efficacy of the drug, increased production of toxic metabolites, and adverse drug interaction. The high metabolic capacity of the intestinal flora is due to its enormous pool of enzymes, which catalyzes reactions in phase I and phase II drug metabolism. Compromised intestinal barrier conditions, when rupture of the intestinal integrity occurs, could increase passive paracellular absorption. It is clear that high microbial intestinal charge following intestinal disturbances, ageing, environment, or food-associated ailments leads to the microbial metabolism of a drug before absorption. The effect of certain bacteria having a benefic action on the intestinal ecosystem has been largely discussed during the past few years by many authors. The aim of the probiotic approach is to repair the deficiencies in the gut flora and establish a protective effect. There is a tentative multifactorial association of the CYP (P450 cytochrome role in the different diseases states, environmental toxic effects or chemical exposures and nutritional status.

  14. Human milk oligosaccharide effects on intestinal function and inflammation after preterm birth in pigs

    DEFF Research Database (Denmark)

    Rasmussen, Stine O.; Martin, Lena; Østergaard, Mette V.

    2017-01-01

    (IF) improves intestinal function, bacterial colonization and NEC resistance immediately after preterm birth, as tested in a preterm pig model. Mixtures of HMOs were investigated in intestinal epithelial cells and in preterm pigs (n=112) fed IF supplemented without (CON) or with a mixture of four HMOs...... (4-HMO) or >25 HMOs (25-HMO, 5-10 g/L given for 5 or 11 days). The 25-HMO blend decreased cell proliferation and both HMO blends decreased lipopolysaccharide-induced interleukin-8 secretion in IPEC-J2 cells, relative to control (P

  15. Modifiable risk factors for typhoid intestinal perforations during a large outbreak of typhoid fever, Kampala Uganda, 2015.

    Science.gov (United States)

    Bulage, Lilian; Masiira, Ben; Ario, Alex R; Matovu, Joseph K B; Nsubuga, Peter; Kaharuza, Frank; Nankabirwa, Victoria; Routh, Janell; Zhu, Bao-Ping

    2017-09-25

    Between January and June, 2015, a large typhoid fever outbreak occurred in Kampala, Uganda, with 10,230 suspected cases. During the outbreak, area surgeons reported a surge in cases of typhoid intestinal perforation (TIP), a complication of typhoid fever. We conducted an investigation to characterize TIP cases and identify modifiable risk factors for TIP. We defined a TIP case as a physician-diagnosed typhoid patient with non-traumatic terminal ileum perforation. We identified cases by reviewing medical records at all five major hospitals in Kampala from 2013 to 2015. In a matched case-control study, we compared potential risk factors among TIP cases and controls; controls were typhoid patients diagnosed by TUBEX TF, culture, or physician but without TIP, identified from the outbreak line-list and matched to cases by age, sex and residence. Cases and controls were interviewed using a standard questionnaire from 1st -23rd December 2015. We used conditional logistic regression to assess risk factors for TIP and control for confounding. Of the 88 TIP cases identified during 2013-2015, 77% (68/88) occurred between January and June, 2015; TIPs sharply increased in January and peaked in March, coincident with the typhoid outbreak. The estimated risk of TIP was 6.6 per 1000 suspected typhoid infections (68/10,230). The case-fatality rate was 10% (7/68). Cases sought care later than controls; Compared with 29% (13/45) of TIP cases and 63% (86/137) of controls who sought treatment within 3 days of onset, 42% (19/45) of cases and 32% (44/137) of controls sought treatment 4-9 days after illness onset (OR adj  = 2.2, 95%CI = 0.83-5.8), while 29% (13/45) of cases and 5.1% (7/137) of controls sought treatment ≥10 days after onset (OR adj  = 11, 95%CI = 1.9-61). 68% (96/141) of cases and 23% (23/100) of controls had got treatment before being treated at the treatment centre (OR adj  = 9.0, 95%CI = 1.1-78). Delay in seeking treatment increased the risk of TIPs

  16. 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. © 2015 Wiley Periodicals, Inc.

  17. Spatiotemporal property and predictability of large-scale human mobility

    Science.gov (United States)

    Zhang, Hai-Tao; Zhu, Tao; Fu, Dongfei; Xu, Bowen; Han, Xiao-Pu; Chen, Duxin

    2018-04-01

    Spatiotemporal characteristics of human mobility emerging from complexity on individual scale have been extensively studied due to the application potential on human behavior prediction and recommendation, and control of epidemic spreading. We collect and investigate a comprehensive data set of human activities on large geographical scales, including both websites browse and mobile towers visit. Numerical results show that the degree of activity decays as a power law, indicating that human behaviors are reminiscent of scale-free random walks known as Lévy flight. More significantly, this study suggests that human activities on large geographical scales have specific non-Markovian characteristics, such as a two-segment power-law distribution of dwelling time and a high possibility for prediction. Furthermore, a scale-free featured mobility model with two essential ingredients, i.e., preferential return and exploration, and a Gaussian distribution assumption on the exploration tendency parameter is proposed, which outperforms existing human mobility models under scenarios of large geographical scales.

  18. Non-biting cyclorrhaphan flies (Diptera) as carriers of intestinal human parasites in slum areas of Addis Ababa, Ethiopia.

    Science.gov (United States)

    Getachew, Sisay; Gebre-Michael, Teshome; Erko, Berhanu; Balkew, Meshesha; Medhin, Girmay

    2007-09-01

    A study was conducted to determine the role of non-biting cyclorrhaphan flies as carriers of intestinal parasites in slum areas of Addis Ababa from January 2004 to June 2004. A total of 9550 flies, comprising of at least seven species were collected from four selected sites and examined for human intestinal parasites using the formol-ether concentration method. The dominant fly species was Chrysomya rufifacies (34.9%) followed by Musca domestica (31%), Musca sorbens (20.5.%), Lucina cuprina (6.8%), Sarcophaga sp. (2.8%), Calliphora vicina (2.2%) and Wohlfahrtia sp. (1.8%). Six intestinal helminths (Ascaris lumbricoides, Trichuris trichiura, hookworms, Hymenolepis nana, Taenia spp. and Strongyloides stercoralis) and at least four protozoan parasites (Entamoeba histolytica/dispar, Entamoeba coli, Giardia lamblia and Cryptosporidium sp.) were isolated from both the external and gut contents of the flies. A. lumbricoides and T. trichiura among the helminths and E. histolytica/dispar and E. coli among the protozoans were the dominant parasites detected both on the external and in the gut contents of the flies, but occurring more in the latter. Among the flies, C. rufifacies and M. sorbens were the highest carriers of the helminth and protozoan parasites, respectively. The public health significance of these findings is highlighted.

  19. 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

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

    Science.gov (United States)

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

    2009-05-01

    Enterotoxigenic Escherichia coli (ETEC) use colonization factors to attach to the human intestinal mucosa, followed by enterotoxin expression that induces net secretion and diarrhoeal illness. ETEC strain H10407 expresses CFA/I fimbriae, which are composed of multiple CfaB structural subunits and a CfaE tip subunit. Currently, the contribution of these individual fimbrial subunits in intestinal binding remains incompletely defined. To identify the role of CfaE in attachment in the native ETEC background, an R181A single-amino-acid substitution was introduced by recombination into the H10407 genome. The substitution of R181A eliminated haemagglutination and binding of intestinal mucosa biopsies in in vitro organ culture assays, without loss of CFA/I fimbriae expression. Wild-type in trans plasmid-expressed cfaE restored the binding phenotype. In contrast, in trans expression of cfaE containing amino acid 181 substitutions with similar amino acids, lysine, methionine and glutamine did not restore the binding phenotype, indicating that the loss of the binding phenotype was due to localized areas of epitope disruption. R181 appears to have an irreplaceable role in the formation of a receptor-binding feature on CFA/I fimbriae. The results specifically indicate that the CfaE tip protein is a required binding factor in CFA/I-mediated ETEC colonization, making it a potentially important vaccine antigen. © 2009 Blackwell Publishing Ltd.

  1. Cellular mechanisms underlying the inhibitory effect of flufenamic acid on chloride secretion in human intestinal epithelial cells

    Directory of Open Access Journals (Sweden)

    Pawin Pongkorpsakol

    2017-06-01

    Full Text Available Intestinal Cl− secretion is involved in the pathogenesis of secretory diarrheas including cholera. We recently demonstrated that flufenamic acid (FFA suppressed Vibrio cholerae El Tor variant-induced intestinal fluid secretion via mechanisms involving AMPK activation and NF-κB-suppression. The present study aimed to investigate the effect of FFA on transepithelial Cl− secretion in human intestinal epithelial (T84 cells. FFA inhibited cAMP-dependent Cl− secretion in T84 cell monolayers with IC50 of ∼8 μM. Other fenamate drugs including tolfenamic acid, meclofenamic acid and mefenamic acid exhibited the same effect albeit with lower potency. FFA also inhibited activities of CFTR, a cAMP-activated apical Cl− channel, and KCNQ1/KCNE3, a cAMP-activated basolateral K+ channel. Mechanisms of CFTR inhibition by FFA did not involve activation of its negative regulators. Interestingly, FFA inhibited Ca2+-dependent Cl− secretion with IC50 of ∼10 μM. FFA inhibited activities of Ca2+-activated Cl− channels and KCa3.1, a Ca2+-activated basolateral K+ channels, but had no effect on activities of Na+–K+–Cl− cotransporters and Na+–K+ ATPases. These results indicate that FFA inhibits both cAMP and Ca2+-dependent Cl− secretion by suppressing activities of both apical Cl− channels and basolateral K+ channels. FFA and other fenamate drugs may be useful in the treatment of secretory diarrheas.

  2. INFLUENCE OF WAY OF FARMING AND TYPES OF FOOD ON THE MORPHOMETRIC CHARACTERISTICS OF THE SMALL AND LARGE INTESTINES IN BROILER TURKEY

    Directory of Open Access Journals (Sweden)

    Rizah Avdić

    2013-08-01

    Full Text Available Morphological characteristics of the digestive systems in birds are direct reflection of evolutionary adaptations of these animals to different type and way of diet. The research conducted on domestic and some wild birds indicate that besides the evolutionary factors, time of start of food intake after the hatching, and amount and composition of food in the period of intensive growth also influence morphological characteristics of digestive systems in birds. The aim of this study was to determine the influence of extensive and intensive way of farming, and different types and amount of food on the morphometric characteristics of the small and large intestines in 45 broiler turkeys (BIG BUT 600. Statistical analysis shows that the way of breeding and the type and quantity of food all have significant impact on the body weight in turkeys but do not influence the length of the intestinal tract in these animals.Key words: turkey, digestive system, morphology

  3. 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 (MDR...

  4. Intestinal handling-induced mast cell activation and inflammation in human postoperative ileus

    NARCIS (Netherlands)

    The, F. O.; Bennink, R. J.; Ankum, W. M.; Buist, M. R.; Busch, O. R. C.; Gouma, D. J.; van der Heide, S.; van den Wijngaard, R. M.; de Jonge, W. J.; Boeckxstaens, G. E.

    2008-01-01

    Background: Murine postoperative ileus results from intestinal inflammation triggered by manipulation-induced mast cell activation. As its extent depends on the degree of handling and subsequent inflammation, it is hypothesised that the faster recovery after minimal invasive surgery results from

  5. Intestinal handling-induced mast cell activation and inflammation in human postoperative ileus

    NARCIS (Netherlands)

    The, F. O.; Bennink, R. J.; Ankum, W. M.; Buist, M. R.; Busch, O. R. C.; Gouma, D. J.; Van der Heide, S.; van den Wijngaard, R. M.; Boeckxstaens, G. E.; de Jonge, Wouter J.

    Background: Murine postoperative ileus results from intestinal inflammation triggered by manipulation-induced mast cell activation. As its extent depends on the degree of handling and subsequent inflammation, it is hypothesised that the faster recovery after minimal invasive surgery results from

  6. Gastric and intestinal surgery.

    Science.gov (United States)

    Fossum, Theresa W; Hedlund, Cheryl S

    2003-09-01

    Gastric surgery is commonly performed to remove foreign bodies and correct gastric dilatation-volvulus and is less commonly performed to treat gastric ulceration or erosion, neoplasia, and benign gastric outflow obstruction. Intestinal surgery, although commonly performed by veterinarians, should never be considered routine. The most common procedures of the small intestinal tract performed in dogs and cats include enterotomy and resection/anastomosis. Surgery of the large intestine is indicated for lesions causing obstruction, perforations, colonic inertia, or chronic inflammation.

  7. Preterm infant gut microbiota affects intestinal epithelial development in a humanized microbiome gnotobiotic mouse model.

    Science.gov (United States)

    Yu, Yueyue; Lu, Lei; Sun, Jun; Petrof, Elaine O; Claud, Erika C

    2016-09-01

    Development of the infant small intestine is influenced by bacterial colonization. To promote establishment of optimal microbial communities in preterm infants, knowledge of the beneficial functions of the early gut microbiota on intestinal development is needed. The purpose of this study was to investigate the impact of early preterm infant microbiota on host gut development using a gnotobiotic mouse model. Histological assessment of intestinal development was performed. The differentiation of four epithelial cell lineages (enterocytes, goblet cells, Paneth cells, enteroendocrine cells) and tight junction (TJ) formation was examined. Using weight gain as a surrogate marker for health, we found that early microbiota from a preterm infant with normal weight gain (MPI-H) induced increased villus height and crypt depth, increased cell proliferation, increased numbers of goblet cells and Paneth cells, and enhanced TJs compared with the changes induced by early microbiota from a poor weight gain preterm infant (MPI-L). Laser capture microdissection (LCM) plus qRT-PCR further revealed, in MPI-H mice, a higher expression of stem cell marker Lgr5 and Paneth cell markers Lyz1 and Cryptdin5 in crypt populations, along with higher expression of the goblet cell and mature enterocyte marker Muc3 in villus populations. In contrast, MPI-L microbiota failed to induce the aforementioned changes and presented intestinal characteristics comparable to a germ-free host. Our data demonstrate that microbial communities have differential effects on intestinal development. Future studies to identify pioneer settlers in neonatal microbial communities necessary to induce maturation may provide new insights for preterm infant microbial ecosystem therapeutics. Copyright © 2016 the American Physiological Society.

  8. 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

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

    International Nuclear Information System (INIS)

    Amin, Md Ruhul; Ghannad, Leda; Othman, Ahmad; Gill, Ravinder K.; Dudeja, Pradeep K.; Ramaswamy, Krishnamurthy; Malakooti, Jaleh

    2009-01-01

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

  10. Acute but not chronic ethanol exposure impairs retinol oxidation in the small and large intestine of the rat

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Ellendt, K.; Lindros, K.

    2005-01-01

    BACKGROUND AND AIM: Ethanol has been shown to inhibit retinol oxidation at the level of alcohol dehydrogenase in liver and colon but not previously in the small intestine. In the present study we investigated how chronic alcohol feeding and acute ethanol exposure affects retinol dehydrogenase...... higher, respectively). While chronic alcohol feeding did not affect these parameters, acute ethanol exposure reduced V(max) and V(max)/K(m) dose-dependently (p

  11. 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....../l, respectively. VIP at a concentration of 10 nmol/l caused a significant increase in [3H]thymidine incorporation, and at 1000 nmol/l a significant increase in oestradiol secretion was observed. VIP had no effect on progesterone secretion. PHM at the concentrations tested did not influence any of the activities...

  12. Live Faecalibacterium prausnitzii Does Not Enhance Epithelial Barrier Integrity in an Apical Anaerobic Co-Culture Model of the Large Intestine

    Directory of Open Access Journals (Sweden)

    Eva Maier

    2017-12-01

    Full Text Available Appropriate intestinal barrier maturation during infancy largely depends on colonization with commensal bacteria. Faecalibacterium prausnitzii is an abundant obligate anaerobe that colonizes during weaning and is thought to maintain colonic health throughout life. We previously showed that F. prausnitzii induced Toll-like receptor 2 (TLR2 activation, which is linked to enhanced tight junction formation. Therefore, we hypothesized that F. prausnitzii enhances barrier integrity, an important factor in appropriate intestinal barrier maturation. In order to test metabolically active bacteria, we used a novel apical anaerobic co-culture system that allows the survival of both obligate anaerobic bacteria and oxygen-requiring intestinal epithelial cells (Caco-2. The first aim was to optimize the culture medium to enable growth and active metabolism of F. prausnitzii while maintaining the viability and barrier integrity, as measured by trans-epithelial electrical resistance (TEER, of the Caco-2 cells. This was achieved by supplementing the apical cell culture medium with bacterial culture medium. The second aim was to test the effect of F. prausnitzii on TEER across Caco-2 cell layers. Live F. prausnitzii did not improve TEER, which indicates that its benefits are not via altering tight junction integrity. The optimization of the novel dual-environment co-culturing system performed in this research will enable the investigation of new probiotics originating from indigenous beneficial bacteria.

  13. Live Faecalibacterium prausnitzii Does Not Enhance Epithelial Barrier Integrity in an Apical Anaerobic Co-Culture Model of the Large Intestine.

    Science.gov (United States)

    Maier, Eva; Anderson, Rachel C; Roy, Nicole C

    2017-12-12

    Appropriate intestinal barrier maturation during infancy largely depends on colonization with commensal bacteria. Faecalibacterium prausnitzii is an abundant obligate anaerobe that colonizes during weaning and is thought to maintain colonic health throughout life. We previously showed that F. prausnitzii induced Toll-like receptor 2 (TLR2) activation, which is linked to enhanced tight junction formation. Therefore, we hypothesized that F. prausnitzii enhances barrier integrity, an important factor in appropriate intestinal barrier maturation. In order to test metabolically active bacteria, we used a novel apical anaerobic co-culture system that allows the survival of both obligate anaerobic bacteria and oxygen-requiring intestinal epithelial cells (Caco-2). The first aim was to optimize the culture medium to enable growth and active metabolism of F. prausnitzii while maintaining the viability and barrier integrity, as measured by trans-epithelial electrical resistance (TEER), of the Caco-2 cells. This was achieved by supplementing the apical cell culture medium with bacterial culture medium. The second aim was to test the effect of F. prausnitzii on TEER across Caco-2 cell layers. Live F. prausnitzii did not improve TEER, which indicates that its benefits are not via altering tight junction integrity. The optimization of the novel dual-environment co-culturing system performed in this research will enable the investigation of new probiotics originating from indigenous beneficial bacteria.

  14. Intestinal colonisation, microbiota and future probiotics

    NARCIS (Netherlands)

    Salminen, S.; Benno, Y.; Vos, de W.M.

    2006-01-01

    The human intestine is colonized by a large number of microorganisms, collectively termed microbiota, which support a variety of physiological functions. As the major part of the microbiota has not yet been cultured, molecular methods are required to determine microbial composition and the impact of

  15. Salmonella Typhi Colonization Provokes Extensive Transcriptional Changes Aimed at Evading Host Mucosal Immune Defense During Early Infection of Human Intestinal Tissue

    Directory of Open Access Journals (Sweden)

    K.P. Nickerson

    2018-05-01

    Full Text Available Commensal microorganisms influence a variety of host functions in the gut, including immune response, glucose homeostasis, metabolic pathways and oxidative stress, among others. This study describes how Salmonella Typhi, the pathogen responsible for typhoid fever, uses similar strategies to escape immune defense responses and survive within its human host. To elucidate the early mechanisms of typhoid fever, we performed studies using healthy human intestinal tissue samples and “mini-guts,” organoids grown from intestinal tissue taken from biopsy specimens. We analyzed gene expression changes in human intestinal specimens and bacterial cells both separately and after colonization. Our results showed mechanistic strategies that S. Typhi uses to rearrange the cellular machinery of the host cytoskeleton to successfully invade the intestinal epithelium, promote polarized cytokine release and evade immune system activation by downregulating genes involved in antigen sampling and presentation during infection. This work adds novel information regarding S. Typhi infection pathogenesis in humans, by replicating work shown in traditional cell models, and providing new data that can be applied to future vaccine development strategies. Keywords: Typhoid fever, Salmonella, Snapwell™ system, Human tissue, Terminal ileum, Immune system, Innate immunity, Immune evasion, Host-pathogen interaction, Vaccine development, Intestinal organoids, Organoid monolayer

  16. Influence of Camembert consumption on the composition and metabolism of intestinal microbiota: a study in human microbiota-associated rats.

    Science.gov (United States)

    Lay, Christophe; Sutren, Malène; Lepercq, Pascale; Juste, Catherine; Rigottier-Gois, Lionel; Lhoste, Evelyne; Lemée, Riwanon; Le Ruyet, Pascale; Doré, Joël; Andrieux, Claude

    2004-09-01

    The objective of the present study was to evaluate the consequence of Camembert consumption on the composition and metabolism of human intestinal microbiota. Camembert cheese was compared with milk fermented by yoghurt starters and Lactobacillus casei as a probiotic reference. The experimental model was the human microbiota-associated (HM) rat. HM rats were fed a basal diet (HMB group), a diet containing Camembert made from pasteurised milk (HMCp group) or a diet containing fermented milk (HMfm group). The level of micro-organisms from dairy products was measured in faeces using cultures on a specific medium and PCR-temporal temperature gradient gel electrophoresis. The metabolic characteristics of the caecal microbiota were also studied: SCFA, NH3, glycosidase and reductase activities, and bile acid degradations. The results showed that micro-organisms from cheese comprised 10(5)-10(8) bacteria/g faecal sample in the HMCp group. Lactobacillus species from fermented milk were detected in HMfm rats. Consumption of cheese and fermented milk led to similar changes in bacterial metabolism: a decrease in azoreductase activity and NH3 concentration and an increase in mucolytic activities. However, specific changes were observed: in HMCp rats, the proportion of ursodeoxycholic resulting from chenodeoxycholic epimerisation was higher; in HMfm rats, alpha and beta-galactosidases were higher than in other groups and both azoreductases and nitrate reductases were lower. The results show that, as for fermented milk, Camembert consumption did not greatly modify the microbiota profile or its major metabolic activities. Ingested micro-organisms were able to survive in part during intestinal transit. These dairy products exert a potentially beneficial influence on intestinal metabolism.

  17. Culturing human intestinal stem cells for regenerative applications in the treatment of inflammatory bowel disease

    DEFF Research Database (Denmark)

    Holmberg, Fredrik Eo; Seidelin, Jakob B; Yin, Xiaolei

    2017-01-01

    models suggests that intestinal stem cell transplantation could constitute a novel treatment strategy to re-establish mucosal barrier function in patients with severe disease. Intestinal stem cells can be grownin vitroin organoid structures, though only a fraction of the cells contained are stem cells...... with regenerative capabilities. Hence, techniques to enrich stem cell populations are being pursued through the development of multiple two-dimensional and three-dimensional culture protocols, as well as co-culture techniques and multiple growth medium compositions. Moreover, research in support matrices allowing...... for efficient clinical application is in progress.In vitroculture is accomplished by modulating the signaling pathways fundamental for the stem cell niche with a suitable culture matrix to provide additional contact-dependent stimuli and structural support. The aim of this review was to discuss medium...

  18. A Mathematical Model of the Human Small Intestine Following Acute Radiation and Burn Exposures

    Science.gov (United States)

    2016-08-01

    intestine epithelial response is built into the Radiation- Induced Performance Decrement (RIPD) model (Anno et al., 1989, Anno et al., 1991). RIPD, a...compartments, simulating dose response with a multitarget single -hit model (Joiner, 2009). This theory proposes that one hit of radiation in n different... single -hit model was implemented to represent dose response. The dose response parameters (D0 and n) were chosen to match experimental data approximated

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

    Energy Technology Data Exchange (ETDEWEB)

    Read, N.W.; Al-Janabi, M.N.; Edwards, C.A.; Barber, D.C.

    1984-04-01

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

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

    Czech Academy of Sciences Publication Activity Database

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

    2001-01-01

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

  1. Prevalence and Risk Factors of Human Intestinal Parasites in Roudehen, Tehran Province, Iran.

    Science.gov (United States)

    Hemmati, Nasrin; Razmjou, Elham; Hashemi-Hafshejani, Saeideh; Motevalian, Abbas; Akhlaghi, Lameh; Meamar, Ahmad Reza

    2017-01-01

    Intestinal parasitic infections are among the most common infections and health problems worldwide. Due to the lack of epidemiologic information of such infections, the prevalence of, and the risk factors for, enteric parasites were investigated in residents of Roudehen, Tehran Province, Iran. In this cross-sectional study, 561 triple fecal samples were collected through a two-stage cluster-sampling protocol from Jun to Dec 2014. The samples were examined by formalin-ether concentration, culture, and with molecular methods. The prevalence of enteric parasites was 32.7% (95% CI 27.3-38). Blastocystis sp. was the most common intestinal protozoan (28.4%; 95% CI 23.7-33.0). The formalin-ether concentration and culture methods detected Blastocystis sp., Entamoeba coli , Giardia intestinalis , Dientamoeba fragilis , Iodamoeba butschlii , Entamoeba complex cysts or trophozoite , Chilomastix mesnilii , and Enterobius vermicularis . Single-round PCR assay for Entamoeba complex were identified Entamoeba dispar and E. moshkovskii . E. histolytica was not observed in any specimen. Multivariate analysis showed a significant association of parasites with water source and close animal contact. There was no correlation between infections and gender, age, occupation, education, or travel history. Protozoan infections were more common than helminth infections. This study revealed a high prevalence of enteric protozoan parasite infection among citizens of Rodehen. As most of the species detected are transmitted through a water-resistant cyst, public and individual education on personal hygiene should be considered to reduce transmission of intestinal parasites in the population.

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

    International Nuclear Information System (INIS)

    Trotter, P.J.; Storch, J.

    1990-01-01

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

  3. 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.

  4. Bioaccessibility, Cellular Uptake, and Transport of Astaxanthin Isomers and their Antioxidative Effects in Human Intestinal Epithelial Caco-2 Cells.

    Science.gov (United States)

    Yang, Cheng; Zhang, Hua; Liu, Ronghua; Zhu, Honghui; Zhang, Lianfu; Tsao, Rong

    2017-11-29

    The bioaccessibility, bioavailability, and antioxidative activities of three astaxanthin geometric isomers were investigated using an in vitro digestion model and human intestinal Caco-2 cells. This study demonstrated that the trans-cis isomerization of all-E-astaxanthin and the cis-trans isomerization of Z-astaxanthins could happen both during in vitro gastrointestinal digestion and cellular uptake processes. 13Z-Astaxanthin showed higher bioaccessibility than 9Z- and all-E-astaxanthins during in vitro digestion, and 9Z-astaxanthin exhibited higher transport efficiency than all-E- and 13Z-astaxanthins. These might explain why 13Z- and 9Z-astaxanthins are found at higher concentrations in human plasma than all-E-astaxanthin in reported studies. All three astaxanthin isomers were effective in maintaining cellular redox homeostasis as seen in the antioxidant enzyme (CAT, SOD) activities ; 9Z- and 13Z- astaxanthins exhibited a higher protective effect than all-E-astaxanthin against oxidative stress as demonstrated by the lower cellular uptake of Z-astaxanthins and lower secretion and gene expression of the pro-inflammatory cytokine IL-8 in Caco-2 cells treated with H 2 O 2 . We conclude, for the first time, that Z-astaxanthin isomers may play a more important role in preventing oxidative stress induced intestinal diseases.

  5. Large-scale determinants of intestinal schistosomiasis and intermediate host snail distribution across Africa: does climate matter?

    Science.gov (United States)

    Stensgaard, Anna-Sofie; Utzinger, Jürg; Vounatsou, Penelope; Hürlimann, Eveline; Schur, Nadine; Saarnak, Christopher F L; Simoonga, Christopher; Mubita, Patricia; Kabatereine, Narcis B; Tchuem Tchuenté, Louis-Albert; Rahbek, Carsten; Kristensen, Thomas K

    2013-11-01

    The geographical ranges of most species, including many infectious disease agents and their vectors and intermediate hosts, are assumed to be constrained by climatic tolerances, mainly temperature. It has been suggested that global warming will cause an expansion of the areas potentially suitable for infectious disease transmission. However, the transmission of infectious diseases is governed by a myriad of ecological, economic, evolutionary and social factors. Hence, a deeper understanding of the total disease system (pathogens, vectors and hosts) and its drivers is important for predicting responses to climate change. Here, we combine a growing degree day model for Schistosoma mansoni with species distribution models for the intermediate host snail (Biomphalaria spp.) to investigate large-scale environmental determinants of the distribution of the African S. mansoni-Biomphalaria system and potential impacts of climatic changes. Snail species distribution models included several combinations of climatic and habitat-related predictors; the latter divided into "natural" and "human-impacted" habitat variables to measure anthropogenic influence. The predictive performance of the combined snail-parasite model was evaluated against a comprehensive compilation of historical S. mansoni parasitological survey records, and then examined for two climate change scenarios of increasing severity for 2080. Future projections indicate that while the potential S. mansoni transmission area expands, the snail ranges are more likely to contract and/or move into cooler areas in the south and east. Importantly, we also note that even though climate per se matters, the impact of humans on habitat play a crucial role in determining the distribution of the intermediate host snails in Africa. Thus, a future contraction in the geographical range size of the intermediate host snails caused by climatic changes does not necessarily translate into a decrease or zero-sum change in human

  6. Late effects of intraoperative radiation therapy on retroperitoneal tissues, intestine, and bile duct in a large animal model

    Energy Technology Data Exchange (ETDEWEB)

    Sindelar, W.F.; Tepper, J.E.; Kinslla, T.J.; Barnes, M.; DeLuca, A.M.; Terrill, R.; Matthews, D.; Johnstone, P.A.S. [National Institutes of Health, Bethesda, MD (United States); Anderson, W.J. [Terre Haute Center for Medical Education, IN (United States); Bollinger, B.K. [National Naval Medical Center, Bethesda, MD (United States)

    1994-07-01

    The late histopathological effects of intraoperative radiotherapy (IORT) on retroperitoneal tissues, intestine, and bile duct were investigated in dogs. Fourteen adult foxhounds were subjected to laparotomy and varying doses (0-45 Gy) of IORT (11 MeV electrons) delivered to retroperitoneal tissues including the great vessels and ureters, to a loop of defunctionalized small bowel, or to the extrahepatic bile duct. One control animal received an aortic transection and reanastomosis at the time of laparotomy; another control received laparotomy alone. This paper describes the late effects of single-fraction IORT occurring 3-5 years following treatment. Dogs receiving IORT to the retroperitoneum through a 4 X 15 cm portal showed few gross or histologic abnormalities at 20 Gy. At doses ranging from 30-45 Gy, radiation changes in normal tissues were consistently observed. Retroperitoneal fibrosis with encasement of the ureters and great vessels developed at doses {ge}30 Gy. Radiation changes were present in the aorta and vena cava at doses {ge}40 Gy. A 30 Gy dog developed an in-field malignant osteosarcoma at 3 years which invaded the vertebral column and compressed the spinal cord. A 40 Gy animal developed obstruction of the right ureter with fatal septic hydronephrosis at 4 years. Animals receiving IORT through a 5 cm IORT portal to an upper abdominal field which included a defunctionalized loop of small bowel, showed few gross or histologic abnormalities at a dose of 20 Gy. At 30 Gy, hyaline degeneration of the intestinal muscularis layer of the bowel occurred. At a dose of 45 Gy, internal intestinal fistulae developed. One 30 Gy animal developed right ureteral obstruction and hydronephrosis at 5 years. A dog receiving 30 Gy IORT through a 5 cm portal to the extrahepatic bile duct showed diffuse fibrosis through the gastroduodenal ligament. These canine studies contribute to the area of late tissue tolerance to IORT. 7 refs., 3 figs., 5 tabs.

  7. Late effects of intraoperative radiation therapy on retroperitoneal tissues, intestine, and bile duct in a large animal model

    International Nuclear Information System (INIS)

    Sindelar, W.F.; Tepper, J.E.; Kinslla, T.J.; Barnes, M.; DeLuca, A.M.; Terrill, R.; Matthews, D.; Johnstone, P.A.S.; Anderson, W.J.; Bollinger, B.K.

    1994-01-01

    The late histopathological effects of intraoperative radiotherapy (IORT) on retroperitoneal tissues, intestine, and bile duct were investigated in dogs. Fourteen adult foxhounds were subjected to laparotomy and varying doses (0-45 Gy) of IORT (11 MeV electrons) delivered to retroperitoneal tissues including the great vessels and ureters, to a loop of defunctionalized small bowel, or to the extrahepatic bile duct. One control animal received an aortic transection and reanastomosis at the time of laparotomy; another control received laparotomy alone. This paper describes the late effects of single-fraction IORT occurring 3-5 years following treatment. Dogs receiving IORT to the retroperitoneum through a 4 X 15 cm portal showed few gross or histologic abnormalities at 20 Gy. At doses ranging from 30-45 Gy, radiation changes in normal tissues were consistently observed. Retroperitoneal fibrosis with encasement of the ureters and great vessels developed at doses ≥30 Gy. Radiation changes were present in the aorta and vena cava at doses ≥40 Gy. A 30 Gy dog developed an in-field malignant osteosarcoma at 3 years which invaded the vertebral column and compressed the spinal cord. A 40 Gy animal developed obstruction of the right ureter with fatal septic hydronephrosis at 4 years. Animals receiving IORT through a 5 cm IORT portal to an upper abdominal field which included a defunctionalized loop of small bowel, showed few gross or histologic abnormalities at a dose of 20 Gy. At 30 Gy, hyaline degeneration of the intestinal muscularis layer of the bowel occurred. At a dose of 45 Gy, internal intestinal fistulae developed. One 30 Gy animal developed right ureteral obstruction and hydronephrosis at 5 years. A dog receiving 30 Gy IORT through a 5 cm portal to the extrahepatic bile duct showed diffuse fibrosis through the gastroduodenal ligament. These canine studies contribute to the area of late tissue tolerance to IORT. 7 refs., 3 figs., 5 tabs

  8. Data Mining and Visualization of Large Human Behavior Data Sets

    DEFF Research Database (Denmark)

    Cuttone, Andrea

    and credit card transactions – have provided us new sources for studying our behavior. In particular smartphones have emerged as new tools for collecting data about human activity, thanks to their sensing capabilities and their ubiquity. This thesis investigates the question of what we can learn about human...... behavior from this rich and pervasive mobile sensing data. In the first part, we describe a large-scale data collection deployment collecting high-resolution data for over 800 students at the Technical University of Denmark using smartphones, including location, social proximity, calls and SMS. We provide...... an overview of the technical infrastructure, the experimental design, and the privacy measures. The second part investigates the usage of this mobile sensing data for understanding personal behavior. We describe two large-scale user studies on the deployment of self-tracking apps, in order to understand...

  9. Occurrence of FSH, inhibin and other hypothalamic-pituitary-intestinal hormones in normal fertility, subfertility, and tumors of human testes.

    Science.gov (United States)

    Mehta, M K; Garde, S V; Sheth, A R

    1995-01-01

    To compare the distribution of peptide hormones in presumably normal human testicular tissues and specimens exhibiting any of five pathologies. Biopsies from patients having testicular malfunctions were prepared as sections and specifically immunohistochemically stained for inhibin, FSH, serotonin, AUP, and oxytocin. Immunocytochemical studies revealed the presence of various hypophysial-pituitary-intestinal hormones, viz., FSH, inhibin, arginine vasopressin (AVP), calcitonin, serotonin, oxytocin, adrenocorticotropin (ACTH), gastrin, secretin, and somatostatin in human testicular biopsies exhibiting normal spermatogenesis, Sertoli-cell-only syndrome, spermatogenic arrest, Leydig cell hyperplasia, Leydig cell tumor, and seminoma. Intensity of immunostaining for all peptides except FSH was stronger in cases of subfertile as compared to normal testis. Intensity of immunostaining with inhibin was maximum in Leydig cell tumor. These regulatory peptides may be involved in the pathophysiology of the testes.

  10. Ascaris Suum Infection Downregulates Inflammatory Pathways in the Pig Intestine In Vivo and in Human Dendritic Cells In Vitro

    DEFF Research Database (Denmark)

    Midttun, Helene L. E.; Acevedo, Nathalie; Skallerup, Per

    2018-01-01

    similar transcriptional pathways in human dendritic cells (DCs) in vitro. DCs exposed to ABF secreted minimal amounts of cytokines and had impaired production of cyclooxygengase-2, altered glucose metabolism, and reduced capacity to induce interferon-gamma production in T cells. Our in vivo and in vitro......Ascaris suum is a helminth parasite of pigs closely related to its human counterpart, A. lumbricoides, which infects almost 1 billion people. Ascaris is thought to modulate host immune and inflammatory responses, which may drive immune hyporesponsiveness during chronic infections. Using...... transcriptomic analysis, we show here that pigs with a chronic A. suum infection have a substantial suppression of inflammatory pathways in the intestinal mucosa, with a broad downregulation of genes encoding cytokines and antigen-processing and costimulatory molecules. A. suum body fluid (ABF) suppressed...

  11. Regional differences of physiological functions and cancer susceptibility in the human large intestine

    NARCIS (Netherlands)

    Cats, A; DeVries, EGE; Mulder, NH; Kleibeuker, JH

    1996-01-01

    Regional differences in function, metabolism and morphology between proximal colon, distal colon and rectum may be important in the pathogenesis and biologic behaviour of tumours originating from these segments. Thus, the effect of primary prevention of colorectal cancer may also differ from one

  12. Effects of pig genotype (Iberian v. Landrace × Large White) on nutrient digestibility, relative organ weight and small intestine structure at two stages of growth.

    Science.gov (United States)

    Barea, R; Nieto, R; Vitari, F; Domeneghini, C; Aguilera, J F

    2011-02-01

    Although the effects of pig genotype on total-tract apparent digestibility (TTAD) have been widely reported in the literature, there is controversial information on the digestive capacity of indigenous breeds compared with lean-type pigs. The strategy of this study was to test the effects of pig genotype and crude protein (CP) supply on performance, digestive utilization of nutrients, relative organ weight and morphometric analysis of the small intestine. Thirty-eight Iberian (IB) and Landrace × Large White (LD) pigs were used. Three pigs per genotype were slaughtered at approximately 15 kg BW. The remaining pigs were fed one of two diets differing in CP content (13% or 17% as fed) using a pair-fed procedure. Feeding level was restricted at 0.8 × ad libitum of IB pigs. Nutrient digestibility and nitrogen (N) balance trials were performed at 30 and 80 kg BW. Four pigs per dietary treatment and genotype were slaughtered at approximately 50 and 115 kg BW. The gastrointestinal tract and the rest of the visceral organs were weighed and samples of the small intestine were taken to carry out histological and histometrical studies. Daily gain and gain-to-feed ratio were higher in LD than in IB pigs during the fattening and growing-fattening periods (P LD pigs at 30 kg BW (P LD pigs at 30 and 80 kg BW (30% as mean value). The proportional weight of the small intestine was greater in LD than in IB pigs at 50 and 115 kg BW. Histometry showed that IB presented a lower muscle layer thickness than LD pigs in ileum, irrespective of the BW (P LD pigs showed approximately 10% higher ileal villi length and villi-to-crypt ratio than IB pigs at 115 kg BW. CP supply affected to a larger extent the small intestinal micro-anatomical structure of LD pigs at 50 kg BW. In conclusion, our results suggests that although the higher growth rate, NR and efficiency of NR observed in LD pigs might be associated with presumably more efficient structural aspects of the small intestine, the main

  13. Probiotic Bifidobacterium species stimulate human SLC26A3 gene function and expression in intestinal epithelial cells

    Science.gov (United States)

    Kumar, Anoop; Hecht, Cameron; Priyamvada, Shubha; Anbazhagan, Arivarasu N.; Alakkam, Anas; Borthakur, Alip; Alrefai, Waddah A.; Gill, Ravinder K.

    2014-01-01

    SLC26A3, or downregulated in adenoma (DRA), plays a major role in mediating Cl− absorption in the mammalian intestine. Disturbances in DRA function and expression have been implicated in intestinal disorders such as congenital Cl− diarrhea and gut inflammation. We previously showed that an increase in DRA function and expression by Lactobacillus acidophilus and its culture supernatant (CS) might underlie antidiarrheal effects of this probiotic strain. However, the effects of Bifidobacterium species, important inhabitants of the human colon, on intestinal Cl−/HCO3− exchange activity are not known. Our current results demonstrate that CS derived from Bifidobacterium breve, Bifidobacterium infantis, and Bifidobacterium bifidum increased anion exchange activity in Caco-2 cells (∼1.8- to 2.4-fold). Consistent with the increase in DRA function, CS also increased the protein, as well as the mRNA, level of DRA (but not putative anion transporter 1). CS of all three Bifidobacterium sp. increased DRA promoter activity (−1,183/+114 bp) in Caco-2 cells (1.5- to 1.8-fold). Furthermore, the increase in DRA mRNA expression by CS of B. breve and B. infantis was blocked in the presence of the transcription inhibitor actinomycin D (5 μM) and the ERK1/2 MAPK pathway inhibitor U0126 (10 μM). Administration of live B. breve, B. infantis, and B. bifidum by oral gavage to mice for 24 h increased DRA mRNA and protein levels in the colon. These data demonstrate an upregulation of DRA via activation of the ERK1/2 pathway that may underlie potential antidiarrheal effects of Bifidobacterium sp. PMID:25143346

  14. Prevalence and Risk Factors of Human Intestinal Parasites in Roudehen, Tehran Province, Iran

    Directory of Open Access Journals (Sweden)

    Nasrin HEMMATI

    2017-09-01

    Full Text Available Background: Intestinal parasitic infections are among the most common infections and health problems worldwide. Due to the lack of epidemiologic information of such infections, the prevalence of, and the risk factors for, enteric parasites were investigated in residents of Roudehen, Tehran Province, Iran.Methods: In this cross-sectional study, 561 triple fecal samples were collected through a two-stage cluster-sampling protocol from Jun to Dec 2014. The samples were examined by formalin-ether concentration, culture, and with molecular methods.Results: The prevalence of enteric parasites was 32.7% (95% CI 27.3–38. Blastocystis sp. was the most common intestinal protozoan (28.4%; 95% CI 23.7–33.0. The formalin-ether concentration and culture methods detected Blastocystis sp., Entamoeba coli, Giardia intestinalis, Dientamoeba fragilis, Iodamoeba butschlii, Entamoeba complex cysts or trophozoite, Chilomastix mesnilii, and Enterobius vermicularis. Single-round PCR assay for Entamoeba complex were identified Entamoeba dispar and E. moshkovskii. E. histolytica was not observed in any specimen. Multivariate analysis showed a significant association of parasites with water source and close animal contact. There was no correlation between infections and gender, age, occupation, education, or travel history. Protozoan infections were more common than helminth infections.Conclusion: This study revealed a high prevalence of enteric protozoan parasite infection among citizens of Rodehen. As most of the species detected are transmitted through a water-resistant cyst, public and individual education on personal hygiene should be considered to reduce transmission of intestinal parasites in the population. 

  15. Diets high in resistant starch and arabinoxylan modulate digestion processes and SCFA pool size in the large intestine and faecal microbial composition in pigs.

    Science.gov (United States)

    Nielsen, Tina S; Lærke, Helle N; Theil, Peter K; Sørensen, Jens F; Saarinen, Markku; Forssten, Sofia; Knudsen, Knud E Bach

    2014-12-14

    The effects of a high level of dietary fibre (DF) either as arabinoxylan (AX) or resistant starch (RS) on digestion processes, SCFA concentration and pool size in various intestinal segments and on the microbial composition in the faeces were studied in a model experiment with pigs. A total of thirty female pigs (body weight 63.1 (sem 4.4) kg) were fed a low-DF, high-fat Western-style control diet (WSD), an AX-rich diet (AXD) or a RS-rich diet (RSD) for 3 weeks. Diet significantly affected the digestibility of DM, protein, fat, NSP and NSP components, and the arabinose:xylose ratio, as well as the disappearance of NSP and AX in the large intestine. RS was mainly digested in the caecum. AX was digested at a slower rate than RS. The digesta from AXD-fed pigs passed from the ileum to the distal colon more than twice as fast as those from WSD-fed pigs, with those from RSD-fed pigs being intermediate (PEubacterium rectale, Bifidobacterium spp. and Lactobacillus spp. in the faeces sampled at week 3 of the experimental period (P< 0.05). In the caecum, proximal and mid colon, AXD feeding resulted in a 3- to 5-fold higher pool size of butyrate compared with WSD feeding, with the RSD being intermediate (P <0.001). In conclusion, the RSD and AXD differently affected digestion processes compared with the WSD, and the AXD most efficiently shifted the microbial composition towards butyrogenic species in the faeces and increased the large-intestinal butyrate pool size.

  16. 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

    of these 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...... 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...

  17. Effect of a Semi-Purified Oligosaccharide-Enriched Fraction from Caprine Milk on Barrier Integrity and Mucin Production of Co-Culture Models of the Small and Large Intestinal Epithelium

    Directory of Open Access Journals (Sweden)

    Alicia M. Barnett

    2016-05-01

    Full Text Available Caprine milk contains the highest amount of oligosaccharides among domestic animals, which are structurally similar to human milk oligosaccharides (HMOs. This suggests caprine milk oligosaccharides may offer similar protective and developmental effects to that of HMOs. However, to date, studies using oligosaccharides from caprine milk have been limited. Thus, this study aimed to examine the impact of a caprine milk oligosaccharide-enriched fraction (CMOF on barrier function of epithelial cell co-cultures of absorptive enterocytes (Caco-2 cells and mucus-secreting goblet cells (HT29-MTX cells, that more closely simulate the cell proportions found in the small (90:10 and large intestine (75:25. Treatment of epithelial co-cultures with 0.4, 1.0, 2.0 and 4.0 mg/mL of CMOF was shown to have no effect on metabolic activity but did enhance cell epithelial barrier integrity as measured by trans-epithelial electrical resistance (TEER, in a dose-dependent manner. The CMOF at the maximum concentration tested (4.0 mg/mL enhanced TEER, mucin gene expression and mucin protein abundance of epithelial co-cultures, all of which are essential components of intestinal barrier function.

  18. Effect of a Semi-Purified Oligosaccharide-Enriched Fraction from Caprine Milk on Barrier Integrity and Mucin Production of Co-Culture Models of the Small and Large Intestinal Epithelium.

    Science.gov (United States)

    Barnett, Alicia M; Roy, Nicole C; McNabb, Warren C; Cookson, Adrian L

    2016-05-06

    Caprine milk contains the highest amount of oligosaccharides among domestic animals, which are structurally similar to human milk oligosaccharides (HMOs). This suggests caprine milk oligosaccharides may offer similar protective and developmental effects to that of HMOs. However, to date, studies using oligosaccharides from caprine milk have been limited. Thus, this study aimed to examine the impact of a caprine milk oligosaccharide-enriched fraction (CMOF) on barrier function of epithelial cell co-cultures of absorptive enterocytes (Caco-2 cells) and mucus-secreting goblet cells (HT29-MTX cells), that more closely simulate the cell proportions found in the small (90:10) and large intestine (75:25). Treatment of epithelial co-cultures with 0.4, 1.0, 2.0 and 4.0 mg/mL of CMOF was shown to have no effect on metabolic activity but did enhance cell epithelial barrier integrity as measured by trans-epithelial electrical resistance (TEER), in a dose-dependent manner. The CMOF at the maximum concentration tested (4.0 mg/mL) enhanced TEER, mucin gene expression and mucin protein abundance of epithelial co-cultures, all of which are essential components of intestinal barrier function.

  19. Loss of LMOD1 impairs smooth muscle cytocontractility and causes megacystis microcolon intestinal hypoperistalsis syndrome in humans and mice

    NARCIS (Netherlands)

    D. Halim (Danny); M.P. Wilson (Michael P.); D. Oliver (Daniel); E. Brosens (Erwin); J.B. Verheij (Joke); Y. Han (Yu); V. Nanda (Vivek); Q. Lyu (Qing); M. Doukas (Michael); H.A. Stoop (Hans A.); R.W.W. Brouwer (Rutger); W.F.J. van IJcken (Wilfred); O.J. Slivano (Orazio J.); A.J. Burns (Alan); C.K. Christie (Christine K.); K.L. De Mesy Bentley (Karen L.); A.S. Brooks (Alice); D. Tibboel (Dick); S. Xu (Suowen); Z.G. Jin (Zheng Gen); T. Djuwantono (Tono); W. Yan (Wei); M.M. Alves (Maria); R.M.W. Hofstra (Robert); J.M. Miano (Joseph M.)

    2017-01-01

    textabstractMegacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a congenital visceral myopathy characterized by severe dilation of the urinary bladder and defective intestinal motility. The genetic basis of MMIHS has been ascribed to spontaneous and autosomal dominant mutations in

  20. Estimation of dependence between mean of fractionation of photons and neutrons dose and intensity of post-irradiation reaction of mouse large intestine

    International Nuclear Information System (INIS)

    Gasinska, A.

    1995-01-01

    The aim of the work was verification of mouse large intestine tolerance on fractionated 250 kV X-rays and 2.3 MeV neutrons doses. Two cm of large intestine of mouse CBA/HT strain were irradiated with various fraction doses: from 0.25 to 35 Gy of X-rays and 0.05-12 Gy of neutrons. The measure of injury was handicap of intestine function. Early post-irradiation reaction was measured by loss of body weight (2-3 weeks after irradiation) and mouse mortality (till 2 months after irradiation, LD50/2). The late reaction was measured on the base of maximal body weight in 1 year period after irradiation, deformation of excrements (after 10 months) and death of animals (till 12. month after irradiation, LD50/12). Fractionation of X-ray dose influenced on decrease of intensification of late irradiation effects. After fractionation of neutrons this effect has not been observed. α/β coefficient for X-rays was 19.9 Gy [15.2; 27.0] for body weight nadir, 13.4 Gy [9.3; 19.5] for early mortality (LD50/2), 6.4 Gy [3.6;11.0] for maximal body weight and 6.9 [4.2; 10.8] for late mortality (LD50/12). Analysis of influence of low doses of photons 90.25-4 Gy) and neutrons (0.05-0.8 Gy) showed trend to reduction α/β for photons only (LD50/2=5.4 Gy; LD50/12=4.6 Gy). α/β coefficient for neutrons was defined by LQ model only for maximal body weight and was 19.9 Gy [9.5; 61.0]. In application of graphic method α/β for neutrons was 230 Gy for early and 48 Gy for late effects. Lower values of α/β coefficient for late irradiation effects for photon radiation demonstrate the big influence of fractionation of photons dose on large intestine tolerance (decrease intensity in all biological effects). Author did not observe increase of intestine tolerance in fractionation of neutrons dose. Effect of irradiation damages repair in interfraction pauses, measured by percent of regenerated dose (F r ) was much bigger for photons. For X-rays it was 50% for early and 63% for late effects. In case of

  1. High Expression of UGT1A1/1A6 in Monkey Small Intestine: Comparison of Protein Expression Levels of Cytochromes P450, UDP-Glucuronosyltransferases, and Transporters in Small Intestine of Cynomolgus Monkey and Human.

    Science.gov (United States)

    Akazawa, Takanori; Uchida, Yasuo; Miyauchi, Eisuke; Tachikawa, Masanori; Ohtsuki, Sumio; Terasaki, Tetsuya

    2018-01-02

    Cynomolgus monkeys have been widely used for the prediction of drug absorption in humans. The purpose of this study was to clarify the regional protein expression levels of cytochromes P450 (CYPs), UDP-glucuronosyltransferases (UGTs), and transporters in small intestine of cynomolgus monkey using liquid chromatography-tandem mass spectrometry, and to compare them with the corresponding levels in human. UGT1A1 in jejunum and ileum were >4.57- and >3.11-fold and UGT1A6 in jejunum and ileum were >16.1- and >8.57-fold, respectively, more highly expressed in monkey than in human. Also, jejunal expression of monkey CYP3A8 (homologue of human CYP3A4) was >3.34-fold higher than that of human CYP3A4. Among apical drug efflux transporters, BCRP showed the most abundant expression in monkey and human, and the expression levels of BCRP in monkey and human were >1.74- and >1.25-fold greater than those of P-gp and >2.76- and >4.50-fold greater than those of MRP2, respectively. These findings should be helpful to understand species differences of the functions of CYPs, UGTs, and transporters between monkey and human. The UGT1A1/1A6 data would be especially important because it is difficult to identify isoforms responsible for species differences of intestinal glucuronidation by means of functional studies due to overlapping substrate specificity.

  2. An update discussion on the current assessment of the safety of veterinary antimicrobial drug residues in food with regard to their impact on the human intestinal microbiome.

    Science.gov (United States)

    Cerniglia, Carl E; Pineiro, Silvia A; Kotarski, Susan F

    2016-05-01

    The human gastrointestinal tract ecosystem consists of complex and diverse microbial communities that have now been collectively termed the intestinal microbiome. Recent scientific breakthroughs and research endeavours have increased our understanding of the important role the intestinal microbiome plays in human health and disease. The use of antimicrobial new animal drugs in food-producing animals may result in the presence of low levels of drug residues in edible foodstuffs. There is concern that antimicrobial new animal drugs in or on animal-derived food products at residue-level concentrations could disrupt the colonization barrier and/or modify the antimicrobial resistance profile of human intestinal bacteria. Therapeutic doses of antimicrobial drugs have been shown to promote shifts in the intestinal microbiome, and these disruptions promote the emergence of antimicrobial-resistant bacteria. To assess the effects of antimicrobial new animal drug residues in food on human intestinal bacteria, many national regulatory agencies and international committees follow a harmonized process, VICH GL36(R), which was issued by a trilateral organization of the European Union, the USA, and Japan called the International Cooperation on Harmonization of Technical Requirements for Veterinary Medicinal Products (VICH). The guidance describes a general approach currently used by national regulatory agencies and international committees to assess the effects of antimicrobial new animal drug residues in animal-derived food on human intestinal bacteria. The purpose of this review is to provide an overview of this current approach as part of the antimicrobial new animal drug approval process in participating countries, give insights on the microbiological endpoints used in this safety evaluation, and discuss the availability of new information. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  3. The effects of the proportions of dietary macronutrients on the digestibility, post-prandial endocrine responses and large intestinal fermentation of carbohydrate in working dogs.

    Science.gov (United States)

    Hill, S R; Rutherfurd-Markwick, K J; Ravindran, G; Ugarte, C E; Thomas, D G

    2009-12-01

    To compare the effects of feeding diets varying in the proportions of macronutrients on the digestibility, post-prandial endocrine responses and large intestinal fermentation of carbohydrate in working dogs. The apparent digestibility of two test diets, one comprising low-carbohydrate, high-protein dry biscuits (Diet 1), and one comprising high-carbohydrate, low-protein dry biscuits (Diet 2), fed to 12 adult Harrier Hounds (n=5 female), was determined using the indigestible-marker and total-collection methods. Serial breath samples were collected from each dog before and after feeding, and analysed for concentrations of hydrogen. Concentrations of glucose and insulin in plasma were established from serial blood samples obtained after feeding. The apparent dry matter, protein, fat and energy digestibility of Diet 1 were higher, but the carbohydrate digestibility was lower (pdogs occurred earlier for Diet 1 than Diet 2 (pdogs fed Diet 2 than Diet 1 (pdogs fed Diet 2 compared with those fed Diet 1 (pdogs, including higher apparent nutrient digestibility, slower release of glucose into the bloodstream, and reduced large intestinal fermentation of carbohydrate. A low-carbohydrate, high-protein diet may be beneficial for specific groups of dogs, including working dogs subjected to prolonged bouts of exercise requiring a sustained energy source, or those with diabetes mellitus requiring better glycaemic control.

  4. Effects of Marine Oils, Digested with Human Fluids, on Cellular Viability and Stress Protein Expression in Human Intestinal Caco-2 Cells

    Directory of Open Access Journals (Sweden)

    Cecilia Tullberg

    2017-11-01

    Full Text Available In vitro digestion of marine oils has been reported to promote lipid oxidation, including the formation of reactive aldehydes (e.g., malondialdehyde (MDA and 4-hydroxy-2-hexenal (HHE. We aimed to investigate if human in vitro digestion of supplemental levels of oils from algae, cod liver, and krill, in addition to pure MDA and HHE, affect intestinal Caco-2 cell survival and oxidative stress. Cell viability was not significantly affected by the digests of marine oils or by pure MDA and HHE (0–90 μM. Cellular levels of HSP-70, a chaperone involved in the prevention of stress-induced protein unfolding was significantly decreased (14%, 28%, and 14% of control for algae, cod and krill oil, respectively; p ≤ 0.05. The oxidoreductase thioredoxin-1 (Trx-1 involved in reducing oxidative stress was also lower after incubation with the digested oils (26%, 53%, and 22% of control for algae, cod, and krill oil, respectively; p ≤ 0.001. The aldehydes MDA and HHE did not affect HSP-70 or Trx-1 at low levels (8.3 and 1.4 μM, respectively, whilst a mixture of MDA and HHE lowered Trx-1 at high levels (45 μM, indicating less exposure to oxidative stress. We conclude that human digests of the investigated marine oils and their content of MDA and HHE did not cause a stress response in human intestinal Caco-2 cells.

  5. 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

  6. Pasteurization Procedures for Donor Human Milk Affect Body Growth, Intestinal Structure, and Resistance against Bacterial Infections in Preterm Pigs.

    Science.gov (United States)

    Li, Yanqi; Nguyen, Duc Ninh; de Waard, Marita; Christensen, Lars; Zhou, Ping; Jiang, Pingping; Sun, Jing; Bojesen, Anders Miki; Lauridsen, Charlotte; Lykkesfeldt, Jens; Dalsgaard, Trine Kastrup; Bering, Stine Brandt; Sangild, Per Torp

    2017-06-01

    Background: Holder pasteurization (HP) destroys multiple bioactive factors in donor human milk (DM), and UV-C irradiation (UVC) is potentially a gentler method for pasteurizing DM for preterm infants. Objective: We investigated whether UVC-treated DM improves gut maturation and resistance toward bacterial infections relative to HP-treated DM. Methods: Bacteria, selected bioactive components, and markers of antioxidant capacity were measured in unpasteurized donor milk (UP), HP-treated milk, and UVC-treated milk (all from the same DM pool). Fifty-seven cesarean-delivered preterm pigs (91% gestation; ratio of males to females, 30:27) received decreasing volumes of parental nutrition (average 69 mL · kg -1 · d -1 ) and increasing volumes of the 3 DM diets ( n = 19 each, average 89 mL · kg -1 · d -1 ) for 8-9 d. Body growth, gut structure and function, and systemic bacterial infection were evaluated. Results: A high bacterial load in the UP (6×10 5 colony forming units/mL) was eliminated similarly by HP and UVC treatments. Relative to HP-treated milk, both UVC-treated milk and UP showed greater activities of lipase and alkaline phosphatase and concentrations of lactoferrin, secretory immunoglobulin A, xanthine dehydrogenase, and some antioxidant markers (all P < 0.05). The pigs fed UVC-treated milk and pigs fed UP showed higher relative weight gain than pigs fed HP-treated milk (5.4% and 3.5%), and fewer pigs fed UVC-treated milk had positive bacterial cultures in the bone marrow (28%) than pigs fed HP-treated milk (68%) ( P < 0.05). Intestinal health was also improved in pigs fed UVC-treated milk compared with those fed HP-treated milk as indicated by a higher plasma citrulline concentration (36%) and villus height (38%) ( P < 0.05) and a tendency for higher aminopeptidase N (48%) and claudin-4 (26%) concentrations in the distal intestine ( P < 0.08). The gut microbiota composition was similar among groups except for greater proportions of Enterococcus in pigs

  7. Dynamics of absorption, metabolism, and excretion of 5-aminolevulinic acid in human intestinal Caco-2 cells

    Directory of Open Access Journals (Sweden)

    Kei Saito

    2017-09-01

    Full Text Available 5-Aminolevulinic acid (ALA is a precursor for the biosynthesis of porphyrins and heme. Although the oral administration of ALA has been widely applied in clinical settings, the dynamics of its absorption, metabolism, and excretion within enterocytes remain unknown. In this study, after enterocytic differentiation, Caco-2 cells were incubated with 200 µM ALA and/or 100 µM sodium ferrous citrate (SFC for up to 72 h. Both ALA and the combination of ALA and SFC promoted the synthesis of heme, without affecting the expression of genes involved in intestinal iron transport, such as DMT1 and FPN. The enhanced heme synthesis in Caco-2 cells was more pronounced under the effect of the combination of ALA and SFC than under the effect of ALA alone, as reflected by the induced expression of heme oxygenase 1 (HO-1, as well as a reduced protein level of the transcriptional corepressor Bach1. Chromatin immunoprecipitation analysis confirmed Bach1 chromatin occupancy at the enhancer regions of HO-1, which were significantly decreased by the addition of ALA and SFC. Finally, Transwell culture of Caco-2 cells suggested that the administered ALA to the intestinal lumen was partially transported into vasolateral space. These findings enhance our understanding of the absorption and metabolism of ALA in enterocytes, which could aid in the development of a treatment strategy for various conditions such as anemia.

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

    International Nuclear Information System (INIS)

    Graham, M.; Perr, H.; Drucker, D.E.; Diegelmann, R.F.

    1986-01-01

    (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 3 H 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

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

    International Nuclear Information System (INIS)

    Klapper, Maja; Boehme, Mike; Nitz, Inke; Doering, Frank

    2007-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Schwartz, S [Children' s Hospital, Mucosal Immunology Laboratory, University of Bonn, Bonn (Germany); Beaulieu, J F [Department of Cell Biology/Anatomy, University of Sherbrooke, Sherbrooke (Canada); Ruemmele, F M [Children' s Hospital, Mucosal Immunology Laboratory, University of Bonn, Bonn (Germany) and INSERM EMI0212, Faculte de Medecine Necker, University Paris V, Paediatric Gastroenterology Unit, Department of Paediatrics, Hopital Necker-Enfants Malades, Assistance-Publique-Hopitaux de Paris, Paris (France)

    2005-11-18

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

  11. The human intestinal fatty acid binding protein (hFABP2) gene is regulated by HNF-4{alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Klapper, Maja [Molecular Nutrition, Institute of Human Nutrition and Food Science, Christian-Albrechts-University of Kiel, Heinrich-Hecht-Platz 10, D-24118 Kiel (Germany); Boehme, Mike [Molecular Nutrition, Institute of Human Nutrition and Food Science, Christian-Albrechts-University of Kiel, Heinrich-Hecht-Platz 10, D-24118 Kiel (Germany); Nitz, Inke [Molecular Nutrition, Institute of Human Nutrition and Food Science, Christian-Albrechts-University of Kiel, Heinrich-Hecht-Platz 10, D-24118 Kiel (Germany); Doering, Frank [Molecular Nutrition, Institute of Human Nutrition and Food Science, Christian-Albrechts-University of Kiel, Heinrich-Hecht-Platz 10, D-24118 Kiel (Germany)

    2007-04-27

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

  12. 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)

    Kokuina, Elena; Dominguez Alvarez, Carlos; Noa Pedroso, Guillermo; Martinez Rodriguez Pedro Ariel

    2009-01-01

    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 -C D56 +) 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

  13. Receptor-like Molecules on Human Intestinal Epithelial Cells Interact with an Adhesion Factor from Lactobacillus reuteri.

    Science.gov (United States)

    Matsuo, Yosuke; Miyoshi, Yukihiro; Okada, Sanae; Satoh, Eiichi

    2012-01-01

    A surface protein of Lactobacillus reuteri, mucus adhesion-promoting protein (MapA), is considered to be an adhesion factor. MapA is expressed in L. reuteri strains and adheres to piglet gastric mucus, collagen type I, and human intestinal epithelial cells such as Caco-2. The aim of this study was to identify molecules that mediate the attachment of MapA from L. reuteri to the intestinal epithelial cell surface by investigating the adhesion of MapA to receptor-like molecules on Caco-2 cells. MapA-binding receptor-like molecules were detected in Caco-2 cell lysates by 2D-PAGE. Two proteins, annexin A13 (ANXA13) and paralemmin (PALM), were identified by MALDI TOF-MS. The results of a pull-down assay showed that MapA bound directly to ANXA13 and PALM. Fluorescence microscopy studies confirmed that MapA binding to ANXA13 and PALM was colocalized on the Caco-2 cell membrane. To evaluate whether ANXA13 and PALM are important for MapA adhesion, ANXA13 and PALM knockdown cell lines were established. The adhesion of MapA to the abovementioned cell lines was reduced compared with that to wild-type Caco-2 cells. These knockdown experiments established the importance of these receptor-like molecules in MapA adhesion.

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

    International Nuclear Information System (INIS)

    Laburthe, M.; Couvineau, A.; Rouyer-Fessard, C.; Moroder, L.

    1985-01-01

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

  15. The Bacterial Species Campylobacter jejuni Induce Diverse Innate Immune Responses in Human and Avian Intestinal Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Daniel A. John

    2017-09-01

    Full Text Available Campylobacter remain the major cause of human gastroenteritis in the Developed World causing a significant burden to health services. Campylobacter are pathogens in humans and chickens, although differences in mechanistic understanding are incomplete, in part because phenotypic strain diversity creates inconsistent findings. Here, we took Campylobacter jejuni isolates (n = 100 from multi-locus sequence typed collections to assess their pathogenic diversity, through their inflammatory, cytotoxicity, adhesion, invasion and signaling responses in a high-throughput model using avian and human intestinal epithelial cells. C. jejuni induced IL-8 and CXCLi1/2 in human and avian epithelial cells, respectively, in a MAP kinase-dependent manner. In contrast, IL-10 responses in both cell types were PI 3-kinase/Akt-dependent. C. jejuni strains showed diverse levels of invasion with high invasion dependent on MAP kinase signaling in both cell lines. C. jejuni induced diverse cytotoxic responses in both cell lines with cdt-positive isolates showing significantly higher toxicity. Blockade of endocytic pathways suggested that invasion by C. jejuni was clathrin- and dynamin-dependent but caveolae- independent in both cells. In contrast, IL-8 (and CXCLi1/2 production was dependent on clathrin, dynamin, and caveolae. This study is important because of its scale, and the data produced, suggesting that avian and human epithelial cells use similar innate immune pathways where the magnitude of the response is determined by the phenotypic diversity of the Campylobacter species.

  16. 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.

  17. Comparative analysis of pyrosequencing and a phylogenetic microarray for exploring microbial community structures in the human distal intestine.

    Directory of Open Access Journals (Sweden)

    Marcus J Claesson

    Full Text Available BACKGROUND: Variations in the composition of the human intestinal microbiota are linked to diverse health conditions. High-throughput molecular technologies have recently elucidated microbial community structure at much higher resolution than was previously possible. Here we compare two such methods, pyrosequencing and a phylogenetic array, and evaluate classifications based on two variable 16S rRNA gene regions. METHODS AND FINDINGS: Over 1.75 million amplicon sequences were generated from the V4 and V6 regions of 16S rRNA genes in bacterial DNA extracted from four fecal samples of elderly individuals. The phylotype richness, for individual samples, was 1,400-1,800 for V4 reads and 12,500 for V6 reads, and 5,200 unique phylotypes when combining V4 reads from all samples. The RDP-classifier was more efficient for the V4 than for the far less conserved and shorter V6 region, but differences in community structure also affected efficiency. Even when analyzing only 20% of the reads, the majority of the microbial diversity was captured in two samples tested. DNA from the four samples was hybridized against the Human Intestinal Tract (HIT Chip, a phylogenetic microarray for community profiling. Comparison of clustering of genus counts from pyrosequencing and HITChip data revealed highly similar profiles. Furthermore, correlations of sequence abundance and hybridization signal intensities were very high for lower-order ranks, but lower at family-level, which was probably due to ambiguous taxonomic groupings. CONCLUSIONS: The RDP-classifier consistently assigned most V4 sequences from human intestinal samples down to genus-level with good accuracy and speed. This is the deepest sequencing of single gastrointestinal samples reported to date, but microbial richness levels have still not leveled out. A majority of these diversities can also be captured with five times lower sampling-depth. HITChip hybridizations and resulting community profiles correlate

  18. [Interaction of effective ingredients from traditional Chinese medicines with intestinal microbiota].

    Science.gov (United States)

    Zu, Xian-Peng; Lin, Zhang; Xie, Hai-Sheng; Yang, Niao; Liu, Xin-Ru; Zhang, Wei-Dong

    2016-05-01

    A large number and wide varieties of microorganisms colonize in the human gastrointestinal tract. They construct an intestinal microecological system in the intestinal environment. The intestinal symbiotic flora regulates a series of life actions, including digestion and absorption of nutrient, immune response, biological antagonism, and is closely associated with the occurrence and development of many diseases. Therefore, it is greatly essential for the host's health status to maintain the equilibrium of intestinal microecological environment. After effective compositions of traditional Chinese medicines are metabolized or biotransformed by human intestinal bacteria, their metabolites can be absorbed more easily, and can even decrease or increase toxicity and then exhibit significant different biological effects. Meanwhile, traditional Chinese medicines can also regulate the composition of the intestinal flora and protect the function of intestinal mucosal barrier to restore the homeostasis of intestinal microecology. The relevant literatures in recent 15 years about the interactive relationship between traditional Chinese medicines and gut microbiota have been collected in this review, in order to study the classification of gut microflora, the relationship between intestinal dysbacteriosis and diseases, the important roles of gut microflora in intestinal bacterial metabolism in effective ingredients of traditional Chinese medicines and bioactivities, as well as the modulation effects of Chinese medicine on intestinal dysbacteriosis. In addition, it also makes a future prospect for the research strategies to study the mechanism of action of traditional Chinese medicines based on multi-omics techniques. Copyright© by the Chinese Pharmaceutical Association.

  19. Amebiasis intestinal Intestinal amebiasis

    Directory of Open Access Journals (Sweden)

    JULIO CÉSAR GÓMEZ

    2007-03-01

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

  20. The magnitude and risk factors of intestinal parasitic infection in relation to Human Immunodeficiency Virus infection and immune status, at ALERT Hospital, Addis Ababa, Ethiopia.

    Science.gov (United States)

    Taye, Biruhalem; Desta, Kassu; Ejigu, Selamawit; Dori, Geme Urge

    2014-06-01

    Human Immunodeficiency Virus (HIV) and intestinal parasitic infections are among the main health problems in developing countries like Ethiopia. Particularly, co-infections of these diseases would worsen the progression of HIV to Acquired Immunodeficiency Syndrome (AIDS). The purpose of this study was to determine the magnitude and risk factors for intestinal parasites in relation to HIV infection and immune status. The study was conducted in (1) HIV positive on antiretroviral therapy (ART) and (2) ART naïve HIV positive patients, and (3) HIV-negative individuals, at All African Leprosy and Tuberculosis (TB) Eradication and Rehabilitation Training Center (ALERT) hospital in Addis Ababa, Ethiopia. Study participants were interviewed using structured questionnaires to obtain socio-demographic characteristics and assess risk factors associated with intestinal parasitic infection. Intestinal parasites were identified from fecal samples by direct wet mount, formol ether concentration, and modified Ziehl-Neelsen staining techniques. The immune status was assessed by measuring whole blood CD4 T-cell count. The overall magnitude of intestinal parasite was 35.08%. This proportion was different among study groups with 39.2% (69/176), 38.83% (40/103) and 27.14% (38/140) in ART naïve HIV positives patients, in HIV negatives, and in HIV positive on ART patients respectively. HIV positive patients on ART had significantly lower magnitude of intestinal parasitic infection compared to HIV negative individuals. Intestinal helminths were significantly lower in HIV positive on ART and ART naïve patients than HIV negatives. Low monthly income, and being married, divorced or widowed were among the socio-demographic characteristics associated with intestinal parasitic infection. No association was observed between the magnitude of intestinal parasites and CD4 T-cell count. However, Cryptosporidium parvum, and Isospora belli were exclusively identified in individuals with CD4 T

  1. Large-Scale Analysis of Network Bistability for Human Cancers

    Science.gov (United States)

    Shiraishi, Tetsuya; Matsuyama, Shinako; Kitano, Hiroaki

    2010-01-01

    Protein–protein interaction and gene regulatory networks are likely to be locked in a state corresponding to a disease by the behavior of one or more bistable circuits exhibiting switch-like behavior. Sets of genes could be over-expressed or repressed when anomalies due to disease appear, and the circuits responsible for this over- or under-expression might persist for as long as the disease state continues. This paper shows how a large-scale analysis of network bistability for various human cancers can identify genes that can potentially serve as drug targets or diagnosis biomarkers. PMID:20628618

  2. Successful application of large microneedle patches by human volunteers

    OpenAIRE

    Ripolin, Anastasia; Quinn, James; Larrañeta, Eneko; Vicente-Perez, Eva Maria; Barry, Johanne; Donnelly, Ryan F.

    2017-01-01

    We describe, for the first time, the design, production and evaluation of large microneedle patches. Such systems, based on 16 individual microneedle arrays (needle height 600??m), were prepared from aqueous blends of 15% w/w Gantrez? S97 and 7.5% w/w poly(ethyleneglycol) 10,000?Da. Ester-based crosslinking was confirmed by FTIR and mechanical strength was good. Insertion depths in a validated skin model were approximately 500??m. Ten human volunteers successfully self-inserted the microneedl...

  3. Human factors guidelines for large-screen displays

    International Nuclear Information System (INIS)

    Collier, Steve

    2005-09-01

    Any control-room project (including upgrades or evolutionary improvements to existing control-rooms) is well advised at the outset first to gather and update related background material for the design. This information-gathering exercise should also take into account experience from similar projects and operating experience. For these reasons, we decided to use our research, and experience in large-screen display design with several clients to update human factors guidance for large-screen displays, to take into account new ergonomics guidelines, operating experience, and work from similar projects. To write the updated guidelines, we drew on much of our experience across several departments at IFE, including research funded by the HRP programme, and experience with individual clients. Guidance here is accordingly focused mainly on recent areas of technical and human innovations in the man-machine interface. One particular area of focus was on the increasing use of large-screen display systems in modern control-rooms, and on how guidelines could be adapted and supplemented for their design. Guidance or reference to recommended sources is also given for control suite arrangement and layout, control-room layout, workstation layout, design of displays and controls, and design of the work environment, especially insofar as these ergonomic issues interact with the effectiveness of modern displays, in particular large screen displays. The work shows that there can be synergy between HRP research and bilateral activities: the one side offers a capability to develop tools and guidelines, while the other side gives an opportunity to test and refine these in practice, to the benefit of both parties. (Author)

  4. Human factors guidelines for large-screen displays

    Energy Technology Data Exchange (ETDEWEB)

    Collier, Steve

    2005-09-15

    Any control-room project (including upgrades or evolutionary improvements to existing control-rooms) is well advised at the outset first to gather and update related background material for the design. This information-gathering exercise should also take into account experience from similar projects and operating experience. For these reasons, we decided to use our research, and experience in large-screen display design with several clients to update human factors guidance for large-screen displays, to take into account new ergonomics guidelines, operating experience, and work from similar projects. To write the updated guidelines, we drew on much of our experience across several departments at IFE, including research funded by the HRP programme, and experience with individual clients. Guidance here is accordingly focused mainly on recent areas of technical and human innovations in the man-machine interface. One particular area of focus was on the increasing use of large-screen display systems in modern control-rooms, and on how guidelines could be adapted and supplemented for their design. Guidance or reference to recommended sources is also given for control suite arrangement and layout, control-room layout, workstation layout, design of displays and controls, and design of the work environment, especially insofar as these ergonomic issues interact with the effectiveness of modern displays, in particular large screen displays. The work shows that there can be synergy between HRP research and bilateral activities: the one side offers a capability to develop tools and guidelines, while the other side gives an opportunity to test and refine these in practice, to the benefit of both parties. (Author)

  5. Intestinal Lymphangiectasia

    Science.gov (United States)

    ... Overview of Crohn Disease Additional Content Medical News Intestinal Lymphangiectasia (Idiopathic Hypoproteinemia) By Atenodoro R. Ruiz, Jr., MD, ... Overview of Malabsorption Bacterial Overgrowth Syndrome Celiac Disease Intestinal ... Intolerance Short Bowel Syndrome Tropical Sprue Whipple ...

  6. Curcumin Encapsulated in Milk Exosomes Resists Human Digestion and Possesses Enhanced Intestinal Permeability in Vitro.

    Science.gov (United States)

    Vashisht, Monika; Rani, Payal; Onteru, Suneel Kumar; Singh, Dheer

    2017-11-01

    Exosomes, the extracellular secretary nano-vesicles, act as carriers of biomolecules to the target cells. They exhibit several attributes of an efficient drug delivery system. Curcumin, despite having numerous bioactive and therapeutic properties, has limited pharmaceutical use due to its poor water solubility, stability, and low systemic bioavailability. Hence, this study aims to enhance the therapeutic potential of curcumin, a model hydrophobic drug, by its encapsulation into milk exosomes. In the present study, we investigated the stability of free curcumin and exosomal curcumin in PBS and in vitro digestive processes. Additionally, their uptake and trans-epithelial transport were studied on Caco-2 cells. Curcumin in milk exosomes had higher stability in PBS, sustained harsh digestive processes, and crossed the intestinal barrier than free curcumin. In conclusion, the encapsulation of curcumin into the exosomes enhances its stability, solubility, and bioavailability. Therefore, the present study demonstrated that milk exosomes act as stable oral drug delivery vehicles.

  7. An essential role of intestinal cell kinase in lung development is linked to the perinatal lethality of human ECO syndrome

    Science.gov (United States)

    Tong, Yixin; Park, So Hyun; Wu, Di; Xu, Wenhao; Guillot, Stacey J.; Jin, Li; Li, Xudong; Wang, Yalin; Lin, Chyuan-Sheng; Fu, Zheng

    2017-01-01

    Human endocrine-cerebro-osteodysplasia (ECO) syndrome, caused by the loss-of-function mutation R272Q in the ICK (intestinal cell kinase) gene, is a neonatal-lethal developmental disorder. To elucidate the molecular basis of ECO syndrome, we constructed an Ick R272Q knock-in mouse model that recapitulates ECO pathological phenotypes. Newborns bearing Ick R272Q homozygous mutations die at birth due to respiratory distress. Ick mutant lungs exhibit not only impaired branching morphogenesis associated with reduced mesenchymal proliferation, but also significant airspace deficiency in primitive alveoli concomitant with abnormal interstitial mesenchymal differentiation. ICK dysfunction induces elongated primary cilia and perturbs ciliary Hedgehog signaling and autophagy during lung sacculation. Our study identifies an essential role for ICK in lung development and advances the mechanistic understanding of ECO syndrome. PMID:28380258

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

    Directory of Open Access Journals (Sweden)

    Tiziana Angrisano

    Full Text Available 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.

  9. Binding of Candida albicans to Human CEACAM1 and CEACAM6 Modulates the Inflammatory Response of Intestinal Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Esther Klaile

    2017-03-01

    Full Text Available Candida albicans colonizes human mucosa, including the gastrointestinal tract, as a commensal. In immunocompromised patients, C. albicans can breach the intestinal epithelial barrier and cause fatal invasive infections. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1; CD66a, CEACAM5 (CEA, and CEACAM6 (CD66c are immunomodulatory receptors expressed on human mucosa and are recruited by bacterial and viral pathogens. Here we show for the first time that a fungal pathogen (i.e., C. albicans also binds directly to the extracellular domain of human CEACAM1, CEACAM3, CEACAM5, and CEACAM6. Binding was specific for human CEACAMs and mediated by the N-terminal IgV-like domain. In enterocytic C2BBe1 cells, C. albicans caused a transient tyrosine phosphorylation of CEACAM1 and induced higher expression of membrane-bound CEACAM1 and soluble CEACAM6. Lack of the CEACAM1 receptor after short hairpin RNA (shRNA knockdown abolished CXCL8 (interleukin-8 secretion by C2BBe1 cells in response to C. albicans. In CEACAM1-competent cells, the addition of recombinant soluble CEACAM6 reduced the C. albicans-induced CXCL8 secretion.

  10. Detection of Puumala hantavirus antigen in human intestine during acute hantavirus infection.

    Directory of Open Access Journals (Sweden)

    Joerg Latus

    Full Text Available BACKGROUND: Puumala virus (PUUV is the most important hantavirus species in Central Europe. Nephropathia epidemica (NE, caused by PUUV, is characterized by acute renal injury (AKI with thrombocytopenia and frequently gastrointestinal symptoms. METHODS: 456 patients with serologically and clinically confirmed NE were investigated at time of follow-up in a single clinic. The course of the NE was investigated using medical reports. We identified patients who had endoscopy with intestinal biopsy during acute phase of NE. Histopathological, immunohistochemical and molecular analyses of the biopsies were performed. RESULTS: Thirteen patients underwent colonoscopy or gastroscopy for abdominal pain, diarrhea, nausea and vomiting during acute phase of NE. Immunohistochemistry (IHC revealed PUUV nucleocapsid antigen in 11 biopsies from 8 patients; 14 biopsies from 5 patients were negative for PUUV nucleocapsid antigen. IHC localized PUUV nucleocapsid antigen in endothelial cells of capillaries or larger vessels in the lamina propria. Rate of AKI was not higher and severity of AKI was not different in the PUUV-positive compared to the PUUV-negative group. All IHC positive biopsies were positive for PUUV RNA using RT-PCR. Phylogenetic reconstruction revealed clustering of all PUUV strains from this study with viruses previously detected from the South-West of Germany. Long-term outcome was favorable in both groups. CONCLUSIONS: In patients with NE, PUUV nucleocapsid antigen and PUUV RNA was detected frequently in the intestine. This finding could explain frequent GI-symptoms in NE patients, thus demonstration of a more generalized PUUV infection. The RT-PCR was an effective and sensitive method to detect PUUV RNA in FFPE tissues. Therefore, it can be used as a diagnostic and phylogenetic approach also for archival materials. AKI was not more often present in patients with PUUV-positive IHC. This last finding should be investigated in larger numbers of

  11. Rapid appraisal of human intestinal helminth infections among schoolchildren in Osh oblast, Kyrgyzstan.

    Science.gov (United States)

    Steinmann, Peter; Usubalieva, Jumagul; Imanalieva, Cholpon; Minbaeva, Gulnara; Stefiuk, Kayte; Jeandron, Aurelie; Utzinger, Jürg

    2010-12-01

    A population-representative lot quality assurance sampling (LQAS) survey was conducted in 2009 to determine the prevalence of intestinal helminth infections among schoolchildren across Osh oblast, Kyrgyzstan. The diagnostic approach consisted of duplicate Kato-Katz thick smears from a single stool sample and an adhesive tape test. A questionnaire was administered to identify risk factors for infections. A total of 1262 schoolchildren aged 6-15 years were recruited; 41% of them harboured at least one of the eight identified helminth species. The two most prevalent helminths were Ascaris lumbricoides (23.1%) and Enterobius vermicularis (19.3%). Lower prevalences were found for Hymenolepis nana (4.4%), Fasciola hepatica (1.9%) and Dicrocoelium dendriticum (1.8%). Washing raw vegetables was a protective factor with regard to A. lumbricoides infection (odds ratio (OR)=0.69, p=0.022); tap water was borderline protective (OR=0.56, p=0.057). Children of the richest families were at a lower risk of E. vermicularis infection than the poorest ones (OR=0.41, p=0.011). Sharing the bed with more than one person was a risk factor for E. vermicularis infection (OR=2.0, p=0.002). The results call for targeted interventions against intestinal helminths in Osh oblast. In a first stage, annual deworming of schoolchildren and other high-risk groups with albendazole or mebendazole should be implemented, and reliable diagnosis and additional anthelminthic drugs should be made available. Subsequently, transmission control including locally-adapted health education, improved water supply and adequate sanitation should become the central features. Copyright © 2010 Elsevier B.V. All rights reserved.

  12. Morphological and molecular evidence for functional organization along the rostrocaudal axis of the adult zebrafish intestine

    Directory of Open Access Journals (Sweden)

    Lam Siew

    2010-06-01

    Full Text Available Abstract Background The zebrafish intestine is a simple tapered tube that is folded into three sections. However, whether the intestine is functionally similar along its length remains unknown. Thus, a systematic structural and functional characterization of the zebrafish intestine is desirable for future studies of the digestive tract and the intestinal biology and development. Results To characterize the structure and function of the adult zebrafish intestine, we divided the intestine into seven roughly equal-length segments, S1-S7, and systematically examined the morphology of the mucosal lining, histology of the epithelium, and molecular signatures from transcriptome analysis. Prominent morphological features are circumferentially-oriented villar ridges in segments S1-S6 and the absence of crypts. Molecular characterization of the transcriptome from each segment shows that segments S1-S5 are very similar while S6 and S7 unique. Gene ontology analyses reveal that S1-S5 express genes whose functions involve metabolism of carbohydrates, transport of lipids and energy generation, while the last two segments display relatively limited function. Based on comparative Gene Set Enrichment Analysis, the first five segments share strong similarity with human and mouse small intestine while S6 shows similarity with human cecum and rectum, and S7 with human rectum. The intestinal tract does not display the anatomical, morphological, and molecular signatures of a stomach and thus we conclude that this organ is absent from the zebrafish digestive system. Conclusions Our genome-wide gene expression data indicate that, despite the lack of crypts, the rostral, mid, and caudal portions of the zebrafish intestine have distinct functions analogous to the mammalian small and large intestine, respectively. Organization of ridge structures represents a unique feature of zebrafish intestine, though they produce similar cross sections to mammalian intestines

  13. Comparison of three contrast radiographic techniques in the dog large intestine; Comparacion de tres tecnicas radiograficas de contraste en el intestino grueso del perro

    Energy Technology Data Exchange (ETDEWEB)

    Vargas, L.; Thibaut, J.; Olhaberry, E.; Born, R.; Deppe, R. [Universidad Austral de Chile, Valdivia (Chile)

    1994-07-01

    In order to compare three radiographic techniques -pneumocolon, barium enema and double contrast- in the large intestine of the dog, three radiographic series in ventrodorsal and right lateral projections were taken. Six healthy adult dogs of both sexes with an approximate weight between 5 to 10 kg were used. Three enemas were administered 24, 12 and 2 hrs. before the series of radiographs were taken. Then dogs were anaesthetized with sodium tiopental (20 mg/kg iv) and the contrast media were introduced. Pneumocolon was carried out in the first series introducing air (20 cc/kg) in the large intestine through a Foley rectal catheter. Radiographs were taken in both projections, after 5 and 15min. respectively. Barium enema was performed in the second series introducing barium sulfate (18%) in the large intestine through a Foley rectal catheter (25 cc/kg); 5 and 15 min. later, the radiographs were taken. In the third series -double contrast- the barium sulfate, which was obtained from each dog using a catheter, was substituted by a volume of air equal to that obtained from the contrast medium. Later the radiographs were taken in both projections. The radiographic plates of each series were analized comparing the characteristics of: radiographic density, outline and volume. With the pneumocolon barium enema and double contrast, the radiographic density was, in most cases, low, high and inter-mediate respectively. The radiographic outline was, in most cases, regular for the three techniques. Thee radiographic volume was similar in all of the series. From the results obtained, it is concluded that double contrast best outlines the intestinal mucosa and more information can be obtained from it [Spanish] Con la finalidad de comparar tres tecnicas radiograficas del intestino grueso del perro -neumocolon, enema baritado y doble contraste-, se tomaron tres series radiograficas en proyeccion ventrodorsal y lateral derecha en 6 perros adultos, de 5 a 10 kg de peso, que

  14. Novel polyfucosylated N-linked glycopeptides with blood group A, H, X and Y determinants from human small intestinal epithelial cells

    NARCIS (Netherlands)

    Vliegenthart, J.F.G.; Finne, J.; Breimer, M.E.; Hansson, G.C.; Karlsson, K.-A.; Leffler, H.; Halbeek, H. van

    1989-01-01

    A novel type of N-linked glycopeptides representing a major part of the glycans in human small intestinal epithelial cells from blood group A and O individuals were isolated by gel filtrations and affinity chromatography on concanavalin A-Sepharose and Bandeiraea simplicifolia lectin I-Sepharose.

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

    DEFF Research Database (Denmark)

    Wilcks, Andrea; Hansen, Bjarne Munk; Hendriksen, Niels Bohse

    2006-01-01

    The fate and effect of Bacillus cereus F4433/73R in the intestine of human-flora-associated rats was studied using bacteriological culturing techniques and PCR-denaturing gradient gel electrophoresis in combination with cell assays and immunoassays for detection of enterotoxins. In faecal samples...

  16. A method for high purity intestinal epithelial cell culture from adult human and murine tissues for the investigation of innate immune function.

    Science.gov (United States)

    Graves, Christina L; Harden, Scott W; LaPato, Melissa; Nelson, Michael; Amador, Byron; Sorenson, Heather; Frazier, Charles J; Wallet, Shannon M

    2014-12-01

    Intestinal epithelial cells (IECs) serve as an important physiologic barrier between environmental antigens and the host intestinal immune system. Thus, IECs serve as a first line of defense and may act as sentinel cells during inflammatory insults. Despite recent renewed interest in IEC contributions to host immune function, the study of primary IEC has been hindered by lack of a robust culture technique, particularly for small intestinal and adult tissues. Here, a novel adaptation for culture of primary IEC is described for human duodenal organ donor tissue as well as duodenum and colon of adult mice. These epithelial cell cultures display characteristic phenotypes and are of high purity. In addition, the innate immune function of human primary IEC, specifically with regard to Toll-like receptor (TLR) expression and microbial ligand responsiveness, is contrasted with a commonly used intestinal epithelial cell line (HT-29). Specifically, TLR expression at the mRNA level and production of cytokine (IFNγ and TNFα) in response to TLR agonist stimulation is assessed. Differential expression of TLRs as well as innate immune responses to ligand stimulation is observed in human-derived cultures compared to that of HT-29. Thus, use of this adapted method to culture primary epithelial cells from adult human donors and from adult mice will allow for more appropriate studies of IECs as innate immune effectors. Published by Elsevier B.V.

  17. Modelling large scale human activity in San Francisco

    Science.gov (United States)

    Gonzalez, Marta

    2010-03-01

    Diverse group of people with a wide variety of schedules, activities and travel needs compose our cities nowadays. This represents a big challenge for modeling travel behaviors in urban environments; those models are of crucial interest for a wide variety of applications such as traffic forecasting, spreading of viruses, or measuring human exposure to air pollutants. The traditional means to obtain knowledge about travel behavior is limited to surveys on travel journeys. The obtained information is based in questionnaires that are usually costly to implement and with intrinsic limitations to cover large number of individuals and some problems of reliability. Using mobile phone data, we explore the basic characteristics of a model of human travel: The distribution of agents is proportional to the population density of a given region, and each agent has a characteristic trajectory size contain information on frequency of visits to different locations. Additionally we use a complementary data set given by smart subway fare cards offering us information about the exact time of each passenger getting in or getting out of the subway station and the coordinates of it. This allows us to uncover the temporal aspects of the mobility. Since we have the actual time and place of individual's origin and destination we can understand the temporal patterns in each visited location with further details. Integrating two described data set we provide a dynamical model of human travels that incorporates different aspects observed empirically.

  18. The immunomodulatory properties of viable Lactobacillus salivarius ssp. salivarius CECT5713 are not restricted to the large intestine.

    Science.gov (United States)

    Arribas, Belén; Garrido-Mesa, Natividad; Perán, Laura; Camuesco, Desirée; Comalada, Mònica; Bailón, Elvira; Olivares, Mónica; Xaus, Jordi; Kruidenier, Laurens; Sanderson, Ian R; Zarzuelo, Antonio; Rodríguez-Cabezas, Maria Elena; Gálvez, Julio

    2012-04-01

    The aim of this study was to better characterise the biological effects of Lactobacillus salivarius ssp. salivarius CECT5713, a probiotic with immunomodulatory properties. Live or dead probiotic was assayed in the TNBS model of rat colitis to determine whether viability was a requisite to exert the beneficial effects. In vitro studies were also performed in Caco-2 cells to evaluate its effects on epithelial cell recovery and IL-8 production. Finally, the probiotic was assayed in the LPS model of septic shock in mice to establish its effects when there is an altered systemic immune response. The viability of the probiotic was required for its anti-inflammatory activity. The probiotic inhibited IL-8 production in stimulated Caco-2 cells and facilitated the recovery of damaged intestinal epithelium. In LPS-treated mice, the probiotic inhibited the production of TNFα in plasma and lungs and increased the hepatic glutathione content. These effects were associated with an improvement in the altered production of the T-cell cytokines in splenocytes, by reducing IL-2 and IL-5 and by increasing IL-10. Finally, it reduced the increased plasma IgG production in LPS-treated mice. The anti-inflammatory effects of viable L. salivarius ssp. salivarius CECT5713 are not restricted to the gastrointestinal tract.

  19. Phenolic profile and fermentation patterns of different commercial gluten-free pasta during in vitro large intestine fermentation.

    Science.gov (United States)

    Rocchetti, Gabriele; Lucini, Luigi; Chiodelli, Giulia; Giuberti, Gianluca; Gallo, Antonio; Masoero, Francesco; Trevisan, Marco

    2017-07-01

    The fate of phenolic compounds, along with short-chain fatty acids (SCFAs) production kinetics, was evaluated on six different commercial gluten-free (GF) pasta samples varying in ingredient compositions, focussing on the in vitro faecal fermentation after the gastrointestinal digestion. A general reduction of both total phenolics and reducing power was observed in all samples, together with a substantial change in phenolic profile over 24h of faecal fermentation, with differences among GF pasta samples. Flavonoids, hydroxycinnamics and lignans degraded over time, with a concurrent increase in low-molecular-weight phenolic acids (hydroxybenzoic acids), alkylphenols, hydroxybenzoketones and tyrosols. Interestingly, discriminant analysis also identified several alkyl derivatives of resorcinol as markers of the changes in phenolic profile during in vitro fermentation. Furthermore, degradation pathways of phenolics by intestinal microbiota have been proposed. Considering the total SCFAs and butyrate production during the in vitro fermentation, different fermentation kinetics were observed among GF pasta post-hydrolysis residues. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Compression method of anastomosis of large intestines by implants with memory of shape: alternative to traditional sutures

    Directory of Open Access Journals (Sweden)

    F. Sh. Aliev

    2015-01-01

    Full Text Available Research objective. To prove experimentally the possibility of forming a compression colonic anastomoses using nickel-titanium devices in comparison with traditional methods of anastomosis. Materials and methods. In experimental studies the quality of the compression anastomosis of the colon in comparison with sutured and stapled anastomoses was performed. There were three experimental groups in mongrel dogs formed: in the 1st series (n = 30 compression anastomoses nickel-titanium implants were formed; in the 2nd (n = 25 – circular stapling anastomoses; in the 3rd (n = 25 – ligature way to Mateshuk– Lambert. In the experiment the physical durability, elasticity, and biological tightness, morphogenesis colonic anastomoses were studied. Results. Optimal sizes of compression devices are 32 × 18 and 28 × 15 mm with a wire diameter of 2.2 mm, the force of winding compression was 740 ± 180 g/mm2. Compression suture has a higher physical durability compared to stapled (W = –33.0; p < 0.05 and sutured (W = –28.0; p < 0.05, higher elasticity (p < 0.05 in all terms of tests and biological tightness since 3 days (p < 0.001 after surgery. The regularities of morphogenesis colonic anastomoses allocated by 4 periods of the regeneration of intestinal suture. Conclusion. Obtained experimental data of the use of compression anastomosis of the colon by the nickel-titanium devices are the convincing arguments for their clinical application. 

  1. Human visual system automatically represents large-scale sequential regularities.

    Science.gov (United States)

    Kimura, Motohiro; Widmann, Andreas; Schröger, Erich

    2010-03-04

    Our brain recordings reveal that large-scale sequential regularities defined across non-adjacent stimuli can be automatically represented in visual sensory memory. To show that, we adopted an auditory paradigm developed by Sussman, E., Ritter, W., and Vaughan, H. G. Jr. (1998). Predictability of stimulus deviance and the mismatch negativity. NeuroReport, 9, 4167-4170, Sussman, E., and Gumenyuk, V. (2005). Organization of sequential sounds in auditory memory. NeuroReport, 16, 1519-1523 to the visual domain by presenting task-irrelevant infrequent luminance-deviant stimuli (D, 20%) inserted among task-irrelevant frequent stimuli being of standard luminance (S, 80%) in randomized (randomized condition, SSSDSSSSSDSSSSD...) and fixed manners (fixed condition, SSSSDSSSSDSSSSD...). Comparing the visual mismatch negativity (visual MMN), an event-related brain potential (ERP) index of memory-mismatch processes in human visual sensory system, revealed that visual MMN elicited by deviant stimuli was reduced in the fixed compared to the randomized condition. Thus, the large-scale sequential regularity being present in the fixed condition (SSSSD) must have been represented in visual sensory memory. Interestingly, this effect did not occur in conditions with stimulus-onset asynchronies (SOAs) of 480 and 800 ms but was confined to the 160-ms SOA condition supporting the hypothesis that large-scale regularity extraction was based on perceptual grouping of the five successive stimuli defining the regularity. 2010 Elsevier B.V. All rights reserved.

  2. 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. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. 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

  4. 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.

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

    International Nuclear Information System (INIS)

    Griessen, M.; Speich, P.V.; Infante, F.; Bartholdi, P.; Cochet, B.; Donath, A.; Courvoisier, B.; Bonjour, J.P.

    1989-01-01

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

  6. Computational Studies of Drug Release, Transport and Absorption in the Human Intestines

    Science.gov (United States)

    Behafarid, Farhad; Brasseur, J. G.; Vijayakumar, G.; Jayaraman, B.; Wang, Y.

    2016-11-01

    Following disintegration of a drug tablet, a cloud of particles 10-200 μm in diameter enters the small intestine where drug molecules are absorbed into the blood. Drug release rate depends on particle size, solubility and hydrodynamic enhancements driven by gut motility. To quantify the interrelationships among dissolution, transport and wall permeability, we apply lattice Boltzmann method to simulate the drug concentration field in the 3D gut released from polydisperse distributions of drug particles in the "fasting" vs. "fed" motility states. Generalized boundary conditions allow for both solubility and gut wall permeability to be systematically varied. We apply a local 'quasi-steady state' approximation for drug dissolution using a mathematical model generalized for hydrodynamic enhancements and heterogeneity in drug release rate. We observe fundamental differences resulting from the interplay among release, transport and absorption in relationship to particle size distribution, luminal volume, motility, solubility and permeability. For example, whereas smaller volume encourages higher bulk concentrations and reduced release rate, it also encourages higher absorption rate, making it difficult to generalize predictions. Supported by FDA.

  7. Monitoring of antibiotic-induced alterations in the human intestinal microflora and detection of probiotic strains by use of terminal restriction fragment length polymorphism.

    Science.gov (United States)

    Jernberg, Cecilia; Sullivan, Asa; Edlund, Charlotta; Jansson, Janet K

    2005-01-01

    Terminal restriction fragment length polymorphism (T-RFLP) was investigated as a tool for monitoring the human intestinal microflora during antibiotic treatment and during ingestion of a probiotic product. Fecal samples from eight healthy volunteers were taken before, during, and after administration of clindamycin. During treatment, four subjects were given a probiotic, and four subjects were given a placebo. Changes in the microbial intestinal community composition and relative abundance of specific microbial populations in each subject were monitored by using viable counts and T-RFLP fingerprints. T-RFLP was also used to monitor specific bacterial populations that were either positively or negatively affected by clindamycin. Some dominant bacterial groups, such as Eubacterium spp., were easily monitored by T-RFLP, while they were hard to recover by cultivation. Furthermore, the two probiotic Lactobacillus strains were easily tracked by T-RFLP and were shown to be the dominant Lactobacillus community members in the intestinal microflora of subjects who received the probiotic.

  8. Response of human populations to large-scale emergencies

    Science.gov (United States)

    Bagrow, James; Wang, Dashun; Barabási, Albert-László

    2010-03-01

    Until recently, little quantitative data regarding collective human behavior during dangerous events such as bombings and riots have been available, despite its importance for emergency management, safety and urban planning. Understanding how populations react to danger is critical for prediction, detection and intervention strategies. Using a large telecommunications dataset, we study for the first time the spatiotemporal, social and demographic response properties of people during several disasters, including a bombing, a city-wide power outage, and an earthquake. Call activity rapidly increases after an event and we find that, when faced with a truly life-threatening emergency, information rapidly propagates through a population's social network. Other events, such as sports games, do not exhibit this propagation.

  9. 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

    to release proglucagon 111-123 (designated spacer peptide 2), which, like proglucagon 126-158 must be considered a potential hormonal entity. By isocratic high pressure liquid chromatography human spacer peptide 2 was indistinguishable from synthetic proglucagon 111-122 amide, suggesting...... that this is the structure of the naturally occurring human peptide....

  10. 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

  11. Successful application of large microneedle patches by human volunteers.

    Science.gov (United States)

    Ripolin, Anastasia; Quinn, James; Larrañeta, Eneko; Vicente-Perez, Eva Maria; Barry, Johanne; Donnelly, Ryan F

    2017-04-15

    We describe, for the first time, the design, production and evaluation of large microneedle patches. Such systems, based on 16 individual microneedle arrays (needle height 600μm), were prepared from aqueous blends of 15% w/w Gantrez ® S97 and 7.5% w/w poly(ethyleneglycol) 10,000Da. Ester-based crosslinking was confirmed by FTIR and mechanical strength was good. Insertion depths in a validated skin model were approximately 500μm. Ten human volunteers successfully self-inserted the microneedles of these larger patches in their skin, following appropriate instruction, as confirmed by transepidermal water loss measurements. The mean insertion depth ranged between 300 and 450μm over the area of the large patches. That this was not significantly different to a single unit MN patch self-applied by the same volunteers is encouraging. Microneedle patch sizes much larger than the 1-2cm 2 will be required if this technology is to be successfully translated to clinic for delivery of drug substances. The work described here suggests that use of such larger patches by patients can be successful, potentially opening up the possibility for a significant expansion of the size of the market for transdermal drug delivery. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

  12. 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. Copyright © 2015. Published by Elsevier B.V.

  13. 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.

  14. The Adhesion of Lactobacillus salivarius REN to a Human Intestinal Epithelial Cell Line Requires S-layer Proteins.

    Science.gov (United States)

    Wang, Ran; Jiang, Lun; Zhang, Ming; Zhao, Liang; Hao, Yanling; Guo, Huiyuan; Sang, Yue; Zhang, Hao; Ren, Fazheng

    2017-03-10

    Lactobacillus salivarius REN, a novel probiotic isolated from Chinese centenarians, can adhere to intestinal epithelial cells and subsequently colonize the host. We show here that the surface-layer protein choline-binding protein A (CbpA) of L. salivarius REN was involved in adherence to the human colorectal adenocarcinoma cell line HT-29. Adhesion of a cbpA deletion mutant was significantly reduced compared with that of wild-type, suggesting that CbpA acts as an adhesin that mediates the interaction between the bacterium and its host. To identify the molecular mechanism of adhesion, we determined the crystal structure of a truncated form of CbpA that is likely involved in binding to its cell-surface receptor. The crystal structure identified CbpA as a peptidase of the M23 family whose members harbor a zinc-dependent catalytic site. Therefore, we propose that CbpA acts as a multifunctional surface protein that cleaves the host extracellular matrix and participates in adherence. Moreover, we identified enolase as the CbpA receptor on the surface of HT-29 cells. The present study reveals a new class of surface-layer proteins as well as the molecular mechanism that may contribute to the ability of L. salivarius REN to colonize the human gut.

  15. Bioactive Milk for Intestinal Maturation in Preterm Neonates

    DEFF Research Database (Denmark)

    Li, Yanqi

    The fetal small intestine grows dramatically fast during the second and third trimester of human pregnancy. Many intestinal functions are therefore affected by preterm birth, including gastrointestinal motility, digestive and absorptive function, mucosal barrier function, and the intestinal...

  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

    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. Consumption of Camembert cheese stimulates commensal enterococci in healthy human intestinal microbiota.

    Science.gov (United States)

    Firmesse, Olivier; Rabot, Sylvie; Bermúdez-Humarán, Luis G; Corthier, Gérard; Furet, Jean-Pierre

    2007-11-01

    Enterococci are natural inhabitants of the human gastrointestinal tract and the main Gram-positive and facultative anaerobic cocci recovered in human faeces. They are also present in a variety of fermented dairy and meat products, and some rare isolates are responsible for severe infections such as endocarditis and meningitis. The aim of the present study was to evaluate the effect of Camembert cheese consumption by healthy human volunteers on the faecal enterococcal population. A highly specific real-time quantitative PCR approach was designed and used to type enterococcal species in human faeces. Two species were found, Enterococcus faecalis and Enterococcus faecium, and only the Enterococcus faecalis population was significantly enhanced after Camembert cheese consumption, whereas Escherichia coli population and the dominant microbiota remained unaffected throughout the trial.

  18. Linking phylogenetic identities of bacteria to starch fermentation in an in vitro model of the large intestine by RNA-based stable isotope probing

    NARCIS (Netherlands)

    Kovatcheva-Datchary, P.; Egert, M.; Maathuis, A.; Rajilić-Stojanović, M.; Graaf, A.A.de; Smidt, H.; Vos, W.M.de; Venema, K.

    2009-01-01

    Summary Carbohydrates, including starches, are an important energy source for humans, and are known for their interactions with the microbiota in the digestive tract. Largely, those interactions are thought to promote human health. Using 16S ribosomal RNA (rRNA)-based stable isotope probing (SIP),

  19. The intestinal absorption of dietary cholesterol by hypercholesterolemic (type II) and normocholesterolemic humans.

    Science.gov (United States)

    Connor, W E; Lin, D S

    1974-04-01

    The incomplete absorption of dietary cholesterol may represent an adaptive intestinal barrier that prevents hypercholesterolemia. To explore this mechanism, we compared cholesterol absorption in 15 normocholesterolemic and 6 hypercholesterolemic (type II) subjects fed background cholesterol-free formula diets with 40% of calories as fat. Each test meal consisted of a breakfast into which was incorporated scrambled egg yolk containing 300-500 mg of cholesterol and [4-(14)C]cholesterol (3-22 muCi), either naturally incorporated into the yolk cholesterol by previous isotope injection into the laying hen or added in peanut oil to the yolk of the test breakfast. In some instances [1alpha-(3)H]cholesterol was the radioactive marker. The radioactivity of the fecal neutral sterol fraction was determined in daily stool samples for the next 7 days to provide an estimate of unabsorbed dietary cholesterol. The amount of absorbed and reexcreted labeled cholesterol proved negligible. Most unabsorbed dietary cholesterol appeared in the stool on the second or third day after the meal, and 95% or more was recovered in the stool by 6 days. Plasma specific activity curves were usually maximal at 48 h. Normal subjects absorbed 44.5+/-9.3 (SD) of the administered cholesterol (range 25.9-60.3). Hypercholesterolemics absorbed the same percentage of cholesterol as normals: 47.6+/-12.6% (range 29.3-67.3). Absorption was similar whether the radiolabeled cholesterol was added to egg yolk or naturally incorporated in it (42.1+/-9.3 vs. 48.9+/-9.8%). Six normal subjects were fed a cholesterol-free formula for 4 wk, and then different amounts of cholesterol (110-610 mg/day) were added for another 4 wk. At the end of each period, single test meals containing either 110, 310, or 610 mg of cholesterol and [1alpha-(3)H]cholesterol were administered. Cholesterol absorption was 42.3+/-6.0% and 45.4+/-8.3% for the two dietary periods, respectively. The absolute cholesterol absorption was linearly

  20. Loss of LMOD1 impairs smooth muscle cytocontractility and causes megacystis microcolon intestinal hypoperistalsis syndrome in humans and mice

    NARCIS (Netherlands)

    Halim, Danny; Wilson, Michael P.; Oliver, Daniel; Brosens, Erwin; Verheij, Joke B. G. M.; Han, Yu; Nanda, Vivek; Lyu, Qing; Doukas, Michael; Stoop, Hans; Brouwer, Rutger W. W.; van IJcken, Wilfred F. J.; Slivano, Orazio J.; Burns, Alan J.; Christie, Christine K.; Bentley, Karen L. de Mesy; Brooks, Alice S.; Tibboel, Dick; Xu, Suowen; Jin, Zheng Gen; Djuwantono, Tono; Yan, Wei; Alves, Maria M.; Hofstra, Robert M. W.; Miano, Joseph M.

    2017-01-01

    Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a congenital visceral myopathy characterized by severe dilation of the urinary bladder and defective intestinal motility. The genetic basis of MMIHS has been ascribed to spontaneous and autosomal dominant mutations in actin gamma 2

  1. A LARGE HUMAN CENTRIFUGE FOR EXPLORATION AND EXPLOITATION RESEARCH

    Directory of Open Access Journals (Sweden)

    Jack J.W.A. van Loon

    2012-06-01

    Full Text Available This paper addresses concepts regarding the development of an Altered Gravity Platform (AGP that will serve as a research platform for human space exploration. Space flight causes a multitude of physiological problems, many of which are due to gravity level transitions. Going from Earth's gravity to microgravity generates fluid shifts, space motion sickness, cardiovascular deconditioning among other changes, and returning to a gravity environment again puts the astronauts under similar stressors. A prolonged stay in microgravity provokes additional deleterious changes such as bone loss, muscle atrophy and loss of coordination or specific psychological stresses. To prepare for future manned space exploration missions, a ground-based research test bed for validating countermeasures against the deleterious effects of g-level transitions is needed. The proposed AGP is a large rotating facility (diameter > 150 m, where gravity levels ranging from 1.1 to 1.5g are generated, covering short episodes or during prolonged stays of weeks or even months. On this platform, facilities are built where a crew of 6 to 8 humans can live autonomously. Adaptation from 1 g to higher g levels can be studied extensively and monitored continuously. Similarly, re-adaptation back to 1 g, after a prolonged period of altered g can also be investigated. Study of the physiological and psychological adaptation to changing g-levels will provide instrumental and predictive knowledge to better define the ultimate countermeasures that are needed for future successful manned space exploration missions to the Moon, Mars and elsewhere. The AGP initiative will allow scientific top experts in Europe and worldwide to investigate the necessary scientific, operational, and engineering inputs required for such space missions. Because so many different physiological systems are involved in adaptation to gravity levels, a multidisciplinary approach is crucial. One of the final and crucial

  2. Intestinal Surgery.

    Science.gov (United States)

    Desrochers, André; Anderson, David E

    2016-11-01

    A wide variety of disorders affecting the intestinal tract in cattle may require surgery. Among those disorders the more common are: intestinal volvulus, jejunal hemorrhage syndrome and more recently the duodenal sigmoid flexure volvulus. Although general principles of intestinal surgery can be applied, cattle has anatomical and behavior particularities that must be known before invading the abdomen. This article focuses on surgical techniques used to optimize outcomes and discusses specific disorders of small intestine. Diagnoses and surgical techniques presented can be applied in field conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Fermentation of D-Tagatose by Human Intestinal Bacteria and Dairy Lactic Acid Bacteria

    OpenAIRE

    Bertelsen, Hans; Andersen, Hans; Tvede, Michael

    2011-01-01

    A number of 174 normal or pathogenic human enteric bacteria and dairy lactic acid bacteria were screened for D-tagatose fermentation by incubation for 48 hours. Selection criteria for fermentation employed included a drop in pH below 5.5 and a distance to controls of more than 0.5. Only a few of the normal occurring enteric human bacteria were able to ferment D-tagatose, among those Enterococcus faecalis, Enterococcus faecium and Lactobacillus strains. D-Tagatose fermentation seems to be comm...

  4. Gastric and intestinal myiasis due to Ornidia obesa (Diptera: Syrphidae in humans. First report in colombia

    Directory of Open Access Journals (Sweden)

    Gustavo López V

    2017-01-01

    Full Text Available Myasis are parasitic infestations of animals and humans tissues and is caused by fly larvae. This kind of infestation has Public Health importance. In the Colombian biomedical literature the reports about myiasis in humans are scarce. In this paper, we report two cases of patients with gastrointestinal myiasis where the etiologic agents involved were Ornidia obesa and Ornidia sp (Diptera: Syrphidae. The taxonomic identification of the larvae was done at the Colombian Institute of Tropical Medicine and taxonomic confirmation was done at the laboratory of medicine veterinary and Zoology of Sao Pablo University. These two cases of myiasis are of first report in Colombia

  5. 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

    . The differences in the nature and severity of presentation between the two cases cannot readily be explained on the basis of allelic heterogeneity, as the nonsense and missense mutations from both subjects had comparably severe effects on the catalytic activity of PC1. Despite Subject A's negligible PC1 activity......We have previously described the only reported case of human proprotein convertase 1 (PC1) deficiency, in a female (Subject A) with obesity, hypogonadism, hypoadrenalism, and reactive hypoglycemia. We now report the second case of human PC1 deficiency (Subject B), also due to compound...

  6. Large Scale System Safety Integration for Human Rated Space Vehicles

    Science.gov (United States)

    Massie, Michael J.

    2005-12-01

    Since the 1960s man has searched for ways to establish a human presence in space. Unfortunately, the development and operation of human spaceflight vehicles carry significant safety risks that are not always well understood. As a result, the countries with human space programs have felt the pain of loss of lives in the attempt to develop human space travel systems. Integrated System Safety is a process developed through years of experience (since before Apollo and Soyuz) as a way to assess risks involved in space travel and prevent such losses. The intent of Integrated System Safety is to take a look at an entire program and put together all the pieces in such a way that the risks can be identified, understood and dispositioned by program management. This process has many inherent challenges and they need to be explored, understood and addressed.In order to prepare truly integrated analysis safety professionals must gain a level of technical understanding of all of the project's pieces and how they interact. Next, they must find a way to present the analysis so the customer can understand the risks and make decisions about managing them. However, every organization in a large-scale project can have different ideas about what is or is not a hazard, what is or is not an appropriate hazard control, and what is or is not adequate hazard control verification. NASA provides some direction on these topics, but interpretations of those instructions can vary widely.Even more challenging is the fact that every individual/organization involved in a project has different levels of risk tolerance. When the discrete hazard controls of the contracts and agreements cannot be met, additional risk must be accepted. However, when one has left the arena of compliance with the known rules, there can be no longer be specific ground rules on which to base a decision as to what is acceptable and what is not. The integrator must find common grounds between all parties to achieve

  7. Intestinal Permeability: The Basics

    Directory of Open Access Journals (Sweden)

    Ingvar Bjarnason

    1995-01-01

    Full Text Available The authors review some of the more fundamental principles underlying the noninvasive assessment of intestinal permeability in humans, the choice of test markers and their analyses, and the practical aspects of test dose composition and how these can be changed to allow the specific assessment of regional permeability changes and other intestinal functions. The implications of increased intestinal permeability in the pathogenesis of human disease is discussed in relation to findings in patients with Crohn’s disease. A common feature of increased intestinal permeability is the development of a low grade enteropathy, and while quantitatively similar changes may be found in Crohn’s disease these seem to predict relapse of disease. Moreover, factors associated with relapse of Crohn’s disease have in common an action to increase intestinal permeability. While increased intestinal permeability does not seem to be important in the etiology of Crohn’s disease it may be a central mechanism in the clinical relapse of disease.

  8. The dose-response relation in human volunteers for gastro-intestinal pathogens

    NARCIS (Netherlands)

    Teunis PFM; Heijden OG van der; Giessen JWB van der; Havelaar AH; MGB

    1996-01-01

    Published data on infection of human hosts with various protozoa, bacteria, and viruses causing gastro-enteritis are used to establish a quantitative relationship between ingested dose and the risk of infection. For all data sets analysed, this relationship is determined by fitting either an

  9. A Large Cystic Variant of Gastro-intestinal Stromal Tumour arising from the Jejunum: A Case Report

    OpenAIRE

    Shaikh, Salman Tehran; Upwanshi, Manish Harinarayan; Shetty, Tilakdas S.; Ghetla, Smruti R.; Gheewala, Hussain

    2015-01-01

    Gastrointestinal stromal tumours (GISTs) represent a mesenchymal neoplasm arising from the interstitial cells of cajal occurring mainly in the gastrointestinal tract. Here, we present a case of a large GIST arising from the jejunum with cystic presentation unlike the usual presentation as a solid mass. A 50-year-old male patient came with complaint of a painless mobile lump in abdomen of approximately 25 cm in size which had gradually increased over two years. Clinically mesenteric cyst was s...

  10. Assessing large-scale wildlife responses to human infrastructure development.

    Science.gov (United States)

    Torres, Aurora; Jaeger, Jochen A G; Alonso, Juan Carlos

    2016-07-26

    Habitat loss and deterioration represent the main threats to wildlife species, and are closely linked to the expansion of roads and human settlements. Unfortunately, large-scale effects of these structures remain generally overlooked. Here, we analyzed the European transportation infrastructure network and found that 50% of the continent is within 1.5 km of transportation infrastructure. We present a method for assessing the impacts from infrastructure on wildlife, based on functional response curves describing density reductions in birds and mammals (e.g., road-effect zones), and apply it to Spain as a case study. The imprint of infrastructure extends over most of the country (55.5% in the case of birds and 97.9% for mammals), with moderate declines predicted for birds (22.6% of individuals) and severe declines predicted for mammals (46.6%). Despite certain limitations, we suggest the approach proposed is widely applicable to the evaluation of effects of planned infrastructure developments under multiple scenarios, and propose an internationally coordinated strategy to update and improve it in the future.

  11. Proteomic profiling of a mouse model of acute intestinal Apc deletion leads to identification of potential novel biomarkers of human colorectal cancer (CRC).

    Science.gov (United States)

    Hammoudi, Abeer; Song, Fei; Reed, Karen R; Jenkins, Rosalind E; Meniel, Valerie S; Watson, Alastair J M; Pritchard, D Mark; Clarke, Alan R; Jenkins, John R

    2013-10-25

    Colorectal cancer (CRC) is the fourth most common cause of cancer-related death worldwide. Accurate non-invasive screening for CRC would greatly enhance a population's health. Adenomatous polyposis coli (Apc) gene mutations commonly occur in human colorectal adenomas and carcinomas, leading to Wnt signalling pathway activation. Acute conditional transgenic deletion of Apc in murine intestinal epithelium (AhCre(+)Apc(fl)(/)(fl)) causes phenotypic changes similar to those found during colorectal tumourigenesis. This study comprised a proteomic analysis of murine small intestinal epithelial cells following acute Apc deletion to identify proteins that show altered expression during human colorectal carcinogenesis, thus identifying proteins that may prove clinically useful as blood/serum biomarkers of colorectal neoplasia. Eighty-one proteins showed significantly increased expression following iTRAQ analysis, and validation of nine of these by Ingenuity Pathaway Analysis showed they could be detected in blood or serum. Expression was assessed in AhCre(+)Apc(fl)(/)(fl) small intestinal epithelium by immunohistochemistry, western blot and quantitative real-time PCR; increased nucelolin concentrations were also detected in the serum of AhCre(+)Apc(fl)(/)(fl) and Apc(Min)(/)(+) mice by ELISA. Six proteins; heat shock 60kDa protein 1, Nucleolin, Prohibitin, Cytokeratin 18, Ribosomal protein L6 and DEAD (Asp-Glu-Ala-Asp) box polypeptide 5,were selected for further investigation. Increased expression of 4 of these was confirmed in human CRC by qPCR. In conclusion, several novel candidate biomarkers have been identified from analysis of transgenic mice in which the Apc gene was deleted in the intestinal epithelium that also showed increased expression in human CRC. Some of these warrant further investigation as potential serum-based biomarkers of human CRC. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Location and pathogenic potential of Blastocystis in the porcine intestine.

    Directory of Open Access Journals (Sweden)

    Wenqi Wang

    Full Text Available Blastocystis is an ubiquitous, enteric protozoan of humans and many other species. Human infection has been associated with gastrointestinal disease such as irritable bowel syndrome, however, this remains unproven. A relevant animal model is needed to investigate the pathogenesis/pathogenicity of Blastocystis. We concluded previously that pigs are likely natural hosts of Blastocystis with a potentially zoonotic, host-adapted subtype (ST, ST5, and may make suitable animal models. In this study, we aimed to characterise the host-agent interaction of Blastocystis and the pig, including localising Blastocystis in porcine intestine using microscopy, PCR and histopathological examination of tissues. Intestines from pigs in three different management systems, i.e., a commercial piggery, a small family farm and a research herd (where the animals were immunosuppressed were examined. This design was used to determine if environment or immune status influences intestinal colonisation of Blastocystis as immunocompromised individuals may potentially be more susceptible to blastocystosis and development of associated clinical signs. Intestines from all 28 pigs were positive for Blastocystis with all pigs harbouring ST5. In addition, the farm pigs had mixed infections with STs 1 and/or 3. Blastocystis organisms/DNA were predominantly found in the large intestine but were also detected in the small intestine of the immunosuppressed and some of the farm pigs, suggesting that immunosuppression and/or husbandry factors may influence Blastocystis colonisation of the small intestine. No obvious pathology was observed in the histological sections. Blastocystis was present as vacuolar/granular forms and these were found within luminal material or in close proximity to epithelial cells, with no evidence of attachment or invasion. These results concur with most human studies, in which Blastocystis is predominantly found in the large intestine in the absence of

  13. No midterm advantages in the middle term using small intestinal submucosa and human amniotic membrane in Achilles tendon transverse tenotomy.

    Science.gov (United States)

    Liu, Yushu; Peng, Yinbo; Fang, Yong; Yao, Min; Redmond, Robert W; Ni, Tao

    2016-11-24

    The study was aimed to compare the effects of small intestinal submucosa (SIS) and human amniotic membrane (HAM) on Achilles tendon healing. A total of 48 New Zealand white rabbits were divided into two groups. A full-thickness transverse tenotomy was made at the right leg of the rabbits. Then, the laceration site was wrapped with HAM (P/A group) or SIS (P/S group). The ultimate stress (US) and Young's modulus (E) of the tendons were detected for biomechanical analysis. Histological evaluation was performed using hematoxylin and eosin, immunohistochemical, and immunofluorescent stain. Expression of collagen I was detected by western blot analysis, and levels of inflammatory cytokines IL-1β, IL-6, and TNF-α were measured. Finally, adhesion formation was evaluated. There were no significant differences in filamentous adhesion, cross-sectional areas of the laceration sites, levels of inflammatory response, and collagen type I expression between the P/A and P/S groups (p > 0.05). Compared with the P/A group, the US and E values were significantly higher in the P/S group at day 7 (p Achilles tendon injury in the early stage of healing.

  14. Effect of carrageenans alone and in combination with casein or lipopolysaccharide on human epithelial intestinal HT-29 cells.

    Science.gov (United States)

    Sokolova, E V; Kuz'mich, A S; Byankina, A O; Yermak, I M

    2017-10-01

    The research described here was focused on the effect on human intestinal epithelial cell monolayers of sulfated red algal polysaccharides (κ-, λ-, and κ/β-carrageenans) alone and in combination with casein or lipopolysaccharide (LPS). HT-29 cells were investigated under normal and stress conditions; stress was induced by exposure to ethanol. Cell viability was monitored with a real-time system. The change in binding properties of negatively sulfated red algal polysaccharides assessed by the measurement of free carrageenans in mixtures with casein or McCoy's 5 A culture medium by means of toluidine blue O. Low sulfate content and the presence of 3,6-anhydogalactose are prerequisites for the recovery of ethanol-exposed HT-29 cells by carrageenans. Analysis of carrageenan binding ability confirmed that casein and LPS should affect carrageenan activity. Whether the combined action of the mucin-containing layer and carrageenans or the action of carrageenans alone was responsible for enhanced cell viability under stress conditions induced by ethanol is a subject for further research. © 2017 Wiley Periodicals Inc. J Biomed Mater Res Part A: 105A: 2843-2850, 2017. © 2017 Wiley Periodicals, Inc.

  15. The prevention of radiation-induced DNA damage and apoptosis in human intestinal epithelial cells by salvianic acid A

    Directory of Open Access Journals (Sweden)

    Yanjun Zhang

    2014-07-01

    Full Text Available The topic of radiation always provokes public debate, and the uses of radiation for therapeutic and other purposes have always been associated with some anxiety. Salvia miltiorrhiza Bunge has been widely used for the treatment of various diseases including cerebrovascular diseases, coronary artery diseases, and myocardial infarction. Salvianolic acid A (SAA d (+-(3,4-dihydroxyphenyl lactic acid is the principal effective, watersoluble constituent of Salvia miltiorrhiza Bunge. In our present study, radiation-induced DNA damage and apoptosis in human intestinal epithelial cells (HIEC in the presence and absence of SAA were examined. We investigated the effects of SAA on ROS formation and the activity of enzymatic antioxidants (SOD, the lipid peroxidative index and the levels of non-enzymatic antioxidant (GSH. Finally, we investigated whether the reduction of radiation-induced cell death caused by SAA might be related to mitochondria-dependent apoptosis. Present findings indicate that SAA is a promising radioprotective agent with a strong antioxidant activity. SAA exerted its protective action on the proliferative activity of HIEC cells as evidenced by decreased cytotoxicity after exposure to γ-radiation. It is possible that SAA achieved its radioprotective action, at least in part, by enhancing DNA repair and the activity of antioxidant enzymes, by scavenging ROS and by inhibiting the mitochondria-dependent apoptotic pathway.

  16. Isolation of a human intestinal anaerobe, Bifidobacterium sp. strain SEN, capable of hydrolyzing sennosides to sennidins.

    OpenAIRE

    Akao, T; Che, Q M; Kobashi, K; Yang, L; Hattori, M; Namba, T

    1994-01-01

    A strictly anaerobic bacterium capable of metabolizing sennosides was isolated from human feces and identified as Bifidobacterium sp., named strain SEN. The bacterium hydrolyzed sennosides A and B to sennidins A and B via sennidin A and B 8-monoglucosides, respectively. Among nine species of Bifidobacterium having beta-glucosidase activity, only Bifidobacterium dentium and B. adolescentis metabolized sennoside B to sennidin B, suggesting that the sennoside-metabolizing bacteria produce a nove...

  17. Multidomain analyses of a longitudinal human microbiome intestinal cleanout perturbation experiment.

    Directory of Open Access Journals (Sweden)

    Julia Fukuyama

    2017-08-01

    Full Text Available Our work focuses on the stability, resilience, and response to perturbation of the bacterial communities in the human gut. Informative flash flood-like disturbances that eliminate most gastrointestinal biomass can be induced using a clinically-relevant iso-osmotic agent. We designed and executed such a disturbance in human volunteers using a dense longitudinal sampling scheme extending before and after induced diarrhea. This experiment has enabled a careful multidomain analysis of a controlled perturbation of the human gut microbiota with a new level of resolution. These new longitudinal multidomain data were analyzed using recently developed statistical methods that demonstrate improvements over current practices. By imposing sparsity constraints we have enhanced the interpretability of the analyses and by employing a new adaptive generalized principal components analysis, incorporated modulated phylogenetic information and enhanced interpretation through scoring of the portions of the tree most influenced by the perturbation. Our analyses leverage the taxa-sample duality in the data to show how the gut microbiota recovers following this perturbation. Through a holistic approach that integrates phylogenetic, metagenomic and abundance information, we elucidate patterns of taxonomic and functional change that characterize the community recovery process across individuals. We provide complete code and illustrations of new sparse statistical methods for high-dimensional, longitudinal multidomain data that provide greater interpretability than existing methods.

  18. Multidomain analyses of a longitudinal human microbiome intestinal cleanout perturbation experiment.

    Science.gov (United States)

    Fukuyama, Julia; Rumker, Laurie; Sankaran, Kris; Jeganathan, Pratheepa; Dethlefsen, Les; Relman, David A; Holmes, Susan P

    2017-08-01

    Our work focuses on the stability, resilience, and response to perturbation of the bacterial communities in the human gut. Informative flash flood-like disturbances that eliminate most gastrointestinal biomass can be induced using a clinically-relevant iso-osmotic agent. We designed and executed such a disturbance in human volunteers using a dense longitudinal sampling scheme extending before and after induced diarrhea. This experiment has enabled a careful multidomain analysis of a controlled perturbation of the human gut microbiota with a new level of resolution. These new longitudinal multidomain data were analyzed using recently developed statistical methods that demonstrate improvements over current practices. By imposing sparsity constraints we have enhanced the interpretability of the analyses and by employing a new adaptive generalized principal components analysis, incorporated modulated phylogenetic information and enhanced interpretation through scoring of the portions of the tree most influenced by the perturbation. Our analyses leverage the taxa-sample duality in the data to show how the gut microbiota recovers following this perturbation. Through a holistic approach that integrates phylogenetic, metagenomic and abundance information, we elucidate patterns of taxonomic and functional change that characterize the community recovery process across individuals. We provide complete code and illustrations of new sparse statistical methods for high-dimensional, longitudinal multidomain data that provide greater interpretability than existing methods.

  19. 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

    2016-09-01

    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.

  20. Intestine transplantation

    Directory of Open Access Journals (Sweden)

    Tadeja Pintar

    2011-02-01

    Conclusion: Intestine transplantation is reserved for patients with irreversible intestinal failure due to short gut syndrome requiring total paranteral nutrition with no possibility of discontinuation and loss of venous access for patient maintenance. In these patients complications of underlying disease and long-term total parenteral nutrition are present.

  1. (Na+ + K+)-ATPase and plasma membrane polarity of intestinal epithelial cells: Presence of a brush border antigen in the distal large intestine that is immunologically related to beta subunit

    Energy Technology Data Exchange (ETDEWEB)

    Marxer, A.; Stieger, B.; Quaroni, A.; Kashgarian, M.; Hauri, H.P. (Univ. of Basel (Switzerland))

    1989-09-01

    The previously produced monoclonal antibody IEC 1/48 against cultured rat intestinal crypt cells was extensively characterized and found to be directed against the beta subunit of (Na+ + K+)-ATPase as assessed by immunological and enzymatic criteria. Under nondenaturing conditions the antibody precipitated the alpha-beta enzyme complex (98,000 and 48,000 Mr). This probe, together with the monoclonal antibody C 62.4 against the alpha subunit was used to localize (Na+ + K+)-ATPase in epithelial cells along the rat intestinal tract by immunofluorescence and immunoelectron microscopy. Both antibodies exclusively labeled the basolateral membrane of small intestine and proximal colon epithelial cells. However, in the distal colon, IEC 1/48, but not C 62.4, also labeled the brush border membrane. The cross-reacting beta-subunit-like antigen on the apical cell pole was tightly associated with isolated brush borders but was apparently devoid of (Na+ + K+)-ATPase activity. Subcellular fractionation of colonocytes in conjunction with limited proteolysis and surface radioiodination of intestinal segments suggested that the cross-reacting antigen in the brush border may be very similar to the beta subunit. The results support the notion that in the small intestine and proximal colon the enzyme subunits are exclusively targeted to the basolateral membrane while in the distal colon nonassembled beta subunit or a beta-subunit-like protein is also transported to the apical cell pole.

  2. Isolation of a human intestinal anaerobe, Bifidobacterium sp. strain SEN, capable of hydrolyzing sennosides to sennidins.

    Science.gov (United States)

    Akao, T; Che, Q M; Kobashi, K; Yang, L; Hattori, M; Namba, T

    1994-01-01

    A strictly anaerobic bacterium capable of metabolizing sennosides was isolated from human feces and identified as Bifidobacterium sp., named strain SEN. The bacterium hydrolyzed sennosides A and B to sennidins A and B via sennidin A and B 8-monoglucosides, respectively. Among nine species of Bifidobacterium having beta-glucosidase activity, only Bifidobacterium dentium and B. adolescentis metabolized sennoside B to sennidin B, suggesting that the sennoside-metabolizing bacteria produce a novel type of beta-glucosidase capable of hydrolyzing sennosides to sennidins. PMID:8161172

  3. Cytotoxic and apoptotic effect of mycotoxins in human small intestinal cells

    DEFF Research Database (Denmark)

    Nielsen, Tina Skau; Sørensen, Izel Fourie; Sørensen, Jens Laurids

    2016-01-01

    Contamination of foods and feeds with mycotoxins is of significant concern due to their adverse effects on pig productivity and on animal and human health. Development of scientifically sound in vitro systems for toxicological screening for mycotoxins is important for improvement of food safety...... with mycotoxins for 72 h, and viability was measured by AlamarBlue reduction. For apoptosis studies, cells were treated with mycotoxins for 24 h, and apoptosis was measured by caspase 3/7 activation. The half maximal inhibitory concentration (IC50) of mycotoxins was calculated from sigmoidal dose-response plots...

  4. 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.

  5. A Large Cystic Variant of Gastro-intestinal Stromal Tumour arising from the Jejunum: A Case Report.

    Science.gov (United States)

    Shaikh, Salman Tehran; Upwanshi, Manish Harinarayan; Shetty, Tilakdas S; Ghetla, Smruti R; Gheewala, Hussain

    2015-04-01

    Gastrointestinal stromal tumours (GISTs) represent a mesenchymal neoplasm arising from the interstitial cells of cajal occurring mainly in the gastrointestinal tract. Here, we present a case of a large GIST arising from the jejunum with cystic presentation unlike the usual presentation as a solid mass. A 50-year-old male patient came with complaint of a painless mobile lump in abdomen of approximately 25 cm in size which had gradually increased over two years. Clinically mesenteric cyst was suspected. Intra-operatively the mass was a 30x25 cm cyst with approximately 2500 ml serous fluid present inside it arising from the anti-mesenteric border of the jejunum, adherent to the jejunum, appendix and the dome of the bladder. The fluid was aspirated and the mass excised along with resection of the involved jejunal segment and appendectomy was done. Diagnosis was confirmed on immunohistochemistry study. Imatinib Mesylate 400 mg OD was started as adjuvant therapy in view of the high risk of metastasis.

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

    Science.gov (United States)

    Kössler, Sonja; Nofziger, Charity; Jakab, Martin; Dossena, Silvia; Paulmichl, Markus

    2012-01-01

    Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1E,6E-heptadiene-3,5-dione or diferuloyl methane) is a polyphenol derived from the Curcuma longa plant, commonly known as turmeric. This substance has been used extensively in Ayurvedic medicine for centuries for its anti-oxidant, analgesic, anti-inflammatory and antiseptic activity. More recently curcumin has been found to possess anti-cancer properties linked to its pro-apoptotic and anti-proliferative actions. The underlying mechanisms of these diverse effects are complex, not fully elucidated and subject of intense scientific debate. Despite increasing evidence indicating that different cation channels can be a molecular target for curcumin, very little is known about the effect of curcumin on chloride channels. Since, (i) the molecular structure of curcumin indicates that the substance could potentially interact with chloride channels, (ii) chloride channels play a role during the apoptotic process and regulation of the cell volume, and (iii) apoptosis is a well known effect of curcumin, we set out to investigate whether or not curcumin could (i) exert a modulatory effect (direct or indirect) on the swelling activated chloride current IClswell in a human cell system, therefore (ii) affect cell volume regulation and (iii) ultimately modulate cell survival. The IClswell channels, which are essential for regulating the cell volume after swelling, are also known to be activated under isotonic conditions as an early event in the apoptotic process. Here we show that long-term exposure of a human kidney cell line to extracellular 0.1–10 μM curcumin modulates IClswell in a dose-dependent manner (0.1 μM curcumin is ineffective, 0.5–5.0 μM curcumin increase, while 10 μM curcumin decrease the current), and short-term exposure to micromolar concentrations of curcumin does not affect IClswell neither if applied from the extracellular nor from the intracellular side – therefore, a direct effect of curcumin on

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

    International Nuclear Information System (INIS)

    Kössler, Sonja; Nofziger, Charity; Jakab, Martin; Dossena, Silvia; Paulmichl, Markus

    2012-01-01

    Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1E,6E-heptadiene-3,5-dione or diferuloyl methane) is a polyphenol derived from the Curcuma longa plant, commonly known as turmeric. This substance has been used extensively in Ayurvedic medicine for centuries for its anti-oxidant, analgesic, anti-inflammatory and antiseptic activity. More recently curcumin has been found to possess anti-cancer properties linked to its pro-apoptotic and anti-proliferative actions. The underlying mechanisms of these diverse effects are complex, not fully elucidated and subject of intense scientific debate. Despite increasing evidence indicating that different cation channels can be a molecular target for curcumin, very little is known about the effect of curcumin on chloride channels. Since, (i) the molecular structure of curcumin indicates that the substance could potentially interact with chloride channels, (ii) chloride channels play a role during the apoptotic process and regulation of the cell volume, and (iii) apoptosis is a well known effect of curcumin, we set out to investigate whether or not curcumin could (i) exert a modulatory effect (direct or indirect) on the swelling activated chloride current ICl swell in a human cell system, therefore (ii) affect cell volume regulation and (iii) ultimately modulate cell survival. The ICl swell channels, which are essential for regulating the cell volume after swelling, are also known to be activated under isotonic conditions as an early event in the apoptotic process. Here we show that long-term exposure of a human kidney cell line to extracellular 0.1–10 μM curcumin modulates ICl swell in a dose-dependent manner (0.1 μM curcumin is ineffective, 0.5–5.0 μM curcumin increase, while 10 μM curcumin decrease the current), and short-term exposure to micromolar concentrations of curcumin does not affect ICl swell neither if applied from the extracellular nor from the intracellular side – therefore, a direct effect of curcumin on ICl

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

    International Nuclear Information System (INIS)

    Youakim, A.; Herscovics, A.

    1985-01-01

    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- 3 H]mannose or L-[5,6- 3 H]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- 3 H]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- 3 H]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- 3 H]glucosamine and L-[1- 14 C]fucose, strong acid hydrolysis of the labeled glycopeptide fraction excluded from Bio-Gel P-6 produced 3 H-labeled N-acetylglucosamine and N-acetylgalactosamine

  9. Transplantation of Expanded Fetal Intestinal Progenitors Contributes to Colon Regeneration after Injury

    DEFF Research Database (Denmark)

    Fordham, Robert P; Yui, Shiro; Hannan, Nicholas R F

    2013-01-01

    Regeneration and homeostasis in the adult intestinal epithelium is driven by proliferative resident stem cells, whose functional properties during organismal development are largely unknown. Here, we show that human and mouse fetal intestine contains proliferative, immature progenitors, which can...... be expanded in vitro as Fetal Enterospheres (FEnS). A highly similar progenitor population can be established during intestinal differentiation of human induced pluripotent stem cells. Established cultures of mouse fetal intestinal progenitors express lower levels of Lgr5 than mature progenitors and propagate...... in the presence of the Wnt antagonist Dkk1, and new cultures can be induced to form mature intestinal organoids by exposure to Wnt3a. Following transplantation in a colonic injury model, FEnS contribute to regeneration of colonic epithelium by forming epithelial crypt-like structures expressing region...

  10. A large outbreak of typhoid fever associated with a high rate of intestinal perforation in Kasese District, Uganda, 2008-2009.

    Science.gov (United States)

    Neil, Karen P; Sodha, Samir V; Lukwago, Luswa; O-Tipo, Shikanga; Mikoleit, Matthew; Simington, Sherricka D; Mukobi, Peter; Balinandi, Stephen; Majalija, Samuel; Ayers, Joseph; Kagirita, Atek; Wefula, Edward; Asiimwe, Frank; Kweyamba, Vianney; Talkington, Deborah; Shieh, Wun-Ju; Adem, Patricia; Batten, Brigid C; Zaki, Sherif R; Mintz, Eric

    2012-04-01

    Salmonella enterica serovar Typhi (Salmonella Typhi) causes an estimated 22 million typhoid fever cases and 216 000 deaths annually worldwide. In Africa, the lack of laboratory diagnostic capacity limits the ability to recognize endemic typhoid fever and to detect outbreaks. We report a large laboratory-confirmed outbreak of typhoid fever in Uganda with a high proportion of intestinal perforations (IPs). A suspected case of typhoid fever was defined as fever and abdominal pain in a person with either vomiting, diarrhea, constipation, headache, weakness, arthralgia, poor response to antimalarial medications, or IP. From March 4, 2009 to April 17, 2009, specimens for blood and stool cultures and serology were collected from suspected cases. Antimicrobial susceptibility testing and pulsed-field gel electrophoresis (PFGE) were performed on Salmonella Typhi isolates. Surgical specimens from patients with IP were examined. A community survey was conducted to characterize the extent of the outbreak. From December 27, 2007 to July 30, 2009, 577 cases, 289 hospitalizations, 249 IPs, and 47 deaths from typhoid fever occurred; Salmonella Typhi was isolated from 27 (33%) of 81 patients. Isolates demonstrated multiple PFGE patterns and uniform susceptibility to ciprofloxacin. Surgical specimens from 30 patients were consistent with typhoid fever. Estimated typhoid fever incidence in the community survey was 8092 cases per 100 000 persons. This typhoid fever outbreak was detected because of an elevated number of IPs. Underreporting of milder illnesses and delayed and inadequate antimicrobial treatment contributed to the high perforation rate. Enhancing laboratory capacity for detection is critical to improving typhoid fever control.

  11. [Observation on changes of oxygen partial pressure in the deep tissues along the large intestine meridian during acupuncture in healthy subjects].

    Science.gov (United States)

    Chen, Ming; Hu, Xiang-long; Wu, Zu-xing

    2010-06-01

    To observe changes of the partial oxygen pressure in the deep tissues along the Large Intestine Meridian (LIM) during acupuncture stimulation, so as to reveal the characteristics of energy metabolism in the tissues along the LIM. Thirty-one healthy volunteer subjects were enlisted in the present study. Partial oxygen pressure (POP) in the tissues (at a depth of about 1.5 cm) of acupoints Binao (LI 14), Shouwuli (LI 13), Shousanli (LI 10), 2 non-acupoints [the midpoints between Quchi (LI 11) and LI 14, and between Yangxi (LI 5) and LI 11) of the LIM, and 10 non-meridian points, 1.5-2.0 cm lateral and medial to each of the tested points of the LIM was detected before, during and after electroacupuncture (EA) stimulation of Hegu (LI 4) by using a tissue oxygen tension needle-like sensor. In normal condition, the POP values in the deep tissues along the LIM were significantly higher than those of the non-meridian control points on its bilateral sides. During and after EA of Hegu (LI 4), the POP levels decreased significantly in the deep tissues along the LIM in comparison with pre-EA (P 0.05). POP is significantly higher in the deep tissues along the LIM of healthy subjects under normal conditions, which can be downregulated by EA of Hegu (LI 4), suggesting an increase of both the utilization rate of oxygen and energy metabolism after EA.

  12. Preliminary Comparison of Oral and Intestinal Human Microbiota in Patients with Colorectal Cancer: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Edda Russo

    2018-01-01

    Full Text Available In this study Next-Generation Sequencing (NGS was used to analyze and compare human microbiota from three different compartments, i.e., saliva, feces, and cancer tissue (CT, of a selected cohort of 10 Italian patients with colorectal cancer (CRC vs. 10 healthy controls (saliva and feces. Furthermore, the Fusobacterium nucleatum abundance in the same body site was investigated through real-time quantitative polymerase chain reaction (qPCR to assess the association with CRC. Differences in bacterial composition, F. nucleatum abundance in healthy controls vs. CRC patients, and the association of F. nucleatum with clinical parameters were observed. Taxonomic analysis based on 16S rRNA gene, revealed the presence of three main bacterial phyla, which includes about 80% of reads: Firmicutes (39.18%, Bacteroidetes (30.36%, and Proteobacteria (10.65%. The results highlighted the presence of different bacterial compositions; in particular, the fecal samples of CRC patients seemed to be enriched with Bacteroidetes, whereas in the fecal samples of healthy controls Firmicutes were one of the major phyla detected though these differences were not statistically significant. The CT samples showed the highest alpha diversity values. These results emphasize a different taxonomic composition of feces from CRC compared to healthy controls. Despite the low number of samples included in the study, these results suggest the importance of microbiota in the CRC progression and could pave the way to the development of therapeutic interventions and novel microbial-related diagnostic tools in CRC patients.

  13. Connexin 26-mediated gap junctional intercellular communication suppresses paracellular permeability of human intestinal epithelial cell monolayers

    International Nuclear Information System (INIS)

    Morita, Hidekazu; Katsuno, Tatsuro; Hoshimoto, Aihiro; Hirano, Noriaki; Saito, Yasushi; Suzuki, Yasuo

    2004-01-01

    In some cell types, gap junctional intercellular communication (GJIC) is associated with tight junctions. The present study was performed to determine the roles of GJIC in regulation of the barrier function of tight junctions. Caco-2 human colonic cells were used as a monolayer model, and barrier function was monitored by measuring mannitol permeability and transepithelial electrical resistance (TER). The monolayers were chemically disrupted by treatment with oleic acid and taurocholic acid. Western blotting analyses were performed to evaluate the protein levels of connexins, which are components of gap junctional intercellular channels. Cx26 expression was detected in preconfluent Caco-2 cells, and its level increased gradually after the monolayer reached confluency. These results prompted us to examine whether overexpression of Cx26 affects barrier function. Monolayers of Caco-2 cells stably expressing Cx26 showed significantly lower mannitol permeability and higher TER than mock transfectants when the monolayers were chemically disrupted. The levels of claudin-4, an important component of tight junctions, were significantly increased in the stable Cx26 transfectant. These results suggest that Cx26-mediated GJIC may play a crucial role in enhancing the barrier function of Caco-2 cell monolayers

  14. Identification of human intestinal parasites affecting an asymptomatic peri-urban Argentinian population using multi-parallel quantitative real-time polymerase chain reaction.

    Science.gov (United States)

    Cimino, Rubén O; Jeun, Rebecca; Juarez, Marisa; Cajal, Pamela S; Vargas, Paola; Echazú, Adriana; Bryan, Patricia E; Nasser, Julio; Krolewiecki, Alejandro; Mejia, Rojelio

    2015-07-17

    In resource-limited countries, stool microscopy is the diagnostic test of choice for intestinal parasites (soil-transmitted helminths and/or intestinal protozoa). However, sensitivity and specificity is low. Improved diagnosis of intestinal parasites is especially important for accurate measurements of prevalence and intensity of infections in endemic areas. The study was carried out in Orán, Argentina. A total of 99 stool samples from a local surveillance campaign were analyzed by concentration microscopy and McMaster egg counting technique compared to the analysis by multi-parallel quantitative real-time polymerase chain reaction (qPCR). This study compared the performance of qPCR assay and stool microscopy for 8 common intestinal parasites that infect humans including the helminths Ascaris lumbricoides, Ancylostoma duodenale, Necator americanus, Strongyloides stercoralis, Trichuris trichiura, and the protozoa Giardia lamblia, Cryptosporidium parvum/hominis, and Entamoeba histolytica, and investigated the prevalence of polyparasitism in an endemic area. qPCR showed higher detection rates for all parasites as compared to stool microscopy except T. trichiura. Species-specific primers and probes were able to distinguish between A. duodenale (19.1%) and N. americanus (36.4%) infections. There were 48.6% of subjects co-infected with both hookworms, and a significant increase in hookworm DNA for A. duodenale versus N. americanus (119.6 fg/μL: 0.63 fg/μL, P parasites in an endemic area that has improved diagnostic accuracy compared to stool microscopy. This first time use of multi-parallel qPCR in Argentina has demonstrated the high prevalence of intestinal parasites in a peri-urban area. These results will contribute to more accurate epidemiological survey, refined treatment strategies on a public scale, and better health outcomes in endemic settings.

  15. 99mTechnetium labelled vasoactive intestinal peptide analogue for rapid localization of tumours in humans

    International Nuclear Information System (INIS)

    Thakur, M.L.; Pallela, V.; Marcus, C.S.; Diggles, L.; Pham, H.L.; Ahdoot, R.; Kalinowski, E.A.; Saeed, S.; Minami, C.

    2001-01-01

    In recent years, imaging tumours with receptor specific biomolecules has been the focus of increasing interest. VIP has a high affinity for specific receptors that are expressed in high density on a large number of malignant tumours. VIP was modified (TP 3654) without compromising its biological activity, and labelled with 99m Tc. Pharmacokinetics and feasibility studies were performed in three normal volunteers and 11 patients with a history of cancer. Imaging was performed for up to two h post-injection. Within 24 h after injection of 99m Tc-TP 3654 (10-15 mCi/5 μg), approximately 70% of the tracer cleared through the kidneys, and 20% through the liver. Blood clearance was rapid. No adverse reaction was noted in any subjects. All known tumours were clearly delineated within 20 min. Findings were compared with the results of 99m Tc-MIBI, CT, MRI, or histology. There was concordance in nine patients. In the other two, only the VIP scan was positive for tumours known to express VIP receptors. The early results of imaging tumours with 99m Tc-VIP are promising and warrant further studies. (author)

  16. Human fibrinogen and thrombin patch for extraluminal protection of intestinal anastomosis

    Directory of Open Access Journals (Sweden)

    Paulo Gustavo Kotze

    2013-07-01

    Full Text Available In spite of recent advances regarding equipment and surgical techniques in colorectal surgery, rates of anastomotic dehiscence (AD have remained stable throughout the years. The development of products to protect anastomosis aiming the reduction of AD rates has shown to be promising. Human fibrinogen and thrombin patch (HFTP Tachosil® have been used in experimental studies in animals and small case series in humans, with promising results. In this study, the authors describe the technique of HFTP use in details, aiming the protection of colorectal anastomosis, and retrospectively demonstrate the preliminary results in a pilot case series. HFTP was used in 4 patients submitted to conventional surgery. The procedures performed were: left colon resection, segmental colectomy (both for colorectal cancer, enteral anastomosis for fistula closure and right ileocolectomy. Anastomotic healing and absence of complications were observed in 3 patients, and the patient submitted to right ileocolectomy developed AD and died after reoperation. The use of HFTP is safe and can be indicated in selected cases. However, AD can occur even after the use of this strategy. Randomized controlled trials with larger samples of patients are needed in order to properly define the real benefits of this strategy in dehiscence prevention Resumo: Apesar dos avanços em equipamentos e técnica cirúrgica na cirurgia colorretal, os índices de deiscência de anastomose (DA tem permanecido estáveis nos últimos anos. O desenvolvimento de produtos que visam proteção das anastomoses para redução das taxas de DA tem se mostrado promissor. A membrana de fibrinogênio e trombina humanos (MFTH vem sendo utilizada em estudos experimentais e em pequenas séries de casos em humanos, com resultados promissores. Neste artigo os autores detalham a descrição técnica da utilização da MFTH na proteção de anastomoses colorretais, e demonstram os resultados preliminares em uma s

  17. A Novel Tightly Regulated Gene Expression System for the Human Intestinal Symbiont Bacteroides thetaiotaomicron

    Directory of Open Access Journals (Sweden)

    Regis Stentz

    2016-07-01

    Full Text Available 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-characterised 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.

  18. Human-Wildlife Conflicts in Nepal: Patterns of Human Fatalities and Injuries Caused by Large Mammals

    Science.gov (United States)

    Acharya, Krishna Prasad; Paudel, Prakash Kumar; Neupane, Prem Raj; Köhl, Michael

    2016-01-01

    Injury and death from wildlife attacks often result in people feeling violent resentment and hostility against the wildlife involved and, therefore, may undermine public support for conservation. Although Nepal, with rich biodiversity, is doing well in its conservation efforts, human-wildlife conflicts have been a major challenge in recent years. The lack of detailed information on the spatial and temporal patterns of human-wildlife conflicts at the national level impedes the development of effective conflict mitigation plans. We examined patterns of human injury and death caused by large mammals using data from attack events and their spatiotemporal dimensions collected from a national survey of data available in Nepal over five years (2010–2014). Data were analyzed using logistic regression and chi-square or Fisher's exact tests. The results show that Asiatic elephants and common leopards are most commonly involved in attacks on people in terms of attack frequency and fatalities. Although one-horned rhinoceros and bears had a higher frequency of attacks than Bengal tigers, tigers caused more fatalities than each of these two species. Attacks by elephants peaked in winter and most frequently occurred outside protected areas in human settlements. Leopard attacks occurred almost entirely outside protected areas, and a significantly greater number of attacks occurred in human settlements. Attacks by one-horned rhinoceros and tigers were higher in the winter, mainly in forests inside protected areas; similarly, attacks by bears occurred mostly within protected areas. We found that human settlements are increasingly becoming conflict hotspots, with burgeoning incidents involving elephants and leopards. We conclude that species-specific conservation strategies are urgently needed, particularly for leopards and elephants. The implications of our findings for minimizing conflicts and conserving these imperiled species are discussed. PMID:27612174

  19. Human-Wildlife Conflicts in Nepal: Patterns of Human Fatalities and Injuries Caused by Large Mammals.

    Science.gov (United States)

    Acharya, Krishna Prasad; Paudel, Prakash Kumar; Neupane, Prem Raj; Köhl, Michael

    2016-01-01

    Injury and death from wildlife attacks often result in people feeling violent resentment and hostility against the wildlife involved and, therefore, may undermine public support for conservation. Although Nepal, with rich biodiversity, is doing well in its conservation efforts, human-wildlife conflicts have been a major challenge in recent years. The lack of detailed information on the spatial and temporal patterns of human-wildlife conflicts at the national level impedes the development of effective conflict mitigation plans. We examined patterns of human injury and death caused by large mammals using data from attack events and their spatiotemporal dimensions collected from a national survey of data available in Nepal over five years (2010-2014). Data were analyzed using logistic regression and chi-square or Fisher's exact tests. The results show that Asiatic elephants and common leopards are most commonly involved in attacks on people in terms of attack frequency and fatalities. Although one-horned rhinoceros and bears had a higher frequency of attacks than Bengal tigers, tigers caused more fatalities than each of these two species. Attacks by elephants peaked in winter and most frequently occurred outside protected areas in human settlements. Leopard attacks occurred almost entirely outside protected areas, and a significantly greater number of attacks occurred in human settlements. Attacks by one-horned rhinoceros and tigers were higher in the winter, mainly in forests inside protected areas; similarly, attacks by bears occurred mostly within protected areas. We found that human settlements are increasingly becoming conflict hotspots, with burgeoning incidents involving elephants and leopards. We conclude that species-specific conservation strategies are urgently needed, particularly for leopards and elephants. The implications of our findings for minimizing conflicts and conserving these imperiled species are discussed.

  20. Chronic intestinal pseudoobstruction syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Yeon, Kyung Mo; Seo, Jeong Kee; Lee, Yong Seok [Seoul National University Children' s Hospital, Seoul (Korea, Republic of)

    1992-03-15

    Chronic intestinal pseudoobstruction syndrome is a rare clinical condition in which impaired intestinal peristalsis causes recurrent symptoms of bowel obstruction in the absence of a mechanical occlusion. This syndrome may involve variable segments of small or large bowel, and may be associated with urinary bladder retention. This study included 6 children(3 boys and 3 girls) of chronic intestinal obstruction. Four were symptomatic at birth and two were of the ages of one month and one year. All had abdominal distension and deflection difficulty. Five had urinary bladder distension. Despite parenteral nutrition and surgical intervention(ileostomy or colostomy), bowel obstruction persisted and four patients expired from sepses within one year. All had gaseous distension of small and large bowel on abdominal films. In small bowel series, consistent findings were variable degree of dilatation, decreased peristalsis(prolonged transit time) and microcolon or microrectum. This disease entity must be differentiated from congenital megacolon, ileal atresia and megacystis syndrome.

  1. 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.

  2. Screening in a Lactobacillus delbrueckii subsp. bulgaricus collection to select a strain able to survive to the human intestinal tract.

    Science.gov (United States)

    Vázquez, Clotilde; Botella-Carretero, José I; García-Albiach, Raimundo; Pozuelo, María J; Rodríguez-Baños, Mercedes; Baquero, Fernando; Baltadjieva, María A; del Campo, Rosa

    2013-01-01

    Genetic diversity and resistance of Lactobacillus bulgaricus sbsp. delbrueckii collection with 100 isolates from different home-made yogurt in rural Bulgarian areas were determined. 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. 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-hydroxy-butyric acids in faeces were detected. 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. Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.

  3. 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

    2014-01-01

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

  4. Intestinal leiomyoma

    Science.gov (United States)

    ... most often found when a person has an upper gastrointestinal (GI) endoscopy or colonoscopy for another reason. Rarely, these tumors can cause bleeding, blockage or rupture of the intestines If this ...

  5. A mucus adhesion promoting protein, MapA, mediates the adhesion of Lactobacillus reuteri to Caco-2 human intestinal epithelial cells.

    Science.gov (United States)

    Miyoshi, Yukihiro; Okada, Sanae; Uchimura, Tai; Satoh, Eiichi

    2006-07-01

    Lactobacillus reuteri is one of the dominant lactobacilli found in the gastrointestinal tract of various animals. A surface protein of L. reuteri 104R, mucus adhesion promoting protein (MapA), is considered to be an adhesion factor of this strain. We investigated the relation between MapA and adhesion of L. reuteri to human intestinal (Caco-2) cells. Quantitative analysis of the adhesion of L. reuteri strains to Caco-2 cells showed that various L. reuteri strains bind not only to mucus but also to intestinal epithelial cells. In addition, purified MapA bound to Caco-2 cells, and this binding inhibited the adhesion of L. reuteri in a concentration-dependent manner. Based on these observations, the adhesion of L. reuteri appears due to the binding of MapA to receptor-like molecules on Caco-2 cells. Further, far-western analysis indicated the existence of multiple receptor-like molecules in Caco-2 cells.

  6. Intestinal health in carnivores

    NARCIS (Netherlands)

    Hagen-Plantinga, Esther A.; Hendriks, W.H.

    2015-01-01

    The knowledge on the influence of gastro-intestinal (GI) microbiota on the health status of humans and animals is rapidly expanding. A balanced microbiome may provide multiple benefits to the host, like triggering and stimulation of the immune system, acting as a barrier against possible pathogenic

  7. Small intestinal motility

    NARCIS (Netherlands)

    Smout, André J. P. M.

    2004-01-01

    PURPOSE OF REVIEW: In the past year, many studies were published in which new and relevant information on small intestinal motility in humans and laboratory animals was obtained. RECENT FINDINGS: Although the reported findings are heterogeneous, some themes appear to be particularly interesting and

  8. Vibrio cholerae cytolysin causes an inflammatory response in human intestinal epithelial cells that is modulated by the PrtV protease.

    Directory of Open Access Journals (Sweden)

    Gangwei Ou

    Full Text Available BACKGROUND: Vibrio cholerae is the causal intestinal pathogen of the diarrheal disease cholera. It secretes the protease PrtV, which protects the bacterium from invertebrate predators but reduces the ability of Vibrio-secreted factor(s to induce interleukin-8 (IL-8 production by human intestinal epithelial cells. The aim was to identify the secreted component(s of V. cholerae that induces an epithelial inflammatory response and to define whether it is a substrate for PrtV. METHODOLOGY/PRINCIPAL FINDINGS: Culture supernatants of wild type V. cholerae O1 strain C6706, its derivatives and pure V. cholerae cytolysin (VCC were analyzed for the capacity to induce changes in cytokine mRNA expression levels, IL-8 and tumor necrosis factor-alpha (TNF-alpha secretion, permeability and cell viability when added to the apical side of polarized tight monolayer T84 cells used as an in vitro model for human intestinal epithelium. Culture supernatants were also analyzed for hemolytic activity and for the presence of PrtV and VCC by immunoblot analysis. CONCLUSIONS/SIGNIFICANCE: We suggest that VCC is capable of causing an inflammatory response characterized by increased permeability and production of IL-8 and TNF-alpha in tight monolayers. Pure VCC at a concentration of 160 ng/ml caused an inflammatory response that reached the magnitude of that caused by Vibrio-secreted factors, while higher concentrations caused epithelial cell death. The inflammatory response was totally abolished by treatment with PrtV. The findings suggest that low doses of VCC initiate a local immune defense reaction while high doses lead to intestinal epithelial lesions. Furthermore, VCC is indeed a substrate for PrtV and PrtV seems to execute an environment-dependent modulation of the activity of VCC that may be the cause of V. cholerae reactogenicity.

  9. Disorders of the Large Intestine

    Science.gov (United States)

    ... of Medicine, Division of Digestive Diseases; Professor of Psychology, University of North Carolina, Chapel Hill, NC, IFFGD Publication #839 by Samuel Nurko, MD, MPH, Center for Motility and Functional Gastrointestinal Disorders, Children’s Hospital Boston, Boston, MA, "Irritable Bowel Syndrome" by ...

  10. Intestinal lymphangiectasia in adults.

    Science.gov (United States)

    Freeman, Hugh James; Nimmo, Michael

    2011-02-15

    diagnosis of intestinal lymphangiectasia. Treatment has been historically defined to include a low fat diet with medium-chain triglyceride supplementation that leads to portal venous rather than lacteal uptake. A number of other pharmacological measures have been reported or proposed but these are largely anecdotal. Finally, rare reports of localized surgical resection of involved areas of small intestine have been described but follow-up in these cases is often limited.

  11. Modeling Synergies in Large Human-Machine Networked Systems

    Science.gov (United States)

    2013-09-25

    Agents and Multi- Agent Systems (AAMAS), Valencia, Spain, June 4-8, 2012. Steven Okamoto_, Praveen Paruchuri, Yonghong Wang, Katia Sycara, Janusz...Society, Santa Monica, CA: Human Factors and Ergonomics Society. 86. Steven Okamoto_, Praveen Paruchuri, Yonghong Wang, Katia Sycara, Janusz

  12. Small Intestine Disorders

    Science.gov (United States)

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

  13. Human-wildlife conflict as a barrier to large carnivore management and conservation in Turkey

    OpenAIRE

    CHYNOWETH, MARK; ÇOBAN, EMRAH; ALTIN, ÇAĞATAY; ŞEKERCİOĞLU, ÇAĞAN

    2016-01-01

    Large carnivorous mammals are wide-ranging animals and thus frequently come into contact with human settlements in agrarian landscapes. This often generates human-wildlife conflict; carnivores potentially damage livestock, agricultural products, or human well-being. In Turkey, the cooccurrence of eight medium-large carnivore species combined with a burgeoning human population and unsustainable consumption of natural resources increasingly threatens carnivore populations. To better understand ...

  14. Intestinal Ostomy.

    Science.gov (United States)

    Ambe, Peter C; Kurz, Nadja Rebecca; Nitschke, Claudia; Odeh, Siad F; Möslein, Gabriela; Zirngibl, Hubert

    2018-03-16

    About 100 000 ostomy carriers are estimated to live in Germany today. The creation of an ostomy represents a major life event that can be associated with impaired quality of life. Optimal ostomy creation and proper ostomy care are crucially important determinants of the success of treatment and of the patients' quality of life. This article is based on pertinent publications retrieved by a selective search in PubMed, GoogleScholar, and Scopus, and on the authors' experience. Intestinal stomata can be created using either the small or the large bowel. More than 75% of all stomata are placed as part of the treatment of colorectal cancer. The incidence of stoma-related complications is reported to be 10-70%. Skin irritation, erosion, and ulceration are the most common early complications, with a combined incidence of 25-34%, while stoma prolapse is the most common late complication, with an incidence of 8-75%. Most early complications can be managed conservatively, while most late complications require surgical revision. In 19% of cases, an ostomy that was initially planned to be temporary becomes permanent. Inappropriate stoma location and inadequate ostomy care are the most common causes of early complications. Both surgical and patient-related factors influence late complications. Every step from the planning of a stoma to its postoperative care should be discussed with the patient in detail. Preoperative marking is essential for an optimal stoma site. Optimal patient management with the involvement of an ostomy nurse increases ostomy acceptance, reduces ostomy-related complications, and improves the quality of life of ostomy carriers.

  15. THE IMPACT OF THE COOKED SAUSAGE ENRICHED WITH LACTULOSE AND FOOD FIBERS ON THE MORPHOFUNCTIONAL CONDITION OF THE MUCOUS MEMBRANE OF THE LARGE INTESTINE AND MICROBIOTA (MICROBIOCENOSIS IN RATS

    Directory of Open Access Journals (Sweden)

    Leonid S. Kudryashov

    2018-01-01

    Full Text Available The researches on the development of medical and medical-preventive food products for people with violation of normal intestinal microflora are presented in the article. It was found that,  the introduction into the formulation of cooked sausage food beet  fibers based on sugar beet, hydrated in a ratio 1:5, in amount 10 %  to weight of mince and lactulose, synthesized from lactose, in  amount 640 mg/kg mince retains the traditional organoleptic  properties of the product. There were carried out comparative  morphometric, histochemical and bacterioscopic studies of boiled  sausage effect without additives and sausage enriched with food  fibers and lactulose on the morphofunctional condition of the mucous membrance of the colon (MMC of rats. Was shown a significant  height  increase of epithelial surface of epithelium, an increase of frequency mitoses in the epithelium crypts of intestinal glands (from 0.6 ± 0.08 % to 1.1 ± 0.04 %, there is a tendency of increasing  content of goblet ekzokrinnye (from 21.3 ± 5.5 % to 32.4 ± 18.7  %, while the mucosal were intensively produced allopathically  mucus, which indicates the stimulation of sausage, enriched with  lactulose on the functional status of the surface epithelium and intestinal glands of the mucous membrane of the colon. Based on the studies results of the effect of food beet fibers and lactulose,  contained in the ration of rats in large and small intestine were fixed  on order greater amount of bifido- and lactobacteries in comparison  with the animals control group. Same time, it was found that in the  large intestine the number of lactobacilli were much higher in  animals receiving experimental sausage.

  16. Characterization of Large Structural Genetic Mosaicism in Human Autosomes

    Science.gov (United States)

    Machiela, Mitchell J.; Zhou, Weiyin; Sampson, Joshua N.; Dean, Michael C.; Jacobs, Kevin B.; Black, Amanda; Brinton, Louise A.; Chang, I-Shou; Chen, Chu; Chen, Constance; Chen, Kexin; Cook, Linda S.; Crous Bou, Marta; De Vivo, Immaculata; Doherty, Jennifer; Friedenreich, Christine M.; Gaudet, Mia M.; Haiman, Christopher A.; Hankinson, Susan E.; Hartge, Patricia; Henderson, Brian E.; Hong, Yun-Chul; Hosgood, H. Dean; Hsiung, Chao A.; Hu, Wei; Hunter, David J.; Jessop, Lea; Kim, Hee Nam; Kim, Yeul Hong; Kim, Young Tae; Klein, Robert; Kraft, Peter; Lan, Qing; Lin, Dongxin; Liu, Jianjun; Le Marchand, Loic; Liang, Xiaolin; Lissowska, Jolanta; Lu, Lingeng; Magliocco, Anthony M.; Matsuo, Keitaro; Olson, Sara H.; Orlow, Irene; Park, Jae Yong; Pooler, Loreall; Prescott, Jennifer; Rastogi, Radhai; Risch, Harvey A.; Schumacher, Fredrick; Seow, Adeline; Setiawan, Veronica Wendy; Shen, Hongbing; Sheng, Xin; Shin, Min-Ho; Shu, Xiao-Ou; VanDen Berg, David; Wang, Jiu-Cun; Wentzensen, Nicolas; Wong, Maria Pik; Wu, Chen; Wu, Tangchun; Wu, Yi-Long; Xia, Lucy; Yang, Hannah P.; Yang, Pan-Chyr; Zheng, Wei; Zhou, Baosen; Abnet, Christian C.; Albanes, Demetrius; Aldrich, Melinda C.; Amos, Christopher; Amundadottir, Laufey T.; Berndt, Sonja I.; Blot, William J.; Bock, Cathryn H.; Bracci, Paige M.; Burdett, Laurie; Buring, Julie E.; Butler, Mary A.; Carreón, Tania; Chatterjee, Nilanjan; Chung, Charles C.; Cook, Michael B.; Cullen, Michael; Davis, Faith G.; Ding, Ti; Duell, Eric J.; Epstein, Caroline G.; Fan, Jin-Hu; Figueroa, Jonine D.; Fraumeni, Joseph F.; Freedman, Neal D.; Fuchs, Charles S.; Gao, Yu-Tang; Gapstur, Susan M.; Patiño-Garcia, Ana; Garcia-Closas, Montserrat; Gaziano, J. Michael; Giles, Graham G.; Gillanders, Elizabeth M.; Giovannucci, Edward L.; Goldin, Lynn; Goldstein, Alisa M.; Greene, Mark H.; Hallmans, Goran; Harris, Curtis C.; Henriksson, Roger; Holly, Elizabeth A.; Hoover, Robert N.; Hu, Nan; Hutchinson, Amy; Jenab, Mazda; Johansen, Christoffer; Khaw, Kay-Tee; Koh, Woon-Puay; Kolonel, Laurence N.; Kooperberg, Charles; Krogh, Vittorio; Kurtz, Robert C.; LaCroix, Andrea; Landgren, Annelie; Landi, Maria Teresa; Li, Donghui; Liao, Linda M.; Malats, Nuria; McGlynn, Katherine A.; McNeill, Lorna H.; McWilliams, Robert R.; Melin, Beatrice S.; Mirabello, Lisa; Peplonska, Beata; Peters, Ulrike; Petersen, Gloria M.; Prokunina-Olsson, Ludmila; Purdue, Mark; Qiao, You-Lin; Rabe, Kari G.; Rajaraman, Preetha; Real, Francisco X.; Riboli, Elio; Rodríguez-Santiago, Benjamín; Rothman, Nathaniel; Ruder, Avima M.; Savage, Sharon A.; Schwartz, Ann G.; Schwartz, Kendra L.; Sesso, Howard D.; Severi, Gianluca; Silverman, Debra T.; Spitz, Margaret R.; Stevens, Victoria L.; Stolzenberg-Solomon, Rachael; Stram, Daniel; Tang, Ze-Zhong; Taylor, Philip R.; Teras, Lauren R.; Tobias, Geoffrey S.; Viswanathan, Kala; Wacholder, Sholom; Wang, Zhaoming; Weinstein, Stephanie J.; Wheeler, William; White, Emily; Wiencke, John K.; Wolpin, Brian M.; Wu, Xifeng; Wunder, Jay S.; Yu, Kai; Zanetti, Krista A.; Zeleniuch-Jacquotte, Anne; Ziegler, Regina G.; de Andrade, Mariza; Barnes, Kathleen C.; Beaty, Terri H.; Bierut, Laura J.; Desch, Karl C.; Doheny, Kimberly F.; Feenstra, Bjarke; Ginsburg, David; Heit, John A.; Kang, Jae H.; Laurie, Cecilia A.; Li, Jun Z.; Lowe, William L.; Marazita, Mary L.; Melbye, Mads; Mirel, Daniel B.; Murray, Jeffrey C.; Nelson, Sarah C.; Pasquale, Louis R.; Rice, Kenneth; Wiggs, Janey L.; Wise, Anastasia; Tucker, Margaret; Pérez-Jurado, Luis A.; Laurie, Cathy C.; Caporaso, Neil E.; Yeager, Meredith; Chanock, Stephen J.

    2015-01-01

    Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 × 10−31) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population. PMID:25748358

  17. Multiplex amplification of large sets of human exons.

    Science.gov (United States)

    Porreca, Gregory J; Zhang, Kun; Li, Jin Billy; Xie, Bin; Austin, Derek; Vassallo, Sara L; LeProust, Emily M; Peck, Bill J; Emig, Christopher J; Dahl, Fredrik; Gao, Yuan; Church, George M; Shendure, Jay

    2007-11-01

    A new generation of technologies is poised to reduce DNA sequencing costs by several orders of magnitude. But our ability to fully leverage the power of these technologies is crippled by the absence of suitable 'front-end' methods for isolating complex subsets of a mammalian genome at a scale that matches the throughput at which these platforms will routinely operate. We show that targeting oligonucleotides released from programmable microarrays can be used to capture and amplify approximately 10,000 human exons in a single multiplex reaction. Additionally, we show integration of this protocol with ultra-high-throughput sequencing for targeted variation discovery. Although the multiplex capture reaction is highly specific, we found that nonuniform capture is a key issue that will need to be resolved by additional optimization. We anticipate that highly multiplexed methods for targeted amplification will enable the comprehensive resequencing of human exons at a fraction of the cost of whole-genome resequencing.

  18. Catechol Groups Enable Reactive Oxygen Species Scavenging-Mediated Suppression of PKD-NFkappaB-IL-8 Signaling Pathway by Chlorogenic and Caffeic Acids in Human Intestinal Cells

    Directory of Open Access Journals (Sweden)

    Hee Soon Shin

    2017-02-01

    Full Text Available Chlorogenic acid (CHA and caffeic acid (CA are phenolic compounds found in coffee, which inhibit oxidative stress-induced interleukin (IL-8 production in intestinal epithelial cells, thereby suppressing serious cellular injury and inflammatory intestinal diseases. Therefore, we investigated the anti-inflammatory mechanism of CHA and CA, both of which inhibited hydrogen peroxide (H2O2-induced IL-8 transcriptional activity. They also significantly suppressed nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB transcriptional activity, nuclear translocation of the p65 subunit, and phosphorylation of IκB kinase (IKK. Additionally, upstream of IKK, protein kinase D (PKD was also suppressed. Finally, we found that they scavenged H2O2-induced reactive oxygen species (ROS and the functional moiety responsible for the anti-inflammatory effects of CHA and CA was the catechol group. Therefore, we conclude that the presence of catechol groups in CHA and CA allows scavenging of intracellular ROS, thereby inhibiting H2O2-induced IL-8 production via suppression of PKD-NF-κB signaling in human intestinal epithelial cells.

  19. R5 HIV-1 envelope attracts dendritic cells to cross the human intestinal epithelium and sample luminal virions via engagement of the CCR5.

    Science.gov (United States)

    Cavarelli, Mariangela; Foglieni, Chiara; Rescigno, Maria; Scarlatti, Gabriella

    2013-05-01

    The gastrointestinal tract is a principal route of entry and site of persistence of human immunodeficiency virus type 1 (HIV-1). The intestinal mucosa, being rich of cells that are the main target of the virus, represents a primary site of viral replication and CD4(+) T-cell depletion. Here, we show both in vitro and ex vivo that HIV-1 of R5 but not X4 phenotype is capable of selectively triggering dendritic cells (DCs) to migrate within 30 min between intestinal epithelial cells to sample virions and transfer infection to target cells. The engagement of the chemokine receptor 5 on DCs and the viral envelope, regardless of the genetic subtype, drive DC migration. Viruses penetrating through transient opening of the tight junctions likely create a paracellular gradient to attract DCs. The formation of junctions with epithelial cells may initiate a haptotactic process of DCs and at the same time favour cell-to-cell viral transmission. Our findings indicate that HIV-1 translocation across the intestinal mucosa occurs through the selective engagement of DCs by R5 viruses, and may guide the design of new prevention strategies. Copyright © 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO.

  20. 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

    BACKGROUND: Glyceryl trinitrate is a donor of nitric oxide that relaxes smooth muscle cells of the gastrointestinal tract. Little is known about the effect of glyceryl trinitrate on gastric emptying and no data exist on the possible effect of glyceryl trinitrate on small intestinal transit. AIM: ...

  1. Exenatide, a Glucagon-like Peptide-1 Receptor Agonist, Acutely Inhibits Intestinal Lipoprotein Production in Healthy Humans

    NARCIS (Netherlands)

    Xiao, Changting; Bandsma, Robert H. J.; Dash, Satya; Szeto, Linda; Lewis, Gary F.

    Objective-Incretin-based therapies for the treatment of type 2 diabetes mellitus improve plasma lipid profiles and postprandial lipemia, but their exact mechanism of action remains unclear. Here, we examined the acute effect of the glucagon-like peptide-1 receptor agonist, exenatide, on intestinal

  2. Nanoparticle formulation of a poorly soluble cannabinoid receptor 1 antagonist improves absorption by rat and human intestine

    NARCIS (Netherlands)

    Siissalo, Sanna; De Waard, Hans; De Jager, Marina H.; Hayeshi, Rose; Frijlink, Henderik W.; Hinrichs, Wouter L.J.; Dinter-Heidorn, Heike; Van Dam, Annie; Proost, Johannes H.; Groothuis, Geny M.M.; De Graaf, Inge A.M.

    The inclusion of nanoparticles dispersed in a hydrophilic matrix is one of the formulation strategies to improve the bioavailability of orally administered Biopharmaceutics Classification System (BCS) class II and IV drugs by increasing their dissolution rate in the intestine. To confirm that the

  3. Characterization of in vitro glucuronidation clearance of a range of drugs in human kidney microsomes: comparison with liver and intestinal glucuronidation and impact of albumin.

    Science.gov (United States)

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

    2012-04-01

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

  4. Temporary intestinal ischemia for radiation protection

    International Nuclear Information System (INIS)

    Lote, K.

    1983-01-01

    The most important determinant of cellular radiosensivity is the tissue oxygen content at the time of irradiation. The purpose of the present experimental work was to assess a new iscemia-inducing method in order to reduce normal tissue radiation damage during radiotherapy. Temporary ischemia was induced in a cat small intestine by degraded starch microspheres. Regional arterial and tissue blod flow immediately fell by 85% with subsequent normalization within 26 minutes after microsphere injection. No tendency of small vessel thrombosis caused by starch sphere embolization in combination with previous or current intestinal irradiation was detected. Starch sphere remenants were rapidly engulfed by, and persisted within tissue macrophages for 14 days without causing intestinal inflammatory reactions. In vitro studies showed that human platelets neither adhered to nor were aggregated by starch microspheres. The new method, wich occlude arteriolar vessels distal to the mesentric arterial arcades and thus largely excludes collateral blood flow, seems suited to provide effictive and selective feline small intestinal hypoxic radiation protection. This conclusion may also be valid in man

  5. Absorption and metabolism of the food contaminant 3-chloro-1,2-propanediol (3-MCPD) and its fatty acid esters by human intestinal Caco-2 cells.

    Science.gov (United States)

    Buhrke, Thorsten; Weisshaar, Rüdiger; Lampen, Alfonso

    2011-10-01

    3-Chloro-1,2-propanediol (3-MCPD) fatty acid esters are formed upon thermal processing of fat-containing foods in the presence of chloride ions. Upon hydrolytic cleavage, these substances could release free 3-MCPD. This compound is toxicologically well characterised and displayed cancerogenic potential in rodent models. Recently, serious contaminations of different food products with 3-MCPD fatty acid esters have been reported. In regard to a risk assessment, the key question is to which degree these 3-MCPD fatty acid esters are hydrolysed in the human gut. Therefore, the aim of the present project was to examine the hydrolysis of 3-MCPD fatty acid esters and the resulting release of free 3-MCPD by using differentiated Caco-2 cells, a cellular in vitro model for the human intestinal barrier. Here, we show that 3-MCPD fatty acid esters at a concentration of 100 μM were neither absorbed by the cells nor the esters were transported via a Caco-2 monolayer. 3-MCPD-1-monoesters were hydrolysed in the presence of Caco-2 cells. In contrast, a 3-MCPD-1,2-diester used in this study was obviously absorbed and metabolised by the cells. Free 3-MCPD was not absorbed by the cells, but the substance migrated through a Caco-2 monolayer by paracellular diffusion. From these in vitro studies, we conclude that 3-MCPD-1-monoesters are likely to be hydrolysed in the human intestine, thereby increasing the burden with free 3-MCPD. In contrast, intestinal cells seem to have the capacity to metabolise 3-MCPD diesters, thereby detoxifying the 3-MCPD moiety.

  6. Aquacultured Rainbow Trout (Oncorhynchus mykiss) Possess a Large Core Intestinal Microbiota That Is Resistant to Variation in Diet and Rearing Density

    Science.gov (United States)

    Wong, Sandi; Waldrop, Thomas; Summerfelt, Steven; Davidson, John; Barrows, Frederic; Kenney, P. Brett; Welch, Timothy; Wiens, Gregory D.; Snekvik, Kevin

    2013-01-01

    As global aquaculture fish production continues to expand, an improved understanding of how environmental factors interact in fish health and production is needed. Significant advances have been made toward economical alternatives to costly fishmeal-based diets, such as grain-based formulations, and toward defining the effect of rearing density on fish health and production. Little research, however, has examined the effects of fishmeal- and grain-based diets in combination with alterations in rearing density. Moreover, it is unknown whether interactions between rearing density and diet impact the composition of the fish intestinal microbiota, which might in turn impact fish health and production. We fed aquacultured adult rainbow trout (Oncorhynchus mykiss) fishmeal- or grain-based diets, reared them under high- or low-density conditions for 10 months in a single aquaculture facility, and evaluated individual fish growth, production, fin indices, and intestinal microbiota composition using 16S rRNA gene sequencing. We found that the intestinal microbiotas were dominated by a shared core microbiota consisting of 52 bacterial lineages observed across all individuals, diets, and rearing densities. Variations in diet and rearing density resulted in only minor changes in intestinal microbiota composition despite significant effects of these variables on fish growth, performance, fillet quality, and welfare. Significant interactions between diet and rearing density were observed only in evaluations of fin indices and the relative abundance of the bacterial genus Staphylococcus. These results demonstrate that aquacultured rainbow trout can achieve remarkable consistency in intestinal microbiota composition and suggest the possibility of developing novel aquaculture strategies without overtly altering intestinal microbiota composition. PMID:23770898

  7. Uncovering urban human mobility from large scale taxi GPS data

    Science.gov (United States)

    Tang, Jinjun; Liu, Fang; Wang, Yinhai; Wang, Hua

    2015-11-01

    Taxi GPS trajectories data contain massive spatial and temporal information of urban human activity and mobility. Taking taxi as mobile sensors, the information derived from taxi trips benefits the city and transportation planning. The original data used in study are collected from more than 1100 taxi drivers in Harbin city. We firstly divide the city area into 400 different transportation districts and analyze the origin and destination distribution in urban area on weekday and weekend. The Density-Based Spatial Clustering of Applications with Noise (DBSCAN) algorithm is used to cluster pick-up and drop-off locations. Furthermore, four spatial interaction models are calibrated and compared based on trajectories in shopping center of Harbin city to study the pick-up location searching behavior. By extracting taxi trips from GPS data, travel distance, time and average speed in occupied and non-occupied status are then used to investigate human mobility. Finally, we use observed OD matrix of center area in Harbin city to model the traffic distribution patterns based on entropy-maximizing method, and the estimation performance verify its effectiveness in case study.

  8. The heterocyclic ring fission and dehydroxylation of catechins and related compounds by Eubacterium sp. strain SDG-2, a human intestinal bacterium.

    Science.gov (United States)

    Wang, L Q; Meselhy, M R; Li, Y; Nakamura, N; Min, B S; Qin, G W; Hattori, M

    2001-12-01

    A human intestinal bacterium, Eubacterium (E.) sp. strain SDG-2, was tested for its ability to metabolize various (3R)- and (3S)-flavan-3-ols and their 3-O-gallates. This bacterium cleaved the C-ring of (3R)- and (3S)-flavan-3-ols to give 1,3-diphenylpropan-2-ol derivatives, but not their 3-O-gallates. Furthermore, E. sp. strain SDG-2 had the ability of p-dehydroxylation in the B-ring of (3R)-flavan-3-ols, such as (-)-catechin, (-)-epicatechin, (-)-gallocatechin and (-)-epigallocatechin, but not of (3S)-flavan-3-ols, such as (+)-catechin and (+)-epicatechin.

  9. Killed Whole-Cell Oral Cholera Vaccine Induces CCL20 Secretion by Human Intestinal Epithelial Cells in the Presence of the Short-Chain Fatty Acid, Butyrate

    Directory of Open Access Journals (Sweden)

    Ju-Ri Sim

    2018-01-01

    Full Text Available Short-chain fatty acids (SCFAs, such as acetate, butyrate, and propionate, modulate immune responses in the gut. However, the effect of SCFAs on mucosal vaccine-induced immune cell migration is poorly understood. Here, we investigated whether SCFAs modulate chemokine expression induced by the killed whole-cell oral cholera vaccine, Shanchol™, in human intestinal epithelial cells. Shanchol™ induced expression of CCL2, CCL5, CCL20, and CXCL10 at the mRNA level, but not at the protein level. Interestingly, CCL20 secretion was substantially increased by co-stimulation with Shanchol™ and butyrate, while neither acetate nor propionate showed such effect. Enhanced CCL20 secretion was associated with GPR109A activation, and histone deacetylase (HDAC inhibition. In addition, co-treatment with Shanchol™ and butyrate synergistically increased the secretion of adenosine triphosphate (ATP. Moreover, CCL20 secretion was decreased by inhibiting the extracellular ATP receptor P2X7. However, neither inflammasomes nor caspases were involved in CCL20 production. The culture supernatant of cells treated with Shanchol™ and butyrate augmented human immature dendritic cell migration. Collectively, these results suggest that butyrate enhances Shanchol™-induced CCL20 production in human intestinal epithelial cells via HDAC inhibition and ATP-P2X7 signaling by activating GPR109A. These effects potentially enhance the mucosal immune responses in the gut induced by this oral cholera vaccine.

  10. CYP1A1 induction and CYP3A4 inhibition by the fungicide imazalil in the human intestinal Caco-2 cells-comparison with other conazole pesticides.

    Science.gov (United States)

    Sergent, Thérèse; Dupont, Isabelle; Jassogne, Coralie; Ribonnet, Laurence; van der Heiden, Edwige; Scippo, Marie-Louise; Muller, Marc; McAlister, Dan; Pussemier, Luc; Larondelle, Yvan; Schneider, Yves-Jacques

    2009-02-10

    Imazalil (IMA) is a widely used imidazole-antifungal pesticide and, therefore, a food contaminant. This compound is also used as a drug (enilconazole). As intestine is the first site of exposure to ingested drugs and pollutants, we have investigated the effects of IMA, at realistic intestinal concentrations, on xenobiotic-metabolizing enzymes and efflux pumps by using Caco-2 cells, as a validated in vitro model of the human intestinal absorptive epithelium. For comparison, other conazole fungicides, i.e. ketoconazole, propiconazole and tebuconazole, were also studied. IMA induced cytochrome P450 (CYP) 1A1 activity to the same extent as benzo(a)pyrene (B(a)P) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), in a dose- and time-dependent manner. Cell-free aryl hydrocarbon receptor (AhR) binding assay and reporter gene assay suggested that IMA is not an AhR-ligand, implying that IMA-mediated induction should involve an AhR-independent pathway. Moreover, IMA strongly inhibited the CYP3A4 activity in 1,25-vitamin D(3)-induced Caco-2 cells. The other fungicides had weak or nil effects on CYP activities. Study of the apical efflux pump activities revealed that ketoconazole inhibited both P-glycoprotein (Pgp) and multidrug resistance-associated protein 2 (MRP-2) or breast cancer resistance protein (BCRP), whereas IMA and other fungicides did not. Our results imply that coingestion of IMA-contaminated food and CYP3A4- or CYP1A1-metabolizable drugs or chemicals could lead to drug bioavailability modulation or toxicological interactions, with possible adverse effects for human health.

  11. Altered cytochrome P450 activities and expression levels in the liver and intestines of the monosodium glutamate-induced mouse model of human obesity.

    Science.gov (United States)

    Tomankova, Veronika; Liskova, Barbora; Skalova, Lenka; Bartikova, Hana; Bousova, Iva; Jourova, Lenka; Anzenbacher, Pavel; Ulrichova, Jitka; Anzenbacherova, Eva

    2015-07-15

    Cytochromes P450 (CYPs) are enzymes present from bacteria to man involved in metabolism of endogenous and exogenous compounds incl. drugs. Our objective was to assess whether obesity leads to changes in activities and expression of CYPs in the mouse liver, small intestine and colon. An obese mouse model with repeated injection of monosodium glutamate (MSG) to newborns was used. Controls were treated with saline. All mice were sacrificed at 8 months. In the liver and intestines, levels of CYP mRNA and proteins were analyzed using RT-PCR and Western blotting. Activities of CYP enzymes were measured with specific substrates of human orthologous forms. At the end of the experiment, body weight, plasma insulin and leptin levels as well as the specific content of hepatic CYP enzymes were increased in obese mice. Among CYP enzymes, hepatic CYP2A5 activity, protein and mRNA expression increased most significantly in obese animals. Higher activities and protein levels of hepatic CYP2E1 and 3A in the obese mice were also found. No or a weak effect on CYPs 2C and 2D was observed. In the small intestine and colon, no changes of CYP enzymes were detected except for increased expression of CYP2E1 and decreased expression of CYP3A mRNAs in the colon of the obese mice. Results of our study suggest that the specific content and activities of some liver CYP enzymes (especially CYP2A5) can be increased in obese mice. Higher activity of CYP2A5 (CYP2A6 human ortholog) could lead to altered metabolism of drug substrates of this enzyme (valproic acid, nicotine, methoxyflurane). Copyright © 2015 Elsevier Inc. All rights reserved.

  12. A strategy for isolation of cDNAs encoding proteins affecting human intestinal epithelial cell growth and differentiation: characterization of a novel gut-specific N-myristoylated annexin.

    Science.gov (United States)

    Wice, B M; Gordon, J I

    1992-01-01

    The human intestinal epithelium is rapidly and perpetually renewed as the descendants of multipotent stem cells located in crypts undergo proliferation, differentiation, and eventual exfoliation during a very well organized migration along the crypt to villus axis. The mechanisms that establish and maintain this balance between proliferation and differentiation are largely unknown. We have utilized HT-29 cells, derived from a human colon adenocarcinoma, as a model system for identifying gene products that may regulate these processes. Proliferating HT-29 cells cultured in the absence of glucose (e.g., using inosine as the carbon source) have some of the characteristics of undifferentiated but committed crypt epithelial cells while postconfluent cells cultured in the absence of glucose resemble terminally differentiated enterocytes or goblet cells. A cDNA library, constructed from exponentially growing HT-29 cells maintained in inosine-containing media, was sequentially screened with a series of probes depleted of sequences encoding housekeeping functions and enriched for intestine-specific sequences that are expressed in proliferating committed, but not differentiated, epithelial cells. Of 100,000 recombinant phage surveyed, one was found whose cDNA was derived from an apparently gut-specific mRNA. It encodes a 316 residue, 35,463-D protein that is a new member of the annexin/lipocortin family. Other family members have been implicated in regulation of cellular growth and in signal transduction pathways. RNA blot and in situ hybridization studies indicate that the gene encoding this new annexin exhibits region-specific expression along both axes of the human gut: (a) highest levels of mRNA are present in the jejunum with marked and progressive reductions occurring distally; (b) its mRNA appears in crypt-associated epithelial cells and increases in concentration as they exit the crypt. Villus-associated epithelial cells continue to transcribe this gene during their

  13. [The character of the morphological changes of the mucous membrane of the large intestine and the genetic polymorphism of IL-1RA, IL-1B, IL-4 TNFA in patient with irritable bowel syndrome].

    Science.gov (United States)

    Sarsenbaeva, A S; Ivanova, E L; Burmistrova, A L; Drozdov, I V

    2013-01-01

    The aim of this study was to evaluate the presence or absence of a relationship between the variants of the course of IBS and their association with genetic polymorphisms of genes and intergenic interaction of cytokines. The sample consisted of 81 patients, the diagnosis was verified according to the criteria of the Rome III, were isolated psychopathological, morphological complications, extra-intestinal symptoms. Polymorphism genotyping IL-1Ra, IL-b, IL-4, TNFa performed by PCR. Statistical treatment are a non-parametric analysis of multiple comparisons, hierarchical log-linear analysis. It is found out the relation between the clinical variants with morphological changes of the mucous membrane of the large intestine, the association between gender characteristics of patients with IBS is established and with genetic polymorphisms of cytokines.

  14. Quantification of Salmonella Survival and Infection in an In vitro Model of the Human Intestinal Tract as Proxy for Foodborne Pathogens

    Directory of Open Access Journals (Sweden)

    Lucas M. Wijnands

    2017-06-01

    Full Text Available Different techniques are available for assessing differences in virulence of bacterial foodborne pathogens. The use of animal models or human volunteers is not expedient for various reasons; the use of epidemiological data is often hampered by lack of crucial data. In this paper, we describe a static, sequential gastrointestinal tract (GIT model system in which foodborne pathogens are exposed to simulated gastric and intestinal contents of the human digestive tract, including the interaction of pathogens with the intestinal epithelium. The system can be employed with any foodborne bacterial pathogens. Five strains of Salmonella Heidelberg and one strain of Salmonella Typhimurium were used to assess the robustness of the system. Four S. Heidelberg strains originated from an outbreak, the fifth S. Heidelberg strain and the S. Typhimurium strain originated from routine meat inspections. Data from plate counts, collected for determining the numbers of surviving bacteria in each stage, were used to quantify both the experimental uncertainty and biological variability of pathogen survival throughout the system. For this, a hierarchical Bayesian framework using Markov chain Monte Carlo (MCMC was employed. The model system is able to distinguish serovars/strains for in vitro infectivity when accounting for within strain biological variability and experimental uncertainty.

  15. Bioengineered 2'-fucosyllactose and 3-fucosyllactose inhibit the adhesion of Pseudomonas aeruginosa and enteric pathogens to human intestinal and respiratory cell lines.

    Science.gov (United States)

    Weichert, Stefan; Jennewein, Stefan; Hüfner, Eric; Weiss, Christel; Borkowski, Julia; Putze, Johannes; Schroten, Horst

    2013-10-01

    Human milk oligosaccharides help to prevent infectious diseases in breastfed infants. Larger scale testing, particularly in animal models and human clinical studies, is still limited due to shortened availability of more complex oligosaccharides. The purpose of this study was to evaluate 2'-fucosyllactose (2'-FL) and 3-fucosyllactose (3-FL) synthesized by whole-cell biocatalysis for their biological activity in vitro. Therefore, we have tested these oligosaccharides for their inhibitory potential of pathogen adhesion in two different human epithelial cell lines. 2'-FL could inhibit adhesion of Campylobacter jejuni, enteropathogenic Escherichia coli, Salmonella enterica serovar fyris, and Pseudomonas aeruginosa to the intestinal human cell line Caco-2 (reduction of 26%, 18%, 12%, and 17%, respectively), as could be shown for 3-FL (enteropathogenic E coli 29%, P aeruginosa 26%). Furthermore, adherence of P aeruginosa to the human respiratory epithelial cell line A549 was significantly inhibited by 2'-FL and 3-FL (reduction of 24% and 23%, respectively). These results confirm the biological and functional activity of biotechnologically synthesized human milk oligosaccharides. Mass-tailored human milk oligosaccharides could be used in the future to supplement infant formula ingredients or as preventatives to reduce the impact of infectious diseases. © 2013 Elsevier Inc. All rights reserved.

  16. 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)

    Maresca, Marc; Yahi, Nouara; Younes-Sakr, Lama; Boyron, Marilyn; Caporiccio, Bertrand; Fantini, Jacques

    2008-01-01

    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

  17. Cytokine responses in primary chicken embryo intestinal cells infected with Campylobacter jejuni strains of human and chicken origin and the expression of bacterial virulence-associated genes

    DEFF Research Database (Denmark)

    Li, Yiping; Ingmer, Hanne; Madsen, Mogens

    2008-01-01

    of the bacterial genes. We have investigated the invasiveness of primary chicken embryo intestinal cells (CEICs) by C. jejuni strains of human and chicken origins and the production of pro-inflammatory cytokines as well as the expression of the bacterial virulence-associated genes during co-cultivation. Results C......-free media from another co-cultivation experiment also increased the expression of the virulence-associated genes in the C. jejuni chicken isolate, indicating that the expression of bacterial genes is regulated by component(s) secreted upon co-cultivation of bacteria and CEICs. Conclusion We show that under...... in vitro culture condition C. jejuni strains of both human and chicken origins can invade avian host cells with a pro-inflammatory response and that the virulence-associated genes of C. jejuni may play a role in this process....

  18. 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.

  19. Effects of selected non-digestible dietary carbohydrates on the composition of the large intestinal microbiota and susceptibility to salmonella infections

    DEFF Research Database (Denmark)

    Petersen, Anne

    The mammalian intestinal tract is a complex ecosystem colonised by a high and diverse number of commensal bacterial. Bacteria colonising the intestinal tract have a profound impact on host health e.g. by acting as a barrier against colonisation by pathogens and by contributing to digestion...... of complex food components. In this regard there is a considerable interest in dietary components that can modulate the gut microbiota and potentially improve gut health. Some gut bacteria, known as probiotics, are belived to improve gut health upond ingestion, whereas non-digestible (ND) dietary...... of the gut microbiota or by stimulating the immune response. Salmonella is a genus of Gram-negative bacteria that are a major cause of food-borne illness globally. Several studies with probiotics have demonstrated protective effects against murine Salmonella infections, while studies with prebiotics have...

  20. Trichinella spiralis in human muscle (image)

    Science.gov (United States)

    This is the parasite Trichinella spiralis in human muscle tissue. The parasite is transmitted by eating undercooked meats, especially pork. The cysts hatch in the intestines and produce large numbers of larvae that migrate into muscle tissue. The cysts ...

  1. Diets high in resistent starch and arabinoxylan modulate digestion processes and SCFA pool size in the large intestine and faecal microbial composition in pigs

    DEFF Research Database (Denmark)

    Nielsen, Tina Skau; Lærke, Helle Nygaard; Theil, Peter Kappel

    2014-01-01

    The effects of a high level of dietary fibre (DF) either as arabinoxylan (AX) or resistant starch (RS) on digestion processes, SCFA co