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Sample records for human intestinal transit

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

    International Nuclear Information System (INIS)

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

  2. [The human intestinal microbiota].

    Science.gov (United States)

    Doré, J; Corthier, G

    2010-09-01

    The human intestinal microbiota constitutes a complex ecosystem which is now well recognized for its impact on human health and well-being. It contributes to maturation of the immune system and provides a direct barrier against colonization by pathogens. Its possible implication in diseases of modern societies, currently increasing in prevalence, has been reported. These include allergies, inflammatory bowel diseases and possibly metabolic and degenerative disorders. The analysis of the molecular composition of the human intestinal microbiota indicates marked inter-individual variations which may seem paradoxical considering the high degree of conservation of major functions of the intestinal microbiota such as anaerobic digestion of alimentary fibres. We have characterized a phylogenetic core within the human intestinal microbiota, in terms of composition, i.e., a set of conserved species that could be responsible for major conserved functions. Based on culture-independent molecular assessments, current knowledge enables a definition of criteria qualifying the normal state of the human intestinal microbiota that we call normobiosis. This further enables the identification of specific deviations from normobiosis, i.e., dysbiosis in immune, metabolic or degenerative diseases. Notably, Crohn's disease, an inflammatory bowel disease of yet unknown aetiology, is associated with intestinal dysbiosis with a lower representation of the Clostridium leptum group among the Firmicutes phylum. We further showed that the bacterial species Faecalibacterium prausnitzii exerts anti-inflammatory properties in vitro and in animal models; this could explain its ability, when detected in the mucosa-associated microbiota of patients in vivo, to protect patients from post-operative recurrence of endoscopic signs of inflammation 6 months after surgical resection of the ileocecal region of the gut. By confirming the major role of the microbiota in bowel-related disorders, which are especially associated with a disruption of homeostasis, we are currently applying high throughput functional metagenomic screens in order to identify signal molecules and mechanisms of bacteria-host cross-talk. Together with the high resolution description of the human intestinal metagenome, as well as explorations of environmental proteins and metabolites, these observations will further our understanding of the functional roles bacteria play in the maintenance of health and well-being in humans. It will open new perspectives for the monitoring and design of strategies for modulating the microbiota for health. PMID:20889008

  3. Tissue transition projection (TTP) of the intestines

    International Nuclear Information System (INIS)

    Tissue transition projection (TTP) represents a three-dimensional reconstruction technique for volumetric image data sets. To demonstrate the principle characteristics of TTP, a simple phantom consisting of two pipes with a simulated, wall-adherent polyp was scanned with spiral CT, and images were reconstructed by means of volume rendering for both opaque surface reconstructions and TTP. Tissue transition projection was used in 7 patients for reconstruction of the small intestine or the colon. Unlike three-dimensional reconstructions with opaque surfaces, TTP enhances surface transitions while suppressing homogeneous areas, allowing delineation of the bowel wall similar to conventional double-contrast studies. (orig.)

  4. Radioimmunoassay of human intestinal alkaline phosphatase

    International Nuclear Information System (INIS)

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

  5. The Human Intestinal Microbiome: A New Frontier of Human Biology

    OpenAIRE

    Hattori, Masahira; Taylor, Todd D.

    2009-01-01

    To analyze the vast number and variety of microorganisms inhabiting the human intestine, emerging metagenomic technologies are extremely powerful. The intestinal microbes are taxonomically complex and constitute an ecologically dynamic community (microbiota) that has long been believed to possess a strong impact on human physiology. Furthermore, they are heavily involved in the maturation and proliferation of human intestinal cells, helping to maintain their homeostasis and can be causative o...

  6. Shiga Toxin Interaction with Human Intestinal Epithelium

    Directory of Open Access Journals (Sweden)

    Stephanie Schüller

    2011-06-01

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

  7. Accurate measurement of intestinal transit in the rat

    International Nuclear Information System (INIS)

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

  8. Accurate measurement of intestinal transit in the rat

    Energy Technology Data Exchange (ETDEWEB)

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

    1981-11-01

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

  9. Small intestinal permeability and orocaecal transit time in cystic fibrosis.

    OpenAIRE

    Dalzell, A M; Freestone, N S; Billington, D.; Heaf, D. P.

    1990-01-01

    Cellobiose and mannitol were used as probe molecules to measure intestinal permeability in 36 children with cystic fibrosis, and 25 age matched controls. Orocaecal transit was also evaluated for each subject using the lactulose/hydrogen breath test. There was a fourfold increase in permeability to disaccharide (cellobiose) in patients with cystic fibrosis, but permeability to the monosaccharide (mannitol) was similar to controls. The orocaecal transit time of lactulose was prolonged in patien...

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

    OpenAIRE

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

    2015-01-01

    Tenofovir-disoproxil-fumarate (TDF) is a double ester prodrug which enables intestinal uptake of tenofovir (TFV) after oral administration in humans. In this study, prodrug stability was monitored in situ in the human intestine and in vitro using biorelevant media. In fasted state human intestinal fluids, the prodrug was completely degraded within 90min, resulting in the formation of the mono-ester intermediate and TFV; in fed state intestinal fluids, the degradation rate of TDF was slightly ...

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

    International Nuclear Information System (INIS)

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

  12. Cholesterol esterase activity of human intestinal mucosa

    Energy Technology Data Exchange (ETDEWEB)

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

    1985-11-01

    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 UC-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.

  13. Cholesterol esterase activity of human intestinal mucosa

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

    Reproducible measurements of small intestine transit for spherical particles of 0.5 ? to 1 mm diameter, have been accomplished in the conscious rat. A short cannula of polyethylene is surgically implanted into the duodenum and exists through the abdominal wall. After recovery, a bolus of saline containing colored or isotopically labeled particulate material and an internal standard of NaCr51O4 is introduced with a modified pipette tip that snugly fills the cannula to prevent back flow. The rats eat and drink during the transit period and are maintained on a reversed light cycle so that transit is measured during their physically active period. Glass microspheres of 1mm, 500 ?, and 50 ? were followed at 30 min, 1 hr, and 2 hr intervals by opening the intestine and photographing 1 cm segments along its length. Polymer beads of 500 ?, 125 ?, and 70 ? were labeled with 125I and located by freezing the exteriorized intestine and counting 1 cm segments in a gamma counter. Movement of the fluid bolus as detected by NaCr51O4 was reproducible with the fluid front moving through 59%, 73%, and 81% of the length at 30 min, 1 hr, and 2 hr. One millimeter to 125 ? glass and polymer beads moved with the fluid bolus. Evidence for separation of the fluid phase and particles under ? 100 ? is accumulating. It is hypothesized that small particles under a critical size may become lodged in the mucus lining of the intestinal wall

  15. The human intestinal microbiome: a new frontier of human biology.

    Science.gov (United States)

    Hattori, Masahira; Taylor, Todd D

    2009-02-01

    To analyze the vast number and variety of microorganisms inhabiting the human intestine, emerging metagenomic technologies are extremely powerful. The intestinal microbes are taxonomically complex and constitute an ecologically dynamic community (microbiota) that has long been believed to possess a strong impact on human physiology. Furthermore, they are heavily involved in the maturation and proliferation of human intestinal cells, helping to maintain their homeostasis and can be causative of various diseases, such as inflammatory bowel disease and obesity. A simplified animal model system has provided the mechanistic basis for the molecular interactions that occur at the interface between such microbes and host intestinal epithelia. Through metagenomic analysis, it is now possible to comprehensively explore the genetic nature of the intestinal microbiome, the mutually interacting system comprising the host cells and the residing microbial community. The human microbiome project was recently launched as an international collaborative research effort to further promote this newly developing field and to pave the way to a new frontier of human biology, which will provide new strategies for the maintenance of human health. PMID:19147530

  16. Compartmentalization of Aquaporins in the Human Intestine

    Directory of Open Access Journals (Sweden)

    Rajendram V. Rajnarayanan

    2008-06-01

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

  17. Adhesion of enteropathogenic Escherichia coli to human intestinal enterocytes and cultured human intestinal mucosa.

    OpenAIRE

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

    1987-01-01

    The adhesion of classic enteropathogenic Escherichia coli (EPEC) strains of human origin to isolated human small intestinal enterocytes and cultured small intestinal mucosa was investigated. An adhesion assay with isolated human enterocytes prepared from duodenal biopsy samples was developed and tested with EPEC strains known to cause diarrhea in healthy adult volunteers. In the assay a mean of 53 and 55% of enterocytes had brush border-adherent E. coli E2348 (O127;H6) and E851 (O142:H6), res...

  18. Vasoactive intestinal peptide in human nasal mucosa.

    OpenAIRE

    Baraniuk, J N; Lundgren, J D; Okayama, M.; Mullol, J.; Merida, M; Shelhamer, J.H.; Kaliner, M A

    1990-01-01

    Vasoactive intestinal peptide (VIP), which is present with acetylcholine in parasympathetic nerve fibers, may have important regulatory functions in mucous membranes. The potential roles for VIP in human nasal mucosa were studied using an integrated approach. The VIP content of human nasal mucosa was determined to be 2.84 +/- 0.47 pmol/g wet weight (n = 8) by RIA. VIP-immunoreactive nerve fibers were found to be most concentrated in submucosal glands adjacent to serous and mucous cells. 125I-...

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

    International Nuclear Information System (INIS)

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

  20. Intestinal transit and bacterial translocation in obstructive pancreatitis.

    Science.gov (United States)

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

    1995-08-01

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

  1. Alternative Functional In Vitro Models of Human Intestinal Epithelia

    Directory of Open Access Journals (Sweden)

    AmandaLKauffman

    2013-07-01

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

  2. Distinct Human Stem Cell Populations in Small and Large Intestine

    OpenAIRE

    Cramer, Julie M.; Thompson, Timothy; Geskin, Albert; LaFramboise, William; Lagasse, Eric

    2015-01-01

    The intestine is composed of an epithelial layer containing rapidly proliferating cells that mature into two regions, the small and the large intestine. Although previous studies have identified stem cells as the cell-of-origin for intestinal epithelial cells, no studies have directly compared stem cells derived from these anatomically distinct regions. Here, we examine intrinsic differences between primary epithelial cells isolated from human fetal small and large intestine, after in vitro e...

  3. 5-Hydroxytryptamine and human small intestinal motility: effect of inhibiting 5-hydroxytryptamine reuptake.

    OpenAIRE

    Gorard, D. A.; Libby, G W; Farthing, M J

    1994-01-01

    Parenteral 5-hydroxytryptamine stimulates small intestinal motility, but the effect of continuous stimulation with 5-hydroxytryptamine on the human migrating motor complex is unknown. Using a selective 5-hydroxytryptamine reuptake inhibitor, paroxetine, this study investigated the effect of indirect 5-hydroxytryptamine agonism on fasting small intestinal motility and transit. Eight healthy subjects were studied while receiving paroxetine 30 mg daily for five days and while receiving no treatm...

  4. Dynamic efficiency of the human intestinal microbiota.

    Science.gov (United States)

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

    2015-06-01

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

  5. Molecular Epidemiology of Human Intestinal Amoebas in Iran

    OpenAIRE

    M. Rezaian; P Rostamkhani; H Hooshyar

    2012-01-01

    Many microscopic-based epidemiological surveys on the prevalence of human intestinal pathogenic and non-pathogenic protozoa including intestinal amoeba performed in Iran show a high prevalence of human intestinal amoeba in different parts of Iran. Such epidemiological studies on amoebiasis are confusing, mainly due to recently appreciated distinction between the Entamoeba histolytica, E. dispar and E. moshkovskii. Differential diagnosis can be done by some methods such as PCR-based methods, m...

  6. Human milk oligosaccharides: the novel modulator of intestinal microbiota

    Directory of Open Access Journals (Sweden)

    Kyunghun Jeong1, Vi Nguyen2 & Jaehan Kim1,*

    2012-08-01

    Full Text Available Human milk, which nourishes the early infants, is a source ofbioactive components for the infant growth, development andcommensal formulation as well. Human milk oligosaccharide is agroup of complex and diverse glycans that is apparently notabsorbed in human gastrointestinal tract. Although mostmammalian milk contains oligosaccharides, oligosaccharides inhuman milk exhibit unique features in terms of their types,amounts, sizes, and functionalities. In addition to the preventionof infectious bacteria and the development of early immunesystem, human milk oligosaccharides are able to facilitate thehealthy intestinal microbiota. Bifidobacterial intestinal microbiotaappears to be established by the unilateral interaction betweenmilk oligosaccharides, human intestinal activity and commensals.Digestibility, membrane transportation and catabolic activity bybacteria and intestinal epithelial cells, all of which are linked tothe structural of human milk oligosaccharides, are crucial indetermining intestinal microbiota.

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

    Directory of Open Access Journals (Sweden)

    Stacy R. Finkbeiner

    2015-11-01

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

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

    International Nuclear Information System (INIS)

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

  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. Human placental alkaline phosphatase in liver and intestine

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2015-05-15

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

  12. Intestinal epithelial cells preferentially attach to a biomatrix derived from human intestinal mucosa.

    OpenAIRE

    Hahn, U.; Cho, A.; Schuppan, D.; Hahn, E. G.; Merker, H J; Riecken, E. O.

    1987-01-01

    Primary intestinal epithelial cells have a very short lifespan in vitro when cultured free of mucosal elements. Support of the basal plasma membrane by a more natural substrate may thus enhance the initiation of primary cell cultures. A cell free biomatrix consisting of native interstitial collagens, basement membrane fragments and microfibrils was extracted from the lamina propria of human intestinal mucosa. Immunofluorescence revealed the presence of collagens type III, IV, and VI and proco...

  13. Efficient genetic engineering of human intestinal organoids using electroporation.

    Science.gov (United States)

    Fujii, Masayuki; Matano, Mami; Nanki, Kosaku; Sato, Toshiro

    2015-10-01

    Gene modification in untransformed human intestinal cells is an attractive approach for studying gene function in intestinal diseases. However, because of the lack of practical tools, such studies have largely depended upon surrogates, such as gene-engineered mice or immortalized human cell lines. By taking advantage of the recently developed intestinal organoid culture method, we developed a methodology for modulating genes of interest in untransformed human colonic organoids via electroporation of gene vectors. Here we describe a detailed protocol for the generation of intestinal organoids by culture with essential growth factors in a basement membrane matrix. We also describe how to stably integrate genes via the piggyBac transposon, as well as precise genome editing using the CRISPR-Cas9 system. Beginning with crypt isolation from a human colon sample, genetically modified organoids can be obtained in 3 weeks. PMID:26334867

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

    OpenAIRE

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

    1998-01-01

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

  15. Cholinergic mediation of small intestinal transit in the rat

    International Nuclear Information System (INIS)

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

  16. Obstructive cholestasis alters intestinal transit in mice: role of opioid system.

    Science.gov (United States)

    Ghaffari, Kamyar; Savadkuhi, Shahab Tour; Honar, Hooman; Riazi, Kiarash; Shafaroodi, Hamed; Moezi, Leila; Ebrahimkhani, Mohammad Reza; Tahmasebi, Mohammad Saeid Radjabzadeh; Dehpour, Ahmad Reza

    2004-12-10

    Acute cholestasis is associated with increased activity of the endogenous opioid system. It is also known that opioid receptor agonists like morphine decrease the intestinal transit. The purpose of the present study was to investigate the effect of cholestasis on the small intestine transit and the possible involvement of opioid system in this phenomenon in mice. Cholestasis was induced by bile duct-ligation and intestinal transit was measured with charcoal meal and calculation of percent of transit through small intestine. The effect of chronic administration of naltrexone and acute pretreatment with morphine on intestinal transit was evaluated in bile duct-ligated (BDL) as well as unoperated (CTL) and sham-operated (SHAM) animals. The plasma alkaline phosphatase and alanine aminotransferase activities were also measured. A significant decrease in small intestine transit (%transit) was observed in BDL mice compared to SHAM animals, which was prominent even after 24 h of cholestasis. Chronic pretreatment with an opioid receptor antagonist, naltrexone, (10 mg/kg, i.p for 2, 4 or 6 days) completely restored the cholestasis-induced decrease in %transit to that of control animals. Although the acute administration of morphine (2 mg/kg, s.c.) 20 min before charcoal feeding caused a significant decrease in the intestinal transit of CTL and SHAM animals, it did not decrease the %transit of BDL animals on the day 5 after operation. Our findings show that acute cholestasis is associated with a prominent decrease in small intestine transit in mice and opioid receptors maybe involved in this phenomenon. PMID:15530502

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

    Science.gov (United States)

    Cramer, Julie M; Thompson, Timothy; Geskin, Albert; LaFramboise, William; Lagasse, Eric

    2015-01-01

    The intestine is composed of an epithelial layer containing rapidly proliferating cells that mature into two regions, the small and the large intestine. Although previous studies have identified stem cells as the cell-of-origin for intestinal epithelial cells, no studies have directly compared stem cells derived from these anatomically distinct regions. Here, we examine intrinsic differences between primary epithelial cells isolated from human fetal small and large intestine, after in vitro expansion, using the Wnt agonist R-spondin 2. We utilized flow cytometry, fluorescence-activated cell sorting, gene expression analysis and a three-dimensional in vitro differentiation assay to characterize their stem cell properties. We identified stem cell markers that separate subpopulations of colony-forming cells in the small and large intestine and revealed important differences in differentiation, proliferation and disease pathways using gene expression analysis. Single cells from small and large intestine cultures formed organoids that reflect the distinct cellular hierarchy found in vivo and respond differently to identical exogenous cues. Our characterization identified numerous differences between small and large intestine epithelial stem cells suggesting possible connections to intestinal disease. PMID:25751518

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  20. Permeation of Four Oral Drugs Through Human Intestinal Mucosa

    OpenAIRE

    Pretorius, Erina; Bouic, Patrick J. D.

    2009-01-01

    The pharmaceutical industry is in need of rapid and accurate methods to screen new drug leads for intestinal permeability potential in the early stages of drug discovery. Excised human jejunal mucosa was used to investigate the permeability of the small intestine to four oral drugs, using a flow-through diffusion system. The four drugs were selected as representative model compounds of drug classes 1 and 3 according to the biopharmaceutics classification system (BCS). The drugs selected were ...

  1. Metabolomics of human intestinal transplant rejection.

    Science.gov (United States)

    Girlanda, R; Cheema, A K; Kaur, P; Kwon, Y; Li, A; Guerra, J; Matsumoto, C S; Zasloff, M; Fishbein, T M

    2012-12-01

    Surveillance endoscopy with biopsy is the standard method to monitor intestinal transplant recipients but it is invasive, costly and prone to sampling error. Early noninvasive biomarkers of intestinal rejection are needed. In this pilot study we applied metabolomics to characterize the metabolomic profile of intestinal allograft rejection. Fifty-six samples of ileostomy fluid or stool from 11 rejection and 45 nonrejection episodes were analyzed by ultraperformance liquid chromatography in conjunction with Quadrupole time-of-flight mass spectrometry (UPLC-QTOFMS). The data were acquired in duplicate for each sample in positive ionization mode and preprocessed using XCMS (Scripps) followed by multivariate data analysis. We detected a total of 2541 metabolites in the positive ionization mode (mass 50-850 Daltons). A significant interclass separation was found between rejection and nonrejection. The proinflammatory mediator leukotriene E4 was the metabolite with the highest fold change in the rejection group compared to nonrejection. Water-soluble vitamins B2, B5, B6, and taurocholate were also detected with high fold change in rejection. The metabolomic profile of rejection was more heterogeneous than nonrejection. Although larger studies are needed, metabolomics appears to be a promising tool to characterize the pathophysiologic mechanisms involved in intestinal allograft rejection and potentially to identify noninvasive biomarkers. PMID:22759354

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

    International Nuclear Information System (INIS)

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

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

    OpenAIRE

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

    1999-01-01

    OBJECTIVE—To investigate gastric emptying and intestinal transit of pelleted pancreatin in relation to food boluses. 
Methods—Dual isotope scintigraphy combined with breath hydrogen sampling was used to track the concurrent gastric emptying and intestinal transit of 111indium labelled microspheres and a 99mtechnetium labelled tin colloid test meal. Twelve pancreatic insufficient cystic fibrosis patients aged 5 to 38 years performed the study.
RESULTS—50% gastric emp...

  4. Vincristine alters myoelectric activity and transit of the small intestine in rats

    International Nuclear Information System (INIS)

    We investigated the motility of the small intestine in unanesthetized rats receiving vincristine (0.075, 0.50, 0.75 mg/kg i.v.). Motility was determined by two methods: myoelectric activity was monitored with indwelling bipolar electrodes, and intestinal transit was measured by the movement of radiochromium (Na51CrO4). Only the animals injected with the two higher doses had two distinct patterns of altered intestinal myoelectric activity within 2 h of drug administration. The first alteration occurred 44 +/- 6 min after vincristine administration and consisted of a marked increase in action potential activity with disruption of the migrating myoelectric complex. The second alteration consisted of a reappearance of the activity front of the migrating myoelectric complex with a significantly shorter periodicity. A marked reduction in spike activity occurred 3 days after vincristine injection in 3 of 10 animals receiving vincristine. A biphasic response was noted in intestinal transit. Disrupted activity front formation was associated with a significant delay in small bowel transit. In contrast, frequent activity front formation in rats was associated with significantly hastened transit. In summary, vincristine administration induces alterations of myoelectric activity of the small intestine in fasted rats and is associated with changes in intestinal transit

  5. Vincristine alters myoelectric activity and transit of the small intestine in rats

    Energy Technology Data Exchange (ETDEWEB)

    Sninsky, C.A.

    1987-02-01

    We investigated the motility of the small intestine in unanesthetized rats receiving vincristine (0.075, 0.50, 0.75 mg/kg i.v.). Motility was determined by two methods: myoelectric activity was monitored with indwelling bipolar electrodes, and intestinal transit was measured by the movement of radiochromium (Na/sup 51/CrO/sub 4/). Only the animals injected with the two higher doses had two distinct patterns of altered intestinal myoelectric activity within 2 h of drug administration. The first alteration occurred 44 +/- 6 min after vincristine administration and consisted of a marked increase in action potential activity with disruption of the migrating myoelectric complex. The second alteration consisted of a reappearance of the activity front of the migrating myoelectric complex with a significantly shorter periodicity. A marked reduction in spike activity occurred 3 days after vincristine injection in 3 of 10 animals receiving vincristine. A biphasic response was noted in intestinal transit. Disrupted activity front formation was associated with a significant delay in small bowel transit. In contrast, frequent activity front formation in rats was associated with significantly hastened transit. In summary, vincristine administration induces alterations of myoelectric activity of the small intestine in fasted rats and is associated with changes in intestinal transit.

  6. Human milk oligosaccharides (HMOs) and their effects on intestinal microorganisms

    OpenAIRE

    Yue, Ke

    2015-01-01

    Human milk oligosaccharides (HMOs), as the third largest components in human milk, are thought to be important for the development of infants for various reasons. Previous in vitro studies support the idea that HMOs help to build up the human gut microbiota in infants. It has been shown that some of the intestinal microorganisms found in feces of infants grow on single HMOs as sole carbon substrate. However, so far, the growth effect of specific HMO fractions whose pattern is strongly influen...

  7. Intestinal-fatty acid binding protein and lipid transport in human intestinal epithelial cells

    International Nuclear Information System (INIS)

    Intestinal-fatty acid binding protein (I-FABP) is a 14-15 kDa cytoplasmic molecule highly expressed in the enterocyte. Although different functions have been proposed for various FABP family members, the specific function of I-FABP in human intestine remains unclear. Here, we studied the role of I-FABP in molecularly modified normal human intestinal epithelial cells (HIEC-6). cDNA transfection resulted in 90-fold I-FABP overexpression compared to cells treated with empty pQCXIP vector. The high-resolution immunogold technique revealed labeling mainly in the cytosol and confirmed the marked phenotype abundance of I-FABP in cDNA transfected cells. I-FABP overexpression was not associated with alterations in cell proliferation and viability. Studies using these transfected cells cultured with [14C]oleic acid did not reveal higher efficiency in de novo synthesis or secretion of triglycerides, phospholipids, and cholesteryl esters compared to cells treated with empty pQCXIP vector only. Similarly, the incubation with [35S]methionine did not disclose a superiority in the biogenesis of apolipoproteins (apo) A-I, A-IV, B-48, and B-100. Finally, cells transfected with I-FABP did not exhibit an increased production of chylomicrons, VLDL, LDL, and HDL. Our observations establish that I-FABP overexpression in normal HIEC-6 is not related to cell proliferation, lipid esterification, apo synthesis, and lipoprotein assembly, and, therefore, exclude its role in intestinal fat transport

  8. Dendritic cells transmit HIV-1 through human small intestinal mucosa

    Science.gov (United States)

    Shen, Ruizhong; Smythies, Lesley E.; Clements, Ronald H.; Novak, Lea; Smith, Phillip D.

    2010-01-01

    To dissect the early events in the transmission of HIV-1 from mother to child, we investigated whether DCs participate in HIV-1 entry into human small intestinal mucosa. We isolated human MNLs from jejunal lamina propria and identified a subpopulation of CD11c+HLA-DR+ MNLs that expressed DC-SIGN, CD83, CD86, CD206, and CCR7, indicating a DC phenotype. Jejunal DCs also expressed the HIV-1 receptor CD4 and coreceptors CCR5 and CXCR4 and in suspension rapidly took up cell-free HIV-1. HIV-1 inoculated onto the apical surface of explanted jejunum was transported by lamina propria DCs through the mucosa and transmitted in trans to blood and intestinal lymphocytes. These findings indicate that in addition to intestinal epithelial cells, which we showed previously transcytose infectious HIV-1 to indicator cells, intestinal DCs play an important role in transporting HIV-1 through the intestinal mucosa and the subsequent transmission to T cells. PMID:20007245

  9. [Mastocytes in the human intestinal mucosa].

    Science.gov (United States)

    Drumcheva, M; Todorov, D; Sto?nov, S; Nikolov, N; Boneva, M

    1986-01-01

    A method has been for counting the mastocytes on 0.1 mm2 of intestinal mucosa in patients with chronic enterocolitis, gluten enteropathy, ulcerous colitis in a stage of exacerbation and in controls. The comparison of the results obtained in the separate groups of patients reveal an increased number of mastocytes in gluten enteropathy--mean = 21.01 +/- 6 as compared with the chronic enterocolitis, where mean = 9.79 +/- 3.83 (p = 0.002). Higher values of mastocytes in rectal mucosa were observed in the patients with ulcerous mucosa--mean = 15.83 +/- 4.49 as compared with the control subjects with means = 3.67 +/- 0.99 (p = 0.001). those data admit the participation of mastocytes in the morbid process in patients with gluten enteropathy and with ulcerous colitis. PMID:3716371

  10. Exopolysaccharides produced by intestinal Bifidobacterium strains act as fermentable substrates for human intestinal bacteria.

    Science.gov (United States)

    Salazar, Nuria; Gueimonde, Miguel; Hernndez-Barranco, Ana Mara; Ruas-Madiedo, Patricia; de los Reyes-Gaviln, Clara G

    2008-08-01

    Eleven exopolysaccharides (EPS) isolated from different human intestinal Bifidobacterium strains were tested in fecal slurry batch cultures and compared with glucose and the prebiotic inulin for their abilities to act as fermentable substrates for intestinal bacteria. During incubation, the increases in levels of short-chain fatty acids (SCFA) were considerably more pronounced in cultures with EPS, glucose, and inulin than in controls without carbohydrates added, indicating that the substrates assayed were fermented by intestinal bacteria. Shifts in molar proportions of SCFA during incubation with EPS and inulin caused a decrease in the acetic acid-to-propionic acid ratio, a possible indicator of the hypolipidemic effect of prebiotics, with the lowest values for this parameter being obtained for EPS from the species Bifidobacterium longum and from Bifidobacterium pseudocatenulatum strain C52. This behavior was contrary to that found with glucose, a carbohydrate not considered to be a prebiotic and for which a clear increase of this ratio was obtained during incubation. Quantitative real-time PCR showed that EPS exerted a moderate bifidogenic effect, which was comparable to that of inulin for some polymers but which was lower than that found for glucose. PCR-denaturing gradient gel electrophoresis of 16S rRNA gene fragments using universal primers was employed to analyze microbial groups other than bifidobacteria. Changes in banding patterns during incubation with EPS indicated microbial rearrangements of Bacteroides and Escherichia coli relatives. Moreover, the use of EPS from B. pseudocatenulatum in fecal cultures from some individuals accounted for the prevalence of Desulfovibrio and Faecalibacterium prausnitzii, whereas incubation with EPS from B. longum supported populations close to Anaerostipes, Prevotella, and/or Oscillospira. Thus, EPS synthesized by intestinal bifidobacteria could act as fermentable substrates for microorganisms in the human gut environment, modifying interactions among intestinal populations. PMID:18539803

  11. Expression of arylamine N-acetyltransferase in human intestine

    OpenAIRE

    Hickman, D.; Pope, J; Patil, S; Fakis, G; Smelt, V; Stanley, L; Payton, M; Unadkat, J; Sim, E.

    1998-01-01

    BackgroundArylamine N-acetyltransferases in humans (NAT1 and NAT2) catalyse the acetylation of arylamines including food derived heterocyclic arylamine carcinogens. Other substrates include the sulphonamide 5-aminosalicylic acid (5-ASA), which is an NAT1 specific substrate; N-acetylation of 5-ASA is a major route of metabolism. NAT1 and NAT2 are both polymorphic. ?AimsTo investigate NAT expression in apparently healthy human intestines in order to understand the possible r...

  12. Molecular Epidemiology of Human Intestinal Amoebas in Iran

    Directory of Open Access Journals (Sweden)

    M Rezaian

    2012-09-01

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

  13. Lactobacillus paracacei subsp. paracasei F19 : Survival, Ecology and Safety in the Human Intestinal Tract-A Survey of Feeding Studies within the PROBDEMO Project

    OpenAIRE

    Crittenden, R.; Saarela, M.; Mättö, J.; Ouwehand, A. C.; Salminen, S; Pelto, L.; Vaughan, E E; Vos, W.M. de; von Wright, A.; Fondén, R.; Mattila-Sandholm, T.

    2002-01-01

    Lactobacillus paracasei F19 is an emerging probiotic strain that shows considerable promise for use in functional foods for intestinal health. In a multicentre European research project, human feeding trials provided an insight into the ability of this strain to survive gastric transit and transiently colonize the human intestinal tract. Analysis of the faecal microbiota in healthy human volunteers showed that a proportion of the subjects carried a strain indistinguishable from L. paracasei F...

  14. Significance of reductive metabolism in human intestine and quantitative prediction of intestinal first-pass metabolism by cytosolic reductive enzymes.

    Science.gov (United States)

    Nishimuta, Haruka; Nakagawa, Tetsuya; Nomura, Naruaki; Yabuki, Masashi

    2013-05-01

    The number of new drug candidates that are cleared via non-cytochrome P450 (P450) enzymes has increased. However, unlike oxidation by P450, the roles of reductive enzymes are less understood. The metabolism in intestine is especially not well known. The purposes of this study were to investigate the significance of reductive metabolism in human intestine, and to establish a quantitative prediction method of intestinal first-pass metabolism by cytosolic reductive enzymes, using haloperidol, mebendazole, and ziprasidone. First, we estimated the metabolic activities for these compounds in intestine and liver using subcellular fractions. Metabolic activities were detected in human intestinal cytosol (HIC) for all three compounds, and the intrinsic clearance values were higher than those in human liver cytosol for haloperidol and mebendazole. These metabolic activities in HIC were NADPH- and/or NADH-dependent. Furthermore, the metabolic activities for all three compounds in HIC were largely inhibited by menadione, which has been used as a carbonyl reductase (CBR)-selective chemical inhibitor. Therefore, considering subcellular location, cofactor requirement, and chemical inhibition, these compounds might be metabolized by CBRs in human intestine. Subsequently, we tried to quantitatively predict intestinal availability (F(g)) for these compounds using human intestinal S9 (HIS9). Our prediction model using apparent permeability of parallel artificial membrane permeability assay and metabolic activities in HIS9 could predict F(g) in humans for the three compounds well. In conclusion, CBRs might have higher metabolic activities in human intestine than in human liver. Furthermore, our prediction method of human F(g) using HIS9 is applicable to substrates of cytosolic reductive enzymes. PMID:23444387

  15. 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: 8.057, year: 2013

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

    OpenAIRE

    Schantz, Markus; Erk, Thomas; Richling, Elke

    2010-01-01

    Abstract Numerous studies have shown that green tea polyphenols can be degraded in the colon, and there is abundant knowledge about the metabolites of these substances that appear in urine and plasma after green tea ingestion. However, there is very little information on the extent and nature of intestinal degradation of green tea catechins in humans. Therefore, the aim of this study presented here was to examine in detail the microbial metabolism and chemical stability of these po...

  17. Diet and the development of the human intestinal microbiome

    OpenAIRE

    Voreades, Noah; Kozil, Anne; Weir, Tiffany L.

    2014-01-01

    The important role of the gut microbiome in maintaining human health has necessitated a better understanding of the temporal dynamics of intestinal microbial communities as well as the host and environmental factors driving these dynamics. Genetics, mode of birth, infant feeding patterns, antibiotic usage, sanitary living conditions and long term dietary habits contribute to shaping the composition of the gut microbiome. This review focuses primarily on diet, as it is one of the most pivotal ...

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

    OpenAIRE

    Rajilic-Stojanovic, M.; Heilig, G. H. J.; TIMS S.; Zoetendal, E. G.; De Vos, 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 microbiota composition of five unrelated and healthy subjects was analysed using a comprehensive and highly reproducible phylogenetic microarray, the HITChip. The results show that the use of antibiotics...

  19. Clinical features of human intestinal capillariasis in Taiwan

    OpenAIRE

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

    2004-01-01

    Human intestinal capillariasis is a rare parasitosis that was first recognized in the Philippines in the 1960 s. Parasitosis is a life threatening disease and has been reported from Thailand, Japan, South of Taiwan (Kaoh-Siung), Korea, Iran, Egypt, Italy and Spain. Its clinical symptoms are characterized by chronic diarrhea, abdominal pain, borborygmus, marked weight loss, protein and electrolyte loss and cachexia. Capillariasis may be fatal if early treatment is not given. We reported 14 cas...

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

    OpenAIRE

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

    2001-01-01

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

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

    OpenAIRE

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

    2011-01-01

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

  2. An iterative workflow for mining the human intestinal metaproteome

    OpenAIRE

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

    2011-01-01

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

  3. Gastric emptying and small intestinal transit in the piebald mouse model for Hirschsprung's disease

    International Nuclear Information System (INIS)

    Gastric emptying and small intestinal transit were investigated in the piebald mouse model for Hirschsprung's disease. These mice exhibited aganglionosis of the terminal segment of the large intestine. This condition was accompanied by fecal stasis and megacolon. Gastric emptying of saline or milk meals was slower in the mice with aganglionic or induced megacolon than in the normal mice, but the rate of emptying was faster than after administration of morphine (10 mg/kg). In the small intestine, the distribution of the radiolabeled marker and the advancing edge of the marker profile were abnormal in the mice with megacolon. There were small differences between the megacolonic and normal mice in the distance traversed by the advancing edge of the intraluminal profile of the marker. These results are evidence for disturbances of gastric and small intestinal motor function that occur in mice secondary to development of megacolon

  4. Radionuclide esophageal and intestinal transit scintigraphy in patients undergoing radiation therapy

    International Nuclear Information System (INIS)

    Radiation esophagitis and enteritis are common and significant side effects of radiation therapy. Non-invasive assessment of functional and/or anatomic changes responsible for the symptoms produced by radiation esophagitis and enteritis has been unsatisfactory. This paper demonstrates the value of radionuclide esophageal and intestinal transit scintigraphy in patients undergoing mediastinal or abdominal radiation. (author)

  5. Dendritic cells transmit HIV-1 through human small intestinal mucosa

    OpenAIRE

    Shen, Ruizhong; Smythies, Lesley E.; Clements, Ronald H.; Novak, Lea; Smith, Phillip D.

    2009-01-01

    To dissect the early events in the transmission of HIV-1 from mother to child, we investigated whether DCs participate in HIV-1 entry into human small intestinal mucosa. We isolated human MNLs from jejunal lamina propria and identified a subpopulation of CD11c+HLA-DR+ MNLs that expressed DC-SIGN, CD83, CD86, CD206, and CCR7, indicating a DC phenotype. Jejunal DCs also expressed the HIV-1 receptor CD4 and coreceptors CCR5 and CXCR4 and in suspension rapidly took up cell-free HIV-1. HIV-1 inocu...

  6. Rates of intestinal absorption of molybdenum in humans

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-06-15

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

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

    Science.gov (United States)

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

    2015-05-01

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

  8. An iterative workflow for mining the human intestinal metaproteome

    Directory of Open Access Journals (Sweden)

    Beauvallet Christian

    2011-01-01

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

  9. Survivability of Kudoa septempunctata in human intestinal conditions.

    Science.gov (United States)

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

    2016-06-01

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

  10. Evaluation of a magnetic method for the measurement of small intestinal transit time.

    Science.gov (United States)

    Benmair, Y; Fischel, B; Frei, E H; Gilat, T

    1977-11-01

    A new method for the measurement of small intestinal transit time is described. An externally applied magnetic transducer senses the presence of an ingested ferromagnetic material--50 gm. of magnesium ferrite dispersed in a test meal--upon its arrival at the cecal area. The mouth-to-cecum transit time is thus determined. The method is noninvasive and is not associated with any radiation. The method was compared to the commonly used x-ray method and good correlation was found in 24 of 28 studies. The mean transit time in a group of 20 normal subjects was 157.5 +/- 63.9 min. PMID:607797

  11. 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.

  12. Vasoactive intestinal peptide signaling axis in human leukemia

    Directory of Open Access Journals (Sweden)

    Glenn Paul Dorsam

    2011-01-01

    Full Text Available The vasoactive intestinal peptide (VIP signaling axis constitutes a master communication coordinator between cells of the nervous and immune systems. To date, VIP and its two main receptors expressed in T lymphocytes, vasoactive intestinal peptide receptor (VPAC1 and VPAC2, mediate critical cellular functions regulating adaptive immunity, including arresting CD4 T cells in G1 of the cell cycle, protection from apoptosis and a potent chemotactic recruiter of T cells to the mucosa associated lymphoid compartment of the gastrointestinal tissues. Since the discovery of VIP in 1970, followed by the cloning of VPAC1 and VPAC2 in the early 1990s, this signaling axis has been associated with common human cancers, including leukemia. This review highlights the present day knowledge of the VIP ligand and its receptor expression profile in T cell leukemia and cell lines. Also, there will be a discussion describing how the anti-leukemic DNA binding transcription factor, Ikaros, regulates VIP receptor expression in primary human CD4 T lymphocytes and T cell lymphoblastic cell lines (e.g. Hut-78. Lastly, future goals will be mentioned that are expected to uncover the role of how the VIP signaling axis contributes to human leukemogenesis, and to establish whether the VIP receptor signature expressed by leukemic blasts can provide therapeutic and/or diagnostic information.

  13. Intestinal permeability and orocaecal transit time in elderly patients with Parkinson's disease.

    OpenAIRE

    Davies, K. N.; King, D; Billington, D.; Barrett, J. A.

    1996-01-01

    The aetiology of weight loss in patients with Parkinson's disease is likely to be multifactorial. We studied 15 patients with Parkinson's disease and 15 age- and sex-matched controls and looked for evidence of malabsorption due to small bowel bacterial overgrowth or alteration of intestinal permeability. There was a marked increase in orocaecal transit time in the patients with Parkinson's disease, although lactulose hydrogen breath testing did not show evidence of small bowel bacterial conta...

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

    Science.gov (United States)

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

    2014-11-01

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

  15. Nonsteroidal antiinflammatory drug-induced intestinal inflammation in humans

    Energy Technology Data Exchange (ETDEWEB)

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

    1987-09-01

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

  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 transmission and pathogenesis is clarified. Probably, bacterial microflora can implement the protective role as well as be abettor of virus. However, an understanding of interaction between microbiota and virus during viral disease may initiate the introduction of new antiviral strategies. Further research is needed to determining the features of relationship between viruses and bacteria in the development of infectious process, and analyze whether the viral and bacterial agents form a symbiotic relationship in human body. This review focuses on precisely these issues.

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

    OpenAIRE

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

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Rivera-Cruz Angélica

    2011-10-01

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

  19. Functional Metagenomic Investigations of the Human Intestinal Microbiota

    DEFF Research Database (Denmark)

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

    2011-01-01

    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...

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

    Science.gov (United States)

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

    2010-07-01

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

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

    Science.gov (United States)

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

    2015-06-01

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

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

    International Nuclear Information System (INIS)

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

  3. Metabolism of green tea catechins by the human small intestine.

    Science.gov (United States)

    Schantz, Markus; Erk, Thomas; Richling, Elke

    2010-10-01

    Numerous studies have shown that green tea polyphenols can be degraded in the colon, and there is abundant knowledge about the metabolites of these substances that appear in urine and plasma after green tea ingestion. However, there is very little information on the extent and nature of intestinal degradation of green tea catechins in humans. Therefore, the aim of this study was to examine in detail the microbial metabolism and chemical stability of these polyphenols in the small intestine using a well-established ex vivo model. For this purpose, fresh ileostomy fluids from two probands were incubated for 24 h under anaerobic conditions with (+)-catechin (C), (-)-epicatechin (EC), (-)-epicatechin 3-O-gallate (ECG), (-)-epigallocatechin (EGC), (-)-epigallocatchin 3-O-gallate (EGCG) and gallic acid (GA). After lyophilisation and extraction, metabolites were separated, identified and quantified by high performance liquid chromatography-photodiode array detection (HPLC-DAD) and HPLC-ESI-tandem mass spectrometry. Two metabolites of EC and C (3', 4', 5'-trihydroxyphenyl-γ-valerolactone and 3', 4'-dihydroxyphenyl-γ-valerolactone) were identified. In addition, 3', 4', 5'-trihydroxyphenyl-γ-valerolactone was detected as a metabolite of EGC, and (after 24-h incubation) pyrogallol as a degradation product of GA. Cleavage of the GA esters of EGCG and ECG was also observed, with variations dependent on the sources (probands) of the ileal fluids, which differed substantially microbiotically. The results provide new information about the degradation of green tea catechins in the gastrointestinal tract, notably that microbiota-dependent liberation of GA esters may occur before these compounds reach the colon. PMID:20931601

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

    Directory of Open Access Journals (Sweden)

    Glen S Patten

    2011-02-01

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

  5. Zingerone regulates intestinal transit, attenuates behavioral and oxidative perturbations in irritable bowel disorder in rats.

    Science.gov (United States)

    Banji, David; Banji, Otilia J F; Pavani, Bandlapalli; Kranthi Kumar, Ch; Annamalai, A R

    2014-03-15

    Stress can lead to the manifestation of functional gastrointestinal disorders, the most prominent being irritable bowel disorder. The present study investigated the impact zingerone in ameliorating chronic water stress induced irritable bowel disorder, brain gut axis dysfunction and dysregulation of the intestinal barrier due to oxidative stress. Rats were randomly allocated to groups and subjected to chronic water stress for a period of 21 days for 1h and the fecal pellet output was measured. At the end of chronic stress, behavioral assessment for anxiety like behavior was recorded and plasma corticosterone levels were measured 60min after water stress. The colonic transit was determined, levels of oxidative and antioxidant biomarkers were measured in the colon homogenate. Myeloperoxidase activity was determined as an indirect index of neutrophil infiltration. Chronic water stress increased the rate of colonic transit, fecal output, induced behavioral changes, and decreased antioxidant levels. An increase in lipid peroxide levels, catalase and corticosterone was observed. Mast cell infiltration was evident in the stressed group. Zingerone significantly reduced colonic transit, fecal output, neutrophil infiltration, and lipid peroxide formation. The levels of catalase were not altered; however, a marginal increase in the levels of glutathione peroxidase was observed. Zingerone significantly enhanced the levels of superoxide dismutase, glutathione and decreased the levels of corticosterone. Zingerone produced marked improvement in stress induced irritable bowel disorder which could be attributed to the powerful antioxidant nature, direct effect on the intestinal smooth muscle and adaptogenic nature. PMID:24262066

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

    DEFF Research Database (Denmark)

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

    2006-01-01

    Although malabsorption of small amounts of fructose-sorbitol mixtures occurs frequently in healthy humans, insights into their effects on gastrointestinal motility are poor. The present study addresses the hypothesis that malabsorption of a fructose-sorbitol challenge changes the small intestinal...... transit rate. Eleven healthy volunteers participated in a double-blind crossover investigation. In random order, the subjects ingested 30 g glucose or a mixture of 25 g fructose and 5 g sorbitol as 10% solutions. As a radiolabeled marker, (99m)Tc-diethylenetriaminepentaacetic acid was added to each test...... solution. Breath hydrogen and methane concentrations and gastrointestinal progress of the radiolabeled marker were followed for the next 6-hr period. Malabsorption of small amounts of the fructose-sorbitol mixture was evident in all subjects. The area under the gastric radioactivity-time curve after...

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

    International Nuclear Information System (INIS)

    There are two forms of pteroylpolyglutamate hydrolase (PPH) in the human intestinal mucosa, one in the brush border membrane and the other intracellular; brush border PPH is an exopeptidase with optimal activity at pH 6.5 and a requirement for zinc. The presence study characterized human intracellular PPH and compared its properties to those of brush border PPH. Intracellular PPH was purified 30-fold. The enzyme had a MW of 75,000 by gel filtration, was optimally active at pH 4.5, and had an isoelectric point at pH 8.0. In contrast to brush border PPH, intracellular PPH was unstable at increasing temperatures, was unaffected by dialysis against chelating agents and showed no requirement for Zn2+. Using PteGlu2[14C]Glu as substrate, they demonstrated a K/sub m/ of 1.2 μM and increasing affinity for folates with longer glutamate chains. Intracellular PPH required the complete folic acid (PteGlu) moiety and a γ-glutamyl linkage for activity. Using ion exchange chromatography and an HPLC method to determine the hydrolytic products of the reaction, they found intracellular PPH could cleave both internal and terminal γ-glutamyl linkages, with PteGlu as an end product. After subcellular fractionation of the mucosa, PPH was found in the lysosomes. In summary, the distinct characteristics of brush border and intracellular PPH suggest that the two hydrolases serve different roles in folate metabolism

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

    Directory of Open Access Journals (Sweden)

    Mie Dilling Kjaer

    2015-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Haina N.I.

    2008-01-01

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

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

    OpenAIRE

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

    2000-01-01

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

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1984-01-01

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

  13. Adequacy of the Human Faecal Microbiota Associated Mouse as a Model for Studying the Ecology of the Human Intestinal Tract

    OpenAIRE

    Wong, W. C.; Hentges, D. J.; Dougherty, S H

    2011-01-01

    The adequacy of a human faecal microbiota associated mouse as a model for studying the activities of human intestinal microorganisms was examined. During a 6 month period, several predominant aerobic and anaerobic components of the human faecal bacteria persisted at stable numbers in the intestinal tracts of the mice. However, Bacillus species and both aerobic and anaerobic Lactobacillus species disappeared within 7 d after association. An inverse relationship existed between the presence of ...

  14. Clinical features of human intestinal capillariasis in Taiwan.

    Science.gov (United States)

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

    2004-08-15

    Human intestinal capillariasis is a rare parasitosis that was first recognized in the Philippines in the 1960 s. Parasitosis is a life threatening disease and has been reported from Thailand, Japan, South of Taiwan (Kaoh-Siung), Korea, Iran, Egypt, Italy and Spain. Its clinical symptoms are characterized by chronic diarrhea, abdominal pain, borborygmus, marked weight loss, protein and electrolyte loss and cachexia. Capillariasis may be fatal if early treatment is not given. We reported 14 cases living in rural areas of Taiwan. Three cases had histories of travelling to Thailand. They might have been infected in Thailand while stayed there. Two cases had the diet of raw freshwater fish before. Three cases received emergency laparotomy due to peritonitis and two cases were found of enteritis cystica profunda. According to the route of transmission, freshwater and brackish-water fish may act as the intermediate host of the parasite. The most simple and convenient method of diagnosing capillariasis is stool examination. Two cases were diagnosed by histology. Mebendazole or albendezole 200 mg orally twice a day for 20-30 d is the treatment of choice. All the patients were cured, and relapses were not observed within 12 mo. PMID:15285025

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1986-03-01

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

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

    DEFF Research Database (Denmark)

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

    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...

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

    OpenAIRE

    Mabbott, Neil A.

    2015-01-01

    A new study by Man and colleagues provides further insight into the effects of aging on small intestinal barrier function in humans. Here, their findings are briefly summarised and the wider implications discussed.

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

    Science.gov (United States)

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

    2016-03-01

    Acteoside, the main and representative phenylethanoid glycosides of Herba Cistanches, possesses wide bioactivities but low oral bioavailability. It may serve as the prodrug and be converted into the active forms in gastrointestinal tract, which mainly occurred in intestinal tract composed of intestinal bacteria and intestinal enzyme. Intestinal bacteria, a new drug target, take a significant role on exerting pharmacological effects of drugs by oral administration. In this paper, acteoside was incubated with human or rat intestinal bacteria or rat intestinal enzyme for 36h to seek metabolites responsible for pharmacodynamics. The samples were analyzed by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Besides the parent compound, 14 metabolites were detected and identified based on their retention times and fragmentation patterns in their MS spectra including 8 degradation metabolites, 2 isomers in intestinal bacteria and intestinal enzyme samples and 4 parent metabolites only found in intestinal enzymes. The metabolic pathway of acteoside was thus proposed. Identification of these metabolites of acteoside by the intestinal bacteria or intestinal enzyme gave an insight to clarify pharmacological mechanism of traditional Chinese medicines and identify the real active molecules. PMID:26705842

  19. Human Rights and Transitional Societies: Contemporary Challenges

    DEFF Research Database (Denmark)

    Hansen, Thomas Obel

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

  20. The Mucin degrader Akkermansia muciniphila is an abundant resident of the human intestinal tract.

    Science.gov (United States)

    Derrien, Muriel; Collado, M Carmen; Ben-Amor, Kaouther; Salminen, Seppo; de Vos, Willem M

    2008-03-01

    A 16S rRNA-targeted probe, MUC-1437, was designed and validated in order to determine the presence and numbers of cells of Akkermansia muciniphila, a mucin degrader, in the human intestinal tract. As determined by fluorescent in situ hybridization, A. muciniphila accounted more than 1% of the total fecal cells and was shown to be a common bacterial component of the human intestinal tract. PMID:18083887

  1. Kinematics of transition during human accelerated sprinting

    OpenAIRE

    Nagahara, Ryu; Matsubayashi, Takeo; Matsuo, Akifumi; Zushi, Koji

    2014-01-01

    This study investigated kinematics of human accelerated sprinting through 50?m and examined whether there is transition and changes in acceleration strategies during the entire acceleration phase. Twelve male sprinters performed a 60-m sprint, during which step-to-step kinematics were captured using 60 infrared cameras. To detect the transition during the acceleration phase, the mean height of the whole-body centre of gravity (CG) during the support phase was adopted as a measure. Detection m...

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

    Science.gov (United States)

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

    2009-07-15

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

  3. Espiroquetosis intestinal humana: serie clnica y revisin de la literatura Human intestinal spirochetosis: clinical series and literature review

    Directory of Open Access Journals (Sweden)

    Carlo Lozano

    2012-08-01

    Full Text Available Introduccin: La espiroquetosis intestinal humana (EIH se define como la colonizacin del intestino grueso por espiroquetas. Se asocia a diarrea crnica. Su incidencia y prevalencia van desde 0,4 a 12% Objetivo: Determinar la prevalencia de EIH en el Hospital Del Salvador, de Santiago, Chile, entre los aos 2003 y 2008, en pacientes con antecedentes clnicos de diarrea crnica y colonoscopia sin hallazgos patolgicos, separados en dos grupos: pacientes con y sin antecedentes de infeccin por VIH. Material y Mtodo: Evaluacin morfolgica retrospectiva de las biopsias endoscpicas de intestino grueso de los grupos seleccionados. Resultados: Se revisaron 115 biopsias, 98 correspondieron a pacientes sin infeccin por VIH y 17 a pacientes seropositivos para VIH. Se detectaron dos casos de espiroquetosis intestinal, ambos en pacientes sin infeccin por VIH, con una prevalencia de 1,7 %. Comentario: La prevalencia de EIH es similar a la publicada en pases occidentales. Se requieren estudios poblacionales para determinar el real impacto epidemiolgico en nuestro medio.Introduction: Human intestinal spirochetosis (HIE is defined as colonization by spirochetes of the large intestine. Is associated with chronic diarrhea. The incidence and prevalence ranges from 0.4% to 12%. Objective: To determine the prevalence of HIE in the Salvador's Hospital, between 2003 and 2008 in patients with a history of chronic diarrhea and without abnormalities in colonoscopy, in 2 separate groups: patients with and without a history of HIV infection. Material and Methods: Retrospective morphology evaluation of the large bowel endoscopic biopsies to the selected groups. Results: We reviewed 115 biopsies, 98 were from HIV-negative and 17 HIV from positive patients. Two cases of intestinal spirochetosis were detected, both HIV negative, with a prevalence of 1.7%. Comment: The prevalence of HIE is similar to that reported in Western countries. Population studies are needed to determine the real epidemiological impact in our environment.

  4. 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. PMID:27025369

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

    Directory of Open Access Journals (Sweden)

    Gondim F. de-A.A.

    1998-01-01

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

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

    Science.gov (United States)

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

    2016-06-01

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

  7. Gastric emptying and small intestinal transit in the piebald mouse model for Hirschsprung's disease

    Energy Technology Data Exchange (ETDEWEB)

    Cooke, H.J.; Pitman, K.; Starr, G.; Wood, J.D.

    1984-08-01

    Gastric emptying and small intestinal transit were investigated in the piebald mouse model for Hirschsprung's disease. These mice exhibited aganglionosis of the terminal segment of the large intestine. This condition was accompanied by fecal stasis and megacolon. Gastric emptying of saline or milk meals was slower in the mice with aganglionic or induced megacolon than in the normal mice, but the rate of emptying was faster than after administration of morphine (10 mg/kg). In the small intestine, the distribution of the radiolabeled marker and the advancing edge of the marker profile were abnormal in the mice with megacolon. There were small differences between the megacolonic and normal mice in the distance traversed by the advancing edge of the intraluminal profile of the marker. These results are evidence for disturbances of gastric and small intestinal motor function that occur in mice secondary to development of megacolon.

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

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Renes Johan

    2007-04-01

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

  10. Electromechanical activity of the equine small intestine and its correlation with transit of fluid through Thiry-Vella loops.

    Science.gov (United States)

    Davies, J V; Gerring, E L

    1983-05-01

    Motility patterns in the equine small intestine were investigated in eight ponies. Muscular activity was assessed by means of extramural strain gauge transducers, bi-polar electrodes and in three of the animals, fitted with Thiry-Vella loops, the transit of fluid. Circular muscle contractions were preceded by spiking superimposed on the slow wave and fluid transit in the loops correlated with both these events. PMID:6878885

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

    International Nuclear Information System (INIS)

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

  12. Isolation and identification of intestinal CYP3A inhibitors from cranberry (Vaccinium macrocarpon) using human intestinal microsomes.

    Science.gov (United States)

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

    2011-02-01

    Cranberry juice is used routinely, especially among women and the elderly, to prevent and treat urinary tract infections. These individuals are likely to be taking medications concomitantly with cranberry juice, leading to concern about potential drug-dietary substance interactions, particularly in the intestine, which, along with the liver, is rich in expression of the prominent drug metabolizing enzyme, cytochrome P450 3A (CYP3A). Using a systematic in vitro-in vivo approach, a cranberry juice product was identified recently that elicited a pharmacokinetic interaction with the CYP3A probe substrate midazolam in 16 healthy volunteers. Relative to water, cranberry juice inhibited intestinal first-pass midazolam metabolism. In vitro studies were initiated to identify potential enteric CYP3A inhibitors from cranberry via a bioactivity-directed fractionation approach involving dried whole cranberry [Vaccinium macrocarpon Ait. (Ericaceae)], midazolam, and human intestinal microsomes (HIM). Three triterpenes (maslinic acid, corosolic acid, and ursolic acid) were isolated. The inhibitory potency (IC(50)) of maslinic acid, corosolic acid, and ursolic acid was 7.4, 8.8, and cranberry juice interaction observed in the clinical study. PMID:20717876

  13. Environmental factors and their impact on the intestinal microbiota: a role for human disease?

    OpenAIRE

    Biedermann, Luc; Rogler, Gerhard

    2012-01-01

    The intestinal microbiota and its potential role in human health and disease have come into the focus of interest in recent years. An important prerequisite for the achieved advances with regard to a better characterization of its complex composition and influencing factors is the increasing availability and affordability of culture-independent methods, such as high-throughput sequencing technologies. We discuss some general aspects of the intestinal microbiota. Recent insights into its poten...

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

    OpenAIRE

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

    1985-01-01

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

  15. Intestinal Bacterial Communities That Produce Active Estrogen-Like Compounds Enterodiol and Enterolactone in Humans

    OpenAIRE

    Clavel, Thomas; Henderson, Gemma; Alpert, Carl-Alfred; Philippe, Catherine; Rigottier-Gois, Lionel; Doré, Joël; Blaut, Michael

    2005-01-01

    Lignans are dietary diphenolic compounds which require activation by intestinal bacteria to exert possible beneficial health effects. The intestinal ecosystem plays a crucial role in lignan metabolism, but the organisms involved are poorly described. To characterize the bacterial communities responsible for secoisolariciresinol (SECO) activation, i.e., the communities that produce the enterolignans enterodiol (ED) and enterolactone (EL), a study with 24 human subjects was undertaken. SECO act...

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

    OpenAIRE

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

    1985-01-01

    Benzidine-based azo dyes are proven mutagens and have been linked to bladder cancer. Previous studies have indicated that their initial reduction is the result of the azo reductase activity of the intestinal microbiota. Metabolism of the benzidine-based dye Direct Black 38 was examined by using a semicontinuous culture system that simulates the lumen of the human large intestine. The system was inoculated with freshly voided feces, and an active flora was maintained as evidenced by volatile f...

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

    OpenAIRE

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

    1994-01-01

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

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

    OpenAIRE

    Nord, C E; Edlund, C

    2011-01-01

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

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

    Science.gov (United States)

    Rouch, Joshua D.; Scott, Andrew; Lei, Nan Ye; Solorzano-Vargas, R. Sergio; Wang, Jiafang; Hanson, Elaine M.; Kobayashi, Masae; Lewis, Michael; Stelzner, Matthias G.; Dunn, James C. Y.; Eckmann, Lars; Martn, Martn G.

    2016-01-01

    Background & Aims 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 Peyers 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. Methods 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. Results 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. Conclusions 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 in vitro setting. We anticipate that this model can be used to generate large numbers of M cells for further functional studies of these key cells of intestinal immune induction and their impact on controlling enteric pathogens and the intestinal microbiome. PMID:26820624

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

    Science.gov (United States)

    Duve, L R; Steenfeldt, S; Thodberg, K; Nielsen, B L

    2011-02-01

    1. The aim of this study was to evaluate how splitting the dark period (scotoperiod) affects feeding behaviour and associated intestinal measures in broilers. 2. Ross 308 broilers were reared to 37 d in groups given either a daily 8-h continuous scotoperiod (DARK 8) or an intermittent light schedule with two equally spaced 4-h scotoperiods (DARK 4 + 4), which yielded the same total duration of darkness per 24 h. 3. Feeding behaviour was recorded weekly from 24-h video recordings of 24 groups each of 64 birds. Empty intestinal weights as well as their contents were measured weekly at 4 time points (n = 192). Digestive transit time was estimated on d 29 using a chromic oxide marker; production variables and the extent of foot pad dermatitis were also recorded. 4. In the 3 h prior to a scotoperiod, feeding activity increased in chickens from DARK 8 but not DARK 4 + 4. This increase was reflected in a higher relative content of the crop in DARK 8 at this time. 5. Immediately following the scotoperiod, feeding activity peaked and, although the chickens in DARK 4 + 4 expressed more feeding behaviour in the first 20 min after the scotoperiod, the chickens in DARK 8 had overall higher feeding activity across the day. However, DARK 4 + 4 had a higher feed intake and weight gain. The occurrence and severity of foot pad dermatitis was similar between treatments. 6. In conclusion, broilers modify their feeding behaviour according to the prevailing light schedule. Eight consecutive hours of darkness reduced growth, but did not affect overall feed conversion efficiency, and did not appear to exacerbate hunger or foot pad dermatitis to any great extent. PMID:21337192

  1. Molecular mechanism of silver nanoparticles in human intestinal cells.

    Science.gov (United States)

    Bhmert, Linda; Niemann, Birgit; Lichtenstein, Dajana; Juling, Sabine; Lampen, Alfonso

    2015-01-01

    Silver nanoparticles are used in consumer products like food contact materials, drinking water technologies and supplements, due to their antimicrobial properties. This leads to an oral uptake and exposure of intestinal cells. In contrast to other studies we found no apoptosis induction by surfactant-coated silver nanoparticles in the intestinal cell model Caco-2 in a previous study, although the particles induced oxidative stress, morphological changes and cell death. Therefore, this study aimed to analyze the molecular mechanism of silver nanoparticles in Caco-2 cells. We used global gene expression profiling in differentiated Caco-2 cells, supported by verification of the microarray data by quantitative real-time RT-PCR and microscopic analysis, impedance measurements and assays for apoptosis and oxidative stress. Our results revealed that surfactant-coated silver nanoparticles probably affect the cells by outside-in signaling. They induce oxidative stress and have an influence on canonical pathways related to FAK, ILK, ERK, MAPK, integrins and adherence and tight junctions, thereby inducing transcription factors like AP1, NFkB and NRF2, which mediate cellular reactions in response to oxidative stress and metal ions and induce changes in the cytoskeleton and cell-cell and cell-matrix contacts. The present data confirm the absence of apoptotic cell death. Non-apoptotic, necrotic cell death, especially in the intestine, can cause inflammation and influence the mucosal immune response. PMID:25997095

  2. Characterization of monocarboxylate transporter 6: expression in human intestine and transport of the antidiabetic drug nateglinide.

    Science.gov (United States)

    Kohyama, Noriko; Shiokawa, Hisae; Ohbayashi, Masayuki; Kobayashi, Yasuna; Yamamoto, Toshinori

    2013-11-01

    Monocarboxylate transporter (MCT) 6, encoded by SLC16A5, is a member of the monocarboxylate transporter family. Nateglinide, an oral hypoglycemic agent, quickly reaches the maximal serum concentration after its premeal administration. Although the functional existence of uptake systems for nateglinide in the intestine has been demonstrated, these transport systems have not yet been identified at the molecular level. The aim of this study was to demonstrate the localization of MCT6 in the human small intestine and characterize the transport properties of nateglinide via MCT6. Immunohistochemical analysis of the human small intestine revealed that anti-MCT6 antiserum stained the luminal side of the epithelial cells. When expressed in Xenopus laevis oocytes, MCT6-mediated uptake of [(14)C]nateglinide was sensitive to extracellular pH and membrane potential. Furthermore, the K(t) value of nateglinide (45.9 μM) for MCT6 was lower than those previously reported in Caco-2 cells and rat intestinal brush-border membrane vesicles. In addition, probenecid, fluorescein, valproic acid, and salicylic acid, which are inhibitors of nateglinide uptake in Caco-2 cells and rat intestine, did not inhibit the uptake of nateglinide via MCT6. These results suggest that MCT6 may play a role in the intestinal absorption of nateglinide, although other transporters are also likely involved. PMID:23935065

  3. Climate change, human health, and epidemiological transition

    OpenAIRE

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

    2014-01-01

    The health of populations depends on the availability of clean air, water, food, and sanitation, exposure to pathogens, toxins and environmental hazards, and numerous genetic, behavioral and social factors. For many thousands of years, human life expectancy was low, and population growth was slow. The development of technology-based civilizations facilitated what Abdel Omran called “epidemiological transition,” with increasing life expectancy and rapid population growth. To a large extent, th...

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

    Directory of Open Access Journals (Sweden)

    Ryan Forster

    2014-06-01

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

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

    OpenAIRE

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

    2015-01-01

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

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

    OpenAIRE

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

    1988-01-01

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

  7. Ability of enteroaggregative Escherichia coli strains to adhere in vitro to human intestinal mucosa.

    OpenAIRE

    Knutton, S; Shaw, R K; Bhan, M. K.; Smith, H.R.; McConnell, M. M.; Cheasty, T; Williams, P. H.; Baldwin, T.J.

    1992-01-01

    A collection of 44 enteroaggregative Escherichia coli (EAggEC) strains isolated from infants with diarrhea in India and the United Kingdom were examined for their ability to adhere in vitro to human intestinal mucosa and by electron microscopy for production of putative adherence factors. None of the strains adhered to human duodenal mucosa, and six strains tested did not adhere to ileal mucosa; all 44 strains, however, adhered to human colonic mucosa in localized aggregates. Electron microsc...

  8. 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; Olsen, Jørgen

    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...

  9. 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

  10. 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

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

    DEFF Research Database (Denmark)

    Buhl, T; Thim, L; Kofod, Hans; Orskov, C; Harling, H; Holst, J J

    1988-01-01

    Recent studies have revealed that the glucagon gene is expressed in the mammalian intestine. Here it codes for "glicentin" (proglucagon 1-69) and a glucagon-like peptide, proglucagon 78-107, recently isolated from porcine intestine. We studied the fate of the remaining COOH-terminal part of...... proglucagon (proglucagon 111-160) using radioimmunoassays against proglucagon 111-123 and 126-160. Two peptides were isolated from acid ethanol extracts of porcine ileal mucosa and sequenced: one corresponding to proglucagon 126-158 and one probably corresponding to proglucagon 111-158. By comparing human and...... porcine proglucagon sequences, Ala117 is replaced by Thr, and Ile138, Ala144, Ile152 and Gln153 are replaced by Val, Thr, Leu, and His. By gel filtration and radioimmunoassay of intestinal extracts it was established that a large part of porcine and virtually all of human proglucagon are processed to...

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

    Science.gov (United States)

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

  13. Identification of the transcriptional response of human intestinal mucosa to Lactobacillus plantarum WCFS1 in vivo

    Directory of Open Access Journals (Sweden)

    Kodde Andrea

    2008-08-01

    Full Text Available Abstract Background There is limited knowledge on the extent and dynamics of the mucosal response to commensal and probiotic species in the human intestinal lumen. This study aimed to identify the acute, time-dependent responses of intestinal mucosa to commensal Lactobacillus plantarum WCFS1 in vivo in two placebo-controlled human intervention studies in healthy volunteers. Transcriptional changes in duodenal mucosa upon continuous intraduodenal infusion of L. plantarum WCFS1 for one- and six h, respectively, were studied using oro- and nasogastric intubations with dedicated orogastric catheters and tissue sampling by standard flexible gastroduodenoscopy. Results One- and six-h exposure of small intestinal mucosa to L. plantarum WCFS1 induced differential expression of 669 and 424 gene reporters, respectively. While short-term exposure to L. plantarum WCFS1 inhibited fatty acid metabolism and cell cycle progression, cells switched to a more proliferative phase after prolonged exposure with an overall expression profile characterized by upregulation of genes involved in lipid metabolism, cellular growth and development. Cell death and immune responses were triggered, but cell death-executing genes or inflammatory signals were not expressed. Proteome analysis showed differential expression of several proteins. Only the microsomal protein 'microsomal triglyceride transfer protein' was regulated on both the transcriptional and the protein level in all subjects. Conclusion Overall, this study showed that intestinal exposure to L. plantarum WCFS1 induced consistent, time-dependent transcriptional responses in healthy intestinal mucosa. This extensive exploration of the human response to L. plantarum WCFS1 could eventually provide molecular support for specific or probiotic activity of this strain or species, and exemplifies the strength of the applied technology to identify the potential bio-activity of microbes in the human intestine.

  14. Effectiveness of dried Carica papaya seeds against human intestinal parasitosis: a pilot study.

    Science.gov (United States)

    Okeniyi, John A O; Ogunlesi, Tinuade A; Oyelami, Oyeku A; Adeyemi, Lateef A

    2007-03-01

    The tropical fruit Carica papaya and its seeds have proven antihelminthic and anti-amoebic activities. To determine the effectiveness of air-dried C. papaya seeds on human intestinal parasitosis, 60 asymptomatic Nigerian children with stool microscopic evidence of intestinal parasites received immediate doses (20 mL) of either an elixir composed with air-dried C. papaya seeds and honey (CPH) or honey alone (placebo) in two randomized treatment groups. Repeat stool microscopic examinations were conducted 7 days postintervention for intestinal parasites. Significantly more subjects given CPH elixir than those given honey had their stools cleared of parasites [23 of 30 (76.7%) vs. five of 30 (16.7%); z = 4.40, P = .0000109]. There were no harmful effects. The stool clearance rate for the various types of parasites encountered was between 71.4% and 100% following CPH elixir treatment compared with 0-15.4% with honey. Thus, air-dried C. papaya seeds are efficacious in treating human intestinal parasites and without significant side effects. Their consumption offers a cheap, natural, harmless, readily available monotherapy and preventive strategy against intestinal parasitosis, especially in tropical communities. Further and large-scale intervention studies to compare C. papaya with standard antiparasitic preparation are desirous. PMID:17472487

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

    Science.gov (United States)

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

    2007-09-01

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

  16. Human Intestinal Raf Kinase Inhibitor Protein (RKIP) Catalyzes Prasugrel as a Bioactivation Hydrolase.

    Science.gov (United States)

    Kazui, Miho; Ogura, Yuji; Hagihara, Katsunobu; Kubota, Kazuishi; Kurihara, Atsushi

    2016-01-01

    Prasugrel is a thienopyridine antiplatelet prodrug that undergoes rapid hydrolysis in vivo to a thiolactone metabolite by human carboxylesterase-2 (hCE2) during gastrointestinal absorption. The thiolactone metabolite is further converted to a pharmacologically active metabolite by cytochrome P450 isoforms. The aim of the current study was to elucidate hydrolases other than hCE2 involved in the bioactivation step of prasugrel in human intestine. Using size-exclusion column chromatography of a human small intestinal S9 fraction, another peak besides the hCE2 peak was observed to have prasugrel hydrolyzing activity, and this protein was found to have a molecular weight of about 20 kDa. This prasugrel hydrolyzing protein was successfully purified from a monkey small intestinal cytosolic fraction by successive four-step column chromatography and identified as Raf-1 kinase inhibitor protein (RKIP) by liquid chromatography-tandem mass spectrometry. Second, we evaluated the enzymatic kinetic parameters for prasugrel hydrolysis using recombinant human RKIP and hCE2 and estimated the contributions of these two hydrolyzing enzymes to the prasugrel hydrolysis reaction in human intestine, which were approximately 40% for hRKIP and 60% for hCE2. Moreover, prasugrel hydrolysis was inhibited by anti-hRKIP antibody and carboxylesterase-specific chemical inhibitor (bis p-nitrophenyl phosphate) by 30% and 60%, respectively. In conclusion, another protein capable of hydrolyzing prasugrel to its thiolactone metabolite was identified as RKIP, and this protein may play a significant role with hCE2 in prasugrel bioactivation in human intestine. RKIP is known to have diverse functions in many intracellular signaling cascades, but this is the first report describing RKIP as a hydrolase involved in drug metabolism. PMID:26558823

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

    DEFF Research Database (Denmark)

    Ito, Go; Okamoto, Ryuichi; Murano, Tatsuro; Shimizu, Hiromichi; Fujii, Satoru; Nakata, Toru; Mizutani, Tomohiro; Yui, Shiro; Akiyama-Morio, Junko; Nemoto, Yasuhiro; Okada, Eriko; Araki, Akihiro; Ohtsuka, Kazuo; Tsuchiya, Kiichiro; Nakamura, Tetsuya; Watanabe, Mamoru

    2013-01-01

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

  18. 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

    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...

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

    Scientific Electronic Library Online (English)

    Virginia, Robles-Alonso; Francisco, Guarner.

    2013-06-01

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

  20. Intestinal transport of manganese from human milk, bovine milk and infant formula in rats

    International Nuclear Information System (INIS)

    The transport of manganese from extrinsically labeled human milk, bovine milk and infant formula was studied by the everted intestinal sac method. Tissue/mucosal flux data indicated that transport of manganese into the intestinal tissue was significantly greater with bovine milk and formula than from human milk. Similarly, the total flux of manganese from the mucosal to serosal surface was less when human milk was used. Smaller molecular weight manganese binding ligands isolated from the milk samples enhanced the mucosal to tissue movement of manganese as contrasted to the higher molecular weight manganese binding ligands. Most significantly the data suggest that the transport and uptake of manganese is less in the presence of human milk and its isolated manganese fractions than it is in bovine milk or infant formula. 15 references, 3 tables

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

    OpenAIRE

    Lapaque, Nicolas; Doré, Joël; Blottière, Hervé

    2015-01-01

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

  2. Human Carboxymethylenebutenolidase as a Bioactivating Hydrolase of Olmesartan Medoxomil in Liver and Intestine

    OpenAIRE

    Ishizuka, Tomoko; Fujimori, Izumi; Kato, Mitsunori; Noji-Sakikawa, Chisa; Saito, Motoko; Yoshigae, Yasushi; Kubota, Kazuishi; Kurihara, Atsushi; Izumi, Takashi; Ikeda, Toshihiko; Okazaki, Osamu

    2010-01-01

    Olmesartan medoxomil (OM) is a prodrug type angiotensin II type 1 receptor antagonist widely prescribed as an antihypertensive agent. Herein, we describe the identification and characterization of the OM bioactivating enzyme that hydrolyzes the prodrug and converts to its pharmacologically active metabolite olmesartan in human liver and intestine. The protein was purified from human liver cytosol by successive column chromatography and was identified by mass spectrometry to be a carboxymethyl...

  3. Thalidomide inhibits inflammatory and angiogenic activation of human intestinal microvascular endothelial cells (HIMEC)

    OpenAIRE

    Rafiee, Parvaneh; Daniel J. Stein; Nelson, Victoria M.; Otterson, Mary F.; Shaker, Reza; Binion, David G

    2009-01-01

    The glutamic acid derivative thalidomide is a transcriptional inhibitor of TNF-? but is also known to affect human blood vessels, which may underlie its teratogenicity. Thalidomide has been used in the treatment of refractory Crohn's disease (CD), but the therapeutic mechanism is not defined. We examined the effect of thalidomide on primary cultures of human intestinal microvascular endothelial cells (HIMEC), the relevant endothelial cell population in inflammatory bowel disease (IBD), to det...

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

    DEFF Research Database (Denmark)

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

    2006-01-01

    BACKGROUND AND AIMS: Perturbation of differentiation of the crypt-villus axis of the human small intestine is associated with several intestinal disorders of clinical importance. At present, differentiation of small intestinal enterocytes in the crypt-villus axis is not well characterised. SUBJECTS...... found and categorised into four functional groups. In enterocytes lining the upper part of crypts, cell cycle promoting genes and transcription/translation related genes were predominantly expressed, whereas in enterocytes lining the middle of villi, high expression of cell cycle inhibiting genes......, metabolism related genes, and vesicle/transport related genes was found. CONCLUSION: Two types of enterocytes were dissected at the molecular level, the non-absorptive enterocyte located in the upper part of crypts and the absorptive enterocyte found in the middle of villi. These data improve our knowledge...

  5. [Effect of human immunoglobulins on microflora of the large intestine in nonspecific ulcerative colitis].

    Science.gov (United States)

    Glad'ko, I A; Pinegin, B V; Korshunov, V M; Khalif, I L; Kirkin, B V

    1986-03-01

    The use of commercial preparations of human immunoglobulin for the treatment of ulcerous colitis produces a positive effect on the microflora of the large intestine, contributing to the disappearance of Proteus, the lactose-negative forms of enterobacteria and the hemolytic variants of staphylococci, as well as to the increase of the amount of useful indigenous microflora (bifidobacteria and lactobacteria). The quantitative and qualitative improvement of the microflora leads, possibly, to the decrease of the intoxication of the body, improvement in the activity of the intestine and increased vitamin formation, thus giving a pronounced clinical effect and improvement in the endoscopic picture of the mucous membrane of the large intestine, peculiar for this disease. PMID:3518310

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

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Jun-Hua Xiao

    2012-01-01

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

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

    International Nuclear Information System (INIS)

    Purpose: To determine whether systemically administered recombinant human epidermal growth factor (rhEGF) accelerates the recovery of mouse small intestinal mucosa after irradiation. Methods and Materials: A mouse mucosal damage model was established by administering radiation to male BALB/c mice with a single dose of 15 Gy applied to the abdomen. After irradiation, rhEGF was administered subcutaneously at various doses (0.04, 0.2, 1.0, and 5.0 mg/kg/day) eight times at 2- to 3-day intervals. The evaluation methods included histologic changes of small intestinal mucosa, change in body weight, frequency of diarrhea, and survival rate. Results: The recovery of small intestinal mucosa after irradiation was significantly improved in the mice treated with a high dose of rhEGF. In the mice that underwent irradiation without rhEGF treatment, intestinal mucosal ulceration, mucosal layer damage, and severe inflammation occurred. The regeneration of villi was noticeable in mice treated with more than 0.2 mg/kg rhEGF, and the villi recovered fully in mice given more than 1 mg/kg rhEGF. The frequency of diarrhea persisting for more than 3 days was significantly greater in the radiation control group than in the rhEGF-treated groups. Conclusions: Systemic administration of rhEGF accelerates recovery from mucosal damage induced by irradiation. We suggest that rhEGF treatment shows promise for the reduction of small intestinal damage after irradiation

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

    International Nuclear Information System (INIS)

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

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

    OpenAIRE

    Corpet, D. E.

    1987-01-01

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

  11. 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; Schller, 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.

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

    Directory of Open Access Journals (Sweden)

    Xue-hong LIU

    2011-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Oku T

    2011-06-01

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

  14. Purification and fermentation in vitro of sesaminol triglucoside from sesame cake by human intestinal microbiota.

    Science.gov (United States)

    Zhu, Xiuling; Zhang, Xin; Sun, Yongkang; Su, Di; Sun, Yi; Hu, Bing; Zeng, Xiaoxiong

    2013-02-27

    Sesaminol triglucoside (STG), the most abundant lignan glycoside existing in sesame cake/meal, has exhibited various biological activities. However, little information about its in vitro fermentation with intestinal microbiota is available. Therefore, the effect of STG from sesame cake on the fermentation of human fecal microbiota was evaluated. First, high-purity STG was successfully prepared from defatted sesame cake by extraction with 80% ethanol and simple purification procedures of polyamide column chromatography and Toyopearl HW-40S column chromatography. Then the influence of STG on intestinal microbiota was conducted by monitoring bacterial populations and analyzing the concentrations of short-chain fatty acids (SCFA). We found that STG could significantly induce an increase in numbers of Lactobacillus - Enterococcus group and Bifidobacterium in fermentation in vitro with human fecal microbiota, while it did not stimulate the bacterial growth of Eubacterium rectale - Clostridium coccoides group, Clostridium histolyticum group, and Bacteroides - Prevotella group. Furthermore, it was found that concentrations of formic, acetic, propionic, and butyric acids in STG culture increased significantly during the fermentation, and its total SCFA concentration was relatively higher than those of the control and glucose cultures at 6 and 12 h fermentation. Our findings provided further evidence for the importance of human intestinal bacteria in the bioactivity of STG and its metabolites in the maintenance of human health. PMID:23387872

  15. 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

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

    International Nuclear Information System (INIS)

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

  17. 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.

  18. Radioimmunodetection of human colon cancer transplanted to nude mice using antibodies to intestinal antigen

    International Nuclear Information System (INIS)

    131I-antibodies (Ab) to human organ-specific intestinal antigen - β1-MA (maconial antigene) were infected intravenously to nude mice to whom various human tumors including colon tumors had been transplanted. Ab distribution in recipient tissues and in tumors was determined over time with the help of a γ-counter. Ab to β1-MA was shown to localize specifically in colon tumors. 131I-Ab accumulation in this tumor exceeded the background level in tumor-bearing tissues. The excess increased with time as a result of slower Ab clearance of colon tumors as compared to normal tissues. β1-MA was detected immunohistochemically in the mouse colon epihtelium however elevated accumulation of Ab to β1-MA injected into the blood flow in the intestine was undetectable

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

    DEFF Research Database (Denmark)

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

    2005-01-01

    . Physiological postprandial ileal lipid concentrations dose dependently inhibited human digestive pancreatic protease and bile acid output, but not intestinal motor activity. Thus physiological postprandial ileal nutrient exposure may be of importance for the termination of digestive secretory responses......Lipid perfusion into the distal ileal lumen at supraphysiological loads inhibits pancreatic exocrine secretion and gastrointestinal motility in humans. In the present study, we sought to determine the effects of physiological postprandial intraileal lipid concentrations on endogenously stimulated...... pancreaticobiliary secretion, intestinal motility, and release of regulatory mediators. Eight healthy volunteers were intubated with an oroileal multilumen tube for continuous duodenal perfusion of essential amino acids (450 mumol/min), ileal perfusion of graded doses of lipids (0, 50 and 100 mg/min, each dose for...

  20. 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; Arumugam, Manimozhiyan; Booijink, Carien C G M; Troost, Freddy J; Bork, Peer; Wels, Michiel; de Vos, Willem M; Kleerebezem, Michiel

    2012-01-01

    samples from a single individual indicated that Streptococcus sp., Escherichia coli, Clostridium sp. and high G+C organisms are most abundant in the small intestine. The compositions of these populations fluctuated in time and correlated to the short-chain fatty acids profiles that were determined in......The human gastrointestinal tract (GI tract) harbors a complex community of microbes. The microbiota composition varies between different locations in the GI tract, but most studies focus on the fecal microbiota, and that inhabiting the colonic mucosa. Consequently, little is known about the...... 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....

  1. Commensal Streptococcus salivarius modulates PPAR? transcriptional activity in human intestinal epithelial cells

    OpenAIRE

    Couvigny, Benoit; Wouters, Tomas; Kaci, Ghalia; Jacouton, Elsa; Delorme, Christine; Dore, Joel; Renault, Pierre; Blottire, Herve

    2015-01-01

    The impact of commensal bacteria in eukaryotic transcriptional regulation has increasingly been demonstrated over the last decades. A multitude of studies have shown direct effects of commensal bacteria from local transcriptional activity to systemic impact. The commensal bacterium Streptococcus salivarius is one of the early bacteria colonizing the oral and gut mucosal surfaces. It has been shown to down-regulate nuclear transcription factor (NF-?B) in human intestinal cells, a central regul...

  2. Ontogeny of fasting small intestinal motor activity in the human infant.

    OpenAIRE

    Bisset, W. M.; Watt, J.B.; Rivers, R. P.; Milla, P. J.

    1988-01-01

    A clearly defined progression of fasting small intestinal motor development is seen in the human infant from disorganised low amplitude motor activity before 31 weeks gestation through an intermediate phase of increasing motor organisation and amplitude to the development of a normal cyclical pattern of motor activity with clearly defined phase I, II, and III activity between 37 weeks gestation and term. With increasing maturity smooth muscle contractility [gastric antral pressure (5-30 mmHg)...

  3. Development and characterisation of T lymphocyte lines from human small intestinal biopsies.

    OpenAIRE

    Kelleher, D; Kagnoff, M F

    1989-01-01

    T lymphocyte lines were developed from human small intestinal biopsies obtained at the time of gastroduodenoscopy. Lines were established as outgrowths from biopsy specimens in microculture using a combination of T cell mitogens, indomethacin, interleukin (IL-2) and autologous irradiated feeder cells. The predominant phenotype of T cells after six to 12 weeks in culture was CD2, CD3, and CD4 positive. Functionally, these T cell lines secreted IL-2 in response to stimulation with phytohemagglu...

  4. Influence of Exposure Time on Gene Expression by Human Intestinal Epithelial Cells Exposed to Lactobacillus acidophilus

    OpenAIRE

    O'Flaherty, Sarah; Klaenhammer, Todd R

    2012-01-01

    Analysis of global temporal gene expression by human intestinal cells when exposed to Lactobacillus acidophilus revealed induction of immune-related pathways and NF-κB target genes after a 1-h exposure, compared to a 4- or 8-h exposure. Additionally, an L. acidophilus derivative expressing covalently bound flagellin resulted in increased induction of il8, cxc1, and cxcl2 compared to the parent L. acidophilus.

  5. Effect of vasoactive intestinal polypeptide on active and passive transport in the human jejunum.

    OpenAIRE

    Davis, G.R.; Santa Ana, C A; Morawski, S. G.; Fordtran, J. S.

    1981-01-01

    The effect of intravenous vasoactive intestinal polypeptide (VIP) on normal transport mechanisms in the human jejunum in vivo was examined with the triple-lumen, steady-state perfusion technique. By using special test solutions that revealed different aspects of jejunal transport, we were able to evaluate the effect of VIP on specific transport processes, such as active bicarbonate absorption, active chloride secretion, and passive absorption or secretion of sodium chloride. At an infusion ra...

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

    OpenAIRE

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

    1984-01-01

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

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

    OpenAIRE

    Huguet, Antoine; Hatton, Aurélie; Villot, Romain; Quenault, Hélène; Blanchard, Yannick; Fessard, Valérie

    2014-01-01

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

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

    OpenAIRE

    Heinsen, Femke-Anouska

    2012-01-01

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

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

    Science.gov (United States)

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

    1992-05-01

    This experiment was carried out as a preliminary study, an attempt to grow new intestinal mucosa on human amniotic membrane in the terminal ileum in 37 rabbits. After ketamin sulfate anesthesia at laparatomy, 5-cm ileal defects were patched with human amniotic membrane (5 x 2 cm). These patched intestines were investigated on the first postoperative day and the 2nd, 5th, 10th, and 20th weeks corresponding to 4, 5, 5, 10, and 10 rabbits, respectively. Only three rabbits died in the early postoperative period. There was no evidence of intestinal obstruction or dilatation with barium meal. Microscopically, the neomucosa consisted of a thin layer of columnar epithelial cells at 2 weeks with more maturity of the villi and less irregularity and branching by 20 weeks. All patches were covered with neomucosa commencing at 2 weeks and covering the whole patch area by 20 weeks. This technique's advantages are the large size and the ease of the availability of the human amniotic membrane for neonates at risk without jeopardizing the neonates tissues. It is hoped that this method might be considered when neonatal material is scarce. PMID:1625130

  10. Human carboxymethylenebutenolidase as a bioactivating hydrolase of olmesartan medoxomil in liver and intestine.

    Science.gov (United States)

    Ishizuka, Tomoko; Fujimori, Izumi; Kato, Mitsunori; Noji-Sakikawa, Chisa; Saito, Motoko; Yoshigae, Yasushi; Kubota, Kazuishi; Kurihara, Atsushi; Izumi, Takashi; Ikeda, Toshihiko; Okazaki, Osamu

    2010-04-16

    Olmesartan medoxomil (OM) is a prodrug type angiotensin II type 1 receptor antagonist widely prescribed as an antihypertensive agent. Herein, we describe the identification and characterization of the OM bioactivating enzyme that hydrolyzes the prodrug and converts to its pharmacologically active metabolite olmesartan in human liver and intestine. The protein was purified from human liver cytosol by successive column chromatography and was identified by mass spectrometry to be a carboxymethylenebutenolidase (CMBL) homolog. Human CMBL, whose endogenous function has still not been reported, is a human homolog of Pseudomonas dienelactone hydrolase involved in the bacterial halocatechol degradation pathway. The ubiquitous expression of human CMBL gene transcript in various tissues was observed. The recombinant human CMBL expressed in mammalian cells was clearly shown to activate OM. By comparing the enzyme kinetics and chemical inhibition properties between the recombinant protein and human tissue preparations, CMBL was demonstrated to be the primary OM bioactivating enzyme in the liver and intestine. The recombinant CMBL also converted other prodrugs having the same ester structure as OM, faropenem medoxomil and lenampicillin, to their active metabolites. CMBL exhibited a unique sensitivity to chemical inhibitors, thus, being distinguishable from other known esterases. Site-directed mutagenesis on the putative active residue Cys(132) of the recombinant CMBL caused a drastic reduction of the OM-hydrolyzing activity. We report for the first time that CMBL serves as a key enzyme in the bioactivation of OM, hydrolyzing the ester bond of the prodrug type xenobiotics. PMID:20177059

  11. Anaerobic Metabolism of 1-Amino-2-Naphthol-Based Azo Dyes (Sudan Dyes) by Human Intestinal Microflora▿

    OpenAIRE

    Xu, Haiyan; Heinze, Thomas M.; Chen, Siwei; Cerniglia, Carl E.; Chen, Huizhong

    2007-01-01

    The rates of metabolism of Sudan I and II and Para Red by human intestinal microflora were high compared to those of Sudan III and IV under anaerobic conditions. Metabolites of the dyes were identified as aniline, 2,4-dimethylaniline, o-toluidine, and 4-nitroaniline through high-performance liquid chromatography and liquid chromatography electrospray ionization tandem mass spectrometry analyses. These data indicate that human intestinal bacteria are able to reduce Sudan dyes to form potential...

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

    International Nuclear Information System (INIS)

    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

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

    OpenAIRE

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

    2009-01-01

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

  14. Structural features of resistant starch at the end of the human small intestine.

    Science.gov (United States)

    Faisant, N; Champ, M; Colonna, P; Buleon, A; Molis, C; Langkilde, A M; Schweizer, T; Flourie, B; Galmiche, J P

    1993-04-01

    Structural features of in vivo resistant starch were assessed using the ileal contents of four humans. Two of the latter were collected by ileostomy after ingestion of bean flakes or potato flakes and the other two were collected by an intubation technique after ingestion of retrograded high-amylose maize starch or complexed high-amylose maize starch. The degree of polymerizations (DP), solubility and crystallinity were assessed. For all samples, starch fractions which escaped digestion in the small intestine were composed of three populations of alpha-glucans with proportions differing according to the substrate. Small quantities of oligosaccharides made up the first population, illustrating a limitation of absorption in the small intestine. The second population, the main resistant fraction, was comprised of retrograded amylose of mean DPn of about 35 glucose units with a melting temperature at 150 degrees C and exhibiting a B-type pattern. Finally high molecular weight semi-crystalline alpha-glucans were attributed to fragments of starch. This study showed that some potentially digestible starch could reach the colon and crystalline fractions constituted only part of the starch that escaped digestion in the human small intestine. PMID:8491166

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

    Science.gov (United States)

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

    2015-05-01

    Adherent-invasive Escherichia coli (AIEC), associated with Crohn's disease, are likely candidate contributory factors in the disease. However, signaling pathways involved in human intestinal mucosa innate host response to AIEC remain unknown. Here we use a 3D model of human intestinal mucosa explant culture to explore the effects of the AIEC strain LF82 on two innate immunity platforms, i.e., the inflammasome through evaluation of caspase-1 status, and NFκB signaling. We showed that LF82 bacteria enter and survive within a few intestinal epithelial cells and macrophages, without altering the mucosa overall architecture. Although 4-h infection with a Salmonella strain caused crypt disorganization, caspase-1 activation, and mature IL-18 production, LF82 bacteria were unable to activate caspase-1 and induce IL-18 production. In parallel, LF82 bacteria activated NFκB signaling in epithelial cells through IκBα phosphorylation, NFκBp65 nuclear translocation, and TNFα secretion. In addition, NFκB activation was crucial for the maintenance of epithelial homeostasis upon LF82 infection. In conclusion, here we decipher at the whole-mucosa level the mechanisms of the LF82-induced subversion of innate immunity that, by maintaining host cell integrity, ensure intracellular bacteria survival. PMID:25269707

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

    International Nuclear Information System (INIS)

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

  17. Interleukin 10 Receptor Signaling: Master Regulator of Intestinal Mucosal Homeostasis in Mice and Humans

    Science.gov (United States)

    Shouval, Dror S.; Ouahed, Jodie; Biswas, Amlan; Goettel, Jeremy A.; Horwitz, Bruce H.; Klein, Christoph; Muise, Aleixo M.; Snapper, Scott B.

    2016-01-01

    Interleukin 10 (IL10) is a key anti-inflammatory cytokine that can inhibit proinflammatory responses of both innate and adaptive immune cells. An association between IL10 and intestinal mucosal homeostasis became clear with the discovery that IL10 and IL10 receptor (IL10R)-deficient mice develop spontaneous intestinal inflammation. Similarly, patients with deleterious mutations in IL10, IL10RA, or IL10RB present with severe enterocolitis within the first months of life. Here, we review recent findings on how IL10- and IL10R-dependent signaling modulates innate and adaptive immune responses in the murine gastrointestinal tract, with implications of their role in the prevention of inflammatory bowel disease (IBD). In addition, we discuss the impact of IL10 and IL10R signaling defects in humans and their relationship to very early-onset IBD (VEO-IBD). PMID:24507158

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

    Science.gov (United States)

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

    2016-03-30

    In order to investigate the modulatory effect of purple sweet potato anthocyanins (PSPAs) on human intestinal microbiota, PSPAs were prepared by column chromatography and their influence on intestinal microbiota was analyzed by monitoring the bacterial populations and analyzing short-chain fatty acid (SCFA) concentrations at different time points. The numbers (log10 cell/mL) of Bifidobacterium and Lactobacillus/Enterococcus spp., Bacteroides-Prevotella, Clostridium histolyticum, and total bacteria after 24 h of culture in anaerobic fermentation broth containing PSPAs were 8.44 ± 0.02, 8.30 ± 0.01, 7.80 ± 0.03, 7.60 ± 0.03, and 9.00 ± 0.02, respectively, compared with 8.21 ± 0.03, 8.12 ± 0.02, 7.95 ± 0.02, 7.77 ± 0.02, and 9.01 ± 0.03, respectively, in the controls. The results showed that PSPAs induced the proliferation of Bifidobacterium and Lactobacillus/Enterococcus spp., inhibited the growth of Bacteroides-Prevotella and Clostridium histolyticum, and did not affect the total bacteria number. Total SCFA concentrations in the cultures with PSPAs were significantly higher than in the controls (P < 0.05). Moreover, during the fermentation, the PSPAs were partially fragmented to phenolic acids, which may exert a better effect on intestinal microecology, suggesting that PSPAs may have prebiotic-like activity by generating SCFAs and modulating the intestinal microbiota, contributing to improvements in human health. PMID:26975278

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Elke Kaemmerer

    2011-01-01

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

  1. Intestinal Coccidia

    OpenAIRE

    MJ Ggaravi

    2007-01-01

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

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

    OpenAIRE

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

    2008-01-01

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

  3. A Novel Method for the Culture and Polarized Stimulation of Human Intestinal Mucosa Explants

    Science.gov (United States)

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

    2013-01-01

    Few models currently exist to realistically simulate the complex human intestine's micro-environment, where a variety of interactions take place. Proper homeostasis directly depends on these interactions, as they shape an entire immunological response inducing tolerance against food antigens while at the same time mounting effective immune responses against pathogenic microbes accidentally ingested with food. Intestinal homeostasis is preserved also through various complex interactions between the microbiota (including food-associated beneficial bacterial strains) and the host, that regulate the attachment/degradation of mucus, the production of antimicrobial peptides by the epithelial barrier, and the "education" of epithelial cells' that controls the tolerogenic or immunogenic phenotype of unique, gut-resident lymphoid cells' populations. These interactions have been so far very difficult to reproduce with in vitro assays using either cultured cell lines or peripheral blood mononuclear cells. In addition, mouse models differ substantially in components of the intestinal mucosa (mucus layer organization, commensal bacteria community) with respect to the human gut. Thus, studies of a variety of treatments to be brought in the clinics for important stress-related or pathological conditions such as irritable bowel syndrome, inflammatory bowel disease or colorectal cancer have been difficult to carry out. To address these issues, we developed a novel system that enables us to stimulate explants of human intestinal mucosa that retain their in situ conditioning by the host microbiota and immune response, in a polarized fashion. Polarized apical stimulation is of great importance for the outcome of the elicited immune response. It has been repeatedly shown that the same stimuli can produce completely different responses when they bypass the apical face of the intestinal epithelium, stimulating epithelial cells basolaterally or coming into direct contact with lamina propria components, switching the phenotype from tolerogenic to immunogenic and causing unnecessary and excessive inflammation in the area. We achieved polarized stimulation by gluing a cave cylinder which delimited the area of stimulation on the apical face of the mucosa as will be described in the protocol. We used this model to examine, among others, differential effects of three different Lactobacilli strains. We show that this model system is very powerful to assess the immunomodulatory properties of probiotics in healthy and disease conditions. PMID:23666550

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

    Directory of Open Access Journals (Sweden)

    ACHMAD DINOTO

    2013-11-01

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

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

    Directory of Open Access Journals (Sweden)

    C. Yi

    2007-01-01

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

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

    OpenAIRE

    Marta G?ogowska; Marta Kopa?ska

    2015-01-01

    Sodium and potassium regulate the total amount of water in the body and the transmission of sodium into and out of individual cells also plays a role in critical body functions. The movement of sodium is critical in generation of these electrical signals. Research was conducted on samples taken from women and men aged 20-90 years, derived from the stomach, small intestine and large intestine. Samples were dried at 80C for 24 hours, and then increased temperature to 105C and dried for seven ...

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

    DEFF Research Database (Denmark)

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

    2006-01-01

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

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2016-11-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1985-07-01

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

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

    OpenAIRE

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

    2009-01-01

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

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

    OpenAIRE

    Ulrike Lodemann; Julia Strahlendorf; Peter Schierack; Shanti Klingspor; Jörg R. Aschenbach; Holger Martens

    2015-01-01

    The aim of this study has been to elucidate the effect of the probiotic Enterococcus faecium NCIMB 10415 on epithelial integrity in intestinal epithelial cells and whether pre- and coincubation with this strain can reproducibly prevent damage induced by enterotoxigenic (ETEC) and enteropathogenic Escherichia coli (EPEC). Porcine (IPEC-J2) and human (Caco-2) intestinal epithelial cells were incubated with bacterial strains and epithelial integrity was assessed by measuring transepithelial elec...

  13. Sodium copper chlorophyllin: in vitro digestive stability and accumulation by Caco-2 human intestinal cells.

    Science.gov (United States)

    Ferruzzi, Mario G; Failla, Mark L; Schwartz, Steven J

    2002-03-27

    Sodium copper chlorophyllin (SCC), a mixture of water-soluble chlorophyll derivatives, is used as both a food colorant and a common dietary supplement. Although the potential antimutagenic and antioxidant properties of this commercial preparation have been demonstrated, limited information is available on its digestion and absorption by humans. Stability of SCC was examined during simulated gastric and small intestinal digestion. Three preparations were subjected to in vitro digestion: SCC in water, SCC in water + 10% corn oil, and SCC in applesauce. SCC components from raw material preparations and in digested samples were analyzed by C(18) HPLC with photodiode array detection. Cu(II)chlorin e(4), the major chlorin component of SCC, was relatively stable during simulated digestion. In contrast, greater than 90% of Cu(II)chlorin e(6) was degraded to undetermined products during digestion. Recovery of Cu(II)chlorin e(6) after digestion was increased by incorporation of SCC into applesauce, suggesting a protective role of the inclusion matrix for stabilization of labile SCC components. Accumulation of SCC derivatives was investigated by using differentiated cultures of the TC7 clone of the Caco-2 human intestinal cell line. Cellular accumulation from media containing 0.5 to 60 ppm SCC was linear with intracellular content ranging between 0.2 and 29.6 microg of total SCC per mg of cellular protein. Uptake of SCC by Caco-2 cells was significantly (p < 0.01) lower in cultures incubated at 4 degrees C than in those incubated at 37 degrees C. Although intracellular SCC was transported into both apical and basolateral compartments when Caco-2 cells were grown on inserts, apical efflux was significantly greater (p < 0.01) than basolateral efflux. Stability of Cu(II)chlorin e(4) during in vitro digestion and effective uptake by Caco-2 enterocyte-like cells support the likelihood that a portion of this SCC component or its metabolites is absorbed from the human intestine. PMID:11902975

  14. 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

    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...

  15. Transport of Aflatoxin M1 in Human Intestinal Caco-2/TC7 Cells

    OpenAIRE

    Caloni, Francesca; Cortinovis, Cristina; Pizzo, Fabiola; DE ANGELIS Isabella

    2012-01-01

    Aflatoxin M1 (AFM1) is a hydroxylated metabolite of aflatoxin B1 (AFB1). After it is formed, it is secreted in the milk of mammals. Despite the potential risk of human exposure to AFM1, data reported in literature on the metabolism, toxicity, and bioavailability of this molecule are limited and out of date. The aim of the present research was to study the absorption profile of AFM1 and possible damage to tight junctions (TJ) of the intestinal Caco-2/TC7 clone grown on microporous filter suppo...

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

    OpenAIRE

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

    2007-01-01

    The objective of the present study was to investigate the effects of recombinant human growth hormone (rhGH) on the intestinal mucosa barrier of septic rats and explore its possible mechanism. Female Sprague-Dawley rats were randomized into three groups: control, Escherichia coli-induced sepsis (S) and treatment (T) groups. Groups S and T were subdivided into subgroups 1d and 3d, respectively. Expression of liver insulin-like growth factor-1 (IGF-1) mRNA, Bcl-2 and Bax protein levels and the ...

  17. Characterization and distribution of alpha 2-adrenergic receptors in the human intestinal mucosa.

    OpenAIRE

    Valet, P; Senard, J. M.; Devedjian, J C; Planat, V; Salomon, R.; Voisin, T.; Drean, G; Couvineau, A.; Daviaud, D.; Denis, C.

    1993-01-01

    The subtype and the expression of the alpha 2-adrenergic receptor were investigated in the normal mucosa from human intestine by means of radioligand binding, RNase mapping, and measurement of adenylate cyclase activity. The study of the binding of the alpha 2-adrenergic antagonist, [3H]RX821002, to epithelial cell membranes indicated the existence of a single class of noninteracting sites displaying a high affinity for the radioligand (Kd = 1.1 +/- 0.5 nM). The rank order of potency of antag...

  18. Stability of Cephalosporin Prodrug Esters in Human Intestinal Juice: Implications for Oral Bioavailability

    OpenAIRE

    Stoeckel, Klaus; Hofheinz, Werner; Laneury, Jean Paul; Duchene, Patrick; Shedlofsky, Steve; Blouin, Robert A.

    1998-01-01

    The levels of degradation of cefetamet pivoxil (CAT), cefuroxime axetil (CAE), and cefpodoxime proxetil (CPD) in 0.6 M phosphate buffer (pH 7.4) and human intestinal juice (pH 7.4) at 37°C over 24 h were compared. Significant differences in the time courses of degradation and in the patterns of degradation products were observed. (i) The relative proportions of the Δ2- and Δ3-cephalosporins were roughly reversed in the two incubation media. In phosphate buffer, the major degradation product w...

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

    OpenAIRE

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

    2005-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    DEFF Research Database (Denmark)

    Duve, Linda Rosager; Steenfeldt, Sanna; Thodberg, Karen; Nielsen, Birte Lindstrøm

    2011-01-01

    1. The aim of this study was to evaluate how splitting the dark period (scotoperiod) affects feeding behaviour and associated intestinal measures in broilers. 2. Ross 308 broilers were reared to 37 d in groups given either a daily 8-h continuous scotoperiod (DARK 8) or an intermittent light...... activity across the day. However, DARK 4þ4 had a higher feed intake and weight gain. The occurrence and severity of foot pad dermatitis was similar between treatments. 6. In conclusion, broilers modify their feeding behaviour according to the prevailing light schedule. Eight consecutive hours of darkness...

  2. 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; Li, Xiaoping; Sonne, Si Brask; dos Santos, Marcelo Bertalan Quintanilha; Dimitrov, Peter; Madsen, Lise; Qin, Junjie; Wang, Jun; Raes, Jeroen; Kristiansen, Karsten; Licht, Tine Rask

    2012-01-01

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

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

    International Nuclear Information System (INIS)

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

  4. Sulfapyridine appearance in plasma after salicylazosulfapyridine. Another simple measure of intestinal transit

    International Nuclear Information System (INIS)

    The appearance of sulfapyridine in plasma after oral administration of salicylazosulfapyridine (SASP) was evaluated as a method for defining arrival time in the cecum, an index of small bowel transit. After direct instillation of SASP and lactulose into the cecum, the appearances of their metabolites (sulfapyridine in plasma and hydrogen in breath) were rapid (1-10 min) and simultaneous. When a mixture of SASP and lactulose was taken by mouth, times of the respective signals varied among individuals from 40 to 180 min (n = 8) but were correlated within individuals. Salicylazosulfapyridine transit times from duodenum to cecum were also very similar to simultaneous measurements of transit by scintigraphic monitoring of technetium 99m. Timing of the sulfapyridine signal corresponded to the arrival of 5%-13% of technetium 99m DTPA in the cecum. Exemplifying the use of this new technique, simultaneous administration of lactulose into the stomach and SASP into the duodenum yielded consistently longer stomach-to-cecum than duodenum-to-cecum transits, attributable to the delay caused by gastric emptying. Therapeutic doses of morphine delayed small bowel transit of SASP. Transit of SASP offers a second marker technique for the cecal arrival of the head of a bolus; the approach may be useful as an inexpensive, noninvasive measurement of transit

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

    Directory of Open Access Journals (Sweden)

    Émile Levy

    2010-01-01

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

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

    Directory of Open Access Journals (Sweden)

    G Barresi

    2009-12-01

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

  7. Inhibition of adhesion of Clostridium difficile to human intestinal cells after treatment with serum and intestinal fluid isolated from mice immunized with nontoxigenic C.difficile membrane fraction.

    Science.gov (United States)

    Senoh, Mitsutoshi; Iwaki, Masaaki; Yamamoto, Akihiko; Kato, Haru; Fukuda, Tadashi; Shibayama, Keigo

    2015-04-01

    Diarrhea and pseudomembrane colitis caused by Clostridium difficile infection is a global health concern because of the high recurrence rate after standard antibiotic therapy. Vaccination presents a powerful countermeasure against disease recurrence. In this study, mice vaccinated with the nontoxigenic C.difficile membrane fraction generated a marked immune response to the antigen, as demonstrated by the serum IgG and intestinal fluid IgA levels. Significantly, pretreatment with harvested IgG- and IgA-containing fluids was sufficient to prevent invitro adhesion of C.difficile to human Caco-2 intestinal cells. These results highlight the potential of nontoxigenic C.difficile membrane fraction as a vaccine candidate for C.difficile infection. PMID:25745878

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    International Nuclear Information System (INIS)

    Highlights: → First description of in vitro cellular uptake of MCs into intestinal cells. → OATP 3A1 and OATP 4A1 are expressed in Caco-2 cell membranes. → MC-LR and MC-RR show similar uptake in Caco-2 cells. → MCs are probably excreted from Caco-2 cells by an active mechanism. -- Abstract: Microcystins (MCs) are cyclic hepatotoxins produced by various species of cyanobacteria. Their structure includes two variable amino acids (AA) leading to more than 80 MC variants. In this study, we focused on the most common variant, microcystin-LR (MC-LR), and microcystin-RR (MC-RR), a variant differing by only one AA. Despite their structural similarity, MC-LR elicits higher liver toxicity than MC-RR partly due to a discrepancy in their uptake by hepatic organic anion transporters (OATP 1B1 and 1B3). However, even though ingestion is the major pathway of human exposure to MCs, intestinal absorption of MCs has been poorly addressed. Consequently, we investigated the cellular uptake of the two MC variants in the human intestinal cell line Caco-2 by immunolocalization using an anti-MC antibody. Caco-2 cells were treated for 30 min to 24 h with several concentrations (1-50 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.

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

    Science.gov (United States)

    Verschuren, P M; Nugteren, D H

    1989-01-01

    The influence of jojoba oil (JO) incorporation in the diet on stomach emptying and intestinal transit time, and the digestion and absorption of JO were investigated in short-term feeding studies in rats. The animals were fed purified diets containing 18% (w/w) fat, of which half consisted of a mixture of lard and sunflower seed oil (SF) supplemented with an equivalent amount of JO. The control animals were fed a mixture of lard and SF (18%). No treatment-related differences were observed in the rate of stomach emptying or the intestinal transit time. Comparative lipid analysis of lymph, intestinal content, intestinal mucosa and faeces indicated that most of the ingested JO was degraded and absorbed. Part of the JO was present as wax ester in the lymph. Hydrolysis of JO was much slower than that of triacylglycerols and continued in the alimentary tract beyond the small intestine due to bacterial processes. JO did not influence the absorption of the conventional fat. PMID:2703193

  12. Quantitative evaluation of neurons in the mucosal plexus of adult human intestines.

    Science.gov (United States)

    Kramer, Kerstin; da Silveira, Alexandre B M; Jabari, Samir; Kressel, Michael; Raab, Marion; Brehmer, Axel

    2011-07-01

    The consequence of presence versus absence of mucosal neurons is not consistently assessed. Here, we addressed two questions. First, based on resected gut specimens of 65 patients/body donors suffering from different diseases, counts of mucosal neurons per mm(2) were analysed with respect to age, gender and region. Second, we evaluated resected megacolonic specimens of four patients suffering from chronic Chagas' disease. Mucosal wholemounts were triple-stained for calretinin (CALR), peripherin (PER) and human neuronal protein Hu C/D (HU). Counts revealed no clear correlation between the presence of mucosal neurons and age, gender or region. Mucosal neurons were present in 30 of 36 specimens derived from males (83%) and in 20 of 29 from females (69%). The numbers per mm(2) increased from duodenum to ileum (1.7-10.8) and from ascending to sigmoid colon (3.2-9.9). Out of 149 small intestinal mucosal neurons, 47% were co-reactive for CALR, PER and HU (large intestine: 76% of 300 neurons) and 48% for PER and HU only (large intestine: 23%). In 12 megacolonic specimens (each 3 from 4 patients), all 23 mucosal neurons found (1.9 per mm(2)) displayed co-reactivity for CALR, PER and HU. We suggest that the presence or the absence of mucosal neurons is variable, ongoing studies will address our assumption that they correspond in their morphochemical characteristics to submucosal neurons. Furthermore, both the architecture and neuron number of the megacolonic mucosal plexus displayed no dramatic changes indicating that mucosal nerves might be less involved in chagasic/megacolonic neurodegeneration as known from the myenteric plexus. PMID:21461752

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

    Science.gov (United States)

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

    2005-03-01

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

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

    Directory of Open Access Journals (Sweden)

    Frank Lehner, Ulf Kulik, Juergen Klempnauer,Juergen Borlak

    2010-08-01

    Full Text Available AIM: To investigate the gene expression pattern of hepatocyte nuclear factor 6 (HNF6 and other liver-enriched transcription factors in various segments of the human intestine to better understand the differentiation of the gut epithelium.METHODS: Samples of healthy duodenum and jejunum were obtained from patients with pancreatic cancer whereas ileum and colon was obtained from patients undergoing right or left hemicolectomy or (rectosigmoid or rectal resection. All surgical specimens were subjected to histopathology. Excised tissue was shock-frozen and analyzed for gene expression of liver-enriched transcription factors by semiquantitative reverse transcription polymerase chain and compared to the human colon carcinoma cell line Caco-2. Protein expression of major liver-enriched transcription factors was determined by Western blotting while the DNA binding of HNF6 was investigated by electromobility shift assays.RESULTS: The gene expression patterning of liver-enriched transcription factors differed in the various segments of the human intestine with HNF6 gene expression being most abundant in the duodenum (P < 0.05 whereas expression of the zinc finger protein GATA4 and of the HNF6 target gene ALDH3A1 was most abundant in the jejunum (P < 0.05. Likewise, expression of FOXA2 and the splice variants 2 and 4 of HNF4α were most abundantly expressed in the jejunum (P < 0.05. Essentially, expression of transcription factors declined from the duodenum towards the colon with the most abundant expression in the jejunum and less in the ileum. The expression of HNF6 and of genes targeted by this factor, i.e. neurogenin 3 (NGN3 was most abundant in the jejunum followed by the ileum and the colon while DNA binding activity of HNF4α and of NGN3 was confirmed by electromobility shift assays to an optimized probe. Furthermore, Western blotting provided evidence of the expression of several liver-enriched transcription factors in cultures of colon epithelial cells, albeit at different levels.CONCLUSION: We describe significant local and segmental differences in the expression of liver-enriched transcription factors in the human intestine which impact epithelial cell biology of the gut.

  15. 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.

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

    International Nuclear Information System (INIS)

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

  17. Intestinal Short Chain Fatty Acids and their Link with Diet and Human Health.

    Science.gov (United States)

    Ríos-Covián, David; Ruas-Madiedo, Patricia; Margolles, Abelardo; Gueimonde, Miguel; de Los Reyes-Gavilán, Clara G; Salazar, Nuria

    2016-01-01

    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-signaling 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. PMID:26925050

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

    OpenAIRE

    Hildebrand, Falk; Ebersbach, Tine; Nielsen, Henrik Bjørn; Li, Xiaoping; Sonne, Si Brask; Bertalan, Marcelo; Dimitrov, Peter; Madsen, Lise; Qin, Junjie; Wang, Jun; Raes, Jeroen; Kristiansen, Karsten; Licht, Tine Rask

    2012-01-01

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

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

    OpenAIRE

    Hildebrand, Falk; Ebersbach, Tine; Nielsen, Henrik Bjørn; Li, Xiaoping; Sonne, Si Brask; dos Santos, Marcelo Bertalan Quintanilha; Dimitrov, Peter; Madsen, Lise; Qin, Junjie; Wang, Jun; Raes, Jeroen; Kristiansen, Karsten; Licht, Tine Rask

    2012-01-01

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

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

    Science.gov (United States)

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

    2016-03-01

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

  1. Human driven transitions in complex model ecosystems

    Science.gov (United States)

    Harfoot, Mike; Newbold, Tim; Tittinsor, Derek; Purves, Drew

    2015-04-01

    Human activities have been observed to be impacting ecosystems across the globe, leading to reduced ecosystem functioning, altered trophic and biomass structure and ultimately ecosystem collapse. Previous attempts to understand global human impacts on ecosystems have usually relied on statistical models, which do not explicitly model the processes underlying the functioning of ecosystems, represent only a small proportion of organisms and do not adequately capture complex non-linear and dynamic responses of ecosystems to perturbations. We use a mechanistic ecosystem model (1), which simulates the underlying processes structuring ecosystems and can thus capture complex and dynamic interactions, to investigate boundaries of complex ecosystems to human perturbation. We explore several drivers including human appropriation of net primary production and harvesting of animal biomass. We also present an analysis of the key interactions between biotic, societal and abiotic earth system components, considering why and how we might think about these couplings. References: M. B. J. Harfoot et al., Emergent global patterns of ecosystem structure and function from a mechanistic general ecosystem model., PLoS Biol. 12, e1001841 (2014).

  2. Transcobalamin derived from bovine milk stimulates apical uptake of vitamin B12 into human intestinal epithelial cells.

    Science.gov (United States)

    Hine, Brad; Boggs, Irina; Green, Ralph; Miller, Joshua W; Hovey, Russell C; Humphrey, Rex; Wheeler, Thomas T

    2014-11-01

    Intestinal uptake of vitamin B12 (hereafter B12) is impaired in a significant proportion of the human population. This impairment is due to inherited or acquired defects in the expression or function of proteins involved in the binding of diet-derived B12 and its uptake into intestinal cells. Bovine milk is an abundant source of bioavailable B12 wherein it is complexed with transcobalamin. In humans, transcobalamin functions primarily as a circulatory protein, which binds B12 following its absorption and delivers it to peripheral tissues via its cognate receptor, CD320. In the current study, the transcobalamin-B12 complex was purified from cows' milk and its ability to stimulate uptake of B12 into cultured bovine, mouse and human cell lines was assessed. Bovine milk-derived transcobalamin-B12 complex was absorbed by all cell types tested, suggesting that the uptake mechanism is conserved across species. Furthermore, the complex stimulated the uptake of B12 via the apical surface of differentiated Caco-2 human intestinal epithelial cells. These findings suggest the presence of an alternative transcobalamin-mediated uptake pathway for B12 in the human intestine other than that mediated by the gastric glycoprotein, intrinsic factor. Our findings highlight the potential for transcobalamin-B12 complex derived from bovine milk to be used as a natural bioavailable alternative to orally administered free B12 to overcome B12 malabsorption. PMID:24913691

  3. 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; Sørensen, Steen; Fahrenkrug, J; Ottesen, B

    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...

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

    Directory of Open Access Journals (Sweden)

    Jerzy Kaleczyc

    2010-11-01

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

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

    Scientific Electronic Library Online (English)

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

    2010-09-01

    Full Text Available Racional- A reconstruo do trnsito intestinal no est isenta de riscos cirrgicos e apresenta taxas considerveis de complicaes ps-operatrias, sendo que a infeco continua a ser um dos maiores desafios existentes neste procedimento. Mtodos- Foram analisados retrospectivamente 86 pronturios [...] de pacientes com colostomia ou ileostomia, atravs de fatores que tivessem impacto sobre a morbimortalidade aps a reconstruo de trnsito intestinal, de janeiro de 2003 a abril de 2009. Resultados- Houve 20 mulheres e 60 homens, com idade mdia de 43 anos. A colostomia em ala (n: 34) e o trauma abdominal indicando colostomia ou ileostomia foram as condies mais frequentes. O intervalo mdio entre a confeco do estoma e a reconstruo de trnsito intestinal foi 15,7 meses. O ndice de morbidade foi 56,8%, sendo a infeco incisional a complicao mais comum (27.47%). A permanncia hospitalar mdia foi 7,6 dias. Houve regresso linear positiva entre permanncia hospitalar ps-operatria e a idade do paciente. Demonstrou-se associao estatisticamente significativa entre o prolongamento da permanncia hospitalar e a ocorrncia de complicaes (p Abstract in english Background - The reconstruction of the intestinal tract is not surgical complications risk-free and is associated to postoperative complications high rates; furthermore, infection remains the hardest challenge in this procedure. Methods - Retrospectively, eighty-six patients with intestinal stomas w [...] ere analyzed through factors that impact on the morbimortality afterwards intestinal transit reconstruction, since January 2003 to April 2009. Results - Loop colostomy (n=34) and abdominal trauma implicating 38.2% of indications to colostomy or ileostomy were the most frequent conditions. The mean interval between stoma confection and intestinal transit reconstruction was 15.7 months. The morbidity frequency was 56.8% and incisional infection was its commonest complication (27.47%). The mean inpatient length of stay was 7.6 days. There was positive linear regression between post-operative inpatient length of stay and inpatient's age. Inpatient length of stay prolongation is associated to occurrence of complications (p

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

    Science.gov (United States)

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

    2007-03-21

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

  7. 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

    (with a continuous basal lamina, caveolae, intermediate filaments, dense bodies, dense bands, and a well-developed subsurface smooth endoplasmic reticulum), but the arrangement of organelles was clearly different, and cisternae of granular endoplasmic reticulum were abundant. Interstitial cells of Cajal...... for identification and further physiological or pathological studies. The deep muscular plexus was sandwiched between a thin inner layer of smooth muscle (one to five cells thick) and the bulk of the circular muscle. Interstitial cells of Cajal in this region very much resembled smooth muscle cells...... muscular plexus, and only few gap junctions with other interstitial cells of Cajal or with the musculature were observed. Compared with interstitial cells of Cajal from other mammals, those associated with the deep muscular plexus in the human small intestine more closely resemble smooth muscle cells, and...

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

    Directory of Open Access Journals (Sweden)

    Marta Głogowska

    2015-02-01

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

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

    International Nuclear Information System (INIS)

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

  10. Epidermal growth factor inhibits glycylsarcosine transport and hPepT1 expression in a human intestinal cell line

    DEFF Research Database (Denmark)

    Nielsen, C U; Amstrup, J; Steffansen, B; Frokjaer, S; Brodin, Birger

    2001-01-01

    The human intestinal cell line Caco-2 was used as a model system to study the effects of epidermal growth factor (EGF) on peptide transport. EGF decreased apical-to-basolateral fluxes of [(14)C]glycylsarcosine ([(14)C]Gly-Sar) up to 50.2 +/- 3.6% (n = 6) of control values. Kinetic analysis of the...

  11. Phase Transition in a Healthy Human Heart Rate

    Science.gov (United States)

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

    2005-07-01

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

  12. Maintaining human productivity during Mars transit

    Science.gov (United States)

    Statler, Irving C.; Billings, Charles E.

    1989-01-01

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

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

    OpenAIRE

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

    2013-01-01

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

  14. 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; Ottenwälder, Birgit; Schnölzer, Martina; Kartenbeck, Jürgen; Lyer, Stefan; Autschbach, Frank; Poustka, Annemarie; Otto, Herwart F; Mollenhauer, Jan

    2004-01-01

    . Screening of antibodies from a hybridoma library led to the identification of an acyl-CoA synthetase 5-specific monoclonal antibody. Protein synthesis, mRNA expression, and the enzyme activity of acyl-CoA synthetase 5 were studied by several methods in human small intestinal tissues with Crohn's disease or...... coeliac disease, respectively. Acyl-CoA synthetase 5 mRNA and protein levels were substantially reduced in injured small intestinal mucosa. Moreover, impaired synthesis of the acyl-CoA synthetase 5 protein was reflected by a decrease in intramucosal enzyme activity. Subtle changes of the acyl...

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

    OpenAIRE

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

    2009-01-01

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

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

    OpenAIRE

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

    2010-01-01

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

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

    OpenAIRE

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

    2013-01-01

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

  18. Institutional change and human development in transition economies

    OpenAIRE

    Pasquale Tridico

    2006-01-01

    Transition economies (i.e. Central Eastern Europe Countries and Former Soviet Union Republics) have undergone an enormous transformation since 1989-1991. After the recession of the early 1990’s, some of these economies experienced a GDP recovery, at a different pace, with different outcomes in terms of economic growth and social performance (i.e. human development, employment, poverty, etc). The aim of this paper is to answer the following research question: was human development concurrent w...

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

    Science.gov (United States)

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

    2015-01-01

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

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

    International Nuclear Information System (INIS)

    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. [3H]-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 [3H]-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

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

    International Nuclear Information System (INIS)

    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

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

    Scientific Electronic Library Online (English)

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

    2008-10-01

    Full Text Available OBJETIVO: Avaliar por mtodo de imagem assistida por computador as alteraes histopatolgicas da parede clica em segmentos providos e desprovidos de trnsito intestinal e relacion-las ao tempo de excluso. MTODOS: Trinta ratos Wistar machos foram submetidos derivao do trnsito no clon esque [...] rdo por meio de colostomia proximal e fstula mucosa distal. Os animais foram divididos em trs grupos experimentais segundo o sacrifcio ter sido realizado seis, doze e dezoito semanas aps o procedimento cirrgico inicial. Segmentos dos clons providos e desprovidos de trnsito foram submetidos a estudo histopatolgico. Foram analisadas as variveis: comprimento das criptas clicas, ulcerao na mucosa, espessura das camadas muscular da mucosa, submucosa e muscular prpria, congesto vascular, nmero de clulas caliciformes e graduao inflamatria comparando os dois segmentos clicos nos diferentes grupos experimentais. As variveis, comprimento das criptas intestinais, espessura das camadas muscular da mucosa, submucosa e muscular prpria foram mensuradas por mtodo de imagem assistida por computador. Na anlise estatstica foram utilizados testes de igualdade de mdias e medianas, anlise de varincia e correlao estabelecendo-se nvel de significncia de cinco por cento. RESULTADOS: A excluso de trnsito mostrou-se associada reduo do comprimento das criptas clicas, aumento da espessura das camadas muscular da mucosa, submucosa e muscular prpria. Verificou-se maior quantidade de ulceraes na mucosa e maior grau de inflamao com o progredir do tempo de excluso. Houve correlao significante entre as ulceraes da mucosa, congesto vascular da submucosa, aumento da espessura das camadas submucosa e muscular prpria, presena de clulas caliciformes, infiltrado inflamatrio, graduao inflamatria e o tempo de excluso de trnsito. CONCLUSES: Alteraes histolgicas ocorrem em todas as camadas da parede clica, em segmentos sem trnsito intestinal. Ulceraes na mucosa intestinal, aumento no nmero de clulas caliciformes, maior congesto vascular na camada submucosa e reao inflamatria estavam relacionadas com o progredir do tempo de excluso intestinal. Abstract in english PURPOSE: To evaluate histopathological alterations of the colon wall in segments with and without intestinal transit, by computer-assisted imaging, and to correlate these with the length of time diversion. METHODS: Thirty male Wistar rats were subjected to intestinal transit diversion by a proximal [...] colostomy and distal mucosa fistula. The animals were divided into three experimental groups according to how long after the initial surgical procedure they were sacrificed: six, twelve and eighteen weeks. Colon segments with and without transit were subjected to histopathological study. The variables colon crypt length, mucosal ulceration, muscle layer thickness of the muscularis mucosa, submucosa and muscularis propria, vascular congestion, number of caliciform cells, inflammatory grade and degree of inflammation, comparing the two colon segments in the different experimental groups were studied. Intestinal crypt length, muscle layer thickness of the mucosa, submucosa and muscularis propria and caliciform cells were measured by computer-assisted imaging method. Mean equality, variance analysis and correlation tests were used in the statistical analysis, and the significance level was set at 5%. RESULTS: Comparison between segments with and without transit showed that the latter presented reduced length of colon crypts and increased muscle layer thickness of the muscularis mucosa, submucosa and muscularis propria. There were greater quantities of ulceration of the mucosal and greater degree of inflammation with increasing time without transit. Mucosal ulceration, submucosal vascular congestion, increased thickness of the submucosal and muscularis propria layers, presence of caliciform cells, inflammatory infiltrate and inflamma

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

    Directory of Open Access Journals (Sweden)

    Hildebrand Falk

    2012-09-01

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

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

    Science.gov (United States)

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

    2014-07-01

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

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

    International Nuclear Information System (INIS)

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

    Energy Technology Data Exchange (ETDEWEB)

    Griessen, M.; Speich, P.V.; Infante, F.; Bartholdi, P.; Cochet, B.; Donath, A.; Courvoisier, B.; Bonjour, J.P.

    1989-03-01

    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.

  7. Evaluation of physicochemical properties and intestinal permeability of six dietary polyphenols in human intestinal colon adenocarcinoma Caco-2 cells.

    Science.gov (United States)

    Rastogi, Himanshu; Jana, Snehasis

    2016-02-01

    Phenolic compounds are common ingredients in many dietary supplements and functional foods. However, data concerning physicochemical properties and permeability of polyphenols on the intestinal epithelial cells are scarce. The aims of this study were to determine the experimental partition coefficient (Log P), and parallel artificial membrane permeability assay (PAMPA), to characterize the bi-directional transport of six phenolic compounds viz. caffeic acid, chrysin, gallic acid, quercetin, resveratrol and rutin in Caco-2 cells. The experimental Log P values of six polyphenols were correlated (R (2)=0.92) well with the calculated Log P values. The apparent permeability (P app) range of all polyphenols in PAMPA for the apical (AP) to basolateral (BL) was 1.180.05נ10(-6) to 5.900.16נ10(-6)cm/s. The apparent Caco-2 permeability (P app) range for the AP-BL was 0.960.03נ10(-6) to 3.800.45נ10(-6)cm/s. The efflux ratio of P app (BL?AP) to P app (AP?BL) for all phenolics was <2, suggesting greater permeability in the absorptive direction. Six compounds exhibited strong correlations between Log P and PAMPA/Caco-2 cell monolayer permeation data. Dietary six polyphenols were poorly absorbed through PAMPA and Caco-2 cells, and their transepithelial transports were mainly by passive diffusion. PMID:25351179

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

    OpenAIRE

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

    2012-01-01

    AIM: To establish a multiple detection method based on comparative polymerase chain reaction (cPCR) and ligase detection reaction (LDR)/ligase chain reaction (LCR) to quantify the intestinal bacterial components. METHODS: Comparative quantification of 16S rDNAs from different intestinal bacterial components was used to quantify multiple intestinal bacteria. The 16S rDNAs of different bacteria were amplified simultaneously by cPCR. The LDR/LCR was examined to actualize the genotyping and quant...

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

    OpenAIRE

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

    2005-01-01

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

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

    Science.gov (United States)

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

    2014-08-01

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

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

    Science.gov (United States)

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

    2014-03-01

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

  12. Evaluation by computerized morphometry of histopathological alterations of the colon wall in segments with and without intestinal transit in rats Avaliação por morfometria computadorizada das alterações histopatológicas da parede cólica em segmentos com e sem trânsito intestinal em ratos

    OpenAIRE

    Marcos Vieira de Sousa; Denise Gonçalves Priolli; Adriana Valim Portes; Izilda Aparecida Cardinalli; José Aires Pereira; Carlos Augusto Real Martinez

    2008-01-01

    PURPOSE: To evaluate histopathological alterations of the colon wall in segments with and without intestinal transit, by computer-assisted imaging, and to correlate these with the length of time diversion. METHODS: Thirty male Wistar rats were subjected to intestinal transit diversion by a proximal colostomy and distal mucosa fistula. The animals were divided into three experimental groups according to how long after the initial surgical procedure they were sacrificed: six, twelve and eightee...

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

    Directory of Open Access Journals (Sweden)

    Ping-Chang Yang

    2009-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Stacy R. Finkbeiner

    2015-06-01

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

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

    Science.gov (United States)

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

    2010-12-01

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

  16. 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. PMID:11252493

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

    Science.gov (United States)

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

    2009-01-01

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

  18. Intestinal parasitic infections and eosinophilia in an human immunedeficiency virus positive population in Honduras

    Directory of Open Access Journals (Sweden)

    Rina G Kaminsky

    2004-11-01

    Full Text Available The occurrence of intestinal parasites, their regional distribution and their relations to eosinophilia were studied in 133 human immunodeficiency virus (HIV positive individuals from Honduras. After signing an informed consent, participants answered a socio-demographic and risk factor questionnaire, a complete physical examination, medical history, and a series of laboratory tests. All participants were HIV positive but not acquired immunodeficiency syndrome positive. Of them, 67% were co-infected with pathogen and non pathogen parasites. Overall occurrence of nematodes was: 44.3% for Trichuris trichiura, 24% for Ascaris lumbricoides, 12% for Hookworm and 7.5% for Strongyloides stercoralis. No cases of Giardia lamblia, acute amebiasis or cryptosporidiasis were diagnosed. Mean eosinophil percents for participants were consistently and significantly higher in infected than in non infected individuals: 22% for Hookworm vs 7.2% (p < 0.001, 11% for Trichuris compared to 5.2% (p < 0.001, 13.2% compared to 7.5% for S. stercoralis (p < 0.05, and 12% compared to 6% for Ascaris cases (p < 0.05. Helminths and non pathogenic protozoa, as single or mixed infections, occurred among the participants. There was a strong correlation between eosinophilia and helminthiasis infections; however, none was identified between CD4 levels and eosinophilia. Because parasitic infections aggravate malnutrition and promote a disbalanced Th2 response in a potentially immuno-compromised host, their effect on HIV disease progression needs further study, mainly in countries were HIV and parasitic infections are highly prevalent.

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

    Science.gov (United States)

    Huguet, Antoine; Hatton, Aurélie; Villot, Romain; Quenault, Hélène; Blanchard, Yannick; Fessard, Valérie

    2014-01-01

    Cylindrospermopsin (CYN) is a cyanotoxin that has been recognised as an emerging potential public health risk. Although CYN toxicity has been demonstrated, the mechanisms involved have not been fully characterised. To identify some key pathways related to this toxicity, we studied the transcriptomic profile of human intestinal Caco-2 cells exposed to a sub-toxic concentration of CYN (1.6 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. PMID:24921660

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

    Science.gov (United States)

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

    1993-07-01

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

  1. Intestine Transplant

    Science.gov (United States)

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

  2. Capacity of Human Nisin- and Pediocin-Producing Lactic Acid Bacteria To Reduce Intestinal Colonization by Vancomycin-Resistant Enterococci?

    OpenAIRE

    Millette, Mathieu; Cornut, Gilbert; Dupont, Claude; Shareck, Franois; Archambault, Denis; Lacroix, Monique

    2008-01-01

    This study demonstrated the capacity of bacteriocin-producing lactic acid bacteria (LAB) to reduce intestinal colonization by vancomycin-resistant enterococci (VRE) in a mouse model. Lactococcus lactis MM19 and Pediococcus acidilactici MM33 are bacteriocin producers isolated from human feces. The bacteriocin secreted by P. acidilactici is identical to pediocin PA-1/AcH, while PCR analysis demonstrated that L. lactis harbors the nisin Z gene. LAB were acid and bile tolerant when assayed under ...

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

    OpenAIRE

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

    2014-01-01

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

  4. Isolation of Nitrofurantoin-Resistant Mutants of Nitroreductase-Producing Clostridium sp. Strains from the Human Intestinal Tract

    OpenAIRE

    Rafii, Fatemeh; Hansen, Eugene B.

    1998-01-01

    Five spontaneous nitrofurantoin-resistant mutants (one each of Clostridium leptum, Clostridium paraputrificum, two other Clostridium spp. strains from the human intestinal microflora, and Clostridium perfringens ATCC 3626) were selected by growth on a nitrofurantoin-containing medium. All of the Clostridium wild-type and mutant strains produced nitroreductase, as was shown by the conversion of 4-nitrobenzoic acid to 4-aminobenzoic acid. High-performance liquid chromatography (HPLC) analysis o...

  5. CD24 and CD44 mark human intestinal epithelial cell populations with characteristics of active and facultative stem cells

    OpenAIRE

    Gracz, Adam D; Fuller, Megan K.; Wang, FengChao; LI, LINHENG; Stelzner, Matthias; Dunn, James C.Y.; Martin, Martin G; Magness, Scott T.

    2013-01-01

    Recent seminal studies have rapidly advanced the understanding of intestinal epithelial stem cell (IESC) biology in murine models. However, the lack of techniques suitable for isolation and subsequent downstream analysis of IESCs from human tissue has hindered the application of these findings toward the development of novel diagnostics and therapies with direct clinical relevance. This study demonstrates that the cluster of differentiation genes CD24 and CD44 are differentially expressed acr...

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

    OpenAIRE

    Parsons-Wingerter, Patricia; Reinecker, Hans-Christian

    2012-01-01

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

  7. Extracellular Matrix-associated Cytokines Regulate CD4+ Effector T-cell Responses in Human Intestinal Mucosa

    Science.gov (United States)

    Huff, Kayci R.; Akhtar, Lisa Nowoslawski; Fox, Anna L.; Cannon, Jamie A.; Smith, Phillip D.; Smythies, Lesley E.

    2010-01-01

    Extracellular matrix (stroma) regulation of mucosal T-cell function is incompletely understood. Here we uncovered a role for intestinal stromal products in the innate regulation of effector T-cells. Stroma-conditioned media (S-CM) derived from normal human intestinal stroma (TGF-βhi/IL-6lo/IL-1βlo) significantly down-regulated T-cell proliferation and IFN-γ production compared to S-CM derived from inflamed Crohn’s mucosa (TGF-βhi/IL-6hi/IL-1βhi). Antibody neutralization studies showed that TGF-β in normal S-CM inhibited T-cell proliferation and IFN-γ production, whereas IL-6 plus IL-1β in Crohn’s S-CM promoted T-cell proliferation, and the IL-1β alone promoted IFN-γ and IL-17 release. Importantly, normal S-CM inhibited T-bet expression, whereas Crohn’s S-CM activated STAT3, suggesting that discordant T-cell responses are regulated at the transcription factor and signaling levels. These findings implicate stromal TGF-β in the down-regulation of T-cell responses in normal intestinal mucosa but stromal IL-6 and IL-1β in the promotion of Th1 and Th17 responses in inflamed Crohn’s mucosa, suggesting innate regulatory function for the intestinal extracellular matrix. PMID:21228771

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

    Science.gov (United States)

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

    2015-01-01

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Nakatsu Cindy H

    2010-05-01

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

  12. Perturbations in the human gut microbiome with antibiotic therapy and intestinal disorders

    OpenAIRE

    Panda, Suchita

    2015-01-01

    La microbiota intestinal es un factor determinante de la homeostasis intestinal, siendo por lo tanto un agente imprescindible del estado de salud. Su composicin podra estar alterada como consecuencia de factores externos tales como tratamientos con antibiticos o causada por enfermedades intestinales como el sndrome del intestino irritable (SII). Esta tesis doctoral se centr en la comprensin de la alteracin de esta ecologa microbiana con respecto a una terapia con antibiticos y la pre...

  13. Indirect evidence for cholinergic inhibition of intestinal bicarbonate absorption in humans

    OpenAIRE

    Mellander, A; Sjovall, H

    1999-01-01

    BACKGROUND—The aim of the study was to test the hypothesis that in the fasting state, proximal intestinal HCO3 absorption, which depends on villus Na+/H+ exchanger activity, is tonically inhibited by a cholinergic atropine sensitive mechanism. 
SUBJECTS—The experiments were performed in 34 healthy volunteers and in eight patients with intestinal villus atrophy. 
METHODS—HCO3 absorption was measured with a modified triple lumen perfusion technique in the distal duodenum,...

  14. Tolerance to cannabinoid response on the myenteric plexus of guinea-pig ileum and human small intestinal strips

    OpenAIRE

    Guagnini, Fabio; Cogliati, Paola; Mukenge, Sylvain; FERLA, GIANFRANCO; Croci, Tiziano

    2006-01-01

    We studied tolerance to cannabinoid agonist action by comparing the in vitro inhibition of electrically evoked contractions of longitudinal muscle from small intestine of human and guinea-pig (myenteric plexus preparations) after 48-h incubation with the synthetic agonist (+) WIN 55,212-2. We also investigated the intrinsic response to the selective cannabinoid CB1 receptor antagonist rimonabant in control and tolerant strips.(+) WIN 55,212-2 inhibited guinea-pig (IC50 4.8?nM) and human small...

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

    Directory of Open Access Journals (Sweden)

    Ricanek P

    2015-01-01

    Full Text Available Petr Ricanek,1,2 Lisa K Lunde,3 Stephan A Frye,1 Mari Støen,1 Ståle Nygård,4 Jens P Morth,5,6 Andreas Rydning,2 Morten H Vatn,7,8 Mahmood Amiry-Moghaddam,3 Tone Tønjum,1,9 1Department of Microbiology, Oslo University Hospital, Rikshospitalet, Oslo, 2Department of Gastroenterology, Akershus University Hospital, Lørenskog and Campus Ahus, Institute of Clinical Medicine, University of Oslo, Lørenskog, 3Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, 4Bioinformatics Core Facility, Institute for Medical Informatics, Oslo University Hospital and University of Oslo, 5Centre for Molecular Medicine, Nordic EMBL Partnership, University of Oslo, 6Institute for Experimental Research, Oslo University Hospital (Ullevaal, Oslo, 7EpiGen Institute, Campus Ahus, Institute of Clinical Medicine, University of Oslo, Lørenskog, 8Section of Gastroenterology, Oslo University Hospital, Rikshospitalet, Oslo, 9Department of Microbiology, University of Oslo, Oslo, Norway Objectives: The aim of this study was to investigate the relationship between aquaporin (AQP water channel expression and the pathological features of early untreated inflammatory bowel disease (IBD in humans. Methods: Patients suspected to have IBD on the basis of predefined symptoms, including abdominal pain, diarrhea, and/or blood in stool for more than 10 days, were examined at the local hospital. Colonoscopy with biopsies was performed and blood samples were taken. Patients who did not meet the diagnostic criteria for IBD and who displayed no evidence of infection or other pathology in the gut were included as symptomatic non-IBD controls. AQP1, 3, 4, 5, 7, 8, and 9 messenger RNA (mRNA levels were quantified in biopsies from the distal ileum and colon by quantitative real-time polymerase chain reaction. Protein expression of selected AQPs was assessed by confocal microscopy. Through multiple alignments of the deduced amino acid sequences, the putative three-dimensional structures of AQP1, 3, 7, and 8 were modeled. Results: AQP1, 3, 7, and 8 mRNAs were detected in all parts of the intestinal mucosa. Notably, AQP1 and AQP3 mRNA levels were reduced in the ileum of patients with Crohn's disease, and AQP7 and AQP8 mRNA levels were reduced in the ileum and the colon of patients with ulcerative colitis. Immunofluorescence confocal microscopy showed localization of AQP3, 7, and 8 at the mucosal epithelium, whereas the expression of AQP1 was mainly confined to the endothelial cells and erythrocytes. The reduction in the level of AQP3, 7, and 8 mRNA was confirmed by immunofluorescence, which also indicated a reduction of apical immunolabeling for AQP8 in the colonic surface epithelium and crypts of the IBD samples. This could indicate loss of epithelial polarity in IBD, leading to disrupted barrier function. Conclusion: AQPs 1 and 8 and the aquaglyceroporins AQPs 3 and 7 are the AQPs predominantly expressed in the lower intestinal tract of humans. Their expression is significantly reduced in patients with IBD, and they are differentially expressed in specific bowel segments in patients with Crohn's disease and ulcerative colitis. The data present a link between gut inflammation and water/solute homeostasis, suggesting that AQPs may play a significant role in IBD pathophysiology. Keywords: inflammatory bowel disease, Crohn's disease, ulcerative colitis, aquaporins, aquaglyceroporins

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

    International Nuclear Information System (INIS)

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

  17. Proteomic responses of human intestinal Caco-2 cells exposed to silver nanoparticles and ionic silver.

    Science.gov (United States)

    Oberemm, Axel; Hansen, Ulf; Böhmert, Linda; Meckert, Christine; Braeuning, Albert; Thünemann, Andreas F; Lampen, Alfonso

    2016-03-01

    Even although quite a number of studies have been performed so far to demonstrate nanoparticle-specific effects of substances in living systems, clear evidence of these effects is still under debate. The present study was designed as a comparative proteomic analysis of human intestinal cells exposed to a commercial silver nanoparticle reference material and ions from AgNO3 . A two-dimensional gel electrophoresis/MALDI mass spectrometry (MS)-based proteomic analysis was conducted after 24-h incubation of differentiated Caco-2 cells with non-cytotoxic and low cytotoxic silver concentrations (2.5 and 25 µg ml(-1) nanosilver, 0.5 and 5 µg ml(-1) AgNO3 ). Out of an overall number of 316 protein spots differentially expressed at a fold change of ≥ 1.4 or ≤ -1.4 in all treatments, 169 proteins could be identified. In total, 231 spots were specifically deregulated in particle-treated groups compared with 41 spots, which were limited to AgNO3 -treatments. Forty-four spots (14 %) were commonly deregulated by both types of treatment. A considerable fraction of the proteins differentially expressed after treatment with nanoparticles is related to protein folding, synthesis or modification of proteins as well as cellular assembly and organization. Overlays of networks obtained for particulate and ionic treatments showed matches, indicating common mechanisms of combined particle and ionic silver exposure and exclusive ionic silver treatment. However, proteomic responses of Caco-2 cells treated with higher concentrations of silver species also showed some differences, for example regarding proteins related to fatty acid and energy metabolism, suggesting an induction of also some different molecular mechanisms for particle exposure and ionic treatment. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26434666

  18. Predicting human intestinal absorption of diverse chemicals using ensemble learning based QSAR modeling approaches.

    Science.gov (United States)

    Basant, Nikita; Gupta, Shikha; Singh, Kunwar P

    2016-04-01

    Human intestinal absorption (HIA) of the drugs administered through the oral route constitutes an important criterion for the candidate molecules. The computational approach for predicting the HIA of molecules may potentiate the screening of new drugs. In this study, ensemble learning (EL) based qualitative and quantitative structure-activity relationship (SAR) models (gradient boosted tree, GBT and bagged decision tree, BDT) have been established for the binary classification and HIA prediction of the chemicals, using the selected molecular descriptors. The structural diversity of the chemicals and the nonlinear structure in the considered data were tested by the similarity index and Brock-Dechert-Scheinkman statistics. The external predictive power of the developed SAR models was evaluated through the internal and external validation procedures recommended in the literature. All the statistical criteria parameters derived for the performance of the constructed SAR models were above their respective thresholds suggesting for their robustness for future applications. In complete data, the qualitative SAR models rendered classification accuracy of >99%, while the quantitative SAR models yielded correlation (R(2)) of >0.91 between the measured and predicted HIA values. The performances of the EL-based SAR models were also compared with the linear models (linear discriminant analysis, LDA and multiple linear regression, MLR). The GBT and BDT SAR models performed better than the LDA and MLR methods. A comparison of our models with the previously reported QSARs for HIA prediction suggested for their better performance. The results suggest for the appropriateness of the developed SAR models to reliably predict the HIA of structurally diverse chemicals and can serve as useful tools for the initial screening of the molecules in the drug development process. PMID:26881740

  19. Role of PTHrP in human intestinal Caco-2 cell response to oxidative stress.

    Science.gov (United States)

    Lezcano, Virginia; Gentili, Claudia; de Boland, Ana Russo

    2013-12-01

    We have previously demonstrated that parathyroid hormone (PTH) induces apoptosis in human colon adenocarcinoma Caco-2 cells but the effects of its tumoral analog PTH-related peptide (PTHrP) in this cell line are still unknown. In the present work we investigated whether PTHrP, as PTH, is able to induce Caco-2 cell apoptosis or if it exerts protective effects under apoptotic conditions. Using Caco-2 cells cultured under serum deprivation in the presence or absence of PTHrP we demonstrated that, differently to PTH, its analog employed at the same concentration (10(-8)M) is not a pro-apoptotic hormone. Cells were exposed to an oxidative insult in the form of hydrogen peroxide to induce apoptosis, which leads to a 50% loss of cell viability determined by MTS assay, morphological changes observed under fluorescence microscopy and Western blot analysis. Herein we demonstrate, for the first time, that pre-treatment with PTHrP prior to H2O2 incubation, prevents cell death induced by the apoptotic inductor; and using specific inhibitors we evidenced that protein kinase B (AKT), extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase 1/2 (JNK1/2) and p38 mitogen-activated protein kinase (MAPK) mediate this anti-apoptotic effect. Also, we found that PTHrP decreases the pro-apoptotic protein BAX levels and increases the protein expression of the anti-apoptotic HSP27. Immunoblot analysis revealed that H2O2 increases the phosphorylation levels of AKT and MAPKs, exhibiting a cellular defense response; and consequently increases phospho-BAD levels. The H2O2-induced activation of protein kinases is reverted when cells are pre-treated with PTHrP. Altogether these results evidence a protective effect of PTHrP under apoptotic conditions in intestinal cells, which may be mediated by AKT and MAPKs. PMID:23845990

  20. Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium.

    Science.gov (United States)

    Derrien, Muriel; Vaughan, Elaine E; Plugge, Caroline M; de Vos, Willem M

    2004-09-01

    The diversity of mucin-degrading bacteria in the human intestine was investigated by combining culture and 16S rRNA-dependent approaches. A dominant bacterium, strain MucT, was isolated by dilution to extinction of faeces in anaerobic medium containing gastric mucin as the sole carbon and nitrogen source. A pure culture was obtained using the anaerobic soft agar technique. Strain MucT was a Gram-negative, strictly anaerobic, non-motile, non-spore-forming, oval-shaped bacterium that could grow singly and in pairs. When grown on mucin medium, cells produced a capsule and were found to aggregate. Strain MucT could grow on a limited number of sugars, including N-acetylglucosamine, N-acetylgalactosamine and glucose, but only when a protein source was provided and with a lower growth rate and final density than on mucin. The G + C content of DNA from strain MucT was 47.6 mol%. 16S rRNA gene sequence analysis revealed that the isolate was part of the division Verrucomicrobia. The closest described relative of strain MucT was Verrucomicrobium spinosum (92 % sequence similarity). Remarkably, the 16S rRNA gene sequence of strain MucT showed 99 % similarity to three uncultured colonic bacteria. According to the data obtained in this work, strain MucT represents a novel bacterium belonging to a new genus in subdivision 1 of the Verrucomicrobia; the name Akkermansia muciniphila gen. nov., sp. nov. is proposed; the type strain is MucT (= ATCC BAA-835T = CIP 107961T). PMID:15388697

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

    Directory of Open Access Journals (Sweden)

    Ma Miao

    2010-04-01

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

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

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Kyoung-Sik, Park

    2004-06-01

    Full Text Available This study was carried to identify the component of Small Intestine Meridian Muscle in human, dividing the regional muscle group into outer, middle, and inner layer. the inner part of body surface were opened widely to demonstrate muscles, nerve, blood vessels and the others, displaying the inner structure of Small Intestine Meridian Muscle. We obtained the results as follows; 1. Small Intestine Meridian Muscle is composed of the muscle, nerve and blood vessels. 2. In human anatomy, it is present the difference between a term of nerve or blood vessels which control the muscle of Meridian Muscle and those which pass near by Meridian Muscle. 3. The inner composition of meridian muscle in human arm is as follows ; 1 Muscle ; Abd. digiti minimi muscle(SI-2, 3, 4, pisometacarpal lig.(SI-4, ext. retinaculum. ext. carpi ulnaris m. tendon.(SI-5, 6, ulnar collateral lig.(SI-5, ext. digiti minimi m. tendon(SI-6, ext. carpi ulnaris(SI-7, triceps brachii(SI-9, teres major(SI-9, deltoid(SI-10, infraspinatus(SI-10, 11, trapezius(Sl-12, 13, 14, 15, supraspinatus(SI-12, 13, lesser rhomboid(SI-14, erector spinae(SI-14, 15, levator scapular(SI-15, sternocleidomastoid(SI-16, 17, splenius capitis(SI-16, semispinalis capitis(SI-16, digasuicus(SI-17, zygomaticus major(Il-18, masseter(SI-18, auriculoris anterior(SI-19 2 Nerve ; Dorsal branch of ulnar nerve(SI-1, 2, 3, 4, 5, 6, br. of mod. antebrachial cutaneous n.(SI-6, 7, br. of post. antebrachial cutaneous n.(SI-6,7, br. of radial n.(SI-7, ulnar n.(SI-8, br. of axillary n.(SI-9, radial n.(SI-9, subscapular n. br.(SI-9, cutaneous n. br. from C7, 8(SI-10, 14, suprascapular n.(SI-10, 11, 12, 13, intercostal n. br. from T2(SI-11, lat. supraclavicular n. br.(SI-12, intercostal n. br. from C8, T1(SI-12, accessory n. br.(SI-12, 13, 14, 15, 16, 17, intercostal n. br. from T1,2(SI-13, dorsal scapular n.(SI-14, 15, cutaneous n. br. from C6, C7(SI-15, transverse cervical n.(SI-16, lesser occipital n. & great auricular n. from cervical plexus(SI-16, cervical n. from C2,3(SI-16, fascial n. br.(SI-17, great auricular n. br.(SI-17, cervical n. br. from C2(SI-17, vagus n.(SI-17,hypoglossal n.(SI-17, glossopharyngeal n.(SI-17, sympathetic trunk(SI-17, zygomatic br. of fascial n.(SI-18, maxillary n. br.(SI-18, auriculotemporal n.(SI-19, temporal br. of fascial n.(SI-19 3 Blood vessels ; Dorsal digital vein.(SI-1, dorsal br. of proper palmar digital artery(SI-1, br. of dorsal metacarpal a. & v.(SI-2, 3, 4, dorsal carpal br. of ulnar a.(SI-4, 5, post. interosseous a. br.(SI-6,7, post. ulnar recurrent a.(SI-8, circuirflex scapular a.(SI-9, 11 , post. circumflex humeral a. br.(SI-10, suprascapular a.(SI-10, 11, 12, 13, first intercostal a. br.(SI-12, 14, transverse cervical a. br.(SI-12,13,14,15, second intercostal a. br.(SI-13, dorsal scapular a. br.(SI-13, 14, 15, ext. jugular v.(SI-16, 17, occipital a. br.(SI-16, Ext. jugular v. br.(SI-17, post. auricular a.(SI-17, int. jugular v.(SI-17, int. carotid a.(SI-17, transverse fascial a. & v.(SI-18,maxillary a. br.(SI-18, superficial temporal a. & v.(SI-19.

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

    Science.gov (United States)

    Parsons-Wingerter, Patricia; Reinecker, Hans-Christian

    2012-10-01

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

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

    Directory of Open Access Journals (Sweden)

    M. Rezaian

    1992-06-01

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

  6. 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

    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...

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

    Directory of Open Access Journals (Sweden)

    Sabir Sadiah

    2008-05-01

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

  8. Cloning and sequencing of human intestinal alkaline phosphatase cDNA

    International Nuclear Information System (INIS)

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

  9. The intestine is a blender

    Science.gov (United States)

    Yang, Patricia; Lamarca, Morgan; Hu, David

    2015-11-01

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

  10. 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)

    Grs, S; Ovesen, P; Andersen, A N; Srensen, Steen; Fahrenkrug, J; Ottesen, B

    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...... fluid and cells were obtained from patients undergoing in-vitro fertilization for tubal infertility. The concentrations of VIP and PHM in pre-ovulatory human follicular fluid were measured radioimmunochemically. Granulosa/lutein cells isolated from follicular fluid were cultured under serum....... We conclude that VIP and PHM are present in human preovulatory follicular fluid and that VIP stimulates DNA synthesis and oestradiol secretion in cultured human granulosa/lutein cells. This indicates that VIP and perhaps PHM participate in the local nervous regulation of human ovarian function....

  11. 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. PMID:19207729

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

    Directory of Open Access Journals (Sweden)

    Pierre-Jean Ferron

    2014-08-01

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

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

    OpenAIRE

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

    2005-01-01

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

  14. Interferon-alpha (IFN-alpha) production by human intestinal mononuclear cells. Response to virus in control subjects and in Crohn's disease.

    OpenAIRE

    Capobianchi, M. R.; Fais, S.; Mercuri, F.; Boirivant, M; Dianzani, F; PALLONE, F

    1992-01-01

    The virus induced production of interferon alpha by human intestinal lamina propria mononuclear cells was investigated. Intestinal and autologous peripheral cells from control subjects and patients with Crohn's disease were cultured in vitro with and without stimulation with the Newcastle disease virus. Interferon alpha was measured and characterised in the culture supernatants after 12 hours and the kinetics of production was evaluated over the following four days of culture. No detectable i...

  15. 1,25-Dihydroxyvitamin D3 increases the expression of the CaT1 epithelial calcium channel in the Caco-2 human intestinal cell line

    OpenAIRE

    Wood, Richard J.; Tchack, Laurie; Taparia, Shveta

    2001-01-01

    Background The active hormonal form of vitamin D (1,25-dihydroxyvitamin D) is the primary regulator of intestinal calcium absorption efficiency. In vitamin D deficiency, intestinal calcium absorption is low leading to an increased risk of developing negative calcium balance and bone loss. 1,25-dihydroxyvitamin D has been shown to stimulate calcium absorption in experimental animals and in human subjects. However, the molecular details of calcium transport across the enterocyte are not fully d...

  16. Monitoring of Antibiotic-Induced Alterations in the Human Intestinal Microflora and Detection of Probiotic Strains by Use of Terminal Restriction Fragment Length Polymorphism

    OpenAIRE

    Jernberg, Cecilia; Sullivan, Åsa; 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...

  17. EphB2 isolates a human marrow stromal cell subpopulation with enhanced ability to contribute to the resident intestinal cellular pool

    OpenAIRE

    Colletti, Evan; El Shabrawy, Deena; Soland, Melisa; Yamagami, Takashi; Mokhtari, Saloomeh; Osborne, Craig; Schlauch, Karen; Zanjani, Esmail D; Porada, Christopher D.; Almeida-Porada, Graça

    2013-01-01

    To identify human bone marrow stromal cell (BMSC) subsets with enhanced ability to engraft/contribute to the resident intestinal cellular pool, we transplanted clonally derived BMSCs into fetal sheep. Analysis at 75 d post-transplantation showed 2 of the 6 clones engrafting the intestine at 4- to 5-fold higher levels (5.03±0.089 and 5.04±0.15%, respectively) than the other clones (P

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

    Directory of Open Access Journals (Sweden)

    Babatunde S.K

    2014-03-01

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

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

    OpenAIRE

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

    2002-01-01

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

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

    Czech Academy of Sciences Publication Activity Database

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

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

  2. Formation of delta 2- and delta 3-cholenoic acids from bile acid 3-sulfates by a human intestinal Fusobacterium strain.

    OpenAIRE

    Robben, J; Janssen, G.; Merckx, R.; Eyssen, H.

    1989-01-01

    We isolated two strains of an unnamed Fusobacterium species from human intestinal microflora, which stereospecifically transformed bile acid 3-sulfates into C-3-unsubstituted, ring A-unsaturated bile acids. Both 3 alpha- and 3 beta-sulfates of 5 beta-bile acids were metabolized to delta 3-5 beta-cholenoic acids; 3 beta-sulfates of 5 alpha-bile acids were converted into a mixture of delta 2-5 alpha-bile acids and 3 alpha-hydroxy-5 alpha-bile acids, whereas 3 alpha-sulfates of 5 alpha-bile acid...

  3. Human Intestinal Lumen and Mucosa-Associated Microbiota in Patients with Colorectal Cancer

    Science.gov (United States)

    Ling, Zongxin; Tong, Xiaojuan; Xiang, Charlie

    2012-01-01

    Recent reports have suggested the involvement of gut microbiota in the progression of colorectal cancer (CRC). We utilized pyrosequencing based analysis of 16S rRNA genes to determine the overall structure of microbiota in patients with colorectal cancer and healthy controls; we investigated microbiota of the intestinal lumen, the cancerous tissue and matched noncancerous normal tissue. Moreover, we investigated the mucosa-adherent microbial composition using rectal swab samples because the structure of the tissue-adherent bacterial community is potentially altered following bowel cleansing. Our findings indicated that the microbial structure of the intestinal lumen and cancerous tissue differed significantly. Phylotypes that enhance energy harvest from diets or perform metabolic exchange with the host were more abundant in the lumen. There were more abundant Firmicutes and less abundant Bacteroidetes and Proteobacteria in lumen. The overall microbial structures of cancerous tissue and noncancerous tissue were similar; howerer the tumor microbiota exhibited lower diversity. The structures of the intestinal lumen microbiota and mucosa-adherent microbiota were different in CRC patients compared to matched microbiota in healthy individuals. Lactobacillales was enriched in cancerous tissue, whereas Faecalibacterium was reduced. In the mucosa-adherent microbiota, Bifidobacterium, Faecalibacterium, and Blautia were reduced in CRC patients, whereas Fusobacterium, Porphyromonas, Peptostreptococcus, and Mogibacterium were enriched. In the lumen, predominant phylotypes related to metabolic disorders or metabolic exchange with the host, Erysipelotrichaceae, Prevotellaceae, and Coriobacteriaceae were increased in cancer patients. Coupled with previous reports, these results suggest that the intestinal microbiota is associated with CRC risk and that intestinal lumen microflora potentially influence CRC risk via cometabolism or metabolic exchange with the host. However, mucosa-associated microbiota potentially affects CRC risk primarily through direct interaction with the host. PMID:22761885

  4. Human intestinal lumen and mucosa-associated microbiota in patients with colorectal cancer.

    Science.gov (United States)

    Chen, Weiguang; Liu, Fanlong; Ling, Zongxin; Tong, Xiaojuan; Xiang, Charlie

    2012-01-01

    Recent reports have suggested the involvement of gut microbiota in the progression of colorectal cancer (CRC). We utilized pyrosequencing based analysis of 16S rRNA genes to determine the overall structure of microbiota in patients with colorectal cancer and healthy controls; we investigated microbiota of the intestinal lumen, the cancerous tissue and matched noncancerous normal tissue. Moreover, we investigated the mucosa-adherent microbial composition using rectal swab samples because the structure of the tissue-adherent bacterial community is potentially altered following bowel cleansing. Our findings indicated that the microbial structure of the intestinal lumen and cancerous tissue differed significantly. Phylotypes that enhance energy harvest from diets or perform metabolic exchange with the host were more abundant in the lumen. There were more abundant Firmicutes and less abundant Bacteroidetes and Proteobacteria in lumen. The overall microbial structures of cancerous tissue and noncancerous tissue were similar; however the tumor microbiota exhibited lower diversity. The structures of the intestinal lumen microbiota and mucosa-adherent microbiota were different in CRC patients compared to matched microbiota in healthy individuals. Lactobacillales was enriched in cancerous tissue, whereas Faecalibacterium was reduced. In the mucosa-adherent microbiota, Bifidobacterium, Faecalibacterium, and Blautia were reduced in CRC patients, whereas Fusobacterium, Porphyromonas, Peptostreptococcus, and Mogibacterium were enriched. In the lumen, predominant phylotypes related to metabolic disorders or metabolic exchange with the host, Erysipelotrichaceae, Prevotellaceae, and Coriobacteriaceae were increased in cancer patients. Coupled with previous reports, these results suggest that the intestinal microbiota is associated with CRC risk and that intestinal lumen microflora potentially influence CRC risk via cometabolism or metabolic exchange with the host. However, mucosa-associated microbiota potentially affects CRC risk primarily through direct interaction with the host. PMID:22761885

  5. Inhibitory effects of extractives from leaves of Morus alba on human and rat small intestinal disaccharidase activity.

    Science.gov (United States)

    Oku, Tsuneyuki; Yamada, Mai; Nakamura, Mariko; Sadamori, Naoki; Nakamura, Sadako

    2006-05-01

    The inhibitory effect on human and rat intestinal disaccharidase by the extractive from the leaves of Morus alba (ELM) containing 0.24 % 1-deoxynojirimycin equivalent and its inhibitory activities were investigated by the modified Dahlqvist method. In the presence of 1000-fold diluted ELM solution, the sucrase activity of four human samples was inhibited by 96 % and that of maltase and isomaltase by 95 and 99 %, respectively. The activities of trehalase and lactase were inhibited by 44 and 38 %, respectively. The human disaccharidase activities varied from sample to sample because the samples were obtained from different resected regions after surgery. However, the ratio of the inhibitory effect for sucrase, maltase, isomaltase, trehalase and lactase was very similar among the four samples, and also that of resembled rat intestinal disaccharides. The inhibitory constant of the 1-deoxynojirimycin equivalent for sucrase, maltase and isomaltase was 2.1 x 10(-4), 2.5 x 10(-4) and 4.5 x 10(-4) mm, respectively, and these inhibitory activities were shown, using rat brush border membrane vesicles, to be competitive. These results demonstrate that digestion is inhibited when an appropriate amount of ELM is orally ingested with sucrose or polysaccharide in man. When ELM was orally administered in a sucrose solution to fasted rats, the elevation in blood glucose was significantly suppressed, depending on the concentration of ELM given. These results suggest that ELM could be used as an ingredient in health foods and in foods that help to prevent diabetes. PMID:16611383

  6. Intestinal Coccidia

    Directory of Open Access Journals (Sweden)

    MJ Ggaravi

    2007-06-01

    Full Text Available Intestinal Coccidia are a subclass of Apicomplexa phylum. Eucoccidida are facultative heteroxenous, but some of them are monoxenous. They have sexual and asexual life cycle. Some coccidia are human pathogens, for example: Cryptosporidium: Cryptosporidiums has many species that are mammalian intestinal parasites.C. Parvum specie is a human pathogenic protozoa. Cryptosporidum has circle or ellipse shapes and nearly 4-6 mm. It is transmitted in warm seasons. Oocyst is obtained insexual life cycle that has 20% thin layer and 80% thick layer. Oocyst with thick layer is able to live a long time in nature. They are the third or forth of gastroentritis disease that have digestive disorder like anorexia, nausea, persistent diarrhoea, malabsorption and leanness. The disease forms choronic and acute stages and it is able to kill the immunodeficiency cases. Sometimes it has HIV symptoms similar to pneumonia and respiratory track infection. Laboratory diagnosis is based on Oocyst finding in stool exam and that shitter floatation and Cr (KOH2 are the best methods. Modified zyh-lnelson and fleocroum are the best staining methods too. This parasite is transmitted by zoonotic and Antroponotic origin. Molecular studies have shown two Genotypes (I&II. Genotype I is aquatic and II is zoonotic. The prevalence rate is 3% in infants and 10% in calves. Cyclospora: This parasite is novel and is bigger than cryptosporidium.It isn't known a clear life cycle but is transmitted by water, vegetables and fruits as raspberries. and mulberries. Human is a specific host. When a parasite is in the intestine it causes inflammatory reaction in Entrocyte.The patient shows watery diarrhoea with nausea, vomitting, pain, Stomach cramp, anorexia, malabsorption and cachexia. The disease period is 3 monthes in immunodeficiency cases but it is selflimited in normal cases. Autofluorescence characteristic is differential diagnosis, prevalence rate of disease is unknown. Isospora: This intestinal parasite is in most parts of the world. Sometimes it is noun traveller diarrhea Syndrom. The egg shapes of Oocyst are disporic tetrazoic. It is transmitted by vegetables and fruits. Trophozoite pass through schizogony step and repeats it several times. In the end of the cycle gametogony is done and the sexual forms will be repelled the human intestine. Symptoms are persistent diarrhoea, epigastric pain, headache, fever, vomitting and leanness, especially when physiologic disorder condition is seen in patient or they are in traveling. Misdiagnosis is a problem in laboratories but floatation method with zinc sulfate or sugar syrup is recommended. Sarcocystis: Sporocyst of S.hominis and S. suihominis is in the human feces, and the cyst form is in pig and cow muscles. It founds in tha tongue, pharynx and oesophagus muscles of habitant buffalo in Iran. Because of the large size of the cyst (1cm, it is seen with naked eyes and the risk of human infection is rare. If human eats raw or uncooked cow and pig meat, he will be infected with it. Sexual cycle is in the human body and sporocyst is repelled by the intestine. The disease may or may not have any symptoms. The symptoms are diarrhoea, stomach cramp, jejenuom and ileum necrosis. Diagnosis is based on concentrated floatation. The prevalence rate is too much in domestic animals.

  7. Comparative analysis of family 1 cytochrome p-450 mRNA expression in human intestinal adenocarcinoma and intact portion of the intestine.

    Science.gov (United States)

    Evteev, V A; Barsukov, Ju A; Aliev, V I; Kobliakov, V A

    2008-08-01

    The expression of mRNA of proteins involved in the transformations of cytostatics (cytochrome P-450 1A1 and 1B1 isoforms) and genes encoding proteins participating in their regulation (Ah receptor, AHRR and ARNT) in intestinal tumors and intact portions of the intestine were studied. The expression of cytochrome P-450 1A1 increased in poorly differentiated tumors in comparison with its expression in intact portions of the intestine (tumor/intact tissue=1.65). The expression of cytochrome P-450 1B1 was higher in well-differentiated tumors (tumor/intact tissue=1.62). The possibility of practical use of high expression of cytochrome P-450 isoforms in tumors in comparison with intact intestinal tissue is discussed. PMID:19145330

  8. Nano- and microscaled particles for drug targeting to inflamed intestinal mucosa: a first in vivo study in human patients.

    Science.gov (United States)

    Schmidt, Carsten; Lautenschlaeger, Christian; Collnot, Eva-Maria; Schumann, Michael; Bojarski, Christian; Schulzke, Jrg-Dieter; Lehr, Claus-Michael; Stallmach, Andreas

    2013-01-28

    Most of the drugs used in the treatment of inflammatory bowel disease (IBD) become systemically bioavailable and potentially bear strong adverse effects. Targeting the inflamed areas of the intestine and keeping the drug localised at its site of action can reduce adverse effects. In animal studies, luminal uptake into inflamed mucosal areas has been shown to be size dependent. We investigated the potential of nano- and microparticle uptake into the rectal mucosa of human IBD patients. Fluorescently labelled placebo nanoparticles (NP) 250nm in size and microparticles (MP) 3.0?m in size were prepared. 2h after rectal application to patients with Crohn's disease (CD) or ulcerative colitis (UC), confocal laser endomicroscopy was performed to visualise the particles in inflamed mucosal areas. In biopsies, ex vivo mucosal transport processes were investigated in miniaturised Ussing chambers. We examined 33 patients with IBD (19 patients with CD, 14 patients with UC) and 6 healthy controls. A significantly enhanced accumulation of MP in ulcerous lesions was observed (covered area=1.28% (range 0.83%-3.45%) vs. 0% in controls; p=0.011), while NP were visible only in traces on mucosal surfaces of all patients. The Ussing chamber experiments suggest persorption of particles through cellular voids; statistical significance was only reached for NP. Drug-containing particles may have great potential to more specifically target intestinal lesions to maximise therapeutic efficacy and minimise potential side effects. Nanoparticles may not be required for local drug delivery to intestinal lesions in humans, thereby minimising the risk of unintended translocation into the blood system. PMID:23127508

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

    Science.gov (United States)

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

    2014-03-01

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

  10. 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

  11. Pressure and frequency dependent linkage between motility and epithelial secretion in human proximal small intestine

    OpenAIRE

    Mellander, A; Jarbur, K; Sjovall, H

    2000-01-01

    BACKGROUND—Motor disturbances are sometimes associated with diarrhoea by unknown mechanisms.
AIM—To determine if there is a quantitative link between intestinal motility and epithelial secretion.
SUBJECTS—Experiments were performed in 21 healthy volunteers and three patients with villus atrophy.
METHODS—Duodenal and jejunal motor activities were registered in the fasted state by open tip manometry. Secretion was measured directly by marker perfusion and indirectly by recording transmural pote...

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

    Science.gov (United States)

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

    2008-03-01

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

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

    OpenAIRE

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

    2001-01-01

    The concentration of fecal mucin and the adhesion of specific probiotics and their combinations in the intestinal mucus of infants during and after rotavirus diarrhea and in healthy children were determined. Mucus was prepared from fecal samples from 20 infants during and after rotavirus diarrhea and from 10 healthy age-matched children. Mucin concentration was determined, and the adhesion of five probiotics—Lactobacillus rhamnosus GG, Lactobacillus casei Shirota, Lactobacillus paracasei F19,...

  14. Metabolism of heme and bilirubin in rat and human small intestinal mucosa.

    OpenAIRE

    Hartmann, F.; Bissell, D. M.

    1982-01-01

    Formation of heme, bilirubin, and bilirubin conjugates has been examined in mucosal cells isolated from the rat upper small intestine. Intact, viable cells were prepared by enzymatic dissociation using a combined vascular and luminal perfusion and incubated with an isotopically labeled precursor, delta-amino-[2,3-3H]levulinic acid. Labeled heme and bile pigment were formed with kinetics similar to those exhibited by hepatocytes. Moreover, the newly formed bilirubin was converted rapidly to bo...

  15. Human Intestinal Lumen and Mucosa-Associated Microbiota in Patients with Colorectal Cancer

    OpenAIRE

    Chen, Weiguang; Liu, Fanlong; Ling, Zongxin; Tong, Xiaojuan; XIANG, CHARLIE

    2012-01-01

    Recent reports have suggested the involvement of gut microbiota in the progression of colorectal cancer (CRC). We utilized pyrosequencing based analysis of 16S rRNA genes to determine the overall structure of microbiota in patients with colorectal cancer and healthy controls; we investigated microbiota of the intestinal lumen, the cancerous tissue and matched noncancerous normal tissue. Moreover, we investigated the mucosa-adherent microbial composition using rectal swab samples because the s...

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

    OpenAIRE

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

    2013-01-01

    Objective: This investigation was undertaken to evaluate the prevalence of intestinal parasitosis in patient addressed to the hospital of Oran and to identify parasites causing this infection. Design: The survey was made on 1042 individuals, external and hospitalized, having between one month and 80 years old, addressed te H.U.C. of Oran. For every patient, an analysis of stool sample was done including direct and complementary methods. Results: The prevalence is about 19,96%. Adultes (71,15%...

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

    Directory of Open Access Journals (Sweden)

    Oshima Masanobu

    2009-12-01

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

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2013-12-11

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

  20. Phase transitions in human IgG solutions

    Science.gov (United States)

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

    2013-09-01

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

  1. 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; Licht, Tine Rask

    2006-01-01

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    1997-01-01

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

  6. Intestinal Stem Cells

    OpenAIRE

    Umar, Shahid

    2010-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

    Inflammatory bowel diseases (IBD) are chronic and relapsing inflammatory conditions of the gastrointestinal tract including Crohn's disease (CD) and ulcerative colitis (UC). Galectins, defined by shared consensus amino acid sequence and affinity for β-galactosides, are critical modulators of the inflammatory response. However, the relevance of the galectin network in the pathogenesis of human IBD has not yet been explored. Here, we analyzed the expression of relevant members of the galectin family in intestinal biopsies, and identified their contribution as novel mucosal markers in IBD. Colonic biopsies were obtained from 59 IBD patients (22 CD and 37 UC), 9 patients with gut rejection after transplantation, 8 adult celiac patients, and 32 non-IBD donors. Galectin mRNA expression was analyzed by RT-PCR and qPCR using specific primers for individual galectins. A linear discriminant analysis (LDA) was used to analyze galectin expression in individual intestinal samples. Expression of common mucosal-associated galectins (Gal-1, -3, -4, -9) is dysregulated in inflamed tissues of IBD patients compared with non-inflamed IBD or control samples. LDA discriminated between different inflammation grades in active IBD and showed that remission IBD samples were clusterized with control samples. Galectin profiling could not distinguish CD and UC. Furthermore, inflamed IBD was discriminated from inflamed tissue of rejected gut in transplanted patients and duodenum of celiac patients, which could not be distinguished from control duodenum samples. The integrative analysis of galectins discriminated IBD from other intestinal inflammatory conditions and could be used as potential mucosal biomarker. © 2016 BioFactors, 42(1):93-105, 2016. PMID:26891020

  8. Enhanced wound healing by recombinant Escherichia coli Nissle 1917 via human epidermal growth factor receptor in human intestinal epithelial cells: therapeutic implication using recombinant probiotics.

    Science.gov (United States)

    Choi, Hye Jin; Ahn, Jung Hoon; Park, Seong-Hwan; Do, Kee Hun; Kim, Juil; Moon, Yuseok

    2012-03-01

    The gastrointestinal mucosa has a remarkable ability to repair damage with the support of epidermal growth factor (EGF), which stimulates epithelial migration and proliferative reepithelialization. For the treatment of mucosal injuries, it is important to develop efficient methods for the localized delivery of mucoactive biotherapeutics. The basic idea in the present study came from the assumption that an intestinal probiotic vehicle can carry and deliver key recombinant medicinal proteins to the injured epithelial target in patients with intestinal ulcerative diseases, including inflammatory bowel disease. The study was focused on the use of the safe probiotic E. coli Nissle 1917, which was constructed to secrete human EGF in conjunction with the lipase ABC transporter recognition domain (LARD). Using the in vitro physically wounded monolayer model, ABC transporter-mediated EGF secretion by probiotic E. coli Nissle 1917 was demonstrated to enhance the wound-healing migration of human enterocytes. Moreover, the epithelial wound closure was dependent on EGF receptor-linked activation, which exclusively involved the subsequent signaling pathway of the mitogen-activated protein kinase kinase (MEK) extracellular-related kinases 1 and 2 (ERK1/2). In particular, the migrating frontier of the wounded edge displayed the strongest EGF receptor-linked signaling activation in the presence of the recombinant probiotic. The present study provides a basis for the clinical application of human recombinant biotherapeutics via an efficient, safe probiotic vehicle. PMID:22184415

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

    Science.gov (United States)

    Barrera, Girolamo J; Sánchez, Gabriela

    2016-08-01

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

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

    Science.gov (United States)

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

    2010-09-01

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

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

    International Nuclear Information System (INIS)

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

  12. 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.

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    OpenAIRE

    Hildebrand Falk; Ebersbach Tine; Nielsen Henrik; Li Xiaoping; Sonne Si; Bertalan Marcelo; Dimitrov Peter; Madsen Lise; Qin Junjie; Wang Jun; Raes Jeroen; Kristiansen Karsten; Licht Tine

    2012-01-01

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

  18. 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 damage. Therefore, Q40P/S47I/H93G is pharmacologically one of the most promising candidates for clinical applications for radiation-induced gastrointestinal syndrome.

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

    OpenAIRE

    Cibele Barreto Mano de Carvalho; Jos Luciano Bezerra Moreira; Maria Candida S. Ferreira

    1996-01-01

    Epidemiological aspects and the antimicrobial susceptibility profile of the Bacteroides fragilis group isolated from clinical and human intestinal specimens were examined in this study. B. fragilis group strains were isolated from 46 (37%) of 124 clinical specimens and the source of the samples was: Blood culture (3), intraabdominal infection (27), brain abscess (2), soft tissue infection (17), respiratory sinus (3), pleural aspirate (9), breast abscess (3), surgical infected wound (22), pelv...

  20. Differentially expressed genes related with injury of human intestinal epithelium cell by ?-ray

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    A. Benouis

    2013-04-01

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

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

    Science.gov (United States)

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

    2016-04-01

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

  3. Urban transitions: on urban resilience and human-dominated ecosystems.

    Science.gov (United States)

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

    2010-12-01

    Urbanization is a global multidimensional process paired with increasing uncertainty due to climate change, migration of people, and changes in the capacity to sustain ecosystem services. This article lays a foundation for discussing transitions in urban governance, which enable cities to navigate change, build capacity to withstand shocks, and use experimentation and innovation in face of uncertainty. Using the three concrete case cities--New Orleans, Cape Town, and Phoenix--the article analyzes thresholds and cross-scale interactions, and expands the scale at which urban resilience has been discussed by integrating the idea from geography that cities form part of "system of cities" (i.e., they cannot be seen as single entities). Based on this, the article argues that urban governance need to harness social networks of urban innovation to sustain ecosystem services, while nurturing discourses that situate the city as part of regional ecosystems. The article broadens the discussion on urban resilience while challenging resilience theory when addressing human-dominated ecosystems. Practical examples of harnessing urban innovation are presented, paired with an agenda for research and policy. PMID:21141773

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

    Science.gov (United States)

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

    2016-05-01

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

  5. The Lactobacillus and Bifidobacterium microflora of the human intestine: composition and succession.

    Science.gov (United States)

    Reuter, G

    2001-09-01

    Lactobacillus and bifidobacterial cultures are increasingly used as probiotics in pharmaceuticals and in foods. The selection of strains is performed often for technological rather than for microecological reasons. Detailed reports about species and strains composition of these microorganisms in the intestinal microflora of man are rare. Our investigations were performed with samples originating from infants and adults, taken from faeces and from upper sections of the intestinal tract including mouth and stomach, and from caecum and colon. Post mortem cases as well as test subjects under physiological conditions were analyzed using an automatic capsule system sampling at defined times in different parts of the intestinal tract. The fate of selected strains after oral intake was studied, too. Furthermore, influences of the microflora originating from food were considered. The identification of autochthonous (indigenous) and allochthonous (transient) species could be achieved with descriptions of new species in the genera Lactobacillus and Bifidobacterium. L. gasseri and L. reuteri proved to be predominant autochthonous Lactobacillus species in infants as well as in adults. Both species were occasionally present even in the stomach. This was also the case with an anaerobic lactic acid bacterium, previously named Catenabacterium catenaforme, later classified as L. ruminis, a non-motile variant of this species. The bifidobacterial microflora differed in composition between infants and adults and in different stages of the host's life. Up to 5 species or special strains of bifidobacteria could be present in different, individually fixed, combinations. Species typical for infants were B. bifidum, B. infantis, B. breve, and B. parvulorum. Typical for adults were 4 different variants of B. adolescentis. B. bifidum and B. longum could often be found in both groups, but in lower numbers. B. longum showed some oxygen tolerance whereas B. bifidum and B. adolescentis required strict anaerobic and fastidious conditions for cultivation. The autochthonous Lactobacillus and Bifidobacterium microflora in man will remain stable life-long. With lactobacilli, however, some successions may be caused by transient species derived from food or from the oral cavity, thus giving the impression of an altered microflora. Nevertheless L. gasseri, L. reuteri, L. ruminis, and to some degree, L. salivarius, may be present as autochthonous species all of the time. With bifidobacteria, a decreasing tendency in counts and in multiple composition in elderly people exists. Furthermore, this microflora is also influenced by consumption habits, which are probably caused by geographical circumstances. PMID:11721280

  6. 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; Ouwehand, A; Hansen, Egon Bech; Romero, D A; Rautonen, N

    2010-01-01

    comparative analysis of the global in vitro transcriptional response of human intestinal epithelial cells to Lactobacillus acidophilus NCFM™, Lactobacillus salivarius Ls-33, Bifidobacterium animalis subsp. lactis 420, and enterohaemorrhagic Escherichia coli O157:H7 (EHEC). Interestingly, L. salivarius Ls-33...... DCE-induced changes were overall more similar to those of B. lactis 420 than to L. acidophilus NCFM™, which is consistent with previously observed in vivo immunomodulation properties. In the gene ontology and pathway analyses both specific and unspecific changes were observed. Common to all was the...... regulation of apoptosis and adipogenesis, and lipid-metabolism related regulation by the probiotics. Specific changes such as regulation of cell-cell adhesion by B. lactis 420, superoxide metabolism by L. salivarius Ls-33, and regulation of MAPK pathway by L. acidophilus NCFM™ were noted. Furthermore...

  7. Release of small phenolic compounds from brewer's spent grain and its lignin fractions by human intestinal microbiota in vitro.

    Science.gov (United States)

    Aura, Anna-Marja; Niemi, Piritta; Mattila, Ismo; Niemel, Klaus; Smeds, Annika; Tamminen, Tarja; Faulds, Craig; Buchert, Johanna; Poutanen, Kaisa

    2013-10-01

    Brewer's spent grain (BSG), the major side-stream from brewing, is rich in protein, lignin, and nonstarch polysaccharides. Lignin is a polyphenolic macromolecule considered resilient toward breakdown and utilization by colon microbiota, although some indications of release of small phenolic components from lignin in animals have been shown. The aim of this study was to investigate if the human intestinal microbiota can release lignans and small phenolic compounds from whole BSG, a lignin-enriched insoluble fraction from BSG and a deferuloylated fraction, in a metabolic in vitro colon model. The formation of short-chain fatty acid (SCFA) was also investigated. More lignin-related monomers and dilignols were detected from the lignin-enriched fraction than from BSG or deferuloylated BSG. SCFA formation was not suppressed by any of the fractions. It was shown that small lignin-like compounds were released from these samples in the in vitro colon model, originating most likely from lignin. PMID:24028071

  8. Endometriosis intestinal / Intestinal endometriosis

    Scientific Electronic Library Online (English)

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

    2008-08-01

    Full Text Available La endometriosis es un trastorno ginecolgico crnico, benigno y frecuente entre las mujeres en edad frtil, estimndose que existe algn grado de endometriosis hasta en el 15% de las mujeres premenopusicas, asocindose a historia de infertilidad, antecedente de cesrea, dismenorrea y anormalidad e [...] n el sangrado uterino. Se cree que es debida al ascenso por las trompas de Falopio de contenido menstrual (menstruacin retrgrada). En la afectacin intestinal, el colon es el segmento ms frecuentemente afectado, sobre todo a nivel rectosigmodeo. La clnica de presentacin es inespecfica, siendo lo ms frecuente el dolor abdominal y/o plvico de tipo clico que coincide o se exacerba con la menstruacin. El diagnstico diferencial incluye la enfermedad inflamatoria intestinal, diverticulitis, colitis isqumica y procesos neoplsicos, siendo el diagnstico definitivo anatomopatolgico. En cuanto al tratamiento, ste depender de la clnica y de la edad de la paciente, as como de sus deseos de embarazo. Abstract in english Endometriosis is a chronic, benign gynaecological disorder that is frequent in women of a child-bearing age. It is estimated that there is some degree of endometriosis in as many as 15% of pre-menopausal women, associated with a history of infertility, caesarean antecedents, dysmenorrhoea and abnorm [...] ality in uterine bleeding. It is believed to be due to the rise of menstrual contents through the Fallopian tubes (retrograde menstruation). In the intestinal affectation, the colon is the segment most frequently affected, above all at the rectosigmoidal level. The clinical features are unspecific, with abdominal pain the most frequent and/or pelvic pain of a cholic type that coincides with, or is exacerbated by, menstruation. Differential diagnosis includes intestinal inflammatory disease, diverticulitis, ischemic colitis and neoplastic processes, with the definitive diagnosis being anatomopathological. With respect to treatment, this will depend on the clinical features and the age of the patient, as well as her wishes with regard to pregnancy.

  9. Evidencing the "robot phase transition" in experimental human-algorithmic markets

    OpenAIRE

    Cartlidge, John; Cliff, Dave

    2013-01-01

    Johnson, Zhao, Hunsader, Meng, Ravindar, Carran, and Tivnan (2012) recently suggested the existence of a phase transition in the dynamics of financial markets in which there is free interaction between human traders and algorithmic trading systems ("robots"). Above a particular time-threshold, humans and robots trade with one another; below the threshold all transactions are robot-to-robot. We refer to this abrupt system transition as the "robot phase transition". Here, we conduct controlled ...

  10. Carriage of intestinal spirochaetes by humans: epidemiological data from Western Australia.

    Science.gov (United States)

    Brook, C J; Clair, A N; Mikosza, A S; Riley, T V; Hampson, D J

    2001-10-01

    The purpose of this study was to investigate carriage of intestinal spirochaetes by selected population groups in Western Australia. Stool specimens from 293 rural patients with gastrointestinal disorders, and from 227 healthy migrants from developing countries were cultured. Spirochaete isolates were identified using PCR, and typed by pulsed field gel electrophoresis (PFGE). Brachyspira aalborgi was not isolated. Brachyspira pilosicoli was recovered from 15 rural patients, all Aboriginal. Prevalence was 9.9% in 151 Aboriginals and 0% in 142 non-Aboriginals. Carriage of B. pilosicoli amongst migrants was 10.6% (24/227). Carriage was significantly increased in Aboriginal children aged 2-5 years (P = 0.0027) and in migrant individuals from the Middle East and Africa (P = 0.0034). Carriage was significantly associated with detection of faecal protozoa in both Aboriginals (P = 0.0021) and migrants (P = 0.012). PFGE results indicated that the B. pilosicoli strains were genetically diverse. PMID:11693517

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

    DEFF Research Database (Denmark)

    Bergström, Anders; Wilcks, Andrea; Ravn-Haren, Gitte; Dragsted, Lars O.; Markowski, J; Licht, Tine Rask

    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...... restriction diet during the control period, and in the four other periods it was supplied with four different apple based supplements. Between the diets there was a 2-week wash-out period still on the restriction diet. The four apple based supplements were: 1) whole apples, 2) clear apple juice (pectin......-free), 3) cloudy juice (apple juice with pulp), and 4) pomace (press cake from the cloudy juice production process). Fecal samples were taken before and after each diet period. After DNA extraction, Denaturing Gradient Gel Electrophoresis (DGGE) with universal primers and specific primers for...

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

    DEFF Research Database (Denmark)

    Bergström, Anders; Wilcks, Andrea; Ravn-Haren, Gitte; Dragsted, Lars O.; Markowski, J; Licht, Tine Rask

    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...... restriction diet during the control period, and in the four other periods it was supplied with four different apple based supplements. Between the diets there was a 2-week wash-out period still on the restriction diet. The four apple based supplements were: 1) whole apples, 2) clear apple juice (pectin......-free), 3) cloudy juice (apple juice with pulp), and 4) pomace (press cake from the cloudy juice production process). Fecal samples were taken before and after each diet period. After DNA extraction, Denaturing Gradient Gel Electrophoresis (DGGE) with universal primers and specific primers for...

  13. 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, Jrg

    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. PMID:20615381

  14. METABOLISM OF 1-NITROPYRENE BY HUMAN, RAT, AND MOUSE INTESTINAL FLORA: NYTAGENICITY OF ISOLATED METABOLITES BY DIRECT ANALYSIS OF HPLC FRACTIONS WITH A MICROSUSPENSION REVERSE MUTATION ASSAY

    Science.gov (United States)

    Among the nitro-substituted polycyclic aromatic hydrocarbons identified in environmental samples and known to be genotoxic, 1-nitropyrene is one of the most abundant. he biotransformation of 1-nitro[14C]pyrene by human, rat, and mouse intestinal microflora and the mutagenicity of...

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

    Scientific Electronic Library Online (English)

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

    2010-09-01

    Full Text Available RACIONAL: A reconstruo do trnsito intestinal no est isenta de riscos cirrgicos e apresenta taxas considerveis de complicaes ps-operatrias, sendo que a infeco continua a ser um dos maiores desafios existentes neste procedimento. OBJETIVO: Perfil epidemiolgico e morbimortalidade dos paci [...] entes submetidos reconstruo de trnsito intestinal. MTODOS: Foram analisados retrospectivamente 86 pronturios de pacientes com colostomia ou ileostomia, atravs de fatores que tivessem impacto sobre a morbimortalidade aps a reconstruo de trnsito intestinal, de janeiro de 2003 a abril de 2009. RESULTADOS: Houve 20 mulheres e 60 homens, com idade mdia de 43 anos. A colostomia em ala (n=34) e o trauma abdominal indicando colostomia ou ileostomia foram as condies mais frequentes. O intervalo mdio entre a confeco do estoma e a reconstruo de trnsito intestinal foi 15,7 meses. O ndice de morbidade foi 56,8%, sendo a infeco incisional a complicao mais comum (27.47%). A permanncia hospitalar mdia foi 7,6 dias. Houve regresso linear positiva entre permanncia hospitalar ps-operatria e a idade do paciente. Demonstrou-se associao estatisticamente significativa entre o prolongamento da permanncia hospitalar e a ocorrncia de complicaes (p Abstract in english BACKGROUND: The reconstruction of the intestinal tract is not surgical complications risk-free and is associated to postoperative complications high rates; furthermore, infection remains the hardest challenge in this procedure. AIM: Epidemiological profile and mortality and morbidity in patients und [...] ergoing reconstruction of intestinal transit. METHODS: Retrospectively, 86 patients with intestinal stomas were analyzed through factors that impact on the morbimortality afterwards intestinal transit reconstruction, since January 2003 to April 2009. RESULTS: Loop colostomy (n=34) and abdominal trauma implicating 38.2% of indications to colostomy or ileostomy, were the most frequent conditions. The mean interval between stoma confection and intestinal transit reconstruction was 15.7 months. The morbidity frequency was 56.8% and incisional infection was its commonest complication (27.47%). The mean inpatient length of stay was 7.6 days. There was positive linear regression between post-operative inpatient length of stay and inpatient's age. Inpatient length of stay prolongation is associated to occurrence of complications (p

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

    Science.gov (United States)

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

    2015-09-01

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

  17. Actin reorganization is involved in vasoactive intestinal peptide induced human mast cells priming to fraktalkine-induced chemotaxis

    Directory of Open Access Journals (Sweden)

    Amr E El-Shazly

    2008-08-01

    Full Text Available Amr E El-ShazlyDepartment of Oto-Rhino-Laryngology and Head and Neck Surgery, Liege University Hospital (Centre hospitalier Universaitaire-C.H.U., Liege, BelgiumAbstract: We recently reported a novel neuro-immuno co-operation between vasoactive intestinal peptide (VIP and fraktalkine (FKN in recruiting human mast cells to the asthmatic airway that provided a classical example of priming effect on mast cells migratory function, but the role of the F-actin in human mast cell chemotaxis’ priming is poorly defined. Therefore the aim of this study was to further investigate the biophysical role of the cytoskeletal element; the F-actin, intracellular reorganization and its polymerization in mast cell priming of chemotaxis function. In the present communication it is shown by immunofluoresence confocal microscopy analysis that physical F-actin intracellular reorganization in a membrane bound manner on uman mast cell is involved in VIP-induced priming of human mast cell chemotaxis against FKN. The F-actin reorganization was calcium independent and without modifi cation of its contents as assessed by fluorescence-activated cell scanning analysis. These results identify a novel role for the biophysical association of F-actin in the crosstalk between neuro-inflammatory mediators and mast cells and may be an important target for therapeutic modalities in allergic inflammation.Keywords: mast cells, chemotaxis, neuroimmuno-axis, F-actin intracellular reorganization, VIP, priming

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

    Science.gov (United States)

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

    2014-08-01

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

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

    Science.gov (United States)

    Li, Jihong; McClane, Bruce A

    2014-11-01

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

  20. 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.

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

    Science.gov (United States)

    Lahti, Leo; Salonen, Anne; Kekkonen, Riina A; Salojärvi, Jarkko; Jalanka-Tuovinen, Jonna; Palva, Airi; Orešič, Matej; de Vos, Willem M

    2013-01-01

    Accumulating evidence indicates that the intestinal microbiota regulates our physiology and metabolism. Bacteria marketed as probiotics confer health benefits that may arise from their ability to affect the microbiota. Here high-throughput screening of the intestinal microbiota was carried out and integrated with serum lipidomic profiling data to study the impact of probiotic intervention on the intestinal ecosystem, and to explore the associations between the intestinal bacteria and serum lipids. We performed a comprehensive intestinal microbiota analysis using a phylogenetic microarray before and after Lactobacillus rhamnosus GG intervention. While a specific increase in the L. rhamnosus-related bacteria was observed during the intervention, no other changes in the composition or stability of the microbiota were detected. After the intervention, lactobacilli returned to their initial levels. As previously reported, also the serum lipid profiles remained unaltered during the intervention. Based on a high-resolution microbiota analysis, intake of L. rhamnosus GG did not modify the composition of the intestinal ecosystem in healthy adults, indicating that probiotics confer their health effects by other mechanisms. The most prevailing association between the gut microbiota and lipid profiles was a strong positive correlation between uncultured phylotypes of Ruminococcus gnavus-group and polyunsaturated serum triglycerides of dietary origin. Moreover, a positive correlation was detected between serum cholesterol and Collinsella (Coriobacteriaceae). These associations identified with the spectrometric lipidome profiling were corroborated by enzymatically determined cholesterol and triglyceride levels. Actinomycetaceae correlated negatively with triglycerides of highly unsaturated fatty acids while a set of Proteobacteria showed negative correlation with ether phosphatidylcholines. Our results suggest that several members of the Firmicutes, Actinobacteria and Proteobacteria may be involved in the metabolism of dietary and endogenous lipids, and provide a scientific rationale for further human studies to explore the role of intestinal microbes in host lipid metabolism. PMID:23638368

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

    Directory of Open Access Journals (Sweden)

    Leo Lahti

    2013-02-01

    Full Text Available Accumulating evidence indicates that the intestinal microbiota regulates our physiology and metabolism. Bacteria marketed as probiotics confer health benefits that may arise from their ability to affect the microbiota. Here high-throughput screening of the intestinal microbiota was carried out and integrated with serum lipidomic profiling data to study the impact of probiotic intervention on the intestinal ecosystem, and to explore the associations between the intestinal bacteria and serum lipids. We performed a comprehensive intestinal microbiota analysis using a phylogenetic microarray before and after Lactobacillus rhamnosus GG intervention. While a specific increase in the L. rhamnosus-related bacteria was observed during the intervention, no other changes in the composition or stability of the microbiota were detected. After the intervention, lactobacilli returned to their initial levels. As previously reported, also the serum lipid profiles remained unaltered during the intervention. Based on a high-resolution microbiota analysis, intake of L. rhamnosus GG did not modify the composition of the intestinal ecosystem in healthy adults, indicating that probiotics confer their health effects by other mechanisms. The most prevailing association between the gut microbiota and lipid profiles was a strong positive correlation between uncultured phylotypes of Ruminococcus gnavus-group and polyunsaturated serum triglycerides of dietary origin. Moreover, a positive correlation was detected between serum cholesterol and Collinsella (Coriobacteriaceae. These associations identified with the spectrometric lipidome profiling were corroborated by enzymatically determined cholesterol and triglyceride levels. Actinomycetaceae correlated negatively with triglycerides of highly unsaturated fatty acids while a set of Proteobacteria showed negative correlation with ether phosphatidylcholines. Our results suggest that several members of the Firmicutes, Actinobacteria and Proteobacteria may be involved in the metabolism of dietary and endogenous lipids, and provide a scientific rationale for further human studies to explore the role of intestinal microbes in host lipid metabolism.

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

  4. How institutions shaped the last major evolutionary transition to large-scale human societies.

    OpenAIRE

    Powers S.T.; van Schaik C.P.; Lehmann L.

    2016-01-01

    What drove the transition from small-scale human societies centred on kinship and personal exchange, to large-scale societies comprising cooperation and division of labour among untold numbers of unrelated individuals? We propose that the unique human capacity to negotiate institutional rules that coordinate social actions was a key driver of this transition. By creating institutions, humans have been able to move from the default 'Hobbesian' rules of the 'game of life', determined by physica...

  5. The impact of in vitro digestion on bioaccessibility of polyphenols from potatoes and sweet potatoes and their influence on iron absorption by human intestinal cells.

    Science.gov (United States)

    Miranda, Lisa; Deußer, Hannah; Evers, Danièle

    2013-11-01

    The composition of potatoes as determined by chemical extraction has been described extensively. It is thus quite well known that, among other compounds, potato is rich in polyphenols, vitamins and in some minerals. This paper underlines the important role of simulated gastro-intestinal in vitro digestion in the bioaccessibility of polyphenols (chlorogenic acid and derivatives, and rutin) from potatoes and sweet potatoes and their impact on iron uptake. Concentrations of polyphenols in the flesh of two potato cultivars (Nicola, white potato, and Vitelotte, purple potato) and sweet potato were measured by Ultra Performance Liquid Chromatography after boiling and after in vitro digestion. Chemical extraction underestimates polyphenol amounts that can be released during digestion and that are actually bioaccessible. Iron uptake, as evaluated by a ferritin assay, by intestinal human cells was decreased after incubation with the intestinal phase of in vitro digestion, presumably due to the presence of polyphenols. PMID:24056541

  6. Microencapsulation of Probiotics by Calcium Alginate-gelatinized Starch with Chitosan Coating and Evaluation of Survival in Simulated Human Gastro-intestinal Condition.

    Science.gov (United States)

    Khosravi Zanjani, Mohammad Ali; Ghiassi Tarzi, Babak; Sharifan, Anousheh; Mohammadi, Nima

    2014-01-01

    Microencapsulation as one of the most modern methods has considerable effects on probiotic survival. In this study Lactobacillus casei (ATCC 39392) and Bifidobacterium bifidum (ATCC 29521) were encapsulated using calcium alginate-gelatinized starch, chitosan coating and inulin via emulsion technique, and were incubated in simulated gastric juice (along with pepsin, pH=1.5) and simulated intestinal juice (along with pancreatin and bile salts, pH = 8) for 2 hours at 37 (o)C. The morphology and size of microcapsules were measured by scanning electron and optical microscopy. The results indicated that the survival of microencapsulated probiotic increased significantly in simulated gastro-intestinal condition (P microencapsulation with alginate-gelatinized starch coated with chitosan could successfully and significantly protect probiotic bacteria against adverse condition of simulated human gastro-intestinal condition. PMID:25276184

  7. Microbial diversity in the human intestine and novel insights from metagenomics

    OpenAIRE

    Ventura, Marco; Turroni, Francesca; Canchaya, Carlos; Vaughan, Elaine E.; O'Toole, Paul W; van Sinderen, Douwe

    2009-01-01

    Bacterial communities reside in very different ecological niches on and within the human host, such as those associated with the alimentary tract. The human gastrointestinal tract is populated with as many as 100 trillion bacterial cells, whose collective genome likely reflects the co-evolution between the microbial community and its host. Recent progress has highlighted the intriguing diversity of these bacterial populations and their important contributions to human physiology. Thus, a thor...

  8. Endometriosis intestinal Intestinal endometriosis

    Directory of Open Access Journals (Sweden)

    C.I. González

    2008-08-01

    Full Text Available La endometriosis es un trastorno ginecológico crónico, benigno y frecuente entre las mujeres en edad fértil, estimándose que existe algún grado de endometriosis hasta en el 15% de las mujeres premenopáusicas, asociándose a historia de infertilidad, antecedente de cesárea, dismenorrea y anormalidad en el sangrado uterino. Se cree que es debida al ascenso por las trompas de Falopio de contenido menstrual (menstruación retrógrada. En la afectación intestinal, el colon es el segmento más frecuentemente afectado, sobre todo a nivel rectosigmodeo. La clínica de presentación es inespecífica, siendo lo más frecuente el dolor abdominal y/o pélvico de tipo cólico que coincide o se exacerba con la menstruación. El diagnóstico diferencial incluye la enfermedad inflamatoria intestinal, diverticulitis, colitis isquémica y procesos neoplásicos, siendo el diagnóstico definitivo anatomopatológico. En cuanto al tratamiento, éste dependerá de la clínica y de la edad de la paciente, así como de sus deseos de embarazo.Endometriosis is a chronic, benign gynaecological disorder that is frequent in women of a child-bearing age. It is estimated that there is some degree of endometriosis in as many as 15% of pre-menopausal women, associated with a history of infertility, caesarean antecedents, dysmenorrhoea and abnormality in uterine bleeding. It is believed to be due to the rise of menstrual contents through the Fallopian tubes (retrograde menstruation. In the intestinal affectation, the colon is the segment most frequently affected, above all at the rectosigmoidal level. The clinical features are unspecific, with abdominal pain the most frequent and/or pelvic pain of a cholic type that coincides with, or is exacerbated by, menstruation. Differential diagnosis includes intestinal inflammatory disease, diverticulitis, ischemic colitis and neoplastic processes, with the definitive diagnosis being anatomopathological. With respect to treatment, this will depend on the clinical features and the age of the patient, as well as her wishes with regard to pregnancy.

  9. Human intestinal epithelial cells secrete interleukin-1 receptor antagonist and interleukin-8 but not interleukin-1 or interleukin-6

    Science.gov (United States)

    Daig, R; Rogler, G; Aschenbrenner, E; Vogl, D; Falk, W; Gross, V; Scholmerich, J; Andus, T

    2000-01-01

    BACKGROUNDThere is growing evidence that intestinal epithelial cells (IECs) are involved in the mucosal immune system.?AIMTo assess the pattern of cytokines secreted by IECs and lamina propria mononuclear cells (LPMNCs). To achieve this, the expression and secretion of interleukin (IL)-1, IL-1 receptor antagonist (IL-1ra), IL-6, and IL-8 in human primary colonic and ileal IECs and LPMNCs from the same patient were studied.?METHODSIECs and LPMNCs were isolated from surgical specimens or endoscopic biopsy samples. mRNA expression was investigated by northern blot analysis. Secretion of IL-1?, IL-6, IL-8, and IL-1ra was measured by enzyme linked immunosorbent assay.?RESULTSIL-1ra mRNA levels were higher in IECs than in LPMNCs in all probands. IL-8 mRNA was only present in low amounts in the IECs from two controls. In none of the specimens were IL-1? and IL-6 mRNA present in IECs. Transcripts encoding IL-1?, IL-1ra, IL-6, and IL-8 were identified in LPMNC preparations of all specimens. IECs from normal mucosa produced no detectable amounts of IL-1? or IL-6, whereas LPMNCs did. IECs secreted some IL-8 (65(9) pg/105 cells) but significantly more was generated by LPMNCs (408(43) pg/105 cells, pulcerative colitis (r=0.76,p<0.0001, n=24).?CONCLUSIONSIECs from normal mucosa express and secrete IL-1ra and low amounts of IL-8, but no IL-1 or IL-6. In inflamed mucosa the secretion of IL-1ra by IECs is slightly increased but may be not sufficient to antagonise the greatly increased production of proinflammatory cytokines by LPMNCs and the IECs themselves.???Keywords: intestinal epithelial cells; lamina propria mononuclear cells; mucosa; cytokines; interleukin; immune system PMID:10673296

  10. PUMA-mediated intestinal epithelial apoptosis contributes to ulcerative colitis in humans and mice

    Science.gov (United States)

    Qiu, Wei; Wu, Bin; Wang, Xinwei; Buchanan, Monica E.; Regueiro, Miguel D.; Hartman, Douglas J.; Schoen, Robert E.; Yu, Jian; Zhang, Lin

    2011-01-01

    Intestinal epithelial cell (IEC) apoptosis contributes to the development of ulcerative colitis (UC), an inflammatory bowel disease (IBD) that affects the colon and rectum. Therapies that target the inflammatory cytokine TNF have been found to inhibit IEC apoptosis in patients with IBD, although the mechanism of IEC apoptosis remains unclear. We therefore investigated the role of p53-upregulated modulator of apoptosis (PUMA), a p53 target and proapoptotic BH3-only protein, in colitis and IEC apoptosis, using patient samples and mouse models of UC. In UC patient samples, PUMA expression was elevated in colitis tissues relative to that in uninvolved tissues, and the degree of elevation of PUMA expression correlated with the severity of colitis and the degree of apoptosis induction. In mice, PUMA was markedly induced in colonic epithelial cells following induction of colitis by either dextran sulfate sodium salt (DSS) or 2,4,6-trinitrobenzene sulfonic acid (TNBS). The induction of PUMA was p53-independent but required NF-?B. Absence of PUMA, but neither absence of p53 nor that of another BH3-only protein (Bid), relieved DSS- and TNBS-induced colitis and inhibited IEC apoptosis. Furthermore, treating mice with infliximab (Remicade), a clinically used TNF-specific antibody, suppressed DSS- and TNBS-induced PUMA expression and colitis. These results indicate that PUMA induction contributes to the pathogenesis of colitis by promoting IEC apoptosis and suggest that PUMA inhibition may be an effective strategy to promote mucosal healing in patients with UC. PMID:21490394

  11. Quantitation of human MAO A and B in liver, intestine and placenta: Reassessment of activity

    International Nuclear Information System (INIS)

    Monoamine oxidases (MAO) oxidize a variety of exogenous and endogenous amines including neurotransmitters such as serotonin, dopamine and norepinephrine as well as the potent dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP). The two forms of MAO (A and B) differ in molecular weight and inhibitor selectivity, and are differentially expressed in the nervous system and many other tissues. Although some substrates are preferentially oxidized by one form of MAO, substrates that can be oxidized by only one MAO form have not been reported. How well each MAO oxidizes various substrates has not been thoroughly characterized because of difficulties in separating and quantitating MAO A and B active sites. By immunoblotting SDS-polyacrylamide gels of mitochondrial extracts with monoclonal antibodies specific for each form of MAO, MAO B protein was detected in intestine and placenta, tissues that have been reported to contain MAO A activity. An improved procedure was developed for quantitating the ratio and amounts of MAO A and B active sites, using the ligand [3H]-pargyline to label MAO and specific monoclonal antibodies to separate MAO A from B. Data from liver, placenta and platelets were used to re-evaluate the molecular activity of both MAO A and B for six commonly studied substrates

  12. 1,25-Dihydroxyvitamin D3 increases the expression of the CaT1 epithelial calcium channel in the Caco-2 human intestinal cell line

    Directory of Open Access Journals (Sweden)

    Taparia Shveta

    2001-08-01

    Full Text Available Abstract Background The active hormonal form of vitamin D (1,25-dihydroxyvitamin D is the primary regulator of intestinal calcium absorption efficiency. In vitamin D deficiency, intestinal calcium absorption is low leading to an increased risk of developing negative calcium balance and bone loss. 1,25-dihydroxyvitamin D has been shown to stimulate calcium absorption in experimental animals and in human subjects. However, the molecular details of calcium transport across the enterocyte are not fully defined. Recently, two novel epithelial calcium channels (CaT1/ECaC2 and ECaC1/CaT2 have been cloned and suggested to be important in regulating intestinal calcium absorption. However, to date neither gene has been shown to be regulated by vitamin D status. We have previously shown that 1,25-dihydroxyvitamin stimulates transcellular calcium transport in Caco-2 cells, a human intestinal cell line. Results In the current study, we have demonstrated that Caco-2 cells express low but detectable levels of CaT1 mRNA in the absence of 1,25-dihydroxyvitamin D treatment. CaT1 mRNA expression is rapidly up regulated (4-fold increase at 4 h and 10-fold at 24 h by treatment with 1,25-dihydroxyvitamin D (10-7 moles/L. Moreover, the increase in CaT1 mRNA expression preceded by several hours the vitamin D induction of calbindin D9K, a putative cytosolic calcium transport protein. Conclusion These observations are the first to demonstrate regulation of CaT1 expression by vitamin D and are consistent with a new model of intestinal calcium absorption wherein vitamin D-mediated changes in brush border membrane CaT1 levels could be the primary gatekeeper regulating homeostatic modulation of intestinal calcium absorption efficiency.

  13. Chip-based human liver-intestine and liver-skin co-cultures--A first step toward systemic repeated dose substance testing in vitro.

    Science.gov (United States)

    Maschmeyer, Ilka; Hasenberg, Tobias; Jaenicke, Annika; Lindner, Marcus; Lorenz, Alexandra Katharina; Zech, Julie; Garbe, Leif-Alexander; Sonntag, Frank; Hayden, Patrick; Ayehunie, Seyoum; Lauster, Roland; Marx, Uwe; Materne, Eva-Maria

    2015-09-01

    Systemic repeated dose safety assessment and systemic efficacy evaluation of substances are currently carried out on laboratory animals and in humans due to the lack of predictive alternatives. Relevant international regulations, such as OECD and ICH guidelines, demand long-term testing and oral, dermal, inhalation, and systemic exposure routes for such evaluations. So-called "human-on-a-chip" concepts are aiming to replace respective animals and humans in substance evaluation with miniaturized functional human organisms. The major technical hurdle toward success in this field is the life-like combination of human barrier organ models, such as intestine, lung or skin, with parenchymal organ equivalents, such as liver, at the smallest biologically acceptable scale. Here, we report on a reproducible homeostatic long-term co-culture of human liver equivalents with either a reconstructed human intestinal barrier model or a human skin biopsy applying a microphysiological system. We used a multi-organ chip (MOC) platform, which provides pulsatile fluid flow within physiological ranges at low media-to-tissue ratios. The MOC supports submerse cultivation of an intact intestinal barrier model and an air-liquid interface for the skin model during their co-culture with the liver equivalents respectively at (1)/100.000 the scale of their human counterparts in vivo. To increase the degree of organismal emulation, microfluidic channels of the liver-skin co-culture could be successfully covered with human endothelial cells, thus mimicking human vasculature, for the first time. Finally, exposure routes emulating oral and systemic administration in humans have been qualified by applying a repeated dose administration of a model substance - troglitazone - to the chip-based co-cultures. PMID:25857839

  14. Differential Regulation of TLR Signaling on the Induction of Antiviral Interferons in Human Intestinal Epithelial Cells Infected with Enterovirus 71.

    Science.gov (United States)

    Wang, Chunyang; Ji, Lianfu; Yuan, Xinhui; Jin, Yu; Cardona, Carol J; Xing, Zheng

    2016-01-01

    Enterovirus 71 (EV71) causes hand-foot-and-mouth disease, which can lead to fatal neurological complications in young children and infants. Few gastrointestinal symptoms are observed clinically, suggesting the presence of a unique immunity to EV71 in the gut. We reported a robust induction of interferons (IFNs) in human intestinal epithelial cells (HT-29), which was suppressed in other types such as RD and HeLa cells. The underlying mechanism for the apparent difference remains obscure. In this study we report that in EV71-infected HT-29 cells, TLR/TRIF signaling was essential to IFN induction; viral replication increased and the induction of IFN-α, -β, -ω, -κ, and -ε decreased markedly in TRIF-silenced HT-29 cells. Importantly, TRIF was degraded by viral 3Cpro in RD cells, but resisted cleavage, and IRF3 was activated and translocated into the nucleus in HT-29 cells. Taken together, our data suggest that IFNs were induced differentially in human HT-29 cells through an intact TLR/TRIF signaling, which differs from other cell types and may be implicated in viral pathogenesis in EV71 infection. PMID:27007979

  15. Localization of receptors for vasoactive intestinal peptide, somatostatin, and substance P in distinct compartments of human lymphoid organs.

    Science.gov (United States)

    Reubi, J C; Horisberger, U; Kappeler, A; Laissue, J A

    1998-07-01

    Regulatory peptides, such as vasoactive intestinal peptide (VIP), somatostatin (SS), or substance P (SP), are considered to play a role in immune regulation. To localize the targets of these peptides in the human immune system, their receptors have been evaluated with in vitro receptor autoradiography in lymph nodes, tonsils, appendix, Peyer's patches, spleen, and thymus. The three peptide receptors were detected in all lymphoid tissues tested, but, unexpectedly, usually in distinct compartments. In lymph nodes, palatine tonsils, vermiform appendix, and Peyer's patches, VIP receptors were found in the CD3 positive zone around lymphoid follicles; SS receptors in the germinal centers of secondary follicles; and SP receptors mainly in interfollicular blood vessels. In the spleen, VIP receptors were detected in periarterial lymphatic sheaths, SS receptors in the red pulp, and SP receptors in the central arteries. In the thymus, VIP receptors were present in cortex and medulla, SS receptors in the medulla, and SP receptors in blood vessels. For comparison, cholecystokinin (CCK)-A and -B receptors were not demonstrated in any of these tissues. These results suggest a strong compartmentalization of the three peptide receptors in human lymphoid tissues and represent the molecular basis for the understanding of a very complex and interactive mode of action of these peptides. PMID:9639516

  16. Differential Regulation of TLR Signaling on the Induction of Antiviral Interferons in Human Intestinal Epithelial Cells Infected with Enterovirus 71

    Science.gov (United States)

    Wang, Chunyang; Ji, Lianfu; Yuan, Xinhui; Jin, Yu; Cardona, Carol J.; Xing, Zheng

    2016-01-01

    Enterovirus 71 (EV71) causes hand-foot-and-mouth disease, which can lead to fatal neurological complications in young children and infants. Few gastrointestinal symptoms are observed clinically, suggesting the presence of a unique immunity to EV71 in the gut. We reported a robust induction of interferons (IFNs) in human intestinal epithelial cells (HT-29), which was suppressed in other types such as RD and HeLa cells. The underlying mechanism for the apparent difference remains obscure. In this study we report that in EV71-infected HT-29 cells, TLR/TRIF signaling was essential to IFN induction; viral replication increased and the induction of IFN-α, -β, -ω, -κ, and -ε decreased markedly in TRIF-silenced HT-29 cells. Importantly, TRIF was degraded by viral 3Cpro in RD cells, but resisted cleavage, and IRF3 was activated and translocated into the nucleus in HT-29 cells. Taken together, our data suggest that IFNs were induced differentially in human HT-29 cells through an intact TLR/TRIF signaling, which differs from other cell types and may be implicated in viral pathogenesis in EV71 infection. PMID:27007979

  17. Adherence of probiotic bacteria to human intestinal mucus in healthy infants and during rotavirus infection.

    Science.gov (United States)

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

    2001-03-01

    The concentration of fecal mucin and the adhesion of specific probiotics and their combinations in the intestinal mucus of infants during and after rotavirus diarrhea and in healthy children were determined. Mucus was prepared from fecal samples from 20 infants during and after rotavirus diarrhea and from 10 healthy age-matched children. Mucin concentration was determined, and the adhesion of five probiotics-Lactobacillus rhamnosus GG, Lactobacillus casei Shirota, Lactobacillus paracasei F19, Lactobacillus acidophilus LA5, and Bifidobacterium lactis Bb12-and their combinations was tested in vitro. The mean concentrations of fecal mucin during and after rotavirus diarrhea, 15.2 and 14.1 mg/g, were comparable to that in healthy children, 14.9 mg/g. The adherence of probiotics ranged from 1 to 34% in healthy subjects as indicated for the following strains: L. rhamnosus GG, 34%; B. lactis Bb12, 31%; L. acidophilus LA5, 4%; L. paracasei F19, 3%; and L. casei Shirota, 1% (P = 0.0001). The distinctive pattern of probiotic adherence was not influenced by rotavirus diarrhea. The adhesion of Bb12 in the presence of GG increased from 31 to 39% in healthy infants (P = 0.018) and in episodes of diarrhea increased from 26 to 44% (P = 0.001). Rotavirus diarrhea does not decrease the production of fecal mucin or with respect to the adhesion of probiotic bacteria tested in vitro. Combination of specific probiotic strains may enhance adherence in a synergistic manner. Optimal clinical application of these interactions may offer novel therapeutic guidelines for the treatment and prevention of gastrointestinal infections. PMID:11238211

  18. Coated capsules for drug targeting to proximal and distal part of human intestine.

    Science.gov (United States)

    Dvorácková, Katerina; Rabisková, Miloslava; Gajdziok, Jan; Vetchý, David; Muselík, Jan; Bernatoniene, Jurga; Bajerová, Martina; Drottnerová, Pavlína

    2010-01-01

    Coated hard capsules are becoming increasingly important for a number of reasons such as administration of new active ingredients, oral vaccination, colon drug delivery or their use in preclinical and clinical trials. The independency of coating composition on capsules filling is the major advantage of this dosage form. In our study, two types of hard capsules (gelatin and hypromellose) were coated by non-aqueous solutions of Eudragit L and S 12.5, respectively, to achieve intestinal and distal ileic drug delivery. Gelatin hard capsules were coated with Eudragit film either directly or using hydroxypropyl cellulose sub-coating prior to the final coating. Hypromellose capsules were coated directly. Coated capsules were evaluated for coating thickness by optical microscope and for dissolution in different pH media. Gelatin capsules do not seem to be suitable for direct coating with Eudragit due to insufficient film adhesion to the smooth capsule surface and a brittleness of formed films. These problems can be solved by hydroxypropyl celullose interlayer application. Hypromellose hard capsules could be directly easily coated with both Eudragit solutions. Dissolution of caffeine from coated capsules showed the potency for enteric delivery in gelatin capsules with interlayer and Eudragit L film in 7.5 and 10.0% concentrations and in hypromellose capsules coated with EudragitL in 5-17.5% coating levels. Gelatine capsules with interlayer and 10% Eudragit S film and hypromellose capsules only with high coating level (20%) provided potential distal ileum targeting of incorporated drug. Eudragit S film sprayed onto hypromellose capsules surface was brittle especially in the junction zone between capsule cap and body. Better plasticity of Eudragit S coating could be probably achieved using a different plasticizer. PMID:20369797

  19. Understanding the human dimensions of a sustainable energy transition

    OpenAIRE

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

    2015-01-01

    Global climate change threatens the health, economic prospects, and basic food and water sources of people. A wide range of changes in household energy behavior is needed to realize a sustainable energy transition. We propose a general framework to understand and encourage sustainable energy behaviors, comprising four key issues. First, we need to identify which behaviors need to be changed. A sustainable energy transition involves changes in a wide range of energy behaviors, including the ad...

  20. 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; Raffin-Sanson, Marie-Laure; Varro, Andrea; Dockray, Graham J; Holst, Jens Juul; Brubaker, Patricia L; Corvol, Pierre; Polonsky, Kenneth S; Ostrega, Diane; Becker, Kenneth L; Bertagna, Xavier; Hutton, John C; White, Anne; Dattani, Mehul T; Hussain, Khalid; Middleton, Stephen J; Nicole, Thomasina M; Milla, Peter J; Lindley, Keith J; O'Rahilly, Stephen

    2003-01-01

    We have previously described the only reported case of human proprotein convertase 1 (PC1) deficiency, in a female (Subject A) with obesity, hypogonadism, hypoadrenalism, and reactive hypoglycemia. We now report the second case of human PC1 deficiency (Subject B), also due to compound heterozygos...... markedly with the phenotype of mice lacking PC1 and suggest that the precise physiological repertoire of this enzyme may vary between mammalian species....

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

    Directory of Open Access Journals (Sweden)

    Song Q

    2014-05-01

    Full Text Available Qinxin Song,13 Danhui Li,3 Yongzhi Zhou,3 Jie Yang,1 Wanqi Yang,1 Guohua Zhou,2 Jingyuan Wen31Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, School of Pharmacy, China Pharmaceutical University, 2Department of Pharmacology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Peoples Republic of China; 3School of Pharmacy, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New ZealandAbstract: The aim of this study was to evaluate (+-catechin and (?-epigallocatechin gallate (EGCG cellular uptake and transport across human intestinal Caco-2 cell monolayer in both the absence and presence of niosomal carrier in variable conditions. The effect of free drugs and drug-loaded niosomes on the growth of Caco-2 cells was studied. The effects of time, temperature, and concentration on drug cellular uptake in the absence or presence of its niosomal delivery systems were investigated. The intestinal epithelial membrane transport of the drug-loaded niosomes was examined using the monolayer of the human Caco-2 cells. The kinetics of transport, and the effect of temperature, adenosine triphosphate inhibitor, permeability glycoprotein inhibitor, multidrug resistance-associated protein 2 inhibitor, and the absorption enhancer on transport mechanism were investigated. It was found that the uptake of catechin, EGCG, and their niosomes by Caco-2 cells was 1.220.16, 0.900.14, 3.250.37, and 1.920.22 g/mg protein, respectively (n=3. The apparent permeability coefficient values of catechin, EGCG, and their niosomes were 1.680.16, 0.880.09, 2.390.31, and 1.420.24 cm/second (n=3 at 37C, respectively. The transport was temperature- and energy-dependent. The inhibitors of permeability glycoprotein and multidrug resistance-associated protein 2 and the absorption enhancer significantly enhanced the uptake amount. Compared with the free drugs, niosomal formulation significantly enhanced drug absorption. Additionally, drug-loaded niosomes exhibited stronger stability and lower toxicity. These findings showed that the oral absorption of tea flavonoids could be improved by using the novel drug delivery systems.Keywords: niosomes, formulation, bioavailability, stability

  2. Recognition of human activity characteristics based on state transitions modeling technique

    Science.gov (United States)

    Elangovan, Vinayak; Shirkhodaie, Amir

    2012-06-01

    Human Activity Discovery & Recognition (HADR) is a complex, diverse and challenging task but yet an active area of ongoing research in the Department of Defense. By detecting, tracking, and characterizing cohesive Human interactional activity patterns, potential threats can be identified which can significantly improve situation awareness, particularly, in Persistent Surveillance Systems (PSS). Understanding the nature of such dynamic activities, inevitably involves interpretation of a collection of spatiotemporally correlated activities with respect to a known context. In this paper, we present a State Transition model for recognizing the characteristics of human activities with a link to a prior contextbased ontology. Modeling the state transitions between successive evidential events determines the activities' temperament. The proposed state transition model poses six categories of state transitions including: Human state transitions of Object handling, Visibility, Entity-entity relation, Human Postures, Human Kinematics and Distance to Target. The proposed state transition model generates semantic annotations describing the human interactional activities via a technique called Casual Event State Inference (CESI). The proposed approach uses a low cost kinect depth camera for indoor and normal optical camera for outdoor monitoring activities. Experimental results are presented here to demonstrate the effectiveness and efficiency of the proposed technique.

  3. Up-regulating the human intestinal microbiome using whole plant foods, polyphenols, and/or fiber.

    Science.gov (United States)

    Tuohy, Kieran M; Conterno, Lorenza; Gasperotti, Mattia; Viola, Roberto

    2012-09-12

    Whole plant foods, including fruit, vegetables, and whole grain cereals, protect against chronic human diseases such as heart disease and cancer, with fiber and polyphenols thought to contribute significantly. These bioactive food components interact with the gut microbiota, with gut bacteria modifying polyphenol bioavailability and activity, and with fiber, constituting the main energy source for colonic fermentation. This paper discusses the consequences of increasing the consumption of whole plant foods on the gut microbiota and subsequent implications for human health. In humans, whole grain cereals can modify fecal bacterial profiles, increasing relative numbers of bifidobacteria and lactobacilli. Polyphenol-rich chocolate and certain fruits have also been shown to increase fecal bifidobacteria. The recent FLAVURS study provides novel information on the impact of high fruit and vegetable diets on the gut microbiota. Increasing whole plant food consumption appears to up-regulate beneficial commensal bacteria and may contribute toward the health effects of these foods. PMID:22607578

  4. Aloe vera non-decolorized whole leaf extract-induced large intestinal tumors in F344 rats share similar molecular pathways with human sporadic colorectal tumors.

    Science.gov (United States)

    Pandiri, Arun R; Sills, Robert C; Hoenerhoff, Mark J; Peddada, Shyamal D; Ton, Thai-Vu T; Hong, Hue-Hua L; Flake, Gordon P; Malarkey, David E; Olson, Greg R; Pogribny, Igor P; Walker, Nigel J; Boudreau, Mary D

    2011-12-01

    Aloe vera is one of the most commonly used botanicals for various prophylactic and therapeutic purposes. Recently, NTP/NCTR has demonstrated a dose-dependent increase in large intestinal tumors in F344 rats chronically exposed to Aloe barbadensis Miller (Aloe vera) non-decolorized whole leaf extract (AVNWLE) in drinking water. The morphological and molecular pathways of AVNWLE-induced large intestinal tumors in the F344 rats were compared to human colorectal cancer (hCRC) literature. Defined histological criteria were used to compare AVNWLE-induced large intestinal tumors with hCRC. The commonly mutated genes (Kras, Ctnnb1, and Tp53) and altered signaling pathways (MAPK, WNT, and TGF-β) important in hCRC were evaluated within AVNWLE-induced large intestinal tumors. Histological evaluation of the large intestinal tumors indicated eight of twelve adenomas (Ads) and four of twelve carcinomas (Cas). Mutation analysis of eight Ads and four Cas identified point mutations in exons 1 and 2 of the Kras gene (two of eight Ads, two of four Cas), and in exon 2 of the Ctnnb1 gene (three of eight Ads, one of four Cas). No Tp53 (exons 5-8) mutations were found in Ads or Cas. Molecular pathways important in hCRC such as MAPK, WNT, and TGF-β signaling were also altered in AVNWLE-induced Ads and Cas. In conclusion, the AVNWLE-induced large intestinal tumors in F344 rats share several similarities with hCRC at the morphological and molecular levels. PMID:21937742

  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; Raffin-Sanson, Marie-Laure; Varro, Andrea; Dockray, Graham J; Holst, Jens Juul; Brubaker, Patricia L; Corvol, Pierre; Polonsky, Kenneth S; Ostrega, Diane; Becker, Kenneth L; Bertagna, Xavier; Hutton, John C; White, Anne; Dattani, Mehul T; Hussain, Khalid; Middleton, Stephen J; Nicole, Thomasina M; Milla, Peter J; Lindley, Keith J; O'Rahilly, Stephen

    2003-01-01

    We have previously described the only reported case of human proprotein convertase 1 (PC1) deficiency, in a female (Subject A) with obesity, hypogonadism, hypoadrenalism, and reactive hypoglycemia. We now report the second case of human PC1 deficiency (Subject B), also due to compound...... 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...

  6. Transitions.

    Science.gov (United States)

    Field, David; And Others

    1992-01-01

    Includes four articles: "Career Aspirations" (Field); "Making the Transition to a New Curriculum" (Baker, Householder); "How about a 'Work to School' Transition?" (Glasberg); and "Technological Improvisation: Bringing CNC to Woodworking" (Charles, McDuffie). (SK)

  7. The Juvenile Transition: A Developmental Switch Point in Human Life History

    Science.gov (United States)

    Del Giudice, Marco; Angeleri, Romina; Manera, Valeria

    2009-01-01

    This paper presents a new perspective on the transition from early to middle childhood (i.e., human juvenility), investigated in an integrative evolutionary framework. Juvenility is a crucial life history stage, when social learning and interaction with peers become central developmental functions; here it is argued that the "juvenile transition"…

  8. The Juvenile Transition: A Developmental Switch Point in Human Life History

    Science.gov (United States)

    Del Giudice, Marco; Angeleri, Romina; Manera, Valeria

    2009-01-01

    This paper presents a new perspective on the transition from early to middle childhood (i.e., human juvenility), investigated in an integrative evolutionary framework. Juvenility is a crucial life history stage, when social learning and interaction with peers become central developmental functions; here it is argued that the "juvenile transition"

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

    OpenAIRE

    Tetens, Inge

    2011-01-01

    Following an application from Nordic Sugar A/S, submitted pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Denmark, the Panel on Dietetic Products, Nutrition and Allergies was asked to deliver an opinion on the scientific substantiation of a health claim based on newly developed scientific evidence related to sugar beet fibre and decreasing intestinal transit time. The food constituent that is the subject of the health claim is sugar beet fibre. This ...

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

    Science.gov (United States)

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

  11. Neolithic transitions: can genetic data help us understand a major demographic event in human prehistory?

    OpenAIRE

    Rasteiro, Rita

    2012-01-01

    The Neolithic transition is probably the most important cultural, economic and demographic revolution in human prehistory. It profoundly modified the distribution of human genes, languages and cultures worldwide. However, the study of the transition from hunting and gathering to farming societies has generated major controversies among archaeologists and geneticists alike, with one side favouring demic diffusion models and the other the cultural diffusion models. As a first ...

  12. Small intestinal bacterial overgrowth syndrome

    OpenAIRE

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

    2010-01-01

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

  13. Small intestinal bacterial overgrowth syndrome.

    OpenAIRE

    Bures, J.; Cyrany, J.; Kohoutova, D.; Förstl, M.; Rejchrt, S.; Kvetina, J.; Vorisek, V.; Kopacova, M.

    2010-01-01

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

  14. An experimental platform using human intestinal epithelial cell lines to differentiate between hazardous and non-hazardous proteins.

    Science.gov (United States)

    Hurley, Bryan P; Pirzai, Waheed; Eaton, Alex D; Harper, Marc; Roper, Jason; Zimmermann, Cindi; Ladics, Gregory S; Layton, Raymond J; Delaney, Bryan

    2016-06-01

    Human intestinal epithelial cell lines (T84, Caco-2, and HCT-8) grown on permeable Transwell™ filters serve as models of the gastrointestinal barrier. In this study, this in vitro model system was evaluated for effectiveness at distinguishing between hazardous and non-hazardous proteins. Indicators of cytotoxicity (LDH release, MTT conversion), monolayer barrier integrity ([(3)H]-inulin flux, horseradish peroxidase flux, trans-epithelial electrical resistance [TEER]), and inflammation (IL-8, IL-6 release) were monitored following exposure to hazardous or non-hazardous proteins. The hazardous proteins examined include streptolysin O (from Streptococcus pyogenes), Clostridium difficile Toxins A and B, heat-labile toxin from enterotoxigenic Escherichia coli, listeriolysin O (from Listeria monocytogenes), melittin (from bee venom), and mastoparan (from wasp venom). Non-hazardous proteins included bovine and porcine serum albumin, bovine fibronectin, and ribulose bisphosphate carboxylase/oxygenase (RuBisco) from spinach. Food allergenic proteins bovine milk β-lactoglobulin and peanut Ara h 2 were also tested as was the anti-nutritive food protein wheat germ agglutinin. Results demonstrated that this model system effectively distinguished between hazardous and non-hazardous proteins through combined analysis of multiple cells lines and assays. This experimental strategy may represent a useful adjunct to multi-component analysis of proteins with unknown hazard profiles. PMID:27060235

  15. Identification of Echinacoside Metabolites Produced by Human Intestinal Bacteria Using Ultraperformance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry.

    Science.gov (United States)

    Li, Yang; Zhou, Guisheng; Xing, Shihua; Tu, Pengfei; Li, Xiaobo

    2015-08-01

    Echinacoside (ECH) is one of the representative phenylethanoid glycosides. It is widely present in plants and exhibits various bioactivities. However, the extremely low oral bioavailability of ECH in rats implies that ECH may go through multiple hydrolysis steps in the gastrointestinal tract prior to its absorption into the blood. Therefore, the gastrointestinal metabolites of ECH are more likely to be the bioactive components. This study established an approach combining ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) with MS(E) technology and MetaboLynx software for rapid analysis of the ECH metabolic profile produced by human intestinal bacteria. As a result, 13 ECH metabolites and 5 possible metabolic pathways (including deglycosylation, dehydroxylation, reduction, hydroxylation, and acetylation) were identified. Furthermore, hydroxytyrosol (HT) and 3-hydroxyphenylpropionic acid (3-HPP) were found to be the two bioactive metabolites of ECH produced by human intestinal bacteria. PMID:26186273

  16. Purification, crystallization and diffraction studies of the methyltransferases BT-2972 and BVU-3255 from antibiotic-resistant pathogens of the genus Bacteroides from the human intestine

    International Nuclear Information System (INIS)

    The expression, purification, crystallization and diffraction of two methyltransferases BT-2972 and BVU-3255 from two Bacteroides species of antibiotic-resistant pathogens from the human intestine are reported. The methyltransferases BT-2972 and BVU-3255 from two different Bacteroides species that are antibiotic-resistant pathogens from the human intestine were cloned, overexpressed and purified, yielding approximately 120 mg of each protein from 1 l culture. Apo BT-2972 and BVU-3255 and their complexes with S-adenosylmethionine or S-adenosylhomocysteine were crystallized in four different crystal forms using the hanging-drop vapour-diffusion method. These crystals diffracted to resolutions ranging from 2.8 to 2.2 Å. Sequence analysis suggested that the two proteins are homologous small-molecule methyltransferases

  17. 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.; Boye, Mette

    2004-01-01

    Sequences of known 16S rRNA genes, derived from sequence analysis of cloned 16S rDNA, were used to design a specific oligonucleotide probe targeting spirochaetes of Brachyspira aalborgi lineages 2 and 3. The probe was used with fluorescent in situ hybridization to study the involvement of these...... 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 as...

  18. The ecology of social transitions in human evolution

    OpenAIRE

    Foley, Robert; Gamble, Clive

    2009-01-01

    We know that there are fundamental differences between humans and living apes, and also between living humans and their extinct relatives. It is also probably the case that the most significant and divergent of these differences relate to our social behaviour and its underlying cognition, as much as to fundamental differences in physiology, biochemistry or anatomy. In this paper, we first attempt to demarcate what are the principal differences between human and other societies in terms of soc...

  19. Human Pancreatic Secretory Trypsin Inhibitor Stabilizes Intestinal Mucosa against Noxious Agents

    OpenAIRE

    Marchbank, Tania; Mahmood, Asif; Fitzgerald, Anthony J.; Domin, Jan; Butler, Matt; Goodlad, Robert A; Elia, George; Cox, Helen M.; van Heel, David A; Ghosh, Subrata; Playford, Raymond J

    2007-01-01

    Pancreatic secretory trypsin inhibitor (PSTI) is a serine protease inhibitor, expressed in gut mucosa, whose function is unclear. We, therefore, examined the effects of PSTI on gut stability and repair. Transgenic mice overexpressing human PSTI within the jejunum (FABPi−1178 to +28 hPSTI construct) showed no change in baseline morphology or morphometry but reduced indomethacin-induced injury in overexpressing hPSTI region by 42% (P < 0.01). Systemic recombinant hPSTI did not affect baseline m...

  20. The genome of Bifidobacterium pseudocatenulatum IPLA 36007, a human intestinal strain with isoflavone-activation activity

    OpenAIRE

    Alegría, Ángel; Delgado, Susana; Guadamuro, Lucía; Flórez García, Ana Belén; Felis, Giovanna E.; Torriani, Sandra; Mayo Pérez, Baltasar

    2014-01-01

    Background Bifidobacterium species, including Bifidobacterium pseudocatenulatum, are among the dominant microbial populations of the human gastrointestinal tract. They are also major components of many commercial probiotic products. Resident and transient bifidobacteria are thought to have several beneficial health effects. However, our knowledge of how these bacteria interact and communicate with host cells remains poor. This knowledge is essential for scientific support of their purported h...

  1. First molecular identification of the zoonotic parasite Anisakis pegreffii (Nematoda: Anisakidae) in a paraffin-embedded granuloma taken from a case of human intestinal anisakiasis in Italy

    Science.gov (United States)

    2011-01-01

    Background Anisakiasis is an important fish-borne zoonosis provoked by larval stages of nematodes belonging to the genus Anisakis. The detection and identification of human infections is difficult. This is due to: a) the low specificity of the clinical features and symptomatology related to human infections; b) the paucity of diagnostic features of larvae found in granulomatous lesions characteristic of "invasive anisakiasis"; and c) the lack morphological characters diagnostic at the specific level when larvae of Anisakis are detected. Thus, molecular-based diagnostic approaches are warranted. Method We have developed a PCR method that amplifies the DNA of Anisakis spp. in fixed paraffin-embedded tissues. This method was applied to a granuloma removed from a human case of intestinal anisakiasis in Italy. Specific primers of the mtDNA cox2 gene were used and sequence analysis was performed according to the procedures already established for species of Anisakis. Results The sequence obtained (629 bp) was compared with those of the other species of Anisakis which have so far been genetically characterized and with sequences obtained from larval stages of Anisakis collected from the Mediterranean fish Engraulis encrasicolus. This enabled the genetic identification of the larva in the human tissue as A. pegreffii. This is the first instance of human intestinal anisakiasis diagnosed using PCR of DNA purified from a fixed eosinophilic granuloma embedded in paraffin. Conclusion The case of human anisakiasis presented reinforces the pathological significance of the species A. pegreffii to humans. The molecular/genetic methodological approach based on mtDNA cox2 sequence analysis, described here, can allow easy and rapid identification of Anisakis spp. in formalin-fixed and paraffin embedded tissues removed from cases of either gastric or intestinal human anisakiasis. PMID:21453522

  2. First molecular identification of the zoonotic parasite Anisakis pegreffii (Nematoda: Anisakidae in a paraffin-embedded granuloma taken from a case of human intestinal anisakiasis in Italy

    Directory of Open Access Journals (Sweden)

    Palumbo Massimo

    2011-03-01

    Full Text Available Abstract Background Anisakiasis is an important fish-borne zoonosis provoked by larval stages of nematodes belonging to the genus Anisakis. The detection and identification of human infections is difficult. This is due to: a the low specificity of the clinical features and symptomatology related to human infections; b the paucity of diagnostic features of larvae found in granulomatous lesions characteristic of "invasive anisakiasis"; and c the lack morphological characters diagnostic at the specific level when larvae of Anisakis are detected. Thus, molecular-based diagnostic approaches are warranted. Method We have developed a PCR method that amplifies the DNA of Anisakis spp. in fixed paraffin-embedded tissues. This method was applied to a granuloma removed from a human case of intestinal anisakiasis in Italy. Specific primers of the mtDNA cox2 gene were used and sequence analysis was performed according to the procedures already established for species of Anisakis. Results The sequence obtained (629 bp was compared with those of the other species of Anisakis which have so far been genetically characterized and with sequences obtained from larval stages of Anisakis collected from the Mediterranean fish Engraulis encrasicolus. This enabled the genetic identification of the larva in the human tissue as A. pegreffii. This is the first instance of human intestinal anisakiasis diagnosed using PCR of DNA purified from a fixed eosinophilic granuloma embedded in paraffin. Conclusion The case of human anisakiasis presented reinforces the pathological significance of the species A. pegreffii to humans. The molecular/genetic methodological approach based on mtDNA cox2 sequence analysis, described here, can allow easy and rapid identification of Anisakis spp. in formalin-fixed and paraffin embedded tissues removed from cases of either gastric or intestinal human anisakiasis.

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

    OpenAIRE

    Oshima Masanobu; Oshima Hiroko; Itadani Hiraku; Kotani Hidehito

    2009-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Sheil Barbara

    2009-10-01

    Full Text Available Abstract 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-?B activation were measured using enzyme-linked immunosorbent assays. Results Compared to untreated cells, S. typhimurium, C. difficile, M. paratuberculosis, and flagellin activated NF-?B 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-?B 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. The SKW 6.4 line of human B lymphocytes specifically binds and responds to vasoactive intestinal peptide.

    Science.gov (United States)

    Cheng, P P; Sreedharan, S P; Kishiyama, J L; Goetzl, E J

    1993-05-01

    Vasoactive intestinal peptide (VIP1-28) is a neuromediator recognized by high-affinity receptors on human lymphocytes, which inhibits T-cell proliferation and cytokine secretion, and suppresses immunoglobulin production by mitogen-stimulated mixed mononuclear leucocytes. The direct interactions of VIP1-28 with B cells were studied in the SKW 6.4 line of EBV-transformed human B cells, that express a mean (+/- SD) of 6116 +/- 969 receptors for [125I]VIP1-28 with a mean Kd of 59 nM, that decreases to 12 nM after exposure to phorbol 12-myristate 13-acetate (PMA). The secretion of IgM by SKW 6.4 B cells stimulated optimally with 100 ng/ml of PMA, but not unstimulated secretion of IgM, was suppressed significantly by 10(-12) M to 10(-9) M VIP1-28 and up to a mean maximum (+/- SD) of 40 +/- 2% by 10(-10) M VIP1-28. VIP1-28 elicited concomitant increases in intracellular cyclic AMP up to a mean maximum of 163% at 10(-10) M VIP1-28. The requirement for specific signal transduction by the occupied VIP receptors to inhibit IgM secretion was demonstrated by the lack of effect of VIP4-28 on both cyclic AMP concentration and IgM secretion, despite the equal affinity of binding of VIP4-28 and VIP1-28. The effects of VIP on immunoglobulin secretion by stimulated mixed mononuclear leucocytes thus may be due in part to a direct action on B cells. PMID:8509142

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

    International Nuclear Information System (INIS)

    Phenol contamination of soil and water has raised concerns among people living near phenol-producing factories and hazardous waste sites containing the chemical. Phenol, particularly in high concentrations, is an irritating and corrosive substance, making mucosal membranes targets of toxicity in humans. However, few data on the effects of phenol after oral exposure exist. We used an in vitro model employing human intestinal epithelial cells (SK-CO15) cultured on permeable supports to examine effects of phenol on epithelial barrier function. We hypothesized that phenol disrupts epithelial barrier by altering tight junction (TJ) protein expression. The dose-response effect of phenol on epithelial barrier function was determined using transepithelial electrical resistance (TER) and FITC-dextran permeability measurements. We studied phenol-induced changes in cell morphology and expression of several tight junction proteins by immunofluorescence and Western blot analysis. Effects on cell viability were assessed by MTT, Trypan blue, propidium iodide and TUNEL staining. Exposure to phenol resulted in decreased TER and increased paracellular flux of FITC-dextran in a dose-dependent manner. Delocalization of claudin-1 and ZO-1 from TJs to cytosol correlated with the observed increase in permeability after phenol treatment. Additionally, the decrease in TER correlated with changes in the distribution of a membrane raft marker, suggesting phenol-mediated effects on membrane fluidity. Such observations were independent of effects of phenol on cell viability as enhanced permeability occurred at doses of phenol that did not cause cell death. Overall, these findings suggest that phenol may affect transiently the lipid bilayer of the cell membrane, thus destabilizing TJ-containing microdomains.

  7. 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.

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

    OpenAIRE

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

    2010-01-01

    Identification of celiac disease, by determining human leucocyte antigens DQ2/DQ8, is important since recent long-term studies have shown that the mortality of celiac disease is increased, if it is unrecognized and untreated. In this sense, we wanted to see the usefulness of genetic tests in celiac disease diagnosis and screening. Material and methods. During 2010 we determined by PCR, DQ2/DQ8 haplotype, in a group of 27 children with celiac disease and 9 of their brothers, serolo...

  9. Before and After: Gender Transitions, Human Capital, and Workplace Experiences

    OpenAIRE

    Schilt Kristen; Wiswall Matthew

    2008-01-01

    We use the workplace experiences of transgender people individuals who change their gender typically with hormone therapy and surgery to provide new insights into the long-standing question of what role gender plays in shaping workplace outcomes. Using an original survey of male-to-female and female-to-male transgender people, we document the earnings and employment experiences of transgender people before and after their gender transitions. We find that while transgender people have the same...

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

    OpenAIRE

    Ernstson H.; Leeuw S.E.V.D.; Redman C.L.; Meffert D.J.; Davis G.; Alfsen C.; Elmqvist T.

    2010-01-01

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

  11. Interaction of graphene-related materials with human intestinal cells: an in vitro approach

    Science.gov (United States)

    Kucki, M.; Rupper, P.; Sarrieu, C.; Melucci, M.; Treossi, E.; Schwarz, A.; León, V.; Kraegeloh, A.; Flahaut, E.; Vázquez, E.; Palermo, V.; Wick, P.

    2016-04-01

    Graphene-related materials (GRM) inherit unique combinations of physicochemical properties which offer a high potential for technological as well as biomedical applications. It is not clear which physicochemical properties are the most relevant factors influencing the behavior of GRM in complex biological environments. In this study we have focused on the interaction of GRM, especially graphene oxide (GO), and Caco-2 cells in vitro. We mimiked stomach transition by acid-treatment of two representative GRM followed by analysis of their physicochemical properties. No significant changes in the material properties or cell viability of exposed Caco-2 cells in respect to untreated GRM could be detected. Furthermore, we explored the interaction of four different GO and Caco-2 cells to identify relevant physicochemical properties for the establishment of a material property-biological response relationship. Despite close interaction with the cell surface and the formation of reactive oxygen species (ROS), no acute toxicity was found for any of the applied GO (concentration range 0-80 μg ml-1) after 24 h and 48 h exposure. Graphene nanoplatelet aggregates led to low acute toxicity at high concentrations, indicating that aggregation, the number of layers or the C/O ratio have a more pronounced effect on the cell viability than the lateral size alone.Graphene-related materials (GRM) inherit unique combinations of physicochemical properties which offer a high potential for technological as well as biomedical applications. It is not clear which physicochemical properties are the most relevant factors influencing the behavior of GRM in complex biological environments. In this study we have focused on the interaction of GRM, especially graphene oxide (GO), and Caco-2 cells in vitro. We mimiked stomach transition by acid-treatment of two representative GRM followed by analysis of their physicochemical properties. No significant changes in the material properties or cell viability of exposed Caco-2 cells in respect to untreated GRM could be detected. Furthermore, we explored the interaction of four different GO and Caco-2 cells to identify relevant physicochemical properties for the establishment of a material property-biological response relationship. Despite close interaction with the cell surface and the formation of reactive oxygen species (ROS), no acute toxicity was found for any of the applied GO (concentration range 0-80 μg ml-1) after 24 h and 48 h exposure. Graphene nanoplatelet aggregates led to low acute toxicity at high concentrations, indicating that aggregation, the number of layers or the C/O ratio have a more pronounced effect on the cell viability than the lateral size alone. Electronic supplementary information (ESI) available: Material characterization details, light microscopy images of Caco-2 cells, cell-free control tests for MTS and DCF assay. See DOI: 10.1039/c6nr00319b

  12. 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.

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

    Scientific Electronic Library Online (English)

    Oscar, Brunser T.

    2013-09-01

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

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

    International Nuclear Information System (INIS)

    Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1E,6E-heptadiene-3,5-dione or diferuloyl methane) is a polyphenol derived from the Curcuma longa plant, commonly known as turmeric. This substance has been used extensively in Ayurvedic medicine for centuries for its anti-oxidant, analgesic, anti-inflammatory and antiseptic activity. More recently curcumin has been found to possess anti-cancer properties linked to its pro-apoptotic and anti-proliferative actions. The underlying mechanisms of these diverse effects are complex, not fully elucidated and subject of intense scientific debate. Despite increasing evidence indicating that different cation channels can be a molecular target for curcumin, very little is known about the effect of curcumin on chloride channels. Since, (i) the molecular structure of curcumin indicates that the substance could potentially interact with chloride channels, (ii) chloride channels play a role during the apoptotic process and regulation of the cell volume, and (iii) apoptosis is a well known effect of curcumin, we set out to investigate whether or not curcumin could (i) exert a modulatory effect (direct or indirect) on the swelling activated chloride current IClswell in a human cell system, therefore (ii) affect cell volume regulation and (iii) ultimately modulate cell survival. The IClswell channels, which are essential for regulating the cell volume after swelling, are also known to be activated under isotonic conditions as an early event in the apoptotic process. Here we show that long-term exposure of a human kidney cell line to extracellular 0.1–10 μM curcumin modulates IClswell in a dose-dependent manner (0.1 μM curcumin is ineffective, 0.5–5.0 μM curcumin increase, while 10 μM curcumin decrease the current), and short-term exposure to micromolar concentrations of curcumin does not affect IClswell neither if applied from the extracellular nor from the intracellular side – therefore, a direct effect of curcumin on IClswell can be ruled out. Furthermore, we show that curcumin exposure induces apoptosis in human kidney cells, and at a concentration of 5.0–10 μM induces the appearance of a sub-population of cells with a dramatically increased volume. In these cells the regulation of the cell volume seems to be impaired, most likely as a consequence of the IClswell blockade. Similarly, 50 μM curcumin induced apoptosis, caused cell cycle arrest in G1-phase and increased the volume of human colorectal adenocarcinoma HT-29 cells. The cell cycle arrest in G1 phase may be the mechanism underlying the volume increase observed in this cell line after exposure to curcumin.

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

    International Nuclear Information System (INIS)

    The cell surface glycopeptides from an epithelial cell line (CCL 239) derived from normal human colon were compared with those from three cell lines (HCT-8R, HCT-15, and CaCo-2) derived independently from human colonic adenocarcinomas. Cells were incubated with D-[2-3H]mannose or L-[5,6-3H]fucose for 24 h and treated with trypsin to release cell surface components which were then digested exhaustively with Pronase and fractionated on Bio-Gel P-6 before and after treatment with endo-beta-N-acetylglucosaminidase H. The most noticeable difference between the labeled glycopeptides from the tumor and CCL 239 cells was the presence in the former of an endo-beta-N-acetylglucosaminidase H-resistant high molecular weight glycopeptide fraction which was eluted in the void volume of Bio-Gel P-6. This fraction was obtained with both labeled mannose and fucose as precursors. However, acid hydrolysis of this fraction obtained after incubation with [2-3H]mannose revealed that as much as 60-90% of the radioactivity was recovered as fucose. Analysis of the total glycopeptides (cell surface and cell pellet) obtained after incubation with [2-3H]mannose showed that from 40-45% of the radioactivity in the tumor cells and less than 10% of the radioactivity in the CCL 239 cells was recovered as fucose. After incubation of the HCT-8R cells with D-[1,6-3H]glucosamine and L-[1-14C]fucose, strong acid hydrolysis of the labeled glycopeptide fraction excluded from Bio-Gel P-6 produced 3H-labeled N-acetylglucosamine and N-acetylgalactosamine

  16. The human intestinal microbiome at extreme ages of life. Dietary intervention as a way to counteract alterations

    OpenAIRE

    Salazar, Nuria; Arboleya, Silvia; Valdés, Lorena; Stanton, Catherine; Ross, Paul; Ruiz, Lorena; Gueimonde, Miguel; de los Reyes-Gavilán, Clara G.

    2014-01-01

    The intestinal microbiome is defined as the assembly of genomes from microorganisms inhabiting the gut. This microbial ecosystem regulates important functions of the host and its correct composition and functionality is essential for a “healthy status.” Metagenomic studies have highlighted variations of the intestinal microbiota as a function of age and diet. Colonization of the infant gut starts at birth and is influenced by feeding habits (formula vs. breast-feeding), birth mode and antibio...

  17. Connexin 26-mediated gap junctional intercellular communication suppresses paracellular permeability of human intestinal epithelial cell monolayers

    International Nuclear Information System (INIS)

    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

  18. Anaerobic Conditions Promote Expression of Sfp Fimbriae and Adherence of Sorbitol-Fermenting Enterohemorrhagic Escherichia coli O157:NM to Human Intestinal Epithelial Cells?

    Science.gov (United States)

    Msken, Anne; Bielaszewska, Martina; Greune, Lilo; Schweppe, Christian H.; Mthing, Johannes; Schmidt, Herbert; Schmidt, M. Alexander; Karch, Helge; Zhang, Wenlan

    2008-01-01

    The sfp gene cluster, unique to sorbitol-fermenting (SF) enterohemorrhagic Escherichia coli (EHEC) O157:NM strains, encodes fimbriae that mediate mannose-resistant hemagglutination in laboratory E. coli strains but are not expressed in wild-type SF EHEC O157:NM strains under standard laboratory conditions. We investigated whether Sfp fimbriae are expressed under conditions that mimic the intestinal environment and whether they contribute to the adherence of SF EHEC O157:NM strains to human intestinal epithelial cells. The transcription of sfpA (encoding the major fimbrial subunit) was upregulated in all strains investigated, and all expressed SfpA and possessed fimbriae that reacted with an anti-SfpA antibody when the strains were grown on solid media under anaerobic conditions. Sfp expression was absent under aerobic conditions and in liquid media. Sfp upregulation under anaerobic conditions was significantly higher on blood agar and a medium simulating the colonic environment than on a medium simulating the ileal environment (P < 0.05). The induction of Sfp fimbriae in SF E. coli O157:NM strains correlates with increased adherence to Caco-2 and HCT-8 cells. Our data indicate that the expression of Sfp fimbriae in SF E. coli O157:NM strains is induced under conditions resembling those of the natural site of infection and that Sfp fimbriae may contribute to the adherence of the organisms to human intestinal epithelium. PMID:18083855

  19. Anaerobic conditions promote expression of Sfp fimbriae and adherence of sorbitol-fermenting enterohemorrhagic Escherichia coli O157:NM to human intestinal epithelial cells.

    Science.gov (United States)

    Msken, Anne; Bielaszewska, Martina; Greune, Lilo; Schweppe, Christian H; Mthing, Johannes; Schmidt, Herbert; Schmidt, M Alexander; Karch, Helge; Zhang, Wenlan

    2008-02-01

    The sfp gene cluster, unique to sorbitol-fermenting (SF) enterohemorrhagic Escherichia coli (EHEC) O157:NM strains, encodes fimbriae that mediate mannose-resistant hemagglutination in laboratory E. coli strains but are not expressed in wild-type SF EHEC O157:NM strains under standard laboratory conditions. We investigated whether Sfp fimbriae are expressed under conditions that mimic the intestinal environment and whether they contribute to the adherence of SF EHEC O157:NM strains to human intestinal epithelial cells. The transcription of sfpA (encoding the major fimbrial subunit) was upregulated in all strains investigated, and all expressed SfpA and possessed fimbriae that reacted with an anti-SfpA antibody when the strains were grown on solid media under anaerobic conditions. Sfp expression was absent under aerobic conditions and in liquid media. Sfp upregulation under anaerobic conditions was significantly higher on blood agar and a medium simulating the colonic environment than on a medium simulating the ileal environment (P < 0.05). The induction of Sfp fimbriae in SF E. coli O157:NM strains correlates with increased adherence to Caco-2 and HCT-8 cells. Our data indicate that the expression of Sfp fimbriae in SF E. coli O157:NM strains is induced under conditions resembling those of the natural site of infection and that Sfp fimbriae may contribute to the adherence of the organisms to human intestinal epithelium. PMID:18083855

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

    LENUS (Irish Health Repository)

    2011-08-30

    Abstract Background The genus Lactobacillus is characterized by an extraordinary degree of phenotypic and genotypic diversity, which recent genomic analyses have further highlighted. However, the choice of species for sequencing has been non-random and unequal in distribution, with only a single representative genome from the L. salivarius clade available to date. Furthermore, there is no data to facilitate a functional genomic analysis of motility in the lactobacilli, a trait that is restricted to the L. salivarius clade. Results The 2.06 Mb genome of the bovine isolate Lactobacillus ruminis ATCC 27782 comprises a single circular chromosome, and has a G+C content of 44.4%. In silico analysis identified 1901 coding sequences, including genes for a pediocin-like bacteriocin, a single large exopolysaccharide-related cluster, two sortase enzymes, two CRISPR loci and numerous IS elements and pseudogenes. A cluster of genes related to a putative pilin was identified, and shown to be transcribed in vitro. A high quality draft assembly of the genome of a second L. ruminis strain, ATCC 25644 isolated from humans, suggested a slightly larger genome of 2.138 Mb, that exhibited a high degree of synteny with the ATCC 27782 genome. In contrast, comparative analysis of L. ruminis and L. salivarius identified a lack of long-range synteny between these closely related species. Comparison of the L. salivarius clade core proteins with those of nine other Lactobacillus species distributed across 4 major phylogenetic groups identified the set of shared proteins, and proteins unique to each group. Conclusions The genome of L. ruminis provides a comparative tool for directing functional analyses of other members of the L. salivarius clade, and it increases understanding of the divergence of this distinct Lactobacillus lineage from other commensal lactobacilli. The genome sequence provides a definitive resource to facilitate investigation of the genetics, biochemistry and host interactions of these motile intestinal lactobacilli.

  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. Altered growth patterns in vitro of human papillary transitional carcinoma cells.

    OpenAIRE

    Reznikoff, C. A.; Gilchrist, K. W.; Norback, D. H.; Cummings, K. B.; ERTÜRK, E.; Bryan, G. T.

    1983-01-01

    In vitro growth patterns and morphologic characteristics of five low-grade human papillary transitional cell carcinomas (TCCs) were compared and contrasted with those of normal human urothelial cells in culture. Biopsies of TCC were performed by transurethral resection. Specimens of normal human ureters were obtained surgically. Singly dispersed TCC cells grew in 0.3% agarose semisolid medium with a cloning efficiency ranging from 0.02% to 0.71%. Singly dispersed normal ureteral urothelial ce...

  3. Interleukin-2 gene transfer into human transitional cell carcinoma of the urinary bladder

    OpenAIRE

    Milella, M.; Jacobelli, J; Cavallo, F. (Federica); Guarini, A; Velotti, F.; Frati, L; Fo, R; Forni, G; Santoni, A.

    1999-01-01

    Transitional cell carcinoma of the bladder is one of the human cancers most responsive to immunotherapy, and local interleukin-2 (IL-2) production appears to be an important requirement for immunotherapy to be effective. In this study, we engineered two human bladder cancer cell lines (RT112 and EJ) to constitutively release human IL-2 by retroviral vector-mediated gene transfer. Following infection and selection, stable and consistent production of biologically active IL-2 was demonstrated a...

  4. Perfil epidemiológico e morbimortalidade dos pacientes submetidos à reconstrução de trânsito intestinal: experiência de um centro secundário do Nordeste Brasileiro Epidemiologic profile and morbimortality of patients undergoing reconstruction intestinal transit: experience of a secundary health service in the Northeast of Brazil

    Directory of Open Access Journals (Sweden)

    Jeany Borges e Silva

    2010-09-01

    Full Text Available RACIONAL: A reconstrução do trânsito intestinal não está isenta de riscos cirúrgicos e apresenta taxas consideráveis de complicações pós-operatórias, sendo que a infecção continua a ser um dos maiores desafios existentes neste procedimento. OBJETIVO: Perfil epidemiológico e morbimortalidade dos pacientes submetidos à reconstrução de trânsito intestinal. MÉTODOS: Foram analisados retrospectivamente 86 prontuários de pacientes com colostomia ou ileostomia, através de fatores que tivessem impacto sobre a morbimortalidade após a reconstrução de trânsito intestinal, de janeiro de 2003 a abril de 2009. RESULTADOS: Houve 20 mulheres e 60 homens, com idade média de 43 anos. A colostomia em alça (n=34 e o trauma abdominal indicando colostomia ou ileostomia foram as condições mais frequentes. O intervalo médio entre a confecção do estoma e a reconstrução de trânsito intestinal foi 15,7 meses. O índice de morbidade foi 56,8%, sendo a infecção incisional a complicação mais comum (27.47%. A permanência hospitalar média foi 7,6 dias. Houve regressão linear positiva entre permanência hospitalar pós-operatória e a idade do paciente. Demonstrou-se associação estatisticamente significativa entre o prolongamento da permanência hospitalar e a ocorrência de complicações (pBACKGROUND: The reconstruction of the intestinal tract is not surgical complications risk-free and is associated to postoperative complications high rates; furthermore, infection remains the hardest challenge in this procedure. AIM: Epidemiological profile and mortality and morbidity in patients undergoing reconstruction of intestinal transit. METHODS: Retrospectively, 86 patients with intestinal stomas were analyzed through factors that impact on the morbimortality afterwards intestinal transit reconstruction, since January 2003 to April 2009. RESULTS: Loop colostomy (n=34 and abdominal trauma implicating 38.2% of indications to colostomy or ileostomy, were the most frequent conditions. The mean interval between stoma confection and intestinal transit reconstruction was 15.7 months. The morbidity frequency was 56.8% and incisional infection was its commonest complication (27.47%. The mean inpatient length of stay was 7.6 days. There was positive linear regression between post-operative inpatient length of stay and inpatient's age. Inpatient length of stay prolongation is associated to occurrence of complications (p<0,001. CONCLUSION: It can be inferred that the occurrence of postoperative complications and age were associated with prolonged hospital stay.

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

    Scientific Electronic Library Online (English)

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

    2013-03-01

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

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

    Directory of Open Access Journals (Sweden)

    Ana Ibis Garca Hernndez

    2013-03-01

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

  7. Human migrating myoelectric complex in relation to gastrointestinal transit of a meal.

    OpenAIRE

    Madsen, J L; Dahl, K.

    1990-01-01

    Feeding interrupts the migrating myoelectric complex in most mammals. This study aimed to assess whether resumption of the migrating myoelectric complex in the human duodenum after eating was related to the gastrointestinal transit of the meal. Five healthy subjects participated in the study. After eating a radiolabelled test meal consisting of mixed liquid and solids, duodenal myoelectric activity and gastrointestinal transit of the meal were determined simultaneously. In spite of considerab...

  8. Human Capital, Consumption, and Housing Wealth in Transition

    OpenAIRE

    Fidrmuc, Jarko; Senaj, Matus

    2012-01-01

    This paper focuses on human capital and physical capital of households in Slovakia during the economic reforms of the last two decades. We compare households who entered the labor market before and after the economic reforms in 1990. On the one hand, we study the returns to education by different labor market cohorts using household consumption surveys. On the other hand, we analyze the determinants of housing wealth and its impact on consumption. We show that old cohorts are characterized by...

  9. Conformational transitions in human translin enable nucleic acid binding

    OpenAIRE

    Pérez-Cano, Laura; Eliahoo, Elad; Lasker, Keren; Wolfson, Haim J; Glaser, Fabian; Manor, Haim; Bernadó, Pau; Fernández-Recio, Juan

    2013-01-01

    Translin is a highly conserved RNA- and DNA-binding protein that plays essential roles in eukaryotic cells. Human translin functions as an octamer, but in the octameric crystallographic structure, the residues responsible for nucleic acid binding are not accessible. Moreover, electron microscopy data reveal very different octameric configurations. Consequently, the functional assembly and the mechanism of nucleic acid binding by the protein remain unclear. Here, we present an integrative stud...

  10. Human biokinetics of strontium--part II: Final data evaluation of intestinal absorption and urinary excretion of strontium in human subjects after stable tracer administration.

    Science.gov (United States)

    Hllriegl, Vera; Li, Wei Bo; Oeh, Uwe

    2006-09-01

    Fractional intestinal absorption (f1 value) and urinary excretion of strontium in healthy human volunteers has been measured by simultaneous oral and intravenous administration of the stable isotopes 86Sr and 84Sr using the double-isotope method. Final evaluation of the complete data set confirmed that ingestion of different foodstuff and nutritional factors could influence the fractional gut uptake of strontium. In some cases, significant deviations from the f1 value adopted by the International Commission on Radiological Protection (ICRP) were found. The arithmetic mean (+/- standard deviation) of the f1 values of all experiments performed was determined to be 0.46 (+/- 0.24). The probability distribution function of the f1 values is represented by a lognormal curve with a geometric mean of 0.38 and a geometric standard deviation of 2.06. Urinary excretion in all subjects varied depending on the administered foodstuff in a wide range and differs from the ICRP model, up to 2 days after tracer administration. No age or gender dependence of the absorbed strontium fraction and of the urinary excretion of strontium after an oral load was found. PMID:16897061

  11. A 3D co-culture of three human cell lines to model the inflamed intestinal mucosa for safety testing of nanomaterials.

    Science.gov (United States)

    Susewind, Julia; de Souza Carvalho-Wodarz, Cristiane; Repnik, Urska; Collnot, Eva-Maria; Schneider-Daum, Nicole; Griffiths, Gareth Wyn; Lehr, Claus-Michael

    2016-02-01

    Oral exposure to nanomaterials is a current concern, asking for innovative biological test systems to assess their safety, especially also in conditions of inflammatory disorders. Aim of this study was to develop a 3D intestinal model, consisting of Caco-2 cells and two human immune cell lines, suitable to assess nanomaterial toxicity, in either healthy or diseased conditions. Human macrophages (THP-1) and human dendritic cells (MUTZ-3) were embedded in a collagen scaffold and seeded on the apical side of transwell inserts. Caco-2 cells were seeded on top of this layer, forming a 3D model of the intestinal mucosa. Toxicity of engineered nanoparticles (NM101 TiO2, NM300 Ag, Au) was evaluated in non-inflamed and inflamed co-cultures, and also compared to non-inflamed Caco-2 monocultures. Inflammation was elicited by IL-1β, and interactions with engineered NPs were addressed by different endpoints. The 3D co-culture showed well preserved ultrastructure and significant barrier properties. Ag NPs were found to be more toxic than TiO2 or Au NPs. But once inflamed with IL-1β, the co-cultures released higher amounts of IL-8 compared to Caco-2 monocultures. However, the cytotoxicity of Ag NPs was higher in Caco-2 monocultures than in 3D co-cultures. The naturally higher IL-8 production in the co-cultures was enhanced even further by the Ag NPs. This study shows that it is possible to mimic inflamed conditions in a 3D co-culture model of the intestinal mucosa. The fact that it is based on three easily available human cell lines makes this model valuable to study the safety of nanomaterials in the context of inflammation. PMID:25738417

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

    Energy Technology Data Exchange (ETDEWEB)

    Ogawa, Eiichi [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Hosokawa, Masaya [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Faculty of Human Sciences, Tezukayama Gakuin University, Osaka (Japan); Harada, Norio; Yamane, Shunsuke; Hamasaki, Akihiro; Toyoda, Kentaro; Fujimoto, Shimpei; Fujita, Yoshihito; Fukuda, Kazuhito [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Tsukiyama, Katsushi; Yamada, Yuichiro [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Department of Internal Medicine, Division of Endocrinology, Diabetes and Geriatric Medicine, Akita University School of Medicine, Akita (Japan); Seino, Yutaka [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Kansai Electric Power Hospital, Osaka (Japan); Inagaki, Nobuya, E-mail: inagaki@metab.kuhp.kyoto-u.ac.jp [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); CREST of Japan Science and Technology Cooperation (JST), Kyoto (Japan)

    2011-01-07

    Research highlights: {yields} Exogenous GIP inhibits intestinal motility through a somatostatin-mediated pathway. {yields} Exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility. {yields} The GIP-receptor-mediated action in intestine does not involve in GLP-1-mediated pathway. -- Abstract: Gastric inhibitory polypeptide (GIP) is released from the small intestine upon meal ingestion and increases insulin secretion from pancreatic {beta} cells. Although the GIP receptor is known to be expressed in small intestine, the effects of GIP in small intestine are not fully understood. This study was designed to clarify the effect of GIP on intestinal glucose absorption and intestinal motility. Intestinal glucose absorption in vivo was measured by single-pass perfusion method. Incorporation of [{sup 14}C]-glucose into everted jejunal rings in vitro was used to evaluate the effect of GIP on sodium-glucose co-transporter (SGLT). Motility of small intestine was measured by intestinal transit after oral administration of a non-absorbed marker. Intraperitoneal administration of GIP inhibited glucose absorption in wild-type mice in a concentration-dependent manner, showing maximum decrease at the dosage of 50 nmol/kg body weight. In glucagon-like-peptide-1 (GLP-1) receptor-deficient mice, GIP inhibited glucose absorption as in wild-type mice. In vitro examination of [{sup 14}C]-glucose uptake revealed that 100 nM GIP did not change SGLT-dependent glucose uptake in wild-type mice. After intraperitoneal administration of GIP (50 nmol/kg body weight), small intestinal transit was inhibited to 40% in both wild-type and GLP-1 receptor-deficient mice. Furthermore, a somatostatin receptor antagonist, cyclosomatostatin, reduced the inhibitory effect of GIP on both intestinal transit and glucose absorption in wild-type mice. These results demonstrate that exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility through a somatostatin-mediated pathway rather than through a GLP-1-mediated pathway.

  13. Transitions in pathways of human development and carbon emissions

    International Nuclear Information System (INIS)

    Countries are known to follow diverse pathways of life expectancy and carbon emissions, but little is known about factors driving these dynamics. In this letter we estimate the cross-sectional economic, demographic and geographic drivers of consumption-based carbon emissions. Using clustering techniques, countries are grouped according to their drivers, and analysed with respect to a criteria of one tonne of carbon emissions per capita and a life expectancy over 70 years (Goldemberg’s Corner). Five clusters of countries are identified with distinct drivers and highly differentiated outcomes of life expectancy and carbon emissions. Representatives from four clusters intersect within Goldemberg’s Corner, suggesting diverse combinations of drivers may still lead to sustainable outcomes, presenting many countries with an opportunity to follow a pathway towards low-carbon human development. By contrast, within Goldemberg’s Corner, there are no countries from the core, wealthy consuming nations. These results reaffirm the need to address economic inequalities within international agreements for climate mitigation, but acknowledge plausible and accessible examples of low-carbon human development for countries that share similar underlying drivers of carbon emissions. In addition, we note differences in drivers between models of territorial and consumption-based carbon emissions, and discuss interesting exceptions to the drivers-based cluster analysis. (paper)

  14. Transition in the Human Exploration of Space at NASA

    Science.gov (United States)

    Koch, Carla A.; Cabana, Robert

    2011-01-01

    NASA is taking the next step in human exploration, beyond low Earth orbit. We have been going to low Earth orbit for the past 50 years and are using this experience to work with commercial companies to perform this function. This will free NASA resources to develop the systems necessary to travel to a Near Earth Asteroid, the Moon, Lagrange Points, and eventually Mars. At KSC, we are positioning ourselves to become a multi-user launch complex and everything we are working on is bringing us closer to achieving this goal. A vibrant multi-use spaceport is to the 21st Century what the airport was to the 20th Century - an invaluable transportation hub that supports government needs while promoting economic development and commercial markets beyond Earth's atmosphere. This past year saw the end of Shuttle, but the announcements of NASA's crew module, Orion, and heavy-lift rocket, the SLS, as well as the establishment of the Commercial Crew Program. We have a busy, but very bright future ahead of us and KSC is looking forward to playing an integral part in the next era of human space exploration. The future is SLS, 21st Century Ground Systems Program, and the Commercial Crew Program; and the future is here.

  15. Law in Transition Biblioessay: Globalization, Human Rights, Environment, Technology

    Directory of Open Access Journals (Sweden)

    Michael Marien

    2012-04-01

    Full Text Available As globalization continues, many transformations in international and domestic laws areunderway or called for. There are too many laws and too few, too much law that is inadequateor obsolete, and too much law-breaking. This biblioessay covers some 100 recentbooks, nearly all recently published, arranged in four categories. 1 International Lawincludes six overviews/textbooks on comparative law, laws related to warfare and security,pushback against demands of globalization, and gender perspectives; 2 Human Rightsencompasses general overviews and normative visions, several books on how some statesviolate human rights, five items on how good laws can end poverty and promote prosperity,and laws regulating working conditions and health rights; 3 Environment/Resources coversgrowth of international environmental law, visions of law for a better environmental future,laws to govern genetic resources and increasingly stressed water resources, two books onprospects for climate change liability, and items on toxic hazards and problems of compliance;4 Technology, Etc. identifies eight books on global crime and the failed war on drugs,books on the response to terrorism and guarding privacy and mobility in our high-tech age,seven books on how infotech is changing law and legal processes while raising intellectualproperty questions, biomedical technologies and the law, and general views on the need forupdated laws and constitutions. In sum, this essay suggests the need for deeper and timelyanalysis of the many books on changes in law.

  16. Bridging the bonding gap: the transition from primates to humans.

    Science.gov (United States)

    Dunbar, R I M

    2012-07-01

    Primate societies are characterized by bonded social relationships of a kind that are rare in other mammal taxa. These bonded relationships, which provide the basis for coalitions, are underpinned by an endorphin mechanism mediated by social grooming. However, bonded relationships of this kind impose constraints on the size of social groups that are possible. When ecological pressures have demanded larger groups, primates have had to evolve new mechanisms to facilitate bonding. This has involved increasing the size of vocal and visual communication repertoires, increasing the time devoted to social interaction and developing a capacity to manage two-tier social relationships (strong and weak ties). I consider the implications of these constraints for the evolution of human social communities and argue that laughter was an early evolutionary innovation that helped bridge the bonding gap between the group sizes characteristic of chimpanzees and australopithecines and those in later hominins. PMID:22641822

  17. Lactic acid bacteria efficiently protect human and animal intestinal epithelial and immune cells from enteric virus infection.

    Science.gov (United States)

    Maragkoudakis, Petros A; Chingwaru, Walter; Gradisnik, Lidija; Tsakalidou, Effie; Cencic, Avrelija

    2010-07-31

    This study aimed to examine the potential antiviral activity of lactic acid bacteria (LAB) using animal and human intestinal and macrophage cell line models of non tumor origin. To this end, LAB strains selected on the basis of previous in vitro trials were co-incubated with cell line monolayers, which were subsequently challenged with rotavirus (RV) and transmissible gastroenteritis virus (TGEV). In order to elucidate the possible mechanism responsible for the antiviral activity, the induction of reactive oxygen species (ROS) release as well as the attachment ability of LAB on the cell lines was investigated. Various strains were found to exhibit moderate to complete monolayer protection against viral RV or TGEV disruption. Highest protection effects were recorded with the known probiotics Lactobacillus rhamnosus GG and Lactobacillus casei Shirota against both RV and TGEV, while notable antiviral activity was also attributed to Enterococcus faecium PCK38, Lactobacillus fermentum ACA-DC179, Lactobacillus pentosus PCA227 and Lactobacillus plantarum PCA236 and PCS22, depending on the cell line and virus combination used. A variable increase (of up to 50%) on the release of NO(-) and H(2)O(2) (ROS) was obtained when LAB strains were co-incubated with the cell lines, but the results were found to be LAB strain and cell line specific, apart from a small number of strains which were able to induce strong ROS release in more than one cell line. In contrast, the ability of the examined LAB strains to attach to the cell line monolayers was LAB strain but not cell line specific. Highest attachment ability was observed with L. plantarum ACA-DC 146, L. paracasei subsp. tolerans ACA-DC 4037 and E. faecium PCD71. Clear indications on the nature of the antiviral effect were evident only in the case of the L. casei Shirota against TGEV and with L. plantarum PCA236 against both RV and TGEV. In the rest of the cases, each interaction was LAB-cell line-virus specific, barring general conclusions. However, it is probable that more than one mechanism is involved in the antiviral effect described here. Further investigations are required to elucidate the underlying mode of action and to develop a cell line model as a system for selection of probiotic strains suited for farm animal applications. PMID:20106541

  18. Studies on mixed populations of human intestinal bacteria grown in single-stage and multistage continuous culture systems.

    OpenAIRE

    Allison, C.; McFarlan, C; Macfarlane, G T

    1989-01-01

    Mixed intestinal bacteria were grown for 336 h in two identical single-stage chemostats at low growth rates in a carbohydrate-limited medium. Complex bacterial populations were maintained and anaerobes always outnumbered aerobes. The predominant organisms belonged to the genera Bacteroides, Bifidobacterium, Lactobacillus, Clostridium, Eubacterium, Propionbacterium, Peptococcus, and Peptostreptococcus. Bacteroides species predominated in both fermentors, particularly B. ovatus and B. thetaiota...

  19. Human capital accumulation and the transition from specialization to multi-tasking

    OpenAIRE

    Boucekkine, Raouf; Crifo, Patricia

    2003-01-01

    This paper provides theoretical foundations to the contemporaneous increase in computer usage, human capital and multi-tasking observed in many OECD countries during the 1990s. The links between work organization, technology and human capital is modelled by establishing the conditions under which firms allocate the workers time among several productive tasks. Organizational change is then analysed in a dynamic perspective as the transition from specialization towards multi-tasking emphasizing...

  20. Human Capital Accumulation and the Transition from Specialisation to Multi-tasking

    OpenAIRE

    Raouf, BOUCEKKINE; Patricia, CRIFO

    2003-01-01

    This paper provides theoretical foundations to the contemporaneous increase in computer usage, human capital and multi-tasking observed in many OECD countries during the 1990s. The links between work organization, technology and human capital is modelled by establishing the conditions under which firms allocate the workers’ time among several productive tasks. Organizational change is then analysed in a dynamic perspective as the transition from specialization towards multi-tasking emphasizin...

  1. Insider ownership, human resource strategies and performance in a transition economy

    OpenAIRE

    Buck, T.; Filatotchev, I; N Demina; Wright, M(SUPA—School of Physics and Astronomy, University of Glasgow, Glasgow, UK)

    2003-01-01

    Researchers and potential investors in transition economies need to understand the Human Resource Management (HRM) strategies of target firms, since human resources are arguably their most valuable assets. Understanding is difficult, however, because HRM strategies help to determine firms' performance, but are in turn influenced by corporate governance, particularly insider ownership. This paper employs a structural equation modeling methodology to examine the relations between governance, HR...

  2. Contributions of NanI Sialidase to Caco-2 Cell Adherence by Clostridium perfringens Type A and C Strains Causing Human Intestinal Disease

    OpenAIRE

    Li, Jihong; McClane, Bruce A.

    2014-01-01

    Previous studies showed that Clostridium perfringens type D animal disease strain CN3718 uses NanI sialidase for adhering to enterocyte-like Caco-2 cells. The current study analyzed whether NanI is similarly important when type A and C human intestinal disease strains attach to Caco-2 cells. A PCR survey determined that the nanI gene was absent from typical type A food poisoning (FP) strains carrying a chromosomal enterotoxin (CPE) gene or the genetically related type C Darmbrand (Db) strains...

  3. The Effect of Lactulose on the Survival of Lactobacillus rhamnosus in the Simulator of the Human Intestinal Microbial Ecosystem (SHIME) and in vivo

    OpenAIRE

    Kontula, Pia; Nollet, Lode; Saarela, Maria; Vilpponen-Salmela, Terttu; Verstraete, Willy; Mattila-Sandholm, Tiina; von Wright, Atte

    2011-01-01

    The effect of lactulose on the survival of Lactobacillus rhamnosus VTT E-97800 and on the colon microbiota and its metabolic activity was studied using the Simulator of the Human Intestinal Microbial Ecosystem (SHIME) model. L. rhamnosus VTT E-97800 and lactulose together enhanced the production of butyric acid and decreased ammonium concentration in the model. The numbers of Bacteroides were observed to decrease 2.5–2.0 log10 cfu:ml during the SHIME experiment. In the subsequent in viv...

  4. Isolation and Characterization of Human Intestinal Bacteria Capable of Transforming the Dietary Carcinogen 2-Amino-1-Methyl-6-Phenylimidazo[4,5-b]Pyridine▿

    OpenAIRE

    Vanhaecke, Lynn; Vercruysse, Filip; Boon, Nico; Verstraete, Willy; Cleenwerck, Ilse; De Wachter, Marjan; Vos, Paul; Wiele, Tom

    2008-01-01

    2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a carcinogenic heterocyclic aromatic amine formed in meat products during cooking. Although the formation of hazardous PhIP metabolites by mammalian enzymes has been extensively reported, research on the putative involvement of the human intestinal microbiota in PhIP metabolism remains scarce. In this study, the in vitro conversion of PhIP into its microbial derivate, 7-hydroxy-5-methyl-3-phenyl-6,7,8,9-tetrahydropyrido[3′,2′:4,5]imida...

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

    OpenAIRE

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

    2006-01-01

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

  6. Human microsomal cyttrochrome P450-mediated reduction of oxysophocarpine, an active and highly toxic constituent derived from Sophora flavescens species, and its intestinal absorption and metabolism in rat.

    Science.gov (United States)

    Wu, Lili; Zhong, Wanping; Liu, Junjin; Han, Weichao; Zhong, Shilong; Wei, Qiang; Liu, Shuwen; Tang, Lan

    2015-09-01

    Oxysophocarpine (OSC), an active and toxic quinolizidine alkaloid, is highly valued in Sophora flavescens Ait. and Subprostrate sophora Root. OSC is used to treat inflammation and hepatitis for thousands of years in China. This study aims to investigate the CYP450-mediated reduction responsible for metabolizing OSC and to evaluate the absorption and metabolism of OSC in rat in situ. Four metabolites were identified, with sophocarpine (SC) as the major metabolite. SC formation was rapid in human and rat liver microsomes (HLMs and RLMs, respectively). The reduction rates in the liver are two fold higher than in the intestine, both in humans and rats. In HLMs, inhibitors of CYP2C9, 3A4/5, 2D6, and 2B6 had strong inhibitory effects on SC formation. Meanwhile, inhibitors of CYP3A and CYP2D6 had significant inhibition on SC formation in RLMs. Human recombinant CYP3A4/5, 2B6, 2D6, and 2C9 contributed significantly to SC production. The permeability in rat intestine and the excretion rates of metabolites were highest in the duodenum (pCYP3A inhibitor ketoconazole. In conclusion, the liver was the main organ responsible for OSC metabolism. First-pass metabolism via CYP3A4/5, 2B6, 2D6, and 2C9 may be the main reason for the poor OSC bioavailability. PMID:26045316

  7. Returns to the market: valuing human capital in the post-transition Czech and Slovak Republics

    Czech Academy of Sciences Publication Activity Database

    Filer, R.; Jurajda, Štěpán; Plánovský, J.

    -, č. 125 (1999), s. 1-26. ISSN 1211-3298 Institutional research plan: CEZ:AV0Z7085904 Keywords : human capital * post-transition Czech and Slovak Republics Subject RIV: AH - Economics http://www.cerge-ei.cz/pdf/wp/Wp125.pdf

  8. Evaluation by computerized morphometry of histopathological alterations of the colon wall in segments with and without intestinal transit in rats Avaliação por morfometria computadorizada das alterações histopatológicas da parede cólica em segmentos com e sem trânsito intestinal em ratos

    Directory of Open Access Journals (Sweden)

    Marcos Vieira de Sousa

    2008-10-01

    Full Text Available PURPOSE: To evaluate histopathological alterations of the colon wall in segments with and without intestinal transit, by computer-assisted imaging, and to correlate these with the length of time diversion. METHODS: Thirty male Wistar rats were subjected to intestinal transit diversion by a proximal colostomy and distal mucosa fistula. The animals were divided into three experimental groups according to how long after the initial surgical procedure they were sacrificed: six, twelve and eighteen weeks. Colon segments with and without transit were subjected to histopathological study. The variables colon crypt length, mucosal ulceration, muscle layer thickness of the muscularis mucosa, submucosa and muscularis propria, vascular congestion, number of caliciform cells, inflammatory grade and degree of inflammation, comparing the two colon segments in the different experimental groups were studied. Intestinal crypt length, muscle layer thickness of the mucosa, submucosa and muscularis propria and caliciform cells were measured by computer-assisted imaging method. Mean equality, variance analysis and correlation tests were used in the statistical analysis, and the significance level was set at 5%. RESULTS: Comparison between segments with and without transit showed that the latter presented reduced length of colon crypts and increased muscle layer thickness of the muscularis mucosa, submucosa and muscularis propria. There were greater quantities of ulceration of the mucosal and greater degree of inflammation with increasing time without transit. Mucosal ulceration, submucosal vascular congestion, increased thickness of the submucosal and muscularis propria layers, presence of caliciform cells, inflammatory infiltrate and inflammatory grade correlated significantly with the length of time without transit. CONCLUSIONS: Histological alterations occurred in all layers of the colon wall, in the segments without intestinal transit. Ulcerations in the intestinal mucosa, increased number of caliciform cells, greater vascular congestion of the submucosal layer and inflammatory reaction were related to increasing length of time without transit.OBJETIVO: Avaliar por método de imagem assistida por computador as alterações histopatológicas da parede cólica em segmentos providos e desprovidos de trânsito intestinal e relacioná-las ao tempo de exclusão. MÉTODOS: Trinta ratos Wistar machos foram submetidos à derivação do trânsito no cólon esquerdo por meio de colostomia proximal e fístula mucosa distal. Os animais foram divididos em três grupos experimentais segundo o sacrifício ter sido realizado seis, doze e dezoito semanas após o procedimento cirúrgico inicial. Segmentos dos cólons providos e desprovidos de trânsito foram submetidos a estudo histopatológico. Foram analisadas as variáveis: comprimento das criptas cólicas, ulceração na mucosa, espessura das camadas muscular da mucosa, submucosa e muscular própria, congestão vascular, número de células caliciformes e graduação inflamatória comparando os dois segmentos cólicos nos diferentes grupos experimentais. As variáveis, comprimento das criptas intestinais, espessura das camadas muscular da mucosa, submucosa e muscular própria foram mensuradas por método de imagem assistida por computador. Na análise estatística foram utilizados testes de igualdade de médias e medianas, análise de variância e correlação estabelecendo-se nível de significância de cinco por cento. RESULTADOS: A exclusão de trânsito mostrou-se associada à redução do comprimento das criptas cólicas, aumento da espessura das camadas muscular da mucosa, submucosa e muscular própria. Verificou-se maior quantidade de ulcerações na mucosa e maior grau de inflamação com o progredir do tempo de exclusão. Houve correlação significante entre as ulcerações da mucosa, congestão vascular da submucosa, aumento da espessura das camadas submucosa e muscular própria, presença de células caliciformes, infiltrado inflamatório, graduação inflamatória e o tempo de exclusão de trânsito. CONCLUSÕES: Alterações histológicas ocorrem em todas as camadas da parede cólica, em segmentos sem trânsito intestinal. Ulcerações na mucosa intestinal, aumento no número de células caliciformes, maior congestão vascular na camada submucosa e reação inflamatória estavam relacionadas com o progredir do tempo de exclusão intestinal.

  9. Human Infections with Liver and Minute Intestinal Flukes in Guangxi, China: Analysis by DNA Sequencing, Ultrasonography, and Immunoaffinity Chromatography

    OpenAIRE

    Jeon, Hyeong-Kyu; Lee, Dongmin; Park, Hansol; Min, Duk-Young; Rim, Han-Jong; Zhang, Hongman; Yang, Yichao; Li, Xueming; Eom, Keeseon S.

    2012-01-01

    The prevalence of liver and intestinal fluke infections was determined by surveying inhabitants of Hengxuan, Fusui, and Shanglin villages which were known to be endemic for liver flukes in Guangxi, China in May 2010. A total of 718 people were examined for helminth eggs by the Kato-Katz thick smear technique, ultrasonography, immunoaffinity chromatography, and DNA sequencing. The overall egg positive rate was found to be 59.6% (28.0-70.6%) that included mixed infections with liver and intesti...

  10. Screening and identification of three typical phenylethanoid glycosides metabolites from Cistanches Herba by human intestinal bacteria using UPLC/Q-TOF-MS.

    Science.gov (United States)

    Li, Yang; Zhou, Guisheng; Peng, Ying; Tu, Pengfei; Li, Xiaobo

    2016-01-25

    Acteoside, isoacteoside, and 2'-acetylacteoside are three representative phenylethanoid glycosides (PhGs), which are widely distributed in many plants and also known as the active components of Cistanches Herba. However, the extremely low oral bioavailability of acteoside in rats implies that these structural similar components may go through multiple sequential routes of hydrolysis in gastrointestinal tract before they are absorbed into blood. Therefore, the metabolites of these three components and other PhGs from gastrointestinal tract such as echinacoside, are supposed to be the bioactive elements. In this study, we established an approach combining ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) with MS(E) technology and MetaboLynx™ software for the rapid metabolic profiling of acteoside, isoacteoside, and 2'-acetylacteoside by human intestinal bacteria. As a result, 11 metabolites of acteoside, 7 metabolites of isoacteoside, and 11 metabolites of 2'-acetylacteoside were identified respectively. 8 metabolic pathways including deglycosylation, de-rhamnose, de-hydroxytyrosol, de-caffeoyl, deacetylation, reduction, acetylation, and sulfate conjugation were proposed to involve in the generation of these metabolites. Furthermore, we found that the degraded metabolites hydroxytyrosol (HT) and 3-hydroxyphenylpropionic (3-HPP) were transformed from acteoside, isoacteoside, and 2'-acetylacteoside by human intestinal bacteria and demonstrated similar bioactivities to their precursors. These findings are significant for our understanding of the metabolism of PhGs and the proposed metabolic pathways of bioactive components might be crucial for further pharmacokinetic evaluations of Cistanches Herba. PMID:26551535

  11. Biotransformation and metabolic profile of catalpol with human intestinal microflora by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

    Science.gov (United States)

    Tao, Jin-Hua; Zhao, Min; Wang, Dong-Geng; Yang, Chi; Du, Le-Yue; Qiu, Wen-Qian; Jiang, Shu

    2016-01-15

    Traditional Chinese medicine (TCM) has been used in clinical practice for thousands of years. Catalpol, an iridoid glucoside, abundantly found in the root of the common used herb medicine Rehmannia glutinosa Libosch, has been reported to show various biological effects and pharmacological activities. After oral administration, the active ingredient might have interactions with the intestinal bacteria, which could help unravel how the medicine was processed in vivo. In this work, different pure bacteria from healthy human feces were isolated and used to bioconvert catalpol. Ultra performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS) technique combined with Metabolynx() software was applied to analyze catalpol metabolites. Compared with blank samples, parent compound (M0) and four metabolites (M1-M4) were detected and tentatively identified based on the characteristics of their protonated ions. The metabolites were likely to be: catalpol aglycone (M1), acetylated catalpol (M2), dimethylated and hydroxylated catalpol aglycone (M3), nitrogen-containing catalpol aglycone (M4). M1 and M4 were generated in the majority of the samples like Bacteroides sp. 45. M3 was obtained in several bacterial samples like Enterococcus sp. 8-2 and M2 was detected only in the sample of Enterococcus sp. 43-1. To our knowledge, the metabolic routes and metabolites of catalpol produced by human intestinal bacteria were all firstly reported. PMID:26741989

  12. Human intestinal mucosa-associated Lactobacillus and Bifidobacterium strains with probiotic properties modulate IL-10, IL-6 and IL-12 gene expression in THP-1 cells.

    Science.gov (United States)

    Čitar, M; Hacin, B; Tompa, G; Štempelj, M; Rogelj, I; Dolinšek, J; Narat, M; Matijašić, B Bogovič

    2015-01-01

    Lactobacilli and bifidobacteria are considered one of the permanent genera of the physiological human intestinal microbiota and represent an enormous pool of potential probiotic candidates. Approximately 450 isolates of presumptive Lactobacillus or Bifidobacterium strains were obtained from bioptic samples of colonic and ileal mucosa from 15 adolescents aged 12 to 18 years. On the basis of randomly amplified polymorphic DNA (RAPD)-PCR analysis, 20 strains were selected for further taxonomic classification and characterisation, as well as assessment of probiotic properties and safety. Importantly, selected strains showed the capability of colonising different parts of the intestine. The most frequently isolated species was Lactobacillus paracasei followed by Lactobacillus fermentum. The majority of isolates were susceptible to antimicrobials of human and veterinary importance, however, tetracycline and/or erythromycin resistance was observed in Lactobacillus plantarum and L. fermentum strains. Thirteen strains were able to ferment more than 19 different carbon sources and three out of five tested strains exerted antagonistic activity against several different indicator strains. Two Lactobacillus isolates (L. paracasei L350 and L. fermentum L930 bb) and one Bifidobacterium isolate (Bifidobacterium animalis subsp. animalis IM386) fulfilled in vitro selection criteria for probiotic strains and exhibited strong downregulation of pro-inflammatory cytokines IL-6 and IL-12 and upregulation of anti-inflammatory IL-10. The selected strains represent suitable candidates for further studies regarding their positive influence on host health and could play an important role in ameliorating the symptoms of inflammatory bowel diseases. PMID:25391349

  13. Both direct and indirect effects account for the pro-inflammatory activity of enteropathogenic mycotoxins on the human intestinal epithelium: Stimulation of interleukin-8 secretion, potentiation of interleukin-1β effect and increase in the transepithelial passage of commensal bacteria

    International Nuclear Information System (INIS)

    Mycotoxins are fungal secondary metabolites responsible of food-mediated intoxication in animals and humans. Deoxynivalenol, ochratoxin A and patulin are the best known enteropathogenic mycotoxins able to alter intestinal functions resulting in malnutrition, diarrhea, vomiting and intestinal inflammation in vivo. Although their effects on intestinal barrier and transport activities have been extensively characterized, the mechanisms responsible for their pro-inflammatory effect are still poorly understood. Here we investigated if mycotoxin-induced intestinal inflammation results from a direct and/or indirect pro-inflammatory activity of these mycotoxins on human intestinal epithelial cells, using differentiated Caco-2 cells as model and interleukin 8 (IL-8) as an indicator of intestinal inflammation. Deoxynivalenol was the only mycotoxin able to directly increase IL-8 secretion (10- to 15-fold increase). We also investigated if these mycotoxins could indirectly stimulate IL-8 secretion through: (i) a modulation of the action of pro-inflammatory molecules such as the interleukin-1beta (IL-1β), and/or (ii) an increase in the transepithelial passage of non-invasive commensal Escherichia coli. We found that deoxynivalenol, ochratoxin A and patulin all potentiated the effect of IL-1β on IL-8 secretion (ranging from 35% to 138% increase) and increased the transepithelial passage of commensal bacteria (ranging from 12- to 1544-fold increase). In addition to potentially exacerbate established intestinal inflammation, these mycotoxins may thus participate in the induction of sepsis and intestinal inflammation in vivo. Taken together, our results suggest that the pro-inflammatory activity of enteropathogenic mycotoxins is mediated by both direct and indirect effects

  14. Perfil epidemiológico e morbimortalidade dos pacientes submetidos à reconstrução de trânsito intestinal: experiência de um centro secundário do nordeste Brasileiro Epidemiologic profile and morbimortality of patients undergoing to intestinal transit reconstruction: experience of a secundary health service in Brazil northeast

    Directory of Open Access Journals (Sweden)

    Jeany Borges e Silva

    2010-09-01

    Full Text Available Racional- A reconstrução do trânsito intestinal não está isenta de riscos cirúrgicos e apresenta taxas consideráveis de complicações pós-operatórias, sendo que a infecção continua a ser um dos maiores desafios existentes neste procedimento. Métodos- Foram analisados retrospectivamente 86 prontuários de pacientes com colostomia ou ileostomia, através de fatores que tivessem impacto sobre a morbimortalidade após a reconstrução de trânsito intestinal, de janeiro de 2003 a abril de 2009. Resultados- Houve 20 mulheres e 60 homens, com idade média de 43 anos. A colostomia em alça (n: 34 e o trauma abdominal indicando colostomia ou ileostomia foram as condições mais frequentes. O intervalo médio entre a confecção do estoma e a reconstrução de trânsito intestinal foi 15,7 meses. O índice de morbidade foi 56,8%, sendo a infecção incisional a complicação mais comum (27.47%. A permanência hospitalar média foi 7,6 dias. Houve regressão linear positiva entre permanência hospitalar pós-operatória e a idade do paciente. Demonstrou-se associação estatisticamente significativa entre o prolongamento da permanência hospitalar e a ocorrência de complicações (pBackground - The reconstruction of the intestinal tract is not surgical complications risk-free and is associated to postoperative complications high rates; furthermore, infection remains the hardest challenge in this procedure. Methods - Retrospectively, eighty-six patients with intestinal stomas were analyzed through factors that impact on the morbimortality afterwards intestinal transit reconstruction, since January 2003 to April 2009. Results - Loop colostomy (n=34 and abdominal trauma implicating 38.2% of indications to colostomy or ileostomy were the most frequent conditions. The mean interval between stoma confection and intestinal transit reconstruction was 15.7 months. The morbidity frequency was 56.8% and incisional infection was its commonest complication (27.47%. The mean inpatient length of stay was 7.6 days. There was positive linear regression between post-operative inpatient length of stay and inpatient's age. Inpatient length of stay prolongation is associated to occurrence of complications (p<0,001. Conclusion - Post-operative complications and age are associated to inpatient length of stay prolongation.

  15. Changes in vasoactive intestinal peptide, pituitary adenylate cyclase-activating polypeptide and neuropeptide Y-ergic structures of the enteric nervous system in the carcinoma of the human large intestine.

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    Ireneusz Miros?aw ?akomy

    2010-08-01

    Full Text Available This investigation was aimed at immunohistochemical analysis of potential changes in the enteric nervous system caused by cancer of the large intestine. In this purpose, neurons and nerve fibers of intestinal plexuses containing neuropeptides: vasoactive intestinal peptide (VIP, pituitary adenylate cyclase-activating polypeptide (PACAP and neuropeptide Y (NPY, in pathologically changed part of the large intestine were microscpically observed and compared. Samples were taken from patients operated due to cancer of the sigmoid colon and rectum. The number of neurons and density of nerve fibres containing neuropeptides found in sections with cancer tissues were compared to those observed in sections from the uninvolved intestinal wall. Changes relating to reductions in the number of NPY-ergic neurons and density of nerve fibres in submucous and myenteric plexuses in the sections with cancer tissues (pathological sections were statistically significant. A statistically similar presence of VIP-ergic and PACAP-ergic neurons in the submucosal and myenteric plexuses was observed in both the pathological and control sections. On the other hand, in the pathological sections, VIP-ergic nerve fibres in the myenteric plexuses and PACAP-ergic nerve fibres in the submucosal and myenteric plexuses were found to be less dense. Analysis revealed changes in pathologically affected part of the large intestine may caused disruption of proper intestinal function. Observed changes in the neural elements which are responsible for relaxation of the intestine may suggest dysfunction in the innervation of this part of the colon.

  16. DNA repair following ultraviolet and N-ethyl-N-nitrosourea treatment of cells cultured from human fetal brain, intestine, kidney, liver, and skin

    Energy Technology Data Exchange (ETDEWEB)

    Gibson-D' Ambrosio, R.E.; Leong, Y.; D' Ambrosio, S.M.

    1983-12-01

    DNA excision repair was measured in cell cultures derived from human fetal brain, intestine, kidney, liver, and skin following ultraviolet (UV) irradiation and N-ethyl-N-nitrosourea (ENU) treatment. Cells in early passages were exposed to 5 or 10 J of UV radiation per sq m or to 25 microM to 3.5 mM ENU. DNA excision repair was determined by (a) scintillation counting and autoradiography to measure unscheduled DNA synthesis (UDS) and (b) the UV-endonuclease-sensitive site assay to measure pyrimidine dimers directly. The level of UDS following treatment of these cell cultures with UV was both time and dose dependent. UDS also increased with increasing doses of ENU up to 350 microM but decreased at doses greater than 500 microM. Cells derived from human fetal brain, kidney, and liver appeared to exhibit lower (50 to 80%) levels of UDS following UV irradiation or ENU treatment than did cells cultured from human fetal skin or intestine. The loss of UV-endonuclease-sensitive sites assayed in skin, liver, and kidney cells over a 24-hr period confirmed the differences observed by UDS in these cells. Skin cells removed 50% of the initial pyrimidine dimers from their DNA within an 8-hr period and 65 to 86% in 24 hr. Kidney and liver cells, on the other hand, removed only 28 and 32% of the initial dimers, respectively, over a 24-hr period. The data suggest differential excision repair responses following UV irradiation and ENU treatment of cells derived from different human fetal organs.

  17. Interaction of CpG-Oligodeoxynucleotides with Toll Like Receptor 9 Induces Apoptosis and Modulates Metaloproteinase-2 Activity in Human Intestinal Epithelium

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Khorramizadeh

    2007-09-01

    Full Text Available Recent reports have indicated different effects of immunostimulatory sequences containing CpG-Oligodeoxynucleotides (ODN on various immune cells. However, the exact role of CpG-ODN in the human gut is unclear. In the present study, we assessed potential effects of CpG-ODN on non lymphoid cell (intestinal epithelial cell line HT-29 on a dose-response and time-course basis. Intestinal epithelial cell line HT-29 was treated with CpG-ODN (CpG 2006 and lipopolysaccharide (LPS at 5, 10, 25, 50 μg/ ml and 1, 5, 10 μg/ ml concentrations, respectively. Following treatments, dose- response and time-course cytotoxicity using a colorimetric method, Metaloproteinase-2 (MMP-2 activity (using gelatin zymography and apoptosis (using annexin-v flowcytometry method assays were performed. Chloroquine treatment was also used for its inhibitory effect on endosomal acidification process to verify specific CpG-ODN and Toll Like Receptor 9 (TLR9 interactions. Cytotoxicity analysis of CpG-ODN showed that CpG-ODN increased significantly the proliferation of CpG-ODN treated cells, as compared to untreated cells, at concentrations of 10-25 μg/ml (pCollectively, our data indicated that intestinal epithelial cell line HT-29 is highly responsive to CpG effect in vitro and exhibits modified activities. The direct CpG-ODN and TLR-9 interactions in HT-29 cells could provide new approaches in malignant tumor therapeutic strategies.

  18. Development of a serum-free co-culture of human intestinal epithelium cell-lines (Caco-2/HT29-5M21

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    Schneider Yves-Jacques

    2006-05-01

    Full Text Available Abstract Background The absorptive and goblet cells are the main cellular types encountered in the intestine epithelium. The cell lineage Caco-2 is a model commonly used to reproduce the features of the bowel epithelium. However, there is a strong debate regarding the value of Caco-2 cell culture to mimick in vivo situation. Indeed, some authors report in Caco-2 a low paracellular permeability and an ease of access of highly diffusible small molecules to the microvilli, due to an almost complete lack of mucus. The HT29-5M21 intestinal cell lineage is a mucin-secreting cellular population. A co-culture system carried out in a serum-free medium and comprising both Caco-2 and HT29-5M21 cells was developed. The systematic use of a co-culture system requires the characterization of the monolayer under a given experimental procedure. Results In this study, we investigated the activity and localization of the alkaline phosphatase and the expression of IAP and MUC5AC genes to determine a correlation between these markers and the cellular composition of a differentiated monolayer obtained from a mixture of Caco-2 and HT29-5M21 cells. We observed that the culture conditions used (serum-free medium did not change the phenotype of each cell type, and produced a reproducible model. The alkaline phosphatase expression characterizing Caco-2 cells was influenced by the presence of HT29-5M21 cells. Conclusion The culture formed by 75% Caco-2 and 25% HT29-5M21 produce a monolayer containing the two main cell types of human intestinal epithelium and characterized by a reduced permeability to macromolecules.

  19. Dysregulated expression of arginine metabolic enzymes in human intestinal tissues of necrotizing enterocolitis and response of CaCO2 cells to bacterial components.

    Science.gov (United States)

    Leung, Kam Tong; Chan, Kathy Yuen Yee; Ma, Terence Ping Yuen; Yu, Jasmine Wai Sum; Tong, Joanna Hung Man; Tam, Yuk Him; Cheung, Hon Ming; To, Ka Fai; Lam, Hugh Simon; Lee, Kim Hung; Li, Karen; Ng, Pak Cheung

    2016-03-01

    The small intestine is the exclusive site of arginine synthesis in neonates. Low levels of circulating arginine have been associated with the occurrence of necrotizing enterocolitis (NEC) but the mechanism of arginine dysregulation has not been fully elucidated. We aimed to investigate (i) expressional changes of arginine synthesizing and catabolic enzymes in human intestinal tissues of NEC, spontaneous intestinal perforation (SIP) and noninflammatory surgical conditions (Surg-CTL) and to investigate the (ii) mechanisms of arginine dysregulation and enterocyte proliferation upon stimulation by bacterial components, arginine depletion, ARG1 overexpression and nitric oxide (NO) supplementation. Our results showed that expressions of arginine synthesizing enzymes ALDH18A1, ASL, ASS1, CPS1, GLS, OAT and PRODH were significantly decreased in NEC compared with Surg-CTL or SIP tissues. Catabolic enzyme ARG1 was increased (>100-fold) in NEC tissues and histologically demonstrated to be expressed by infiltrating neutrophils. No change in arginine metabolic enzymes was observed between SIP and Surg-CTL tissues. In CaCO2 cells, arginine metabolic enzymes were differentially dysregulated by lipopolysaccharide or lipoteichoic acid. Depletion of arginine reduced cell proliferation and this phenomenon could be partially rescued by NO. Overexpression of ARG1 also reduced enterocyte proliferation. We provided the first expressional profile of arginine metabolic enzymes at the tissue level of NEC. Our findings suggested that arginine homeostasis was severely disturbed and could be triggered by inflammatory responses of enterocytes and infiltrating neutrophils as well as bacterial components. Such reactions could reduce arginine and NO, resulting in mucosal damage. The benefit of arginine supplementation for NEC prophylaxis merits further clinical evaluation. PMID:26895666

  20. Survival, growth and toxicity of Microcystis aeruginosa PCC 7806 in experimental conditions mimicking some features of the human gastro-intestinal environment.

    Science.gov (United States)

    Stefanelli, Mara; Vichi, Susanna; Stipa, Giuseppe; Funari, Enzo; Testai, Emanuela; Scardala, Simona; Manganelli, Maura

    2014-05-25

    Cyanotoxins (CTX) are widely produced by several cyanobacteria (CB), increasingly spreading in most water bodies and terrestrial habitats, and represent a risk for human health. CB are prokaryotes, and although mostly autotrophic, several examples of heterotrophy in symbiotic relationship with different organisms have been described. In addition to the known routes of exposure, it has been hypothesized that CB might 'colonize' human intestine with relevant implications for human health. Colonization is a complex process and requires specific features of the possible invaders. Still, a short-term persistence as living and toxin-producing organisms within the intestinal lumen of the host could represent an 'internal' source of exposure to CTX. In this work we ran microcosm experiments (4-18days), looking at Microcystis aeruginosa PCC7806 resistance and cyanotoxin-producing capabilities in darkness, 37°C, pH 2, and subsequent recovery in a rich medium, in darkness, 37°C, in the presence of enteric bacteria, mimicking few important features of the gastrointestinal environment. We measured cyanobacterial populations and growth, microcystin (MC) production and the presence of mcyB gene. M. aeruginosa could grow in the dark at 37°C up to 17days, and survive at pH 2 at a rate between 30% and 70%, depending on the age and toxicity of the starting culture. Cell lysis resulted in a substantial amounts of MC released, not degraded at gastric pH. Following the acidic passage, still in the dark at 37°C, M. aeruginosa restarted to grow within 24h for the next 3-4days, independently on the presence of intestinal bacteria, maintaining the MC cell quota and mcyB gene. Our results show new features of CB: a significant resistance of M. aeruginosa in conditions far from its optimal one, that is an environment mimicking some of the important characteristics of human gastrointestinal tract, suggesting the possibility of an internal source of exposure to CTX, with implications for the risk assessment. PMID:24667652

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

    Directory of Open Access Journals (Sweden)

    Li-li SONG

    2013-11-01

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

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

    Scientific Electronic Library Online (English)

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

    2013-12-01

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

  3. Intestinal Helminths Recovered from Humans in Xieng Khouang Province, Lao PDR with a Particular Note on Haplorchis pumilio Infection

    OpenAIRE

    Chai, Jong-Yil; Sohn, Woon-Mok; Jung, Bong-Kwang; Yong, Tai-Soon; Eom, Keeseon S.; Min, Duk-Young; Insisiengmay, Bounnaloth; Insisiengmay, Sithat; Phommasack, Bounlay; Rim, Han-Jong

    2015-01-01

    A survey of intestinal helminths was undertaken in riparian people in Xieng Khouang Province, Lao PDR. Fecal specimens were collected from 643 people (289 males and 354 females) residing in 4 districts (Nonghet, Kham, Phoukout, and Pek) and were examined by the Kato-Katz technique. The overall helminth egg positive rate was 41.2%, and hookworms revealed the highest prevalence (32.7%) followed by Trichuris trichiura (7.3%) and Ascaris lumbricoides (5.6%). The positive rate for small trematode ...

  4. Radioimmunoimaging in human transitional cell carcinoma xenografted nude mice with monoclonal antibody L4B4

    International Nuclear Information System (INIS)

    The monoclonal antibody L4B4 against transitional cell carcinoma (TCC) was prepared and radioimmunoimaging (RII) was studied in nude mice bearing human TCC using L4B4. L4B4 was identified in vitro by immunohistochemistry. Radioimmunoimaging was performed in human transitional cell carcinoma xenografted nude mice. Immunohistochemistry study showed that L4B4 had high specificity for TCC (23/24), compared to that for other malignant tumors (2/24) and benign tumors (0/7). RII study showed that xenografted tumor was demonstrated clearly on the 3rd and 5th day after injection of 125I labeled L4B4. The T/NT was greater than 4 on the 5th day. The results indicated that L4B4 might be useful in the study of TCC and is worthy to do further investigation

  5. Triclosan Potentiates Epithelial-To-Mesenchymal Transition in Anoikis-Resistant Human Lung Cancer Cells

    OpenAIRE

    Winitthana, Thidarat; Lawanprasert, Somsong; Chanvorachote, Pithi

    2014-01-01

    Alteration of cancer cell toward mesenchymal phenotype has been shown to potentiate tumor aggressiveness by increasing cancer cell metastasis. Herein, we report the effect of triclosan, a widely used antibacterial agent found in many daily products, in enhancing the epithelial-to-mesenchymal transition (EMT) in aggressive anoikis resistant human H460 lung cancer cells. EMT has been long known to increase abilities of the cells to increase migration, invasion, and survival in circulating syste...

  6. The causes of human rights abuses in the countries in transition summary

    Directory of Open Access Journals (Sweden)

    Šijaković Ivan

    2002-01-01

    Full Text Available Author analyzes causes that lead to violation of human rights in countries in transition and in undeveloped countries. He points to the following factors: 'vacuum' in creating of values of the system, some problems in the process of democratization, high grade of homogenization in society (ethnical, religious, ideological, political, economic stagnation and poverty, social climate - the 'production' of enemies, anti-intellectualism etc.

  7. TGF-β1 induces human alveolar epithelial to mesenchymal cell transition (EMT)

    OpenAIRE

    Kamimura Takashi; Mason Roger M; Allen Jeremy T; Kasai Hidenori; Zhang Zhi

    2005-01-01

    Abstract Background Fibroblastic foci are characteristic features in lung parenchyma of patients with idiopathic pulmonary fibrosis (IPF). They comprise aggregates of mesenchymal cells which underlie sites of unresolved epithelial injury and are associated with progression of fibrosis. However, the cellular origins of these mesenchymal phenotypes remain unclear. We examined whether the potent fibrogenic cytokine TGF-β1 could induce epithelial mesenchymal transition (EMT) in the human alveolar...

  8. Fermentation by gut microbiota cultured in a simulator of the human intestinal microbial ecosystem is improved by probiotic Enterococcus faecium CRL 183

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    Elizeu A. Rossi

    2011-10-01

    Full Text Available Background: Enterococci are used in a large number of dairy products, such as starter cultures in food supplements and in foods considered functional. In vitro gut fermentation models present an unmatched opportunity of performing studies frequently allenged in humans and animals owing to ethical concerns. A dynamic model of the human intestinal microbial ecosystem (SHIME was designed to better simulate conditions intestinal microbiota.Methods: The SHIME model was used to study the effect of Enterococuus faecium CRL 183 on the fermentation pattern of the colon microbiota. Initially, an inoculum prepared from human feces was introduced into the reactor vessels and stabilized over 2 wk using a culture medium. This stabilization period was followed by a 2-wk control period during which the microbiota were monitored. The microbiota were then subjected to a 4-wk treatment period by adding 108 CFU/mL of the Enterococcus faecium CRL 183 to vessel one (the stomach compartment.Results: The addition resulted into an overall increase of bacterial marker populations (Enterobacteriaceae, Lactobacillus spp., Bifidobacterium spp. and Clostridium spp., with a significant increase of the Lactobacillus sp. and Bifidobacterium sp populations. The short-chain fatty acid (SCFA concentration increased during the supplementation period; this was due mainly to a significant increase in the levels of acetic, butyric and propionic acids. Ammonium concentrations increased during the supplementation period.Conclusions: Results showed that the major effect of E. faecium CRL 183 was found in the ascendant and transverse colonFunctional Foods in Health and Disease 2011; 10:389-402

  9. How institutions shaped the last major evolutionary transition to large-scale human societies.

    Science.gov (United States)

    Powers, Simon T; van Schaik, Carel P; Lehmann, Laurent

    2016-02-01

    What drove the transition from small-scale human societies centred on kinship and personal exchange, to large-scale societies comprising cooperation and division of labour among untold numbers of unrelated individuals? We propose that the unique human capacity to negotiate institutional rules that coordinate social actions was a key driver of this transition. By creating institutions, humans have been able to move from the default 'Hobbesian' rules of the 'game of life', determined by physical/environmental constraints, into self-created rules of social organization where cooperation can be individually advantageous even in large groups of unrelated individuals. Examples include rules of food sharing in hunter-gatherers, rules for the usage of irrigation systems in agriculturalists, property rights and systems for sharing reputation between mediaeval traders. Successful institutions create rules of interaction that are self-enforcing, providing direct benefits both to individuals that follow them, and to individuals that sanction rule breakers. Forming institutions requires shared intentionality, language and other cognitive abilities largely absent in other primates. We explain how cooperative breeding likely selected for these abilities early in the Homo lineage. This allowed anatomically modern humans to create institutions that transformed the self-reliance of our primate ancestors into the division of labour of large-scale human social organization. PMID:26729937

  10. Characterization of tight junction disruption and immune response modulation in a miniaturized Caco-2/U937 coculture-based in vitro model of the human intestinal barrier.

    Science.gov (United States)

    Ramadan, Qasem; Jing, Lin

    2016-02-01

    A microfluidic-based dynamic in vitro model of the human intestinal barrier has been constructed and characterized. The intestinal epithelial monolayer was mimicked by culturing caco-2 cells on a porous membrane in a double-layered microfluidic chip and interfaced with a co-culture of U937 as a model of immune responsive cells. The physiological flow was also mimicked by a continuous perfusion of culture media from the apical and basolateral side of the porous membrane. This dynamic "in vivo-like" environment maintains a continuous supply of cell nutrient and waste removal and create mechanical shear stress within the physiological ranges which promotes uniform cell growth and tight junction formation. The monolayer permeability to soluble ion changes after treating with LPS, and TNF ? as indicated by the reduction of the TEER value. In addition, the immune competent caco-2/U937-based model allowed the investigating the role of the epithelial layer as a protection barrier to biological hazards as indicated by the suppressing of the pro-inflammatory cytokine expression. PMID:26809386

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

    Directory of Open Access Journals (Sweden)

    Kabiri F

    2011-03-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 st1":*{behavior:url(#ieooui } /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Lactobacillus species are genetically diverse groups of Lactic Acid Bacteria (LAB that have been introduced as probiotics, because of some characteristics such as their anti-tumor properties, helping the intestinal flora balance, production of antibiotics, stimulation of host immune response, etc. The aim of this study was to investigate the effects of cytoplasmic extraction and cell wall of Lactobacillus species isolated from the intestine of common carp on human chronic myelocytic leukemia or K562 cancer cell lines."n"nMethods: The intestinal contents of 115 common carp captured from the natural resources of West Azerbaijan province in Iran were examined for LAB. After isolation, the identification of Lactobacilli was done according to traditional and molecular bacteriological tests. Subsequently, a suspension of each bacterium was prepared and the protein content of the cytoplasm was extracted. Cell wall disintegration was done by cell lysis buffer and sonication. The effects of cytoplasmic extraction and cell wall on K562 cell line proliferation were investigated by MTT assays."n"nResults: The cytoplasmic extraction of the isolated Lactobacilli had significant (p<0.05 anti-proliferative effects on K562 cells. The cytoplasmic extractions of Lactobacillus paracasei and Lactobacillus casei inhibited K562 cell proliferation by 66.56% and 54.28% at 83.33 μg/ml concentration, respectively. Nevertheless, the Lactobacillus cell wall could not inhibit the proliferations of K562 cells (p<0.05."n"nConclusion: In this study, the cytoplasmic extractions of the isolated Lactobacilli from the intestine of common carp had anti-proliferative effects on K562 cell line.

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

    OpenAIRE

    Leo Lahti; Anne Salonen; Riina A Kekkonen; Jarkko Salojärvi; Jonna Jalanka-Tuovinen; Airi Palva; Matej Orešič; Willem M. de Vos

    2013-01-01

    Accumulating evidence indicates that the intestinal microbiota regulates our physiology and metabolism. Bacteria marketed as probiotics confer health benefits that may arise from their ability to affect the microbiota. Here high-throughput screening of the intestinal microbiota was carried out and integrated with serum lipidomic profiling data to study the impact of probiotic intervention on the intestinal ecosystem, and to explore the associations between the intestinal bacteria and serum li...

  13. Occupation of alphavbeta3-integrin by endogenous ligands modulates IGF-I receptor activation and proliferation of human intestinal smooth muscle.

    Science.gov (United States)

    Kuemmerle, John F

    2006-06-01

    We have previously shown that endogenous IGF-I regulates growth of human intestinal smooth muscle cells by stimulating proliferation and inhibiting apoptosis. In active Crohn's disease, expression of IGF-I and the alpha(v)beta(3)-integrin receptor ligands fibronectin and vitronectin is increased. The aim of the present study was to determine whether occupation of the alpha(v)beta(3)-receptor influences IGF-I receptor tyrosine kinase activation and function in human intestinal smooth muscle cells. In untreated cells, IGF-I elicited time-dependent tyrosine phosphorylation of its cognate receptor that was maximal within 2 min and sustained for 30 min. In the presence of the alpha(v)beta(3)-ligand fibronectin, IGF-I-stimulated IGF-I receptor activation was augmented. Conversely, in the presence of the alpha(v)beta(3)-specific disintegrin echistatin, IGF-I-stimulated IGF-I receptor tyrosine kinase phosphorylation was inhibited. IGF-I-stimulated IGF-I receptor activation was accompanied by recruitment of the adapter protein IRS-1, activation of Erk1/2, p70S6 kinase, and proliferation. These effects were augmented by fibronectin and attenuated by echistatin. IGF-I also elicited time-dependent recruitment of protein tyrosine phosphatase SHP-2 that coincided with dephosphorylation of the tyrosine phosphorylated IGF-I receptor tyrosine kinase. The alpha(v)beta(3)-disintegrin echistatin accelerated the rate of SHP-2 recruitment and deactivation of the IGF-I receptor tyrosine kinase. The results show that occupancy of the alpha(v)beta(3)-integrin receptor modulates IGF-I-induced IGF-I receptor activation and function in human intestinal muscle cells. We hypothesize that the concomitant increases in the expression of alpha(v)beta(3)-ligands and of IGF-I in active Crohn's disease may contribute to muscle hyperplasia and stricture formation by acting in concert to augment IGF-I-stimulated IGF-I receptor tyrosine kinase activity and IGF-I-mediated muscle cell growth. PMID:16195423

  14. Chemical, physical and enzymatic pre-treatments of probiotic lactobacilli alter their adhesion to human intestinal mucus glycoproteins.

    Science.gov (United States)

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

    2000-09-15

    Intestinal mucus glycoproteins extracted from faeces of healthy adult subjects were used as a substratum for bacterial adhesion to investigate the effects of physical, chemical and enzymatic pre-treatments of the bacteria on their adhesion. The strains studied were Lactobacillus acidophilus 1 (LCI, Nestlé), L. rhamnosus strain GG (ATCC 53103), L. rhamnosus LC-705, and L. casei strain Shirota (Yakult, Yakult Ltd). Hereafter the strains are referred to as LA1, LGG, LC-705, and Shirota, respectively. Strains LA1 and LGG adhered greatly whereas the adhesion of strains LC-705 and Shirota to intestinal mucus glycoproteins was low. Adhesion of LA1 and LGG was reduced by boiling, autoclaving and by pepsin and trypsin treatments suggesting that the bacterial protein structures are essential for their adhesion. Treatment in ethanol and in propanol prior to adhesion significantly increased the adhesion of LA1 and LC-705, respectively. Adhesion of Shirota strain was not altered by any of the treatments. PMID:11014524

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

    Science.gov (United States)

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

    2015-06-01

    Casein phosphopeptides (CPPs), derived by casein proteolysis, can bind calcium ions and keep them in solution. In vitro studies have demonstrated CPP-induced cell calcium uptake, depending on the formation of (CPP + calcium) complexes and on the degree of differentiation of the intestinal cells. With the present study, we address the persistence of the complexes and of the CPP-induced calcium uptake in intestinal like cells after the digestion process, thus examining their eligibility to serve as nutraceuticals. A calcium-preloaded CPP preparation of commercial origin (Ca-CPPs) was subjected to in vitro digestion. The evolution of the supramolecular structure of the Ca-CPP complexes was studied using laser-light and X-ray scattering. The bioactivity of the pre- and post-digestion Ca-CPPs was determined in differentiated Caco2 and HT-29 cells by video imaging experiments using Fura-2. We found that Ca-CPP aggregates keep a complex supramolecular organization upon digestion, despite getting smaller in size and increasing internal calcium dispersion. Concomitantly and most interestingly, digested Ca-CPPs clearly enhance the uptake of calcium ions, especially in Caco2 cells. In contrast, digestion depletes the ability of post-loaded decalcified-CPPs (Ca-dekCPPs), with a weaker internal structure, to induce calcium uptake. The enhanced bioactivity reached upon digestion strongly suggests a recognized role of Ca-CPPs, in the form used here, as nutraceuticals. PMID:25927875

  16. Decreased expression of Intestinal I- and L-FABP levels in rare human genetic lipid malabsorption syndromes.

    Science.gov (United States)

    Guilmeau, S; Niot, I; Laigneau, J P; Devaud, H; Petit, V; Brousse, N; Bouvier, R; Ferkdadji, L; Besmond, C; Aggerbeck, L P; Bado, A; Samson-Bouma, M E

    2007-08-01

    We investigated, for the first time, the expression of I- and L-FABP in two very rare hereditary lipid malabsorption syndromes as compared with normal subjects. Abetalipoproteinemia (ABL) and Anderson's disease (AD) are characterized by an inability to export alimentary lipids as chylomicrons that result in fat loading of enterocytes. Duodeno-jejunal biopsies were obtained from 14 fasted normal subjects, and from four patients with ABL and from six with AD. Intestinal FABP expression was investigated by immuno-histochemistry, western blot, ELISA and Northern blot analysis. In contrast to normal subjects, the cellular immunostaining for both FABPs was clearly decreased in patients, as the enterocytes became fat-laden. In patients with ABL, the intestinal contents of I- (60.7 +/- 13.38 ng/mg protein) and L-FABP (750.3 +/- 121.3 ng/mg protein) are significantly reduced (50 and 35%, P < 0.05, respectively) as compared to normal subjects (I-135.3 +/- 11.1 ng, L-1211 +/- 110 ng/mg protein). In AD, the patients also exhibited decreased expression (50%, P < 0.05; I-59 +/- 11.88 ng, L-618.2 +/- 104.6 ng/mg protein). Decreased FABP expression was not associated with decreased mRNA levels. The results suggest that enterocytes might regulate intracellular FABP content in response to intracellular fatty acids, which we speculate may act as lipid sensors to prevent their intracellular transport. PMID:17605029

  17. Human rights in the transition to a 'green economy' – Norway and a 'just transition' to a low-carbon society

    OpenAIRE

    2013-01-01

    Climate change challenges human rights (HRs) "as the dominant language of justice." A HRs and climate change discourse has accepted this challenge but this discourse remains marginal – both in traditionally-technocratic international climate policy and debates around transitions to ‘green economies’ (the transition discourse). This reflects HRs’ marginal status vis-à-vis the environment, development and economics generally. Suggesting these are HRs issues is a reframing of traditional approac...

  18. Imaging of the intestinal microcirculation

    Directory of Open Access Journals (Sweden)

    Christian Lehmann

    2012-09-01

    Full Text Available Microcirculatory dysfunction is important in different intestinal pathologies. Therefore, it is essential for adequate therapeutic strategies to be based on reliable microcirculatory diagnostics. Intestinal microvascular perfusion is regulated by an intricate interplay of neuroendocrine, paracrine and mechano-sensory pathways. While rectal microvascular bed can be readily examined at the patients bedside, microcirculation of other parts of the gut can only be assessed intra-operatively or by means of enterostomies. Changes in intestinal microcirculation in various diseases, as observed in animal experiments, further contribute to our understanding of intestinal microcirculation in humans. If microcirculatory changes are not adequately taken care of, perfusion will be reduced and tissue oxygenation may be endangered. Relevant clinical studies are presented in this article. Future developments, e. g. miniaturization of optical probes or swallow-able cameras, will facilitate sophisticated diagnostics and thus improve treatment results.

  19. Enhanced Wound Healing by Recombinant Escherichia coli Nissle 1917 via Human Epidermal Growth Factor Receptor in Human Intestinal Epithelial Cells: Therapeutic Implication Using Recombinant Probiotics

    OpenAIRE

    Choi, Hye Jin; Ahn, Jung Hoon; Park, Seong-Hwan; Do, Kee Hun; Kim, Juil; Moon, Yuseok

    2012-01-01

    The gastrointestinal mucosa has a remarkable ability to repair damage with the support of epidermal growth factor (EGF), which stimulates epithelial migration and proliferative reepithelialization. For the treatment of mucosal injuries, it is important to develop efficient methods for the localized delivery of mucoactive biotherapeutics. The basic idea in the present study came from the assumption that an intestinal probiotic vehicle can carry and deliver key recombinant medicinal proteins to...

  20. In vitro investigations on microbial incorporation of nitrogen from [15N2]urea and [15N2]ammonium chloride by the human intestinal flora

    International Nuclear Information System (INIS)

    6 typical bacteria species of the human intestinal flora (E. coli, Klebsiella pneumoniae, Proteus vulgaris, Streptococcus faecalis, Bacteroides fragilis, Bifidobacterium sp.) were incubated in a liquid medium for 48 h with [15N2]urea and [15N]ammonium chloride. The rates of 15N incorporation were calculated. They depend reproducibly on the species examined, on the kind of the offered NPN substance and on the amount of NPN substance in the medium. With [15N2]urea the minimal rate of incorporation was 3.8% (E. coli) and the maximal one 95.6% (Bifidobacterium sp.). With [15N]ammonium chloride the corresponding figures were 31.0 (Proteus vulg.) and 98.0% (Bifidobacterium sp.). The findings are discussed with regard to a possible enteral detoxification in uremic patients by bacterial utilization and elimination of urea and ammonia. (author)

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

    International Nuclear Information System (INIS)

    A method was developed, by which actively transported substrates can accumulationarily be measured out in vitro on biopsy material. The applicability of this method as index for an active transport performance could then be examined on the example of a control group with sound small intestine and on patients with diabetes mellitus. In order to complete this parameter of the transport function, the specific saccharase activity in the overall homogenate of the mucous membrane was determined. The basis of this determination were the previous investigations on the experimental diabetes mellitus, in which morphologic and functional alterations had been detected. The various influences are discussed, which may be important for the detected alterations. However, a comparison with the results obtained in animal experiments is possible only to a very limited extent, since the situation in human diabetes mellitus is very complicated. (orig./MG)

  2. Intestinal Helminths Recovered from Humans in Xieng Khouang Province, Lao PDR with a Particular Note on Haplorchis pumilio Infection.

    Science.gov (United States)

    Chai, Jong-Yil; Sohn, Woon-Mok; Jung, Bong-Kwang; Yong, Tai-Soon; Eom, Keeseon S; Min, Duk-Young; Insisiengmay, Bounnaloth; Insisiengmay, Sithat; Phommasack, Bounlay; Rim, Han-Jong

    2015-08-01

    A survey of intestinal helminths was undertaken in riparian people in Xieng Khouang Province, Lao PDR. Fecal specimens were collected from 643 people (289 males and 354 females) residing in 4 districts (Nonghet, Kham, Phoukout, and Pek) and were examined by the Kato-Katz technique. The overall helminth egg positive rate was 41.2%, and hookworms revealed the highest prevalence (32.7%) followed by Trichuris trichiura (7.3%) and Ascaris lumbricoides (5.6%). The positive rate for small trematode eggs (STE), which may include Opisthorchis viverrini, heterophyids, and lecithodendriids, was 4.4%. For recovery of adult helminths, 12 STE or nematode/cestode egg-positive people were treated with 40 mg/kg praziquantel and 15 mg/kg pyrantel pamoate, and then purged. Mixed infections with 2 Haplorchis species (H. pumilio and H. taichui), Centrocestus formosanus, Opisthorchis viverrini, a species of cestode (Taenia saginata), and several species of nematodes including hookworms and Enterobius vermicularis were detected. The worm load for trematodes was the highest for H. pumilio with an average of 283.5 specimens per infected person followed by C. formosanus, H. taichui, and O. viverrini. The worm load for nematodes was the highest for hookworms (21.5/infected case) followed by E. vermicularis (3.2/infected case). The results revealed that the surveyed areas of Xieng Khouang Province, Lao PDR are endemic areas of various species of intestinal helminths. The STE found in the surveyed population were verified to be those of heterophyids, particularly H. pumilio. PMID:26323842

  3. Isquemia intestinal

    Directory of Open Access Journals (Sweden)

    Ileana Guerra Macías

    2014-03-01

    Full Text Available La isquemia intestinal está considerada como la causa más letal del síndrome de abdomen agudo; su consecuencia, el infarto del intestino delgado, ocurre por fenómenos tromboembólicos e isquemia no oclusiva. El objetivo del presente artículo es proporcionar una revisión bibliográfica actualizada acerca del tema y facilitar la actuación del cirujano ante este problema de salud de repercusión sistémica y que no es tan infrecuente como se piensa

  4. Returns to human capital under the communist wage grid and during the transition to a market economy

    Czech Academy of Sciences Publication Activity Database

    Münich, Daniel; Švejnar, Jan; Terrell, K.

    Praha : CERGE-EI, 2011 - (Dušek, L.; Lízal, L.), s. 127-174 ISBN 978-80-7344-238-5 Institutional research plan: CEZ:AV0Z70850503 Keywords : human capital * wages * transition Subject RIV: AH - Economics http://www.cerge-ei.cz/pdf/books/cerge-ei-tackles-transition.pdf

  5. Graded effects of unregulated smooth muscle myosin on intestinal architecture, intestinal motility and vascular function in zebrafish.

    Science.gov (United States)

    Abrams, Joshua; Einhorn, Zev; Seiler, Christoph; Zong, Alan B; Sweeney, H Lee; Pack, Michael

    2016-05-01

    Smooth muscle contraction is controlled by the regulated activity of the myosin heavy chain ATPase (Myh11). Myh11 mutations have diverse effects in the cardiovascular, digestive and genitourinary systems in humans and animal models. We previously reported a recessive missense mutation, meltdown (mlt), which converts a highly conserved tryptophan to arginine (W512R) in the rigid relay loop of zebrafish Myh11. The mlt mutation disrupts myosin regulation and non-autonomously induces invasive expansion of the intestinal epithelium. Here, we report two newly identified missense mutations in the switch-1 (S237Y) and coil-coiled (L1287M) domains of Myh11 that fail to complement mlt Cell invasion was not detected in either homozygous mutant but could be induced by oxidative stress and activation of oncogenic signaling pathways. The smooth muscle defect imparted by the mlt and S237Y mutations also delayed intestinal transit, and altered vascular function, as measured by blood flow in the dorsal aorta. The cell-invasion phenotype induced by the three myh11 mutants correlated with the degree of myosin deregulation. These findings suggest that the vertebrate intestinal epithelium is tuned to the physical state of the surrounding stroma, which, in turn, governs its response to physiologic and pathologic stimuli. Genetic variants that alter the regulation of smooth muscle myosin might be risk factors for diseases affecting the intestine, vasculature, and other tissues that contain smooth muscle or contractile cells that express smooth muscle proteins, particularly in the setting of redox stress. PMID:26893369

  6. Humanized Foxp2 accelerates learning by enhancing transitions from declarative to procedural performance.

    Science.gov (United States)

    Schreiweis, Christiane; Bornschein, Ulrich; Burguière, Eric; Kerimoglu, Cemil; Schreiter, Sven; Dannemann, Michael; Goyal, Shubhi; Rea, Ellis; French, Catherine A; Puliyadi, Rathi; Groszer, Matthias; Fisher, Simon E; Mundry, Roger; Winter, Christine; Hevers, Wulf; Pääbo, Svante; Enard, Wolfgang; Graybiel, Ann M

    2014-09-30

    The acquisition of language and speech is uniquely human, but how genetic changes might have adapted the nervous system to this capacity is not well understood. Two human-specific amino acid substitutions in the transcription factor forkhead box P2 (FOXP2) are outstanding mechanistic candidates, as they could have been positively selected during human evolution and as FOXP2 is the sole gene to date firmly linked to speech and language development. When these two substitutions are introduced into the endogenous Foxp2 gene of mice (Foxp2(hum)), cortico-basal ganglia circuits are specifically affected. Here we demonstrate marked effects of this humanization of Foxp2 on learning and striatal neuroplasticity. Foxp2(hum/hum) mice learn stimulus-response associations faster than their WT littermates in situations in which declarative (i.e., place-based) and procedural (i.e., response-based) forms of learning could compete during transitions toward proceduralization of action sequences. Striatal districts known to be differently related to these two modes of learning are affected differently in the Foxp2(hum/hum) mice, as judged by measures of dopamine levels, gene expression patterns, and synaptic plasticity, including an NMDA receptor-dependent form of long-term depression. These findings raise the possibility that the humanized Foxp2 phenotype reflects a different tuning of corticostriatal systems involved in declarative and procedural learning, a capacity potentially contributing to adapting the human brain for speech and language acquisition. PMID:25225386

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

    Directory of Open Access Journals (Sweden)

    Bours Martijn JL

    2007-06-01

    Full Text Available Abstract Background It is well-known that nonsteroidal anti-inflammatory drugs (NSAIDs can cause damage to the small bowel associated with disruption of mucosal barrier function. In healthy human volunteers, we showed previously that topical administration of adenosine 5'-triphosphate (ATP by naso-intestinal tube attenuated a rise in small intestinal permeability induced by short-term challenge with the NSAID indomethacin. This finding suggested that ATP may be involved in the preservation of intestinal barrier function. Our current objective was to corroborate the favourable effect of ATP on indomethacin-induced permeability changes in healthy human volunteers when ATP is administered via enteric-coated capsules, which is a more practically feasible mode of administration. Since ATP effects may have been partly mediated through its breakdown to adenosine, effects of encapsulated adenosine were tested also. Methods By ingesting a test drink containing 5 g lactulose and 0.5 g L-rhamnose followed by five-hour collection of total urine, small intestinal permeability was assessed in 33 healthy human volunteers by measuring the urinary lactulose/rhamnose excretion ratio. Urinary excretion of lactulose and L-rhamnose was determined by fluorescent detection high-pressure liquid chromatography (HPLC. Basal permeability of the small intestine was assessed as a control condition (no indomethacin, no ATP/adenosine. As a model of increased small intestinal permeability, two dosages of indomethacin were ingested at 10 h (75 mg and 1 h (50 mg before ingesting the lactulose/rhamnose test drink. At 1.5 h before indomethacin ingestion, two dosages of placebo, ATP (2 g per dosage or adenosine (1 g per dosage were administered via enteric-coated hydroxypropyl methylcellulose (HPMC capsules with Eudragit L30D-55. Results Median urinary lactulose/rhamnose excretion ratio (g/g in the control condition was 0.032 (interquartile range: 0.0220.044. Compared to the control condition, lactulose/rhamnose ratio after ingestion of indomethacin plus placebo was significantly increased to 0.039 (0.0350.068; P Conclusion In this study, either ATP or adenosine administered via enteric-coated capsules had no effect on indomethacin-induced small intestinal permeability changes in healthy human volunteers. The observed lack of effect of encapsulated ATP/adenosine may have been caused by opening of the enteric-coated supplement at a site distal from the indomethacin-inflicted site. Further studies on site-specific effectiveness of ATP/adenosine on intestinal permeability changes are warranted.

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

    OpenAIRE

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

    1998-01-01

    The effect of amphetamine on gastrointestinal (GI) transit and the plasma levels of cholecystokinin (CCK) were studied in male rats.Gastric emptying was inhibited both acutely and chronically by the administration of amphetamine. GI transit was decreased by the acute administration of amphetamine but not affected by the chronic administration of amphetamine.Plasma CCK levels were increased dose-dependently by amphetamine.Proglumide, a CCK receptor antagonist, prevented amphetamine-induced inh...

  9. Lycopene absorption in human intestinal cells and in mice involves scavenger receptor class B type I but not Niemann-Pick C1-like 1.

    Science.gov (United States)

    Moussa, Myriam; Landrier, Jean-Franois; Reboul, Emmanuelle; Ghiringhelli, Odette; Comra, Christine; Collet, Xavier; Frhlich, Kati; Bhm, Volker; Borel, Patrick

    2008-08-01

    Cholesterol membrane transporters scavenger receptor class B type I (SR-BI) and (cluster determinant 36) are involved in intestinal uptake of lutein and beta-carotene, 2 of the 3 main carotenoids of the human diet. The aim of this work was therefore to determine whether SR-BI and NPC1L1 (Niemann-Pick C1-like 1), another cholesterol transporter, are implicated in absorption of lycopene, the 3rd main carotenoid of the human diet. Anti-human SR-BI antibody and block lipid transport 1 (BLT1) (a chemical inhibitor of lipid transport by SR-BI) impaired up to 60% (all-E) and (5Z)-lycopene uptake (P antibody nor ezetimibe, used as inhibitors of lycopene uptake via NPC1L1, significantly impaired (all-E) or (5Z)-lycopene uptake by Caco-2 monolayers. Thus, the present data show that lycopene absorption is, at least in part, mediated by SR-BI but not by NPC1L1. PMID:18641187

  10. A human breast cell model of pre-invasive to invasive transition

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-03-10

    A crucial step in human breast cancer progression is the acquisition of invasiveness. There is a distinct lack of human cell culture models to study the transition from pre-invasive to invasive phenotype as it may occur 'spontaneously' in vivo. To delineate molecular alterations important for this transition, we isolated human breast epithelial cell lines that showed partial loss of tissue polarity in three-dimensional reconstituted-basement membrane cultures. These cells remained non-invasive; however, unlike their non-malignant counterparts, they exhibited a high propensity to acquire invasiveness through basement membrane in culture. The genomic aberrations and gene expression profiles of the cells in this model showed a high degree of similarity to primary breast tumor profiles. The xenograft tumors formed by the cell lines in three different microenvironments in nude mice displayed metaplastic phenotypes, including squamous and basal characteristics, with invasive cells exhibiting features of higher grade tumors. To find functionally significant changes in transition from pre-invasive to invasive phenotype, we performed attribute profile clustering analysis on the list of genes differentially expressed between pre-invasive and invasive cells. We found integral membrane proteins, transcription factors, kinases, transport molecules, and chemokines to be highly represented. In addition, expression of matrix metalloproteinases MMP-9,-13,-15,-17 was up regulated in the invasive cells. Using siRNA based approaches, we found these MMPs to be required for the invasive phenotype. This model provides a new tool for dissection of mechanisms by which pre-invasive breast cells could acquire invasiveness in a metaplastic context.

  11. Fasting inhibits human cancer progression via the epithelial-mesenchymal transition process: Important evidence unraveled

    OpenAIRE

    Ala-Eddin Al Moustafa

    2012-01-01

    Metastatic cancer disease is responsible for the majority of cancer-related deaths in human cancer patients. In parallel, recently it was pointed-out that fasting could play an important role during cancer treatment and progression via the deregulation of insulin-like growth factor-1 (IGF-1) as well as others growth factors and genes. Meanwhile, it is established that the epithelial-mesenchymal transition (EMT) is a major process for the progression of cancer cells from non-invasive to invasi...

  12. Perfluorinated compounds: Levels, trophic web enrichments and human dietary intakes in transitional water ecosystems

    International Nuclear Information System (INIS)

    Highlights: • PFOA/S levels in a trophic web of a heavily human-stressed lagoon are measured. • High levels were found in mussels, clams and crabs. • The principal PFCs inflow sources for the ecosystem is the river. • Biota (i.e. macroalgae proliferation) contributes to redistribute pollutants in the lagoon. • Human daily dietary intakes are below maximum tolerable levels suggested by the EFSA. -- Abstract: The results of a study on levels of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), analyzed in terms of HPLC-ESI-MS in water, sediment, macrophyte, bivalve, crustacean and fish samples, are reported here. The aim of the research is to define, for the first time, PFOA/S levels in a heavily human-stressed transitional water ecosystem (Orbetello lagoon, Italy) and evaluate trophic web enrichments and human dietary intakes. The results obtained show that: (i) levels significantly higher than those reported in the literature were found in mussels, clams and crabs; (ii) the river is a significant pollution source; (iii) although absolute levels are relatively low, macroalgae proliferation contributes to redistribute pollutants from river-affected areas throughout the entire lagoon basin; (iv) to the best of our current knowledge, water-filtering species considered in this study are the most exposed to PFOA/S pollution; (v) human daily dietary intakes of PFOA/S through Slow Food-endorsed product consumption are below maximum tolerable levels suggested by the EFSA

  13. Small intestinal bacterial overgrowth syndrome

    Directory of Open Access Journals (Sweden)

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

    2010-06-01

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

  14. Extra virgin olive oil phenolic extracts counteract the pro-oxidant effect of dietary oxidized lipids in human intestinal cells.

    Science.gov (United States)

    Incani, Alessandra; Serra, Gessica; Atzeri, Angela; Melis, Maria Paola; Serreli, Gabriele; Bandino, Giovanni; Sedda, Piergiorgio; Campus, Marco; Tuberoso, Carlo I G; Deiana, Monica

    2016-04-01

    The phenolic fraction of extra virgin olive oil (EVOO) concentrates before absorption in the intestinal lumen, where it may contribute to the modulation of enterocytes response to oxidative and inflammatory stimuli. We evaluated the ability of two monovarietal EVOOs phenolic extracts, Bosana and Nera di Gonnos/Tonda di Cagliari, typical and widespread varieties in Sardinia (Italy), to counteract in enterocytes like Caco-2 cells the pro-oxidant action of oxidized lipids, tert-butyl hydroperoxide (TBH) or a mixture of oxysterols of dietary origin. We confirmed that TBH treatment causes a significant increase of ROS production, GSH depletion, increase of MDA, fatty acids hydroperoxides and 7-ketocholesterol, and showed first evidence of oxidative imbalance and cell damage due to oxysterols exposure. Preincubation of cells with the phenolic extracts significantly attenuated oxidative modifications. Bosana extract showed the highest concentration of total phenols, mainly hydroxytyrosol and tyrosol, and was the most active in presence of TBH, where the free radical scavenging activity of these simple phenols seems to be a determining factor. The two extracts were equally effective, in spite of the different composition, in presence of oxysterols, where ROS production probably occurs according to different and more complex mechanisms. PMID:26911552

  15. Inhibitory effect of Avene spring water on vasoactive intestinal peptide-induced inflammation in surviving human skin.

    Science.gov (United States)

    Boisnic, S; Branchet-Gumila, M C; Segard, C

    2001-01-01

    The aim of this study was to evaluate the antiinflammatory effect of Avene spring water on skin fragments stimulated by a neuromediator, vasoactive intestinal peptide (VIP). Skin fragments (from plastic surgery) were maintained for 6 h. To induce inflammation, VIP was applied on contact with the dermis by culture medium. Cellulose patches containing Avene spring water were applied over the epidermis at the same time. Histological analysis was then performed on hematoxylin and eosin stained slides. Edema was evaluated with semiquantitative scores. Vasodilation was studied by calculating the percentage of dilated vessels according to scores and by measuring the surface of these dilated vessels by morphometrical image analysis. Tumor necrosis factor (TNF)-alpha dosage was made on culture supernatants. Edema was significantly increased after application of VIP compared with untreated skin. Treatment with cellulose patches containing Avene spring water showed decreased edema in comparison with cellulose patches containing distilled water. Vasodilation was significantly increased after application of VIP. After treatment with Avene spring water, the percentage and the surface of dilated vessels were significantly decreased. Moreover, treatment with cellulose patches containing Avene spring water showed a decrease in TNF-alpha compared with skins treated with VIP. PMID:11517855

  16. Evaluating learning models with transitions of human interests based on objective rule evaluation indices.

    Science.gov (United States)

    Abe, Hidenao; Yokoi, Hideto; Tsumoto, Shusaku; Ohsaki, Miho; Yamaguchi, Takahira

    2007-01-01

    This paper presents a method to support the evaluation procedure of a data mining process using human-system interaction. The post-processing of mined results is one of the key factors for successful data mining process. However, it is difficult for human experts to completely evaluate several thousands of rules from a large dataset containing noise. We have designed a method based on objective rule evaluation indices to support the rule evaluation procedure; the indices are calculated to evaluate each if-then rule mathematically. We have evaluated five representative learning algorithms to construct rule evaluation models of the actual data mining results from a chronic hepatitis data set. Further, we discuss the relationship between the transitions of the subjective criterion of a medical expert and the performances of the rule evaluation models. PMID:17911783

  17. Expression of recombinant human α-lactalbumin in milk of transgenic cloned pigs is sufficient to enhance intestinal growth and weight gain of suckling piglets.

    Science.gov (United States)

    Ma, Jin; Li, Qiuyan; Li, Yan; Wen, Xiao; Li, Zhiyuan; Zhang, Zaihu; Zhang, Jiuming; Yu, Zhengquan; Li, Ning

    2016-06-10

    Human α-lactalbumin (HLA) has very high nutritional value and important physiological functions during the neonatal period. The peptides derived from HLA provide diverse health benefits including antimicrobial, antiviral, immune-modulating, and antihypertensive effects. Thus, it is worth investigating the effects on offspring development of increasing HLA in milk. In this study, we found that recombinant human α-lactalbumin (rHLA) exhibits efficient inhibition of dipeptidyl peptidase-IV (DPP-IV) activity in an in vitro simulated gastrointestinal digestion system. Using a BAC clone containing the complete HLA gene as a candidate vector, we generated two lines of transgenic cloned sows via somatic cell nuclear transfer that over-expressed rHLA. The average concentrations of rHLA in milk from the two lines of transgenic cloned sows were 2.24±0.71mg/ml and 2.67±1.29mg/ml. The feeding experiments revealed that rHLA represses dipeptidyl peptidase-IV (DPP-IV) activity in vivo. Furthermore, the piglets reared by rHLA transgenic cloned sows exhibit better performance in gain of body weight and intestine growth than the control piglets reared by non-transgenic sows. Therefore, these findings indicate that rHLA could serve as a natural precursor for a DPP-IV inhibitor, and the transgenic technology that produced the over-expression of rHLA could be a useful method for pig breeders to improve lactation performance. PMID:26899869

  18. Transition-state analysis of 2-O-acetyl-ADP-ribose hydrolysis by human macrodomain 1.

    Science.gov (United States)

    Hirsch, Brett M; Burgos, Emmanuel S; Schramm, Vern L

    2014-10-17

    Macrodomains, including the human macrodomain 1 (MacroD1), are erasers of the post-translational modification of monoadenosinediphospho-ribosylation and hydrolytically deacetylate the sirtuin product O-acetyl-ADP-ribose (OAADPr). OAADPr has been reported to play a role in cell signaling based on oocyte microinjection studies, and macrodomains affect an array of cell processes including transcription and response to DNA damage. Here, we investigate human MacroD1 by transition-state (TS) analysis based on kinetic isotope effects (KIEs) from isotopically labeled OAADPr substrates. Competitive radiolabeled-isotope effects and mass spectrometry were used to obtain KIE data to yield intrinsic KIE values. Intrinsic KIEs were matched to a quantum chemical structure of the TS that includes the active site residues Asp184 and Asn174 and a structural water molecule. Transition-state analysis supports a concerted mechanism with an early TS involving simultaneous nucleophilic water attack and leaving group bond cleavage where the breaking C-O ester bond=1.60 and the C-O bond to the attacking water nucleophile=2.30 . The MacroD1 TS provides mechanistic understanding of the OAADPr esterase chemistry. PMID:25051211

  19. Selective survival of calretinin- and vasoactive-intestinal-peptide-containing nerve elements in human chagasic submucosa and mucosa.

    Science.gov (United States)

    Jabari, Samir; da Silveira, Alexandre B M; de Oliveira, Enio C; Neto, Salustiano G; Quint, Karl; Neuhuber, Winfried; Brehmer, Axel

    2012-08-01

    Chronic Chagas' disease is frequently characterized by massive myenteric neuron loss resulting in megacolon with severely and irreversibly disturbed motility. Here, we focused on two submucosal neuron populations, immunoreactive for calretinin (CALR) or somatostatin (SOM), and their respective mucosal nerve fibres in chagasic megacolon. Surgically removed megacolonic segments of seven chagasic patients were compared with seven age- and region-matched non-chagasic control segments. Evaluation included immunohistochemical triple-staining of cryosections for CALR, SOM and peripherin or for CALR and vasoactive intestinal peptide (VIP) and of submucosal whole-mounts for CALR, SOM and the pan-neuronal marker anti-HuC/D. Submucosal neuron counts in chagasic tissue revealed neuron numbers reduced to 51.2% of control values. In cryosections, nerve fibre area measurements revealed 8.6% nerve fibre per mucosal area in control segments, but this value decreased to 1.5% in megacolonic segments. In both evaluations, a disproportionate decrease of SOM-reactive nerve elements was observed. The proportions of SOM-positive neurons related to the total neuron number declined to 2% (control 10%) and the proportion of SOM-reactive mucosal nerve fibres related to the whole mucosal area to 0.014% (control 1.8%)in chagasic tissue. The second set of cryosections revealed extensive colocalization of CALR with VIP in both surviving submucosal perikarya and mucosal nerve fibres. We suggest that VIP, a neuroprotective and neuroeffectory peptide typically contained in submucosal neurons, allows both the VIP-containing neurons to endure and the patients to survive by maintaining their mucosal barrier, despite the almost complete loss of colonic motility for decades. PMID:22555304

  20. Four Generations of Transition State Analogues for Human Purine Nucleoside Phosphorylase

    Energy Technology Data Exchange (ETDEWEB)

    Ho, M.; Shi, W; Rinaldo-Mathis, A; Tyler, P; Evans, G; Almo, S; Schramm, V

    2010-01-01

    Inhibition of human purine nucleoside phosphorylase (PNP) stops growth of activated T-cells and the formation of 6-oxypurine bases, making it a target for leukemia, autoimmune disorders, and gout. Four generations of ribocation transition-state mimics bound to PNP are structurally characterized. Immucillin-H (K*{sub i} = 58 pM, first-generation) contains an iminoribitol cation with four asymmetric carbons. DADMe-Immucillin-H (K*{sub i} = 9 pM, second-generation), uses a methylene-bridged dihydroxypyrrolidine cation with two asymmetric centers. DATMe-Immucillin-H (K*{sub i} = 9 pM, third-generation) contains an open-chain amino alcohol cation with two asymmetric carbons. SerMe-ImmH (K*{sub i} = 5 pM, fourth-generation) uses achiral dihydroxyaminoalcohol seramide as the ribocation mimic. Crystal structures of PNPs establish features of tight binding to be; (1) ion-pair formation between bound phosphate (or its mimic) and inhibitor cation, (2) leaving-group interactions to N1, O6, and N7 of 9-deazahypoxanthine, (3) interaction between phosphate and inhibitor hydroxyl groups, and (4) His257 interacting with the 5{prime}-hydroxyl group. The first generation analogue is an imperfect fit to the catalytic site with a long ion pair distance between the iminoribitol and bound phosphate and weaker interactions to the leaving group. Increasing the ribocation to leaving-group distance in the second- to fourth-generation analogues provides powerful binding interactions and a facile synthetic route to powerful inhibitors. Despite chemical diversity in the four generations of transition-state analogues, the catalytic site geometry is almost the same for all analogues. Multiple solutions in transition-state analogue design are available to convert the energy of catalytic rate enhancement to binding energy in human PNP.