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Sample records for human intestinal transit

  1. Human anaerobic intestinal "rope" parasites

    OpenAIRE

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

    2013-01-01

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

  2. Human intestinal spirochetosis – a review

    Directory of Open Access Journals (Sweden)

    Gebbers, Jan-Olaf

    2010-01-01

    Full Text Available Human intestinal spirochetosis (IS is a condition defined histologically by the presence of spirochetal microorganisms attached to the apical cell membrane of the colorectal epithelium. Intestinal spirochetes comprise a heterogeneous group of bacteria. In humans, Brachyspira aalborgi and Brachyspira pilosicoli predominate. Prevalence rates of IS are low where living standards are high, in contrast to poorly developed areas where IS is common. Homosexuals and HIV-infected individuals are at high risk of being colonized. Clinical significance in individual cases has remained unclear up to now. A review of the literature assumes that invasion of spirochetes beyond the surface epithelium may be associated with gastrointestinal symptoms which respond to antibiotic treatment (metronidazole, whereas individuals lacking this feature may be mostly asymptomatic. Of unknown reason, homosexual and HIV-positive men as well as children are more likely to be symptomatic irrespective of invasion. Rare cases of spirochetemia and multiple organ failure have been reported in critically ill patients with IS.

  3. Human intestinal capillariasis in Thailand

    OpenAIRE

    Saichua, Prasert; Nithikathkul, Choosak; Kaewpitoon, Natthawut

    2008-01-01

    Intestinal capillariasis caused by Capillaria philippinensis appeared first in the Philippines and subsequently in Thailand, Japan, Iran, Egypt and Taiwan; major outbreaks have occurred in the Philippines and Thailand. This article reviews the epidemiology, history and sources of C. philippinensis infection in Thailand. The annual epidemiological surveillance reports indicated that 82 accumulated cases of intestinal capillariasis were found in Thailand from 1994-2006. That made Thailand a Cap...

  4. Human intestinal capillariasis in Thailand

    Directory of Open Access Journals (Sweden)

    Prasert Saichua, Choosak Nithikathkul, Natthawut Kaewpitoon

    2008-01-01

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

  5. Human intestinal capillariasis in Thailand.

    Science.gov (United States)

    Saichua, Prasert; Nithikathkul, Choosak; Kaewpitoon, Natthawut

    2008-01-28

    Intestinal capillariasis caused by Capillaria philippinensis appeared first in the Philippines and subsequently in Thailand, Japan, Iran, Egypt and Taiwan; major outbreaks have occurred in the Philippines and Thailand. This article reviews the epidemiology, history and sources of C. philippinensis infection in Thailand. The annual epidemiological surveillance reports indicated that 82 accumulated cases of intestinal capillariasis were found in Thailand from 1994-2006. That made Thailand a Capillaria-prevalent area. Sisaket, in northeast Thailand, was the first province which has reported intestinal capillariasis. Moreover, Buri Ram presented a high prevalence of intestinal capillariasis, totaling 24 cases from 1994-2006. About half of all cases have consumed raw or undercooked fish. However, even if the numbers of the intestinal capillariasis cases in Thailand is reduced, C. philippinensis infection cases are still reported. The improvement of personal hygiene, specifically avoiding consumption of undercooked fish and promoting a health education campaign are required. These strategies may minimize or eliminate C. philippinensis infection in Thailand. PMID:18203280

  6. Compartmentalization of Aquaporins in the Human Intestine

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    Rajendram V. Rajnarayanan

    2008-06-01

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

  7. Alternative Functional In Vitro Models of Human Intestinal Epithelia

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    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.

  8. Human intestinal microbial metabolism of naringin.

    Science.gov (United States)

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

    2015-09-01

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

  9. 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

  10. Molecular Epidemiology of Human Intestinal Amoebas in Iran

    OpenAIRE

    Rezaian, M.; 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...

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

    DEFF Research Database (Denmark)

    Worsoe, Jonas; Fynne, Lotte

    2011-01-01

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

  12. 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

  13. 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.

  14. 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

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

    OpenAIRE

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

    2001-01-01

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

  16. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Korman, L.Y.; Sayadi, H.; Bass, B.; Moody, T.W.; Harmon, J.W.

    1989-07-01

    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 (/sup 125/I)VIP binding and (/sup 125/I)substance P in human colon and small intestine using autoradiographic techniques. (/sup 125/I)VIP binding was present in high density in the mucosal layer of colon and small intestine. (/sup 125/I)VIP binding was not significantly greater than nonspecific binding in smooth muscle layers or the lymphoid follicles. In contrast, (/sup 125/I)substance P binding was present in high density over the colonic muscle but was not present over the mucosal layer. In human colon cancer, (/sup 125/I)VIP grain density over the malignant tissue was only slightly higher than background. These autoradiographic studies of (/sup 125/I)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.

  18. Impaired transit and tolerance of intestinal gas in the irritable bowel syndrome

    OpenAIRE

    Serra, J; Azpiroz, F; Malagelada, J

    2001-01-01

    Abstract Background—Patients with irritable bowel syndrome (IBS) frequently complain of excessive gas but their fasting volume of intestinal gas is apparently normal. We hypothesised that the pathophysiological mechanism involved may be impairment of intestinal gas transit. Aim—To investigate intestinal gas transit and tolerance in IBS patients compared with healthy subjects. Methods—A gas mixture (N2, O2, and CO2 in venous proportions) was infused into the jejunum of 20 patients with IBS and...

  19. A Gutsy Task: Generating Intestinal Tissue from Human Pluripotent Stem Cells

    OpenAIRE

    Finkbeiner, Stacy R.; Spence, Jason R.

    2013-01-01

    Many significant advances in our understanding of intestine development, intestinal stem cell homeostasis and differentiation have been made in recent years. These advances include novel techniques to culture primary human and mouse intestinal epithelium in three-dimensional matrices, and de novo generation of human intestinal tissue from embryonic and induced pluripotent stem cells. This short review will focus on the directed differentiation of human pluripotent stem cells into intestinal t...

  20. Understanding drug resistance in human intestinal protozoa.

    Science.gov (United States)

    El-Taweel, Hend Aly

    2015-05-01

    Infections with intestinal protozoa continue to be a major health problem in many areas of the world. The widespread use of a limited number of therapeutic agents for their management and control raises concerns about development of drug resistance. Generally, the use of any antimicrobial agent should be accompanied by meticulous monitoring of its efficacy and measures to minimize resistance formation. Evidence for the occurrence of drug resistance in different intestinal protozoa comes from case studies and clinical trials, sometimes with a limited number of patients. Large-scale field-based assessment of drug resistance and drug sensitivity testing of clinical isolates are needed. Furthermore, the association of drug resistance with certain geographic isolates or genotypes deserves consideration. Drug resistance has been triggered in vitro and has been linked to modification of pyruvate:ferredoxin oxidoreductase, nitroreductases, antioxidant defense, or cytoskeletal system. Further mechanistic studies will have important implications in the development of second generation therapeutic agents. PMID:25782683

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

    Directory of Open Access Journals (Sweden)

    Gui-zhen XIAO

    2013-07-01

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

  2. A model for Vibrio cholerae colonization of the human intestine

    OpenAIRE

    Spagnuolo, Anna Maria; DiRita, Victor; Kirschner, Denise

    2011-01-01

    Vibrio cholerae is a strict human pathogen that causes the disease cholera. It is an old-world pathogen that has re-emerged as a new threat since the early 1990s. V. cholerae colonizes the upper, small intestine where it produces a toxin that leads to watery diarrhea, characterizing the disease [36]. The dynamics of colonization by the bacteria of the intestines are largely unknown. Although a large initial infectious dose is required for infection, data suggests that only a smaller sub-popul...

  3. Alpha2 adrenoceptors regulate proliferation of human intestinal epithelial cells

    OpenAIRE

    Schaak, S; Cussac, D; Cayla, C; Devedjian, J; Guyot, R.; Paris, H; Denis, C

    2000-01-01

    BACKGROUND AND AIMS—Previous studies on rodents have suggested that catecholamines stimulate proliferation of the intestinal epithelium through activation of ?2 adrenoceptors located on crypt cells. The occurrence of this effect awaits demonstration in humans and the molecular mechanisms involved have not yet been elucidated. Here, we examined the effect of ?2 agonists on a clone of Caco2 cells expressing the human ?2A adrenoceptor.?METHODS—Cells were transfected with a bicistronic plasmid co...

  4. Functional Metagenomic Investigations of the Human Intestinal Microbiota

    OpenAIRE

    Moore, Aimee M.; Munck, Christian; Sommer, Morten O. A.; Dantas, Gautam

    2011-01-01

    The human intestinal microbiota encode multiple critical functions impacting human health, including metabolism of dietary substrate, prevention of pathogen invasion, immune system modulation, and provision of a reservoir of antibiotic resistance genes accessible to pathogens. The complexity of this microbial community, its recalcitrance to standard cultivation, and the immense diversity of its encoded genes has necessitated the development of novel molecular, microbiological, and genomic too...

  5. 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

    Background—Arylamine 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. ?Aims—To investigate NAT expression in apparently healthy human intestines in order to understand the possible r...

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

    OpenAIRE

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

    2013-01-01

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

  7. 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.

  8. Síndrome estreñimiento: métodos para medir la velocidad de tránsito intestinal / Constipation syndrome: methods for measuring the speed of intestinal transit

    Scientific Electronic Library Online (English)

    Raúl, León-Barúa.

    2012-01-01

    Full Text Available En el presente artículo, recuerdo lo que presenté, en un simposio llevado a cabo en nuestra Sociedad sobre el síndrome estreñimiento, en relación con la definición y los factores determinantes de este síndrome, y, además, con los métodos que hemos creado para medir en forma fisiológica la velocidad [...] del tránsito intestinal, especialmente colónico. Abstract in english In the present article, I remind what I presented, in a symposium performed in our Society on the constipation syndrome, in relation with the definition and the determinant factores of this syndrome, and, in addition, with the methods we have created to determine physiologically the velocity of the [...] intestinal transit, specially colonic.

  9. 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% ...

  10. 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...

  11. Halophilic archaea in the human intestinal mucosa.

    Science.gov (United States)

    Oxley, Andrew P A; Lanfranconi, Mariana P; Würdemann, Dieco; Ott, Stephan; Schreiber, Stefan; McGenity, Terry J; Timmis, Kenneth N; Nogales, Balbina

    2010-09-01

    The human gastrointestinal tract microbiota, despite its key roles in health and disease, remains a diverse, variable and poorly understood entity. Current surveys reveal a multitude of undefined bacterial taxa and a low diversity of methanogenic archaea. In an analysis of the microbiota in colonic mucosal biopsies from patients with inflammatory bowel disease we found 16S rDNA sequences representing a phylogenetically rich diversity of halophilic archaea from the Halobacteriaceae (haloarchaea), including novel phylotypes. As the human colon is not considered a salty environment and haloarchaea are described as extreme halophiles, we evaluated and further discarded the possibility that these sequences originated from pre-colonoscopy saline lavage solutions. Furthermore, aerobic enrichment cultures prepared from a patient biopsy at low salinity (2.5% NaCl) yielded haloarchaeal sequence types. Microscopic observation after fluorescence in situ hybridization provided evidence of the presence of viable archaeal cells in these cultures. These results prove the survival of haloarchaea in the digestive system and suggest that they may be members of the mucosal microbiota, even if present in low numbers in comparison with methanogenic archaea. Investigation of a potential physiological basis of this association may lead to new insights into gastrointestinal health and disease. PMID:20438582

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

    DEFF Research Database (Denmark)

    Denton, Paul W.; Nochi, T

    2012-01-01

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

  13. Age-associated modifications of intestinal permeability and innate immunity in human small intestine.

    Science.gov (United States)

    Man, Angela L; Bertelli, Eugenio; Rentini, Silvia; Regoli, Mari; Briars, Graham; Marini, Mario; Watson, Alastair J M; Nicoletti, Claudio

    2015-10-01

    The physical and immunological properties of the human intestinal epithelial barrier in aging are largely unknown. Ileal biopsies from young (7-12 years), adult (20-40 years) and aging (67-77 years) individuals not showing symptoms of gastrointestinal (GI) pathologies were used to assess levels of inflammatory cytokines, barrier integrity and cytokine production in response to microbial challenges. Increased expression of interleukin (IL)-6, but not interferon (IFN)?, tumour necrosis factor (TNF)-? and IL-1? was observed during aging; further analysis showed that cluster of differentiation (CD)11c(+) dendritic cells (DCs) are one of the major sources of IL-6 in the aging gut and expressed higher levels of CD40. Up-regulated production of IL-6 was accompanied by increased expression of claudin-2 leading to reduced transepithelial electric resistance (TEER); TEER could be restored in in vitro and ex vivo cultures by neutralizing anti-IL-6 antibody. In contrast, expression of zonula occludens-1 (ZO-1), occludin and junctional-adhesion molecule-A1 did not vary with age and overall permeability to macromolecules was not affected. Finally, cytokine production in response to different microbial stimuli was assessed in a polarized in vitro organ culture (IVOC). IL-8 production in response to flagellin declined progressively with age although the expression and distribution of toll-like receptor (TLR)-5 on intestinal epithelial cells (IECs) remained unchanged. Also, flagellin-induced production of IL-6 was less pronounced in aging individuals. In contrast, TNF-? production in response to probiotics (VSL#3) did not decline with age; however, in our experimental model probiotics did not down-regulate the production of IL-6 and expression of claudin-2. These data suggested that aging affects properties of the intestinal barrier likely to impact on age-associated disturbances, both locally and systemically. PMID:25948052

  14. Functional Metagenomic Investigations of the Human Intestinal Microbiota

    DEFF Research Database (Denmark)

    Moore, Aimee M.; Munck, Christian

    2011-01-01

    The human intestinal microbiota encode multiple critical functions impacting human health, including metabolism of dietary substrate, prevention of pathogen invasion, immune system modulation, and provision of a reservoir of antibiotic resistance genes accessible to pathogens. The complexity of this microbial community, its recalcitrance to standard cultivation, and the immense diversity of its encoded genes has necessitated the development of novel molecular, microbiological, and genomic tools. Functional metagenomics is one such culture-independent technique, used for decades to study environmental microorganisms, but relatively recently applied to the study of the human commensal microbiota. Metagenomic functional screens characterize the functional capacity of a microbial community, independent of identity to known genes, by subjecting the metagenome to functional assays in a genetically tractable host. Here we highlight recent work applying this technique to study the functional diversity of the intestinal microbiota, and discuss how an approach combining high-throughput sequencing, cultivation, and metagenomic functional screens can improve our understanding of interactions between this complex community and its human host.

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

    Directory of Open Access Journals (Sweden)

    Paola Andrea Gómez Buitrago

    2015-10-01

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

  16. Nonsteroidal antiinflammatory drug-induced intestinal inflammation in humans

    International Nuclear Information System (INIS)

    This study examines the effects of nonsteroidal antiinflammatory drugs on the small intestine in humans. Using an 111In-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 111In 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 (75Se) 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

  17. Intestinal Microbiota Modulates Gluten-Induced Immunopathology in Humanized Mice.

    Science.gov (United States)

    Galipeau, Heather J; McCarville, Justin L; Huebener, Sina; Litwin, Owen; Meisel, Marlies; Jabri, Bana; Sanz, Yolanda; Murray, Joseph A; Jordana, Manel; Alaedini, Armin; Chirdo, Fernando G; Verdu, Elena F

    2015-11-01

    Celiac disease (CD) is an immune-mediated enteropathy triggered by gluten in genetically susceptible individuals. The recent increase in CD incidence suggests that additional environmental factors, such as intestinal microbiota alterations, are involved in its pathogenesis. However, there is no direct evidence of modulation of gluten-induced immunopathology by the microbiota. We investigated whether specific microbiota compositions influence immune responses to gluten in mice expressing the human DQ8 gene, which confers moderate CD genetic susceptibility. Germ-free mice, clean specific-pathogen-free (SPF) mice colonized with a microbiota devoid of opportunistic pathogens and Proteobacteria, and conventional SPF mice that harbor a complex microbiota that includes opportunistic pathogens were used. Clean SPF mice had attenuated responses to gluten compared to germ-free and conventional SPF mice. Germ-free mice developed increased intraepithelial lymphocytes, markers of intraepithelial lymphocyte cytotoxicity, gliadin-specific antibodies, and a proinflammatory gliadin-specific T-cell response. Antibiotic treatment, leading to Proteobacteria expansion, further enhanced gluten-induced immunopathology in conventional SPF mice. Protection against gluten-induced immunopathology in clean SPF mice was reversed after supplementation with a member of the Proteobacteria phylum, an enteroadherent Escherichia coli isolated from a CD patient. The intestinal microbiota can both positively and negatively modulate gluten-induced immunopathology in mice. In subjects with moderate genetic susceptibility, intestinal microbiota changes may be a factor that increases CD risk. PMID:26456581

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

    OpenAIRE

    Castellanos-Gonzalez, Alejandro; Cabada, Miguel M; Nichols, Joan; Gomez, Guillermo; White, A Clinton

    2013-01-01

    The study of human intestinal pathogens has been limited by the lack of methods for the long-term culture of primary human intestinal epithelial cells (PECs). The development of infection models with PECs would allow a better understanding of host-parasite interactions. The objective of this study was to develop a novel method for prolonged in vitro cultivation of PECs that can be used to study Cryptosporidium infection. We isolated intact crypts from human intestines removed during weight lo...

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    Intestinal immune cells are important in host defense, yet the determinants for human lymphoid homeostasis in the intestines are poorly understood. In contrast, lymphoid homeostasis has been studied extensively in mice, where the requirement for a functional common ?-chain molecule has been established. We hypothesized that humanized mice could offer insights into human intestinal lymphoid homeostasis if generated in a strain with an intact mouse common ?-chain molecule. To address this hypothes...

  20. Small intestinal transit, absorption, and permeability in patients with AIDS with and without diarrhoea

    OpenAIRE

    Sharpstone, D; Neild, P; Crane, R.; Taylor, C.; Hodgson, C.; Sherwood, R; Gazzard, B.; Bjarnason, I.

    1999-01-01

    BACKGROUND—Diarrhoea in AIDS is associated with anorexia and weight loss. The importance of gastrointestinal transit in such symptoms has not been addressed.?AIMS—To assess jejunal to caecal transit times in subjects with AIDS related diarrhoea and weight loss and correlate these with measures of absorptive capacity and intestinal permeability.?METHODS—Jejunal to caecal transit times were assessed in 20 seronegative controls and 60 HIV seropositive subjects from serum analysis of 3-O-methyl-D...

  1. 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.

  2. Alpha2 adrenoceptors regulate proliferation of human intestinal epithelial cells

    Science.gov (United States)

    Schaak, S; Cussac, D; Cayla, C; Devedjian, J; Guyot, R; Paris, H; Denis, C

    2000-01-01

    BACKGROUND AND AIMS—Previous studies on rodents have suggested that catecholamines stimulate proliferation of the intestinal epithelium through activation of ?2 adrenoceptors located on crypt cells. The occurrence of this effect awaits demonstration in humans and the molecular mechanisms involved have not yet been elucidated. Here, we examined the effect of ?2 agonists on a clone of Caco2 cells expressing the human ?2A adrenoceptor.?METHODS—Cells were transfected with a bicistronic plasmid containing the ?2C10 and neomycin phosphotransferase genes. G418 resistant clones were assayed for receptor expression using radioligand binding. Receptor functionality was assessed by testing its ability to couple Gi proteins and to inhibit cAMP production. Mitogen activated protein kinase (MAPK) phosphorylation was followed by western blot, and cell proliferation was estimated by measuring protein and DNA content.?RESULTS—Permanent transfection of Caco2 cells allowed us to obtain a clone (Caco2-3B) expressing ?2A adrenoceptors at a density similar to that found in normal human intestinal epithelium. Caco2-3B retained morphological features and brush border enzyme expression characteristic of enterocytic differentiation. The receptor was coupled to Gi2/Gi3 proteins and its stimulation caused marked diminution of forskolin induced cAMP production. Treatment of Caco2-3B with UK14304 (?2 agonist) induced a rapid increase in the phosphorylation state of MAPK, extracellular regulated protein kinase 1 (Erk1), and 2 (Erk2). This event was totally abolished in pertussis toxin treated cells and in the presence of kinase inhibitors (genistein or PD98059). It was unaffected by protein kinase C downregulation but correlated with a transient increase in Shc tyrosine phosphorylation. Finally, sustained exposure of Caco2-3B to UK14304 resulted in modest but significant acceleration of cell proliferation. None of these effects was observed in the parental cell line Caco2.?CONCLUSION—The results obtained in the present study support a regulatory role for ?2 adrenoceptors in intestinal cell proliferation.???Keywords: ?2 adrenoceptor; Caco2; mitogen activated protein kinase; intestinal cell proliferation PMID:10896916

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

    Science.gov (United States)

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

    2015-07-01

    When functioning properly, the intestine is one of the key interfaces between the human body and its environment. It is responsible for extracting nutrients from our food and excreting our waste products. It provides an environment for a host of healthful microbes and serves as a first defense against pathogenic ones. These processes require tight homeostatic controls, which are provided by the interactions of a complex mix of epithelial, stromal, neural and immune cells, as well as the resident microflora. This homeostasis can be disrupted by invasive microbes, genetic lesions, and carcinogens, resulting in diseases such Clostridium difficile infection, inflammatory bowel disease (IBD) and cancer. Enormous strides have been made in understanding how this important organ functions in health and disease using everything from cell culture systems to animal models to human tissue samples. This has resulted in better therapies for all of these diseases, but there is still significant room for improvement. In the United States alone, 14,000 people per year die of C. difficile, up to 1.6 million people suffer from IBD, and more than 50,000 people die every year from colon cancer. Because these and other intestinal diseases arise from complex interactions between the different components of the gut ecosystem, we propose that systems approaches that address this complexity in an integrative manner may eventually lead to improved therapeutics that deliver lasting cures. This review will discuss the use of systems biology for studying intestinal diseases in vivo with particular emphasis on mouse models. Additionally, it will focus on established experimental techniques that have been used to drive this systems-level analysis, and emerging techniques that will push this field forward in the future. PMID:26040649

  4. 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

  5. Salmonella interactions with polarized human intestinal Caco-2 epithelial cells.

    Science.gov (United States)

    Finlay, B B; Falkow, S

    1990-11-01

    Polarized monolayers of the human intestinal epithelial Caco-2 cell line were grown on permeable filters and infected apically with either Salmonella choleraesuis or Salmonella typhimurium. Both Salmonella species penetrated through the monolayer, requiring 2 h before appearing in the basolateral medium. Both species caused a loss in transepithelial resistance by 3-4 h, and the monolayer's integrity was completely disrupted by 6 h. Scanning and transmission electron microscopy revealed that the bacteria interacted with well-defined apical microvilli and caused disruptions in the brush border, including elongation and denuding of the microvilli. The cytoplasm was also disrupted locally, with blebs protruding from the apical surface. The bacteria entered (invaded) these cells and were enclosed in membrane-bound vacuoles within the cytoplasm. By 6 h there were many bacteria within most Caco-2 cells, and these organisms caused serious cytopathic consequences. These morphologic observations correlated well with animal infection models, indicating that this in vitro system will be useful to study pathogens that interact with human intestinal epithelia. PMID:2230236

  6. 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.

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

    DEFF Research Database (Denmark)

    Karlsen, Stine; Fynne, Lotte

    2012-01-01

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

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

    Scientific Electronic Library Online (English)

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

    2010-05-01

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

  9. 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

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

    OpenAIRE

    Ben Amor, K.

    2004-01-01

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

  11. Cloning and expression of the human vasoactive intestinal peptide receptor

    Energy Technology Data Exchange (ETDEWEB)

    Sreedharan, S.P.; Robichon, A.; Peterson, K.E.; Goetzl, E.J. (Univ. of California Medical Center, San Francisco (United States))

    1991-06-01

    Vasoactive intestinal peptide (VIP) is a neuroendocrine mediator found in the central and peripheral nervous systems. Distinct subsets of neural, respiratory, gastrointestinal, and immune cells bear specific high-affinity receptors for VIP, which are associated with a guanine nucleotide-binding (G) protein capable of activatingadenylate cyclase. A cDNA clone (GPRN1) encoding the human VIP receptor was identified in librares prepared from the Nalm 6 line of leukemic pre-B lymphoblasts and the HT-29 line of colon carcinoma cells. The deduced 362-amino acid polypeptide sequence encoded by GPRN1 shares a seven-transmembrane-segment hydropathicity profile with other G protein-coupled receptors. Northern blot analyses identified a 2.7-kilobase transcript of the VIP receptor in Nalm 6 and HT-29 cells as well as in tissues from rat brain, colon, heart, lung, kidney, spleen, and small intestine. COS-6 cells transfected with GPRN1 bound {sup 125}I-labeled VIP specifically with a dissociation constant (K{sub d}) of 2.5 nM. VIP--and less effectively secretin, peptide histidine isoleucine (PHI), and glucagon competitively displaced bound {sup 125}I-VIP from transfected COS-6 cells, with potencies in the order VIP > secretin = PHI >> glucagon. VIP stimulated adenylate cyclase activity in stably transfected Chinese hanster ovary K1 cells, indicing a 3-fold increase in the intracellular level of cAMP. The VIP receptor cloned exhibits {le}24% homology with other receptors in the same superfamily and thus represents a subset of G protein-coupled receptors for peptide ligands.

  12. Movement and Fixation of Intestinal Microbiota after Administration of Human Feces to Germfree Mice

    OpenAIRE

    Kibe, Ryoko; Sakamoto, Mitsuo; Yokota, Hiroshi; Ishikawa, Hiroki; Aiba, Yuji; Koga, Yasuhiro; BENNO, Yoshimi

    2005-01-01

    Human flora-associated (HFA) mice have been considered a tool for studying the ecology and metabolism of intestinal bacteria in humans, although they have some limitations as a model. Shifts in dominant species of microbiota in HFA mice after the administration of human intestinal microbiota was revealed by 16S rRNA gene sequence and terminal restriction fragment length polymorphism (T-RFLP) analyses. Characteristic terminal restriction fragments (T-RFs) were quantified as the proportion of t...

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

    OpenAIRE

    Shah, Uzma; Dickinson, Bonny L; BLUMBERG, RICHARD S.; Simister, Neil E.; LENCER, WAYNE I.; Walker, W. Allan

    2003-01-01

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

  14. 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.

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

    Science.gov (United States)

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

    2013-01-01

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

  16. Effect of insulin on small intestinal transit in normal mice is independent of blood glucose level

    OpenAIRE

    Dkhar Steven; Reddy Peddyreddy; Subramanian Ramaswamy

    2006-01-01

    Abstract Background Insulin is the drug of choice in the management of diabetes mellitus (DM). About 76 % of diabetic patients suffer from gastrointestinal (GI) disorders. Therapy of DM with insulin primarily involves lowering of elevated blood glucose levels. Hence, on any organ in addition to insulin's effect, hypoglycaemic effect also prevails. A systematic study exploring the effect of insulin on small intestinal transit in normal laboratory animals is lacking. Hence, in the present study...

  17. The effects of pharmaceutical excipients on small intestinal transit.

    OpenAIRE

    Adkin, D A; Davis, S. S.; Sparrow, R.A.; Huckle, P D; Phillips, A J; Wilding, I R

    1995-01-01

    1. The effect of three iso-osmotic pharmaceutical excipient solutions on gastrointestinal transit were investigated in eight healthy male volunteers. Each subject received 200 ml radiolabelled purified water, or a 200 ml solution of sodium acid pyrophosphate ((SAPP) 1.1 g/200 ml), mannitol (2.264 g/200 ml) or sucrose (4.08 g/200 ml) in a four way cross over design. On each of the study days the volunteers also received five 6 mm diameter non-disintegrating tablets. Dual isotope gamma scintigr...

  18. Loperamide effects on hepatobiliary function, intestinal transit and analgesia in mice.

    Science.gov (United States)

    Hurwitz, A; Sztern, M I; Looney, G A; Ben-Zvi, Z

    1994-01-01

    Loperamide effects on hepatobiliary function, analgesia and gut transit were studied in mice. Varying doses of the antidiarrheal drug, loperamide, were administered to mice by intracerebroventricular, intravenous, subcutaneous and intragastric routes. Gut motility was determined by intestinal transit of India ink, analgesia by warm water tail flick latency, and hepatobiliary function by retention of the anionic dye, sulfobromophthalein in plasma and liver. When given by all routes at modest doses, loperamide slowed intestinal transit. Analgesia, a centrally mediated opiate effect, was only detected after intracerebroventricular or subcutaneous loperamide at high, near-toxic doses. Elevations of plasma and liver sulfobromophthalein were noted at routes and doses which slowed gut transit, well below those needed for analgesia. Intragastric loperamide at one fortieth its LD50 caused marked elevation of sulfobromophthalein levels and gut slowing, but no analgesia. Sulfobromophthalein elevation and gut slowing by intragastric loperamide were not affected by spinal cord transection but were reversed by naltrexone, an opiate antagonist. Non-toxic doses of loperamide slow gut transit and modify hepatobiliary function in mice by opiate actions at peripheral sites. PMID:8177010

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

    Directory of Open Access Journals (Sweden)

    L.E.A. Troncon

    2000-09-01

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

  20. YadA mediates specific binding of enteropathogenic Yersinia enterocolitica to human intestinal submucosa.

    OpenAIRE

    Skurnik, M.; el Tahir, Y; Saarinen, M (Mika); Jalkanen, S; P. Toivanen

    1994-01-01

    The binding of live Yersinia enterocolitica to frozen sections of human intestine was investigated qualitatively by monitoring the binding of bacteria by using Gram or immunoperoxidase staining as well as quantitatively by a new enzyme immunoassay-on-slide method. We have demonstrated that the binding of various Y. enterocolitica serotypes and Escherichia coli clones to frozen sections of human intestine is mediated by the Yersinia adhesin, YadA. The YadA-mediated binding occurs mainly at the...

  1. 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

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

    OpenAIRE

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

    2008-01-01

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

  3. Espiroquetosis intestinal humana: serie clínica y revisión 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 Introducción: La espiroquetosis intestinal humana (EIH se define como la colonización del intestino grueso por espiroquetas. Se asocia a diarrea crónica. 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 años 2003 y 2008, en pacientes con antecedentes clínicos de diarrea crónica y colonoscopia sin hallazgos patológicos, separados en dos grupos: pacientes con y sin antecedentes de infección por VIH. Material y Método: Evaluación morfológica retrospectiva de las biopsias endoscópicas de intestino grueso de los grupos seleccionados. Resultados: Se revisaron 115 biopsias, 98 correspondieron a pacientes sin infección por VIH y 17 a pacientes seropositivos para VIH. Se detectaron dos casos de espiroquetosis intestinal, ambos en pacientes sin infección por VIH, con una prevalencia de 1,7 %. Comentario: La prevalencia de EIH es similar a la publicada en países occidentales. Se requieren estudios poblacionales para determinar el real impacto epidemiológico 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. Espiroquetosis intestinal humana: serie clínica y revisión de la literatura / Human intestinal spirochetosis: clinical series and literature review

    Scientific Electronic Library Online (English)

    Carlo, Lozano; Leonardo, Arellano; Pamela, Yaquich.

    2012-08-01

    Full Text Available Introducción: La espiroquetosis intestinal humana (EIH) se define como la colonización del intestino grueso por espiroquetas. Se asocia a diarrea crónica. 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 años 2003 y 2008, en pacientes con antecedentes clínicos de diarrea crónica y colonoscopia sin hallazgos patológicos, separados en dos grupos: pacientes con y sin antecedentes de infección por VIH. Material y Método: Evaluación morfológica retrospectiva de las biopsias endoscópicas de intestino grueso de los grupos seleccionados. Resultados: Se revisaron 115 biopsias, 98 correspondieron a pacientes sin infección por VIH y 17 a pacientes seropositivos para VIH. Se detectaron dos casos de espiroquetosis intestinal, ambos en pacientes sin infección por VIH, con una prevalencia de 1,7 %. Comentario: La prevalencia de EIH es similar a la publicada en países occidentales. Se requieren estudios poblacionales para determinar el real impacto epidemiológico en nuestro medio. Abstract in english 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 2 [...] 008 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.

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

    DEFF Research Database (Denmark)

    Madsen, Jan L; Linnet, Jan

    2006-01-01

    Although malabsorption of small amounts of fructose-sorbitol mixtures occurs frequently in healthy humans, insights into their effects on gastrointestinal motility are poor. The present study addresses the hypothesis that malabsorption of a fructose-sorbitol challenge changes the small intestinal transit rate. Eleven healthy volunteers participated in a double-blind crossover investigation. In random order, the subjects ingested 30 g glucose or a mixture of 25 g fructose and 5 g sorbitol as 10% solutions. As a radiolabeled marker, (99m)Tc-diethylenetriaminepentaacetic acid was added to each test solution. Breath hydrogen and methane concentrations and gastrointestinal progress of the radiolabeled marker were followed for the next 6-hr period. Malabsorption of small amounts of the fructose-sorbitol mixture was evident in all subjects. The area under the gastric radioactivity-time curve after ingestion of glucose did not differ from that after ingestion of the fructose-sorbitol mixture (P = 0.7897). However, the mouth-to-cecum transit of the radiolabeled marker was faster (P = 0.0033) and the percentage content of the marker in colon was higher after ingestion of the fructose-sorbitol mixture than after ingestion of glucose (P = 0.0128). In healthy humans, malabsorption of small amounts of a fructose-sorbitol mixture accelerates small bowel transit.

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    Glen S Patten

    2011-02-01

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

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

    Science.gov (United States)

    2015-01-01

    In the intestine, a single layer of epithelial cells sealed together at their apical surfaces by tight junctions helps to prevent the luminal commensal and pathogenic micro-organisms and their toxins from entering host tissues. The intestinal epithelium also helps to maintain homoeostasis in the mucosal immune system by expressing anti-inflammatory cytokines in the steady state and inflammatory cytokines in response to pathogens. Although the function of the mucosal immune system is impaired in elderly humans, the molecular mechanisms which cause this dramatic functional decline are poorly understood. Our current understanding of the effects of aging on the physical and immunological properties of the intestinal epithelial barrier is also very limited. In this issue of Clinical Science, Man et al. provide further insight into the effects of aging on small intestinal barrier function in humans and the influence that gut luminal micro-organisms may have on it. Using human terminal ileal biopsy tissues they show that intestinal permeability to solutes, but not macromolecules, was significantly increased in the intestines of elderly humans. This was accompanied by elevated expression of the pro-inflammatory cytokine interleukin (IL)-6 which appeared to modulate claudin-2 expression and solute permeability in the epithelium. Conversely, IL-8 synthesis in response to flagellin stimulation was reduced in intestines of the elderly subjects, but was not associated with effects on Toll-like receptor 5 (TLR5) expression. These data provide an important advance in our understanding on the effects of aging on intestinal permeability and innate mucosal immune responsiveness in elderly humans. PMID:26186738

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

    Science.gov (United States)

    Mabbott, Neil A

    2015-10-01

    In the intestine, a single layer of epithelial cells sealed together at their apical surfaces by tight junctions helps to prevent the luminal commensal and pathogenic micro-organisms and their toxins from entering host tissues. The intestinal epithelium also helps to maintain homoeostasis in the mucosal immune system by expressing anti-inflammatory cytokines in the steady state and inflammatory cytokines in response to pathogens. Although the function of the mucosal immune system is impaired in elderly humans, the molecular mechanisms which cause this dramatic functional decline are poorly understood. Our current understanding of the effects of aging on the physical and immunological properties of the intestinal epithelial barrier is also very limited. In this issue of Clinical Science, Man et al. provide further insight into the effects of aging on small intestinal barrier function in humans and the influence that gut luminal micro-organisms may have on it. Using human terminal ileal biopsy tissues they show that intestinal permeability to solutes, but not macromolecules, was significantly increased in the intestines of elderly humans. This was accompanied by elevated expression of the pro-inflammatory cytokine interleukin (IL)-6 which appeared to modulate claudin-2 expression and solute permeability in the epithelium. Conversely, IL-8 synthesis in response to flagellin stimulation was reduced in intestines of the elderly subjects, but was not associated with effects on Toll-like receptor 5 (TLR5) expression. These data provide an important advance in our understanding on the effects of aging on intestinal permeability and innate mucosal immune responsiveness in elderly humans. PMID:26186738

  10. 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

  11. 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...

  12. Host-Microbe Interactions in the Neonatal Intestine: Role of Human Milk Oligosaccharides123

    OpenAIRE

    Donovan, Sharon M; Wang, Mei; Li, Min; Friedberg, Iddo; Schwartz, Scott L.; Chapkin, Robert S.

    2012-01-01

    The infant intestinal microbiota is shaped by genetics and environment, including the route of delivery and early dietary intake. Data from germ-free rodents and piglets support a critical role for the microbiota in regulating gastrointestinal and immune development. Human milk oligosaccharides (HMO) both directly and indirectly influence intestinal development by regulating cell proliferation, acting as prebiotics for beneficial bacteria and modulating immune development. We have shown that ...

  13. The nature of the natural killer (NK) cell of human intestinal mucosa and mesenteric lymph node.

    OpenAIRE

    Gibson, PR; Jewell, DP.

    1985-01-01

    The relationship of the mononuclear cell (MNC) from human intestinal mucosa and mesenteric lymph node mediating anti-K-562 activity with that of peripheral blood has been assessed. Depletion of macrophages did not alter the measured cytotoxicity confirming that the effector cells were lymphocytes. Complement lysis of Leu 7 and Leu 11b coated cells reduced intestinal natural killer (NK) activity by a similar degree to that of peripheral blood but mesenteric lymph node NK activity was affected ...

  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. Surface expression, polarization, and functional significance of CD73 in human intestinal epithelia.

    OpenAIRE

    Strohmeier, G R; Lencer, W I; Patapoff, T W; Thompson, L. F.; Carlson, S L; Moe, S J; Carnes, D K; Mrsny, R J; Madara, J L

    1997-01-01

    During active intestinal inflammation polymorphonuclear leukocytes (PMN) transmigrate into the lumen and release 5'-AMP (J. Clin. Invest. 1993. 91:2320-2325). 5'-AMP is converted to adenosine by the apical epithelial surface with subsequent activation of electrogenic Cl- secretion (the basis of secretory diarrhea) via apical A2b adenosine receptors (J. Biol. Chem. 1995. 270:2387-2394). Using a polarized human intestinal epithelial monolayer (T84), we now characterize the basis of the observed...

  16. Rapid and Accurate Diagnosis of Human Intestinal Spirochetosis by Fluorescence In Situ Hybridization?

    OpenAIRE

    Schmiedel, Dinah; Epple, Hans-Jörg; Loddenkemper, Christoph; Ignatius, Ralf; Wagner, Jutta; Hammer, Bettina; Petrich, Annett; Stein, Harald; Göbel, Ulf B.; Schneider, Thomas; Moter, Annette

    2009-01-01

    Human intestinal spirochetosis (HIS) is associated with overgrowth of the large intestine by spirochetes of the genus Brachyspira. The microbiological diagnosis of HIS is hampered by the fastidious nature and slow growth of Brachyspira spp. In clinical practice, HIS is diagnosed histopathologically, and a significant portion of cases may be missed. Fluorescence in situ hybridization (FISH) is a molecular method that allows the visualization and identification of single bacteria within tissue ...

  17. 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...

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

    DEFF Research Database (Denmark)

    Tetens, Inge

    2011-01-01

    Following an application from Nordic Sugar A/S, submitted pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Denmark, the Panel on Dietetic Products, Nutrition and Allergies was asked to deliver an opinion on the scientific substantiation of a health claim based on newly developed scientific evidence related to sugar beet fibre and “decreasing intestinal transit time”. The food constituent that is the subject of the health claim is sugar beet fibre. This opinion applies to sugar beet fibre naturally present in foods and to those forms added to foods. The Panel considers that sugar beet fibre is sufficiently characterised in relation to the claimed effect. The claimed effect is “decreasing intestinal transit time”. The target population proposed by the applicant is people who want to improve or maintain normal bowel function. The Panel considers that decreasing intestinal (orofaecal) transit time may be a beneficial physiological effect. The applicant provided four human studies as pertinent to the health claim. The Panel considers that no conclusion can be drawn from three studies for the scientific substantiation of the claim owing to methodological weaknesses whereas one human intervention study showed no effect of the consumption of sugar beet fibre on decreasing intestinal (orofaecal) transit time. In weighing the evidence the Panel took into account that one human study from which conclusions could be drawn for the scientific substantiation of the claim showed no effect of sugar beet fibre on intestinal (orofaecal) transit time. The Panel concludes that a cause and effect relationship has not been established between the consumption of sugar beet fibre and decreasing intestinal transit time. © European Food Safety Authority, 2011

  19. The study on the impact of glycated pea proteins on human intestinal bacteria.

    Science.gov (United States)

    ?wi?tecka, Dominika; Dominika, ?wi?tecka; Narbad, Arjan; Arjan, Narbad; Ridgway, Karyn P; Karyn, Ridgway P; Kostyra, Henryk; Henryk, Kostyra

    2011-01-31

    The traditionally perceived function of nutrition includes supplying the consumer with the appropriate quantity and quality of substrates. As nutritional substrates, proteins are prone to spontaneously occurring non-enzymatic glycosylation (glycation) which can alter their molecular structure, making them highly bioactive. Glycated food proteins are able to modify the bacterial intestinal ecosystem, which is of great importance for the optimal usage of nutrients and maintenance of both intestinal homeostasis and balanced health status of the consumer. This study aimed to determine the impact of glycated pea proteins on the intestinal bacteria from a healthy human. The analyses were conducted with the use of experimental batch-type simulator models imitating human intestinal conditions. The glycated pea proteins affected the growth of gut commensal bacteria, particularly lactobacilli and bifidobacteria, whose levels increased significantly. There was a corresponding shift in the bacterial metabolites with increased levels of the short chain fatty acids (SCFAs); acetate, propionate lactate and butyrate. Intestinal bacteria were able to utilize these pea proteins thus indicating that the energy encrypted in glycated pea proteins, partially inaccessible for gastric enzymes, may be salvaged by gut microbiota. Such changes in microbial composition may beneficially impact the intestinal environment and exert a health-promoting effect in humans. PMID:21276631

  20. 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.

  1. Human Rights and Transitional Societies: Contemporary Challenges

    DEFF Research Database (Denmark)

    Hansen, Thomas Obel

    2008-01-01

    This paper will assess how alternative approaches to transitional justice have the potential for overcoming tensions in between human rights standards. A rule in international law prescribing that states have a duty to prosecute gross human rights violations has emerged. Accordingly, transitional societies are said to have an obligation to apply criminal justice in dealing with such past violations. In Rwanda, the transitional government decided to prosecute the perpetrators of the 1994 genocide...

  2. 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

  3. Study of the Biotransformation of Tongmai Formula by Human Intestinal Flora and Its Intestinal Permeability across the Caco-2 Cell Monolayer

    Directory of Open Access Journals (Sweden)

    Shuai Wu

    2015-10-01

    Full Text Available Tongmai formula (TMF is a well-known Chinese medicinal preparation that contains isoflavones as its major bioactive constituents. As traditional Chinese medicines (TCMs are usually used by oral administration, their fate inside the intestinal lumen, including their biotransformation by human intestinal flora (HIF and intestinal absorption deserves study. In this work TMF extract was incubated with human intestinal bacteria under anaerobic conditions and the changes in the twelve main constituents of TMF were then investigated. Their intestinal permeabilities, i.e., the transport capability across the intestinal brush border were investigated with a human colon carcinoma cell line (Caco­2 cell monolayer model to predict the absorption mechanism. Meanwhile, rapid HPLC-DAD methods were established for the assay. According to the biotransformation curves of the twelve constituents and the permeability coefficients, the intestinal absorption capacity of the typical compounds was elevated from the levels of 10?7 cm/s to 10?5 cm/s from those of the original compounds in TMF. Among them the main isoflavone glycosides puerarin (4, mirificin (6 and daidzin (7 were transformed into the same aglycone, daidzein (10. Therefore it was predicted that the aglycone compounds might be the real active ingredients in TMF. The models used can represent a novel path for the TCM studies.

  4. Effect of insulin on small intestinal transit in normal mice is independent of blood glucose level

    Directory of Open Access Journals (Sweden)

    Dkhar Steven

    2006-02-01

    Full Text Available Abstract Background Insulin is the drug of choice in the management of diabetes mellitus (DM. About 76 % of diabetic patients suffer from gastrointestinal (GI disorders. Therapy of DM with insulin primarily involves lowering of elevated blood glucose levels. Hence, on any organ in addition to insulin's effect, hypoglycaemic effect also prevails. A systematic study exploring the effect of insulin on small intestinal transit in normal laboratory animals is lacking. Hence, in the present study, the possible effect of insulin with or without associated hypoglycaemia on small intestinal transit in normal mice was examined. Results Insulin in all the doses tested (2 ?, 2 m and 2 U/kg elicited a significant acceleration of SIT. The lower doses of insulin (2 ? and 2 m U/kg produced significant acceleration of SIT and were associated with normal blood glucose levels. However, the highest dose of insulin (2 U/kg produced an acceleration of SIT that was associated with significant fall in blood glucose levels. Further, the 2 m and 2 U doses of insulin significantly elevated serum insulin and C-peptide levels. Conclusion Insulin at the lowest dose produced an acceleratory effect on SIT that was independent of blood glucose and serum insulin levels in normal mice.

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

    Scientific Electronic Library Online (English)

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

    2000-09-01

    Full Text Available The effects of a fraction (T1) of Tityus serrulatus scorpion venom prepared by gel filtration on gastric emptying and small intestinal transit were investigated in male Wistar rats. Fasted animals were anesthetized with urethane, submitted to tracheal intubation and right jugular vein cannulation. S [...] corpion toxin (250 µg/kg) or saline was injected iv and 1 h later a bolus of saline (1.0 ml/100 g) labeled with 99m technetium-phytate (10 MBq) was administered by gavage. After 15 min, animals were sacrificed and the radioactivity remaining in the stomach was determined. Intestinal transit was evaluated by instillation of a technetium-labeled saline bolus (1.0 ml) through a cannula previously implanted in the duodenum. After 60 min, the progression of the marker throughout 7 consecutive gut segments was estimated by the geometric center method. Gastric retention of the liquid test meal in rats injected with scorpion toxin (median: 88%; range: 52-95%) was significantly higher (P

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

    Scientific Electronic Library Online (English)

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

    2008-01-01

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

  7. Human intestinal tissue with adult stem cell properties derived from pluripotent stem cells.

    Science.gov (United States)

    Forster, Ryan; Chiba, Kunitoshi; Schaeffer, Lorian; Regalado, Samuel G; Lai, Christine S; Gao, Qing; Kiani, Samira; Farin, Henner F; Clevers, Hans; Cost, Gregory J; Chan, Andy; Rebar, Edward J; Urnov, Fyodor D; Gregory, Philip D; Pachter, Lior; Jaenisch, Rudolf; Hockemeyer, Dirk

    2014-06-01

    Genetically engineered human pluripotent stem cells (hPSCs) have been proposed as a source for transplantation therapies and are rapidly becoming valuable tools for human disease modeling. However, many applications are limited due to the lack of robust differentiation paradigms that allow for the isolation of defined functional tissues. Here, using an endogenous LGR5-GFP reporter, we derived adult stem cells from hPSCs that gave rise to functional human intestinal tissue comprising all major cell types of the intestine. Histological and functional analyses revealed that such human organoid cultures could be derived with high purity and with a composition and morphology similar to those of cultures obtained from human biopsies. Importantly, hPSC-derived organoids responded to the canonical signaling pathways that control self-renewal and differentiation in the adult human intestinal stem cell compartment. This adult stem cell system provides a platform for studying human intestinal disease in vitro using genetically engineered hPSCs. PMID:24936470

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

    Directory of Open Access Journals (Sweden)

    Ryan Forster

    2014-06-01

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

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

    Science.gov (United States)

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

    2015-10-01

    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

  10. 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.

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

    OpenAIRE

    Forster, Ryan; Chiba, Kunitoshi; Schaeffer, Lorian; Regalado, Samuel G.; Lai, Christine S.; Gao, Qing(MOE Key Laboratory of Fundamental Quantities Measurement, School of Physics, Huazhong University of Science and Technology, 430074, Wuhan, Hubei, China); Kiani, Samira; Farin, Henner F.; Clevers, Hans; Cost, Gregory J.; Chan, Andy; Rebar, Edward J.; Urnov, Fyodor D.; Gregory, Philip D.; Pachter, Lior

    2014-01-01

    Genetically engineered human pluripotent stem cells (hPSCs) have been proposed as a source for transplantation therapies and are rapidly becoming valuable tools for human disease modeling. However, many applications are limited due to the lack of robust differentiation paradigms that allow for the 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...

  12. Listeria monocytogenes ?B Contributes to Invasion of Human Intestinal Epithelial Cells

    OpenAIRE

    Kim, Heesun; Boor, Kathryn J.; Marquis, Hélène

    2004-01-01

    The role of ?B in Listeria monocytogenes infection of human intestinal epithelial cells was investigated. Invasion defects associated with loss of ?B paralleled those of a ?inlA strain independently of the ?B-dependent P2prfA promoter. Concomitantly, amounts of inlA transcript and InlA protein were significantly decreased in the ?sigB strain.

  13. Isolation of a human intestinal bacterium capable of transforming barbaloin to aloe-emodin anthrone.

    Science.gov (United States)

    Che, Q M; Akao, T; Hattori, M; Kobashi, K; Namba, T

    1991-02-01

    A strictly anaerobic bacterium, Eubacterium sp. BAR, was isolated from human feces as one of the intestinal bacteria capable of metabolizing barbaloin. The bacterium grew in PYF broth containing barbaloin and converted barbaloin to aloe-emodin anthrone. On the other hand, the bacterium had little metabolic activity in GAM broth. PMID:2062951

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

    OpenAIRE

    Marcelo Luiz Carvalho Gonçalves; Adauto Araújo; Luiz Fernando Ferreira

    2003-01-01

    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 ...

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

    Scientific Electronic Library Online (English)

    Virginia, Robles-Alonso; Francisco, Guarner.

    2013-06-01

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

  16. Stem Cell-Derived Human Intestinal Organoids as an Infection Model for Rotaviruses

    OpenAIRE

    Finkbeiner, Stacy R.; Zeng, Xi-Lei; Utama, Budi; Atmar, Robert L.; Shroyer, Noah F; Estes, Mary K

    2012-01-01

    Directed differentiation of stem cell lines into intestine-like tissue called induced human intestinal organoids (iHIOs) is now possible (J. R. Spence, C. N. Mayhew, S. A. Rankin, M. F. Kuhar, J. E. Vallance, K. Tolle, E. E. Hoskins, V. V. Kalinichenko, S. I. Wells, A. M. Zorn, N. F. Shroyer, and J. M. Wells, Nature 470:105-109, 2011). We tested iHIOs as a new model to cultivate and study fecal viruses. Protocols for infection of iHIOs with a laboratory strain of rotavirus, simian SA11, were ...

  17. 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

  18. PDX1 regulation of FABP1 and novel target genes in human intestinal epithelial Caco-2 cells

    OpenAIRE

    Chen, Chin; Fang, Rixun; Chou, Lin-Chiang; Lowe, Anson W.; Sibley, Eric

    2012-01-01

    The transcription factor pancreatic and duodenal homeobox 1 (PDX1) plays an essential role in pancreatic development and in maintaining proper islet function via target gene regulation. Few intestinal PDX1 targets, however, have been described. We sought to define novel PDX1-regulated intestinal genes. Caco-2 human intestinal epithelial cells were engineered to overexpress PDX1 and gene expression profiles relative to control cells were assessed. Expression of 80 genes significantly increased...

  19. Human CD8+ T Cells Clear Cryptosporidium parvum from Infected Intestinal Epithelial Cells

    OpenAIRE

    Pantenburg, Birte; Castellanos-Gonzalez, Alejandro; Dann, Sara M.; Connelly, Rhykka L.; Lewis, Dorothy E; Ward, Honorine D.; A. Clinton White

    2010-01-01

    Intracellular protozoans of the genus Cryptosporidium are a major cause of diarrheal illness worldwide, especially in immunocompromised individuals. CD4+ T cells and interferon-gamma are key factors in the control of cryptosporidiosis in human and murine models. Previous studies led us to hypothesize that CD8+ T cells contribute to clearance of intestinal epithelial Cryptosporidium infection in humans. We report here that antigen expanded sensitized CD8+ T cells reduce the parasite load in in...

  20. Dclk1 facilitates intestinal tumor growth via enhancing pluripotency and epithelial mesenchymal transition

    OpenAIRE

    Chandrakesan, Parthasarathy; Weygant, Nathaniel; May, Randal; Qu, Dongfeng; Chinthalapally, Harisha R.; Sureban, Sripathi M; Ali, Naushad; Lightfoot, Stan A; Umar, Shahid; Houchen, Courtney W

    2014-01-01

    Doublecortin-like kinase 1 (Dclk1) is overexpressed in many cancers including colorectal cancer (CRC) and it specifically marks intestinal tumor stem cells. However, the role of Dclk1 in intestinal tumorigenesis in Apc mutant conditions is still poorly understood. We demonstrate that Dclk1 expression and Dclk1+ cells are significantly increased in the intestinal epithelium of elderly ApcMin/+ mice compared to young ApcMin/+ mice and wild type mice. Intestinal epithelial cells of ApcMin/+ mice...

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

    Science.gov (United States)

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

    2004-09-01

    The objective of the present study was to evaluate the consequence of Camembert consumption on the composition and metabolism of human intestinal microbiota. Camembert cheese was compared with milk fermented by yoghurt starters and Lactobacillus casei as a probiotic reference. The experimental model was the human microbiota-associated (HM) rat. HM rats were fed a basal diet (HMB group), a diet containing Camembert made from pasteurised milk (HMCp group) or a diet containing fermented milk (HMfm group). The level of micro-organisms from dairy products was measured in faeces using cultures on a specific medium and PCR-temporal temperature gradient gel electrophoresis. The metabolic characteristics of the caecal microbiota were also studied: SCFA, NH3, glycosidase and reductase activities, and bile acid degradations. The results showed that micro-organisms from cheese comprised 10(5)-10(8) bacteria/g faecal sample in the HMCp group. Lactobacillus species from fermented milk were detected in HMfm rats. Consumption of cheese and fermented milk led to similar changes in bacterial metabolism: a decrease in azoreductase activity and NH3 concentration and an increase in mucolytic activities. However, specific changes were observed: in HMCp rats, the proportion of ursodeoxycholic resulting from chenodeoxycholic epimerisation was higher; in HMfm rats, alpha and beta-galactosidases were higher than in other groups and both azoreductases and nitrate reductases were lower. The results show that, as for fermented milk, Camembert consumption did not greatly modify the microbiota profile or its major metabolic activities. Ingested micro-organisms were able to survive in part during intestinal transit. These dairy products exert a potentially beneficial influence on intestinal metabolism. PMID:15469646

  2. Mice lacking a Myc enhancer that includes human SNP rs6983267 are resistant to intestinal tumors.

    Science.gov (United States)

    Sur, Inderpreet Kaur; Hallikas, Outi; Vähärautio, Anna; Yan, Jian; Turunen, Mikko; Enge, Martin; Taipale, Minna; Karhu, Auli; Aaltonen, Lauri A; Taipale, Jussi

    2012-12-01

    Multiple cancer-associated single-nucleotide polymorphisms (SNPs) have been mapped to conserved sequences within a 500-kilobase region upstream of the MYC oncogene on human chromosome 8q24. These SNPs may affect cancer development through altered regulation of MYC expression, but this hypothesis has been difficult to confirm. We generated mice deficient in Myc-335, a putative MYC regulatory element that contains rs6983267, a SNP accounting for more human cancer-related morbidity than any other genetic variant or mutation. In Myc-335 null mice, Myc transcripts were expressed in the intestinal crypts in a pattern similar to that in wild-type mice but at modestly reduced levels. The mutant mice displayed no overt phenotype but were markedly resistant to intestinal tumorigenesis induced by the APCmin mutation. These results establish that a cancer-associated SNP identified in human genome-wide association studies has a functional effect in vivo. PMID:23118011

  3. 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

    2011-01-01

    1. The aim of this study was to evaluate how splitting the dark period (scotoperiod) affects feeding behaviour and associated intestinal measures in broilers. 2. Ross 308 broilers were reared to 37 d in groups given either a daily 8-h continuous scotoperiod (DARK 8) or an intermittent light schedule with two equally spaced 4-h scotoperiods (DARK 4þ4), which yielded the same total duration of darkness per 24 h. 3. Feeding behaviour was recorded weekly from 24-h video recordings of 24 groups each of 64 birds. Empty intestinal weights as well as their contents were measured weekly at 4 time points (n¼192). Digestive transit time was estimated on d 29 using a chromic oxide marker; production variables and the extent of foot pad dermatitis were also recorded. 4. In the 3 h prior to a scotoperiod, feeding activity increased in chickens from DARK 8 but not DARK 4þ4. This increase was reflected in a higher relative content of the crop in DARK 8 at this time. 5. Immediately following the scotoperiod, feeding activity peaked and, although the chickens in DARK 4þ4 expressed more feeding behaviour in the first 20 min after the scotoperiod, the chickens in DARK 8 had overall higher feeding activity 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 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.

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

    DEFF Research Database (Denmark)

    Machado, Ana Manuel; Sommer, Morten

    2014-01-01

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

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

    OpenAIRE

    Corpet, D E

    1987-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Oku T

    2011-06-01

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

  7. 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.

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2015-03-15

    Cell culture models are currently used to predict absorption pattern of new compounds and formulations in the human gastro-intestinal tract (GIT). One major drawback is the lack of relevant apical incubation fluids allowing mimicking luminal conditions in the GIT. Here, we suggest a culture model compatible with biorelevant media, namely Fasted State Simulated Intestinal Fluid (FaSSIF) and Fed State Simulated Intestinal Fluid (FeSSIF). Co-culture was set up from Caco-2 and mucus-secreting HT29-MTX cells using an original seeding procedure. Viability and cytotoxicity assays were performed following incubation of FeSSIF and FaSSIF with co-culture. Influence of biorelevant fluids on paracellular permeability or transporter proteins were also evaluated. Results were compared with Caco-2 and HT29-MTX monocultures. While Caco-2 viability was strongly affected with FeSSIF, no toxic effect was detected for the co-cultures in terms of viability and lactate dehydrogenase release. The addition of FeSSIF to the basolateral compartment of the co-culture induced cytotoxic effects which suggested the apical mucus barrier being cell protective. In contrast to FeSSIF, FaSSIF induced a slight increase of the paracellular transport and both tested media inhibited partially the P-gp-mediated efflux in the co-culture. Additionally, the absorptive transport of propranolol hydrochloride, a lipophilic ?-blocker, was strongly affected by biorelevant fluids. This study demonstrated the compatibility of the Caco-2/HT29-MTX model with some of the current biorelevant media. Combining biorelevant intestinal fluids with features such as mucus secretion, adjustable paracellular and P-gp mediated transports, is a step forward to more realistic in-vitro models of the human intestine. PMID:25601199

  10. 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.

  11. 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; ?epi?ka, I.

    2012-01-01

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

  12. 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

  13. Dipeptide model prodrugs for the intestinal oligopeptide transporter. Affinity for and transport via hPepT1 in the human intestinal Caco-2 cell line

    DEFF Research Database (Denmark)

    Nielsen, C U; Andersen, R; Brodin, Birger; Frokjaer, S; Taub, M E; Steffansen, B

    2001-01-01

    The human intestinal di/tri-peptide carrier, hPepT1, has been suggested as a drug delivery target via increasing the intestinal transport of low permeability compounds by designing peptidomimetic prodrugs. Model ester prodrugs using the stabilized dipeptides D-Glu-Ala and D-Asp-Ala as pro-moieties for benzyl alcohol have been shown to maintain affinity for hPepT1. The primary aim of the present study was to investigate if modifications of the benzyl alcohol model drug influence the corresponding...

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

    OpenAIRE

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

    1987-01-01

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

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

    OpenAIRE

    Booijink, C.C.G.M.

    2009-01-01

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

  16. 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,...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1988-09-01

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

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

    International Nuclear Information System (INIS)

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

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

    DEFF Research Database (Denmark)

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

    1992-01-01

    Evidence showing that interstitial cells of Cajal have important regulatory functions in the gut musculature is accumulating. In the current study, the ultrastructure of the deep muscular plexus and associated interstial cells of Cajal in human small intestine were studied to provide a reference 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 cir...

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

    OpenAIRE

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

    2010-01-01

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

  1. 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-?B 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.

  2. Analysis of drug transporter expression in human intestinal Caco-2 cells by real-time PCR.

    Science.gov (United States)

    Maubon, Nathalie; Le Vee, Marc; Fossati, Lina; Audry, Mathilde; Le Ferrec, Eric; Bolze, Sebastien; Fardel, Olivier

    2007-12-01

    Expression of drug transporters corresponds to a crucial parameter in intestinal Caco-2 cells widely used for investigating drug absorption. In order to characterize it in an accurate, reproducible and comparative manner, we analyzed mRNA levels of 19 influx and efflux drug transporters through real-time quantitative polymerase chain reaction assays combined with the use of a total RNA reference standard. Profiles of transporter expression were found to be significantly correlated in two independent Caco-2 cell clones and in human small intestine, which may support the use of Caco-2 cells for investigating intestinal drug transport. Several transporters were nevertheless quantitatively expressed at higher (MRP2, MRP3, MRP4, MRP5, MRP6, OATP-A, OATP-B, OCT1 and MCT1) or lower (BCRP) levels in Caco-2 cells comparatively to small intestine. Moreover, MDR1, MRP2, OATP-A and PEPT1 mRNA relative expression were found to differ in the two analyzed Caco-2 cell clones by at least a twofold factor, highlighting that some variations in transporter expression may occur in Caco-2 cells depending on cell origin, and therefore underlining the interest of carefully characterizing transporter levels in any Caco-2 cell clone before its use for drug transport assays. PMID:18034668

  3. Human Rights and Transitional Societies: Contemporary Challenges

    DEFF Research Database (Denmark)

    Hansen, Thomas Obel

    2008-01-01

    This paper will assess how alternative approaches to transitional justice have the potential for overcoming tensions in between human rights standards. A rule in international law prescribing that states have a duty to prosecute gross human rights violations has emerged. Accordingly, transitional societies are said to have an obligation to apply criminal justice in dealing with such past violations. In Rwanda, the transitional government decided to prosecute the perpetrators of the 1994 genocide. As a result of widespread participation in the genocide and a devastated legal sector, difficulties in respecting the rights of the accused arose. A group of paralegals known as the "Corps of Judicial Defenders" was thus relied upon as to provide legal assistance for genocide suspects, but also for civil parties. This paper describes the work of these paralegals relating to the transitional trials, and, more generally, asserts how Judicial Defenders may have contributed to justice in other ways in post conflict Rwanda. The author argues that an efficient transitional justice policy must take sufficiently into account the context of the society in question, and aim at establishing linkages between justice in transitions and justice in the long-term.

  4. Common occurrence of antibacterial agents in human intestinal microbiota

    OpenAIRE

    Drissi, Fatima; Buffet, Sylvain; Raoult, Didier; Merhej, Vicky

    2015-01-01

    Laboratory experiments have revealed many active mechanisms by which bacteria can inhibit the growth of other organisms. Bacteriocins are a diverse group of natural ribosomally synthesized antimicrobial peptides produced by a wide range of bacteria and which seem to play an important role in mediating competition within bacterial communities. In this study, we have identified and established the structural classification of putative bacteriocins encoded by 317 microbial genomes in the human i...

  5. Transport of Chitosan-DNA nanoparticles in human intestinal M-cell model versus normal intestinal enterocytes

    OpenAIRE

    Kadiyala, Irina; Loo, Yihua; Roy, Krishnendu; Rice, Janet; Kam W. Leong

    2009-01-01

    Oral vaccination is one of the most promising applications of polymeric nanoparticles. Using two different in vitro cellular models to partially reproduce the characteristics of intestinal enterocytes and M-cells, this study demonstrates that nanoparticle transport through the M-cell co-culture model is 5 fold that of the intestinal epithelial monolayer, with at least 80% of the chitosan-DNA nanoparticles uptaken in the first 30 minutes. Among the properties of nanoparticles studied, ligand d...

  6. Tea Catechin Auto-oxidation Dimers are Accumulated and Retained by Caco-2 Human Intestinal Cells

    OpenAIRE

    Neilson, Andrew P; Song, Brian J; Sapper, Teryn N.; Bomser, Joshua A.; Ferruzzi, Mario G.

    2010-01-01

    Despite the presence of bioactive catechin B-ring auto-oxidation dimers in tea, little is known regarding their absorption in humans. Our hypothesis for this research is that catechin auto-oxidation dimers are present in teas and are absorbable by human intestinal epithelial cells. Dimers [theasinensins (THSNs) and P-2 analogs) were quantified in commercial teas by HPLC-MS. (?)-Epigallocatechin (EGC) and (?)-epigallocatechin gallate (EGCG) homodimers were present at 10–43 and 0–62 µmol/g leaf...

  7. Anthocyanin Absorption and Metabolism by Human Intestinal Caco-2 Cells-A Review.

    Science.gov (United States)

    Kamiloglu, Senem; Capanoglu, Esra; Grootaert, Charlotte; Van Camp, John

    2015-01-01

    Anthocyanins from different plant sources have been shown to possess health beneficial effects against a number of chronic diseases. To obtain any influence in a specific tissue or organ, these bioactive compounds must be bioavailable, i.e., effectively absorbed from the gut into the circulation and transferred to the appropriate location within the body while still maintaining their bioactivity. One of the key factors affecting the bioavailability of anthocyanins is their transport through the gut epithelium. The Caco-2 cell line, a human intestinal epithelial cell model derived from a colon carcinoma, has been proven to be a good alternative to animal studies for predicting intestinal absorption of anthocyanins. Studies investigating anthocyanin absorption by Caco-2 cells report very low absorption of these compounds. However, the bioavailability of anthocyanins may be underestimated since the metabolites formed in the course of digestion could be responsible for the health benefits associated with anthocyanins. In this review, we critically discuss recent findings reported on the anthocyanin absorption and metabolism by human intestinal Caco-2 cells. PMID:26370977

  8. Anthocyanin Absorption and Metabolism by Human Intestinal Caco-2 Cells—A Review

    Science.gov (United States)

    Kamiloglu, Senem; Capanoglu, Esra; Grootaert, Charlotte; Van Camp, John

    2015-01-01

    Anthocyanins from different plant sources have been shown to possess health beneficial effects against a number of chronic diseases. To obtain any influence in a specific tissue or organ, these bioactive compounds must be bioavailable, i.e., effectively absorbed from the gut into the circulation and transferred to the appropriate location within the body while still maintaining their bioactivity. One of the key factors affecting the bioavailability of anthocyanins is their transport through the gut epithelium. The Caco-2 cell line, a human intestinal epithelial cell model derived from a colon carcinoma, has been proven to be a good alternative to animal studies for predicting intestinal absorption of anthocyanins. Studies investigating anthocyanin absorption by Caco-2 cells report very low absorption of these compounds. However, the bioavailability of anthocyanins may be underestimated since the metabolites formed in the course of digestion could be responsible for the health benefits associated with anthocyanins. In this review, we critically discuss recent findings reported on the anthocyanin absorption and metabolism by human intestinal Caco-2 cells. PMID:26370977

  9. Vasoactive Intestinal Peptide Inhibits Human Small-Cell Lung Cancer Proliferation in vitro and in vivo

    Science.gov (United States)

    Maruno, Kaname; Absood, Afaf; Said, Sami I.

    1998-11-01

    Small-cell lung carcinoma (SCLC) is an aggressive, rapidly growing and metastasizing, and highly fatal neoplasm. We report that vasoactive intestinal peptide inhibits the proliferation of SCLC cells in culture and dramatically suppresses the growth of SCLC tumor-cell implants in athymic nude mice. In both cases, the inhibition was mediated apparently by a cAMP-dependent mechanism, because the inhibition was enhanced by the adenylate cyclase activator forskolin and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine in proportion to increases in intracellular cAMP levels, and the inhibition was abolished by selective inhibition of cAMP-dependent protein kinase. If confirmed in clinical trials, this antiproliferative action of vasoactive intestinal peptide may offer a new and promising means of suppressing SCLC in human subjects, without the toxic side effects of chemotherapeutic agents.

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

    International Nuclear Information System (INIS)

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

  11. Functional distance in human gait transition.

    Science.gov (United States)

    Abdolvahab, Mohammad; Carello, Claudia

    2015-10-01

    The emerging understanding of the behavioral transitions that accompany the ascending and descending method of limits is in terms of "functional distance" - the degree to which a perceiver is disengaged from ordinary exploratory activities. Increasing functional distance results in negative hysteresis in contrast to the classical positive hysteresis more typical of ongoing activity. In the present study of human gait transitions on a treadmill, the functional distance between a perceiver and ordinary exploratory activities was manipulated in two ways: (1) "Active" participants, walking or running on a treadmill, were asked to anticipate the gait that would be required if treadmill speed were increased or decreased; and (2) "passive" participants, standing off a moving treadmill, were asked to report the gait they would use if they were on the treadmill at its current speed. As expected, the increase of functional distance from (1) to (2) reduced the amount of classical hysteresis and promoted negative hysteresis, that is, a lower transition speed for walk-to-run transitions (ascending trials) than for run-to-walk transitions (descending trials). These results complement empirical findings in other behavioral transition experiments. More broadly, they signify the role of perception-action cycles for grounding natural on-going perception. In particular, they support the assertion that perception and action are intertwined and that lack of information about an impending action has consequences for perceptual judgments. PMID:26408863

  12. 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.

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

    DEFF Research Database (Denmark)

    Ito, Go; Okamoto, Ryuichi

    2013-01-01

    Intestinal epithelial cells (IECs) regulate the absorption and secretion of anions, such as HCO3(-) or Cl(-). Bestrophin genes represent a newly identified group of calcium-activated Cl(-) channels (CaCCs). Studies have suggested that, among the four human bestrophin-family genes, bestrophin-2 (BEST2) and bestrophin-4 (BEST4) might be expressed within the intestinal tissue. Consistently, a study showed that BEST2 is expressed by human colonic goblet cells. However, their precise expression pattern along the gastrointestinal tract, or the lineage specificity of the cells expressing these genes, remains largely unknown. Here, we show that BEST2 and BEST4 are expressed in vivo, each in a distinct, lineage-specific manner, in human IECs. While BEST2 was expressed exclusively in colonic goblet cells, BEST4 was expressed in the absorptive cells of both the small intestine and the colon. In addition, we found that BEST2 expression is significantly down-regulated in the active lesions of ulcerative colitis, where goblet cells were depleted, suggesting that BEST2 expression is restricted to goblet cells under both normal and pathologic conditions. Consistently, the induction of goblet cell differentiation by a Notch inhibitor, LY411575, significantly up-regulated the expression of not BEST4 but BEST2 in MUC2-positive HT-29 cells. Conversely, the induction of absorptive cell differentiation up-regulated the expression of BEST4 in villin-positive Caco-2 cells. In addition, we found that the up- or down-regulation of Notch activity leads to the preferential expression of either BEST4 or BEST2, respectively, in LS174T cells. These results collectively confirmed that BEST2 and BEST4 could be added to the lineage-specific genes of humans IECs due to their abilities to clearly identify goblet cells of colonic origin and a distinct subset of absorptive cells, respectively.

  14. Tryptophan from human milk induces oxidative stress and upregulates the Nrf-2-mediated stress response in human intestinal cell lines.

    Science.gov (United States)

    Elisia, Ingrid; Tsopmo, Apollinaire; Friel, James K; Diehl-Jones, William; Kitts, David D

    2011-08-01

    Chemical screening of digested human milk protein using the oxygen radical absorbance capacity (ORAC(FL)) antioxidant assay confirmed the presence of a peptide fraction (PF23) with high antioxidant activity [5.53 mmol Trolox equivalents (TE)/g] that contained tryptophan as a main component. We evaluated the effects of both PF23 and tryptophan alone on the modulation of oxidative stress in cultured intestinal cells using a dichlorofluorescein diacetate probe. Despite the high ORAC(FL) value, PF23 enhanced (P human adenocarcinoma cell line, suggesting prooxidant activity. Compared to selected peptide fractions with relatively lower ORAC(FL) values, PF23 induced oxidative stress more than all other peptide fractions tested (P antioxidant enzymes was therefore investigated in FHs 74 Int cells. Exposure of infant intestinal cells to tryptophan resulted in Nrf-2 activation and an increase in the gene transcript level of glutathione peroxidase 2. We conclude that tryptophan-induced oxidative stress associated with tryptophan-containing milk peptides induces an adaptive response that involves the activation of the antioxidant responsive signaling pathway in intestinal cells. PMID:21677072

  15. 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

  16. Inhibition of inflammatory mediators by polyphenolic plant extracts in human intestinal Caco-2 cells.

    Science.gov (United States)

    Romier-Crouzet, Béatrice; Van De Walle, Jacqueline; During, Alexandrine; Joly, Aurélie; Rousseau, Charline; Henry, Olivier; Larondelle, Yvan; Schneider, Yves-Jacques

    2009-06-01

    The mitogen-activated protein kinases (MAPK) and nuclear factor kappaB (NF-kappaB) are involved in transduction cascades that play a key role in inflammatory response. We tested the ability of preselected natural polyphenolic extracts (grape seed, cocoa, sugar cane, oak, mangosteen and pomegranate) to modulate intestinal inflammation using human intestinal Caco-2 cells treated for 4h with these extracts and then stimulated by cytokines for 24 or 48h. The effect of polyphenolic extracts, at 50 micromol of gallic acid equivalent/l, was investigated on inflammation-related cellular events: (i) NF-kappaB activity (cells transfected with a NF-kappaB-luciferase construct), (ii) activation of Erk1/2 and JNK (western blotting), (iii) secretion of interleukin 8 (IL-8) (ELISA), (iv) secretion of prostaglandin (PG) E(2) (ELISA), (v) production of NO (Griess method). Results show that: (i) sugar cane, oak and pomegranate extracts inhibited NF-kappaB activity (from 1.6 to 1.9-fold) (Pextract could be particularly promising in dietary prevention of intestinal inflammation. PMID:19233242

  17. The mycotoxin deoxynivalenol affects nutrient absorption in human intestinal epithelial cells.

    Science.gov (United States)

    Maresca, Marc; Mahfoud, Radhia; Garmy, Nicolas; Fantini, Jacques

    2002-09-01

    Deoxynivalenol (DON) is a mycotoxin belonging to the tricothecene family that has many toxic effects in animals, including diarrhea and weight loss. Using the human epithelial intestinal cell line HT-29-D4 as an in vitro model, we studied the effect of DON on the uptake of different classes of nutrients, including sugars, amino acids and lipids. At low concentrations (below 10 micro mol/L), DON selectively modulated the activities of intestinal transporters: the D-glucose/D-galactose sodium-dependent transporter (SGLT1) was strongly inhibited by the mycotoxin (50% inhibition at 10 micro mol DON, P < 0.05), followed by the D-fructose transporter GLUT5 (42% inhibition at 10 micro mol/L, P < 0.001), active and passive L-serine transporters (30 and 38% inhibition, respectively, at 10 micro mol/L, P < 0.05). The passive transporters of D-glucose (GLUT) were slightly inhibited by DON (15% inhibition at 1 micro mol/L, P < 0.01), whereas the transport of palmitate was increased by 35% at 10 micro mol/L DON (P < 0.001). In contrast, the uptake of cholesterol was not affected by the mycotoxin. At high concentrations (100 micro mol/L), SGLT1 activity was inhibited by 76% (P < 0.01), whereas the activities of all other transporters were increased. The selective effects of DON on intestinal transporters were mimicked by cycloheximide and deoxycholate, suggesting that inhibition of protein synthesis and induction of apoptosis are the main mechanisms of DON toxicity in intestinal cells. PMID:12221236

  18. Evidence against vasoactive intestinal polypeptide as the relaxant neurotransmitter in human cavernosal smooth muscle.

    OpenAIRE

    Pickard, R. S.; Powell, P.H.; Zar, M.A.

    1993-01-01

    1. The putative role of vasoactive intestinal polypeptide (VIP) as the relaxant neurotransmitter in human cavernosal smooth muscle has been studied in isolated tissue preparations. 2. Consistent neurogenic relaxations were evoked by electrical field stimulation (EFS; 2-64 pulses/train, 0.8 ms pulse duration, 10 Hz). VIP (0.1-3 microM) relaxed cavernosal smooth muscle in a dose-dependent fashion. Relaxant responses to both EFS and VIP were reduced in tissue from impotent men. 3. Neurogenic rel...

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

    OpenAIRE

    Derrien, M.M.N.; Vaughan, E.E.; Plugge, C. M.; De Vos, W. M.

    2004-01-01

    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...

  20. 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 ?2- and ?3-cephalosporins were roughly reversed in the two incubation media. In phosphate buffer, the major degradation product w...

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

    DEFF Research Database (Denmark)

    Cowell, G M; Kønigshøfer, E; Danielsen, E M; Hansen, O C; Engberg, J; Hunziker, W; Olsen, Jørgen; Møller, Jette; Laustsen, Lotte; Welinder, K G

    1988-01-01

    The complete primary structure (967 amino acids) of an intestinal human aminopeptidase N (EC 3.4.11.2) was deduced from the sequence of a cDNA clone. Aminopeptidase N is anchored to the microvillar membrane via an uncleaved signal for membrane insertion. A domain constituting amino acid 250-555 positioned within the catalytic domain shows very clear homology to E. coli aminopeptidase N and contains Zn2+ ligands. Therefore these residues are part of the active site. However, no homology of the an...

  2. Immunomodulation of human intestinal T cells by the synthetic CD80 antagonist RhuDex®

    OpenAIRE

    Heninger, Anne-Kristin; Wentrup, Sabine; Al-Saeedi, Mohammed; Schiessling, Serin; GIESE, THOMAS; Wartha, Florian; Meuer, Stefan; Schröder-Braunstein, Jutta

    2014-01-01

    Deregulated activation of mucosal lamina propria T cells plays a central role in the pathogenesis of intestinal inflammation. One of the means to attenuate T cell activation is by blocking the CD28/CD80 co-stimulatory pathway. Here we investigate RhuDex®, a small molecule that binds to human CD80, for its effects on the activation of lamina propria T cells employing a gut-culture model of inflammation. To this end, lamina propria leukocytes (LPL) and peripheral blood lymphocytes (PBL) were st...

  3. Spatial heterogeneity and co-occurrence patterns of human mucosal-associated intestinal microbiota.

    Science.gov (United States)

    Zhang, Zhigang; Geng, Jiawei; Tang, Xiaodan; Fan, Hong; Xu, Jinchao; Wen, Xiujun; Ma, Zhanshan Sam; Shi, Peng

    2014-04-01

    Human gut microbiota shows high inter-subject variations, but the actual spatial distribution and co-occurrence patterns of gut mucosa microbiota that occur within a healthy human instestinal tract remain poorly understood. In this study, we illustrated a model of this mucosa bacterial communities' biogeography, based on the largest data set so far, obtained via 454-pyrosequencing of bacterial 16S rDNAs associated with 77 matched biopsy tissue samples taken from terminal ileum, ileocecal valve, ascending colon, transverse colon, descending colon, sigmoid colon and rectum of 11 healthy adult subjects. Borrowing from macro-ecology, we used both Taylor's power law analysis and phylogeny-based beta-diversity metrics to uncover a highly heterogeneous distribution pattern of mucosa microbial inhabitants along the length of the intestinal tract. We then developed a spatial dispersion model with an R-squared value greater than 0.950 to map out the gut mucosa-associated flora's non-linear spatial distribution pattern for 51.60% of the 188 most abundant gut bacterial species. Furthermore, spatial co-occurring network analysis of mucosa microbial inhabitants together with occupancy (that is habitat generalists, specialists and opportunist) analyses implies that ecological relationships (both oppositional and symbiotic) between mucosa microbial inhabitants may be important contributors to the observed spatial heterogeneity of mucosa microbiota along the human intestine and may even potentially be associated with mutual cooperation within and functional stability of the gut ecosystem. PMID:24132077

  4. A synergetic model for human gait transitions

    Science.gov (United States)

    Abdolvahab, Mohammad

    2015-09-01

    Gait transitions have been considered as bifurcations between states (e.g. walking or running modes) of a nonlinear dynamical system. A top-down synergetic approach to model gait transitions has been adapted from Frank et al. (2009) and applied to two sets of empirical observations. In this approach, it is assumed that the amplitudes of the spatio-temporal modes of locomotion satisfy a generic form of evolution equations that are known to hold for animate and inanimate self-organizing systems. The presented experimental results focus on hysteresis in human walk-to-run and run-to-walk transitions on a treadmill as a function of treadmill inclination and acceleration, the rate at which speed was increased or decreased during experimental trials. The bi-stability in the synergetic model is assumed to account for the hysteretic transitions. Accordingly, the relevant parameters of the model were estimated from the empirical data and the model's efficacy in predicting the observed hysteresis effects was evaluated.

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

    Directory of Open Access Journals (Sweden)

    Larry E Miller

    2013-01-01

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

  6. 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 in vitro 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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    OpenAIRE

    KIM, EUNKYUNG; Sy-Cordero, Arlene; Graf, Tyler N.; Brantley, Scott J; Paine, Mary F.; OBERLIES, NICHOLAS H.

    2010-01-01

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

  9. Nonimmunoglobulin fraction of human milk inhibits the adherence of certain enterotoxigenic Escherichia coli strains to guinea pig intestinal tract.

    Science.gov (United States)

    Ashkenazi, S; Mirelman, D

    1987-08-01

    The protecting effect of human milk against intestinal infections has been well documented, but its mechanism not completely understood. We have examined the effect of the nonimmunoglobulin fraction (NIgF) of human milk and colostrum on bacterial adherence to the intestinal tract. The NIgF was prepared by passing the milk through an immunosorbent column containing rabbit antihuman gamma-globulin (IgG and IgA). The effluent fraction did not contain gamma-globulins as shown by immunodiffusion on agarose and by using rabbit antihuman Ig, that was then detected with fluorescently-labeled goat antirabbit Ig. The effect of the NIgF of human milk on the adherence of enterotoxigenic Escherichia coli strains to guinea pig intestinal tract was quantitatively determined using radiolabeled bacteria which were incubated with suspensions of viable intestinal cells. Thirteen to 17 bacteria adhered per intestinal cell. NIgF of human milk and colostrum (300 microliter, 6.7 mg) caused about 50% inhibition of the adherence of enterotoxigenic E. coli strains whose attachment was mediated by colonization factor antigen I and II. No inhibition was noted on the adherence of enterotoxigenic E. coli strains containing type I pili. The inhibitory activity resisted boiling and proteolytic digestion with trypsin, but was completely abolished by periodate treatment, indicating that carbohydrate residues were probably involved. Examination of the effect of NIgF of human milk on bacterial adherence to intact intestinal surfaces revealed comparable results. Observations with scanning electron microscopy confirmed, morphologically, the attachment of the bacteria and the inhibitory effect of human milk.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3309855

  10. Involvement of Vitamin D receptor in the intestinal induction of human ABCB1.

    Science.gov (United States)

    Tachibana, Shuko; Yoshinari, Kouichi; Chikada, Tsubasa; Toriyabe, Takayoshi; Nagata, Kiyoshi; Yamazoe, Yasushi

    2009-08-01

    ABCB1 (P-glycoprotein) is an efflux transporter that limits the cellular uptake levels of various drugs in intestine, brain, and other tissues. The expression of human ABCB1 has recently been reported to be under the control of nuclear receptor NR1I subfamily members, pregnane X receptor (PXR, NR1I2) and constitutive androstane receptor (CAR, NR1I3). Here, we have investigated the involvement of another NR1I member, vitamin D receptor (VDR, NR1I1), in ABCB1 expression. In the human colorectal adenocarcinoma cell line LS174T, which abundantly expresses VDR, both 1alpha,25-dihydroxyvitamin D(3) (1,25-VD3) and lithocholic acid (LCA) increased ABCB1 mRNA levels. Reporter gene assays in LS174T cells with constructs containing various lengths of the ABCB1 regulatory region revealed that the region containing multiple nuclear receptor binding motifs located at -7.8 kilobases [termed nuclear receptor-responsive module (NURREM)], to which PXR and CAR also bind, is essential for the VDR-mediated ABCB1 transactivation. Further reporter assays with constructs containing truncated NURREM and gel shift assays suggested simultaneous binding of multiple VDR/retinoid X receptor alpha heterodimers to NURREM. Furthermore, knockdown of VDR expression in LS174T cells blocked the LCA- and the 1,25-VD3-induced transcription of ABCB1 reporter genes. In human hepatoma HepG2 cells, in contrast with LS174T cells, 1,25-VD3 activated the ABCB1 transcription only in the presence of ectopically expressed VDR. These results suggest that the NR1I subfamily members regulate the ABCB1 expression sharing the binding sites within NURREM and that the physiologically produced LCA and 1,25-VD3 may modulate the ABCB1 expression in human intestines, possibly associated with interindividual variations of ABCB1 expression. PMID:19460946

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

    Directory of Open Access Journals (Sweden)

    Frank Lehner, Ulf Kulik, Juergen Klempnauer,Juergen Borlak

    2010-08-01

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

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

    Scientific Electronic Library Online (English)

    Marcelo Luiz Carvalho, Gonçalves; Adauto, Araújo; Luiz Fernando, Ferreira.

    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.

  13. 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.

  14. Glyceroglycolipids Affect Uptake of Carotenoids Solubilized in Mixed Micelles by Human Intestinal Caco-2 Cells.

    Science.gov (United States)

    Kotake-Nara, Eiichi; Yonekura, Lina; Nagao, Akihiko

    2015-09-01

    We previously reported that phospholipids markedly affected the uptake of carotenoids solubilized in mixed micelles by human intestinal Caco-2 cells. In the present study, we found that two classes of dietary glyceroglycolipids and the corresponding lysoglyceroglycolipids affected uptake of ?-carotene and lutein by differentiated Caco-2 cells. The levels of carotenoid uptake from micelles containing digalactosyldiacylglycerol or sulfoquinovosyldiacylglycerol were significantly lower than that from control micelles. On the other hand, the uptakes from micelles containing digalactosylmonoacylglycerol or sulfoquinovosylmonoacylglycerol were significantly higher than that from control micelles. In dispersed cells and Caco-2 cells with poor cell-to-cell adhesion, however, the levels of uptake from micelles containing these lyso-lipids were much lower than that from control micelles. The uptake levels from control micelles were markedly decreased depending on the development of cell-to-cell/cell-matrix adhesion in Caco-2 cells, but the uptake levels from the micelles containing these lyso-lipids were not substantially changed, suggesting that the intercellular barrier formed by cell-to-cell/cell-matrix adhesion inhibited the uptake from control micelles, but not from the lyso-lipid-containing micelles. The lyso-lipids appeared to enhance carotenoid uptake by decreasing the intercellular barrier integrity. The results showed that some types of glyceroglycolipids have the potential to modify the intestinal uptake of carotenoids. PMID:26012480

  15. Utilização do método videolaparoscopico na reconstituição do trânsito intestinal após a operação de Hartmann / The use of videolaparoscopic approach in the intestinal transit restoration after Hartmann's procedure

    Scientific Electronic Library Online (English)

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

    2000-02-01

    Full Text Available O objetivo é apresentar a padronização da técnica operatória e os resultados obtidos com a utilização do acesso videolaparoscópico na reconstituição do trânsito intestinal em pacientes previamente submetidos à operação de Hartmann por causas diversas. Foram analisados prospectivamente 32 pacientes, [...] no período de dezembro de 1991 a junho de 1997, com distribuição semelhante com relação ao sexo e com idade média de 42,4 anos. Todos os pacientes foram submetidos ao mesmo preparo pré-operatório e à mesma técnica cirúrgica. Ocorreram três (9,3%) complicações transoperatórias. Uma (3,1 %) anastomose mecânica incompleta, necessitando de endossutura manual, uma (3,1 %) laceração do reto com o grampeador mecânico e uma (3,1 %) lesão da artéria epigástrica direita. Ocorreram ainda três (9,3%) conversões, sendo uma (3,1 %) devido à laceração do reto com o grampeador mecânico, outra (3.1 %) pela invasão tumoral na pelve e outra (3,1 %) pela presença de excessivas aderências intraperitoneais. O tempo operatório variou de 30 a 240 minutos, na média de 126,2 minutos (2,1 horas). A evolução clínica pós-operatória foi satisfatória. Nove (31,0%) pacientes não referiram dor, enquanto 13 (44,8%) a referiram em pequena intensidade, e apenas sete (24,0%) queixaram-se de dor com maior intensidade. A dieta líquida via oral foi instituída no período médio de 1,6 dias, e a primeira evacuação ocorreu na média de 3,2 dias de pós-operatório. O período médio de hospitalização foi de 4,7 dias. Ocorreram complicações pós-operatórias em oito (27,5%) pacientes. Duas (6,8%) infecções da ferida do estoma, dois pacientes (6,8%) com dor no ombro direito, uma (3,4%) deiscência de anastomose, um (3,4%) caso de peritonite por provável contaminação do material cirúrgico, uma coleção líquida pélvica e uma hérnia incisional. Em conclusão, a reconstituição do trânsito intestinal por videolaparoscopia apresentou-se segura e eficaz, podendo constituir-se no método cirúrgico de escolha, pois foi utilizada com sucesso em 90,6% dos pacientes. Abstract in english We present the operative technique and the results of the laparoscopic approach for Hartmann's colostomy reversal. Thirty two patients were prospectively analysed from december 1991 to june 1997. They presented a similar incidence regarding sex distribution, and a median age of 42.4 years old. Ali p [...] atients underwent the same preoperative preparation and operative technique. Three (9.3%) intraoperative complications were observed: an uncompleted anastomosis (3.1%), requiring an endosuture, a rectal perforation by the mechanical stapler and a right epigastric artery lesion. There were convertion to open surgery in three (9.3%) patients: one (3.1%) due to rectal perforation by the mechanical staple1; one (3.1%) for tumoral pelvic invasion and another because of excessive intra-peritoneal adhesions. Operative time varied from 30 to 240 minutes, with a mean time of 126;2 minutes. Nine (31.0%) patients didn't present pain, while 13 (44.8%) referred minimal pain and seven (24.0%) complained severe pain. Oral liquid diet intake occurred within a mean time of 1.6 days and the first evacuation observed after a mean 3.2 postoperative days. Mean hospitalization time was 4.7 days. Postoperative complications occurred in eight (27.5%) patients. Two (6.8%) stoma wound infections, right shoulder pain in two (6.8%) patients, one (3.4%) anastomotic dehiscence, one peritonitis probably due to contaminationfrom surgical instruments, a liquid pelvic coliection and an incisional haernia. 1n conclusion, videolaparoscopic restoration of the intestinal transit demonstrated to be safe and effective. It could be the method of choice because of its success in 90.6 per cent of the patients.

  16. 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.

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

    Scientific Electronic Library Online (English)

    Rina G, Kaminsky; Ramón J, Soto; Adriana, Campa; Marianna K, Baum.

    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 questionnair [...] e, 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

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

    Directory of Open Access Journals (Sweden)

    Chavin Kenneth D

    2004-09-01

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

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

    DEFF Research Database (Denmark)

    Bergström, Anders; Wilcks, Andrea

    2010-01-01

    Background and objective: The present project is part of the large ISAFRUIT project, where one of the objectives is to identify effects of apple and apple product on parameters related to gut health. In a previous rat study we observed changes in the intestinal microbiota of rats fed whole apples, pomace or apple pectin ([1], and we were interested in finding out if the same effect can be observed in humans. Method: The study was conducted as a randomized, controlled 5 x 28 days cross-over study with 24 healthy persons of both genders. The persons were following a pectin- and polyphenol free restriction diet during the control period, and in the four other periods it was supplied with four different apple based supplements. Between the diets there was a 2-week wash-out period still on the restriction diet. The four apple based supplements were: 1) whole apples, 2) clear apple juice (pectin-free), 3) cloudy juice (apple juice with pulp), and 4) pomace (press cake from the cloudy juice production process). Fecal samples were taken before and after each diet period. After DNA extraction, Denaturing Gradient Gel Electrophoresis (DGGE) with universal primers and specific primers for bifidobacteria and Clostridium cluster XIVa was performed. Bands differing between the periods were sequenced, and qPCR was performed to verify the changes observed by DGGE. Results: Changes in the microbiota was observed by DGGE in persons consuming whole apples and pomace. In contrast, the two juice supplements did not show any effect on the microbiota by DGGE. Conclusion: Consumption of whole apples or pomace is able to modify the intestinal microbiota of humans.

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

    Science.gov (United States)

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

    2015-01-01

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

  1. Absorption and transport of pachymic acid in the human intestinal cell line Caco-2 monolayers

    Directory of Open Access Journals (Sweden)

    Yan ZHENG

    2008-07-01

    Full Text Available Objective: To study the absorption and transport of pachymic acid (PA isolated from the sclerotium of Poria cocos (Schw. Wolf. in human intestinal epithelium.Methods: By using Caco-2 (the human colonic adenocarcinoma cell lines cell monolayers as an intestinal epithelial cell model, the permeability of PA was studied from apical side (AP side to basolateral side (BL side or from BL side to AP side. The PA was measured by reversed-phase high performance liquid chromatography coupled with UV detector at maximum absorption wavelength of 210 nm. Transport parameters and apparent permeability coefficients (Papp were then calculated and compared with those of propranolol and atenolol, which were the transcellular transport markers for high and poor permeability respectively.Results: The Papp values of PA were (9.50±2.20 10?7 cm/s from AP side to BL side, and (11.30±5.90 10?7 cm/s from BL side to AP side, respectively. Under the condition of this experiment, the Papp values were 1.45×10?5 cm/s for propranolol and 4.22×10?7 cm/s for atenolol.Conclusion: PA is transported through the Caco-2 cell monolayer in a concentration-dependent manner and the transport was linear with time. The absorption in apical to basolateral direction and secretion in basolateral to apical direction were poor and their Papp values were comparable to atenolol. Besides passive diffusion of PA, ATP is partially involved in its transport

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

    Directory of Open Access Journals (Sweden)

    Marta G?ogowska

    2015-02-01

    Full Text Available Sodium and potassium regulate the total amount of water in the body and the transmission of sodium into and out of individual cells also plays a role in critical body functions. The movement of sodium is critical in generation of these electrical signals. Research was conducted on samples taken from women and men aged 20-90 years, derived from the stomach, small intestine and large intestine. Samples were dried at 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 ?g•g-1d.m., compared to a sodium content in tissues adjacent to the tumor (1813,958 ?g•g-1d.m. and tumor tissues (2029,442 ?g•g-1d.m.. In the case of colon, control tissues have lower average content of sodium (2160,886 ?g•g-1d.m., than the tissues surrounding the tumor (3325,963 ?g•g-1d.m. and tumor tissues (3037,121 ?g•g-1d.m.. The potassium level is higher in the control tissues of stomach (1428,993 ?g•g-1d.m., than in the tissues adjacent to the tumor (1091,544 ?g•g-1d.m. and tumor tissues (1220,471 ?g•g-1d.m.. In the large intestine higher average content of potassium is characterized by tumor tissues (2307,234 ?g•g-1d.m. and tissues adjacent to the tumor (1712,779 ?g•g-1d.m., than control tissue (1389,703 ?g•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.

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

    OpenAIRE

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

    2012-01-01

    A surface protein of Lactobacillus reuteri, mucus adhesion-promoting protein (MapA), is considered to be an adhesion factor. MapA is expressed in L. reuteri strains and adheres to piglet gastric mucus, collagen type I, and human intestinal epithelial cells such as Caco-2. The aim of this study was to identify molecules that mediate the attachment of MapA from L. reuteri to the intestinal epithelial cell surface by investigating the adhesion of MapA to receptor-like molecules...

  4. Cooperation between HNF-1?, Cdx2, and GATA-4 in initiating an enterocytic differentiation program in a normal human intestinal epithelial progenitor cell line

    OpenAIRE

    Benoit, Yannick D.; Paré, Fréderic; Francoeur, Caroline; Jean, Dominique; Tremblay, Eric; Boudreau, François; Escaffit, Fabrice; Beaulieu, Jean-François

    2010-01-01

    In the intestinal epithelium, the Cdx, GATA, and HNF transcription factor families are responsible for the expression of differentiation markers such as sucrase-isomaltase. Although previous studies have shown that Cdx2 can induce differentiation in rat intestinal IEC-6 cells, no data are available concerning the direct implication of transcription factors on differentiation in human normal intestinal epithelial cell types. We investigated the role of Cdx2, GATA-4, and HNF-1? using the undiff...

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

    International Nuclear Information System (INIS)

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

  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

    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 s...

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    In Cambodia, intestinal parasitic infections are prevalent in humans and particularly in children. Yet, information on potentially zoonotic parasites in animal reservoir hosts is lacking. In May 2012, faecal samples from 218 humans, 94 dogs and 76 pigs were collected from 67 households in Dong village, Preah Vihear province, Cambodia. Faecal samples were examined microscopically using sodium nitrate and zinc sulphate flotation methods, the Baermann method, Koga Agar plate culture, formalin-ether...

  8. 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 schedule with two equally spaced 4-h scotoperiods (DARK 4þ4), which yielded the same total duration of darkness per 24 h. 3. Feeding behaviour was recorded weekly from 24-h video recordings of 24 groups each ...

  9. 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

  10. 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.

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

    DEFF Research Database (Denmark)

    Hildebrand, Falk; Ebersbach, Tine

    2012-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1997-04-15

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

  13. 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 ?-strands which form two nearly orthogonal ?-sheets of five strands each, and two short ?-helices that connect the ?-strands A and B. The interior of the protein consists of a water-filled cavity between the two ?-sheets. The NMR solution structure of human I-FABP is similar to the crystal structure of rat I-FABP.The NMR results show significant conformational variability of certain backbone segments around the postulated portal region for the entry and exit of fatty acid ligand

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

    DEFF Research Database (Denmark)

    Avram-Hananel, L.; Stock, J.

    2010-01-01

    PURPOSE: The aim of this study was to evaluate in vitro and in vivo effects of a unique high-butyrate-producing bacterial strain from human colonic flora, Enterococcus durans, in prevention and treatment of intestinal inflammation. METHODS: A compartmentalized Caco-2/leukocyte coculture model was used to examine the in vitro effects of E durans and its metabolite butyrate on basal and Escherichia coli–stimulated secretion of proinflammatory immune factors (IL-8, IL-6, and TNF-?) and the anti-inflammatory cytokine IL-10. A murine model of dextran sodium sulfate-induced colitis was used to examine in vivo effects of prevention and therapy with E durans on clinical, biochemical, and histologic parameters of inflammation. RESULTS: In the coculture model, treatment with E durans and with butyrate reduced basal as well as E coli stimulated secretion of IL-8, IL-6, and TNF-? and increased secretion of IL-10. In the in vivo murine model, preventive administration of E durans significantly ameliorated clinical disease activity index (weight loss, fecal bleeding, and stool consistency), reduced myeloperoxidase concentration in colon tissue extracts, improved histologic scores of colonic inflammation, and inhibited colonic transcription of proinflammatory immune factors. The effect of therapeutic treatment alone on these parameters was more moderate but still significant. CONCLUSIONS: We conclude that E durans strain M4 to 5 and its metabolic product butyrate induce significant anti-inflammatory effects, mediated by regulation of pro- and anti-inflammatory immune factors as well as preservation of intestine epithelial integrity, suggesting that this novel anti-inflammatory bacterium may be preferentially a useful prophylactic treatment to avoid inflammatory bowel disease.

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

    Science.gov (United States)

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

    2014-07-01

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

  16. Immunomodulation of human intestinal T cells by the synthetic CD80 antagonist RhuDex®.

    Science.gov (United States)

    Heninger, Anne-Kristin; Wentrup, Sabine; Al-Saeedi, Mohammed; Schiessling, Serin; Giese, Thomas; Wartha, Florian; Meuer, Stefan; Schröder-Braunstein, Jutta

    2014-11-01

    Deregulated activation of mucosal lamina propria T cells plays a central role in the pathogenesis of intestinal inflammation. One of the means to attenuate T cell activation is by blocking the CD28/CD80 co-stimulatory pathway. Here we investigate RhuDex®, a small molecule that binds to human CD80, for its effects on the activation of lamina propria T cells employing a gut-culture model of inflammation. To this end, lamina propria leukocytes (LPL) and peripheral blood lymphocytes (PBL) were stimulated either through the CD3/T-cell-receptor complex or the CD2-receptor (CD2) employing agonistic monoclonal antibodies. Co-stimulatory signals were provided by CD80/CD86 present on lamina propria myeloid cells or LPS-activated peripheral blood monocytes. Results show that RhuDex® caused a profound reduction of LPL and PBL proliferation, while Abatacept (CTLA-4-Ig) inhibited LPL proliferation to a small degree, and had no effect on PBL proliferation. Furthermore, Abatacept significantly inhibited IL-2, TNF-?, and IFN-? release from LPL, primarily produced by CD4(+) T cells, where IL-2 blockage was surprisingly strong, suggesting a down-regulating effect on regulatory T cells. In contrast, in the presence of RhuDex®, secretion of IL-17, again mostly by CD4(+) T cells, and IFN-? was inhibited in LPL and PBL, yet IL-2 remained unaffected. Thus, RhuDex® efficiently inhibited lamina propria and peripheral blood T-cell activation in this pre-clinical study making it a promising drug candidate for the treatment of intestinal inflammation. PMID:25505551

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

    OpenAIRE

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

    2007-01-01

    The gastrointestinal tract is the main site where the conversion and absorption of food components takes place. The host-derived physiological processes and the residing microorganisms, especially in the small intestine, contribute to this nutrient supply. To circumvent sampling problems of the small intestine, several model systems have been developed to study microbial diversity and functionality in the small intestine. In addition, metagenomics offers novel possibilities to gain insight in...

  18. Studies of the immunoglobulin-producing cells of the human intestine: the defunctioned bowel.

    OpenAIRE

    Wijesinha, S S; Steer, H. W.

    1982-01-01

    An indirect immunoperoxidase method was used to visualise immunoglobulin-containing cells in the large intestinal mucosa of 10 children who had defunctioning colostomies. Intestine deprived of its usual exposure to intraluminal antigens contained less immunocytes per unit area than intestinal mucosa subjected to normal stimulation by dietary and microbial antigens. These findings substantiate in man the conclusion based on observations made on animals that continued mucosal exposure to antige...

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

    Directory of Open Access Journals (Sweden)

    Canzonieri Vincenzo

    2009-03-01

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

  20. 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

  1. 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.

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

    Science.gov (United States)

    Morris, David J

    2015-10-01

    The main purpose of this review article is threefold (a) to try to address the question "why are two adrenal glucocorticoids, cortisol and corticosterone, secreted by humans and other mammalian species?", (b) to outline a hypothesis that under certain physiological conditions, corticosterone has additional biochemical functions over and above those of cortisol, and (c) to emphasize the role of gastrointestinal bacteria in chemically transforming corticosterone into metabolites and that these re-cycled metabolites can be reabsorbed from the enterohepatic circuit. Cortisol and its metabolites are not secreted into the bile and thus are excluded from the enterohepatic circuit. Corticosterone was the first steroid hormone isolated from adrenal gland extracts. Many believe that corticosterone functions identically to cortisol. Yet, corticosterone causes significant sodium retention and potassium secretion in Addisonian patients, unlike cortisol. In humans, corticosterone and its metabolite, 3?,5?-TH-corticosterone, are excreted via the bile in humans where they are transformed in the intestine by anaerobic bacteria into 21-dehydroxylated products: 11?-OH-progesterone or 11?-OH-(allo)-5?-preganolones. These metabolites inhibit 11?-HSD2 and 11?-HSD1 dehydrogenase, being many-fold more potent than 3?,5?-TH-cortisol. Corticosterone has significantly lower Km's for both 11?-HSD2 and 11?-HSD1 enzymatic dehydrogenase activity, compared to cortisol. Patients diagnosed with 17?-hydroxylase deficiency have elevated blood pressure and high levels of circulating corticosterone, 3?,5?-TH-corticosterone, and their 21-dehydroxlated corticosterone derivatives. In humans, these 5?-corticosterone metabolites are likely to influence blood pressure regulation and Na(+) retention by inhibiting the rate of deactivation of cortisol by 11?-HSD isoforms. PMID:26144050

  3. 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.

  4. Perfil epidemiológico e morbimortalidade dos pacientes submetidos à reconstrução de trânsito intestinal: experiência de um centro secundário do nordeste Brasileiro / Epidemiologic profile and morbimortality of patients undergoing to intestinal transit reconstruction: experience of a secundary health service in Brazil northeast

    Scientific Electronic Library Online (English)

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

    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 (p Abstract in english Background - The reconstruction of the intestinal tract is not surgical complications risk-free and is associated to postoperative complications high rates; furthermore, infection remains the hardest challenge in this procedure. Methods - Retrospectively, eighty-six patients with intestinal stomas w [...] ere analyzed through factors that impact on the morbimortality afterwards intestinal transit reconstruction, since January 2003 to April 2009. Results - Loop colostomy (n=34) and abdominal trauma implicating 38.2% of indications to colostomy or ileostomy were the most frequent conditions. The mean interval between stoma confection and intestinal transit reconstruction was 15.7 months. The morbidity frequency was 56.8% and incisional infection was its commonest complication (27.47%). The mean inpatient length of stay was 7.6 days. There was positive linear regression between post-operative inpatient length of stay and inpatient's age. Inpatient length of stay prolongation is associated to occurrence of complications (p

  5. Cloning of a pig homologue of the human lactoferrin receptor: expression and localization during intestinal maturation in piglets.

    Science.gov (United States)

    Liao, Yalin; Lopez, Veronica; Shafizadeh, Tracy B; Halsted, Charles H; Lönnerdal, Bo

    2007-11-01

    The presence of a small intestinal lactoferrin receptor (SI-LfR) has been suggested in the pig, but remains to be identified. LfR has been suggested to play a key role in the internalization of lactoferrin (Lf) and to facilitate absorption of iron bound to Lf. The aim of this study was to identify the pig SI-LfR cDNA, determine its mRNA and protein expression during different stages of intestinal development. The coding region of the pig LfR cDNA was cloned by PCR using conserved sequences among species. LfR mRNA expression and protein abundance were measured in proximal small intestine from piglets at 1 week (pre-weaning), 3 weeks (weaning) and 6 months (post-weaning) of age by quantitative real-time PCR (Q-PCR) and Western blot, respectively. Intestinal brush border membrane vesicles (BBMV) were also isolated to examine LfR abundance on the apical membrane. We determined the pig SI-LfR open reading frame (ORF) consists of 972 bp, resulting in a protein with a molecular mass approximately 135 kD and approximately 35 kD under non-reducing and reducing conditions, respectively. Using Q-PCR, we determined LfR expression significantly increased with age in the duodenum and reciprocally decreased in the jejunum. Intestinal LfR protein expression was maintained at all timepoints in the jejunum; however, in the duodenum LfR abundance reached maximum levels at 6 months. In BBMV fractions, LfR abundance significantly increased with age. Taken together our findings demonstrate the presence of a human SI-LfR homologue in pig, with mRNA and protein expression concomitantly regulated in the duodenum and inversely regulated in the jejunum. These findings suggest a mechanism by which pig Lf can be internalized in the intestine. PMID:17766154

  6. Evidence for an innate immune response in the immature human intestine: toll-like receptors on fetal enterocytes.

    Science.gov (United States)

    Fusunyan, R D; Nanthakumar, N N; Baldeon, M E; Walker, W A

    2001-04-01

    The intestinal epithelium is an active participant in the mucosal immune response against luminal pathogens. Microorganisms and their cell wall products, i.e. lipopolysaccharide (LPS), can stimulate the enterocyte to produce an innate immune response with the increased production of IL-8 via an activation of the transcription factor NFkappaB. The innate response mechanism, however, has not been understood until the recent description of a family of human toll-like receptors (hTLR) on immune cells that interact with LPS and modulate the IL-8 response via an intracellular signal transduction pathway similar to that of the IL-1 receptor family. Accordingly, in this study we have sought to determine the constitutive and regulated expression of hTLR on a nonmalignant human fetal primary small intestinal cell line (H4 cells) and on small intestinal samples of ileum from human fetuses (age 18-21 wk). Specimens were examined by reverse-transcription PCR, Western blot analysis, and immunofluorescence for hTLR2 and hTLR4 mRNA and protein and to determine whether their expression was regulated by LPS or by an endogenous inflammatory stimulus, IL-1beta. hTLR2 and hTLR4 were expressed constitutively on H4 cells and on human fetal small intestinal enterocytes, predominantly on the basolateral surface of crypt enterocytes. Inflammatory stimuli appeared to regulate hTLR transcription (IL-1beta increased both hTLR2 and hTLR4 whereas LPS decreased hTLR4) and possibly translation (qualitative observations). The presence of hTLR on human fetal enterocyte suggests a mechanism for the innate immune response to pathogens and could provide the basis for further study of the accentuated inflammatory response in age-dependent gastrointestinal diseases such as necrotizing enterocolitis. PMID:11264445

  7. Vasoactive intestinal polypeptide immunoreactivity in the human cerebellum: qualitative and quantitative analyses.

    Science.gov (United States)

    Benagiano, Vincenzo; Flace, Paolo; Lorusso, Loredana; Rizzi, Anna; Bosco, Lorenzo; Cagiano, Raffaele; Ambrosi, Glauco

    2009-09-01

    Although autoradiographic, reverse transcription-polymerase chain reaction and immunohistochemical studies have demonstrated receptors for vasoactive intestinal polypeptide (VIP) in the cerebellum of various species, immunohistochemistry has never shown immunoreactivity for VIP within cerebellar neuronal bodies and processes. The present study aimed to ascertain whether VIP immunoreactivity really does exist in the human cerebellum by making a systematic analysis of samples removed post-mortem from all of the cerebellar lobes. The study was carried out using light microscopy immunohistochemical techniques based on a set of four different antibodies (three polyclonal and one monoclonal) against VIP, carefully selected on the basis of control tests performed on human colon. All of the antibodies used showed VIP-immunoreactive neuronal bodies and processes distributed in the cerebellar cortex and subjacent white matter of all of the cerebellum lobes, having similar qualitative patterns of distribution. Immunoreactive neurons included subpopulations of the main neuron types of the cortex. Statistical analysis of the quantitative data on the VIP immunoreactivity revealed by the different antibodies in the different cerebellar lobes did not demonstrate any significant differences. In conclusion, using four different anti-VIP antibodies, the first evidence of VIP immunoreactivity is herein supplied in the human post-mortem cerebellum, with similar qualitative/quantitative patterns of distribution among the different cerebellum lobes. Owing to the function performed by VIP as a neurotransmitter/neuromodulator, it is a candidate for a role in intrinsic and extrinsic (projective) circuits of the cerebellum, in agreement with previous demonstrations of receptors for VIP in the cerebellar cortex and nuclei. As VIP signalling pathways are implicated in the regulation of cognitive and psychic functions, cerebral blood flow and metabolism, processes of histomorphogenesis, differentiation and outgrowth of nervous tissues, the results of this study could be applied to clinical neurology and psychiatry, opening new perspectives for the interpretation of neurodevelopment disorders and development of new therapeutic strategies in cerebellar diseases. PMID:19552726

  8. 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

  9. [Influence of sodium alginate on the intestinal transit in low birth weight newborn infants].

    Science.gov (United States)

    Chouraqui, J P; Morer, I; Renard, P; Bielsky, M C; Richard-Berthe, C; Rambaud, P

    1993-01-01

    Sodium alginate (Gaviscon) is used in the management of gastro-oesophageal reflux in infants. No digestive disadvantages have as yet been reported with the use of the Gaviscon formula available in France, which contains neither aluminium hydroxide nor thickener. Twenty-two healthy neonates were prospectively studied before and after Gaviscon treatment in order to characterize their whole gut transit time with the use of a carmine index. The head of the marker appeared within the same time in both experiments but the appearance of the tail was earlier in the treated infants (P Gaviscon can be regarded as having no deleterious effect on transit time in neonates. PMID:8247649

  10. Heparin induces the expression of specific matrix proteins by human intestinal smooth muscle cells

    International Nuclear Information System (INIS)

    Human intestinal smooth muscle (HISM) cells have recently been identified as the major cell type responsible for stricture formation in Crohn's disease. Heparin, a sulfated glycosaminoglycan, has been shown to be a key modulator of vascular smooth muscle cell (VSMC) growth both in vivo and in vitro and to affect the phenotypic expression of proteins made by VSMC. Heparin has also been shown to effect the growth of HISM cells and in this report the authors demonstrate that heparin also has very specific effects on proteins released by HISM cells in vitro. Examination of the proteins in the culture medium of heparin-treated HISM cells observed at 3 time points following sparse plating and proliferation revealed an increase in 35S-methionine-labeled 200, 37, and 35 kd proteins. A transient effect on a 48 kd protein was observed in substrate-attached material left on the culture dish after the cells were removed with EGTA. No effects on intracellular labeled proteins could be demonstrated. The protein phenotype of HISM cells exposed to heparin appears very similar to that observed in VSMC. The release of specific proteins following exposure to heparin does not appear to be species specific. This response to heparin may reflect a significant influence of this glycosaminoglycan on the phenotypic expression of these cells

  11. Comparative Morphology of Minute Intestinal Fluke Eggs That Can Occur in Human Stools in the Republic of Korea

    OpenAIRE

    Lee, Jin-Joo; Jung, Bong-Kwang; Lim, Hyemi; Lee, Mi Youn; Choi, Sung-Yil; Shin, Eun-Hee; Chai, Jong-Yil

    2012-01-01

    The egg morphology of minute intestinal flukes (MIF) that can occur as human infections in the Republic of Korea, i.e., Metagonimus yokogawai, M. miyatai, M. takahashii, Heterophyes nocens, Heterophyopsis continua, Stellantchasmus falcatus, Stictodora fuscata, Pygidiopsis summa, and Gymnophalloides seoi, was studied in comparison with Clonorchis sinensis. The adult worms were obtained from residents of endemic areas, and their intrauterine eggs were studied and measured using light microscopy...

  12. Lipoteichoic acid from Lactobacillus plantarum inhibits Pam2CSK4-induced IL-8 production in human intestinal epithelial cells.

    Science.gov (United States)

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

    2015-03-01

    Lactobacilli are probiotic bacteria that are considered to be beneficial in the gastrointestinal tract of humans. Although lactobacilli are well known to alleviate intestinal inflammation, the molecular basis of this phenomenon is poorly understood. In this study, we investigated the effect of Lactobacillus plantarum lipoteichoic acid (Lp.LTA), which is a major cell wall component of this species, on the production of interleukin (IL)-8 in human intestinal epithelial Caco-2 cells. Treatment with Pam2CSK4, a synthetic lipopeptide that is known to mimic Gram-positive bacterial lipoproteins as an important virulence factor, significantly induced IL-8 expression in Caco-2 cells. However, neither heat-inactivated L. plantarum nor L. plantarum peptidoglycan inhibited Pam2CSK4-induced IL-8 mRNA expression. In addition, both a deacylated form and a dealanylated form of Lp.LTA failed to inhibit Pam2CSK4-induced IL-8 expression, indicating that the lipid and D-alanine moieties are critical for Lp.LTA-mediated inhibition. Moreover, Lp.LTA inhibited Pam2CSK4-induced activation of p38 kinase, JNK, and NF-?B transcription factor by suppressing toll-like receptor 2 activation. Collectively, these results suggest that Lp.LTA exerts anti-inflammatory effects on human intestinal epithelial cells by blocking IL-8 production. PMID:25481370

  13. Fermentation by gut microbiota cultured in a simulator of the human intestinal microbial ecosystem is improved by probiotic Enterococcus faecium CRL 183

    OpenAIRE

    Rossi, Elizeu A; Fernanda Bianchi; Katia Sivieri; Maria A. Tallarico

    2011-01-01

    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...

  14. 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 ?g 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 ?g 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

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

    Science.gov (United States)

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

    2015-02-01

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

  16. 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...

  17. D-cycloserine uses an active transport mechanism in the human intestinal cell line Caco 2.

    OpenAIRE

    Ranaldi, G; Islam, K.; Sambuy, Y

    1994-01-01

    In a previous study we have shown that cultured epithelial cell lines can be used to measure the transepithelial passage of antimicrobial agents across the intestine and to obtain information on the mechanisms of transport utilized and predict the bioavailability of the antimicrobial agents after oral administration. In particular, among the drugs investigated, D-cycloserine had been shown to be transported in a polarized manner only in the intestinal cells. In the present work, further chara...

  18. Human defensin 5 expression in intestinal metaplasia of the upper gastrointestinal tract

    OpenAIRE

    Shen, B.; Porter, E. M.; Reynoso, E.; Shen, C.; Ghosh, D.; Connor, J T; Drazba, J; Rho, H K; Gramlich, T L; Li, R; Ormsby, A H; Sy, M-S; Ganz, T.; Bevins, C L

    2005-01-01

    Background: Upper gastrointestinal tract intestinal metaplasia (IM) is termed Barrett’s oesophagus (BO) or gastric intestinal metaplasia (GIM), depending on its location. BO and GIM are associated with chemical exposure resulting from gastro–oesophageal reflux and chronic Helicobacter pylori infection, respectively. Paneth cells (PCs), characterised by cytoplasmic eosinophilic granules, are found in a subset of IM at these sites, but histology may not accurately detect them.

  19. PEPT1-Mediated Cefixime Uptake into Human Intestinal Epithelial Cells Is Increased by Ca2+ Channel Blockers

    OpenAIRE

    Wenzel, Uwe; Kuntz, Sabine; Diestel, Simone; Daniel, Hannelore

    2002-01-01

    Ca2+ channel blockers like nifedipine have been shown to increase the oral bioavailability of ?-lactam antibiotics, such as cefixime, in humans. The molecular mode of action of Ca2+ channel blockers on ?-lactam absorption, however, has not yet been defined. Using the Caco-2 human intestinal epithelial cell line, we assessed whether alterations in intracellular free Ca2+ ion (Ca2+in) concentrations by Ca2+ channel blockers or by Ca2+ ionophores affect [14C]cefixime absorption. Reduction of Ca2...

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

    Directory of Open Access Journals (Sweden)

    Ekaette Godwin Edelduok

    2013-01-01

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

  1. Secretion of human meprin from intestinal epithelial cells depends on differential expression of the alpha and beta subunits.

    Science.gov (United States)

    Lottaz, D; Hahn, D; Müller, S; Müller, C; Sterchi, E E

    1999-01-01

    Human meprin (N-benzoyl-l-tyrosyl-p-aminobenzoic acid hydrolase, EC 3.4.24.18), an astacin-type metalloprotease, is expressed by intestinal epithelial cells as a dimeric protein complex of alpha and beta subunits. In transfected cells, intracellular proteolytic removal of the membrane anchor from the alpha subunit results in its secretion, while the beta subunit and alpha/beta heterodimers are retained at the cell membrane. We investigated the consequence of differential intracellular processing of alpha and beta subunits in the human small and large intestine using subunit-specific immunohistochemistry, in situ hybridization and biosynthetic studies in organ culture. In the ileum, both subunits localize to the brush-border membrane of villus enterocytes. In contrast, the beta subunit is not expressed in the colon, which leads to the secretion of the alpha subunit. We conclude that differential expression of meprin alpha and beta subunits is a unique means of targeting the proteolytic activity of the alpha subunit either to the brush-border membrane in the ileum or to the lumen in the colon, suggesting dual functions of cell-associated and luminal meprin. Meprin alpha and beta subunits are also coexpressed in distinct lamina propria leukocytes, suggesting an additional role for this protease in leukocyte function in the intestinal mucosa. PMID:9914532

  2. 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

  3. Intestinal microsporidiosis due to Enterocytozoon bieneusi in elderly human immunodeficiency virus--negative patients from Vigo, Spain.

    Science.gov (United States)

    Lores, Beatriz; López-Miragaya, Isabel; Arias, Cristina; Fenoy, Soledad; Torres, Julio; del Aguila, Carmen

    2002-04-01

    We report what is, to our knowledge, the first study in which microsporidial infection was detected in elderly human immunodeficiency virus (HIV)--negative patients. Of the 60 elderly patients studied, 47 had diarrhea. Intestinal microsporidiosis due to Enterocytozoon bieneusi was diagnosed in 8 patients (17.02%) by use of Weber's chromotrope-based stain and polymerase chain reaction with species-specific primers. The mean age of these 8 patients was 75 years; 7 had chronic diarrhea and 1 had nonchronic diarrhea. Six of the patients with chronic diarrhea had no other pathogens isolated. In our opinion, elderly patients, because of their special immunological characteristics, should be considered a group at risk for the acquisition of intestinal microsporidiosis. PMID:11880956

  4. High affinity receptors for vasoactive intestinal peptide on a human glioma cell line

    Energy Technology Data Exchange (ETDEWEB)

    Nielsen, F.C.; Gammeltoft, S.; Westermark, B.; Fahrenkrug, J. (Bispebjerg Hospital, Copenhagen NV (Denmark))

    1990-11-01

    Vasoactive intestinal peptide (VIP) bound with high affinity (Kd 0.13 nmol/l) to receptors on the human glioma cell line U-343 MG Cl 2:6. The receptors bound the related peptides helodermin, PHM and secretin with 10, 400 and 5000 times lower affinity, respectively. Deamidated VIP (VIP-COOH) and (des-His1)VIP bound with 10 and 100 times lower affinity. The fragment VIP(7-28) displaced 25% of the receptor-bound {sup 125}I-VIP whereas VIP(16-28) and VIP(1-22-NH2) were inactive. The binding of {sup 125}I-VIP could be completely inhibited by 10 mumol/l of the antagonists (N-Ac-Tyr1,D-Phe2)GRF(1-29)-NH2, (pCl-D-Phe6,Leu17)VIP and VIP(10-28); in contrast, the antagonist L-8-K was inactive. Affinity labeling showed that VIP bound to proteins with Mr's of 75 kDa, 66 kDa and 50 kDa, respectively. Following binding, the peptide was rapidly internalized, and at steady-state only 20% of cell-associated {sup 125}I-VIP was bound to receptors on the cell surface. The internalized {sup 125}I-VIP was completely degraded to {sup 125}I-tyrosine which was released from the cells. Degradation of internalized {sup 125}I-VIP was significantly reduced by chloroquine phenanthroline and pepstatin-A. Surface binding and internalization of {sup 125}I-VIP was increased 3 times by phenanthroline, and pepstatin-A caused a 5 times increase in surface binding. Chloroquine reduced surface-bound {sup 125}I-VIP, but caused retention of internalized {sup 125}I-VIP.

  5. High affinity receptors for vasoactive intestinal peptide on a human glioma cell line

    International Nuclear Information System (INIS)

    Vasoactive intestinal peptide (VIP) bound with high affinity (Kd 0.13 nmol/l) to receptors on the human glioma cell line U-343 MG Cl 2:6. The receptors bound the related peptides helodermin, PHM and secretin with 10, 400 and 5000 times lower affinity, respectively. Deamidated VIP (VIP-COOH) and [des-His1]VIP bound with 10 and 100 times lower affinity. The fragment VIP(7-28) displaced 25% of the receptor-bound 125I-VIP whereas VIP(16-28) and VIP(1-22-NH2) were inactive. The binding of 125I-VIP could be completely inhibited by 10 mumol/l of the antagonists [N-Ac-Tyr1,D-Phe2]GRF(1-29)-NH2, [pCl-D-Phe6,Leu17]VIP and VIP(10-28); in contrast, the antagonist L-8-K was inactive. Affinity labeling showed that VIP bound to proteins with Mr's of 75 kDa, 66 kDa and 50 kDa, respectively. Following binding, the peptide was rapidly internalized, and at steady-state only 20% of cell-associated 125I-VIP was bound to receptors on the cell surface. The internalized 125I-VIP was completely degraded to 125I-tyrosine which was released from the cells. Degradation of internalized 125I-VIP was significantly reduced by chloroquine phenanthroline and pepstatin-A. Surface binding and internalization of 125I-VIP was increased 3 times by phenanthroline, and pepstatin-A caused a 5 times increase in surface binding. Chloroquine reduced surface-bound 125I-VIP, but caused retention of internalized 125I-VIP

  6. 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

  7. 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.

  8. PKQuest: measurement of intestinal absorption and first pass metabolism – application to human ethanol pharmacokinetics

    Directory of Open Access Journals (Sweden)

    Levitt David G

    2002-08-01

    Full Text Available Abstract Background PKQuest, a new physiologically based pharmacokinetic (PBPK program, is applied to human ethanol data. The classical definition of first pass metabolism (FPM based on the differences in the area under the curve (AUC for identical intravenous and oral doses is invalid if the metabolism is non-linear (e.g. ethanol. Uncertainties in the measurement of FPM have led to controversy about the magnitude of gastric alcohol metabolism. PKQuest implements a new, rigorous definition of FPM based on finding the equivalent intravenous input function that would produce a blood time course identical to that observed for the oral intake. This input function equals the peripheral availability (PA and the FPM is defined by: FPM = Total oral dose – PA. PKQuest also provides a quantitative measurement of the time course of intestinal absorption. Methods PKQuest was applied to previously published ethanol pharmacokinetic data. Results The rate of ethanol absorption is primarily limited by the rate of gastric emptying. For oral ethanol with a meal: absorption is slow (? 3 hours and the fractional PKQuest FPM was 36% (0.15 gm/Kg dose and 7% (0.3 gm/Kg. In contrast, fasting oral ethanol absorption is fast (? 50 minutes and FPM is small. Conclusions The standard AUC and one compartment methods significantly overestimate the FPM. Gastric ethanol metabolism is not significant. Ingestion of a coincident meal with the ethanol can reduce the peak blood level by about 4 fold at low doses. PKQuest and all the examples are freely available on the web at http://www.pkquest.com.

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

    Science.gov (United States)

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

    2012-12-01

    Oxidative stress is a major mediator of tissue and cell injuries. The injury in chronic nephrotic syndrome, acute renal failure, myeloma kidney injury and other kidney diseases is initiated by oxidative stress. We have previously demonstrated that vasoactive intestinal peptide (VIP) acts as an antiproliferative agent in renal cancer cells. This study was designed to evaluate the renoprotective activity of VIP against H(2)O(2)-induced oxidative damage in a proximal tubule kidney cell line (human, non-tumor, HK2 cells) in order to investigate the potential usefulness of this peptide in the treatment of oxidative-stress related kidney diseases. HK2 cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Propidium iodide was used to identify cells undergoing apoptosis. Western blotting was performed with anti-Bcl-2, anti-Bax and anti-formyl peptide receptor (low-affinity variant FPRL-1) monoclonal antibodies whereas 2,7-dichlorofluorescein diacetate was used for measurement of levels of intracellular reactive oxygen species (ROS). HK2 cells were injured with H(2)O(2) in order to induce apoptosis: the effect was time- and dose-dependent. VIP increased the levels of the antiapoptotic protein Bcl-2 and decreased those of the proapoptotic protein Bax. VIP decreased the intracellular ROS levels reached by H(2)O(2)-induced oxidative stress. VIP effect on ROS levels involved FPLR-1 but not VPAC(1,2) receptors as evidenced by the use of the respective antagonists WRW4 and JV-1-53. Thus, VIP protects HK2 cells from apoptosis by increasing Bcl-2 levels and this effect is initiated through FPLR1 receptor. In conclusion, VIP might exert a renoprotective effect by the suppression of oxidative stress. PMID:23000305

  10. 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.

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

    Science.gov (United States)

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

    2015-06-01

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

  12. Regional unemployment and human capital in transition economies.

    Czech Academy of Sciences Publication Activity Database

    Jurajda, Št?pán; Terrell, K.

    -, ?. 77 (2007), s. 1-34 Institutional research plan: CEZ:AV0Z70850503 Keywords : unemployment * human capital * regional labor markets Subject RIV: AH - Economics http://ipc.umich.edu/workingpapers/ipc-77-jurajda,terrell,regional- unemployment -human-capital-transition-economies.pdf

  13. Transcriptional and functional profiling of human intestinal dendritic cells reveals conserved specialization and a role for Bcl-6 and Blimp-1 in terminal subset differentiation

    OpenAIRE

    Watchmaker, Payal B.; Lahl, Katharina; Lee, Mike; Baumjohann, Dirk; Morton, John; Kim, Sun Jung; Zeng, Ruizhu; Dent, Alexander; Ansel, K Mark; Diamond, Betty; Hadeiba, Husein; Butcher, Eugene C

    2013-01-01

    Dendritic cells (DCs) that orchestrate mucosal immunity have been studied in mice. Here we characterize human gut DC populations, and define their relationship to previously studied human and mouse DCs. CD103+Sirp?? DCs were related to human blood CD141+ and to mouse intestinal CD103+CD11b? DCs and expressed markers of cross-presenting DCs. CD103+Sirp?+ DCs aligned with human blood CD1c+ DCs and mouse intestinal CD103+CD11b+ DCs and supported regulatory T cell induction. Both CD103+ DC subset...

  14. In Vivo Transfer of the vanA Resistance Gene from an Enterococcus faecium Isolate of Animal Origin to an E. faecium Isolate of Human Origin in the Intestines of Human Volunteers

    OpenAIRE

    Lester, Camilla H; Frimodt-Møller, Niels; Sørensen, Thomas Lund; Monnet, Dominique L; Hammerum, Anette M.

    2006-01-01

    Transient colonization by vancomycin-resistant enterococci of animal origin has been documented in the intestines of humans. However, little is known about whether transfer of the vanA gene occurs in the human intestine. Six volunteers ingested a vancomycin-resistant Enterococcus faecium isolate of chicken origin, together with a vancomycin-susceptible E. faecium recipient of human origin. Transconjugants were recovered in three of six volunteers. In one volunteer, not only was vancomycin res...

  15. Intestinal invagination Invaginación intestinal.

    Directory of Open Access Journals (Sweden)

    Dayamnelys Aguilar Atanay

    Full Text Available Intestinal intussusceptions are the most frequent cause of acute surgical occlusive syndrome in infants; it is idiopathic in more than 90% of cases. Their treatment can be conservative, with reduction by means of imaging and hydrostatic procedures, or surgical. We presented the Good Clinical Practices Guideline for Intestinal intussusceptions, approved by consensus in the 3th National Good Clinical Practices Workshop in Pediatric Surgery (Camagüey, Cuba; February 23 – 26, 2004.
    La invaginación intestinal es la causa más frecuente del síndrome de abdomen agudo quirúrgico oclusivo en lactantes y es idiopática en más del 90 % de los casos. Su tratamiento puede ser conservador, con reducción mediante procedimientos hidrostáticos combinados con vigilancia imaginológica, o quirúrgico. Se presenta la Guía de Buenas Prácticas Clínicas para invaginación intestinal, aprobada por consenso en el 3er Taller Nacional de Buenas Prácticas Clínicas en Cirugía Pediátrica (Camagüey, 23 al 26 de febrero de 2004.

  16. Intestinal Cancer

    Science.gov (United States)

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

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

    Science.gov (United States)

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

    2014-08-01

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

  18. 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-?B 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.

  19. Diagnostic examination of human intestinal spirochetosis by fluorescent in situ hybridization for Brachyspira aalborgi, Brachyspira pilosicoli, and other species of the genus Brachyspira (Serpulina)

    DEFF Research Database (Denmark)

    Jensen, Tim Kåre; Boye, Mette; Ahrens, Peter; Korsager, B.; Teglbjaerg, P. S.; Lindboe, C.F.; Møller, Kristian

    2001-01-01

    Human intestinal spirochetosis, characterized by end-on attachment of densely packed spirochetes to the epithelial surface of the large intestines as a fringe has been associated with the weakly beta-hemolytic spirochetes Brachyspira aalborgi and Brachyspira (Serpulina) pilosicoli. In this study, fluorescent in situ hybridization with oligonucleotide probes targeting 16S or 23S rRNA of B. aalborgi, B. pilosicoli, and the genus Brachyspira was applied to 40 sections of formalin-fixed, paraffin-em...

  20. DNA–Methylome Analysis of Mouse Intestinal Adenoma Identifies a Tumour-Specific Signature That Is Partly Conserved in Human Colon Cancer

    OpenAIRE

    Grimm, Christina; Chavez, Lukas; Vilardell, Mireia; Farrall, Alexandra L.; Tierling, Sascha; Böhm, Julia W.; Grote, Phillip; Lienhard, Matthias; Dietrich, Jörn; Timmermann, Bernd; Walter, Jörn; Schweiger, Michal R; Lehrach, Hans; Herwig, Ralf; Bernhard G. Herrmann10

    2013-01-01

    Aberrant CpG methylation is a universal epigenetic trait of cancer cell genomes. However, human cancer samples or cell lines preclude the investigation of epigenetic changes occurring early during tumour development. Here, we have used MeDIP-seq to analyse the DNA methylome of APCMin adenoma as a model for intestinal cancer initiation, and we present a list of more than 13,000 recurring differentially methylated regions (DMRs) characterizing intestinal adenoma of the mouse. We show that Polyc...

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

    OpenAIRE

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

    2007-01-01

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

  2. Intestinal 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.

  3. What Future Expects Humanity After the Demographic Transition Time?

    CERN Document Server

    Kobelev, L Yu

    2000-01-01

    The variant of phenomenological theory of humankind future existence after time of demographic transition based on treating the time of demographic transition as a point of phase transition and taking into account an appearing of the new phase of mankind is proposed. The theory based on physical phenomenological theories of phase transitions and classical equations for system predatory-preys for two phases of mankind, take into account assumption about a multifractal nature of the set of number of people in temporal axis and contains control parameters. The theory includes scenario of destroying of existent now human population by new phase of humanity and scenario of old and new phases co-existence. In particular cases when the new phase of mankind is absent the equations of theory may be formulated as equations of Kapitza, Foerster, Hoerner, Kobelev and Nugaeva, Johansen and Sornette phenomenological theories of growth of mankind.

  4. D-cycloserine transport in human intestinal epithelial (Caco-2) cells: mediation by a H(+)-coupled amino acid transporter.

    OpenAIRE

    Thwaites, D. T.; Armstrong, G; Hirst, B.H.; Simmons, N L

    1995-01-01

    1. The ability of D-cycloserine to act as a substrate for H+/amino acid symport has been tested in epithelial layers of Caco-2 human intestinal cells. 2. In Na(+)-free media with the apical bathing media held at pH 6.0, D-cycloserine (20 mM) is an effective inhibitor of net transepithelial transport (Jnet) of L-alanine (100 microM) and its accumulation (across the apical membrane) in a similar manner to amino acid substrates (L-alanine, beta-alanine, L-proline and glycine). In contrast L-vali...

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

    International Nuclear Information System (INIS)

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

  6. Transcriptional regulation of the human Na{sup +}/H{sup +} exchanger NHE3 by serotonin in intestinal epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Amin, Md Ruhul; Ghannad, Leda; Othman, Ahmad; Gill, Ravinder K. [Section of Digestive Diseases and Nutrition, Department of Medicine, University of Illinois at Chicago, 840 S. Wood Street, Chicago, IL 60612 (United States); Dudeja, Pradeep K.; Ramaswamy, Krishnamurthy [Section of Digestive Diseases and Nutrition, Department of Medicine, University of Illinois at Chicago, 840 S. Wood Street, Chicago, IL 60612 (United States); Jesse Brown VAMC, Chicago, IL 60612 (United States); Malakooti, Jaleh, E-mail: malakoot@uic.edu [Section of Digestive Diseases and Nutrition, Department of Medicine, University of Illinois at Chicago, 840 S. Wood Street, Chicago, IL 60612 (United States)

    2009-05-08

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

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

    Science.gov (United States)

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

    2015-11-01

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

  8. 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).

  9. Human population growth and the demographic transition

    OpenAIRE

    Bongaarts, John

    2009-01-01

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

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

    Science.gov (United States)

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

    2009-03-01

    Oxidative stress has been implicated as an important pathogenic factor in the pathophysiology of various life-threatening diseases such as cancer, cardiovascular diseases and diabetes. It occurs when the production of free radicals (generated during aerobic metabolism, inflammation, and infections) overcome the antioxidant defences in the body. Although previous studies have implied that oxidative stress is present in serum of patients with parasitic infection there have been no studies confirming oxidative stress levels in the Malaysian population infected with intestinal parasites. Three biochemical assays namely hydrogen peroxide (H2O2), lipid peroxidation (LP) and advanced oxidative protein product (AOPP) assays were carried out to measure oxidative stress levels in the urine of human subjects whose stools were infected with parasites such as Blastocystis hominis, Ascaris, Trichuris, hookworm and microsporidia. The levels of H2O2, AOPP and LP were significantly higher (P<0.001, P<0.05 and P<0.05 respectively) in the parasite-infected subjects (n=75) compared to the controls (n=95). In conclusion, the study provides evidence that oxidative stress is elevated in humans infected by intestinal parasites. This study may influence future researchers to consider free radical-related pathways to be a target in the interventions of new drugs against parasitic infection and related diseases. PMID:19154644

  11. Small & Large Intestine

    Science.gov (United States)

    ... Glossary Citation Help Home » Cancer Registration & Surveillance Modules » Anatomy & Physiology » Digestive System » Regions of the Digestive System » Small & Large Intestine Cancer Registration & Surveillance Modules Anatomy & Physiology Intro to the Human Body Body Functions & Life ...

  12. PUMA-mediated intestinal epithelial apoptosis contributes to ulcerative colitis in humans and mice

    OpenAIRE

    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 ...

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

    DEFF Research Database (Denmark)

    Larsen, U L; Hyldahl Olesen, L

    2007-01-01

    P-glycoprotein (Pgp) plays a part in the intestinal uptake of xenobiotics and has been associated with susceptibility to ulcerative colitis. The aim of this study was to examine Pgp activity in relation to age, gender, medical treatment (rifampicin or ketoconazole) and the multidrug resistance (MDR1) gene single nucleotide polymorphisms (SNPs) G2677T and C3435T using the model drug digoxin.

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

    Czech Academy of Sciences Publication Activity Database

    Šloncová, Eva; Fri?, P.; Ku?erová, Dana; Lojda, Z.; Tuhá?ková, Zdena; Sovová, Vlasta

    2001-01-01

    Ro?. 33, ?. 1 (2001), s. 13-17. ISSN 0018-2214 R&D Projects: GA ?R GV312/96/K205; GA ?R 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

  15. Human intestinal mucosal mast cells: expanded population in untreated coeliac disease.

    OpenAIRE

    Strobel, S.; Busuttil, A.; A. Ferguson

    1983-01-01

    Previous retrospective studies of intestinal mucosal mast cells in coeliac disease have given divergent results, and we have recently reported that inappropriate methodology could account for these discrepancies. In this prospective study, mucosal mast cell counts were performed in Carnoy fixed, peroral jejunal biopsy specimens from patients with coeliac disease, both untreated and treated with a gluten-free diet; and from controls (mainly irritable bowel syndrome). Mean mucosal mast cell cou...

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

    Science.gov (United States)

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

    2015-07-01

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

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

    DEFF Research Database (Denmark)

    Langelueddecke, Christian; Roussa, Eleni

    2013-01-01

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

  18. 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 ...

  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; 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...

  20. 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.

  1. Immunohistochemical characterization of the lymphocyte and the immunoglobulin-containing cell in the epithelium and the lamina propria of normal human intestines.

    Directory of Open Access Journals (Sweden)

    Matsueda,Kazuhiro

    1991-06-01

    Full Text Available In order to clarify difference of the mucosal immunity in various sites of normal large and small intestines, we studied the population of lymphocyte subsets and immunoglobulin (Ig-containing cells in situ in biopsy specimens taken from various sites (ascending colon, sigmoid colon and rectum of the large intestine and from the duodenum using an immunohistochemical method. Monoclonal antibodies against pan-T (Leu 1, cytotoxic/suppressor T (Leu2a, helper/inducer T (Leu3a, suppressor T (Leu15 and natural killer/K (Leu7 cells, and polyclonal antibodies to human IgG, IgA and IgM were used. In the duodenum, intraepithelial lymphocytes (IELs were more prominent than in the large intestine. Immunoelectron microscopic observation revealed that some Leu2a+ IELs possessed pseudopods extending into intestinal epithelial cells, indicating that some IELs belong to the cytotoxic T cell subset. Leu7+ IELs were scarcely observed and Leu7+/Leu1+ ratio was higher in the large intestine than in the duodenum. Furthermore, the number of Leu7+ cells were more in the distal than the proximal colon. In the lamina propria Ig-containing cells tended to be fewer in the rectum than in the duodenum and the proximal colon. Our findings may suggest the variation of local immune responses and the difference of assigned immunological functions among the various sites of the intestines.

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

    Science.gov (United States)

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

    2015-03-15

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-01-17

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

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2012-01-01

    A surface protein of Lactobacillus reuteri, mucus adhesion-promoting protein (MapA), is considered to be an adhesion factor. MapA is expressed in L. reuteri strains and adheres to piglet gastric mucus, collagen type I, and human intestinal epithelial cells such as Caco-2. The aim of this study was to identify molecules that mediate the attachment of MapA from L. reuteri to the intestinal epithelial cell surface by investigating the adhesion of MapA to receptor-like molecules on Caco-2 cells. MapA-binding receptor-like molecules were detected in Caco-2 cell lysates by 2D-PAGE. Two proteins, annexin A13 (ANXA13) and paralemmin (PALM), were identified by MALDI TOF-MS. The results of a pull-down assay showed that MapA bound directly to ANXA13 and PALM. Fluorescence microscopy studies confirmed that MapA binding to ANXA13 and PALM was colocalized on the Caco-2 cell membrane. To evaluate whether ANXA13 and PALM are important for MapA adhesion, ANXA13 and PALM knockdown cell lines were established. The adhesion of MapA to the abovementioned cell lines was reduced compared with that to wild-type Caco-2 cells. These knockdown experiments established the importance of these receptor-like molecules in MapA adhesion. PMID:24936355

  6. 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

  7. 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

  8. DNA-methylome analysis of mouse intestinal adenoma identifies a tumour-specific signature that is partly conserved in human colon cancer.

    Science.gov (United States)

    Grimm, Christina; Chavez, Lukas; Vilardell, Mireia; Farrall, Alexandra L; Tierling, Sascha; Böhm, Julia W; Grote, Phillip; Lienhard, Matthias; Dietrich, Jörn; Timmermann, Bernd; Walter, Jörn; Schweiger, Michal R; Lehrach, Hans; Herwig, Ralf; Herrmann, Bernhard G; Morkel, Markus

    2013-01-01

    Aberrant CpG methylation is a universal epigenetic trait of cancer cell genomes. However, human cancer samples or cell lines preclude the investigation of epigenetic changes occurring early during tumour development. Here, we have used MeDIP-seq to analyse the DNA methylome of APC(Min) adenoma as a model for intestinal cancer initiation, and we present a list of more than 13,000 recurring differentially methylated regions (DMRs) characterizing intestinal adenoma of the mouse. We show that Polycomb Repressive Complex (PRC) targets are strongly enriched among hypermethylated DMRs, and several PRC2 components and DNA methyltransferases were up-regulated in adenoma. We further demonstrate by bisulfite pyrosequencing of purified cell populations that the DMR signature arises de novo in adenoma cells rather than by expansion of a pre-existing pattern in intestinal stem cells or undifferentiated crypt cells. We found that epigenetic silencing of tumour suppressors, which occurs frequently in colon cancer, was rare in adenoma. Quite strikingly, we identified a core set of DMRs, which is conserved between mouse adenoma and human colon cancer, thus possibly revealing a global panel of epigenetically modified genes for intestinal tumours. Our data allow a distinction between early conserved epigenetic alterations occurring in intestinal adenoma and late stochastic events promoting colon cancer progression, and may facilitate the selection of more specific clinical epigenetic biomarkers. PMID:23408899

  9. Endometriosis intestinal / Intestinal endometriosis

    Scientific Electronic Library Online (English)

    C.I., González; M., Cires; F.J., Jiménez; T., Rubio.

    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 e [...] n 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. 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.

  10. Esquistosomiasis intestinal / Intestinal schistosomiasis

    Scientific Electronic Library Online (English)

    José Abel, García Acosta; Ariel Efrain, Delgado Rodríguez.

    2014-08-01

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

  11. 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)

  12. 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; Niemelä, 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

  13. Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry for rapid analysis of the metabolites of morroniside produced by human intestinal bacteria.

    Science.gov (United States)

    Zhao, Min; Du, Leyue; Tao, Jinhua; Qian, Dawei; Guo, Jianming; Jiang, Shu; Shang, Er-xin; Duan, Jin-ao; Wu, Chen

    2015-01-22

    Morroniside, the most abundant iridoid glycoside in the valuable traditional Chinese medicine Fructus Corni, exhibits various pharmacological activities and biological effects. Intestinal flora plays an important role in the metabolism of drug compounds, which might lead to the variation of ethnopharmacological profile of the medicine. However, little is known of the interactions of the morroniside with human intestinal bacteria. In this study, different pure bacteria were isolated from human feces and their capability to convert morroniside were investigated. The metabolites of morroniside were analyzed by ultra high performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) technique using Metabolynx™ software. Parent compound and three metabolites were detected and tentatively identified based on the characteristics of their protonated ions. The parent is proposed to be metabolized by three main metabolic pathways including deglycosylation, dehydroxylation and methylation. Morroniside was firstly metabolized to its aglycone (M1), and then was further converted to dehydroxylated aglycone (M2) and methylated aglycone (M3). This is the first report of the metabolism of morroniside by human intestinal bacteria. These metabolites might influence the biological activities of morroniside in vivo, which could affect the clinical effects of medicines. Thus, the study on the metabolism of morroniside by human intestinal bacteria is very helpful to unravel how traditional medicines work. PMID:25482010

  14. Acute Small-Bowel Obstruction From Intestinal Anisakiasis After the Ingestion of Raw Clams; Documenting a New Method of Marine-to-Human Parasitic Transmission

    OpenAIRE

    Shweiki, Ehyal; Rittenhouse, David W.; Ochoa, Joana E.; Punja, Viren P.; Zubair, Muhammad H; Baliff, Jeffrey P.

    2014-01-01

    Enteric anisakiasis is a known parasitic infection. To date, human infection has been reported as resulting from the inadvertent ingestion of the anisakis larvae when eating raw/undercooked fish, squid, or eel. We present a first reported case of intestinal obstruction caused by anisakiasis, after the ingestion of raw clams.

  15. Activation of AMP-activated protein kinase by a plant-derived dihydroisosteviol in human intestinal epithelial cell.

    Science.gov (United States)

    Muanprasat, Chatchai; Sirianant, Lalida; Sawasvirojwong, Sutthipong; Homvisasevongsa, Sureeporn; Suksamrarn, Apichart; Chatsudthipong, Varanuj

    2013-01-01

    Our previous study has shown that dihydroisosteviol (DHIS), a derivative of stevioside isolated from Stevia rebaudiana (Bertoni), inhibits cystic fibrosis transmembrane conductance regulator (CFTR)-mediated transepithelial chloride secretion across monolayers of human intestinal epithelial (T84) cells and prevents cholera toxin-induced intestinal fluid secretion in mouse closed loop models. In this study, we aimed to investigate a mechanism by which DHIS inhibits CFTR activity. Apical chloride current measurements in Fisher rat thyroid cells stably transfected with wild-type human CFTR (FRT-CFTR cells) and T84 cells were used to investigate mechanism of CFTR inhibition by DHIS. In addition, effect of DHIS on AMP-activated protein kinase (AMPK) activation was investigated using Western blot analysis. Surprisingly, it was found that DHIS failed to inhibit CFTR-mediated apical chloride current in FRT-CFTR cells. In contrast, DHIS effectively inhibited CFTR-mediated apical chloride current induced by a cell permeable cAMP analog CPT-cAMP and a direct CFTR activator genistein in T84 cell monolayers. Interestingly, this inhibitory effect of DHIS on CFTR was significantly (p<0.05) reduced by pretreatment with compound C, an AMPK inhibitor. AICAR, a known AMPK activator, was able to inhibit CFTR activity in both FRT-CFTR and T84 cells. Western blot analysis showed that DHIS induced AMPK activation in T84 cells, but not in FRT-CFTR cells. Our results indicate that DHIS inhibits CFTR-mediated chloride secretion in T84 cells, in part, by activation of AMPK activity. DHIS therefore represents a novel candidate of AMPK activators. PMID:23343619

  16. Moderate consumption of red wine can modulate human intestinal inflammatory response.

    Science.gov (United States)

    Muñoz-González, Irene; Espinosa-Martos, Irene; Rodríguez, Juan M; Jiménez-Girón, Ana; Martín-Álvarez, Pedro J; Bartolomé, Begoña; Moreno-Arribas, M Victoria

    2014-10-29

    In this study, 24 immune markers were analyzed in feces from healthy volunteers (n = 34) before and after consumption of a red wine (12% ethanol, 1758 mg/L total polyphenols) for 4 weeks. Analysis of the data permitted the differentiation of a six-volunteer subgroup showing unusually high basal values of cytokines. For this subgroup, consumption of wine significantly (P wine consumption for the rest of the volunteers. Additionally, significant and negative correlations among cytokines IFN-?, IL-8, and IL-6 and the total fecal content of phenolic metabolites were found for the high-cytokines-values subgroup, before wine intake. This study shows, for the first time, that moderate consumption of red wine could modulate inflammatory intestinal response in vivo. PMID:25263395

  17. 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.

  18. Model Systems of Human Intestinal Flora, to Set Acceptable Daily Intakes of Antimicrobial Residues

    OpenAIRE

    Corpet, Denis E.

    2000-01-01

    The veterinary use of antimicrobial drugs in food producing animals may result in residues in food, that might modify the consumer gut flora. This review compares three model systems that maintain a complex flora of human origin: (i) human flora associated (HFA) continuous flow cultures in chemostats, (ii) HFA mice, and (iii) human volunteers. The "No Microbial Effect Level" of an antibiotic on human flora, measured in one of these models, is used to set the accept¬able daily intake (ADI) for...

  19. 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

    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-free conditions with VIP and PHM in varying concentrations (0.1, 10, 1000 nmol/l). [3H]Thymidine incorporation in the cells and oestradiol as well as progesterone concentrations in the culture medium were measured. The mean (+/- SEM) concentrations of VIP and PHM were 6.8 +/- 0.1 and 7.7 +/- 0.8 pmol/l, respectively. VIP at a concentration of 10 nmol/l caused a significant increase in [3H]thymidine incorporation, and at 1000 nmol/l a significant increase in oestradiol secretion was observed. VIP had no effect on progesterone secretion. PHM at the concentrations tested did not influence any of the activities. 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.

  20. 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; Radovi?, Nikola; Jadrijevi?, Stipe; Aleksic, Ivan; Walles, Thorsten; Sauvant, Christoph; Saboli?, 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

  1. 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.

  2. 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

  3. Intestinal spirochetosis

    Scientific Electronic Library Online (English)

    Luis Roberto Manzione, Nadal; Sidney Roberto, Nadal.

    2011-12-01

    Full Text Available A espiroquetose intestinal está definida histologicamente como a presença de micro-organismos da família spirochetaceae ligadas ao ápice das células do epitélio cólico. A doença pode ser provocada por um grupo heterogêneo de bactérias. Em humanos, a Brachyspira aalborgi e a Brachyspira pilosicoli pr [...] edominam. A incidência varia desde 1%, nos países desenvolvidos, até 34% nas áreas mais pobres, atingindo taxas de colonização de 62,5%, em homens que fazem sexo com homens (HSH) e vírus da imunodeficiência humana (HIV) positivo. O significado clínico dessa colonização ainda é incerto e a maioria dos infectados permanece assintomática. Quando há sintomas gastrointestinais, o tratamento com metronidazol é efetivo. Por razões desconhecidas, HSH positivos para o HIV, apresentam mais infestação sintomática. A infecção pelo Treponema pallidum dever ser excluída, pois os tratamentos são diferentes e as complicações por essa última são mais graves e definitivas. Abstract in english The intestinal spirochetosis (IS) is a histologically defined by the presence of spirochetal microorganisms connected to the apical cell membrane of the colorectal epithelium. The disease is caused by a heterogeneous group of bacteria. In humans, Brachyspira aalborgi and Brachyspira pilosicoli are p [...] revalent. The incidence ranges from 1% in developed countries to 34% in poorer areas. It affects 62.5% of colonized areas, as well as men who have intercourse with men (MSM) and those with the human immunodeficiency virus (HIV) infected. Clinical significance of such colonization is still not clear. Most infected people are asymptomatic. At the presence of gastrointestinal symptoms, treatment with metronidazole is effective. Due to unknown reasons, MSM and HIV-positive men are more likely to be symptomatic. Treponema pallidum infection must be excluded, since this agent may cause serious and permanent complications, and because the treatment is different.

  4. 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.

  5. 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

  6. Transcriptional down-regulation of human alpha(2A)-adrenoceptors by IFNgamma and TNFalpha in intestinal cells.

    Science.gov (United States)

    Cayla, Cécile; Schaak, Stéphane; Crassous, Pierre-Antoine; Buffin-Meyer, Bénédicte; Delage, Christine; Paris, Hervé; Senard, Jean-Michel; Denis, Colette

    2008-06-24

    alpha(2A)-adrenoceptors are expressed on intestinal cells and they participate in the control of epithelial functions such as solute and water transport or cell proliferation. In pathological conditions, pro-inflammatory cytokines secreted by lymphocytes are responsible for modification of intestinal cell characteristics including phenotype switch and changes in the expression of pumps and ion channels. Using the HT29 cell line as a model, the present work examined the effect of two inflammatory cytokines, interferon-gamma (IFNgamma) and tumor necrosis factor-alpha (TNFalpha), on the expression of the human alpha(2A)-adrenoceptor. Exposure of cells to either IFNgamma or TNFalpha resulted in a concentration- and time-dependent diminution of [(3)H]RX821002 binding sites, which is preceded by a large decrease in the amount of alpha(2A)-adrenoceptor mRNA. The cytokines did not affect the receptor mRNA half-life, but inhibited the activity of a luciferase construct containing the promoter region of alpha(2A)-adrenoceptor gene, indicating that a decrease in the transcription rate is primarily responsible for the diminution of receptor expression. Exposure of cells to either IFNgamma or TNFalpha caused increased production of reactive oxygen species and transient phosphorylation of extracellular signal-regulated kinase (Erk1/2). The effect of cytokines was mimicked by H(2)O(2) but was unaffected by the addition of anti-oxidants. The blockade of Erk1/2 activation by PD98059 blunted the effect of TNFalpha but not of IFNgamma. In conclusion, the present findings demonstrate that IFNgamma and TNFalpha diminish the alpha(2A)-adrenoceptor expression in HT29 cells by decreasing the transcription rate without modifying the stability of mRNA. The transcription inhibition is however triggered via different signalling pathways. The results suggest that cytokine-mediated down-regulation of alpha(2A)-adrenoceptor could contribute to the pathogenesis of inflammatory bowel disease. PMID:18457828

  7. 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.

  8. Human intestinal mucosal mast cells: evaluation of fixation and staining techniques.

    OpenAIRE

    Strobel, S.; H. R. Miller; A. Ferguson

    1981-01-01

    The staining properties of tissue mast cells are influenced by the method of fixation. Differences in fixation and staining techniques may explain the contradictory results in the published reports on the number of human mucosal mast cells (MMC) in the gastrointestinal mucosa in health and disease. We have examined the influence of fixatives on the staining properties of human MMC in operative biopsy specimens of human jejunum. Specimens were divided into pieces, each of which was fixed in on...

  9. Carrier-mediated uptake of nobiletin, a citrus polymethoxyflavonoid, in human intestinal Caco-2 cells.

    Science.gov (United States)

    Kimura, Osamu; Ohta, Chiho; Koga, Nobuyuki; Haraguchi, Koichi; Kato, Yoshihisa; Endo, Tetsuya

    2014-07-01

    The mechanism of intestinal absorption of nobiletin (NBL) was investigated using Caco-2 cells. The uptake of NBL from the apical membranes of Caco-2 cells was rapid and temperature-dependent and the presence of metabolic inhibitors, NaN3 and carbonylcyanide p-trifluoromethoxyphenylhydrazone, did not cause a decrease in NBL uptake. The relationship between the initial uptake of NBL and its concentration was saturable, suggesting the involvement of a carrier-mediated process. The Km and uptake clearance (Vmax/Km) values for NBL were 50.6 and 168.1?l/mg protein/min, respectively. This clearance value was about 9-fold greater than that of the non-saturable uptake clearance (Kd: 18.5?l/mg protein/min). The presence of structurally similar compounds, such as quercetin and luteolin, competitively inhibited NBL uptake. These results suggest that uptake of NBL from the apical membranes of Caco-2 cells is mainly mediated by an energy-independent facilitated diffusion process. PMID:24518326

  10. A theoretical model of phase transitions in the human brain.

    Science.gov (United States)

    Jirsa, V K; Friedrich, R; Haken, H; Kelso, J A

    1994-01-01

    An experiment using a multisensor SQUID (superconducting quantum interference device) array was performed by Kelso and colleagues (1992) which combined information from three different sources: perception, motor response, and brain signals. When an acoustic stimulus frequency is changed systematically, a spontaneous transition in coordination occurs at a critical frequency in both motor behavior and brain signals. Qualitatively analogous transitions are known for physical and biological systems such as changes in the coordination of human hand movements (Kelso 1981, 1984). In this paper we develop a theoretical model based on methods from the interdisciplinary field of synergetics (Haken 1983, 1987) and nonlinear oscillator theory that reproduces the main experimental features very well and suggests a formulation of a fundamental biophysical coupling. PMID:8054384

  11. A theoretical model of phase transitions in human hand movements.

    Science.gov (United States)

    Haken, H; Kelso, J A; Bunz, H

    1985-01-01

    Earlier experimental studies by one of us (Kelso, 1981a, 1984) have shown that abrupt phase transitions occur in human hand movements under the influence of scalar changes in cycling frequency. Beyond a critical frequency the originally prepared out-of-phase, antisymmetric mode is replaced by a symmetrical, in-phase mode involving simultaneous activation of homologous muscle groups. Qualitatively, these phase transitions are analogous to gait shifts in animal locomotion as well as phenomena common to other physical and biological systems in which new "modes" or spatiotemporal patterns arise when the system is parametrically scaled beyond its equilibrium state (Haken, 1983). In this paper a theoretical model, using concepts central to the interdisciplinary field of synergetics and nonlinear oscillator theory, is developed, which reproduces (among other features) the dramatic change in coordinative pattern observed between the hands. PMID:3978150

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

    OpenAIRE

    SCOTT, D; Scott, B.

    1994-01-01

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

  13. Acute intestinal infections in children

    OpenAIRE

    Smiyan, K.O.

    2013-01-01

    Acute intestinal infections - a large group of human infectious diseases caused by pathogenic and opportunistic bacteria, viruses and protozoa. Intestinal infections until now occupy a leading position in infectious diseases, especially in childhood, second in incidence only to influenza and acute respiratory infections. Registered in the world each year to 1-1.2 billion diarrheal diseases, about 5 million children die each year from intestinal infections and their complications. When you ...

  14. Geometrical guidance and trapping transition of human sperm cells

    CERN Document Server

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

    2014-01-01

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

  15. 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

  16. Spatial heterogeneity and co-occurrence patterns of human mucosal-associated intestinal microbiota

    OpenAIRE

    Zhang, Zhigang; Geng, Jiawei; Tang, Xiaodan; Hong FAN; Xu, Jinchao; Wen, Xiujun; Ma, Zhanshan; Shi, Peng

    2013-01-01

    Human gut microbiota shows high inter-subject variations, but the actual spatial distribution and co-occurrence patterns of gut mucosa microbiota that occur within a healthy human instestinal tract remain poorly understood. In this study, we illustrated a model of this mucosa bacterial communities' biogeography, based on the largest data set so far, obtained via 454-pyrosequencing of bacterial 16S rDNAs associated with 77 matched biopsy tissue samples taken from terminal ileum, ileocecal valv...

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

  18. Insuficiencia intestinal

    Directory of Open Access Journals (Sweden)

    Adriana Fernández

    2005-06-01

    Full Text Available The intestinal failure is an entity produced by different etiologies. The short bowel syndrome (SBS is the most frequent in children. Almost 90% of neonates with massive intestinal resections survive if the adequate nutritional support is implemented. The 80% of the neonates with SBS will reach a definitive adaptation according to the remnant intestine. This group of patients demands expert professionals to avoid and control the associated complications.

  19. 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

    Scientific Electronic Library Online (English)

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

    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 paci [...] entes 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 (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

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

    Science.gov (United States)

    Wang, Xiangwen; Pleimling, Michel

    2015-03-01

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

  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,1–3 Danhui Li,3 Yongzhi Zhou,3 Jie Yang,1 Wanqi Yang,1 Guohua Zhou,2 Jingyuan Wen31Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, School of Pharmacy, China Pharmaceutical University, 2Department of Pharmacology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, People’s Republic of China; 3School of Pharmacy, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New ZealandAbstract: The aim of this study was to evaluate (+-catechin and (?-epigallocatechin gallate (EGCG cellular uptake and transport across human intestinal Caco-2 cell monolayer in both the absence and presence of niosomal carrier in variable conditions. The effect of free drugs and drug-loaded niosomes on the growth of Caco-2 cells was studied. The effects of time, temperature, and concentration on drug cellular uptake in the absence or presence of its niosomal delivery systems were investigated. The intestinal epithelial membrane transport of the drug-loaded niosomes was examined using the monolayer of the human Caco-2 cells. The kinetics of transport, and the effect of temperature, adenosine triphosphate inhibitor, permeability glycoprotein inhibitor, multidrug resistance-associated protein 2 inhibitor, and the absorption enhancer on transport mechanism were investigated. It was found that the uptake of catechin, EGCG, and their niosomes by Caco-2 cells was 1.22±0.16, 0.90±0.14, 3.25±0.37, and 1.92±0.22 µg/mg protein, respectively (n=3. The apparent permeability coefficient values of catechin, EGCG, and their niosomes were 1.68±0.16, 0.88±0.09, 2.39±0.31, and 1.42±0.24 cm/second (n=3 at 37°C, respectively. The transport was temperature- and energy-dependent. The inhibitors of permeability glycoprotein and multidrug resistance-associated protein 2 and the absorption enhancer significantly enhanced the uptake amount. Compared with the free drugs, niosomal formulation 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. Transition toward Human Cytomegalovirus Susceptibility in Early Human Embryonic Stem Cell-Derived Neural Precursors.

    Science.gov (United States)

    Berger, Amnon A; Gil, Yaniv; Panet, Amos; Weisblum, Yiska; Oiknine-Djian, Esther; Gropp, Michal; Steiner, Debora; Reubinoff, Benjamin E; Wolf, Dana G

    2015-11-01

    Congenital human cytomegalovirus (HCMV) infection is associated with neurodevelopmental disabilities. To dissect the earliest events of infection in the developing human brain, we studied HCMV infection during controlled differentiation of human embryonic stem cells (hESC) into neural precursors. We traced a transition from viral restriction in hESC, mediated by a block in viral binding, toward HCMV susceptibility in early hESC-derived neural precursors. We further revealed the role of platelet-derived growth factor receptor alpha (PDGFR?) as a determinant of the developmentally acquired HCMV susceptibility. PMID:26292329

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

    Energy Technology Data Exchange (ETDEWEB)

    Butler, P. [St George Hospital, Kogarah, NSW, (Australia). Departemnt of Nuclear Medicine

    1997-09-01

    Full text: VIP labelled with iodine-123 has recently been reported to be useful ligand for the in vivo localisation of various tumours, including colorectal, pancreatic, gastric adenocarcinomas, and both Iymph node and liver metastases. The aim of this investigation was to determine the dosimetry and biodistribution of [{sup 123}I] iodo VIP in humans. Synthetic human VIP was reacted with [{sup 123}I]Nal in the presence of lodogen to afford, after purification of the reaction mixture using HPLC, two isomeric [{sup 123}I] iodotyrosylMet(O) vasoactive intestinal polypeptides, both of which are ligands for VIP receptors. After intravenous administration of these two iodinated peptides (160-200 MBq, <400 pmol of iodoVIP/patient), simultaneous anterior and posterior whole-body images were acquired at times 0, 0.5, 1, 2, 4, and 24 hours together with blood and urine samples. The biodistribution and dosimetry were calculated from these data. [{sup 123}l]iodo VIP was rapidly cleared from the blood and primarily localised in the lungs, which accounted for 30. per cent of the injected dose at times 2,4 and 24 h post-injection, respectively. The radioactivity measured in the urine amounted to 30 per cent of the injected dose at 6 h and 80 per cent at 24 h postinjection. The effective dose was calculated to be 3.7 mSv/160 MBq. The dosimetry and biodistribution of the [{sup 123}I]iodo VIP prepared in our institution is similar to that reported in the literature. Furthermore, the dosimetry of this radiolabelled peptide is such that it is safe to use in humans.

  4. Drug discovery and regulatory considerations for improving in silico and in vitro predictions that use Caco-2 as a surrogate for human intestinal permeability measurements.

    Science.gov (United States)

    Larregieu, Caroline A; Benet, Leslie Z

    2013-04-01

    There is a growing need for highly accurate in silico and in vitro predictive models to facilitate drug discovery and development. Results from in vitro permeation studies across the Caco-2 cell monolayer are commonly used for drug permeability screening in industry and are also accepted as a surrogate for human intestinal permeability measurements by the US FDA to support new drug class="hlt">applications. Countless studies carried out in this cell line with published permeability measurements have enabled the development of many in silico prediction models. We identify several common cases that illustrate how using Caco-2 permeability measurements in these in silico and in vitro predictive models will not correlate with human intestinal permeability and will further lead to inaccuracies in these models. We provide guidelines and recommendations for improving these models to more accurately predict clinically relevant information, thereby enhancing the drug discovery, development, and regulatory approval processes. PMID:23344793

  5. 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

  6. 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.

  7. Testing of the Small Intestine (Intestinal Dysmotility)

    Science.gov (United States)

    ... Disorders of the Large Intestine Disorders of the Pelvic Floor Motility Testing Personal Stories Who We Are Contact ... Disorders of the Large Intestine Disorders of the Pelvic Floor Motility Testing Esophagus Stomach Small Intestine Large Intestine ...

  8. 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 ...

  9. Alpinia katsumadai Extracts Inhibit Adhesion and Invasion of Campylobacter jejuni in Animal and Human Foetal Small Intestine Cell Lines.

    Science.gov (United States)

    Poga?ar, Maja Šiki?; Klan?nik, Anja; Bucar, Franz; Langerholc, Tomaž; Možina, Sonja Smole

    2015-10-01

    Alpinia katsumadai is used in traditional Chinese medicine for abdominal distention, pain, and diarrhoea. Campylobacter jejuni is the most common cause of bacterial food-borne diarrhoeal illnesses worldwide. Adhesion to gut epithelium is a prerequisite in its pathogenesis. The antimicrobial, cytotoxic, and anti-adhesive activities of a chemically characterised extract (SEE) and its residual material of hydrodistillation (hdSEE-R) from A. katsumadai seeds were evaluated against C. jejuni. Minimal inhibitory concentrations for SEE and hdSEE-R were 0.5?mg/mL and 0.25?mg/mL, respectively, and there was no cytotoxic influence in the anti-adhesion tests, as these were performed at much lower concentrations of these tested plant extracts. Adhesion of C. jejuni to pig (PSI) and human foetal (H4) small-intestine cell lines was significantly decreased at lower concentrations (0.2 to 50?µg/mL). In the same concentration range, the invasiveness of C. jejuni in PSI cells was reduced by 45% to 65% when they were treated with SEE or hdSEE-R. The hdSEE-R represents a bioactive waste with a high phenolic content and an anti-adhesive activity against C. jejuni and thus has the potential for use in pharmaceutical and food products. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26058384

  10. Stimulation of beta-adrenoceptors with isoprenaline inhibits small intestinal activity fronts and induces a postprandial-like motility pattern in humans.

    OpenAIRE

    Thollander, M; Svensson, T H; Hellström, P M

    1997-01-01

    AIMS: To investigate the effects of beta-adrenoceptor stimulation, using the agonist isoprenaline and the antagonist propranolol, on migrating motor complexes in the upper intestine of 16 healthy human volunteers. METHODS: Fasting motility was monitored using a tube with water perfused side holes connected to a pneumohydraulic system. Continuous eight hour recordings were obtained from each volunteer after a 12 hour fasting period. In all experiments, saline was given as control for the first...

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

    OpenAIRE

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

    2012-01-01

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

  12. Pituitary Adenylate-Cyclase-Activating Polypeptide (PACAP) Binding Sites and PACAP/Vasoactive Intestinal Polypeptide Receptor Expression in Human Pituitary Adenomas

    OpenAIRE

    Oka, Hidehiro; JIN, LONG; REUBI, Jean Claude; Qian, Xiang; Scheithauer, Bernd W.; Fujii, Kiyotaka; Kameya, Toru; Lloyd, Ricardo V.

    1998-01-01

    Pituitary adenylate-cyclase-activating polypeptide (PACAP) stimulates release of several anterior pituitary hormones by interacting with PACAP receptors on pituitary cells. To learn more about the distribution and possible regulatory roles of PACAP and its receptors in human pituitary adenomas, we investigated the expression of vasoactive intestinal polypeptide (VIP) and PACAP binding sites using receptor autoradiography, PACAP and PACAP/VIP receptor (PVR) mRNAs by reverse transcription polym...

  13. The effect of liquid fibre on gastric emptying in the rat and humans and the distribution of small intestinal contents in the rat.

    OpenAIRE

    Tomlin, J; Brown, N; Ellis, A.; Carlsson, A.; Bogentoft, C; Read, N.W.

    1993-01-01

    A combination of the polysaccharide ethyl-hydroxyethyl-cellulose (EHEC) and the surfactant sodium-dodecylsulphate (SDS) has the extraordinary physical property of being liquid at room temperature but gelling firmly at 37 degrees C. It has been named 'liquid fibre' and its effect on gastric emptying has been tested in rats and humans, as well as its effect on intestinal distribution in rats. Rats were gavaged with 5 ml of radiolabelled liquid fibre, SDS in water, or water control. Subgroups we...

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

    DEFF Research Database (Denmark)

    Csati, A; Tajti, J; Kuris, A; Tuka, B; Edvinsson, L; Warfvinge, K

    2012-01-01

    Cranial parasympathetic outflow is mediated through the sphenopalatine ganglion (SPG). The present study was performed to examine the expression of the parasympathetic signaling transmitters and their receptors in human and rat SPG. Indirect immunofluorescence technique was used for the demonstration of vasoactive intestinal peptide (VIP), pituitary adenylate cyclase-activating peptide (PACAP), nitric oxide synthase (NOS), glutamine synthetase (GS), glial fibrillary acidic protein (GFAP), VIP an...

  15. Population dynamics of some relevant intestinal microbial groups in human fecal batch cultures with added fermentable xylooligosaccharides obtained from rice husks

    OpenAIRE

    Valdés, Lorena; Gullón, Patricia; Salazar, Nuria; Rios-Covián, David; González Muñoz, María Jesús; Parajó, Juan Carlos; Ruas-Madiedo, Patricia; Gueimonde Fernández, Miguel; González de los Reyes-Gavilán, Clara

    2013-01-01

    Xylooligosaccharides (XOS) obtained by autohydrolysis of rice husks were demonstrated in a previous study to act as fermentable substrates by the intestinal microbiota in human fecal slurry cultures, leading to the generation of acetic and lactic acids and supporting the growth of bifidobacteria (Gullón et al. 2011). The purpose of the present study was to provide new insights into other possible targets of XOS action by determining (in the same fecal cultures) the levels of some relevant int...

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

    Directory of Open Access Journals (Sweden)

    Doru Dejica

    2010-06-01

    Full Text Available Identification of celiac disease, by determining human leucocyte antigens DQ2/DQ8, is important since recent long-term studies have shown that the mortality of celiac disease is increased, if it is unrecognized and untreated. In this sense, we wanted to see the usefulness of genetic tests in celiac disease diagnosis and screening. Material and methods. During 2010 we determined by PCR, DQ2/DQ8 haplotype, in a group of 27 children with celiac disease and 9 of their brothers, serologically negative for celiac disease. Results. 22 children and 7 of their brothers confirmed the diagnosis of celiac disease, DR3-DQ2 haplotype was predominant in children with celiac disease and DR4-DQ8 to their brothers. Conclusions. Genetic testing to determine human lecocyte antigens remain the most reliable test in the diagnosis of celiac disease but also in identifying family risk for people with celiac disease.

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

    OpenAIRE

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

    2014-01-01

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

  18. PKQuest: measurement of intestinal absorption and first pass metabolism – application to human ethanol pharmacokinetics

    OpenAIRE

    Levitt David G

    2002-01-01

    Abstract Background PKQuest, a new physiologically based pharmacokinetic (PBPK) program, is applied to human ethanol data. The classical definition of first pass metabolism (FPM) based on the differences in the area under the curve (AUC) for identical intravenous and oral doses is invalid if the metabolism is non-linear (e.g. ethanol). Uncertainties in the measurement of FPM have led to controversy about the magnitude of gastric alcohol metabolism. PKQuest implements a new, rigorous definitio...

  19. 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.

  20. 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.

  1. 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.

  2. Chronic intestinal pseudoobstruction syndrome

    International Nuclear Information System (INIS)

    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

  3. 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.

  4. 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 ?M curcumin modulates IClswell in a dose-dependent manner (0.1 ?M curcumin is ineffective, 0.5–5.0 ?M curcumin increase, while 10 ?M curcumin decrease the current), and short-term exposure to micromolar concentrations of curcumin does not affect IClswell neither if applied from the extracellular nor from the intracellular side – therefore, a direct effect of curcumin on IClswell can be ruled out. Furthermore, we show that curcumin exposure induces apoptosis in human kidney cells, and at a concentration of 5.0–10 ?M induces the appearance of a sub-population of cells with a dramatically increased volume. In these cells the regulation of the cell volume seems to be impaired, most likely as a consequence of the IClswell blockade. Similarly, 50 ?M curcumin induced apoptosis, caused cell cycle arrest in G1-phase and increased the volume of human colorectal adenocarcinoma HT-29 cells. The cell cycle arrest in G1 phase may be the mechanism underlying the volume increase observed in this cell line after exposure to curcumin.

  5. Circulating and gut-resident human Th17 cells express CD161 and promote intestinal inflammation

    OpenAIRE

    Kleinschek, Melanie A.; Boniface, Katia; Sadekova, Svetlana; Grein, Jeff; Murphy, Erin E; Turner, Scott P.; Raskin, Lisa; Desai, Bela; Faubion, William A; de Waal Malefyt, Rene; Pierce, Robert H; McClanahan, Terrill; Kastelein, Robert A.

    2009-01-01

    The C-type lectin-like receptor CD161, which has recently been described to promote T cell expansion, is expressed on a discrete subset of human CD4 T cells. The function of such cells, however, has remained elusive. We now demonstrate that CD161+ CD4 T cells comprise a circulating and gut-resident T helper 17 (Th17) cell population. During Crohn's disease (CD), these CD161+ cells display an activated Th17 phenotype, as indicated by increased expression of interleukin (IL)-17, IL-22, and IL-2...

  6. El desarrollo de la microbiota intestinal humana, el concepto de probiótico y su relación 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 probióticos son microorganismos vivos que al ser ingeridos en cantidades adecuadas confieren beneficios para la salud del huésped. Provienen mayormente de la microbiota del colon de seres humanos aunque algunas cepas provienen del ambiente. El colon del recién 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 años de edad alberga unas 1500 especies y recuentos de 1014 bacterias. En la colonización del tubo digestivo de los prematuros el bajo peso de nacimiento, la inmadurez de las defensas y la alimentación artificial cuando la madre es incapaz de amamantar, llevan en una proporción de los casos a la enterocolitis necrosante, que puede afectar la pared ileal o colónica, con perforación y peritonitis en algunos prematuros. La colonización microbiológica anormal jugaría un papel importante. Los probióticos 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 probióticos. El riesgo de septicemia asociado con los probióticos ha sido ampliamente discutido. Estudios en Finlandia no han demostrado que durante 10 años de su consumo masivo se produjeran aumentos de su incidencia ni cambios de su etiología en comparación con resultados previos a su introducción. Las septicemias han sido detectadas principalmente en individuos con graves alteraciones de su salud, pérdida de la función de barrera de su mucosa intestinal, trastornos congénitos graves de la inmunidad, lesiones valvulares cardíacas 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 probióticos esté 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.

  7. Prebiotic effect of fructooligosaccharide in the simulator of the human intestinal microbial ecosystem (SHIME® model).

    Science.gov (United States)

    Sivieri, Katia; Morales, Martha L Villarreal; Saad, Susana M I; Adorno, Maria A Tallarico; Sakamoto, Isabel Kimiko; Rossi, Elizeu A

    2014-08-01

    Maintaining "gut health" is a goal for scientists throughout the world. Therefore, microbiota management models for testing probiotics, prebiotics, and synbiotics have been developed. The SHIME(®) model was used to study the effect of fructooligosaccharide (FOS) on the fermentation pattern of the colon microbiota. Initially, an inoculum prepared from human feces was introduced into the reactor vessels and stabilized over 2 weeks using a culture medium. This stabilization period was followed by a 2-week control period during which the microbiota was monitored. The microbiota was then subjected to a 4-week treatment period by adding 5?g/day-1 FOS to vessel one (the "stomach" compartment). Plate counts, Denaturing Gradient Gel Electrophoresis (DGGE), short-chain fatty acid (SCFA), and ammonium analyses were used to observe the influence of FOS treatment in simulated colon compartments. A significant increase (P<.01) in the Lactobacillus spp. and Bifidobacterium spp. populations was observed during the treatment period. The DGGE obtained showed the overall microbial community was changed in the ascending colon compartment of the SHIME reactor. FOS induced increase of the SCFA concentration (P<.05) during the treatment period, mainly due to significant increased levels of acetic and butyric acids. However, ammonium concentrations increased during the same period (P<.01). This study indicates the usefulness of in vitro methods that simulate the colon region as part of research towards the improvement of human health. PMID:24654949

  8. Structural Transformation of 8-5-Coupled Dehydrodiferulates by Human Intestinal Microbiota.

    Science.gov (United States)

    Schendel, Rachel R; Karrer, Cecile; Bunzel, Diana; Huch, Melanie; Hildebrand, Andreas A; Kulling, Sabine E; Bunzel, Mirko

    2015-09-16

    Ingested dehydrodiferulates (DFAs) are partially released from cereal dietary fiber by human colonic microbiota, but little research has explored the further microbial metabolism of 8-5-coupled DFAs. This study investigated the in vitro microbial metabolism and elucidated major metabolites of free 8-5-DFAs (benzofuran and open forms) and an esterified analogue, 8-5-DFA diethyl ester (benzofuran). Synthesized standard compounds were incubated with fresh human fecal suspensions. Metabolites were isolated and structurally elucidated using high-resolution-LC-time-of-flight-(ToF)-MS, GC-MS, and NMR. Nine metabolite structures were unambiguously characterized with NMR, and four additional metabolites were tentatively identified to reveal structural conversion motifs: propenyl side chain hydrogenation (all substrates), O-demethylation and reductive ring-opening (8-5-DFA diethyl ester and free 8-5-DFA [benzofuran]), and de-esterification (8-5-DFA diethyl ester). A pathway of microbial 8-5-DFA metabolism was proposed based on metabolite formation kinetics. Importantly, de-esterification of the 8-5-DFA diethyl ester occurred primarily after and/or concurrently with other metabolism steps. Cleavage to monomers was not observed. PMID:26287944

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

    DEFF Research Database (Denmark)

    Nielsen, Carsten Uhd; Carstensen, Mette; Brodin, Birger

    2012-01-01

    The aim of the present study was to investigate the transport of ¿-aminobutyric acid (GABA) across the basolateral membrane of intestinal cells. The proton-coupled amino acid transporter, hPAT1, mediates the influx of GABA and GABA mimetic drug substances such as vigabatrin and gaboxadol and the anticancer prodrug d-aminolevulinic acid across the apical membrane of small intestinal enterocytes. Little is however known about the basolateral transport of these substances. We investigated basolater...

  10. 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

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

    Directory of Open Access Journals (Sweden)

    Jianping Kong

    2011-09-01

    Full Text Available The incidence of esophageal adenocarcinoma (EAC is rising in the United States. An important risk factor for EAC is the presence of Barrett esophagus (BE. BE is the replacement of normal squamous esophageal epithelium with a specialized columnar epithelium in response to chronic acid and bile reflux. However, the emergence of BE from squamous keratinocytes has not yet been demonstrated. Our research has focused on this. Wnt and cyclooxygenase 2 (Cox2 are two pathways whose activation has been associated with BE and progression to EAC, but their role has not been tested experimentally. To explore their contribution, we engineered a human esophageal keratinocyte cell line to express either a dominant-active Wnt effector CatCLef or a Cox2 complementary DNA. In a two-dimensional culture environment, Cox2 expression increases cell proliferation and migration, but neither transgene induces known BE markers. In contrast, when these cells were placed into three-dimensional organotypic culture conditions, we observed more profound effects. CatCLef-expressing cells were more proliferative, developed a thicker epithelium, and upregulated Notch signaling and several BE markers including NHE2. Cox2 expression also increased cell proliferation and induced a thicker epithelium. More importantly, we observed cysts form within the epithelium, filled with intestinal mucins including Muc5B and Muc17. This suggests that Cox2 expression in a three-dimensional culture environment induces a lineage of mucin-secreting cells and supports an important causal role for Cox2 in BE pathogenesis. We conclude that in vitro modeling of BE pathogenesis can be improved by enhancing Wnt signaling and Cox2 activity and using three-dimensional organotypic culture conditions.

  12. 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.

  13. Differential multidrug resistance-associated protein 1 through 6 isoform expression and function in human intestinal epithelial Caco-2 cells.

    Science.gov (United States)

    Prime-Chapman, Hannah M; Fearn, Richard A; Cooper, Anne E; Moore, Vanessa; Hirst, Barry H

    2004-11-01

    Multidrug resistance-associated protein (MRP) isoforms 1 through 6 mRNA are expressed in the human intestine and Caco-2 cells. In Caco-2 cells, the rank order for mRNA expression was MRP2 > or = MRP6 > MRP4 > or = MRP3 > MRP1 = MRP5. The functional expression of MRP-like activity was quantified as the efflux of the fluorescent probe calcein from confluent, polarized monolayers of Caco-2 cells. Calcein efflux was sensitive to temperature, energy depletion, and the MRP antagonist MK571 [3-[[3-[2-(7-chloroquinolin-2-yl)vinyl]phenyl]-(2-dimethylcarbamoylethylsulfanyl)methylsulfanyl] propionic acid]. Calcein efflux across the apical membrane of Caco-2 cells exceeded that across the basolateral by approximately 2-fold, correlating with the apical localization of MRP2 visualized by immunocytochemical staining. T84 cells do not express MRP2 and show a predominance of basolateral calcein efflux over apical efflux. MRP3 was localized by immunocytochemical staining to the basolateral membrane. MRP1 staining was not localized to either membrane domain and MRP5 staining was not detected. Thus, basolateral calcein efflux may reflect a function of MRP3 or MRP4 and 6 inferred by their basolateral localization in other tissues. Basolateral, but not apical, calcein efflux was sensitive to glutathione depletion with buthioninesulfoximine, indicating that whereas MRP2-mediated apical efflux is independent of glutathione, basolateral efflux is glutathione-dependent. Benzbromarone, probenecid, pravastatin, and diclofenac were able to inhibit both apical and basolateral calcein efflux. The apical calcein efflux in Caco-2 cells was selectively sensitive to indomethacin and propranolol, but not verapamil or erythromycin, whereas the converse was observed for basal efflux. The differential pharmacological sensitivity of apical (MRP2) and basolateral calcein efflux provides tools for dissecting MRP isoform functional roles. PMID:15210835

  14. Intestinal stem cells.

    OpenAIRE

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

    2005-01-01

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

  15. Immunoglobulin A cell distribution in the human small intestine: phenotypic and functional characteristics.

    Science.gov (United States)

    Farstad, I N; Carlsen, H; Morton, H C; Brandtzaeg, P

    2000-11-01

    We compared B-cell phenotypes in Peyer's patches and solitary lymphoid follicles (organized gut-associated lymphoid tissue, GALT) with those in jejunal or ileal lamina propria. In situ, immunostaining showed that small B cells of naive [surface immunoglobulin D-positive (sIgD+) CD27-] and memory (sIgD+/- CD27+) phenotypes occurred almost exclusively in GALT, whereas the lamina propria contained only scattered sIgA+ CD27+ memory cells. In contrast, B-cell blasts and plasma cells negative for CD20 and often also for CD19 but with strong expression of CD38, CD27 and cytoplasmic IgA (cIgA), dominated in the lamina propria but were scarce in GALT. By flow cytometry, the proportion of dispersed CD19+ B lymphocytes varied from 4 to 42% among jejunal mucosal samples; between 5 and 50% of these were sIgD+, suggesting a variable contamination with GALT cells. B-cell blasts and plasma cells, identified by their large size and strong expression of CD38, were regularly found (25-35% of the total mononuclear cell population). Distinction between B-cell blasts and mature plasma cells was made by the presence or absence of human leucocyte antigen (HLA) class II molecules, CD45RA, CD19 and surface immunoglobulin. No CD19+ B cells outside GALT expressed CD5, but a very small portion of the lamina propria B-cell blasts were positive for CD28. Dispersed sIgA+ lamina propria cells expressed low levels of CD40, proliferated on CD40 ligation and constitutively secreted IgA in vitro. We concluded that the lamina propria B-cell compartment consists mainly of B-cell blasts and plasma cells but also has scattered, small sIgA+ cells that can proliferate in response to CD40 ligation and may therefore function as local memory cells for recall antigens. PMID:11106939

  16. 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.

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

    International Nuclear Information System (INIS)

    Research highlights: ? Exogenous GIP inhibits intestinal motility through a somatostatin-mediated pathway. ? Exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility. ? The GIP-receptor-mediated action in intestine does not involve in GLP-1-mediated pathway. -- Abstract: Gastric inhibitory polypeptide (GIP) is released from the small intestine upon meal ingestion and increases insulin secretion from pancreatic ? cells. Although the GIP receptor is known to be expressed in small intestine, the effects of GIP in small intestine are not fully understood. This study was designed to clarify the effect of GIP on intestinal glucose absorption and intestinal motility. Intestinal glucose absorption in vivo was measured by single-pass perfusion method. Incorporation of [14C]-glucose into everted jejunal rings in vitro was used to evaluate the effect of GIP on sodium-glucose co-transporter (SGLT). Motility of small intestine was measured by intestinal transit after oral administration of a non-absorbed marker. Intraperitoneal administration of GIP inhibited glucose absorption in wild-type mice in a concentration-dependent manner, showing maximum decrease at the dosage of 50 nmol/kg body weight. In glucagon-like-peptide-1 (GLP-1) receptor-deficient mice, GIP inhibited glucose absorption as in wild-type mice. In vitro examination of [14C]-glucose uptake revealed that 100 nM GIP did not change SGLT-dependent glucose uptake in wild-type mice. After intraperitoneal administration of GIP (50 nmol/kg body weight), small intestinal transit was inhibited to 40% in both wild-type and GLP-1 receptor-deficient mice. Furthermore, a somatostatin receptor antagonist, cyclosomatostatin, reduced the inhibitory effect of GIP on both intestinal transit and glucose absorption in wild-type mice. These results demonstrate that exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility through a somatostatin-mediated pathway rather than through a GLP-1-mediated pathway.

  18. Intestinal absorption mechanism of mirabegron, a potent and selective ??-adrenoceptor agonist: involvement of human efflux and/or influx transport systems.

    Science.gov (United States)

    Takusagawa, Shin; Ushigome, Fumihiko; Nemoto, Hiroyuki; Takahashi, Yutaka; Li, Qun; Kerbusch, Virginie; Miyashita, Aiji; Iwatsubo, Takafumi; Usui, Takashi

    2013-05-01

    Mirabegron, a weak-basic compound, is a potent and selective ?3-adrenoceptor agonist for the treatment of overactive bladder. Mirabegron extended release formulation shows dose-dependent oral bioavailability in humans, which is likely attributable to saturation of intestinal efflux abilities leading to higher absorption with higher doses. This study evaluated the membrane permeability of mirabegron and investigated the involvement of human intestinal transport proteins in the membrane permeation of mirabegron. Transcellular transport and cellular/vesicular uptake assays were performed using Caco-2 cells and/or human intestinal efflux (P-glycoprotein [P-gp], breast cancer resistance protein [BCRP], and multidrug resistance associated protein 2 [MRP2]) and influx (peptide transporter 1 [PEPT1], OATP1A2, and OATP2B1) transporter-expressing cells, vesicles, or Xenopus laevis oocytes. The absorptive permeability coefficients of mirabegron in Caco-2 cells (1.68-1.83 × 10(-6) cm/s) at the apical and basal pH of 6.5 and 7.4, respectively, were slightly higher than those of nadolol (0.97-1.41 × 10(-6) cm/s), a low permeability reference standard, but lower than those of metoprolol and propranolol (both ranged from 8.49 to 11.6 × 10(-6) cm/s), low/high permeability boundary reference standards. Increasing buffer pH at the apical side from 5.5 to 8.0 gradually increased the absorptive permeation of mirabegron from 0.226 to 1.66 × 10(-6) cm/s, but was still less than the value in the opposite direction (11.0-14.2 × 10(-6) cm/s). The time- and concentration-dependent transport of mirabegron was observed in P-gp-expressing cells and OATP1A2-expressing oocytes with apparent Km values of 294 and 8.59 ?M, respectively. In contrast, no clear BCRP-, MRP2-, PEPT1-, or OATP2B1-mediated uptake of mirabegron was observed in their expressing vesicles or cells. These findings suggest that mirabegron has low-to-moderate membrane permeability and P-gp is likely to be involved in its efflux into the lumen in the intestinal absorption process. The results also suggest that mirabegron could possibly be transported by intestinal influx transporters as well as simple diffusion. PMID:23560393

  19. TGF-?2, a Protective Intestinal Cytokine, Is Abundant in Maternal Human Milk and Human-Derived Fortifiers but Not in Donor Human Milk

    OpenAIRE

    Reeves, Aaron A.; Johnson, Marney C.; Vasquez, Margarita M.; MAHESHWARI, AKHIL; Blanco, Cynthia L.

    2013-01-01

    Objective: This study compared cytokines (in particular transforming growth factor [TGF]-?2) and lactoferrin in maternal human milk (MHM), human-derived milk fortifier (HDMF), and donor human milk (DHM).

  20. Cloning of a pig homologue of the human lactoferrin receptor: Expression and localization during intestinal maturation in piglets

    OpenAIRE

    Liao, Yalin; Lopez, Veronica; Shafizadeh, Tracy B.; Halsted, Charles H.; Lönnerdal, Bo

    2007-01-01

    The presence of a small intestinal lactoferrin receptor (SI-LfR) has been suggested in the pig, but remains to be identified. LfR has been suggested to play a key role in the internalization of lactoferrin (Lf) and to facilitate absorption of iron bound to Lf. The aim of this study was to identify the pig SI-LfR cDNA, determine its mRNA and protein expression during different stages of intestinal development. The coding region of the pig LfR cDNA was cloned by PCR using conserved sequences am...

  1. Methotrexate-induced intestinal mucositis delays gastric emptying and gastrointestinal transit of liquids in awake rats / Mucosite induzida pelo metotrexato retarda o esvaziamento gástrico e o trânsito gastrointestinal de líquidos em ratos acordados

    Scientific Electronic Library Online (English)

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

    2011-03-01

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

  2. Carboxypeptidase-B-like processing of the C-terminus of glucagon-like peptide-2 in pig and human small intestine

    DEFF Research Database (Denmark)

    Orskov, C; Buhl, T; Rabenhøj, L; Kofod, Hans; Holst, J J

    1989-01-01

    We developed specific, C-terminal radioimmunoassays for three proglucagon (PG) fragments: PG 151-158, PG 151-160 and PG 126-159 (glucagon-like peptide-2 (GLP-2] in order to determine the exact C-terminal sequence of the newly isolated GLP-2 in man and pig. The antigens and the antisera showed no mutual cross-reactivity. By gel filtration of extracts of pig and human small intestine, the immunoreactivity eluting at the position of GLP-2 was identified by the radioimmunoassays for glucagon-like pe...

  3. Precolonized Human Commensal Escherichia coli Strains Serve as a Barrier to E. coli O157:H7 Growth in the Streptomycin-Treated Mouse Intestine?

    OpenAIRE

    Leatham, Mary P.; Banerjee, Swati; Autieri, Steven M.; Mercado-Lubo, Regino; Conway, Tyrrell; Cohen, Paul S.

    2009-01-01

    Different Escherichia coli strains generally have the same metabolic capacity for growth on sugars in vitro, but they appear to use different sugars in the streptomycin-treated mouse intestine (Fabich et al., Infect. Immun. 76:1143-1152, 2008). Here, mice were precolonized with any of three human commensal strains (E. coli MG1655, E. coli HS, or E. coli Nissle 1917) and 10 days later were fed 105 CFU of the same strains. While each precolonized strain nearly eliminated its isogenic strain, co...

  4. Colonization of the streptomycin-treated mouse large intestine by a human fecal Escherichia coli strain: role of growth in mucus.

    OpenAIRE

    Wadolkowski, E A; Laux, D C; Cohen, P S

    1988-01-01

    The relative colonizing abilities of Escherichia coli F-18, isolated from the feces of a healthy human, and E. coli F-18col-, a strain derived from it which does not make the E. coli F-18 colicin, were studied. In a previous report, it was shown that when each strain was fed individually to streptomycin-treated mice, at approximately 10(10) CFU per mouse, each colonized the large intestine at between 10(7) and 10(8) CFU/g of feces indefinitely. However, when simultaneously fed to mice, althou...

  5. Dysbiosis gut microbiota associated with inflammation and impaired mucosal immune function in intestine of humans with non-alcoholic fatty liver disease

    OpenAIRE

    Jiang, Weiwei; Wu, Na; Wang, Xuemei; Chi, Yujing; Zhang, Yuanyuan; Qiu, Xinyun; Hu, Ying; Li, Jing; Liu, Yulan

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) has recently been considered to be under the influence of the gut microbiota, which might exert toxic effects on the human host after intestinal absorption and delivery to the liver via the portal vein. In this study, the composition of the gut microbiota in NAFLD patients and healthy subjects was determined via 16S ribosomal RNA Illumina next-generation sequencing. Among those taxa displaying greater than 0.1% average abundance in all samples, five g...

  6. Enteral nutrients potentiate glucagon-like peptide-2 action and reduce dependence on parenteral nutrition in a rat model of human intestinal failure

    OpenAIRE

    Brinkman, Adam S.; Murali, Sangita G.; Hitt, Stacy; Solverson, Patrick M.; Holst, Jens J.; Ney, Denise M

    2012-01-01

    Glucagon-like peptide-2 (GLP-2) is a nutrient-dependent, proglucagon-derived gut hormone that shows promise for the treatment of short bowel syndrome (SBS). Our objective was to investigate how combination GLP-2 + enteral nutrients (EN) affects intestinal adaption in a rat model that mimics severe human SBS and requires parenteral nutrition (PN). Male Sprague-Dawley rats were assigned to one of five groups and maintained with PN for 18 days: total parenteral nutrition (TPN) alone, TPN + GLP-2...

  7. Recombinant human epidermal growth factor (rhEGF) protects radiation-induced intestine injury in murine system

    International Nuclear Information System (INIS)

    This study was to investigate whether rhEGF protects radiation induced intestine injury without compromising antitumor effect of radiation in murine system. A radiation induced intestinal injury model was established in mice by whole body irradiation. Using this model, 4 groups were set; control, rhEGF (100 ?g/kg intraperitoneally), radiation (10 Gy), and a combination (rhEGF and radiation). The level of apoptosis and proliferation were analyzed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and proliferation cell nuclear antigen (PCNA) immunohistochemical staining, respectively, as well as observation of survival and body weight change. A tumor growth delay assay was performed using murine syngeneic tumors; one radioresistant tumor, HCa-I and one radiosensitive tumor, MCa-K. In the radiation induced intestinal injury model, the 10 Gy group had significantly more weight loss with less number of crypt cells and higher apoptosis than the 8 Gy group. Using 10 Gy model, radioprotective effect of rhEGF was tested. Addition of rhEGF improved not only the body weight loss but also survival following radiation. It also induced suppression of apoptosis as well as increase of PCNA expression and recovery of villi. rhEGF did not enhance the tumor growth after radiation exposure in the tested tumors. These findings suggest that combination of exogenous rhEGF and radiation can be a new anticancer strategy by protecting radiation-induced intestinal injury without alleviating antitumor effect of radiation. (author)

  8. Human intestinal dendritic cells as controllers of mucosal immunity / Células dendríticas del intestino humano como controladoras de la inmunidad mucosa

    Scientific Electronic Library Online (English)

    David, Bernardo.

    2013-06-01

    Full Text Available Las células dendríticas son las células profesionales presentadoras de antígenos más potentes que existen y, tras realizar la presentación antigénica, controlan el tipo de respuesta inmune que se establecerá (proinflamatoria/reguladora), así como su localización. Debido a su gran plasticidad y capac [...] idad de maduración en respuesta a señales de peligro locales derivadas de la inmunidad innata, las células dendríticas son un elemento clave en la conexión entre la inmunidad innata y las respuestas de la inmunidad adaptativa. En el intestino, las células dendríticas controlan los mecanismos de la tolerancia inmunológica frente a los antígenos de la dieta y/o la flora comensal, a la vez que son capaces de iniciar una respuesta inmunológica activa en presencia de un patógeno invasor. Las células dendríticas son pues muy eficientes en controlar el delicado balance entre tolerancia/inmunidad en un ambiente tan cargado de antígenos como es el intestino, y cualquier factor que las afecte puede tener repercusiones en su funcionalidad, pudiendo en última instancia desarrollarse patologías intestinales como la enfermedad celiaca o las enfermedades inflamatorias intestinales. En esta revisión sintetizaremos nuestro conocimiento de las células dendríticas del intestino humano, su capacidad para expresar e inducir marcadores de migración, los diversos factores ambientales que modulan sus propiedades, los diferentes subtipos de células dendríticas que nos encontramos en el intestino y los problemas derivados de su estudio incluyendo sus diferentes estrategias de identificación, las diferencias entre humanos y modelos murinos y sus variaciones fenotípicas a lo largo del tracto gastrointestinal. Abstract in english Dendritic cells are the most potent, professional antigen-presenting cells in the body; following antigen presentation they control the type (proinflammatory/regulatory) of immune response that will take place, as well as its location. Given their high plasticity and maturation ability in response t [...] o local danger signals derived from innate immunity, dendritic cells are key actors in the connection between innate immunity and adaptive immunity responses. In the gut dendritic cells control immune tolerance mechanisms against food and/or commensal flora antigens, and are also capable of initiating an active immune response in the presence of invading pathogens. Dendritic cells are thus highly efficient in controlling the delicate balance between tolerance and immunity in an environment so rich in antigens as the gut, and any factor involving these cells may impact their function, ultimately leading to the development of bowel conditions such as celiac disease or inflammatory bowel disease. In this review we shall summarize our understanding of human intestinal dendritic cells, their ability to express and induce migration markers, the various environmental factors modulating their properties, their subsets in the gut, and the problems entailed by their study, including identification strategies, differences between humans and murine models, and phenotypical variations along the gastrointestinal tract.

  9. Disminución de tránsito intestinal y ausencia de toxicología aguda preclínicas de la decocción de partes aéreas 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, García Hernández; María del Carmen, Victoria Amador; Francisco, Morón Rodríguez; Marisol, López Barreiro; Elisa, Boucourt Rodríguez; María J, Martínez Guerra; Zulema, Morejón Rodríguez.

    2013-03-01

    Full Text Available Introducción: la decocción de partes aéreas 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 validación preclínica del efecto antidiarreico y su s [...] eguridad. Objetivos: evaluar la acción sobre el tránsito intestinal y la toxicología aguda oral y tópica en modelos preclínicos de la decocción de partes aéreas frescas de Phania matricarioides. Métodos: se colectaron las partes aéreas frescas de Phania matricarioides y se realizó decocción (30 y 50 %). Se aplicó el modelo experimental: tránsito intestinal en ratones con una sola administración de la decocción al 30 % en dosis de 1,0, 5,0 y 10,0 g de material vegetal/kg de peso corporal por 1 día; y en dosis de 1,0 y 5,0 g de material vegetal/kg de peso corporal por 4 días. El estudio toxicológico oral y tópico (decocción 50 %) se efectuó en los modelos: clases tóxicas agudas y toxicidad dérmica aguda en ratas con dosis de 2 000 mg/kg de peso corporal e irritabilidad dérmica primaria en conejos. Resultados: la decocción administrada por 1 día no modificó de forma significativa el tránsito intestinal, la administración por 4 días disminuyó de forma significativa y dosis dependiente el tránsito intestinal (5,0 g/kg). en el estudio toxicológico no se produjo ninguna muerte, no se evidenciaron signos de toxicidad ni lesiones macroscópicas en los órganos de las ratas, el aumento de peso fue el esperado. El índice de irritación primaria reflejó 0. Conclusiones: los resultados permiten validar el efecto antidiarreico de la decocción de partes aéreas frescas de Phania matricarioides para afecciones digestivas y no clasifica como tóxico. 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.

  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. A purgative action of barbaloin is induced by Eubacterium sp. strain BAR, a human intestinal anaerobe, capable of transforming barbaloin to aloe-emodin anthrone.

    Science.gov (United States)

    Akao, T; Che, Q M; Kobashi, K; Hattori, M; Namba, T

    1996-01-01

    Orally administered barbaloin (100 mg/kg) did not induce any diarrhea in male Wistar rats, in spite of severe diarrhea with sennoside B (40 mg/kg). Also, in gnotobiote rats mono-associated with Peptostreptococcus intermedius, a human intestinal anaerobe capable of reducing sennidins to rhein anthrone, barbaloin did not induce diarrhea; the faecal water content (71.9%) 8 h after the administration of barbaloin was not increased, compared with that (73.9%) just before the treatment. However, severe diarrhea was induced with barbaloin in gnotobiote rats mono-associated with Eubacterium sp. strain BAR, another human intestinal anaerobe capable of transforming barbaloin to aloe-emodin anthrone; the faecal water content was significantly increased to 85.5% 8 h after the administration, from 73.2% before the treatment. At this time, barbaloin was transformed to aloe-emodin anthrone in the feces from the gnotobiote rats mono-associated with the strain BAR, but not in feces from the conventional rats or the gnotobiote rats mono-associated with P. intermedius. These facts indicate that barbaloin is inactive as a laxative itself but is activated to aloe-emodin anthrone, a genuine purgative component, by Eubacterium sp. strain BAR. PMID:8820926

  12. Epidemiology and antimicrobial resistance of B. fragilis group organisms isolated from clinical specimen and human intestinal microbiota Epidemiologia e resistência a antimicrobianos de microorganismos do grupo B. fragilis isolados de espécime clínico e microbiota intestinal humana

    Directory of Open Access Journals (Sweden)

    Cibele Barreto Mano de Carvalho

    1996-10-01

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

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

    International Nuclear Information System (INIS)

    Mycotoxins are fungal secondary metabolites responsible of food-mediated intoxication in animals and humans. Deoxynivalenol, ochratoxin A and patulin are the best known enteropathogenic mycotoxins able to alter intestinal functions resulting in malnutrition, diarrhea, vomiting and intestinal inflammation in vivo. Although their effects on intestinal barrier and transport activities have been extensively characterized, the mechanisms responsible for their pro-inflammatory effect are still poorly understood. Here we investigated if mycotoxin-induced intestinal inflammation results from a direct and/or indirect pro-inflammatory activity of these mycotoxins on human intestinal epithelial cells, using differentiated Caco-2 cells as model and interleukin 8 (IL-8) as an indicator of intestinal inflammation. Deoxynivalenol was the only mycotoxin able to directly increase IL-8 secretion (10- to 15-fold increase). We also investigated if these mycotoxins could indirectly stimulate IL-8 secretion through: (i) a modulation of the action of pro-inflammatory molecules such as the interleukin-1beta (IL-1?), and/or (ii) an increase in the transepithelial passage of non-invasive commensal Escherichia coli. We found that deoxynivalenol, ochratoxin A and patulin all potentiated the effect of IL-1? on IL-8 secretion (ranging from 35% to 138% increase) and increased the transepithelial passage of commensal bacteria (ranging from 12- to 1544-fold increase). In addition to potentially 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. Pancreatoduodenectomy as a source of human small intestine for Ussing Chamber Investigations and comparative studies with rat tissue

    OpenAIRE

    Haslam, Iain Stuart; O'Reilly, Derek A; Sherlock, David J; Kauser, Ambareen; Womack, Chris; Coleman, Tanya

    2011-01-01

    Abstract A clear understanding of oral drug absorption is an important aspect of the drug development process. The permeability of drug compounds across intact sections of small intestine from numerous species, including man, has often been investigated using modified Ussing Chambers. The maintenance of viable, intact tissue is critical to the success of this technique. This study therefore aimed to assess the viability and integrity of tissue from patients undergoing pancreatod...

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

    OpenAIRE

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

    2010-01-01

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

  16. Changes in vasoactive intestinal peptide, pituitary adenylate cyclase-activating polypeptide and neuropeptide Y-ergic structures of the enteric nervous system in the carcinoma of the human large intestine.

    Directory of Open Access Journals (Sweden)

    Ireneusz 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.

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

    Science.gov (United States)

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

    2015-06-21

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

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

    DEFF Research Database (Denmark)

    Li, Yiping; Vegge, Christina S.

    2011-01-01

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

  19. 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 ...

  20. Human Rights Violations and the Paradox of Democratic Transition. A Study of Chile and Argentina

    OpenAIRE

    Elin SKAAR

    1994-01-01

    This comparative analysis of recent transitions to democracy in Argentina and Chile examines (1) the impact of the type of transition on democratic consolidation; (2) how resolving the problem of past human rights violations has influenced civil-military relations and democratic stability; and (3) what has been the role of human rights NGOs, the Catholic Church, andd political parties. A major conclusion is that state-civil society linkages are important to understanding demodratic transitio...

  1. Understanding the human dimensions of a sustainable energy transition

    OpenAIRE

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

    2015-01-01

    Global climate change threatens the health, economic prospects, and basic food and water sources of people. A wide range of changes in household energy behavior is needed to realize a sustainable energy transition. We propose a general framework to understand and encourage sustainable energy behaviors, comprising four key issues. First, we need to identify which behaviors need to be changed. A sustainable energy transition involves changes in a wide range of energy behaviors, including the ad...

  2. The human ventromedial prefrontal cortex is critical for transitive inference

    OpenAIRE

    Koscik, Timothy R; TRANEL, DANIEL

    2012-01-01

    We hypothesized that the ventromedial prefrontal cortex (vmPFC) is critical for making transitive inferences (e.g., the logical operation that if A > B and B > C, then A > C). To test this, participants with focal vmPFC damage, brain-damaged comparison participants, and neurologically normal participants completed a transitive inference task consisting of an ordered set of arbitrary patterns. Participants first learned through trial-and-error the relationships of the patterns (e.g., Pattern A...

  3. The kiwi fruit peptide kissper displays anti-inflammatory and anti-oxidant effects in in-vitro and ex-vivo human intestinal models.

    Science.gov (United States)

    Ciacci, C; Russo, I; Bucci, C; Iovino, P; Pellegrini, L; Giangrieco, I; Tamburrini, M; Ciardiello, M A

    2014-03-01

    Literature reports describe kiwi fruit as a food with significant effects on human health, including anti-oxidant and anti-inflammatory activity. Fresh fruit or raw kiwi fruit extracts have been used so far to investigate these effects, but the molecule(s) responsible for these health-promoting activities have not yet been identified. Kissper is a kiwi fruit peptide displaying pore-forming activity in synthetic lipid bilayers, the composition of which is similar to that found in intestinal cells. The objective of this study was to investigate the kissper influence on intestinal inflammation using cultured cells and ex-vivo tissues from healthy subjects and Crohn's disease (CD) patients. The anti-oxidant and anti-inflammatory properties of kissper were tested on Caco-2 cells and on the colonic mucosa from 23 patients with CD, by challenging with the lipopolysaccharide from Escherichia coli (EC-LPS) and monitoring the appropriate markers by Western blot and immunofluorescence. EC-LPS challenge determined an increase in the intracellular concentration of calcium and reactive oxygen species (ROS). The peptide kissper was highly effective in preventing the increase of LPS-induced ROS levels in both the Caco-2 cells and CD colonic mucosa. Moreover, it controls the calcium increase, p65-nuclear factor (NF)-kB induction and transglutaminase 2 (TG2) activation inflammatory response in Caco-2 cells and CD colonic mucosa. Kissper efficiently counteracts the oxidative stress and inflammatory response in valuable model systems consisting of intestinal cells and CD colonic mucosa. This study reports the first evidence supporting a possible correlation between some beneficial effects of kiwi fruit and a specific protein molecule rather than generic nutrients. PMID:24168016

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

    OpenAIRE

    Eugenia Elefterios Venizelos Bezirtzoglou

    2012-01-01

    Cytochromes P450 (CYPs) enzymes metabolize a large variety of xenobiotic substances. In this vein, a plethora of studies were conducted to investigate their role, as cytochromes are located in both liver and intestinal tissues. The P450 profile of the human intestine has not been fully characterized. Human intestine serves primarily as an absorptive organ for nutrients, although it has also the ability to metabolize drugs. CYPs are responsible for the majority of phase I drug metabolism react...

  5. Fermentation by gut microbiota cultured in a simulator of the human intestinal microbial ecosystem is improved by probiotic Enterococcus faecium CRL 183

    Directory of Open Access Journals (Sweden)

    Elizeu A. Rossi

    2011-10-01

    Full Text Available Background: Enterococci are used in a large number of dairy products, such as starter cultures in food supplements and in foods considered functional. In vitro gut fermentation models present an unmatched opportunity of performing studies frequently allenged in humans and animals owing to ethical concerns. A dynamic model of the human intestinal microbial ecosystem (SHIME was designed to better simulate conditions intestinal microbiota.Methods: The SHIME model was used to study the effect of Enterococuus faecium CRL 183 on the fermentation pattern of the colon microbiota. Initially, an inoculum prepared from human feces was introduced into the reactor vessels and stabilized over 2 wk using a culture medium. This stabilization period was followed by a 2-wk control period during which the microbiota were monitored. The microbiota were then subjected to a 4-wk treatment period by adding 108 CFU/mL of the Enterococcus faecium CRL 183 to vessel one (the stomach compartment.Results: The addition resulted into an overall increase of bacterial marker populations (Enterobacteriaceae, Lactobacillus spp., Bifidobacterium spp. and Clostridium spp., with a significant increase of the Lactobacillus sp. and Bifidobacterium sp populations. The short-chain fatty acid (SCFA concentration increased during the supplementation period; this was due mainly to a significant increase in the levels of acetic, butyric and propionic acids. Ammonium concentrations increased during the supplementation period.Conclusions: Results showed that the major effect of E. faecium CRL 183 was found in the ascendant and transverse colonFunctional Foods in Health and Disease 2011; 10:389-402

  6. Microbiota intestinal: sus repercusiones clínicas 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 función en la salud: estimula el sistema inmunitario, protege de la invasión por patógenos y obtiene energía de los nutrientes. Los cambios en la confguración de l [...] a microbiota alteran la homeostasis huésped-comunidad microbiana y repercuten en la salud. En el presente trabajo se comenta cómo se adquiere la microbiota, cuál es su dinámica desde el nacimiento hasta la vejez, cómo es la relación bidireccional que la microbiota establece con los seres humanos, y su repercusión en la salud, la enfermedad y la biodisponibilidad de los medicamentos.

  7. The mononuclear cells of human mesenteric blood, intestinal mucosa and mesenteric lymph nodes: compartmentalization of NK cells.

    OpenAIRE

    Gibson, PR; Verhaar, HJ; Selby, WS; Jewell, DP.

    1984-01-01

    The proportions of T cell subsets and Leu 7+ cells and the spontaneous cell-mediated cytotoxicity (SCMC) of isolated mononuclear cells have been determined across the mesenteric vascular bed and along the intestinal mucosal-mesenteric lymph node (MLN) axis in patients undergoing abdominal surgery. Whereas the proportion of T4+ and T8+ cells were similar in simultaneously taken PVB and mesenteric venous blood (MVB), the proportion of Leu 7+ cells was higher in MVB in 16 of 17 studies (15.4 +/-...

  8. Imunofluorescência para neuropeptídeos na mucosa nasal humana: avaliação de técnica para peptídeo intestinal vasoativo (VIP) / Neuropeptide immunofluorescence in human nasal mucosa: assessment of the technique for vasoactive intestinal peptide (VIP)

    Scientific Electronic Library Online (English)

    Jeferson Cedaro de, Mendonça; José Eduardo Lutaif, Dolci.

    2005-04-01

    Full Text Available Os neuropeptídeos são neurotransmissores relevantes na fisiologia nasal e o conhecimento crescente acerca de seu papel na fisiopatologia de doenças nasais abre novas perspectivas. A sua investigação na mucosa nasal humana baseia-se em grande parte em marcação imunológica, método complexo e sujeito a [...] inúmeros fatores de erro. Com o intuito de viabilizar este tipo de pesquisa em nosso meio, um método de imunofluorescência para peptídeo intestinal vasoativo (VIP) na mucosa nasal humana é proposto e avaliado. FORMA DE ESTUDO: Coorte transversal. MATERIAL E MÉTODO: Oito pacientes submetidos a cirurgia funcional do nariz têm um fragmento de mucosa coletado da concha inferior. O tecido foi fixado em solução de Zamboni (paraformaldeído 4% tamponado e ácido pícrico 0,4%), congelado em nitrogênio líquido e armazenado. Cortes de 14 µm foram realizados e submetidos à reação de imunofluorescência para VIP (Península Laboratories). As imagens microscópicas foram documentadas em fotografia convencional. A especificidade, sensibilidade e reprodutibilidade de execução foram avaliadas. A reprodutibilidade de interpretação de resultados foi avaliada através da comparação de graus de marcação (0 a 4) atribuídos às fotos por seis observadores. RESULTADOS: Os resultados mostraram ser o método suficientemente específico, sensível, além de reprodutível em sua execução. A interpretação de resultados mostrou depender do perfeito esclarecimento do observador no julgamento das imagens de imunofluorescência, mas mostrou uniformidade. CONCLUSÃO: O método proposto foi considerado útil na pesquisa de neuropeptídeos na mucosa nasal humana. Abstract in english Neuropeptides are important neurotransmitters in nasal physiology and the increasing knowledge of their role in nasal diseases brings new therapeutic perspectives. The investigation of human nasal mucosa neuropeptides is based mostly on immunocytochemistry, a complex approach whose resulting factors [...] may be variable. Aiming to make this kind of research available, an immunofluorescence approach for vasoactive intestinal peptide (VIP) in human nasal mucosa is proposed and evaluated. STUDY DESIGN: Transversal cohort. MATERIAL AND METHOD: Human inferior turbinate samples were obtained at time of nasal surgery from eight patients. The samples were fixed in Zamboni solution (4% phosphate-buffered paraformaldehyde and 0.4% picric acid), snap-frozen and stored at -70ºC. 14 µm sections were then obtained. Immunofluorescence staining for VIP (Peninsula Laboratories) was performed and its images documented by conventional photography. The method's specificity, sensitivity and reproducibility of execution were evaluated. Additionally, the reproducibility of interpretation of results was evaluated through the comparison of staining scores (0 to 4) attributed to the images by six observers. RESULTS: The results showed the approach to be very specific and sensible, besides being reproducible in its execution. The interpretation of results may depend on the observer's accuracy in judging immunofluorescence images, but it showed uniformity. CONCLUSION: The proposed method was highly useful for research purposes in neuropeptides in human nasal mucosa.

  9. Imunofluorescência para neuropeptídeos na mucosa nasal humana: avaliação de técnica para peptídeo intestinal vasoativo (VIP Neuropeptide immunofluorescence in human nasal mucosa: assessment of the technique for vasoactive intestinal peptide (VIP

    Directory of Open Access Journals (Sweden)

    Jeferson Cedaro de Mendonça

    2005-04-01

    Full Text Available Os neuropeptídeos são neurotransmissores relevantes na fisiologia nasal e o conhecimento crescente acerca de seu papel na fisiopatologia de doenças nasais abre novas perspectivas. A sua investigação na mucosa nasal humana baseia-se em grande parte em marcação imunológica, método complexo e sujeito a inúmeros fatores de erro. Com o intuito de viabilizar este tipo de pesquisa em nosso meio, um método de imunofluorescência para peptídeo intestinal vasoativo (VIP na mucosa nasal humana é proposto e avaliado. FORMA DE ESTUDO: Coorte transversal. MATERIAL E MÉTODO: Oito pacientes submetidos a cirurgia funcional do nariz têm um fragmento de mucosa coletado da concha inferior. O tecido foi fixado em solução de Zamboni (paraformaldeído 4% tamponado e ácido pícrico 0,4%, congelado em nitrogênio líquido e armazenado. Cortes de 14 µm foram realizados e submetidos à reação de imunofluorescência para VIP (Península Laboratories. As imagens microscópicas foram documentadas em fotografia convencional. A especificidade, sensibilidade e reprodutibilidade de execução foram avaliadas. A reprodutibilidade de interpretação de resultados foi avaliada através da comparação de graus de marcação (0 a 4 atribuídos às fotos por seis observadores. RESULTADOS: Os resultados mostraram ser o método suficientemente específico, sensível, além de reprodutível em sua execução. A interpretação de resultados mostrou depender do perfeito esclarecimento do observador no julgamento das imagens de imunofluorescência, mas mostrou uniformidade. CONCLUSÃO: O método proposto foi considerado útil na pesquisa de neuropeptídeos na mucosa nasal humana.Neuropeptides are important neurotransmitters in nasal physiology and the increasing knowledge of their role in nasal diseases brings new therapeutic perspectives. The investigation of human nasal mucosa neuropeptides is based mostly on immunocytochemistry, a complex approach whose resulting factors may be variable. Aiming to make this kind of research available, an immunofluorescence approach for vasoactive intestinal peptide (VIP in human nasal mucosa is proposed and evaluated. STUDY DESIGN: Transversal cohort. MATERIAL AND METHOD: Human inferior turbinate samples were obtained at time of nasal surgery from eight patients. The samples were fixed in Zamboni solution (4% phosphate-buffered paraformaldehyde and 0.4% picric acid, snap-frozen and stored at -70ºC. 14 µm sections were then obtained. Immunofluorescence staining for VIP (Peninsula Laboratories was performed and its images documented by conventional photography. The method's specificity, sensitivity and reproducibility of execution were evaluated. Additionally, the reproducibility of interpretation of results was evaluated through the comparison of staining scores (0 to 4 attributed to the images by six observers. RESULTS: The results showed the approach to be very specific and sensible, besides being reproducible in its execution. The interpretation of results may depend on the observer's accuracy in judging immunofluorescence images, but it showed uniformity. CONCLUSION: The proposed method was highly useful for research purposes in neuropeptides in human nasal mucosa.

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

    DEFF Research Database (Denmark)

    Tetens, Inge

    2011-01-01

    Following an application from Nordic Sugar A/S, submitted pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Denmark, the Panel on Dietetic Products, Nutrition and Allergies was asked to deliver an opinion on the scientific substantiation of a health claim based on newly developed scientific evidence related to sugar beet fibre and “decreasing intestinal transit time”. The food constituent that is the subject of the health claim is sugar beet fibre. This opi...

  11. 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...

  12. PREFERRED AND ENERGETICALLY OPTIMAL TRANSITION SPEEDS DURING BACKWARD HUMAN LOCOMOTION

    Directory of Open Access Journals (Sweden)

    Alan Hreljac

    2005-12-01

    Full Text Available Some aspects of backward locomotion are similar to forward locomotion, while other aspects are not related to their forward counterpart. The backward preferred transition speed (BPTS has never been directly compared to the energetically optimal transition speed (EOTS, nor has it been compared to the preferred transition speed (PTS during forward locomotion. The purpose of this study was to determine whether the BPTS occurs at the EOTS, and to examine the relationship between the backward and forward preferred gait transition speeds. The preferred backward and forward transition speeds of 12 healthy, young subjects (7 males, 5 females were determined after subjects were familiarized with forward and backward treadmill locomotion. On a subsequent day, subjects walked backward at speeds of 70, 80, 90, 100, and 110% of the BPTS and ran backward at speeds of 60, 75, 90, 100, and 120% of the BPTS while VO2 and RPE data were collected. After subtracting standing VO2, exercise VO2 was normalized to body mass and speed. For each subject, energy-speed curves for walking and running were fit to the normalized data points. The intersection of these curves was defined as the EOTS which was compared to the BPTS using a paired t-test (p < 0.05. RPE and VO2 at the BPTS were also compared between walking and running conditions, and the correlation between BPTS and PTS was calculated. The EOTS (1.85 ± 0.09 m·s-1 was significantly greater than the BPTS (1.63 ± 0.11 m·s-1. Even though RPE was equal for walking and running at the BPTS, VO2 was significantly greater when running. There was a strong correlation (r = 0.82 between the BPTS and the PTS. Similar to forward locomotion, the determinants of the BPTS must include factors other than metabolic energy. The gait transition during backward locomotion exhibits several similarities to its forward counterpart

  13. 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)

  14. Update on Transanal NOTES for Rectal Cancer: Transitioning to Human Trials

    OpenAIRE

    Patricia Sylla; Rattner, David W.; Bordeianou, Liliana G.; Berger, David L.; Telem, Dana A.

    2012-01-01

    The feasibility of natural orifice translumenal endoscopic surgery (NOTES) resection for rectal cancer has been demonstrated in both survival swine and fresh human cadaveric models. In preparation for transitioning to human application, our group has performed transanal NOTES rectal resection in a large series of human cadavers. This experience both solidified the feasibility of resection and allowed optimization of technique prior to clinical application. Improvement in specimen length and o...

  15. Epidemiological Interactions between Urogenital and Intestinal Human Schistosomiasis in the Context of Praziquantel Treatment across Three West African Countries

    Science.gov (United States)

    Knowles, Sarah C. L.; Webster, Bonnie L.; Garba, Amadou; Sacko, Moussa; Diaw, Oumar T.; Fenwick, Alan; Rollinson, David; Webster, Joanne P.

    2015-01-01

    Background In many parts of sub-Saharan Africa, urogenital and intestinal schistosomiasis co-occur, and mixed species infections containing both Schistosoma haematobium and S. mansoni can be common. During co-infection, interactions between these two species are possible, yet the extent to which such interactions influence disease dynamics or the outcome of control efforts remains poorly understood. Methodology/Principal Findings Here we analyse epidemiological data from three West African countries co-endemic for urogenital and intestinal schistosomiasis (Senegal, Niger and Mali) to test whether the impact of praziquantel (PZQ) treatment, subsequent levels of re-infection or long-term infection dynamics are altered by co-infection. In all countries, positive associations between the two species prevailed at baseline: infection by one species tended to predict infection intensity for the other, with the strength of association varying across sites. Encouragingly, we found little evidence that co-infection influenced PZQ efficacy: species-specific egg reduction rates (ERR) and cure rates (CR) did not differ significantly with co-infection, and variation in treatment success was largely geographical. In Senegal, despite positive associations at baseline, children with S. mansoni co-infection at the time of treatment were less intensely re-infected by S. haematobium than those with single infections, suggesting competition between the species may occur post-treatment. Furthermore, the proportion of schistosome infections attributable to S. mansoni increased over time in all three countries examined. Conclusions/Significance These findings suggest that while co-infection between urinary and intestinal schistosomes may not directly affect PZQ treatment efficacy, competitive interspecific interactions may influence epidemiological patterns of re-infection post-treatment. While re-infection patterns differed most strongly according to geographic location, interspecific interactions also seem to play a role, and could cause the community composition in mixed species settings to shift as disease control efforts intensify, a situation with implications for future disease management in this multi-species system. PMID:26469347

  16. Retrospective analysis of patients undergoing bowel transit reconstruction in a tertiary referral hospital of São Paulo's east side / Análise retrospectiva dos pacientes submetidos à reconstrução de trânsito intestinal em hospital terciário de referência da zona leste de São Paulo

    Scientific Electronic Library Online (English)

    Isaac José Felippe, Corrêa Neto; Otávio Nunes, Siá; Eduardo Augusto, Lopes; Rodrigo, Padilla; Katiucia Tereza Molezin, Portugal; Alexander Sá, Rolim; Rogério Freitas Lino, Souza; Hugo Henriques, Watté; Laércio, Robles.

    2014-12-01

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

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

    DEFF Research Database (Denmark)

    Fjællegaard, Cecilie Bryld

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

  18. 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...

  19. 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

  20. A mathematical model of intestinal oedema formation.

    Science.gov (United States)

    Young, Jennifer; Rivière, Béatrice; Cox, Charles S; Uray, Karen

    2014-03-01

    Intestinal oedema is a medical condition referring to the build-up of excess fluid in the interstitial spaces of the intestinal wall tissue. Intestinal oedema is known to produce a decrease in intestinal transit caused by a decrease in smooth muscle contractility, which can lead to numerous medical problems for the patient. Interstitial volume regulation has thus far been modelled with ordinary differential equations, or with a partial differential equation system where volume changes depend only on the current pressure and not on updated tissue stress. In this work, we present a computational, partial differential equation model of intestinal oedema formation that overcomes the limitations of past work to present a comprehensive model of the phenomenon. This model includes mass and momentum balance equations which give a time evolution of the interstitial pressure, intestinal volume changes and stress. The model also accounts for the spatially varying mechanical properties of the intestinal tissue and the inhomogeneous distribution of fluid-leaking capillaries that create oedema. The intestinal wall is modelled as a multi-layered, deforming, poroelastic medium, and the system of equations is solved using a discontinuous Galerkin method. To validate the model, simulation results are compared with results from four experimental scenarios. A sensitivity analysis is also provided. The model is able to capture the final submucosal interstitial pressure and total fluid volume change for all four experimental cases, and provide further insight into the distribution of these quantities across the intestinal wall. PMID:23036806

  1. 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.

  2. Cytokine responses in primary chicken embryo intestinal cells infected with Campylobacter jejuni strains of human and chicken origin and the expression of bacterial virulence-associated genes

    DEFF Research Database (Denmark)

    Li, Yiping; Ingmer, Hanne

    2008-01-01

    Background Campylobacter jejuni is a major cause of inflammatory diarrhoea in humans and is considered a commensal of the gastroenteric tract of the avian host. However, little is known about the interaction between C. jejuni and the avian host including the cytokine responses and the expression of the bacterial genes. We have investigated the invasiveness of primary chicken embryo intestinal cells (CEICs) by C. jejuni strains of human and chicken origins and the production of pro-inflammatory cytokines as well as the expression of the bacterial virulence-associated genes during co-cultivation. Results C. jejuni strains are capable of invading the CEICs and stimulate these cells in a pro-inflammatory manner and during this interaction the expression of the bacterial virulence-associated genes ciaB, dnaJ and racR is increased. Furthermore, incubation of bacteria with conditioned cell- and bacteria-free media from another co-cultivation experiment also increased the expression of the virulence-associated genesin the C. jejuni chicken isolate, indicating that the expression of bacterial genes is regulated by component(s) secreted upon co-cultivation of bacteria and CEICs. Conclusion We show that under in vitro culture condition C. jejuni strains of both human and chicken origins can invade avian host cells with a pro-inflammatory response and that the virulence-associated genes of C. jejuni may play a role in this process.

  3. Bioactive Milk for Intestinal Maturation in Preterm Neonates

    DEFF Research Database (Denmark)

    Li, Yanqi

    2014-01-01

    The fetal small intestine grows dramatically fast during the second and third trimester of human pregnancy. Many intestinal functions are therefore affected by preterm birth, including gastrointestinal motility, digestive and absorptive function, mucosal barrier function, and the intestinal inflammatory response. This immaturity predisposes preterm infants to various nutritional challenges and clinical conditions, including feeding intolerance, growth restriction, necrotizing enterocolitis (NEC)...

  4. HUMAN RESOURCE MANAGEMENT IN TRANSITIONAL ECONOMY IN VIETNAM

    OpenAIRE

    THI HOE, PHAM

    2013-01-01

    Concerning the "Doi moi" policy in 1986, Vietnam economy began to change from a centrally planned economy into a socialist-oriented market economy. However, starting of something new is always starting of new challenges. After more than 20 years, Vietnam economy is complicated and still looking for a better solution to be improved faster and be able to adapt to new changes in the world. It is easily seen that society is built up by humans. Economy can be changed by humans. Products or service...

  5. Influences of task concreteness upon transitive responding in humans

    OpenAIRE

    Siemann, Martina; Delius, Juan

    1996-01-01

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

  6. Establishment and characterization of monoclonal and polyclonal antibodies against human intestinal fatty acid-binding protein (I-FABP) using synthetic regional peptides and recombinant I-FABP.

    Science.gov (United States)

    Kajiura, Satoshi; Yashiki, Tetsuya; Funaoka, Hiroyuki; Ohkaru, Yasuhiko; Nishikura, Ken; Kanda, Tatsuo; Ajioka, Yoichi; Igarashi, Michihiro; Hatakeyama, Katsuyoshi; Fujii, Hiroshi

    2008-01-01

    We have succeeded in raising highly specific anti-human intestinal fatty acid-binding protein (I-FABP) monoclonal antibodies by immunizing animals with three synthetic regional peptides, i.e., the amino terminal (RP-1: N-acetylated 1-19-cysteine), middle portion (RP-2: cysteinyl-91-107) and carboxylic terminal (RP-3: cysteinyl-121-131) regions of human I-FABP, and the whole I-FABP molecule as antigens. We also raised a polyclonal antibody by immunizing with a recombinant (r) I-FABP. To ascertain the specificity of these antibodies for human I-FABP, the immunological reactivity of each was examined by a binding assay using rI-FABP, partially purified native I-FABP and related proteins such as liver-type (L)-FABP, heart-type (H)-FABP, as well as the regional peptides as reactants, and by Western blot analysis. In addition, the expression and distribution of I-FABP in the human gastrointestinal tract were investigated by an immunohistochemical technique using a carboxylic terminal region-specific monoclonal antibody, 8F9, and a polyclonal antibody, DN-R2. Our results indicated that both the monoclonal and polyclonal antibodies established in this study were highly specific for I-FABP, but not for L-FABP and H-FABP. Especially, the monoclonal antibodies raised against the regional peptides, showed regional specificity for the I-FABP molecule. Immunoreactivity of I-FABP was demonstrated in the mucosal epithelium of the jejunum and ileum by immunohistochemical staining, and the immunoreactivity was based on the presence of the whole I-FABP molecule but not the presence of any precursors or degradation products containing a carboxylic terminal fragment. It is concluded that some of these monoclonal and polyclonal antibodies, such as 8F9, 4205, and DN-R2, will be suitable for use in research on the immunochemistry and clinical chemistry of I-FABP because those antibodies can recognize both types of native and denatured I-FABP. In order to detect I-FABP in blood samples, it is essential to use this type of antibody, reactive to native type of I-FABP. It is anticipated that, in the near future, such a method for measuring I-FABP will be developed as a useful tool for diagnosing intestinal ischemia by using some of these antibodies. PMID:18080878

  7. Regional unemployment and human capital in transition economies.

    Czech Academy of Sciences Publication Activity Database

    Jurajda, Št?pán; Terrell, K.

    2009-01-01

    Ro?. 17, ?. 2 (2009), s. 241-274. ISSN 0967-0750 R&D Projects: GA MŠk LC542 Institutional research plan: CEZ:AV0Z70850503 Keywords : unemployment * human capital * regional labour markets Subject RIV: AH - Economics Impact factor: 0.774, year: 2009

  8. Regional unemployment and human capital in transition economies.

    Czech Academy of Sciences Publication Activity Database

    Jurajda, Št?pán; Terrell, K.

    -, ?. 345 (2007), s. 1-34. ISSN 1211-3298 R&D Projects: GA MŠk LC542 Institutional research plan: CEZ:AV0Z70850503 Keywords : unemployment * human capital * regional labor markets Subject RIV: AH - Economics http://www.cerge-ei.cz/pdf/wp/Wp345.pdf

  9. Regional unemployment and human capital in transition economies.

    Czech Academy of Sciences Publication Activity Database

    Jurajda, Št?pán; Terrell, K.

    -, ?. 6569 (2007), s. 1-34. ISSN 0265-8003 R&D Projects: GA MŠk LC542 Institutional research plan: CEZ:AV0Z70850503 Keywords : human capital * unemployment * labour mobility Subject RIV: AH - Economics http://www.cepr.org/pubs/new-dps/dplist.asp?dpno=6569.asp

  10. Síndrome de intestino corto: definición, causas, adaptación intestinal y sobrecrecimiento bacteriano / Short bowel syndrome: definition, causes, intestinal adaptation and bacterial overgrowth

    Scientific Electronic Library Online (English)

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

    2007-05-01

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

  11. Transition of nitro musks and polycyclic musks into human milk.

    Science.gov (United States)

    Liebl, B; Mayer, R; Ommer, S; Sönnichsen, C; Koletzko, B

    2000-01-01

    Synthetic musks are widely used in various consumer products. The identification of nitro musks in human milk in the early 1990s in connection with evidence for cancerogenicity in animal experiments have caused public concern. However, the validity of previously reported quantitative data has been questioned. Polycylic musks have hardly been investigated so far. The present study aimed at providing accurate current data on the occurrence of nitro and polycyclic musks in human milk. Samples from 40 healthy breast feeding mothers were analysed under carefully controlled conditions avoiding secondary contamination. As in earlier studies, among the nitro compounds musk xylene and ketone were the most frequently detected substances. However, much lower concentrations (roughly by a factor of 10) were found (musk xylene: median 6.1 ng/kg fat). Among the polycylic musks HHCB was found in most samples (median 64 ng/kg fat). Scientific knowledge on possible routes of exposure and health risk aspects is summarized and discussed. PMID:11065081

  12. Age-Dependent Transition from Cell-Level to Population-Level Control in Murine Intestinal Homeostasis Revealed by Coalescence Analysis

    OpenAIRE

    Hu, Zheng; Fu, Yun-Xin; Greenberg, Anthony J.; Wu, Chung-I.; Zhai, Weiwei

    2013-01-01

    In multi-cellular organisms, tissue homeostasis is maintained by an exquisite balance between stem cell proliferation and differentiation. This equilibrium can be achieved either at the single cell level (a.k.a. cell asymmetry), where stem cells follow strict asymmetric divisions, or the population level (a.k.a. population asymmetry), where gains and losses in individual stem cell lineages are randomly distributed, but the net effect is homeostasis. In the mature mouse intestinal crypt, previ...

  13. Selection of bacteria originating from a human intestinal microbiota in the gut of previously germ-free rats

    DEFF Research Database (Denmark)

    Licht, Tine Rask; Madsen, Bodil

    2007-01-01

    Denaturing gradient gel electrophoresis (DGGE) was applied to separate PCR-amplified 16S rRNA genes originating from human microbiota associated (HMA) rat faeces as well as from the human faecal sample used for inoculation of the animals. Subsequently, a total of 15 dominant bands were excised from the DGGE gels, cloned and sequenced. Comparison of the obtained sequences with the Ribosomal Database revealed that species of Bacteroides/Prevotella and Faecalibacterium gave rise to the majority of the dominant bands in the human sample and in the HMA rats. In the HMA rats, two dominant bands, which were not present in the human DGGE profile, originated from species of Ruminococcus. With the exception of the Ruminococcus sequences, sequences originating from both rats and human samples were represented in all major branches of a maximum parsimony tree, indicating that the rat feed and gut environment allows colonization of the dominant taxonomic units from the human microbiota, but additionally selects for Ruminococci. Bands representing Prevotella and Faecalibacterium, which were found in identical positions of the DGGE gels originating from human and HMA rat faecal samples, originated from completely identical sequences, indicating that the same strains of these species were dominating in the human and rat samples.

  14. Establishment of Intestinal Bacteriology

    OpenAIRE

    Mitsuoka, Tomotari

    2014-01-01

    Research on intestinal bacteria began around the end of the 19th century. During the last 5 decades of the 20th century, research on the intestinal microbiota made rapid progress. At first, in my work, I first developed a method of comprehensive analysis of the intestinal microbiota, and then I established classification and identification methods for intestinal anaerobes. Using these methods I discovered a number of ecological rules governing the intestinal microbiota and the ...

  15. Marmoset cytochrome P450 2D8 in livers and small intestines metabolizes typical human P450 2D6 substrates, metoprolol, bufuralol and dextromethorphan.

    Science.gov (United States)

    Uehara, Shotaro; Uno, Yasuhiro; Hagihira, Yuya; Murayama, Norie; Shimizu, Makiko; Inoue, Takashi; Sasaki, Erika; Yamazaki, Hiroshi

    2015-01-01

    1.?Although the New World non-human primate, the common marmoset (Callithrix jacchus), is a potentially useful animal model, comprehensive understanding of drug metabolizing enzymes is insufficient. 2.?A cDNA encoding a novel cytochrome P450 (P450) 2D8 was identified in marmosets. The amino acid sequence deduced from P450 2D8 cDNA showed a high sequence identity (83-86%) with other primate P450 2Ds. Phylogenetic analysis showed that marmoset P450 2D8 was closely clustered with human P450 2D6, unlike P450 2Ds of miniature pig, dog, rabbit, guinea pig, mouse or rat. 3.?Marmoset P450 2D8 mRNA was predominantly expressed in the liver and small intestine among the tissues types analyzed, whereas marmoset P450 2D6 mRNA was expressed predominantly in the liver where P450 2D protein was detected by immunoblotting. 4.?By metabolic assays using marmoset P450 2D8 protein heterologously expressed in Escherichia coli, although P450 2D8 exhibits lower catalytic efficiency compared to marmoset and human P450 2D6 enzymes, P450 2D8 mediated O-demethylations of metoprolol and dextromethorphan and bufuralol 1'-hydroxylation. 5.?These results suggest that marmoset P450 2D8 (also expressed in the extrahepatic tissues) has potential roles in drug metabolism in a similar manner to those of human and marmoset P450 2D6. PMID:25801057

  16. Antioxidant and Radical Scavenging Activity of Human Colostrum, Transitional and Mature Milk

    OpenAIRE

    Zarban, Asghar; Taheri, Fatemeh; Chahkandi, Taiebeh; SHARIFZADEH, Gholamreza; Khorashadizadeh, Mohsen

    2009-01-01

    Human milk from healthy women contains numerous nutrients such as antioxidants which are necessary for newborns. The aim of this study was to evaluate the changes of total antioxidant capacity (TAC) and free radical scavenging activity in human milk during the first six month period of lactation and also its relationship to maternal plasma. A total of 505 milk samples (colostrum, transitional and mature milks) collected from 115 healthy women with full term newborns. Blood plasma was obtained...

  17. 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)

  18. Up-regulation of early growth response gene 1 (EGR-1) via ERK1/2 signals attenuates sulindac sulfide-mediated cytotoxicity in the human intestinal epithelial cells

    International Nuclear Information System (INIS)

    Non-steroidal anti-inflammatory drugs (NSAIDs) are used to relieve pain and inflammation and have also received considerable attention because of their preventive effects against human cancer. However, the drug application is sometimes limited by the severe gastrointestinal ulcers and mucosal complications. In the present study, NSAID sulindac sulfide was investigated for the cytotoxic injury in the intestinal epithelial cells in association with an immediate inducible factor, early growth response gene 1 (EGR-1). Previously we reported that sulindac sulfide can suppress tumor cell invasion by inducing EGR-1. Extending the previous study, EGR-1 induction by sulindac sulfide was observed both in the non-transformed and transformed human intestinal epithelial cell lines. In terms of signaling pathway, ERK1/2 MAP kinases and its substrate Elk-1 transcription factor were involved in the sulindac sulfide-induced EGR-1 gene expression. Moreover, sulindac sulfide stimulated the nuclear translocation of the transcription factor EGR-1, which was also mediated by ERK1/2 signaling pathway. The roles of EGR-1 signals in the apoptotic cell death were assessed in the intestinal epithelial cells. Suppression of EGR-1 expression retarded cellular growth and colony forming activity in the intestinal epithelial cells. Moreover, induced EGR-1 ameliorated sulindac sulfide-mediated apoptotic cell death and enhanced the cellular survival. Taken all together, sulindac sulfide activated ERK1/2 MAP kinases which then mediated EGR-1 induction and nuclear translocation, all of which played important roles in the cellular survival from NSAID-mediated cytotoxicity in the human intestinal epithelial cells, implicating the protective roles of EGR-1 in the NSAID-mediated mucosal injuries

  19. 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.

  20. Campylobacter jejuni outer membrane vesicles play an important role in bacterial interactions with human intestinal epithelial cells.

    Science.gov (United States)

    Elmi, Abdi; Watson, Eleanor; Sandu, Pamela; Gundogdu, Ozan; Mills, Dominic C; Inglis, Neil F; Manson, Erin; Imrie, Lisa; Bajaj-Elliott, Mona; Wren, Brendan W; Smith, David G E; Dorrell, Nick

    2012-12-01

    Campylobacter jejuni is the most prevalent cause of food-borne gastroenteritis in the developed world; however, the molecular basis of pathogenesis is unclear. Secretion of virulence factors is a key mechanism by which enteric bacterial pathogens interact with host cells to enhance survival and/or damage the host. However, C. jejuni lacks the virulence-associated secretion systems possessed by other enteric pathogens. Many bacterial pathogens utilize outer membrane vesicles (OMVs) for delivery of virulence factors into host cells. In the absence of prototypical virulence-associated secretion systems, OMVs could be an important alternative for the coordinated delivery of C. jejuni proteins into host cells. Proteomic analysis of C. jejuni 11168H OMVs identified 151 proteins, including periplasmic and outer membrane-associated proteins, but also many determinants known to be important in survival and pathogenesis, including the cytolethal distending toxin (CDT). C. jejuni OMVs contained 16 N-linked glycoproteins, indicating a delivery mechanism by which these periplasm-located yet immunogenic glycoproteins can interact with host cells. C. jejuni OMVs possess cytotoxic activity and induce a host immune response from T84 intestinal epithelial cells (IECs), which was not reduced by OMV pretreatment with proteinase K or polymyxin B prior to coincubation with IECs. Pretreatment of IECs with methyl-beta-cyclodextrin partially blocks OMV-induced host immune responses, indicating a role for lipid rafts in host cell plasma membranes during interactions with C. jejuni OMVs. OMVs isolated from a C. jejuni 11168H cdtA mutant induced interleukin-8 (IL-8) to the same extent as did wild-type OMVs, suggesting OMV induction of IL-8 is independent of CDT. PMID:22966047

  1. 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, Št?pán; Plánovský, J.

    -, ?. 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

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

    Science.gov (United States)

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

    2015-10-01

    The reported inverse association between the intake of plant-based foods and a reduction in the prevalence of colorectal cancer may be partly mediated by interactions between insoluble fibre and (poly)phenols and the intestinal microbiota. In the present study, we assessed the impact of palm date consumption, rich in both polyphenols and fibre, on the growth of colonic microbiota and markers of colon cancer risk in a randomised, controlled, cross-over human intervention study. A total of twenty-two healthy human volunteers were randomly assigned to either a control group (maltodextrin-dextrose, 37·1 g) or an intervention group (seven dates, approximately 50 g). Each arm was of 21 d duration and was separated by a 14-d washout period in a cross-over manner. Changes in the growth of microbiota were assessed by fluorescence in situ hybridisation analysis, whereas SCFA levels were assessed using HPLC. Further, ammonia concentrations, faecal water genotoxicity and anti-proliferation ability were also assessed using different assays, which included cell work and the Comet assay. Accordingly, dietary intakes, anthropometric measurements and bowel movement assessment were also carried out. Although the consumption of dates did not induce significant changes in the growth of select bacterial groups or SCFA, there were significant increases in bowel movements and stool frequency (P<0·01; n 21) and significant reductions in stool ammonia concentration (P<0·05; n 21) after consumption of dates, relative to baseline. Furthermore, date fruit intake significantly reduced genotoxicity in human faecal water relative to control (P<0·01; n 21). Our data indicate that consumption of date fruit may reduce colon cancer risk without inducing changes in the microbiota. PMID:26428278

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

    DEFF Research Database (Denmark)

    Csati, A; Tajti, J

    2012-01-01

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

  4. Expression of Toll-like receptor 9 and response to bacterial CpG oligodeoxynucleotides in human intestinal epithelium

    DEFF Research Database (Denmark)

    Pedersen, G; Andresen, Lars

    2005-01-01

    Recognition of repeat CpG motifs, which are common in bacterial, but not in mammalian, DNA, through Toll-like receptor (TLR)9 is an integral part of the innate immune system. As the role of TLR9 in the human gut is unknown, we determined the spectrum of TLR9 expression in normal and inflamed colon and examined how epithelial cells respond to specific TLR9 ligand stimulation. TLR9 expression was measured in human colonic mucosal biopsies, freshly isolated human colonic epithelial cells and HT-29 cells by reverse transcriptase-polymerase chain reaction or Western blotting. Colonic epithelial cell cultures were stimulated with a synthetic CpG-oligodeoxynucleotide (ODN), exhibiting strong immunostimulatory effects in B cells. Interleukin (IL)-8 secretion was determined by enzyme-linked immunosorbent assay, nuclear factor-kappaB (NF-kB) activity by electrophoretic mobility shift assay and IkB phosphorylation by Western blotting. TLR9 mRNA was equally expressed in colonic mucosa from controls (n = 6) and patients with ulcerative colitis or Crohn's disease disease (n = 13). HT-29 cells expressed TLR9 mRNA and protein and responded to CpG-ODN (P <0.01), but not to non-CpG-ODN stimulation, by secreting IL-8, apparently in the absence of NF-kB activation. Primary epithelial cells isolated from normal human colon expressed TLR9 mRNA, but were completely unresponsive to CpG-ODN stimulation in vitro. In conclusion, differentiated human colonic epithelial cells are unresponsive to TLR9 ligand stimulation in vitro despite spontaneous TLR9 gene expression. This suggests that the human epithelium is able to avoid inappropriate immune responses to luminal bacterial products through modulation of the TLR9 pathway.

  5. Diverse patterns of expression of the 67-kD laminin receptor in human small intestinal mucosa: potential binding sites for prion proteins?

    Science.gov (United States)

    Shmakov, A N; Bode, J; Kilshaw, P J; Ghosh, S

    2000-07-01

    It has been shown that the 67-kD laminin receptor (LR) may function as a receptor for Sindbis and tick-born encephalitis viruses. Recent data indicate that the 37-kD precursor (LRP) for this molecule acts as a receptor for prion proteins (PrP), self-proteins implicated in the pathogenesis of transmissible spongiform encephalopathies including new variant Creutzfeldt-Jakob disease (nvCJD). Laminin and PrP share the same binding site on LRP, which is incorporated into the mature LR as a functional binding domain. To localize PrP binding sites potentially relevant to oral infection, the expression of the LR in human small intestinal mucosa was studied. Expression of the LR was determined by immunohistochemistry in duodenal and jejunal biopsies using a monoclonal antibody (MLuC5) which specifically recognizes the 67-kD LR. Biopsy material was obtained from 39 control patients, 15 patients with ulcerative colitis, 15 patients with Crohn's disease and uninvolved small bowel, and 28 patients with active coeliac disease. Two distinctive patterns of LR expression were found within each group of patients. One pattern was characterized by LR expression in the brush border and Golgi apparatus region of villus and crypt enterocytes. Paneth cell secretory granules were positive for LR in these samples. Brush border expression of LR was found in approximately 40% of samples, with the exception of Crohn's disease (6.7% of samples were positive). Another pattern of LR expression was characterized by positively stained endothelium, while the epithelium was generally negative (45 of 97). The use of two polyclonal antibodies which recognize both the LRP and the LR confirmed brush border and paranuclear expression of the LR, but also showed varying cytoplasmic and apical surface immunoreactivity in MLuC5-negative epithelium, reflecting the distribution of LRP as opposed to the mature receptor. In conclusion, expression of the LR in the brush border and in Paneth cell secretory granules suggests that this molecule might be involved in both secretory and endocytotic functions. The major implication of intestinal epithelial/brush border expression of the LR may be an increased susceptibility to oral infection with prion proteins. PMID:10878555

  6. Enteral nutrients potentiate glucagon-like peptide-2 action and reduce dependence on parenteral nutrition in a rat model of human intestinal failure

    DEFF Research Database (Denmark)

    Brinkman, Adam S; Murali, Sangita G

    2012-01-01

    Glucagon-like peptide-2 (GLP-2) is a nutrient-dependent, proglucagon-derived gut hormone that shows promise for the treatment of short bowel syndrome (SBS). Our objective was to investigate how combination GLP-2 + enteral nutrients (EN) affects intestinal adaption in a rat model that mimics severe human SBS and requires parenteral nutrition (PN). Male Sprague-Dawley rats were assigned to one of five groups and maintained with PN for 18 days: total parenteral nutrition (TPN) alone, TPN + GLP-2 (100 ?g·kg(-1)·day(-1)), PN + EN + GLP-2(7 days), PN + EN + GLP-2(18 days), and a nonsurgical oral reference group. Animals underwent massive distal bowel resection followed by jejunocolic anastomosis and placement of jugular catheters. Starting on postoperative day 4, rats in the EN groups were allowed ad libitum access to EN. Groups provided PN + EN + GLP-2 had their rate of PN reduced by 0.25 ml/day starting on postoperative day 6. Groups provided PN + EN + GLP-2 demonstrated significantly greater body weight gain with similar energy intake and a safe 80% reduction in PN compared with TPN ± GLP-2. Groups provided PN + EN + GLP-2 for 7 or 18 days showed similar body weight gain, residual jejunal length, and digestive capacity. Groups provided PN + EN + GLP-2 showed increased jejunal GLP-2 receptor (GLP-2R), insulin-like growth factor-I (IGF-I), and IGF-binding protein-5 (IGFBP-5) expression. Treatment with TPN + GLP-2 demonstrated increased jejunal expression of epidermal growth factor. Cessation of GLP-2 after 7 days with continued EN sustained the majority of intestinal adaption and significantly increased expression of colonic proglucagon compared with PN + EN + GLP-2 for 18 days, and increased plasma GLP-2 concentrations compared with TPN alone. In summary, EN potentiate the intestinotrophic actions of GLP-2 by improving body weight gain allowing for a safe 80% reduction in PN with increased jejunal expression of GLP-2R, IGF-I, and IGFBP-5 following distal bowel resection in the rat.

  7. ID1 Is a Functional Marker for Intestinal Stem and Progenitor Cells Required for Normal Response to Injury

    Directory of Open Access Journals (Sweden)

    Ning Zhang

    2014-11-01

    Full Text Available LGR5 and BMI1 mark intestinal stem cells in crypt base columnar cells and +4 position cells, respectively, but characterization of functional markers in these cell populations is limited. ID1 maintains the stem cell potential of embryonic, neural, and long-term repopulating hematopoietic stem cells. Here, we show in both human and mouse intestine that ID1 is expressed in cycling columnar cells, +4 position cells, and transit-amplifying cells in the crypt. Lineage tracing revealed ID1+ cells to be self-renewing, multipotent stem/progenitor cells that are responsible for the long-term renewal of the intestinal epithelium. Single ID1+ cells can generate long-lived organoids resembling mature intestinal epithelium. Complete knockout of Id1 or selective deletion of Id1 in intestinal epithelium or in LGR5+ stem cells sensitizes mice to chemical-induced colon injury. These experiments identify ID1 as a marker for intestinal stem/progenitor cells and demonstrate a role for ID1 in maintaining the potential for repair in response to colonic injury.

  8. Regulation of taurine transport by Escherichia coli heat-stable enterotoxin and guanylin in human intestinal cell lines.

    OpenAIRE

    Brandsch, M; Ramamoorthy, S; Marczin, N; Catravas, J. D.; Leibach, J W; Ganapathy, V.; Leibach, F H

    1995-01-01

    The human colon carcinoma cell lines Caco-2 and HT-29 take up taurine actively. Treatment of Caco-2 cells with Escherichia coli heat-stable enterotoxin (STa) or with guanylin inhibited taurine uptake by approximately 40%. In contrast, neither STa nor guanylin changed the uptake of taurine in HT-29 cells. The inhibition in Caco-2 cells was associated with a decrease in the maximal velocity as well as in the affinity of the transporter. STa caused a 21-fold increase in guanosine 3',5'-cyclic mo...

  9. Neighboring Group Participation in the Transition State of Human Purine Nucleoside Phosphorylase

    Energy Technology Data Exchange (ETDEWEB)

    Murkin,A.; Birck, M.; Rinaldo-Matthis, A.; Shi, W.; Taylor, E.; Almo, S.; Schramm, V.

    2007-01-01

    The X-ray crystal structures of human purine nucleoside phosphorylase (PNP) with bound inosine or transition-state analogues show His{sup 257} within hydrogen bonding distance of the 5'-hydroxyl. The mutants His257Phe, His257Gly, and His257Asp exhibited greatly decreased affinity for Immucillin-H (ImmH), binding this mimic of an early transition state as much as 370-fold (K{sub m}/K{sub i}) less tightly than native PNP. In contrast, these mutants bound DADMe-ImmH, a mimic of a late transition state, nearly as well as the native enzyme. These results indicate that His{sup 257} serves an important role in the early stages of transition-state formation. Whereas mutation of His{sup 257} resulted in little variation in the PNP{center_dot}DADMe-ImmH{center_dot}SO{sub 4} structures, His257Phe{center_dot}ImmH{center_dot}PO{sub 4} showed distortion at the 5'-hydroxyl, indicating the importance of H-bonding in positioning this group during progression to the transition state. Binding isotope effect (BIE) and kinetic isotope effect (KIE) studies of the remote 5'-{sup 3}H for the arsenolysis of inosine with native PNP revealed a BIE of 1.5% and an unexpectedly large intrinsic KIE of 4.6%. This result is interpreted as a moderate electronic distortion toward the transition state in the Michaelis complex with continued development of a similar distortion at the transition state. The mutants His257Phe, His257Gly, and His257Asp altered the 5'-{sup 3}H intrinsic KIE to -3, -14, and 7%, respectively, while the BIEs contributed 2, 2, and -2%, respectively. These surprising results establish that forces in the Michaelis complex, reported by the BIEs, can be reversed or enhanced at the transition state.

  10. Giardia induces proliferation and interferon ? production by intestinal lymphocytes

    OpenAIRE

    Ebert, E

    1999-01-01

    BACKGROUND—Murine intraepithelial lymphocytes kill Giardia lambia; responses of human intestinal lymphocytes to this parasite are unknown. ?AIMS—To examine giardia induced proliferation, interferon ? production, migration, and cytotoxicity by lymphocytes from the human intestine and peripheral blood. ?METHODS—Giardia were added to intraepithelial lymphocytes, lamina propria lymphocytes, and peripheral blood lymphocytes, obtained from jejunal mucosa and blood of otherwise ...

  11. Update on Transanal NOTES for Rectal Cancer: Transitioning to Human Trials

    Science.gov (United States)

    Telem, Dana A.; Berger, David L.; Bordeianou, Liliana G.; Rattner, David W.; Sylla, Patricia

    2012-01-01

    The feasibility of natural orifice translumenal endoscopic surgery (NOTES) resection for rectal cancer has been demonstrated in both survival swine and fresh human cadaveric models. In preparation for transitioning to human application, our group has performed transanal NOTES rectal resection in a large series of human cadavers. This experience both solidified the feasibility of resection and allowed optimization of technique prior to clinical application. Improvement in specimen length and operative time was demonstrated with increased experience and newer platforms. This extensive laboratory experience has paved the way for successful clinical translation resulting in an ongoing clinical trial. To date, based on published reports, 4 human subjects have undergone successful hybrid transanal NOTES resection of rectal cancer. While promising, instrument limitations continue to hinder a pure transanal approach. Careful patient selection and continued development of new endoscopic and flexible-tip instruments are imperative prior to pure NOTES clinical application. PMID:22685646

  12. 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

  13. 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

  14. Select Listeria monocytogenes Subtypes Commonly Found in Foods Carry Distinct Nonsense Mutations in inlA, Leading to Expression of Truncated and Secreted Internalin A, and Are Associated with a Reduced Invasion Phenotype for Human Intestinal Epithelial Cells

    OpenAIRE

    Nightingale, K. K.; Windham, K.; Martin, K. E.; Yeung, M.; Wiedmann, M.

    2005-01-01

    The surface protein internalin A (InlA) contributes to the invasion of human intestinal epithelial cells by Listeria monocytogenes. Screening of L. monocytogenes strains isolated from human clinical cases (n = 46), foods (n = 118), and healthy animals (n = 58) in the United States revealed mutations in inlA leading to premature stop codons (PMSCs) in L. monocytogenes ribotypes DUP-1052A and DUP-16635A (PMSC mutation type 1), DUP-1025A and DUP-1031A (PMSC mutation type 2), and DUP-1046B and DU...

  15. Vasoactive intestinal peptide (VIP) differentially affects inflammatory immune responses in human monocytes infected with viable Salmonella or stimulated with LPS.

    Science.gov (United States)

    Askar, Basim; Ibrahim, Hiba; Barrow, Paul; Foster, Neil

    2015-09-01

    We compared the effect of VIP on human blood monocytes infected with Salmonella typhimurium 4/74 or stimulated with LPS. VIP (10(-7)M) increased monocyte viability by 24% and 9% when cultured for 24h with 4/74 or Salmonella LPS (100ng/ml), respectively. Significantly increased (P<0.05) numbers of 4/74 were also recovered from monocytes co-cultured with VIP after 6h post-infection (pi) and this remained high after 24h pi. Both 4/74 and LPS increased (P<0.05) the concentration of TNF-?, IL-1? and IL-6 measured in monocyte supernatants. However, LPS induced this effect more rapidly while, with the exception of IL-6, 4/74 induced higher concentrations (P<0.05). VIP significantly decreased (P<0.05) TNF-? and IL-1? production by 4/74-infected monocytes after 6 pi, but only after 24h in LPS-cultured monocytes. This trend was reversed for IL-6 production. However, TNF-? and IL-1? production by 4/74-infected monocytes, cultured with VIP, still remained higher (P<0.05) than concentrations measured in supernatants cultured only with LPS. VIP also increased (P<0.05) production of anti-inflammatory IL-10 in both 4/74 and LPS cultures after 24h. We also show a differential effect of VIP on the expression of TNF? and IL-6 receptors, since VIP was only able to decreased expression in LPS-stimulated monocytes but not in 4/74-infected monocytes. In conclusion, we show a differential effect of VIP on human monocytes infected with virulent Salmonella or stimulated with LPS. Our study suggests that the use of VIP in bacteraemia and/or sepsis may be limited to an adjunctive therapy to antibiotic treatment. PMID:26206287

  16. Remembering the bad old days: Human rights, economic conditions, and democratic performance in transitional regimes

    OpenAIRE

    Klingemann, Hans-Dieter; Hofferbert, Richard I.

    1998-01-01

    Using the natural laboratory of 18 post-communist Central and Eastern European countries, this article presents a basic model for democratic transition, specifically testing two alternative explanations for the degree of citizen satisfaction with the performance of their fledgling democracies: 1) virtues of omission, which include bad actions from which the state refrains, namely violations of individual human rights, and 2) virtues of commission, which include positive state actions, in part...

  17. Human origins and the transition from promiscuity to pair-bonding

    OpenAIRE

    Gavrilets, Sergey

    2012-01-01

    A crucial step in recent theories of human origins is the emergence of strong pair-bonding between males and females accompanied by a dramatic reduction in the male-to-male conflict over mating and an increased investment in offspring. How such a transition from promiscuity to pair-bonding could be achieved is puzzling. Many species would, indeed, be much better off evolutionarily if the effort spent on male competition over mating was redirected to increasing female fertility or survivorship...

  18. Space Competition and Time Delays in Human Range Expansions. Application to the Neolithic Transition

    OpenAIRE

    Isern Sardó, Neus; Fort, Joaquim; Vander Linden, Marc

    2012-01-01

    Space competition effects are well-known in many microbiological and ecological systems. Here we analyze such an effect in human populations. The Neolithic transition (change from foraging to farming) was mainly the outcome of a demographic process that spread gradually throughout Europe from the Near East. In Northern Europe, archaeological data show a slowdown on the Neolithic rate of spread that can be related to a high indigenous (Mesolithic) population density hindering the advance as a ...

  19. All in transition - Human resource management and labour relations in the Chinese industrial sector

    OpenAIRE

    yu, Nan

    2012-01-01

    This discussion paper is a literature study reviewing the development of human resource management in China, with a particular focus (where possible) on the automobile industry. It presents the Chinese context for HRM discussing the normative debate about the adaptation of Western management methods and the heritage of Chinese philosophy and values, and it describes the economic, cultural, and transition-specific factors which influence HRM in China. In more detail, the paper deals with work ...

  20. The causes of human rights abuses in the countries in transition summary

    Directory of Open Access Journals (Sweden)

    Šijakovi? 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.

  1. 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...

  2. TGF-?1 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-?1 could induce epithelial mesenchymal transition (EMT) in the human alveolar...

  3. Biomodelo para la evaluación de cepas atenuadas como candidatos vacunales contra el cólera humano. I: Estudio de la virulencia, capacidad de colonización y adherencia a la mucosa intestinal / Biomodel for evaluating attenuated Vibrio cholerae strains as human cholera vaccine candidates. I: Virulence, colonizing capacity and adherence to the intestinal mucosa

    Scientific Electronic Library Online (English)

    Reynaldo, Oliva; Hilda, García; Juan F, Infante; Luis, García; José L, Pérez; Bárbara, Cedré; Tania, Balmaceda; Arturo, Talavera; Gemma, Año.

    2008-04-01

    Full Text Available El cólera continúa siendo en muchos países un problema para la salud humana, manteniéndose como una enfermedad epidémica o endémica que afecta tanto a niños como adultos y causa la muerte en casos no tratados. Una vacuna viva oral contra esta enfermedad puede ser la solución. En el presente trabajo [...] se seleccionó y aplicó un biomodelo para la evaluación de cepas atenuadas genéticamente de Vibrio cholerae como candidatas vacunales contra el cólera. La virulencia, capacidad de colonización y adherencia a la mucosa intestinal de las cepas fueron evaluadas mediante el uso de ratones neonatos de 2 a 4 días de nacidos de la línea Balb/c, con un peso entre 1,5-2 g. Los resultados obtenidos con este biomodelo demostraron que las cepas atenuadas genéticamente son no virulentas, colonizan y se adhieren a la mucosa intestinal. Se concluye que el biomodelo utilizado permite la evaluación y selección de cepas candidatas para vacunas vivas orales contra el cólera. Abstract in english Cholera is still a human health problem in many countries. It is an epidemic or endemic disease affecting both children and adults that causes death of untreated cases. A live oral vaccine could be the solution against this disease. In the present study a biomodel was selected and applied for the ev [...] aluation of genetically attenuated Vibrio cholerae strains as vaccine candidates. The virulence, colonizing capacity and adherence to the intestinal mucosa of the strains were evaluated using 2-4 day-old neonatal Balb/c mice, weighing from 1.5-2 g. The results obtained with this biomodel showed that genetically attenuated strains are not virulent, colonize and adhere to the intestinal mucosa. The conclusion was that the biomodel used allows the evaluation and selection of candidate strains for live oral cholera vaccines.

  4. Dietary whole-grain wheat increases intestinal levels of bifidobacteria in humans and bifidobacterial abundance is negatively correlated with the effect of fecal water on trans-epithelial resistance in vitro.

    DEFF Research Database (Denmark)

    Christensen, Ellen Gerd; Licht, Tine Rask

    Consumption of whole grain products are considered to have beneficial effects on human health including decreased risk of cardiovascular disease. However, effects on gut microbial composition have only been studied limitedly. We used quantitative PCR to determine changes in the gut bacterial composition in post-menopausal women following a 12-week energy restricted intervention with whole-grain wheat (WW, n=37) or refined wheat (RW, n=33). The WW intervention significantly increased the relative abundance of Bifidobacterium. Caco-2 cells were exposed to fecal water to determine effects of the bacterial community metabolites on the trans-epithelial resistance (TER). Fecal water increased TER independent of diet, indicating that commensal bacteria provide metabolites facilitating an increase in intestinal integrity. TER was unexpectedly found to be negatively correlated to the relative abundance of Bifidobacterium. The present study suggests that increase of specific bacterial groups, which are considered beneficial, may in some circumstances increase the permeability of the intestinal wall.

  5. Estudio de un cálculo intestinal en un paciente con adenocarcinoma de colón: ¿es similar a los cálculos renales? / Study of a intestinal enteroliths in human patient with colon adenocarcinome: Is it similar to renal calculi?

    Scientific Electronic Library Online (English)

    M.L., Traba Villameytide; J.A., Orts Costa; M., Morell.

    2006-02-01

    Full Text Available Este trabajo muestra el estudio realizado a enterolitos intestinales procedentes de un paciente de 91 años que padecía una enterolitiasis múltiple confirmada por estudio radiológico abdominal y TAC, mostrando cálculos en el tracto intestinal, renal y biliar. Además esta enterolitiasis estaba asociad [...] a a un adenocarcinoma de colon. Los enterolitos analizados proceden de una intervención quirúrgica en la que se practicó una hemicolectomía derecha. Los enterolitos se sometieron a un análisis por espectrometría de infrarrojos (IR) observándose un espectro de carbonato apatita no-estequiométrica, tipo whitloquita, posiblemente con materia orgánica. Con el fin de estudiar el posible contenido de diversos elementos químicos, se practicó un análisis por espectrometría de emisión atómica encontrándose, fundamentalmente, los iones Ca, Mg, K, Na y K (del orden de mg/100 mg de cálculo) y Zn, Ba, Mn, Fe, Cu, Si, Ti y Br en menor proporción (del orden de µg/100 mg de cálculo). Dada la morfología del cálculo y su espectro de IR (carbonato apatita no estequiométrica) se determinó la posible presencia de porfirinas por cromatografía líquida de alta resolución (HPLC) encontrándose, fundamentalmente, coproporfirina (µg/g de cálculo) y en menor proporción uroporfirina, protoporfirina y hepta-carboxi porfirina. El estudio se completó con el análisis de los enterolitos mediante microscopía electrónica de barrido y EDX. El análisis por difracción de rayos X detectó la presencia de CaP4O11. Los resultados obtenidos de los diferentes análisis muestran que la composición de los enterolitos es similar a la de los cálculos renales, aunque su morfología difiera de estos. Abstract in english This work shows the study performance to intestinal enterolithis from a 91 year old patient with multiple enterolithiasis confirmed by abdominal X-ray and TAC analyses showing the presence of intestinal, renal and bile stones. This enterolithis is associated with colon adenocarcinoma. The enterolith [...] s were obtained by hemicolectomia and were analyzed by infrared spectroscopy (IR), giving nonstoichiometry carbonate apatite whitloquite-like with, possibly, organic material. By atomic emission spectroscopy we found Ca, Mg, K, Na y K (mg/100 mg of calculi) and Zn, Ba, Mn, Fe, Cu, Si, Ti and Br in minor proportion (µg/100 mg of calculi). Because of calculi morphology and the IR spectra (non-stoichiometry carbonate apatite) we carried out analysis by high performance liquid chromatography (HPLC) and found coproporphyrin (about µg/g of calculi) and uroporphyrin, protoporphyrin and heptacarboxy-porphyrin in minor extent. Calculi were also studied by scanning electronic microscopy and EDX and X-ray diffraction giving crystals of CaP4O11. All these results show that intestinal enteroliths composition are similar to renal calculi although its morphology differs from renal calculi.

  6. Loss of HLTF function promotes intestinal carcinogenesis

    Directory of Open Access Journals (Sweden)

    Sandhu Sumit

    2012-03-01

    Full Text Available Abstract Background HLTF (Helicase-like Transcription Factor is a DNA helicase protein homologous to the SWI/SNF family involved in the maintenance of genomic stability and the regulation of gene expression. HLTF has also been found to be frequently inactivated by promoter hypermethylation in human colon cancers. Whether this epigenetic event is required for intestinal carcinogenesis is unknown. Results To address the role of loss of HLTF function in the development of intestinal cancer, we generated Hltf deficient mice. These mutant mice showed normal development, and did not develop intestinal tumors, indicating that loss of Hltf function by itself is insufficient to induce the formation of intestinal cancer. On the Apcmin/+ mutant background, Hltf- deficiency was found to significantly increase the formation of intestinal adenocarcinoma and colon cancers. Cytogenetic analysis of colon tumor cells from Hltf -/-/Apcmin/+ mice revealed a high incidence of gross chromosomal instabilities, including Robertsonian fusions, chromosomal fragments and aneuploidy. None of these genetic alterations were observed in the colon tumor cells derived from Apcmin/+ mice. Increased tumor growth and genomic instability was also demonstrated in HCT116 human colon cancer cells in which HLTF expression was significantly decreased. Conclusion Taken together, our results demonstrate that loss of HLTF function promotes the malignant transformation of intestinal or colonic adenomas to carcinomas by inducing genomic instability. Our findings highly suggest that epigenetic inactivation of HLTF, as found in most human colon cancers, could play an important role in the progression of colon tumors to malignant cancer.

  7. Multiplex real-time PCR monitoring of intestinal helminths in humans reveals widespread polyparasitism in Northern Samar, the Philippines.

    Science.gov (United States)

    Gordon, Catherine A; McManus, Donald P; Acosta, Luz P; Olveda, Remigio M; Williams, Gail M; Ross, Allen G; Gray, Darren J; Gobert, Geoffrey N

    2015-06-01

    The global socioeconomic importance of helminth parasitic disease is underpinned by the considerable clinical impact on millions of people. While helminth polyparasitism is considered common in the Philippines, little has been done to survey its extent in endemic communities. High morphological similarity of eggs between related species complicates conventional microscopic diagnostic methods which are known to lack sensitivity, particularly in low intensity infections. Multiplex quantitative PCR diagnostic methods can provide rapid, simultaneous identification of multiple helminth species from a single stool sample. We describe a multiplex assay for the differentiation of Ascaris lumbricoides, Necator americanus, Ancylostoma, Taenia saginata and Taenia solium, building on our previously published findings for Schistosoma japonicum. Of 545 human faecal samples examined, 46.6% were positive for at least three different parasite species. High prevalences of S. japonicum (90.64%), A. lumbricoides (58.17%), T. saginata (42.57%) and A. duodenale (48.07%) were recorded. Neither T. solium nor N. americanus were found to be present. The utility of molecular diagnostic methods for monitoring helminth parasite prevalence provides new information on the extent of polyparasitism in the Philippines municipality of Palapag. These methods and findings have potential global implications for the monitoring of neglected tropical diseases and control measures. PMID:25858090

  8. Extraction of Antioxidant Components from Bidens pilosa Flowers and Their Uptake by Human Intestinal Caco-2 Cells

    Directory of Open Access Journals (Sweden)

    Charng-Cherng Chyau

    2013-01-01

    Full Text Available Bidens pilosa L. var. radiata (BPR, Asteraceae is a commonly used folk medicine for treating various disorders such as diabetes, inflammation and hypertension. Recent studies to determine its chemical composition have revealed three di-O-caffeoylquinic acids (DiCQAs and three polyacetylene glucosides (PGAs to be among the major bioactive markers. To obtain the major compounds of these two chemical classes, the ethyl acetate fraction (EM obtained using liquid-liquid partition from the methanol extract resulted in a fraction with the highest total phenolic and total flavonoid contents and antioxidant activities in radical scavenging and ferric reducing power assays. To assess the bioavailability of EM, we examined the in vitro uptake using the Caco-2 human colonic cell line. The apparent permeability coefficient (Papp for each of the compounds within PGAs measured in both apical (AP to basolateral (BL and BL to AP was found to preferentially appear BL to AP direction, indicated that a basolateral to apical efflux system was detected in the study. DiCQAs had a lower efflux ratio than those from PGAs (2.32–3.67 vs. 6.03–78.36. Thus, it strongly implies that most of the DiCQAs are better absorbed than the PGAs.

  9. Glutamine and intestinal barrier function.

    Science.gov (United States)

    Wang, Bin; Wu, Guoyao; Zhou, Zhigang; Dai, Zhaolai; Sun, Yuli; Ji, Yun; Li, Wei; Wang, Weiwei; Liu, Chuang; Han, Feng; Wu, Zhenlong

    2015-10-01

    The intestinal barrier integrity is essential for the absorption of nutrients and health in humans and animals. Dysfunction of the mucosal barrier is associated with increased gut permeability and development of multiple gastrointestinal diseases. Recent studies highlighted a critical role for glutamine, which had been traditionally considered as a nutritionally non-essential amino acid, in activating the mammalian target of rapamycin cell signaling in enterocytes. In addition, glutamine has been reported to enhance intestinal and whole-body growth, to promote enterocyte proliferation and survival, and to regulate intestinal barrier function in injury, infection, weaning stress, and other catabolic conditions. Mechanistically, these effects were mediated by maintaining the intracellular redox status and regulating expression of genes associated with various signaling pathways. Furthermore, glutamine stimulates growth of the small intestinal mucosa in young animals and also enhances ion transport by the gut in neonates and adults. Growing evidence supports the notion that glutamine is a nutritionally essential amino acid for neonates and a conditionally essential amino acid for adults. Thus, as a functional amino acid with multiple key physiological roles, glutamine holds great promise in protecting the gut from atrophy and injury under various stress conditions in mammals and other animals. PMID:24965526

  10. Nano-enhanced food contact materials and the in vitro toxicity to human intestinal cells of nano-ZnO at low dose

    Science.gov (United States)

    Claonadh, Niall Ó.; Casey, Alan; Lyons, Sean; Higginbotham, Clement; Gupta Mukherjee, Sanchali; Chambers, Gordon

    2011-07-01

    Nano Zinc Oxide (nZnO) has been shown to display antimicrobial effects which have lead to its application in a number of areas such as antimicrobial surface coatings, anti bacterial wound dressings and more recently in polymer composite systems for use in food contact materials. Concerns have been raised due to the incorporation of nanoparticles in food packaging stemming from the possibility of repeated low dose direct exposure, through ingestion, primarily due to degradation and nanoparticle leaching from the polymer composite. To address these concerns, composites consisting of nZnO and polyethylene were formed using twin screw extrusion to mimic commercial methods of food contact material production. A leaching study was performed using Atomic Absorption Spectroscopy in order to determine the concentration of nZnO leached from the composite. Composite stability studies were performed and a leached nZnO concentration was evaluated. This concentration range was then utilised in a series of tests aimed at determining the toxicity response associated with nZnO when exposed to an intestinal model. In this study two human colorectal carcinoma cell lines, HT29 (ATCC No: HTB-38) and SW480 (ATTC No: CCL-228), were employed as a model to represent areas exposed by ingestion. These lines were exposed to a concentration range of nZnO which incorporated the concentration leached from the composites. The cytotoxic effects of nZnO were evaluated using four cytotoxic endpoints namely the Neutral Red, Alamar Blue, Coomassie Blue and MTT assays. The results of these studies are presented and their implications for the use on nano ZnO in direct food contact surfaces will be discussed.

  11. Novel GM1 ganglioside-like peptide mimics prevent the association of cholera toxin to human intestinal epithelial cells in vitro.

    Science.gov (United States)

    Yu, Robert K; Usuki, Seigo; Itokazu, Yutaka; Wu, Han-Chung

    2016-01-01

    Cholera is an acute diarrheal disease caused by infection in the gastrointestinal tract by the gram-negative bacterium, Vibrio cholerae, and is a serious public health threat worldwide. There has not been any effective treatment for this infectious disease. Cholera toxin (CT), which is secreted by V. cholerae, can enter host cells by binding to GM1, a monosialoganglioside widely distributed on the plasma membrane surface of various animal epithelial cells. The present study was undertaken to generate peptides that are conformationally similar to the carbohydrate epitope of GM1 for use in the treatment of cholera and related bacterial infection. For this purpose, we used cholera toxin B (CTB) subunit to select CTB-binding peptides that structurally mimic GM1 from a dodecamer phage-display library. Six GM1-replica peptides were selected by biopanning based on CTB recognition. Five of the six peptides showed inhibitory activity for GM1 binding to CTB. To test the potential of employing the peptide mimics for intervening with the bacterial infection, those peptides were examined for their binding capacity, functional inhibitory activity and in vitro effects using a human intestinal epithelial cell line, Caco-2 cells. One of the peptides, P3 (IPQVWRDWFKLP), was most effective in inhibiting cellular uptake of CTB and suppressing CT-stimulated cyclic adenosine monophosphate production in the cells. Our results thus provide convincing evidence that GM1-replica peptides could serve as novel agents to block CTB binding on epithelial cells and prevent the ensuing physiological effects of CT. PMID:26405107

  12. Receptor-dependent inhibition by vasoactive intestinal peptide of phorbol ester-enhanced IgM secretion by a human B cell line

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, P.P.J.; Sreedharan, S.P.; Robichon, A.; Gronroos, E.; Goetzl, E.J. (Univ. of California, San Francisco (United States))

    1991-03-15

    Vasoactive intestinal peptide (VIP) is a 28 amino acid neuromediator, which is released into tissues during inflammatory reactions. To examine the mechanisms of VIP effects on lymphocyte functions, replicate 5 ml suspensions of 2{times}10{sup 6} cultured SKW 6.4 human B lymphocytes per ml of RPMI 1640 medium with 10% FCS were incubated with phorbol myristate acetate (PMA) at 37C. After 2 hr of exposure of SKW 6.4 cells to 100 ng/ml of PMA, the specific high-affinity binding of ({sup 125}I)VIP was decreased by 43{plus minus}7.8% and remained suppressed for up to 8 hr. Continued incubation of SKW 6.4 cells with PMA for 7 days increased the specific high-affinity binding of ({sup 125}I)VIP by 55{plus minus}16%. The secretion of IgM by SKW 6.4 cells, as quantified in an ELISA assay, was enhanced a mean of 3.6 fold by 100 ng/ml of PMA after 7 days. The concurrent addition of 10{sup {minus}12}M-10{sup {minus}6}M VIP to the SKW 6.4 cells inhibited the PMA-enhanced secretion of IgM in an concentration-dependent manner with maximal mean inhibition ({plus minus}S.D.) of 40{plus minus}2% by 10{sup {minus}10}M VIP at 7 days, without an effect on unstimulated levels of IgM. The potent inhibition of immunoglobulin production by VIP has apparent specificity for stimulated B cells with an increased number of VIP receptors.

  13. Two tyrosine residues in the first transmembrane helix of the human vasoactive intestinal peptide receptors play a role in supporting the active conformation

    Science.gov (United States)

    Perret, J; Vertongen, P; Solano, R M; Langer, I; Cnudde, J; Robberecht, P; Waelbroeck, M

    2002-01-01

    We investigated the human vasoactive intestinal polypeptide (VIP) receptors VPAC1 and VPAC2 mutated at conserved tyrosine residues in the first transmembrane helix (VPAC1 receptor Y146A and Y150A and VPAC2 receptor Y130A and Y134A). [125I]-Acetyl-His1 [D-Phe2, K15, R16, L27]-VIP (1–7)/GRF (8–27) (referred to as [125I]-VPAC1 antagonist) labelled VPAC1 binding sites, that displayed high and low affinities for VIP (IC50 values and per cent of high affinity binding sites: wild-type, 1 nM (57±9%) and 160 nM; Y146A, 30 nM (40±8%) and 800 nM; Y150A, 4 nM (27±8%) and 300 nM). [R16]-VIP behaved as a ‘super agonist' at both mutated VPAC1 receptors and the efficacies of VIP analogues modified in positions 1, 3 and 6 were significantly decreased. VIP was less potent at the Y130A and Y134A mutated VPAC2 receptors (EC50 200 and 400 nM, respectively) than at the wild-type VPAC2 receptor (EC50 7 nM). Furthermore, [hexanoyl-His1]-VIP behaved as a ‘super agonist' at the two mutated VPAC2 receptors, and VIP analogues modified in positions 1, 3 and 6 were less potent and efficient at the mutated than at wild-type VPAC2 receptors. However, the Y130A and Y134A mutants could not be studied in binding assays Our results suggest that the conserved tyrosine residues do not interact directly with the VIP His1, Asp3 or Phe6 residues (that are necessary for receptor activation), but stabilize the correct active receptor conformation. PMID:12145104

  14. Nano-enhanced food contact materials and the in vitro toxicity to human intestinal cells of nano-ZnO at low dose

    Energy Technology Data Exchange (ETDEWEB)

    Claonadh, Niall O; Casey, Alan; Mukherjee, Sanchali Gupta; Chambers, Gordon [Nanolab Research Centre, Focas Institute, Dublin Institute of Technology, Dublin (Ireland); Lyons, Sean; Higginbotham, Clement, E-mail: Niall.OClaonadh@DIT.ie, E-mail: Alan.Casey@DIT.ie [Materials Research Institute, Athlone Institute of Technology, Westmeath (Ireland)

    2011-07-06

    Nano Zinc Oxide (nZnO) has been shown to display antimicrobial effects which have lead to its application in a number of areas such as antimicrobial surface coatings, anti bacterial wound dressings and more recently in polymer composite systems for use in food contact materials. Concerns have been raised due to the incorporation of nanoparticles in food packaging stemming from the possibility of repeated low dose direct exposure, through ingestion, primarily due to degradation and nanoparticle leaching from the polymer composite. To address these concerns, composites consisting of nZnO and polyethylene were formed using twin screw extrusion to mimic commercial methods of food contact material production. A leaching study was performed using Atomic Absorption Spectroscopy in order to determine the concentration of nZnO leached from the composite. Composite stability studies were performed and a leached nZnO concentration was evaluated. This concentration range was then utilised in a series of tests aimed at determining the toxicity response associated with nZnO when exposed to an intestinal model. In this study two human colorectal carcinoma cell lines, HT29 (ATCC No: HTB-38) and SW480 (ATTC No: CCL-228), were employed as a model to represent areas exposed by ingestion. These lines were exposed to a concentration range of nZnO which incorporated the concentration leached from the composites. The cytotoxic effects of nZnO were evaluated using four cytotoxic endpoints namely the Neutral Red, Alamar Blue, Coomassie Blue and MTT assays. The results of these studies are presented and their implications for the use on nano ZnO in direct food contact surfaces will be discussed.

  15. Nano-enhanced food contact materials and the in vitro toxicity to human intestinal cells of nano-ZnO at low dose

    International Nuclear Information System (INIS)

    Nano Zinc Oxide (nZnO) has been shown to display antimicrobial effects which have lead to its application in a number of areas such as antimicrobial surface coatings, anti bacterial wound dressings and more recently in polymer composite systems for use in food contact materials. Concerns have been raised due to the incorporation of nanoparticles in food packaging stemming from the possibility of repeated low dose direct exposure, through ingestion, primarily due to degradation and nanoparticle leaching from the polymer composite. To address these concerns, composites consisting of nZnO and polyethylene were formed using twin screw extrusion to mimic commercial methods of food contact material production. A leaching study was performed using Atomic Absorption Spectroscopy in order to determine the concentration of nZnO leached from the composite. Composite stability studies were performed and a leached nZnO concentration was evaluated. This concentration range was then utilised in a series of tests aimed at determining the toxicity response associated with nZnO when exposed to an intestinal model. In this study two human colorectal carcinoma cell lines, HT29 (ATCC No: HTB-38) and SW480 (ATTC No: CCL-228), were employed as a model to represent areas exposed by ingestion. These lines were exposed to a concentration range of nZnO which incorporated the concentration leached from the composites. The cytotoxic effects of nZnO were evaluated using four cytotoxic endpoints namely the Neutral Red, Alamar Blue, Coomassie Blue and MTT assays. The results of these studies are presented and their implications for the use on nano ZnO in direct food contact surfaces will be discussed.

  16. Age-dependent transition from cell-level to population-level control in murine intestinal homeostasis revealed by coalescence analysis.

    Science.gov (United States)

    Hu, Zheng; Fu, Yun-Xin; Greenberg, Anthony J; Wu, Chung-I; Zhai, Weiwei

    2013-01-01

    In multi-cellular organisms, tissue homeostasis is maintained by an exquisite balance between stem cell proliferation and differentiation. This equilibrium can be achieved either at the single cell level (a.k.a. cell asymmetry), where stem cells follow strict asymmetric divisions, or the population level (a.k.a. population asymmetry), where gains and losses in individual stem cell lineages are randomly distributed, but the net effect is homeostasis. In the mature mouse intestinal crypt, previous evidence has revealed a pattern of population asymmetry through predominantly symmetric divisions of stem cells. In this work, using population genetic theory together with previously published crypt single-cell data obtained at different mouse life stages, we reveal a strikingly dynamic pattern of stem cell homeostatic control. We find that single-cell asymmetric divisions are gradually replaced by stochastic population-level asymmetry as the mouse matures to adulthood. This lifelong process has important developmental and evolutionary implications in understanding how adult tissues maintain their homeostasis integrating the trade-off between intrinsic and extrinsic regulations. PMID:23468655

  17. INTESTINAL PARASITIC PREVALENCE IN HUMAN IMMUNO-DEFICIENT VIRUS (HIV INFECTED PATIENTS WITH AND WITHOUT DIARRHOEA AND ITS ASSOCIATION WITH CD4 T CELLS COUNTS

    Directory of Open Access Journals (Sweden)

    Namita A. Raytekar

    2012-12-01

    Full Text Available Background & objectives: Intestinal parasitic infections are major cause of diarrhoea in HIV infected individuals. The present study was undertaken to detect intestinal parasites in HIV infected patients with and without diarrhoea and to determine association between enteric parasites and CD4 T cell count. Methods: The study was carried out at Department of Microbiology, Rural Medical College, Loni, India, between September 2010 and August 2012 among consecutively enrolled 127 HIV infected patients presenting with and without diarrhoea. Stool samples were collected and examined for enteric parasites by microscopy and special staining methods. CD4 cell counts records of patients were taken from Antiretroviral Treatment Centre (ARTC of the hospital. Results: Out of total 127 cases intestinal parasites were detected in 27 cases. The incidence of intestinal parasitic infection was 21.25%. Of 27 cases where parasites detected in total, Entamoeba histolytica 13 (48.14 % was found to be most prevalent parasite followed by Cryptosporidium parvum 9 (33.33% followed by Giardia lamblia 3 (11.11 % followed by Taenia spp. 2 (7.40%. In HIV infected patients with CD4 count < 200 cells/?l, C. parvum was the most commonly observed (88.88% parasite. Whereas the proportion of intestinal parasites in patients with CD4 count 200 – 499 cells/?l was significantly higher as compared with other two groups of patients with CD4 count < 200 and ? 500 cells/?l

  18. Gastrointestinal adaptation to enhanced small intestinal lipid exposure.

    OpenAIRE

    Brown, N.J.; Rumsey, R. D.; Read, N.W.

    1994-01-01

    Studies were performed on 20 male adult rats to investigate the effects of chronic intermittent infusion of lipid and physiological emulsifier into the distal small intestine on stomach to caecum transit time (SCTT) of the head of a test meal. SCTT was measured using environmental hydrogen analysis. Ileal lipid infusion normally delays gastric emptying and small intestinal transit (p < 0.001), but chronic intermittent infusion of lipid, given three times a week gradually reduced the delay in ...

  19. Drug Transporters in the Intestine

    DEFF Research Database (Denmark)

    Steffansen, Bente

    2015-01-01

    The enterocyte monolayer in the intestinal membrane impacts on the bioavailability (BA) of many orally administered active pharmaceutical ingredients (APIs). The monolayer expresses a multitude of membrane transporters belonging to the solute carrier (SLC) and ATP-binding cassette (ABC) families that may impact drug absorption. Thus absorptive transporters may facilitate BA of APIs that are substrates/victims for the transporters and have permeability-limited absorption, i.e. those that are classified in the biopharmaceutics classification system (BCS) Class 3 and 4. On the other hand, exsorptive transporters may restrict BA of APIs that are victims for these efflux transporters, especially those APIs classified to have solubility-limited absorption, i.e. compounds in BCS Class 2 and 4. The aim of the present Chapter is to review drug transporters (DTs) present within the intestine and to discuss and exemplify their roles in drug absorption/exsorption and in drug-drug interactions (DDIs). Although focus in the present Chapter is on DTs that are mentioned in American and European regulatory guidances, the intestinal transporters for nutrients and endogens (endogenous compounds) are also briefly considered, since some nutrient transporters (NTs) are also DTs. An example of a NT, which is also a DT is the peptide transporter 1 (PEPT1)/ SLC15A1. Thus absorption of di/tri-peptides rely on this transporter as do several APIs such as cefadroxile. Many APIs are substrates and/or inhibitors to the intestinal exsorptive DTs. An example is the API sulfasalazine, which is a substrate for breast cancer resistance protein (BCRP)/ABCG2. Sulfasalazine absorption is found to increase when human volunteers are administered high concentrations together with the inhibitor and spice curcumin. In conclusion, to date 51 intestinal transporters have been identified of which 14 are known to play a role in drug BA.

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

    Directory of Open Access Journals (Sweden)

    Eugenia Elefterios Venizelos Bezirtzoglou

    2012-09-01

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

  1. Intestinal perfusion in the study of intestinal absorption

    International Nuclear Information System (INIS)

    Several techniques for studying absorption by means of intestinal perfusion have been developed. While the principle is simple, the practice is complicated by absorption of the solvent and by excretion of fluid into the lumen. To improve reliability a ''marker'' is incorporated into the system; it should behave as nearly as possible like the nutrient of interest, except that it should be unabsorbable. A great many markers, including several labelled with radionuclides, have been developed for use with numerous nutrients, and perfusion methods using double or triple tubes or occlusive balloons have been tested. The perfusion technique is too complicated for routine diagnostic use, but it offers at present the only possibility of studying the function of defined sections of the small intestine in the intact human. (author)

  2. Interactions Between the Intestinal Microbiome and Liver Diseases

    OpenAIRE

    Schnabl, Bernd; David A Brenner

    2014-01-01

    The human intestine harbors a diverse community of microbes that promote metabolism and digestion in their symbiotic relationship with the host. Disturbance of its homeostasis can result in disease. We review factors that disrupt intestinal homeostasis and contribute to non-alcoholic fatty liver disease (NAFLD), steatohepatitis (NASH), alcoholic liver disease, and cirrhosis. Liver disease has long been associated with qualitative and quantitative (overgrowth) dysbiotic changes in the intestin...

  3. The association between multiple intestinal helminth infections and blood group, anaemia and nutritional status in human populations from Dore Bafeno, southern Ethiopia.

    Science.gov (United States)

    Degarege, A; Animut, A; Medhin, G; Legesse, M; Erko, B

    2014-06-01

    In this cross-sectional study, the associations between helminth infections and ABO blood group, anaemia and undernutrition were investigated in 480 febrile outpatients who visited Dore Bafeno Health Centre, southern Ethiopia, in December 2010. Stool specimens were processed using the Kato-Katz method and examined for intestinal helminth infections. Haemoglobin level was measured using a HemoCue machine and blood group was determined using an antisera haemagglutination test. Nutritional status of the study participants was assessed using height and weight measurements. Among the study participants, 50.2% were infected with intestinal helminths. Ascaris lumbricoides (32.7%), Trichuris trichiura (12.7%), Schistosoma mansoni (11.9%) and hookworm (11.0%) were the most frequently diagnosed helminths. The odds of infection and mean eggs per gram of different intestinal helminth species were comparable between the various blood groups. Among individuals who were infected with intestinal helminth(s), the mean haemoglobin level was significantly lower in individuals harbouring three or more helminth species and blood type AB compared to cases with double or single helminth infection and blood type O, respectively. The odds of being underweight was significantly higher in A. lumbricoides and T. trichiura infected individuals of age ? 5 and ? 20 years, respectively, when compared to individuals of the matching age group without intestinal helminths. In conclusion, infection with multiple intestinal helminths was associated with lower haemoglobin level, which was more severe in individuals with blood type AB. Future studies should focus on mechanisms by which blood group AB exacerbates the helminth-related reduction in mean haemoglobin level. PMID:23286203

  4. Biotransformation and metabolic profile of caudatin-2,6-dideoxy-3-O-methy-?-d-cymaropyranoside with human intestinal microflora by liquid chromatography quadrupole time-of-flight mass spectrometry.

    Science.gov (United States)

    Zhang, Wei; Peng, Yun-Ru; Ding, Yong-Fang

    2015-11-01

    In our previous studies, caudatin-2,6-dideoxy-3-O-methy-?-d- cymaropyranoside (CDMC) was for the first time isolated from Cynanchum auriculatum Royle ex Wightand and was reported to possess a wide range of biological activities. However, the routes and metabolites of CDMC produced by intestinal bacteria are not well understood. In this study, ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) technique combined with Metabolynx(TM) software was applied to analyze metabolites of CDMC by human intestinal bacteria. The incubated samples collected for 48 h in an anaerobic incubator and extracted with ethyl acetate were analyzed by UPLC-Q-TOF-MS within 12 min. Eight metabolites were identified based on MS and MS/MS data. The results indicated that hydrolysis, hydrogenation, demethylation and hydroxylation were the major metabolic pathways of CDMC in vitro. Seven strains of bacteria including Bacillus sp. 46, Enterococcus sp. 30 and sp. 45, Escherichia sp. 49A, sp. 64, sp. 68 and sp. 75 were further identified using 16S rRNA gene sequencing owing to their relatively strong metabolic capacity toward CDMC. The present study provides important information about metabolic routes of CDMC and the roles of different intestinal bacteria in the metabolism of CDMC. Moreover, those metabolites might influence the biological effect of CDMC in vivo, which affects the clinical effects of this medicinal plant. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26018801

  5. Intestinal permeability in strongyloidiasis

    Directory of Open Access Journals (Sweden)

    A.L. Werneck-Silva

    2001-03-01

    Full Text Available The objective of the present study was to assess intestinal permeability in patients with infection caused by Strongyloides stercoralis. Twenty-six patients (16 women and 10 men, mean age 45.9, with a diagnosis of strongyloidiasis were evaluated. For comparison, 25 healthy volunteers (18 women and 7 men, mean age 44.9, without digestive disorders or intestinal parasites served as normal controls. Intestinal permeability was measured on the basis of urinary radioactivity levels during the 24 h following oral administration of chromium-labeled ethylenediaminetetraacetic acid (51Cr-EDTA expressed as percentage of the ingested dose. The urinary excretion of 51Cr-EDTA was significantly reduced in patients with strongyloidiasis compared to controls (1.60 ± 0.74 and 3.10 ± 1.40, respectively, P = 0.0001. Intestinal permeability is diminished in strongyloidiasis. Abnormalities in mucus secretion and intestinal motility and loss of macromolecules could explain the impaired intestinal permeability.

  6. Intestinal permeability in strongyloidiasis

    Scientific Electronic Library Online (English)

    A.L., Werneck-Silva; A.M., Sipahi; A.O.M.C., Damião; C.A., Buchpigue; K., Iriya; A.A., Laudanna.

    2001-03-01

    Full Text Available The objective of the present study was to assess intestinal permeability in patients with infection caused by Strongyloides stercoralis. Twenty-six patients (16 women and 10 men), mean age 45.9, with a diagnosis of strongyloidiasis were evaluated. For comparison, 25 healthy volunteers (18 women and [...] 7 men), mean age 44.9, without digestive disorders or intestinal parasites served as normal controls. Intestinal permeability was measured on the basis of urinary radioactivity levels during the 24 h following oral administration of chromium-labeled ethylenediaminetetraacetic acid (51Cr-EDTA) expressed as percentage of the ingested dose. The urinary excretion of 51Cr-EDTA was significantly reduced in patients with strongyloidiasis compared to controls (1.60 ± 0.74 and 3.10 ± 1.40, respectively, P = 0.0001). Intestinal permeability is diminished in strongyloidiasis. Abnormalities in mucus secretion and intestinal motility and loss of macromolecules could explain the impaired intestinal permeability.

  7. Primer reporte de pseudomiasis intestinal humana por Eristalis tenax (Diptera, Syrphidae) en zona semiárida urbana del estado Falcón, Venezuela / First report of human intestinal pseudomiasis by Eristalis tenax (Diptera, Syrphidae) in urban semiarid area from Falcon state, Venezuela

    Scientific Electronic Library Online (English)

    Dalmiro J, Cazorla Perfetti; Pedro, Morales Moreno; María, Acosta; Sergio, Bermúdez.

    2011-12-01

    Full Text Available Pseudomiasis es el término empleado cuando se considera que las larvas y/o huevos de moscas se adquieren accidentalmente per os y atraviesan con inmediatez a lo largo del tracto digestivo. Se documenta un caso de una pseudomiasis intestinal por larvas de Eristalis tenax (Diptera: Syrphidae) en una p [...] aciente femenina de 39 años de edad, proveniente de un sector periférico de la ciudad de Coro, estado Falcón, Venezuela. La paciente observó inmediatamente la presencia de la larva viva en sus heces. Aunque refirió sufrir eventualmente de cólicos, al examen físico se presentó normal. La paciente aparentemente no sufre de trastornos mentales, y posee un nivel socioeconómico bajo. El presente trabajo constituye el primer reporte documentado de una pseudomiasis entérica por E. tenax en la zona semiárida del estado Falcón, en la región nor-occidental de Venezuela. Abstract in english Pseudomyiasis is the term used for the accidental entrapment of swallowed fly maggots and/or eggs immediately passing through the digestive tract. We report a case of intestinal pseudomyasis caused by the larvae of the cosmopolitan drone fly Eristalis tenax (Diptera: Syrphidae) in a 39 year old woma [...] n, resident in a suburban sector from Coro city, Falcon state, Venezuela. The patient immediately noticed a living larva in her stool. Although patient referred eventually became colic, her physical examination was normal, with no mental disturbance. She was in a low socioeconomic level. This is the first report of an enteric pseudomyasis by E. tenax in the semiarid zone of Falcon state, in the northwestern region of Venezuela.

  8. Intestinal permeability in strongyloidiasis

    OpenAIRE

    A.L. Werneck-Silva; A.M. Sipahi; A.O.M.C. Damião; C.A. Buchpigue; K. Iriya; A.A. Laudanna

    2001-01-01

    The objective of the present study was to assess intestinal permeability in patients with infection caused by Strongyloides stercoralis. Twenty-six patients (16 women and 10 men), mean age 45.9, with a diagnosis of strongyloidiasis were evaluated. For comparison, 25 healthy volunteers (18 women and 7 men), mean age 44.9, without digestive disorders or intestinal parasites served as normal controls. Intestinal permeability was measured on the basis of urinary radioactivity levels during the 24...

  9. Dietary xylo-oligosaccharide stimulates intestinal bifidobacteria and lactobacilli but has limited effect on intestinal integrity in rats

    DEFF Research Database (Denmark)

    Christensen, Ellen Gerd; Licht, Tine Rask; Leser, Thomas Dyrmann; Bahl, Martin Iain

    2014-01-01

    Background: Consumption of prebiotics may modulate gut microbiota, subsequently affecting the bacterial composition, metabolite profile, and human health. Previous studies indicate that also changes in intestinal integrity may occur. In order to explore this further we have investigated the effect of the putative prebiotic xylo-oligosaccharides (XOS) on the gut microbiota and intestinal integrity in male Wistar rats. As changes in intestinal integrity may be related to the expected bifidogenic e...

  10. 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

  11. 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.

  12. Human Embryonic Stem Cell–Derived Mesoderm-like Epithelium Transitions to Mesenchymal Progenitor Cells

    OpenAIRE

    Nolan L. Boyd; Robbins, Kelly R.; Dhara, Sujoy K.; West, Franklin D; Stice, Steven L.

    2009-01-01

    Human embryonic stem cells (hESC) have the potential to produce all of the cells in the body. They are able to self-renew indefinitely, potentially making them a source for large-scale production of therapeutic cell lines. Here, we developed a monolayer differentiation culture that induces hESC (WA09 and BG01) to form epithelial sheets with mesodermal gene expression patterns (BMP4, RUNX1, and GATA4). These E-cadherin+ CD90low cells then undergo apparent epithelial–mesenchymal transition for ...

  13. Influence of various bile acids on the metabolism of glycyrrhizin and glycyrrhetic acid by Ruminococcus sp. PO1-3 of human intestinal bacteria.

    Science.gov (United States)

    Akao, T

    1999-08-01

    Ruminococcus sp. PO1-3, an intestinal bacterium isolated from human feces, metabolized glycyrrhizin (GL) to glycyrrhetic acid (GA) and GA to 3-oxo-glycyrrhetic acid (3-oxo-GA) and possessed GL beta-D-glucuronidase and 3beta-hydroxysteroid dehydrogenase (3beta-HSD) involved in the metabolism of GL. This bacterial growth was enhanced by GL at a concentration of 0.4 mm and was suppressed by GA at concentration of 1.0 mM. Chenodeoxycholic acid, deoxycholic acid and lithocholic acid among the bile acids added to this bacterium suppressed the growth and GL beta-D-glucuronidase activity and 3beta-HSD activity incident to it at a concentration of 1.0 mM, while cholic acid, hyodeoxycholic acid and glycine and taurin conjugates of cholic acid, chenodeoxycholic acid, deoxycholic acid and lithocholic acid had almost no effect on this bacterium at a concentration of 0.2 to 1.0 mm. However, these enzyme activities of this sonicated bacteria were inhibited by all of these bile acids. Although each bile acid and GL added to bacteria at the same time suppressed the growth and the amount of metabolite GA by all bile acids used except cholic acid, taurocholic acid and taurodeoxycholic acid with GL, a combination of each bile acid and GA eased the growth inhibition caused by GA at a concentration of 0.2 mM and enhanced the amount of metabolite 3-oxo-GA by the glycine conjugate of bile acids with GA. GL or GA added after 6 h culture with each of these bile acids and bacteria was metabolized to a relatively large amount of GA by chenodeoxycholic acid and lithocholic acid and their glycine and taurine conjugates, glycocholic acid and taurodeoxycholic acid, or had almost no effect on the amount of metabolite 3-oxo-GA, respectively. These results showed that although GL added after the exposure to bile acid and GA and bile acid added at the same time as bacteria had different bile acid action, these conditions enhanced the amount of metabolite GA from GL and metabolite 3-oxo-GA from GA. PMID:10480314

  14. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to chitosan and reduction in body weight (ID 679, 1499), maintenance of normal blood LDL-cholesterol concentrations (ID 4663), reduction of intestinal transit time (ID 4664) and reduction of inflammation (ID 1985) pursuant to Article 13(1) of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    2011-01-01

    Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies was asked to provide a scientific opinion on a list of health claims pursuant to Article 13 of Regulation (EC) No 1924/2006. This opinion addresses the scientific substantiation of health claims in relation to chitosan and reduction in body weight, maintenance of normal blood LDL-cholesterol concentrations, reduction of intestinal transit time and reduction of inflammation. The scientific su...

  15. Prevalence of intestinal microsporidiosis in Human Immunodeficiency Virus-infected patients with diarrhea in major United States cities Prevalência de microsporidiose intestinal em pacientes infectados pelo HIV com diarréia nas principais cidades dos Estados Unidos da América do Norte

    Directory of Open Access Journals (Sweden)

    Mark S. Dworkin

    2007-12-01

    Full Text Available To determine the prevalence of intestinal microsporidiosis in HIV-infected patients, we performed a prospective study of HIV-infected patients with diarrheal illnesses in three US hospitals and examined an observational database of HIV-infected patients in 10 US cities. Among 737 specimens from the three hospitals, results were positive for 11 (prevalence 1.5%; seven (64% acquired HIV through male-to-male sexual contact, two (18% through male-to-male sexual contact and injection drug use, and one (9% through heterosexual contact; one (9% had an undetermined mode of transmission. Median CD4 count within six months of diagnosis of microsporidiosis was 33 cells/µL (range 3 to 319 cells/µL. For the national observational database (n = 24,098, the overall prevalence of microsporidiosis was 0.16%. Prevalence of microsporidiosis among HIV-infected patients with diarrheal disease is low, and microsporidiosis is most often diagnosed in patients with very low CD4+ cell counts. Testing for microsporidia appears to be indicated, especially for patients with very low CD4+ cell counts.Para determinar a prevalência de microsporidiose intestinal em pacientes infectados pelo HIV foi realizado um estudo prospectivo em três hospitais dos Estados Unidos da América do Norte (EUA e analizada uma base de dados nacional composta de dados coletados de pacientes infectados pelo HIV em 10 cidades dos EUA. De um total de 737 amostras de fezes de pacientes infectados pelo HIV que apresentavam diarréia, amostras de 11 pacientes (prevalência de 1,5% foram positivas para microsporídios. Todos os positivos eram do sexo masculino e, entre eles, sete (64% pacientes adquiriram a infecção pelo HIV através de relação homossexual, dois (18% através de relação sexual e drogas injetáveis e um (9% através de contato heterosexual, enquanto que em um paciente o modo de transmissão do HIV não foi determinado. A contagem média de linfócitos CD4 realizada até seis meses do diagnóstico de microsporidiose foi de 33 células/microlitro (3 a 319 células/microlitro. A análise da base de dados nacional (n = 24.098 mostrou uma prevalência de microsporidiose de 0,16%. A prevalência de microsporidiose em pacientes HIV-positivos com diarréia é baixa. Entretando, como a microsporidiose é mais frequentemente diagnosticada em pacientes com contagens de CD4 muito baixas, a indicação de pesquisa de microsporídios é justificada, especialmente para estes pacientes.

  16. Pulmonary artery and intestinal temperatures during heat stress and cooling

    DEFF Research Database (Denmark)

    Pearson, James; Ganio, Matthew S

    2012-01-01

    In humans, whole body heating and cooling are used to address physiological questions where core temperature is central to the investigated hypotheses. Core temperature can be measured in various locations throughout the human body. The measurement of intestinal temperature is increasingly used in laboratory settings as well as in athletics. However, it is unknown whether intestinal temperature accurately tracks pulmonary artery blood temperature, the gold standard, during thermal stimuli in resting humans, which is the investigated hypothesis.

  17. Joint-level mechanics of the walk-to-run transition in humans.

    Science.gov (United States)

    Pires, Neville J; Lay, Brendan S; Rubenson, Jonas

    2014-10-01

    Two commonly proposed mechanical explanations for the walk-to-run transition (WRT) include the prevention of muscular over-exertion (effort) and the minimization of peak musculoskeletal loads and thus injury risk. The purpose of this study was to address these hypotheses at a joint level by analysing the effect of speed on discrete lower-limb joint kinetic parameters in humans across a wide range of walking and running speeds including walking above and running below the WRT speed. Joint work, peak instantaneous joint power, and peak joint moments in the sagittal and frontal plane of the ankle, knee and hip from eight participants were collected for 10 walking speeds (30-120% of their WRT) and 10 running speeds (80-170% of their WRT) on a force plate instrumented treadmill. Of the parameters analysed, three satisfied our statistical criteria of the 'effort-load' hypothesis of the WRT. Mechanical parameters that provide an acute signal (peak moment and peak power) were more strongly associated with the gait transition than parameters that reflect the mechanical function across a portion of the stride. We found that both the ankle (peak instantaneous joint power during swing) and hip mechanics (peak instantaneous joint power and peak joint moments in stance) can influence the transition from walking to running in human locomotion and may represent a cascade of mechanical events beginning at the ankle and leading to an unfavourable compensation at the hip. Both the ankle and hip mechanisms may contribute to gait transition by lowering the muscular effort of running compared with walking at the WRT speed. Although few of the examined joint variables satisfied our hypothesis of the WRT, most showed a general marked increase when switching from walking to running across all speeds where both walking and running are possible, highlighting the fundamental differences in the mechanics of walking and running. While not eliciting the WRT per se, these variables may initiate the transition between stable walking and running patterns. Those variables that were invariant of gait were predominantly found in the swing phase. PMID:25104752

  18. 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.

  19. Epigenetic regulation of the intestinal epithelium.

    Science.gov (United States)

    Elliott, Ellen N; Kaestner, Klaus H

    2015-11-01

    The intestinal epithelium is an ideal model system for the study of normal and pathological differentiation processes. The mammalian intestinal epithelium is a single cell layer comprising proliferative crypts and differentiated villi. The crypts contain both proliferating and quiescent stem cell populations that self-renew and produce all the differentiated cell types, which are replaced every 3-5 days. The genetics of intestinal development, homeostasis, and disease are well defined, but less is known about the contribution of epigenetics in modulating these processes. Epigenetics refers to heritable phenotypic traits, including gene expression, which are independent of mutations in the DNA sequence. We have known for several decades that human colorectal cancers contain hypomethylated DNA, but the causes and consequences of this phenomenon are not fully understood. In contrast, tumor suppressor gene promoters are often hypermethylated in colorectal cancer, resulting in decreased expression of the associated gene. In this review, we describe the role that epigenetics plays in intestinal homeostasis and disease, with an emphasis on results from mouse models. We highlight the importance of producing and analyzing next-generation sequencing data detailing the epigenome from intestinal stem cell to differentiated intestinal villus cell. PMID:26220502

  20. Intestinal Transcriptomes of Nematodes: Comparison of the Parasites Ascaris suum and Haemonchus contortus with the Free-living Caenorhabditis elegans

    OpenAIRE

    Yin, Yong; Martin, John; Abubucker, Sahar; Scott, Alan L.; McCarter, James P.; Wilson, Richard K.; Jasmer, Douglas P.; Mitreva, Makedonka

    2008-01-01

    Biological properties of the nematode intestine warrant in-depth investigation, the results of which can be utilized in the control of parasitic nematodes that infect humans, livestock, and plants. Both the importance of intestinal antigens from Haemonchus contortus in immunity and the damage to H. contortus intestine by anthelmintic fenbendazole have highlighted the versatility of the intestine as an emerging target. However, biological information regarding fundamental intestinal cell funct...

  1. Nuclear Thermal Propulsion (NTP): A Proven, Growth Technology for Fast Transit Human Missions to Mars

    Science.gov (United States)

    Borowski, Stanley K.; McCurdy, David R.; Packard, Thomas W.

    2014-01-01

    The "fast conjunction" long surface stay mission option was selected for NASA's recent Mars Design Reference Architecture (DRA) 5.0 study because it provided adequate time at Mars (approx. 540 days) for the crew to explore the planet's geological diversity while also reducing the "1-way" transit times to and from Mars to approx. 6 months. Short transit times are desirable in order to reduce the debilitating physiological effects on the human body that can result from prolonged exposure to the zero-gravity (0-gE) and radiation environments of space. Recent measurements from the RAD detector attached to the Curiosity rover indicate that astronauts would receive a radiation dose of approx. 0.66 Sv (approx. 66 rem)-the limiting value established by NASA-during their 1-year journey in deep space. Proven nuclear thermal rocket (NTR) technology, with its high thrust and high specific impulse (Isp approx. 900 s), can cut 1-way transit times by as much as 50 percent by increasing the propellant capacity of the Mars transfer vehicle (MTV). No large technology scale-ups in engine size are required for these short transit missions either since the smallest engine tested during the Rover program-the 25 klbf "Pewee" engine is sufficient when used in a clustered arrangement of three to four engines. The "Copernicus" crewed MTV developed for DRA 5.0 is a 0-gE design consisting of three basic components: (1) the NTP stage (NTPS); (2) the crewed payload element; and (3) an integrated "saddle truss" and LH2 propellant drop tank assembly that connects the two elements. With a propellant capacity of approx. 190 t, Copernicus can support 1-way transit times ranging from approx. 150 to 220 days over the 15-year synodic cycle. The paper examines the impact on vehicle design of decreasing transit times for the 2033 mission opportunity. With a fourth "upgraded" SLS/HLV launch, an "in-line" LH2 tank element can be added to Copernicus allowing 1-way transit times of 130 days. To achieve 100 to 120 day transit times, Copernicus' saddle truss/drop tank assembly is replaced by a "star truss" assembly with paired modular drop tanks to further increase the vehicle's propellant capacity. The HLV launch count increases (from approx. 5 to 7) and a fourth engine is needed to reduce total mission burn time and gravity losses. Using a "split mission" approach, the NTPS, in-line tank and the saddle truss/LH2 drop tank elements can be configured as a pre-deployed Earth Return Vehicle/propellant tanker supporting 90-day crewed mission transits. The split mission approach also eliminates the need for on-orbit assembly. Mission scenario descriptions, key features and operational characteristics for five different vehicle configurations are presented.

  2. Human FcRn can mediate the transport across intestinal mucosal barrier and prolong the half-life of rabbit IgG in vivo

    Scientific Electronic Library Online (English)

    Guangchang, Pang; Yufang, Wang; Junbo, Xie; Qingsen, Chen; Zhihe, Hu.

    2015-06-01

    Full Text Available FcRn (neonatal Fc receptor) plays an important role in IgG transportation, antigen presentation and signal transmission. In this study, the complement fixation test and flow cytometry test were performed to verify whether the heterologous antibody could be transmitted to the serum or leukocyte with [...] Fc?R (Fc gamma receptor) across the intestinal mucosa. The results showed that rabbit anti-bovine IgG could be detected in both the serum and the leukocytes, which indicated that the heterologous antibody could transport across the intestinal mucosa to enter the blood and be effectively delivered to the leukocytes with Fc?R. In addition, the results also showed that the rabbit anti-bovine IgG still could be detected in the leukocyte group (P=0.044

  3. Evaluation of Intestinal Protozoan Morphology in Human Fecal Specimens Preserved in EcoFix: Comparison of Wheatley’s Trichrome Stain and EcoStain

    OpenAIRE

    Garcia, Lynne S.; Shimizu, Robyn Y.

    1998-01-01

    As a result of disposal problems related to the use of mercury compounds, many laboratories have switched from mercuric chloride-based Schaudinn’s and polyvinyl alcohol (PVA) stool preservatives to other, non-mercury-based preservatives. A comparison of organism recoveries and morphologies of the intestinal protozoa was undertaken with PVA containing the EcoFix zinc-based Schaudinn’s preservative (Meridian Diagnostics, Inc.); both Wheatley’s modification of Gomori’s trichrome stain (WT) and E...

  4. First characterization of bioactive components in soybean tempe that protect human and animal intestinal cells against enterotoxigenic Escherichia coli (ETEC) infection

    OpenAIRE

    Roubos-van den Hil, P.J.; Schols, H.A.; Nout, M.J.R.; Zwietering, M H; Gruppen, H.

    2010-01-01

    Tempe extracts can inhibit the adhesion of enterotoxigenic Escherichia coli (ETEC) to intestinal cells and thereby can play a role in controlling ETEC-induced diarrhea. The component responsible for this adhesion inhibition activity is still unknown. This research describes the purification and partial characterization of this bioactive component of tempe. After heating, defatting, and protease treatment, the extracts were found to remain active. However, after treatment with polysaccharide-d...

  5. Vancomycin-resistant Enterococcus domination of intestinal microbiota is enabled by antibiotic treatment in mice and precedes bloodstream invasion in humans

    OpenAIRE

    Ubeda, Carles; Taur, Ying; Jenq, Robert R.; Equinda, Michele J.; Son, Tammy; Samstein, Miriam; Viale, Agnes; Socci, Nicholas D.; van den Brink, Marcel R.M.; Kamboj, Mini; Pamer, Eric G.

    2010-01-01

    Bloodstream infection by highly antibiotic-resistant bacteria, such as vancomycin-resistant Enterococcus (VRE), is a growing clinical problem that increasingly defies medical intervention. Identifying patients at high risk for bacterial sepsis remains an important clinical challenge. Recent studies have shown that antibiotics can alter microbial diversity in the intestine. Here, we characterized these effects using 16s rDNA pyrosequencing and demonstrated that antibiotic treatment of mice ena...

  6. Detection of inflammation- and neoplasia-associated alterations in human large intestine using plant/invertebrate lectins, galectin-1 and neoglycoproteins

    OpenAIRE

    Brinck, U.; Korabiowska, M; Bosbach, R.; Gabius, Hans-Joachim

    1998-01-01

    Commonly, plant and invertebrate lectins are accepted glycohistochemical tools for the analysis of normal and altered structures of glycans in histology and pathology. Mammalian lectins and neoglycoproteins are recent additions to this panel for the detection of lectin-reactive carbohydrate epitopes and glycoligand-binding sites. The binding profiles of these three types of probes were comparatively analyzed in normal, inflamed and neoplastic large intestine. In normal colonic mucosa the intr...

  7. Gut-trophic feed additives and their effects upon the gut structure and intestinal metabolism. State of the art in the pig, and perspectives towards humans

    OpenAIRE

    C. Domeneghini; Di Giancamillo, A.; S Arrighi; Bosi, G.

    2006-01-01

    The correct functional development of the gastrointestinal tract is of special importance during the neonatal and weaning phases of reared piglets. Nutrition is obviously a critical determinant in the growth of the gut in the young swine. The mucosal epithelium of the small intestine is reputed anatomically and functionally immature in neonatal pigs, a feature that appears to be exacerbated at weaning, when a colonization of the gut occurs by “new” microrganism...

  8. New glucosidase inhibitors from an ayurvedic herbal treatment for type 2 diabetes: structures and inhibition of human intestinal maltase-glucoamylase with compounds from Salacia reticulata.

    Science.gov (United States)

    Sim, Lyann; Jayakanthan, Kumarasamy; Mohan, Sankar; Nasi, Ravindranath; Johnston, Blair D; Pinto, B Mario; Rose, David R

    2010-01-26

    An approach to controlling blood glucose levels in individuals with type 2 diabetes is to target alpha-amylases and intestinal glucosidases using alpha-glucosidase inhibitors acarbose and miglitol. One of the intestinal glucosidases targeted is the N-terminal catalytic domain of maltase-glucoamylase (ntMGAM), one of the four intestinal glycoside hydrolase 31 enzyme activities responsible for the hydrolysis of terminal starch products into glucose. Here we present the X-ray crystallographic studies of ntMGAM in complex with a new class of alpha-glucosidase inhibitors derived from natural extracts of Salacia reticulata, a plant used traditionally in Ayuverdic medicine for the treatment of type 2 diabetes. Included in these extracts are the active compounds salacinol, kotalanol, and de-O-sulfonated kotalanol. This study reveals that de-O-sulfonated kotalanol is the most potent ntMGAM inhibitor reported to date (K(i) = 0.03 microM), some 2000-fold better than the compounds currently used in the clinic, and highlights the potential of the salacinol class of inhibitors as future drug candidates. PMID:20039683

  9. Pediatric intestinal motility disorders.

    Science.gov (United States)

    Gfroerer, Stefan; Rolle, Udo

    2015-09-01

    Pediatric intestinal motility disorders affect many children and thus not only impose a significant impact on pediatric health care in general but also on the quality of life of the affected patient. Furthermore, some of these conditions might also have implications for adulthood. Pediatric intestinal motility disorders frequently present as chronic constipation in toddler age children. Most of these conditions are functional, meaning that constipation does not have an organic etiology, but in 5% of the cases, an underlying, clearly organic disorder can be identified. Patients with organic causes for intestinal motility disorders usually present in early infancy or even right after birth. The most striking clinical feature of children with severe intestinal motility disorders is the delayed passage of meconium in the newborn period. This sign is highly indicative of the presence of Hirschsprung disease (HD), which is the most frequent congenital disorder of intestinal motility. HD is a rare but important congenital disease and the most significant entity of pediatric intestinal motility disorders. The etiology and pathogenesis of HD have been extensively studied over the last several decades. A defect in neural crest derived cell migration has been proven as an underlying cause of HD, leading to an aganglionic distal end of the gut. Numerous basic science and clinical research related studies have been conducted to better diagnose and treat HD. Resection of the aganglionic bowel remains the gold standard for treatment of HD. Most recent studies show, at least experimentally, the possibility of a stem cell based therapy for HD. This editorial also includes rare causes of pediatric intestinal motility disorders such as hypoganglionosis, dysganglionosis, chronic intestinal pseudo-obstruction and ganglioneuromatosis in multiple endocrine metaplasia. Underlying organic pathologies are rare in pediatric intestinal motility disorders but must be recognized as early as possible. PMID:26361414

  10. Obesity, non-alcoholic fatty liver disease, and atherothrombosis: a role for the intestinal microbiota?

    OpenAIRE

    Knaapen, M.; Kootte, R.S.; Zoetendal, E. G.; De Vos, W.M.; Dallinga-Thie, G M; Levi, M.; Stroes, E.S.; Nieuwdorp, M.

    2013-01-01

    Whereas the association between intestinal microorganisms and health has been widely accepted in the area of infectious disease, recent advances have now implied a role for the intestinal microbiota in human energy balance. In fact, numerous studies support an intricate relationship between the intestinal microbiota and obesity, as well as subsequent insulin resistance and non-alcoholic fatty liver disease. Intestinal microorganisms also seem to be involved in haemostatic tone and atherogenes...

  11. Loss of prostasin (PRSS8) in human bladder transitional cell carcinoma cell lines is associated with epithelial-mesenchymal transition (EMT)

    International Nuclear Information System (INIS)

    The glycosylphosphatidylinositol (GPI)-anchored epithelial extracellular membrane serine protease prostasin (PRSS8) is expressed abundantly in normal epithelia and essential for terminal epithelial differentiation, but down-regulated in human prostate, breast, and gastric cancers and invasive cancer cell lines. Prostasin is involved in the extracellular proteolytic modulation of the epidermal growth factor receptor (EGFR) and is an invasion suppressor. The aim of this study was to evaluate prostasin expression states in the transitional cell carcinomas (TCC) of the human bladder and in human TCC cell lines. Normal human bladder tissues and TCC on a bladder cancer tissue microarray (TMA) were evaluated for prostasin expression by means of immunohistochemistry. A panel of 16 urothelial and TCC cell lines were evaluated for prostasin and E-cadherin expression by western blot and quantitative PCR, and for prostasin gene promoter region CpG methylation by methylation-specific PCR (MSP). Prostasin is expressed in the normal human urothelium and in a normal human urothelial cell line, but is significantly down-regulated in high-grade TCC and lost in 9 (of 15) TCC cell lines. Loss of prostasin expression in the TCC cell lines correlated with loss of or reduced E-cadherin expression, loss of epithelial morphology, and promoter DNA hypermethylation. Prostasin expression could be reactivated by demethylation or inhibition of histone deacetylase. Re-expression of prostasin or a serine protease-inactive variant resulted in transcriptional up-regulation of E-cadherin. Loss of prostasin expression in bladder transitional cell carcinomas is associated with epithelial-mesenchymal transition (EMT), and may have functional implications in tumor invasion and resistance to chemotherapy

  12. Loss of prostasin (PRSS8 in human bladder transitional cell carcinoma cell lines is associated with epithelial-mesenchymal transition (EMT

    Directory of Open Access Journals (Sweden)

    Chai Karl X

    2009-10-01

    Full Text Available Abstract Background The glycosylphosphatidylinositol (GPI-anchored epithelial extracellular membrane serine protease prostasin (PRSS8 is expressed abundantly in normal epithelia and essential for terminal epithelial differentiation, but down-regulated in human prostate, breast, and gastric cancers and invasive cancer cell lines. Prostasin is involved in the extracellular proteolytic modulation of the epidermal growth factor receptor (EGFR and is an invasion suppressor. The aim of this study was to evaluate prostasin expression states in the transitional cell carcinomas (TCC of the human bladder and in human TCC cell lines. Methods Normal human bladder tissues and TCC on a bladder cancer tissue microarray (TMA were evaluated for prostasin expression by means of immunohistochemistry. A panel of 16 urothelial and TCC cell lines were evaluated for prostasin and E-cadherin expression by western blot and quantitative PCR, and for prostasin gene promoter region CpG methylation by methylation-specific PCR (MSP. Results Prostasin is expressed in the normal human urothelium and in a normal human urothelial cell line, but is significantly down-regulated in high-grade TCC and lost in 9 (of 15 TCC cell lines. Loss of prostasin expression in the TCC cell lines correlated with loss of or reduced E-cadherin expression, loss of epithelial morphology, and promoter DNA hypermethylation. Prostasin expression could be reactivated by demethylation or inhibition of histone deacetylase. Re-expression of prostasin or a serine protease-inactive variant resulted in transcriptional up-regulation of E-cadherin. Conclusion Loss of prostasin expression in bladder transitional cell carcinomas is associated with epithelial-mesenchymal transition (EMT, and may have functional implications in tumor invasion and resistance to chemotherapy.

  13. Deciphering the porcine intestinal microRNA transcriptome

    Directory of Open Access Journals (Sweden)

    Keller Andreas

    2010-04-01

    Full Text Available Abstract Background While more than 700 microRNAs (miRNAs are known in human, a comparably low number has been identified in swine. Because of the close phylogenetic distance to humans, pigs serve as a suitable model for studying e.g. intestinal development or disease. Recent studies indicate that miRNAs are key regulators of intestinal development and their aberrant expression leads to intestinal malignancy. Results Here, we present the identification of hundreds of apparently novel miRNAs in the porcine intestine. MiRNAs were first identified by means of deep sequencing followed by miRNA precursor prediction using the miRDeep algorithm as well as searching for conserved miRNAs. Second, the porcine miRNAome along the entire intestine (duodenum, proximal and distal jejunum, ileum, ascending and transverse colon was unraveled using customized miRNA microarrays based on the identified sequences as well as known porcine and human ones. In total, the expression of 332 intestinal miRNAs was discovered, of which 201 represented assumed novel porcine miRNAs. The identified hairpin forming precursors were in part organized in genomic clusters, and most of the precursors were located on chromosomes 3 and 1, respectively. Hierarchical clustering of the expression data revealed subsets of miRNAs that are specific to distinct parts of the intestine pointing to their impact on cellular signaling networks. Conclusions In this study, we have applied a straight forward approach to decipher the porcine intestinal miRNAome for the first time in mammals using a piglet model. The high number of identified novel miRNAs in the porcine intestine points out their crucial role in intestinal function as shown by pathway analysis. On the other hand, the reported miRNAs may share orthologs in other mammals such as human still to be discovered.

  14. Monomer/Dimer Transition of the Caspase-Recruitment Domain of Human Nod1

    Energy Technology Data Exchange (ETDEWEB)

    Srimathi,T.; Robbins, S.; Dubas, R.; Hasegawa, M.; Inohara, N.; Park, Y.

    2008-01-01

    Nod1 is an essential cytoplasmic sensor for bacterial peptidoglycans in the innate immune system. The caspase-recruitment domain of Nod1 (Nod1{_}CARD) is indispensable for recruiting a downstream kinase, receptor-interacting protein 2 (RIP2), that activates nuclear factor-?B (NF-?B). The crystal structure of human Nod1{_}CARD at 1.9 Angstroms resolution reveals a novel homodimeric conformation. Our structural and biochemical analysis shows that the homodimerization of Nod1{_}CARD is achieved by swapping the H6 helices at the carboxy termini and stabilized by forming an interchain disulfide bond between the Cys39 residues of the two monomers in solution and in the crystal. In addition, we present experimental evidence for a pH-sensitive conformational change of Nod1{_}CARD. Our results suggest that the pH-sensitive monomer/dimer transition is a unique molecular property of Nod1{_}CARD.

  15. Fasting inhibits human cancer progression via the epithelial-mesenchymal transition process: Important evidence unraveled

    Directory of Open Access Journals (Sweden)

    Ala-Eddin Al Moustafa

    2012-01-01

    Full Text Available 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 invasive form. We believe that fasting can inhibit cancer progression and metastasis though the reduction of IGF-1 level and consequently the inhibition of EMT; in this paper, we present some evidence to confirm this association.

  16. Experimental evidence for phase synchronization transitions in human cardio-respiratory system

    CERN Document Server

    Bartsch, R; Kantelhardt, J W; Penzel, T; Bartsch, Ronny; Havlin, Shlomo; Kantelhardt, Jan W.; Penzel, Thomas

    2007-01-01

    Transitions in the dynamics of complex systems can be characterized by changes in the synchronization behavior of their components. Taking the human cardio-respiratory system as an example and using an automated procedure for screening the synchrograms of 112 healthy subjects we study the frequency and the distribution of synchronization episodes under different physiological conditions that occur during sleep. We find that phase synchronization between heartbeat and breathing is significantly enhanced during non-rapid-eye-movement (non-REM) sleep (deep sleep and light sleep) and reduced during REM sleep. Our results suggest that the synchronization is mainly due to a weak influence of the breathing oscillator upon the heartbeat oscillator, which is disturbed in the presence of long-term correlated noise, superimposed by the activity of higher brain regions during REM sleep.

  17. Experimental Evidence for Phase Synchronization Transitions in the Human Cardiorespiratory System

    Science.gov (United States)

    Bartsch, Ronny; Kantelhardt, Jan W.; Penzel, Thomas; Havlin, Shlomo

    2007-02-01

    Transitions in the dynamics of complex systems can be characterized by changes in the synchronization behavior of their components. Taking the human cardiorespiratory system as an example and using an automated procedure for screening the synchrograms of 112 healthy subjects we study the frequency and the distribution of synchronization episodes under different physiological conditions that occur during sleep. We find that phase synchronization between heartbeat and breathing is significantly enhanced during non-rapid-eye-movement (non-REM) sleep (deep sleep and light sleep) and reduced during REM sleep. Our results suggest that the synchronization is mainly due to a weak influence of the breathing oscillator upon the heartbeat oscillator, which is disturbed in the presence of long-term correlated noise, superimposed by the activity of higher brain regions during REM sleep.

  18. Cannabinoids cool the intestine

    OpenAIRE

    Kunos, George; PACHER, PÁL

    2004-01-01

    Cannabinoids inhibit motility and secretion in the intestine. They are now assigned the additional task of curbing excessive inflammation, suggesting that drugs targeting the endogenous cannabinoid system could be exploited for inflammatory bowel disease.

  19. Small Intestine Cancer Treatment

    Science.gov (United States)

    ... that may be caused by small intestine cancer. Endoscopy : A procedure to look at organs and tissues ... for abnormal areas. There are different types of endoscopy: Upper endoscopy : A procedure to look at the ...

  20. Intestinal Complications of IBD

    Science.gov (United States)

    ... narrowed intestinal passage. These narrowed areas are called strictures . Strictures may be mild or severe, depending on how ... at CCFA Privacy Policy Sitemap CONTACT + Visit our mobile site Full Site

  1. Dyslipidaemia--hepatic and intestinal cross-talk.

    LENUS (Irish Health Repository)

    Tomkin, Gerald H

    2010-06-01

    Cholesterol metabolism is tightly regulated with the majority of de novo cholesterol synthesis occurring in the liver and intestine. 3 Hydroxy-3-methylglutaryl coenzyme A reductase, a major enzyme involved in cholesterol synthesis, is raised in both liver and intestine in diabetic animals. Niemann PickC1-like1 protein regulates cholesterol absorption in the intestine and facilitates cholesterol transport through the liver. There is evidence to suggest that the effect of inhibition of Niemann PickC1-like1 lowers cholesterol through its effect not only in the intestine but also in the liver. ATP binding cassette proteins G5\\/G8 regulate cholesterol re-excretion in the intestine and in the liver, cholesterol excretion into the bile. Diabetes is associated with reduced ATP binding cassette protein G5\\/G8 expression in both the liver and intestine in animal models. Microsomal triglyceride transfer protein is central to the formation of the chylomicron in the intestine and VLDL in the liver. Microsomal triglyceride transfer protein mRNA is increased in diabetes in both the intestine and liver. Cross-talk between the intestine and liver is poorly documented in humans due to the difficulty in obtaining liver biopsies but animal studies are fairly consistent in showing relationships that explain in part mechanisms involved in cholesterol homeostasis.

  2. Issues for resolving adverse effects on the safety culture of human work underload and workload transitions in complex human-machine systems

    International Nuclear Information System (INIS)

    A workshop was conducted whose specific purpose was to build on earlier work of the US National Research Council, US federal government agencies, and the larger human factors community to: (1) clarify human factors issues pertaining to degraded safety performance in advanced human-machine systems(e.g., nuclear production, transportation, aerospace) due to human work underload and workload transition, and (2) develop strategies for resolving these issues. The workshop affirmed that: (1) work underload and workload transition are issues that will have to be addressed by designers of advanced human-machine systems, especially those relying on automation, if cost, performance, safety, and operator acceptability are to be optimized, (2) human machine allocation models, standards and guidelines which go beyond simple capability approaches will be needed to preclude or seriously diminish the work underload and workload transition problems, and (3) the 16 workload definition, measurement, situational awareness, and trust issues identified during the workshop, need resolution if these models, standards, and guidelines are to be achieved

  3. Small intestinal bacteria overgrowth decreases small intestinal motility in the NASH rats

    Directory of Open Access Journals (Sweden)

    Wan-Chun Wu, Wei Zhao, Sheng Li

    2008-01-01

    Full Text Available AIM: To explore the relationship between small intestinal motility and small intestinal bacteria overgrowth (SIBO in Nonalcoholic steatohepatitis (NASH, and to investigate the effect of SIBO on the pathogenesis of NASH in rats. The effect of cidomycin in alleviating severity of NASH is also studied.METHODS: Forty eight rats were randomly divided into NASH group (n = 16, cidomycin group (n = 16 and control group (n = 16. Then each group were subdivided into small intestinal motility group (n = 8, bacteria group (n = 8 respectively. A semi-solid colored marker was used for monitoring small intestinal transit. The proximal small intestine was harvested under sterile condition and processed for quantitation for aerobes (E. coli and anaerobes (Lactobacilli. Liver pathologic score was calculated to qualify the severity of hepatitis. Serum ALT, AST levels were detected to evaluate the severity of hepatitis.RESULTS: Small intestinal transit was inhibited in NASH group (P < 0.01. Rats treated with cidomycin had higher small intestine transit rate than rats in NASH group (P < 0.01. High fat diet resulted in quantitative alterations in the aerobes (E. coli but not in the anoerobics (Lactobacill. There was an increase in the number of E. coli in the proximal small intestinal flora in NASH group than in control group (1.70 ± 0.12 log10 (CFU/g vs 1.28 ± 0.07 log10 (CFU/g, P < 0.01. TNF-? concentration was significantly higher in NASH group than in control group (1.13 ± 0.15 mmol/L vs 0.57 ± 0.09 mmol/L, P < 0.01. TNF-?concentration was lower in cidomycin group than in NASH group (0.63 ± 0.09 mmol/L vs 1.13 ± 0.15 mmol/L, P < 0.01. Treatment with cidomycin showed its effect by significantly lowering serum ALT, AST and TNF-? levels of NASH rats.CONCLUSION: SIBO may decrease small intestinal movement in NASH rats. SIBO may be an important pathogenesis of Nash. And treatment with cidomycin by mouth can alleviate the severity of NASH.

  4. The intestinal stem cell

    OpenAIRE

    Barker, Nick; van de Wetering, Marc; Clevers, Hans

    2008-01-01

    The epithelium of the adult mammalian intestine is in a constant dialog with its underlying mesenchyme to direct progenitor proliferation, lineage commitment, terminal differentiation, and, ultimately, cell death. The epithelium is shaped into spatially distinct compartments that are dedicated to each of these events. While the intestinal epithelium represents the most vigorously renewing adult tissue in mammals, the stem cells that fuel this self-renewal process have been identified only rec...

  5. Reduction of malachite green to leucomalachite green by intestinal bacteria.

    Science.gov (United States)

    Henderson, A L; Schmitt, T C; Heinze, T M; Cerniglia, C E

    1997-10-01

    Intestinal microfloras from human, rat, mouse, and monkey fecal samples and 14 pure cultures of anaerobic bacteria representative of those found in the human gastrointestinal tract metabolized the triphenylmethane dye malachite green to leucomalachite green. The reduction of malachite green to the leuco derivative suggests that intestinal microflora could play an important role in the metabolic activation of the triphenylmethane dye to a potential carcinogen. PMID:9327576

  6. Pulmonary artery and intestinal temperatures during heat stress and cooling

    DEFF Research Database (Denmark)

    Pearson, James; Ganio, Matthew S; Seifert, Thomas; Overgaard, Morten; Secher, Niels H; Crandall, Craig G

    2012-01-01

    In humans, whole body heating and cooling are used to address physiological questions where core temperature is central to the investigated hypotheses. Core temperature can be measured in various locations throughout the human body. The measurement of intestinal temperature is increasingly used in laboratory settings as well as in athletics. However, it is unknown whether intestinal temperature accurately tracks pulmonary artery blood temperature, the gold standard, during thermal stimuli in res...

  7. Use of the dynamic gastro-intestinal model TIM to explore the survival of the yogurt bacterium Streptococcus thermophilus and the metabolic activities induced in the simulated human gut.

    Science.gov (United States)

    Uriot, Ophélie; Galia, Wessam; Awussi, Ahoefa Ablavi; Perrin, Clarisse; Denis, Sylvain; Chalancon, Sandrine; Lorson, Emilie; Poirson, Chantal; Junjua, Maira; Le Roux, Yves; Alric, Monique; Dary, Annie; Blanquet-Diot, Stéphanie; Roussel, Yvonne

    2016-02-01

    Streptococcus thermophilus, a lactic acid bacterium used to produce yogurts and cheeses is more and more considered for its potential probiotic properties. This implies that additional information should be obtained regarding its survival and metabolic activity in the human Gastro-Intestinal Tract (GIT). In this study, we screened 30 S. thermophilus strains for urease, small heat shock protein, and amino-acid decarboxylase functions which may play a role in survival in the upper part of the GIT. The survival kinetics of 4 strains was investigated using the TIM, a physiologically relevant in vitro dynamic gastric and small intestinal model. The three strains LMD9, PB18O and EBLST20 showed significantly higher survival than CNRZ21 in all digestive compartments of the TIM, which may be related to the presence of urease and heat shock protein functions. When LMD9 bacterial cells were delivered in a fermented milk formula, a significant improvement of survival in the TIM was observed compared to non-fermented milk. With the RIVET (Recombinase In Vivo Expression Technology) method applied to the LMD9 strain, a promoter located upstream of hisS, responsible for the histidyl-transfer RNA synthesis, was found to be specifically activated in the artificial stomach. The data generated on S. thermophilus survival and its adaptation capacities to the digestive tract are essential to establish a list of biomarkers useful for the selection of probiotic strains. PMID:26611166

  8. Colonization of the streptomycin-treated mouse large intestine by a human fecal Escherichia coli strain: role of adhesion to mucosal receptors.

    OpenAIRE

    Wadolkowski, E A; Laux, D C; Cohen, P S

    1988-01-01

    Escherichia coli F-18, a normal fecal isolate, was previously shown to be an excellent colonizer of the streptomycin-treated CD-1 mouse large intestine, whereas E. coli F-18col-, a derivative of E. coli F-18 that no longer makes the E. coli F-18 colicin, was shown to be a poor mouse colonizer. It was also shown that E. coli F-18 bound two to three times more soluble colonic mucus protein than did E. coli F-18col- and that a major receptor in CD-1 mouse colonic mucus was a 50.5-kilodalton glyc...

  9. Construction of stable cloning vectors that do not segregate from a human fecal Escherichia coli strain in the streptomycin-treated mouse large intestine.

    OpenAIRE

    Burghoff, R L; Laux, D C; Cohen, P S

    1990-01-01

    Escherichia coli F-18 Col- was previously shown to be a poor colonizer of the streptomycin-treated mouse large intestine, relative to its parent, E. coli F-18. Prior to attempting to clone genes responsible for the colonization phenotype of E. coli F-18 into E. coli F-18 Col-, a suitable cloning vector had to be found. In this investigation, we report that the commonly used cloning vectors pBR322, pHC79, and pBR329 all segregate from E. coli F-18 Col- both when grown in L broth under conditio...

  10. Normal variations in the isotopic composition of metabolically relevant transition metals in human blood

    Science.gov (United States)

    Van Heghe, L.; Cloquet, C.; Vanhaecke, F.

    2012-04-01

    Cu, Fe and Zn are transition metals with great catalytic, structural and regulating importance in the human body. Hence, an aberrant metabolism of these elements can have serious implications on the health of a person. It is assumed that, due to differences in isotope fractionation, the isotopic composition of these elements in whole blood of patients can be different from that in blood of healthy subjects. Therefore, isotopic analysis of the element affected by the disease can be a promising approach for early diagnosis. A method for isotopic analysis of Cu, Fe and Zn in human whole blood was developed. The simultaneous chromatographic isolation of these elements and the conditions for isotope ratio measurement via multi-collector ICP - mass spectrometry (MC-ICP-MS) were optimized. So far, only whole blood of supposedly healthy volunteers (reference population) was analyzed. Results for Fe confirmed the known differences in isotopic composition between male and female blood. It is also shown that other parameters can have influence as well, e.g., the isotopic composition of Zn seems to be governed by the diet.

  11. Concurrent encoding of frequency and amplitude modulation in human auditory cortex: encoding transition.

    Science.gov (United States)

    Luo, Huan; Wang, Yadong; Poeppel, David; Simon, Jonathan Z

    2007-12-01

    Complex natural sounds (e.g., animal vocalizations or speech) can be characterized by specific spectrotemporal patterns the components of which change in both frequency (FM) and amplitude (AM). The neural coding of AM and FM has been widely studied in humans and animals but typically with either pure AM or pure FM stimuli. The neural mechanisms employed to perceptually unify AM and FM acoustic features remain unclear. Using stimuli with simultaneous sinusoidal AM (at rate f(AM) = 37 Hz) and FM (with varying rates f(FM)), magnetoencephalography (MEG) is used to investigate the elicited auditory steady-state response (aSSR) at relevant frequencies (f(AM), f(FM), f(AM) + f(FM)). Previous work demonstrated that for sounds with slower FM dynamics (f(FM) modulation" encoding. This study explores the neural coding mechanism for stimuli with faster FM dynamics ( 5 Hz), there is a transition from pure phase modulation encoding to a single-upper-sideband (SSB) response (at frequency f(AM) + f(FM)) pattern. We propose that this unexpected SSB response can be explained by the additional involvement of subsidiary AM encoding responses simultaneously to, and in quadrature with, the ongoing phase modulation. These results, using MEG to reveal a possible neural encoding of specific acoustic properties, demonstrate more generally that physiological tests of encoding hypotheses can be performed noninvasively on human subjects, complementing invasive, single-unit recordings in animals. PMID:17898148

  12. Activated STAT5 Confers Resistance to Intestinal Injury by Increasing Intestinal Stem Cell Proliferation and Regeneration

    Directory of Open Access Journals (Sweden)

    Shila Gilbert

    2015-02-01

    Full Text Available Intestinal epithelial stem cells (IESCs control the intestinal homeostatic response to inflammation and regeneration. The underlying mechanisms are unclear. Cytokine-STAT5 signaling regulates intestinal epithelial homeostasis and responses to injury. We link STAT5 signaling to IESC replenishment upon injury by depletion or activation of Stat5 transcription factor. We found that depletion of Stat5 led to deregulation of IESC marker expression and decreased LGR5+ IESC proliferation. STAT5-deficient mice exhibited worse intestinal histology and impaired crypt regeneration after ?-irradiation. We generated a transgenic mouse model with inducible expression of constitutively active Stat5. In contrast to Stat5 depletion, activation of STAT5 increased IESC proliferation, accelerated crypt regeneration, and conferred resistance to intestinal injury. Furthermore, ectopic activation of STAT5 in mouse or human stem cells promoted LGR5+ IESC self-renewal. Accordingly, STAT5 promotes IESC proliferation and regeneration to mitigate intestinal inflammation. STAT5 is a functional therapeutic target to improve the IESC regenerative response to gut injury.

  13. Intestinal carriage of Campylobacter jejuni and Campylobacter coli among cattle from South-western Norway and comparative genotyping of bovine and human isolates by amplified-fragment length polymorphism

    Directory of Open Access Journals (Sweden)

    Vardund T

    2006-06-01

    Full Text Available Abstract In a survey conducted in 1999–2001, the carriage of thermotolerant Campylobacters in cattle was investigated, and the genetic diversity of C. jejuni within one herd was examined and compared with human isolates. C. jejuni, C. coli and other thermotolerant Campylobacter spp. were isolated from intestinal contents from 26%, 3% and 2% of 804 cattle, respectively. The carriage rate was higher in calves (46% than in adults (29%. Twenty-nine C. jejuni isolates from one herd and 31 human isolates from the study area were genotyped with amplified-fragment length polymorphism (AFLP. Eighty-three % of the bovine isolates fell into three distinct clusters with 95–100% similarity, persistent in the herd for 5–10 months. Among human isolates, 58% showed >90% similarity with bovine isolates. The results show that cattle are a significant and stable reservoir for C. jejuni in the study area. Transmission between individuals within the herd may be sufficient to maintain a steady C. jejuni population independent of environmental influx. The results of this study have provided new information on C. jejuni and C. coli transmission, and also on the carriage in cattle, genotypes stability and similarity between bovine and human isolates.

  14. Intestinal and multivisceral transplantation.

    Science.gov (United States)

    Meira Filho, Sérgio Paiva; Guardia, Bianca Della; Evangelista, Andréia Silva; Matielo, Celso Eduardo Lourenço; Neves, Douglas Bastos; Pandullo, Fernando Luis; Felga, Guilherme Eduardo Gonçalves; Alves, Jefferson André da Silva; Curvelo, Lilian Amorim; Diaz, Luiz Gustavo Guedes; Rusi, Marcela Balbo; Viveiros, Marcelo de Melo; Almeida, Marcio Dias de; Epstein, Marina Gabrielle; Pedroso, Pamella Tung; Salvalaggio, Paolo; Meirelles Júnior, Roberto Ferreira; Rocco, Rodrigo Andrey; Almeida, Samira Scalso de; Rezende, Marcelo Bruno de

    2015-01-01

    Intestinal transplantation has shown exceptional growth over the past 10 years. At the end of the 1990's, intestinal transplantation moved out of the experimental realm to become a routine practice in treating patients with severe complications related to total parenteral nutrition and intestinal failure. In the last years, several centers reported an increasing improvement in survival outcomes (about 80%), during the first 12 months after surgery, but long-term survival is still a challenge. Several advances led to clinical application of transplants. Immunosuppression involved in intestinal and multivisceral transplantation was the biggest gain for this procedure in the past decade due to tacrolimus, and new inducing drugs, mono- and polyclonal anti-lymphocyte antibodies. Despite the advancement of rigid immunosuppression protocols, rejection is still very frequent in the first 12 months, and can result in long-term graft loss. The future of intestinal transplantation and multivisceral transplantation appears promising. The major challenge is early recognition of acute rejection in order to prevent graft loss, opportunistic infections associated to complications, post-transplant lymphoproliferative disease and graft versus host disease; and consequently, improve results in the long run. PMID:25993080

  15. Intestinal dendritic cells in the regulation of mucosal immunity.

    DEFF Research Database (Denmark)

    Bekiaris, Vasileios; Persson, Emma K.

    2014-01-01

    The intestine presents a huge surface area to the outside environment, a property that is of critical importance for its key functions in nutrient digestion, absorption, and waste disposal. As such, the intestine is constantly exposed to dietary and microbial-derived foreign antigens, to which immune cells within the mucosa must suitably respond to maintain intestinal integrity, while also providing the ability to mount effective immune responses to potential pathogens. Dendritic cells (DCs) are sentinel immune cells that play a central role in the initiation and differentiation of adaptive immune responses. In the intestinal mucosa, DCs are located diffusely throughout the intestinal lamina propria, within gut-associated lymphoid tissues, including Peyer's patches and smaller lymphoid aggregates, as well as in intestinal-draining lymph nodes, including mesenteric lymph nodes. The recognition that dietary nutrients and microbial communities in the intestine influence both mucosal and systemic immune cell development and function as well as immune-mediated disease has led to an explosion of literature in mucosal immunology in recent years and a growing interest in the functionality of intestinal DCs. In the current review, we discuss recent findings from our group and others that have provided important insights regarding murine and human intestinal lamina propria DCs and highlighted marked developmental and functional heterogeneity within this compartment. A thorough understanding of the role these subsets play in the regulation of intestinal immune homeostasis and inflammation will help to define novel strategies for the treatment of intestinal pathologies and contribute to improved rational design of mucosal vaccines.

  16. Transcriptome changes during intestinal cell differentiation

    DEFF Research Database (Denmark)

    Tadjali, Mehrdad; Seidelin, Jakob B

    2002-01-01

    The expression of 18149 genes have been analysed during the differentiation of the human intestinal cell line Caco-2. cDNA probes from undifferentiated and differentiated Caco-2 cells were separately hybridised to EST DNAs spotted in an array on a nylon membrane. A remarkable change in the transcriptome was observed during the differentiation of the Caco-2 cells. 8762 of the 18149 genes analysed were expressed above background level in the undifferentiated Caco-2 cells, whereas only 5767 genes were expressed above background in differentiated Caco-2 cells. This pattern of expression was caused by a general down-regulation of genes in the low abundance class. Similar results were found using mouse small intestinal crypt and villus cells, suggesting that the phenomenon also occurs in the intestine in vivo. The expression data were subsequently used in a search for markers for subsets of epithelial cells by performing reverse transcriptase-polymerase chain reaction on RNA extracted from laser dissected intestinal crypt and villi. In a screen of eight transcripts one - SART3 - was identified as a marker for human colonic crypts.

  17. Spinal motor outputs during step-to-step transitions of diverse human gaits

    Directory of Open Access Journals (Sweden)

    Francesco Lacquaniti

    2014-05-01

    Full Text Available Aspects of human motor control can be inferred from the coordination of muscles during movement. For instance, by combining multimuscle electromyographic (EMG recordings with human neuroanatomy, it is possible to estimate alpha-motoneuron (MN pool activations along the spinal cord. It has previously been shown that the spinal motor output fluctuates with the body’s center-of-mass motion, with bursts of activity around foot-strike and foot lift-off during walking. However, it is not known whether these MN bursts are generalizable to other ambulation tasks, nor is it clear if the spatial locus of the activity (along the rostrocaudal axis of the spinal cord is fixed or variable. Here we sought to address these questions by investigating the spatiotemporal characteristics of the spinal motor output during various tasks: walking forward, backward, tiptoe and uphill. We reconstructed spinal maps from 26 leg muscle EMGs, including some intrinsic foot muscles. We discovered that the various walking tasks shared qualitative similarities in their temporal spinal activation profiles, exhibiting peaks around foot-strike and foot-lift. However, we also observed differences in the segmental level and intensity of spinal activations, particularly following foot-strike. For example, forward level-ground walking exhibited a mean motor output roughly 2 times lower than the other gaits. Finally, we found that the reconstruction of the spinal motor output from multimuscle EMG recordings was relatively insensitive to the subset of muscles analyzed. In summary, our results suggested temporal similarities, but spatial differences in the segmental spinal motor outputs during the step-to-step transitions of disparate walking behaviors.

  18. Intestinal anisakidosis (anisakiosis).

    Science.gov (United States)

    Takei, Hidehiro; Powell, Suzanne Z

    2007-10-01

    A case of intestinal anisakidosis in a 42-year-old man in Japan is presented. His chief complaint was an acute onset of severe abdominal pain. Approximately 12 hours before the onset of this symptom, he had eaten sliced raw mackerel ("sashimi"). Upper endoscopy was unremarkable. At exploratory laparotomy, an edematous, diffusely thickened segment of jejunum was observed, which was resected. The postoperative course was uneventful. The segment of small intestine showed a granular indurated area on the mucosal surface, and microscopically, a helminthic larva penetrating the intestinal wall, which was surrounded by a cuff of numerous neutrophils and eosinophils, as well as diffuse acute serositis. A cross section of the larva revealed the internal structures, pathognomonic of Anisakis simplex. Although anisakidosis is rare in the United States, with the increasing popularity of Japanese cuisine, the incidence is expected to increase, and pathologists should be familiar with this disease. PMID:17870022

  19. ER stress transcription factor Xbp1 suppresses intestinal tumorigenesis and directs intestinal stem cells.

    Science.gov (United States)

    Niederreiter, Lukas; Fritz, Teresa M J; Adolph, Timon E; Krismer, Anna-Maria; Offner, Felix A; Tschurtschenthaler, Markus; Flak, Magdalena B; Hosomi, Shuhei; Tomczak, Michal F; Kaneider, Nicole C; Sarcevic, Edina; Kempster, Sarah L; Raine, Tim; Esser, Daniela; Rosenstiel, Philip; Kohno, Kenji; Iwawaki, Takao; Tilg, Herbert; Blumberg, Richard S; Kaser, Arthur

    2013-09-23

    Unresolved endoplasmic reticulum (ER) stress in the epithelium can provoke intestinal inflammation. Hypomorphic variants of ER stress response mediators, such as X-box-binding protein 1 (XBP1), confer genetic risk for inflammatory bowel disease. We report here that hypomorphic Xbp1 function instructs a multilayered regenerative response in the intestinal epithelium. This is characterized by intestinal stem cell (ISC) expansion as shown by an inositol-requiring enzyme 1? (Ire1?)-mediated increase in Lgr5(+) and Olfm4(+) ISCs and a Stat3-dependent increase in the proliferative output of transit-amplifying cells. These consequences of hypomorphic Xbp1 function are associated with an increased propensity to develop colitis-associated and spontaneous adenomatous polyposis coli (APC)-related tumors of the intestinal epithelium, which in the latter case is shown to be dependent on Ire1?. This study reveals an unexpected role for Xbp1 in suppressing tumor formation through restraint of a pathway that involves an Ire1?- and Stat3-mediated regenerative response of the epithelium as a consequence of ER stress. As such, Xbp1 in the intestinal epithelium not only regulates local inflammation but at the same time also determines the propensity of the epithelium to develop tumors. PMID:24043762

  20. The intestinal calcistat

    Directory of Open Access Journals (Sweden)

    M K Garg

    2013-01-01

    Full Text Available The main physiological function of vitamin D is maintenance of calcium homeostasis by its effect on calcium absorption, and bone health in association with parathyroid gland. Vitamin D deficiency (VDD is defined as serum 25-hydroxy vitamin D (25OHD levels <20 ng/ml. Do all subjects with VDD have clinical disease according to this definition? We hypothesize that there exist an intestinal calcistat, which controls the calcium absorption independent of PTH levels. It consists of calcium sensing receptor (CaSR on intestinal brush border, which senses calcium in intestinal cells and vitamin D system in intestinal cells. CaSR dampens the generation of active vitamin D metabolite in intestinal cells and decrease active transcellular calcium transport. It also facilitates passive paracellular diffusion of calcium in intestine. This local adaptation adjusts the fractional calcium absorption according the body requirement. Failure of local adaptation due to decreased calcium intake, decreased supply of 25OHD, mutation in CaSR or vitamin D system decreases systemic calcium levels and systemic adaptations comes into the play. Systemic adaptations consist of rise in PTH and increase in active vitamin D metabolites. These adaptations lead to bone resorption and maintenance of calcium homeostasis. Not all subjects with varying levels of VDD manifest with secondary hyperparathyroidism and decreased in bone mineral density. We suggest that rise in PTH is first indicator of VDD along with decrease in BMD depending on duration of VDD. Hence, subjects with any degree of VDD with normal PTH and BMD should not be labeled as vitamin D deficient. These subjects can be called subclinical VDD, and further studies are required to assess beneficial effect of vitamin D supplementation in this subset of population.

  1. Intestinal Failure (Short Bowel Syndrome)

    Science.gov (United States)

    ... intestine (bacterial overgrowth) N Liver disease due to TPN (Total Parenteral Nutrition) N Infections of the blood from the intravenous catheter used for TPN (continued on next page) Intestinal Failure continued N ...

  2. Mogoltacin enhances vincristine cytotoxicity in human transitional cell carcinoma (TCC) cell line.

    Science.gov (United States)

    Behnam Rassouli, F; Matin, M M; Iranshahi, M; Bahrami, A R; Neshati, V; Mollazadeh, S; Neshati, Z

    2009-03-01

    Bladder cancer is the second common cancer of the genitourinary system throughout the world and intravesical chemotherapy is usually used to reduce tumour recurrence and progression. Human transitional cell carcinoma (TCC) is an epithelial-like adherent cell line originally established from primary bladder carcinoma. Here we report the effect of mogoltacin, a sesquiterpene coumarin from Ferula badrakema on TCC cells. Mogoltacin was isolated from the fruits of F. badrakema, using silica gel column chromatography and preparative thin layer chromatography. Mogoltacin did not have any significant cytotoxicity effect on neoplastic TCC cells at 16, 32, 64, 128, 200 and 600 microg ml(-1) concentrations. In order to analyse its combination effect, TCC cells were cultured in the presence of various combining concentrations of mogoltacin and vincristine. Cells were then observed for morphological changes (by light microscopy) and cytotoxicity using MTT assay. The effect of mogoltacin on vincristine toxicity was studied after 24, 48 and 72 h of drug administration. The results of MTT assay showed that mogoltacin can significantly enhance the cytotoxicity of vincristine and confirmed the morphological observations. Results revealed that combination of 40 microg ml(-1) vincristine with 16 microg ml(-1) mogoltacin increased the cytotoxicity of vincristine after 48 h by 32.8%. PMID:18707855

  3. Space competition and time delays in human range expansions. Application to the neolithic transition.

    Science.gov (United States)

    Isern, Neus; Fort, Joaquim; Vander Linden, Marc

    2012-01-01

    Space competition effects are well-known in many microbiological and ecological systems. Here we analyze such an effect in human populations. The Neolithic transition (change from foraging to farming) was mainly the outcome of a demographic process that spread gradually throughout Europe from the Near East. In Northern Europe, archaeological data show a slowdown on the Neolithic rate of spread that can be related to a high indigenous (Mesolithic) population density hindering the advance as a result of the space competition between the two populations. We measure this slowdown from a database of 902 Early Neolithic sites and develop a time-delayed reaction-diffusion model with space competition between Neolithic and Mesolithic populations, to predict the observed speeds. The comparison of the predicted speed with the observations and with a previous non-delayed model show that both effects, the time delay effect due to the generation lag and the space competition between populations, are crucial in order to understand the observations. PMID:23251430

  4. Targeting canine bladder transitional cell carcinoma with a human bladder cancer-specific ligand

    Directory of Open Access Journals (Sweden)

    Li Bin

    2011-01-01

    Full Text Available Abstract Objective To determine if a human bladder cancer-specific peptide named PLZ4 can target canine bladder cancer cells. Experimental Design The binding of PLZ4 to five established canine invasive transitional cell carcinoma (TCC cell lines and to normal canine bladder urothelial cells was determined using the whole cell binding assay and an affinitofluorescence assay. The WST-8 assay was performed to determine whether PLZ4 affected cell viability. In vivo tumor-specific homing/targeting property and biodistribution of PLZ4 was performed in a mouse xenograft model via tail vein injection and was confirmed with ex vivo imaging. Results PLZ4 exhibited high affinity and specific dose-dependent binding to canine bladder TCC cell lines, but not to normal canine urothelial cells. No significant changes in cell viability or proliferation were observed upon incubation with PLZ4. The in vivo and ex vivo optical imaging study showed that, when linked with the near-infrared fluorescent dye Cy5.5, PLZ4 substantially accumulated at the canine bladder cancer foci in the mouse xenograft model as compared to the control. Conclusions and Clinical Relevance PLZ4 can specifically bind to canine bladder cancer cells. This suggests that the preclinical studies of PLZ4 as a potential diagnostic and therapeutic agent can be performed in dogs with naturally occurring bladder cancer, and that PLZ4 can possibly be developed in the management of canine bladder cancer.

  5. The Influence of the Aspheric Profiles for Transition Zone on Optical Performance of Human Eye After Conventional Ablation

    Science.gov (United States)

    Fang, L.

    2014-12-01

    The analysis in the impact of transition zone on the optical performance of human eye after laser refractive surgery is important for improving visual correction technology. By designing the ablation profiles of aspheric transition zone and creating the ablation profile for conventional refractive surgery in optical zone, the influence of aspheric transition zone on residual aberrations was studied. The results indicated that the ablation profiles of transition zone had a significant influence on the residual wavefront aberrations. For a hyperopia correction, the profile #9 shows a larger induced coma and spherical aberration when the translation of the centre of pupil remains constant. However, for a myopia astigmatism correction, the induced coma and spherical aberration in profile #1 shows relatively larger RMS values than those in other profiles. Therefore, the residual higher order aberrations may be decreased by optimizing ablation profiles of transition zone, but they cannot be eliminated. In order to achieve the best visual performance, the design of ablation pattern of transition zone played a crucial role.

  6. Asociación del virus herpes humano 8 y la hiperplasia linfoide nodular difusa del intestino delgado en la inmunodeficiencia variable común Association between the human herpesvirus 8 and the diffuse nodular lymphoid hyperplasia of the small intestine in common variable immunodeficiency

    Directory of Open Access Journals (Sweden)

    Elena Kokuina

    2009-12-01

    Full Text Available La inmunodeficiencia variable común (IDVC es la inmunodeficiencia primaria más frecuente en el terreno clínico y sus formas de presentación son muy variables. Se describe una paciente con IDVC de adulto con síndrome diarreico crónico, pérdida de peso y linfoadenopatías difusas. Sus características inmunológicas más notables fueron una profunda hipogammaglobulinemia de las 3 clases mayores de inmunoglobulinas y la disminución numérica de las células B (CD19+ y células NK (CD3-CD56+ en sangre periférica. La biopsia del intestino delgado obtenida por panendoscopia asistida por video, reveló hiperplasia linfoide multinodular con atrofia parcial de las vellosidades. La inmunohistoquímica mostró que los nódulos consistían en centros germinales aumentados de tamaño con una distribución de células B (CD20+ y células T (CD3+, similar a la del folículo normal. No se encontró expresión diferencial de cadenas ligeras ? y ?. El método de la reacción en cadena de la polimerasa en tiempo real (QRT-PCR detectó un número apreciable de copias del genoma del virus del herpes humano tipo 8 (VHH-8 (133 copias/µL de ADN en el ADN del nódulo intestinal biopsiado. La infección con el VHH-8 puede ser un factor importante en la patogenia de los trastornos linfoproliferativos en pacientes con IDVC.The common variable immunodeficiency (CVID is the more frequent primary immunodeficiency in clinical field and its presentation forms are very variable. We describe the case of a women presenting with adult CVID with chronic diarrhea syndrome, weight loss and diffuse lymphadenopathies, where the more marked immunologic features were a deep hypogammaglobulinemia of the three major kinds of immunoglobulins and numerical decrease of B cells (CD19+ and NK cells (CD3-CD56+ in peripheral blood. Biopsy of small intestine obtained by video-assisted panendoscope, showed the presence of a multinodular lymphoid hyperplasia with partial atrophy of hairinesses. Immunohistochemistry showed that nodules were high germinal centers with distribution of B cells (CD20+ and T cells (CD3+, similar to that of normal follicle. There was not differential expression of the K and ? light chains. The real time polymerase chain reaction (QRT-PCR method detected many copies from the genome of type 8 human herpesvirus (VHH-8 (133 copies/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.

  7. Asociación del virus herpes humano 8 y la hiperplasia linfoide nodular difusa del intestino delgado en la inmunodeficiencia variable común / Association between the human herpesvirus 8 and the diffuse nodular lymphoid hyperplasia of the small intestine in common variable immunodeficiency

    Scientific Electronic Library Online (English)

    Elena, Kokuina; Carlos, Domínguez Álvarez; Guillermo, Noa Pedroso; Pedro Ariel, Martínez Rodríguez; Vivian, Kourí Cardellá; Yoan, Gutiérrez Pérez; Agustín, Chong López; Delsy, Marrero Hernández; Guillermo, Pérez Román.

    2009-12-01

    Full Text Available La inmunodeficiencia variable común (IDVC) es la inmunodeficiencia primaria más frecuente en el terreno clínico y sus formas de presentación son muy variables. Se describe una paciente con IDVC de adulto con síndrome diarreico crónico, pérdida de peso y linfoadenopatías difusas. Sus características [...] inmunológicas más notables fueron una profunda hipogammaglobulinemia de las 3 clases mayores de inmunoglobulinas y la disminución numérica de las células B (CD19+) y células NK (CD3-CD56+) en sangre periférica. La biopsia del intestino delgado obtenida por panendoscopia asistida por video, reveló hiperplasia linfoide multinodular con atrofia parcial de las vellosidades. La inmunohistoquímica mostró que los nódulos consistían en centros germinales aumentados de tamaño con una distribución de células B (CD20+) y células T (CD3+), similar a la del folículo normal. No se encontró expresión diferencial de cadenas ligeras ? y ?. El método de la reacción en cadena de la polimerasa en tiempo real (QRT-PCR) detectó un número apreciable de copias del genoma del virus del herpes humano tipo 8 (VHH-8) (133 copias/µL de ADN) en el ADN del nódulo intestinal biopsiado. La infección con el VHH-8 puede ser un factor importante en la patogenia de los trastornos linfoproliferativos en pacientes con IDVC. Abstract in english 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 mo [...] re marked immunologic features were a deep hypogammaglobulinemia of the three major kinds of immunoglobulins and numerical decrease of B cells (CD19+) and NK cells (CD3-CD56+) in peripheral blood. Biopsy of small intestine obtained by video-assisted panendoscope, showed the presence of a multinodular lymphoid hyperplasia with partial atrophy of hairinesses. Immunohistochemistry showed that nodules were high germinal centers with distribution of B cells (CD20+) and T cells (CD3+), similar to that of normal follicle. There was not differential expression of the K and ? light chains. The real time polymerase chain reaction (QRT-PCR) method detected many copies from the genome of type 8 human herpesvirus (VHH-8) (133 copies/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.

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

    Directory of Open Access Journals (Sweden)

    Lam Siew

    2010-06-01

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

  9. Multiple Intestinal Lymphoma.

    Science.gov (United States)

    Mastalier, B; Deaconescu, Violeta; Elaiah, W; Dr?ghici, C; Popp, Cristiana; Zurac, Sabina; Balea, M; Tevet, Mihaela; Botezatu, C

    2015-01-01

    Gastrointestinal tract is the most common location for extralymphonodular lymphomas. The small intestine is affected only in 9% of the cases. Intestinal lymphoma may have single or multiple location. This paper describes a case of multiple location in the small intestine of a non-Hodgkin B-cell in a 53 years old patient, who was initially diagnosed with bilateral pneumonia with pleurisy with E. coli, steeper on the right side, but the persistence of symptoms as fever, malaise, despite appropriate treatment, required further investigation. The CT exam observed fluid collection in the hypogastrium around a digestive loop. The patient underwent surgery, the intraoperative foundings being: a large mesenteric tumor - 5 cm in diameter, a terminal ileal mesenteric tumor, a mesenteric tumor - 6 cm in diameter, omentum with nodular formations, a tumor - 3.3/2.5.1 cm in the abdominal wall, pseudotumoral appendix. Segmental. enterectomy with entero-enterostomy, excision of mesenteric tumors, appendectomy and omentectomy were performed. Pathological diagnosis was non-Hodgkin marginal zone B-cell MALT type lymphoma of the small intestine with extension to the appendix, meso, omentum and abdominal wall. Postoperatively, the patient received chemotherapy for remission. PMID:26076564

  10. [Pancreatitis in intestinal diseases].

    Science.gov (United States)

    Gubergrits, N B; Lukashevich, G M; Golubova, O A; Fomenko, P G

    2010-01-01

    In article review of the literature and own data about pathogenesis of pancreatitis and secondary pancreatic insufficiency in various diseases of small and large intestines is presented. The special attention is given to pancreatic insufficiency in celiac disease and in inflammatory bowel disease. The main directions of pancreatitis and exocrine pancreatic insufficiency therapy are grounded. PMID:21268323

  11. Selective proliferation of intestinal Barnesiella under fucosyllactose supplementation in mice

    OpenAIRE

    Weiss, Gisela A; Chassard, Christophe; Hennet, Thierry

    2014-01-01

    The oligosaccharides 2-fucosyllactose and 3-fucosyllactose are major constituents of human breast milk but are not found in mouse milk. Milk oligosaccharides have a prebiotic action, thus affecting the colonisation of the infant intestine by microbiota. To determine the specific effect of fucosyllactose exposure on intestinal microbiota in mice, in the present study, we orally supplemented newborn mice with pure 2-fucosyllactose and 3-fucosyllactose. Exposure to 2-fucosyllactose and 3-fucosyl...

  12. Escherichia coli Pathotypes Occupy Distinct Niches in the Mouse Intestine

    OpenAIRE

    Meador, Jessica P.; Caldwell, Matthew E.; Cohen, Paul S.; Conway, Tyrrell

    2014-01-01

    Since the first step of the infection process is colonization of the host, it is important to understand how Escherichia coli pathogens successfully colonize the intestine. We previously showed that enterohemorrhagic O157:H7 strain E. coli EDL933 colonizes a niche in the streptomycin-treated mouse <