WorldWideScience

Sample records for intestinal biomarkers guanylyl

  1. Loss of guanylyl cyclase C (GCC signaling leads to dysfunctional intestinal barrier.

    Directory of Open Access Journals (Sweden)

    Xiaonan Han

    2011-01-01

    Full Text Available Guanylyl Cyclase C (GCC signaling via uroguanylin (UGN and guanylin activation is a critical mediator of intestinal fluid homeostasis, intestinal cell proliferation/apoptosis, and tumorigenesis. As a mechanism for some of these effects, we hypothesized that GCC signaling mediates regulation of intestinal barrier function.Paracellular permeability of intestinal segments was assessed in wild type (WT and GCC deficient (GCC-/- mice with and without lipopolysaccharide (LPS challenge, as well as in UGN deficient (UGN-/- mice. IFNγ and myosin light chain kinase (MLCK levels were determined by real time PCR. Expression of tight junction proteins (TJPs, phosphorylation of myosin II regulatory light chain (MLC, and STAT1 activation were examined in intestinal epithelial cells (IECs and intestinal mucosa. The permeability of Caco-2 and HT-29 IEC monolayers, grown on Transwell filters was determined in the absence and presence of GCC RNA interference (RNAi. We found that intestinal permeability was increased in GCC-/- and UGN-/- mice compared to WT, accompanied by increased IFNγ levels, MLCK and STAT1 activation in IECs. LPS challenge promotes greater IFNγ and STAT1 activation in IECs of GCC-/- mice compared to WT mice. Claudin-2 and JAM-A expression were reduced in GCC deficient intestine; the level of phosphorylated MLC in IECs was significantly increased in GCC-/- and UGN-/- mice compared to WT. GCC knockdown induced MLC phosphorylation, increased permeability in IEC monolayers under basal conditions, and enhanced TNFα and IFNγ-induced monolayer hyperpermeability.GCC signaling plays a protective role in the integrity of the intestinal mucosal barrier by regulating MLCK activation and TJ disassembly. GCC signaling activation may therefore represent a novel mechanism in maintaining the small bowel barrier in response to injury.

  2. Inhibition of Heat-Stable Toxin-Induced Intestinal Salt and Water Secretion by a Novel Class of Guanylyl Cyclase C Inhibitors.

    Science.gov (United States)

    Bijvelds, Marcel J C; Loos, Michaela; Bronsveld, Inez; Hellemans, Ann; Bongartz, Jean-Pierre; Ver Donck, Luc; Cox, Eric; de Jonge, Hugo R; Schuurkes, Jan A J; De Maeyer, Joris H

    2015-12-01

    Many enterotoxigenic Escherichia coli strains produce the heat-stable toxin, STa, which, by activation of the intestinal receptor-enzyme guanylyl cyclase (GC) C, triggers an acute, watery diarrhea. We set out to identify GCC inhibitors that may be of benefit for the treatment of infectious diarrheal disease. Compounds that inhibit STa-induced cyclic guanosine 3',5'-monophosphate (cGMP) production were selected by performing cyclase assays on cells and membranes containing GCC, or the related GCA. The effect of leads on STa/GCC-dependent activation of the cystic fibrosis transmembrane conductance regulator anion channel was investigated in T84 cells, and in porcine and human intestinal tissue. Their effect on STa-provoked fluid transport was assessed in ligated intestinal loops in piglets. Four N-2-(propylamino)-6-phenylpyrimidin-4-one-substituted piperidines were shown to inhibit GCC-mediated cellular cGMP production. The half maximal inhibitory concentrations were ≤ 5 × 10(-7) mol/L, whereas they were >10 times higher for GCA. In T84 monolayers, these leads blocked STa/GCC-dependent, but not forskolin/adenylyl cyclase-dependent, cystic fibrosis transmembrane conductance regulator activity. GCC inhibition reduced STa-provoked anion secretion in pig jejunal tissue, and fluid retention and cGMP levels in STa-exposed loops. These GCC inhibitors blocked STa-provoked anion secretion in rectal biopsy specimens. We have identified a novel class of GCC inhibitors that may form the basis for development of future therapeutics for (infectious) diarrheal disease. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. Metabolomics analysis identifies intestinal microbiota-derived biomarkers of colonization resistance in clindamycin-treated mice.

    Directory of Open Access Journals (Sweden)

    Robin L P Jump

    Full Text Available The intestinal microbiota protect the host against enteric pathogens through a defense mechanism termed colonization resistance. Antibiotics excreted into the intestinal tract may disrupt colonization resistance and alter normal metabolic functions of the microbiota. We used a mouse model to test the hypothesis that alterations in levels of bacterial metabolites in fecal specimens could provide useful biomarkers indicating disrupted or intact colonization resistance after antibiotic treatment.To assess in vivo colonization resistance, mice were challenged with oral vancomycin-resistant Enterococcus or Clostridium difficile spores at varying time points after treatment with the lincosamide antibiotic clindamycin. For concurrent groups of antibiotic-treated mice, stool samples were analyzed using quantitative real-time polymerase chain reaction to assess changes in the microbiota and using non-targeted metabolic profiling. To assess whether the findings were applicable to another antibiotic class that suppresses intestinal anaerobes, similar experiments were conducted with piperacillin/tazobactam.Colonization resistance began to recover within 5 days and was intact by 12 days after clindamycin treatment, coinciding with the recovery bacteria from the families Lachnospiraceae and Ruminococcaceae, both part of the phylum Firmicutes. Clindamycin treatment caused marked changes in metabolites present in fecal specimens. Of 484 compounds analyzed, 146 (30% exhibited a significant increase or decrease in concentration during clindamycin treatment followed by recovery to baseline that coincided with restoration of in vivo colonization resistance. Identified as potential biomarkers of colonization resistance, these compounds included intermediates in carbohydrate or protein metabolism that increased (pentitols, gamma-glutamyl amino acids and inositol metabolites or decreased (pentoses, dipeptides with clindamycin treatment. Piperacillin

  4. Characterization of two unusual guanylyl cyclases from Dictyostelium

    NARCIS (Netherlands)

    Roelofs, Jeroen; Haastert, Peter J.M. van

    2002-01-01

    Guanylyl cyclase A (GCA) and soluble guanylyl cyclase (sGC) encode GCs in Dictyostelium and have a topology similar to 12-transmembrane and soluble adenylyl cyclase, respectively. We demonstrate that all detectable GC activity is lost in a cell line in which both genes have been inactivated. Cell

  5. Fecal lipocalin 2, a sensitive and broadly dynamic non-invasive biomarker for intestinal inflammation.

    Science.gov (United States)

    Chassaing, Benoit; Srinivasan, Gayathri; Delgado, Maria A; Young, Andrew N; Gewirtz, Andrew T; Vijay-Kumar, Matam

    2012-01-01

    Inflammation has classically been defined histopathologically, especially by the presence of immune cell infiltrates. However, more recent studies suggest a role for "low-grade" inflammation in a variety of disorders ranging from metabolic syndrome to cancer, which is defined by modest elevations in pro-inflammatory gene expression. Consequently, there is a need for cost-effective, non-invasive biomarkers that, ideally, would have the sensitivity to detect low-grade inflammation and have a dynamic range broad enough to reflect classic robust intestinal inflammation. Herein, we report that, for assessment of intestinal inflammation, fecal lipocalin 2 (Lcn-2), measured by ELISA, serves this purpose. Specifically, using a well-characterized mouse model of DSS colitis, we observed that fecal Lcn-2 and intestinal expression of pro-inflammatory cytokines (IL-1β, CXCL1, TNFα) are modestly but significantly induced by very low concentrations of DSS (0.25 and 0.5%), and become markedly elevated at higher concentrations of DSS (1.0 and 4.0%). As expected, careful histopathologic analysis noted only modest immune infiltrates at low DSS concentration and robust colitis at higher DSS concentrations. In accordance, increased levels of the neutrophil product myeloperoxidase (MPO) was only detected in mice given 1.0 and 4.0% DSS. In addition, fecal Lcn-2 marks the severity of spontaneous colitis development in IL-10 deficient mice. Unlike histopathology, MPO, and q-RT-PCR, the assay of fecal Lcn-2 requires only a stool sample, permits measurement over time, and can detect inflammation as early as 1 day following DSS administration. Thus, assay of fecal Lcn-2 by ELISA can function as a non-invasive, sensitive, dynamic, stable and cost-effective means to monitor intestinal inflammation in mice.

  6. Changes in nitrosative stress biomarkers in swine intestine following dietary intervention with verbascoside.

    Science.gov (United States)

    Di Giancamillo, Alessia; Rossi, Raffaella; Vitari, Francesca; Carollo, Valentina; Deponti, Daniela; Corino, Carlo; Domeneghini, Cinzia

    2013-06-01

    In farm animals, oxidative stress can be involved in several intestinal pathological disorders, and many antioxidant molecules, especially those of plant origin, can counteract free radicals, thus stabilizing the gut environment and enhancing health. The aim of the study was to investigate whether the use of verbascoside (VB), a polyphenol plant compound, in pig feeding could modulate oxidative and/or nitrosative stress in the gut. Eighteen male piglets (Dalland) were assigned to two groups, which were fed with either a control diet (CON) or a diet supplemented with 5 mg/kg of verbascoside (VB) for 166 days. At slaughter, duodenum and jejunum specimens were collected. Immunohistochemistry and Western blot analyses were performed on the samples to evaluate free radical adducts, including acrolein (ACR), 8-hydroxydeoxyguanosine (8-OHdg) and nitrotyrosine (NT). A KRL test was also used to assess the total blood antioxidant activity, and no difference was observed. Immunohistochemistry and Western blot showed that dietary treatment decreased the levels of nitrotyrosine in enteroendocrine cell populations(P<0.05). Characterization of the enteroendocrine cell typology was then performed, and serotonin-immunoreactive cells were revealed to be directly involved in decreasing the nitrosative stress status. This preliminary study demonstrates the important role of dietary VB in decreasing stress biomarkers in swine gut, thus highlighting a possible intervention aimed at building a large prospective for antioxidant dietary supplementation in food animal species.

  7. Corruption of homeostatic mechanisms in the guanylyl cyclase C signaling pathway underlying colorectal tumorigenesis

    Science.gov (United States)

    Waldman, Scott A

    2010-01-01

    Colon cancer, the second leading cause of cancer-related mortality worldwide, originates from the malignant transformation of intestinal epithelial cells. The intestinal epithelium undergoes a highly organized process of rapid regeneration along the crypt-villus axis, characterized by proliferation, migration, differentiation and apoptosis, whose coordination is essential to maintaining the mucosal barrier. Disruption of these homeostatic processes predisposes cells to mutations in tumor suppressors or oncogenes, whose dysfunction provides transformed cells an evolutionary growth advantage. While sequences of genetic mutations at different stages along the neoplastic continuum have been established, little is known of the events initiating tumorigenesis prior to adenomatous polyposis coli (APC) mutations. Here, we examine a role for the corruption of homeostasis induced by silencing novel tumor suppressors, including the intestine-specific transcription factor CDX2 and its gene target guanylyl cyclase C (GCC), as early events predisposing cells to mutations in APC and other sequential genes that initiate colorectal cancer. CDX2 and GCC maintain homeostatic regeneration in the intestine by restricting cell proliferation, promoting cell maturation and adhesion, regulating cell migration and defending the intestinal barrier and genomic integrity. Elimination of CDX2 or GCC promotes intestinal tumor initiation and growth in aged mice, mice carrying APC mutations or mice exposed to carcinogens. The roles of CDX2 and GCC in suppressing intestinal tumorigenesis, universal disruption in their signaling through silencing of hormones driving GCC, and the uniform overexpression of GCC by tumors underscore the potential value of oral replacement with GCC ligands as targeted prevention and therapy for colorectal cancer. PMID:20592492

  8. Corruption of homeostatic mechanisms in the guanylyl cyclase C signaling pathway underlying colorectal tumorigenesis.

    Science.gov (United States)

    Li, Peng; Waldman, Scott A

    2010-08-01

    Colon cancer, the second leading cause of cancer-related mortality worldwide, originates from the malignant transformation of intestinal epithelial cells. The intestinal epithelium undergoes a highly organized process of rapid regeneration along the crypt-villus axis, characterized by proliferation, migration, differentiation and apoptosis, whose coordination is essential to maintaining the mucosal barrier. Disruption of these homeostatic processes predisposes cells to mutations in tumor suppressors or oncogenes, whose dysfunction provides transformed cells an evolutionary growth advantage. While sequences of genetic mutations at different stages along the neoplastic continuum have been established, little is known of the events initiating tumorigenesis prior to adenomatous polyposis coli (APC) mutations. Here, we examine a role for the corruption of homeostasis induced by silencing novel tumor suppressors, including the intestine-specific transcription factor CDX2 and its gene target guanylyl cyclase C (GCC), as early events predisposing cells to mutations in APC and other sequential genes that initiate colorectal cancer. CDX2 and GCC maintain homeostatic regeneration in the intestine by restricting cell proliferation, promoting cell maturation and adhesion, regulating cell migration and defending the intestinal barrier and genomic integrity. Elimination of CDX2 or GCC promotes intestinal tumor initiation and growth in aged mice, mice carrying APC mutations or mice exposed to carcinogens. The roles of CDX2 and GCC in suppressing intestinal tumorigenesis, universal disruption in their signaling through silencing of hormones driving GCC, and the uniform overexpression of GCC by tumors underscore the potential value of oral replacement with GCC ligands as targeted prevention and therapy for colorectal cancer.

  9. Nutrition and biomarkers in psychiatry: research on micronutrient deficiencies in schizophrenia, the role of the intestine in the hyperserotonemia of autism, and a method for non-hypothesis driven discovery of biomarkers in urine

    OpenAIRE

    Kemperman, Ramses Franciscus Jacobus

    2007-01-01

    This thesis describes the study of markers of nutrition and intestinal motility in mental disorders with a focus on schizophrenia and autism, and the development, evaluation and application of a biomarker discovery method for urine. The aim of the thesis is to investigate the role of long-chain polyunsaturated fatty acids (LCPUFA), B-vitamins and platelet (PLT) serotonin (5-HT) in schizophrenia and autism. The thesis proposes also that biomarker research in psychiatric disease is of great rel...

  10. Identification of biomarkers for radiation-induced acute intestinal symptoms (RIAISs) in cervical cancer patients by serum protein profiling

    International Nuclear Information System (INIS)

    Chai Yanlan; Wang Juan; Gao Ying

    2015-01-01

    Radiation-induced acute intestinal symptoms (RIAISs) are the most frequent complication of radiotherapy that causes great pain and limits the treatment efficacy. The aim of this study was to identify serum biomarkers of RIAISs in cervical cancer patients by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). Serum samples were collected from 66 cervical cancer patients prior to pelvic radiotherapy. In our study, RIAISs occurred in 11 patients. An additional 11 patients without RIAISs were selected as controls, whose age, stage, histological type and treatment methods were matched to RIAISs patients. The 22 sera were subsequently analyzed by SELDI-TOF MS, and the resulting protein profiles were evaluated to identify biomarkers using appropriate bioinformatics tools. Comparing the protein profiles of serum samples from the RIAIS group and the control group, it was found that 22 protein peaks were significantly different (P < 0.05), and six of these peaks with mass-to-charge (m/z) ratios of 7514.9, 4603.94, 6887.41, 2769.21, 3839.72 and 4215.7 were successfully identified. A decision tree model of biomarkers was constructed based on three biomarkers (m/z 1270.88, 1503.23 and 7514.90), which separated RIAIS-affected patients from the control group with an accuracy of 81%. This study suggests that serum proteomic analysis by SELDI-TOF MS can identify cervical cancer patients that are susceptible to RIAISs prior to pelvic radiotherapy. (author)

  11. Nutrition and biomarkers in psychiatry : research on micronutrient deficiencies in schizophrenia, the role of the intestine in the hyperserotonemia of autism, and a method for non-hypothesis driven discovery of biomarkers in urine

    NARCIS (Netherlands)

    Kemperman, Ramses Franciscus Jacobus

    2007-01-01

    This thesis describes the study of markers of nutrition and intestinal motility in mental disorders with a focus on schizophrenia and autism, and the development, evaluation and application of a biomarker discovery method for urine. The aim of the thesis is to investigate the role of long-chain

  12. Guanylyl cyclase C in colorectal cancer: susceptibility gene and potential therapeutic target.

    Science.gov (United States)

    Lin, Jieru E; Li, Peng; Pitari, Giovanni M; Schulz, Stephanie; Waldman, Scott A

    2009-05-01

    Colorectal cancer is one of the leading causes of tumor-related morbidity and mortality worldwide. While mechanisms underlying this disease have been elucidated over the past two decades, these molecular insights have failed to translate into efficacious therapy. The oncogenomic view of cancer suggests that terminal transformation reflects the sequential corruption of signal transduction circuits regulating key homeostatic mechanisms, whose multiplicity underlies the therapeutic resistance of most tumors to interventions targeting individual pathways. Conversely, the paucity of mechanistic insights into proximal pathophysiological processes that initiate and amplify oncogenic circuits preceding accumulation of mutations and transformation impedes development of effective prevention and therapy. In that context, guanylyl cyclase C (GCC), the intestinal receptor for the paracrine hormones guanylin and uroguanylin, whose early loss characterizes colorectal transformation, has emerged as a component of lineage-specific homeostatic programs organizing spatiotemporal patterning along the crypt-surface axis. Dysregulation of GCC signaling, reflecting hormone loss, promotes tumorigenesis through reprogramming of replicative and bioenergetic circuits and genomic instability. Compensatory upregulation of GCC in response to hormone loss provides a unique translational opportunity for prevention and treatment of colorectal tumors by hormone-replacement therapy.

  13. Inferring biological functions of guanylyl cyclases with computational methods

    KAUST Repository

    Alquraishi, May Majed

    2013-09-03

    A number of studies have shown that functionally related genes are often co-expressed and that computational based co-expression analysis can be used to accurately identify functional relationships between genes and by inference, their encoded proteins. Here we describe how a computational based co-expression analysis can be used to link the function of a specific gene of interest to a defined cellular response. Using a worked example we demonstrate how this methodology is used to link the function of the Arabidopsis Wall-Associated Kinase-Like 10 gene, which encodes a functional guanylyl cyclase, to host responses to pathogens. © Springer Science+Business Media New York 2013.

  14. Multiple lineage specific expansions within the guanylyl cyclase gene family

    Directory of Open Access Journals (Sweden)

    O'Halloran Damien M

    2006-03-01

    Full Text Available Abstract Background Guanylyl cyclases (GCs are responsible for the production of the secondary messenger cyclic guanosine monophosphate, which plays important roles in a variety of physiological responses such as vision, olfaction, muscle contraction, homeostatic regulation, cardiovascular and nervous function. There are two types of GCs in animals, soluble (sGCs which are found ubiquitously in cell cytoplasm, and receptor (rGC forms which span cell membranes. The complete genomes of several vertebrate and invertebrate species are now available. These data provide a platform to investigate the evolution of GCs across a diverse range of animal phyla. Results In this analysis we located GC genes from a broad spectrum of vertebrate and invertebrate animals and reconstructed molecular phylogenies for both sGC and rGC proteins. The most notable features of the resulting phylogenies are the number of lineage specific rGC and sGC expansions that have occurred during metazoan evolution. Among these expansions is a large nematode specific rGC clade comprising 21 genes in C. elegans alone; a vertebrate specific expansion in the natriuretic receptors GC-A and GC-B; a vertebrate specific expansion in the guanylyl GC-C receptors, an echinoderm specific expansion in the sperm rGC genes and a nematode specific sGC clade. Our phylogenetic reconstruction also shows the existence of a basal group of nitric oxide (NO insensitive insect and nematode sGCs which are regulated by O2. This suggests that the primordial eukaryotes probably utilized sGC as an O2 sensor, with the ligand specificity of sGC later switching to NO which provides a very effective local cell-to-cell signalling system. Phylogenetic analysis of the sGC and bacterial heme nitric oxide/oxygen binding protein domain supports the hypothesis that this domain originated from a cyanobacterial source. Conclusion The most salient feature of our phylogenies is the number of lineage specific expansions

  15. Estradiol rapidly inhibits soluble guanylyl cyclase expression in rat uterus

    Science.gov (United States)

    Krumenacker, J. S.; Hyder, S. M.; Murad, F.

    2001-01-01

    Previous reports that investigated the regulation of the NO/soluble guanylyl cyclase (sGC)/cGMP pathway by estrogenic compounds have focused primarily on the levels of NO, NO-producing enzymes, and cGMP in various tissues. In this study, we demonstrate that 17beta-estradiol (E2) regulates the alpha(1) and beta(1) subunits of the NO receptor, sGC, at the mRNA and protein levels in rat uterus. Using real-time quantitative PCR, we found that within 1 h of in vivo E2 administration to rats, sGC mRNA levels begin to diminish. After 3 h, there is a maximal diminution of sGC mRNA expression (sGC alpha(1) 10% and sGC beta(1) 33% of untreated). This effect was blocked by the estrogen receptor antagonist, ICI 182,780, indicating that estrogen receptor is required. The effect of E2 also was observed in vitro with incubations of uterine tissue, indicating that the response does not depend on the secondary release of other hormones or factors from other tissues. Puromycin did not block the effect, suggesting the effects occur because of preexisting factors in uterine tissues and do not require new protein synthesis. Using immunoblot analysis, we found that sGC protein levels also were reduced by E2 over a similar time course as the sGC mRNA. We conclude that sGC plays a vital role in the NO/sGC/cGMP regulatory pathway during conditions of elevated estrogen levels in the rat uterus as a result of the reduction of sGC expression.

  16. Soluble guanylyl cyclase is involved in PDT-induced injury of crayfish glial cells

    Science.gov (United States)

    Kovaleva, V. D.; Uzdensky, A. B.

    2016-04-01

    Photodynamic therapy (PDT) is a potential tool for selective destruction of malignant brain tumors. However, not only malignant but also healthy neurons and glial cells may be damaged during PDT. Nitric oxide is an important modulator of cell viability and intercellular neuroglial communications. NO have been already shown to participate in PDT-induced injury of neurons and glial cells. As soluble guanylyl cyclase is the only known receptor for NO, we have studied the possible role of soluble guanylyl cyclase in the regulation of survival and death of neurons and surrounding glial cells under photo-oxidative stress induced by photodynamic treatment (PDT). The crayfish stretch receptor consisting of a single identified sensory neuron enveloped by glial cells is a simple but informative model object. It was photosensitized with alumophthalocyanine photosens (10 nM) and irradiated with a laser diode (670 nm, 0.4 W/cm2). Using inhibitory analysis we have shown that during PDT soluble guanylyl cyclase, probably, has proapoptotic and antinecrotic effect on the glial cells of the isolated crayfish stretch receptor. Proapoptotic effect of soluble guanylyl cyclase could be mediated by protein kinase G (PKG). Thus, the involvement of NO/sGC/cGMP/PKG signaling pathway in PDT-induced apoptosis of glial cells was indirectly demonstrated.

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

    Science.gov (United States)

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

    2016-04-01

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

  18. Characterization of the Human ?1?1 Soluble Guanylyl Cyclase Promoter

    OpenAIRE

    Marro, Mart?n L.; Peir?, Concepci?n; Panayiotou, Catherine M.; Baliga, Reshma S.; Meurer, Sabine; Schmidt, Harald H. H. W.; Hobbs, Adrian J.

    2008-01-01

    Soluble guanylyl cyclase (sGC) is the principal receptor for NO and plays a ubiquitous role in regulating cellular function. This is exemplified in the cardiovascular system where sGC governs smooth muscle tone and growth, vascular permeability, leukocyte flux, and platelet aggregation. As a consequence, aberrant NO-sGC signaling has been linked to diseases including hypertension, atherosclerosis, and stroke. Despite these key (patho)physiological roles, little is known about the expressional...

  19. CD4+ CD25+ FOXP3+ T cell frequency in the peripheral blood is a biomarker that distinguishes intestinal tuberculosis from Crohn's disease.

    Science.gov (United States)

    Tiwari, Veena; Kedia, Saurabh; Garg, Sushil Kumar; Rampal, Ritika; Mouli, V Pratap; Purwar, Anuja; Mitra, D K; Das, Prasenjit; Dattagupta, S; Makharia, Govind; Acharya, S K; Ahuja, Vineet

    2018-01-01

    Distinguishing between Crohn's Disease (CD) and Intestinal Tuberculosis (ITB) has been a challenging task for clinicians due to their similar presentation. CD4+FOXP3+ T regulatory cells (Tregs) have been reported to be increased in patients with pulmonary tuberculosis. However, there is no such data available in ITB. The aim of this study was to investigate the differential expression of FOXP3+ T cells in patients with ITB and CD and its utility as a biomarker. The study prospectively recruited 124 patients with CD, ITB and controls: ulcerative colitis (UC) and patients with only haemorrhoidal bleed. Frequency of CD4+CD25+FOXP3+ Tregs in peripheral blood (flow cytometry), FOXP3 mRNA expression in blood and colonic mucosa (qPCR) and FOXP3+ T cells in colonic mucosa (immunohistochemistry) were compared between controls, CD and ITB patients. Frequency of CD4+CD25+FOXP3+ Treg cells in peripheral blood was significantly increased in ITB as compared to CD. Similarly, significant increase in FOXP3+ T cells and FOXP3 mRNA expression was observed in colonic mucosa of ITB as compared to CD. ROC curve showed that a value of >32.5% for FOXP3+ cells in peripheral blood could differentiate between CD and ITB with a sensitivity of 75% and a specificity of 90.6%. Phenotypic enumeration of peripheral CD4+CD25+FOXP3+ Treg cells can be used as a non-invasive biomarker in clinics with a high diagnostic accuracy to differentiate between ITB and CD in regions where TB is endemic.

  20. Membrane Guanylyl Cyclase Complexes Shape the Photoresponses of Retinal Rods and Cones

    Directory of Open Access Journals (Sweden)

    Xiao-Hong eWen

    2014-06-01

    Full Text Available In vertebrate rods and cones, photon capture by rhodopsin leads to the destruction of cyclic GMP (cGMP and the subsequent closure of cyclic nucleotide gated (CNG ion channels in the outer segment plasma membrane. Replenishment of cGMP and reopening of the channels limit the growth of the photon response and are requisite for its recovery. In different vertebrate retinas, there may be as many as four types of membrane guanylyl cyclases (GCs for cGMP synthesis. Ten neuronal Ca2+ sensor proteins could potentially modulate their activities. The mouse is proving to be an effective model for characterizing the roles of individual components because its relative simplicity can be reduced further by genetic engineering. There are two types of guanylyl cyclase activating proteins (GCAPs and two types of GCs in mouse rods, whereas cones express one type of GCAP and one type of GC. Mutant mouse rods and cones bereft of both GCAPs have large, long lasting photon responses. Thus, GCAPs normally mediate negative feedback tied to the light-induced decline in intracellular Ca2+ that accelerates GC activity to curtail the growth and duration of the photon response. Rods from other mutant mice that express a single GCAP type reveal how the two GCAPs normally work together as a team. Because of its lower Ca2+ affinity, GCAP1 is the first responder that senses the initial decrease in Ca2+ following photon absorption and acts to limit response amplitude. GCAP2, with a higher Ca2+ affinity, is recruited later during the course of the photon response as Ca2+ levels continue to decline further. The main role of GCAP2 is to provide for a timely response recovery and it is particularly important after exposure to very bright light. The multiplicity of GC isozymes and GCAP homologs in the retinas of other vertebrates confers greater flexibility in shaping the photon responses in order to tune visual sensitivity, dynamic range and frequency response.

  1. The Receptor Guanylyl Cyclase Type D (GC-D) Ligand Uroguanylin Promotes the Acquisition of Food Preferences in Mice

    OpenAIRE

    Arakawa, Hiroyuki; Kelliher, Kevin R.; Zufall, Frank; Munger, Steven D.

    2013-01-01

    Rodents rely on olfactory stimuli to communicate information between conspecifics that is critical for health and survival. For example, rodents that detect a food odor simultaneously with the social odor carbon disulfide (CS2) will acquire a preference for that food. Disruption of the chemosensory transduction cascade in CS2-sensitive olfactory sensory neurons (OSNs) that express the receptor guanylyl cyclase type D (GC-D; GC-D+ OSNs) will prevent mice from acquiring these preferences. GC-D+...

  2. Mapping Soluble Guanylyl Cyclase and Protein Disulfide Isomerase Regions of Interaction.

    Directory of Open Access Journals (Sweden)

    Erin J Heckler

    Full Text Available Soluble guanylyl cyclase (sGC is a heterodimeric nitric oxide (NO receptor that produces cyclic GMP. This signaling mechanism is a key component in the cardiovascular system. NO binds to heme in the β subunit and stimulates the catalytic conversion of GTP to cGMP several hundred fold. Several endogenous factors have been identified that modulate sGC function in vitro and in vivo. In previous work, we determined that protein disulfide isomerase (PDI interacts with sGC in a redox-dependent manner in vitro and that PDI inhibited NO-stimulated activity in cells. To our knowledge, this was the first report of a physical interaction between sGC and a thiol-redox protein. To characterize this interaction between sGC and PDI, we first identified peptide linkages between sGC and PDI, using a lysine cross-linking reagent and recently developed mass spectrometry analysis. Together with Flag-immunoprecipitation using sGC domain deletions, wild-type (WT and mutated PDI, regions of sGC involved in this interaction were identified. The observed data were further explored with computational modeling to gain insight into the interaction mechanism between sGC and oxidized PDI. Our results indicate that PDI interacts preferentially with the catalytic domain of sGC, thus providing a mechanism for PDI inhibition of sGC. A model in which PDI interacts with either the α or the β catalytic domain is proposed.

  3. Biased activity of soluble guanylyl cyclase: the Janus face of thymoquinone

    Directory of Open Access Journals (Sweden)

    Charlotte Detremmerie

    2017-07-01

    Full Text Available The natural compound thymoquinone, extracted from Nigella sativa (black cumin, is widely used in humans for its anti-oxidative properties. Thymoquinone is known for its acute endothelium-independent vasodilator effects in isolated rat aortae and pulmonary arteries, depending in part on activation of adenosine triphosphate-sensitive potassium channels and inhibition of voltage-dependent calcium channels. The compound also improves endothelial dysfunction in mesenteric arteries of ageing rodents and in aortae of rabbits treated with pyrogallol, by inhibiting oxidative stress. Serendipitously, thymoquinone was found to augment contractions in isolated arteries with endothelium of both rats and pigs. The endothelium-dependent augmentation it causes counterintuitively depends on biased activation of soluble guanylyl cyclase (sGC producing inosine 3ʹ,5ʹ-cyclic monophosphate (cyclic IMP rather than guanosine 3ʹ,5ʹ-cyclic monophosphate. This phenomenon shows a striking mechanistic similarity to the hypoxic augmentation previously observed in porcine coronary arteries. The cyclic IMP preferentially produced under thymoquinone exposure causes an increased contractility of arterial smooth muscle by interfering with calcium homeostasis. This brief review summarizes the vascular pharmacology of thymoquinone, focussing in particular on how the compound causes endothelium-dependent contractions by biasing the activity of sGC.

  4. The plant natriuretic peptide receptor is a guanylyl cyclase and enables cGMP-dependent signaling

    KAUST Repository

    Turek, Ilona

    2016-03-05

    The functional homologues of vertebrate natriuretic peptides (NPs), the plant natriuretic peptides (PNPs), are a novel class of peptidic hormones that signal via guanosine 3′,5′-cyclic monophosphate (cGMP) and systemically affect plant salt and water balance and responses to biotrophic plant pathogens. Although there is increasing understanding of the complex roles of PNPs in plant responses at the systems level, little is known about the underlying signaling mechanisms. Here we report isolation and identification of a novel Leucine-Rich Repeat (LRR) protein that directly interacts with A. thaliana PNP, AtPNP-A. In vitro binding studies revealed that the Arabidopsis AtPNP-A binds specifically to the LRR protein, termed AtPNP-R1, and the active region of AtPNP-A is sufficient for the interaction to occur. Importantly, the cytosolic part of the AtPNP-R1, much like in some vertebrate NP receptors, harbors a catalytic center diagnostic for guanylyl cyclases and the recombinant AtPNP-R1 is capable of catalyzing the conversion of guanosine triphosphate to cGMP. In addition, we show that AtPNP-A causes rapid increases of cGMP levels in wild type (WT) leaf tissue while this response is significantly reduced in the atpnp-r1 mutants. AtPNP-A also causes cGMP-dependent net water uptake into WT protoplasts, and hence volume increases, whereas responses of the protoplasts from the receptor mutant are impaired. Taken together, our results suggest that the identified LRR protein is an AtPNP-A receptor essential for the PNP-dependent regulation of ion and water homeostasis in plants and that PNP- and vertebrate NP-receptors and their signaling mechanisms share surprising similarities. © 2016 Springer Science+Business Media Dordrecht

  5. Nitroxyl (HNO stimulates soluble guanylyl cyclase to suppress cardiomyocyte hypertrophy and superoxide generation.

    Directory of Open Access Journals (Sweden)

    Eliane Q Lin

    Full Text Available New therapeutic targets for cardiac hypertrophy, an independent risk factor for heart failure and death, are essential. HNO is a novel redox sibling of NO• attracting considerable attention for the treatment of cardiovascular disorders, eliciting cGMP-dependent vasodilatation yet cGMP-independent positive inotropy. The impact of HNO on cardiac hypertrophy (which is negatively regulated by cGMP however has not been investigated.Neonatal rat cardiomyocytes were incubated with angiotensin II (Ang II in the presence and absence of the HNO donor Angeli's salt (sodium trioxodinitrate or B-type natriuretic peptide, BNP (all 1 µmol/L. Hypertrophic responses and its triggers, as well as cGMP signaling, were determined.We now demonstrate that Angeli's salt inhibits Ang II-induced hypertrophic responses in cardiomyocytes, including increases in cardiomyocyte size, de novo protein synthesis and β-myosin heavy chain expression. Angeli's salt also suppresses Ang II induction of key triggers of the cardiomyocyte hypertrophic response, including NADPH oxidase (on both Nox2 expression and superoxide generation, as well as p38 mitogen-activated protein kinase (p38MAPK. The antihypertrophic, superoxide-suppressing and cGMP-elevating effects of Angeli's salt were mimicked by BNP. We also demonstrate that the effects of Angeli's salt are specifically mediated by HNO (with no role for NO• or nitrite, with subsequent activation of cardiomyocyte soluble guanylyl cyclase (sGC and cGMP signaling (on both cGMP-dependent protein kinase, cGK-I and phosphorylation of vasodilator-stimulated phosphoprotein, VASP.Our results demonstrate that HNO prevents cardiomyocyte hypertrophy, and that cGMP-dependent NADPH oxidase suppression contributes to these antihypertrophic actions. HNO donors may thus represent innovative pharmacotherapy for cardiac hypertrophy.

  6. 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 ...

  7. The Arabidopsis thaliana proteome harbors undiscovered multi-domain molecules with functional guanylyl cyclase catalytic centers

    KAUST Repository

    Wong, Aloysius Tze

    2013-07-08

    Background: Second messengers link external cues to complex physiological responses. One such messenger, 3\\',5\\'-cyclic guanosine monophosphate (cGMP), has been shown to play a key role in many physiological responses in plants. However, in higher plants, guanylyl cyclases (GCs), enzymes that generate cGMP from guanosine-5\\'-triphosphate (GTP) have remained elusive until recently. GC search motifs constructed from the alignment of known GCs catalytic centers form vertebrates and lower eukaryotes have led to the identification of a number of plant GCs that have been characterized in vitro and in vivo.Presentation of the hypothesis.Recently characterized GCs in Arabidopsis thaliana contributed to the development of search parameters that can identify novel candidate GCs in plants. We hypothesize that there are still a substantial number (> 40) of multi-domain molecules with potentially functional GC catalytic centers in plants that remain to be discovered and characterized. Testing the hypothesis. The hypothesis can be tested, firstly, by computational methods constructing 3D models of selected GC candidates using available crystal structures as templates. Homology modeling must include substrate docking that can provide support for the structural feasibility of the GC catalytic centers in those candidates. Secondly, recombinant peptides containing the GC domain need to be tested in in vitro GC assays such as the enzyme-linked immune-sorbent assay (ELISA) and/or in mass spectrometry based cGMP assays. In addition, quantification of in vivo cGMP transients with fluorescent cGMP-reporter assays in wild-type or selected mutants will help to elucidate the biological role of novel GCs.Implications of the hypothesis.If it turns out that plants do harbor a large number of functional GC domains as part of multi-domain enzymes, then major new insights will be gained into the complex signal transduction pathways that link cGMP to fundamental processes such as ion transport

  8. C-type natriuretic peptide and the guanylyl cyclase receptors in the rat ovary are modulated by the estrous cycle.

    Science.gov (United States)

    Jankowski, M; Reis, A M; Mukaddam-Daher, S; Dam, T V; Farookhi, R; Gutkowska, J

    1997-01-01

    We have previously shown that rat ovaries synthesize atrial natriuretic peptide (ANP) and express the cognate guanylyl cyclase (GC-A and GC-B) receptors for ANP. Since another natriuretic peptide, termed the C-type natriuretic peptide (CNP), can also interact with these receptors, we have investigated whether rat ovaries express CNP and if so, whether the concentration of this natriuretic peptide and the guanylyl-cyclase receptors are influenced by the estrous cycle. CNP mRNA was detected in rat ovaries using a reverse transcription (RT) polymerase chain reaction (PCR) strategy. RIA of ovarian extracts, obtained at the individual days of the estrous cycle, revealed the presence of immunoreactive CNP. The highest levels of CNP were detected at proestrus and were approximately 4-fold higher than the levels seen at any other stage of the cycle. GC-A and GC-B receptors were detected using quantitative autoradiography after application of either [125I]ANP or [125I]-tyr0CNP to sections of frozen ovaries. The highest specific binding of each radiolabeled ligand was seen in ovaries from proestrous animals. The GC-B receptors were localized to the membrana granulosa of developing ovarian follicles. Using quantitative PCR, we determined that levels of GC-A and GC-B mRNAs were highest in the ovaries of proestrous animals and were approximately 2- to 3-fold higher than the levels seen at diestrus. These findings demonstrate that a natriuretic peptide system, consisting of ligands and receptors, is present in the rat ovary. Since CNP and the GC receptors show coordinate estrous cycle-dependent variation with maximal expression at proestrus, we speculate that the natriuretic peptides may play an important role in either the development of ovulatory follicles or in the ovulatory process.

  9. Intestinal Obstruction

    Science.gov (United States)

    ... the obstruction along the intestines. Treatment Suction via nasogastric tube Fluids given by vein Surgery for strangulation Sometimes ... nose and placed in the stomach (called a nasogastric tube) or into the intestine. Suction is applied to ...

  10. CD-NP: a novel engineered dual guanylyl cyclase activator with anti-fibrotic actions in the heart.

    Directory of Open Access Journals (Sweden)

    Fernando L Martin

    Full Text Available Natriuretic peptides (NPs are cardioprotective through the activation of guanylyl cyclase (GC receptors A and B. CD-NP, also known as cenderitide, is a novel engineered NP that was designed to uniquely serve as a first-in-class dual GC receptor agonist. Recognizing the aldosterone suppressing actions of GC-A activation and the potent inhibitory actions on collagen synthesis and fibroblast proliferation through GC-B activation, the current study was designed to establish the anti-fibrotic actions of CD-NP, administered subcutaneously, in an experimental rat model of early cardiac fibrosis induced by unilateral nephrectomy (UNX. Our results demonstrate that a two week subcutaneous infusion of CD-NP significantly suppresses left ventricular fibrosis and circulating aldosterone, while preserving both systolic and diastolic function, in UNX rats compared to vehicle treated UNX rats. Additionally we also confirmed, in vitro, that CD-NP significantly generates the second messenger, cGMP, through both the GC-A and GC-B receptors. Taken together, this novel dual GC receptor activator may represent an innovative anti-fibrotic therapeutic agent.

  11. Clathrin-dependent internalization, signaling, and metabolic processing of guanylyl cyclase/natriuretic peptide receptor-A.

    Science.gov (United States)

    Somanna, Naveen K; Mani, Indra; Tripathi, Satyabha; Pandey, Kailash N

    2018-04-01

    Cardiac hormones, atrial and brain natriuretic peptides (ANP and BNP), have pivotal roles in renal hemodynamics, neuroendocrine signaling, blood pressure regulation, and cardiovascular homeostasis. Binding of ANP and BNP to the guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) induces rapid internalization and trafficking of the receptor via endolysosomal compartments, with concurrent generation of cGMP. However, the mechanisms of the endocytotic processes of NPRA are not well understood. The present study, using 125 I-ANP binding assay and confocal microscopy, examined the function of dynamin in the internalization of NPRA in stably transfected human embryonic kidney-293 (HEK-293) cells. Treatment of recombinant HEK-293 cells with ANP time-dependently accelerated the internalization of receptor from the cell surface to the cell interior. However, the internalization of ligand-receptor complexes of NPRA was drastically decreased by the specific inhibitors of clathrin- and dynamin-dependent receptor internalization, almost 85% by monodansylcadaverine, 80% by chlorpromazine, and 90% by mutant dynamin, which are specific blockers of endocytic vesicle formation. Visualizing the internalization of NPRA and enhanced GFP-tagged NPRA in HEK-293 cells by confocal microscopy demonstrated the formation of endocytic vesicles after 5 min of ANP treatment; this effect was blocked by the inhibitors of clathrin and by mutant dynamin construct. Our results suggest that NPRA undergoes internalization via clathrin-mediated endocytosis as part of its normal itinerary, including trafficking, signaling, and metabolic degradation.

  12. The receptor guanylyl cyclase type D (GC-D) ligand uroguanylin promotes the acquisition of food preferences in mice.

    Science.gov (United States)

    Arakawa, Hiroyuki; Kelliher, Kevin R; Zufall, Frank; Munger, Steven D

    2013-06-01

    Rodents rely on olfactory stimuli to communicate information between conspecifics that is critical for health and survival. For example, rodents that detect a food odor simultaneously with the social odor carbon disulfide (CS(2)) will acquire a preference for that food. Disruption of the chemosensory transduction cascade in CS(2-)sensitive olfactory sensory neurons (OSNs) that express the receptor guanylyl cyclase type D (GC-D; GC-D+ OSNs) will prevent mice from acquiring these preferences. GC-D+ OSNs also respond to the natriuretic peptide uroguanylin, which is excreted into urine and feces. We analyzed if uroguanylin could also act as a social stimulus to promote the acquisition of food preferences. We found that feces of mice that had eaten odored food, but not unodored food, promoted a strong preference for that food in mice exposed to the feces. Olfactory exploration of uroguanylin presented with a food odor similarly produced a preference that was absent when mice were exposed to the food odor alone. Finally, the acquisition of this preference was dependent on GC-D+ OSNs, as mice lacking GC-D (Gucy2d(-)(/-) mice) showed no preference for the demonstrated food. Together with our previous findings, these results demonstrate that the diverse activators of GC-D+ OSNs elicit a common behavioral result and suggest that this specialized olfactory subsystem acts as a labeled line for a type of associative olfactory learning.

  13. Intestine transplantation

    Directory of Open Access Journals (Sweden)

    Tadeja Pintar

    2011-02-01

    Conclusion: Intestine transplantation is reserved for patients with irreversible intestinal failure due to short gut syndrome requiring total paranteral nutrition with no possibility of discontinuation and loss of venous access for patient maintenance. In these patients complications of underlying disease and long-term total parenteral nutrition are present.

  14. Intestinal Ischemia

    Science.gov (United States)

    ... weight loss Intestinal ischemia Symptoms & causes Diagnosis & treatment Advertisement Mayo Clinic does not endorse companies or products. ... a Job Site Map About This Site Twitter Facebook Google YouTube Pinterest Mayo Clinic is a not- ...

  15. Intestinal Coccidia

    OpenAIRE

    MJ Ggaravi

    2007-01-01

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

  16. Receptor-Type Guanylyl Cyclase at 76C (Gyc76C Regulates De Novo Lumen Formation during Drosophila Tracheal Development.

    Directory of Open Access Journals (Sweden)

    Monn Monn Myat

    Full Text Available Lumen formation and maintenance are important for the development and function of essential organs such as the lung, kidney and vasculature. In the Drosophila embryonic trachea, lumena form de novo to connect the different tracheal branches into an interconnected network of tubes. Here, we identify a novel role for the receptor type guanylyl cyclase at 76C (Gyc76C in de novo lumen formation in the Drosophila trachea. We show that in embryos mutant for gyc76C or its downsteam effector protein kinase G (PKG 1, tracheal lumena are disconnected. Dorsal trunk (DT cells of gyc76C mutant embryos migrate to contact each other and complete the initial steps of lumen formation, such as the accumulation of E-cadherin (E-cad and formation of an actin track at the site of lumen formation. However, the actin track and E-cad contact site of gyc76C mutant embryos did not mature to become a new lumen and DT lumena did not fuse. We also observed failure of the luminal protein Vermiform to be secreted into the site of new lumen formation in gyc76C mutant trachea. These DT lumen formation defects were accompanied by altered localization of the Arf-like 3 GTPase (Arl3, a known regulator of vesicle-vesicle and vesicle-membrane fusion. In addition to the DT lumen defect, lumena of gyc76C mutant terminal cells were shorter compared to wild-type cells. These studies show that Gyc76C and downstream PKG-dependent signaling regulate de novo lumen formation in the tracheal DT and terminal cells, most likely by affecting Arl3-mediated luminal secretion.

  17. Small Intestine Disorders

    Science.gov (United States)

    ... disease Crohn's disease Infections Intestinal cancer Intestinal obstruction Irritable bowel syndrome Ulcers, such as peptic ulcer Treatment of disorders of the small intestine depends on the cause.

  18. Biomarkers in inflammatory bowel diseases

    DEFF Research Database (Denmark)

    Bennike, Tue; Birkelund, Svend; Stensballe, Allan

    2014-01-01

    or stool later can be screened for. When considering the protein complexity encountered in intestinal biopsy-samples and the recent development within the field of mass spectrometry driven quantitative proteomics, a more thorough and accurate biomarker discovery endeavor could today be performed than ever......Unambiguous diagnosis of the two main forms of inflammatory bowel diseases (IBD): Ulcerative colitis (UC) and Crohn's disease (CD), represents a challenge in the early stages of the diseases. The diagnosis may be established several years after the debut of symptoms. Hence, protein biomarkers...... for early and accurate diagnostic could help clinicians improve treatment of the individual patients. Moreover, the biomarkers could aid physicians to predict disease courses and in this way, identify patients in need of intensive treatment. Patients with low risk of disease flares may avoid treatment...

  19. Fluorescent fusion proteins of soluble guanylyl cyclase indicate proximity of the heme nitric oxide domain and catalytic domain.

    Directory of Open Access Journals (Sweden)

    Tobias Haase

    Full Text Available BACKGROUND: To examine the structural organisation of heterodimeric soluble guanylyl cyclase (sGC Förster resonance energy transfer (FRET was measured between fluorescent proteins fused to the amino- and carboxy-terminal ends of the sGC beta1 and alpha subunits. METHODOLOGY/PRINCIPAL FINDINGS: Cyan fluorescent protein (CFP was used as FRET donor and yellow fluorescent protein (YFP as FRET acceptor. After generation of recombinant baculovirus, fluorescent-tagged sGC subunits were co-expressed in Sf9 cells. Fluorescent variants of sGC were analyzed in vitro in cytosolic fractions by sensitized emission FRET. Co-expression of the amino-terminally tagged alpha subunits with the carboxy-terminally tagged beta1 subunit resulted in an enzyme complex that showed a FRET efficiency of 10% similar to fluorescent proteins separated by a helix of only 48 amino acids. Because these findings indicated that the amino-terminus of the alpha subunits is close to the carboxy-terminus of the beta1 subunit we constructed fusion proteins where both subunits are connected by a fluorescent protein. The resulting constructs were not only fluorescent, they also showed preserved enzyme activity and regulation by NO. CONCLUSIONS/SIGNIFICANCE: Based on the ability of an amino-terminal fragment of the beta1 subunit to inhibit activity of an heterodimer consisting only of the catalytic domains (alphacatbetacat, Winger and Marletta (Biochemistry 2005, 44:4083-90 have proposed a direct interaction of the amino-terminal region of beta1 with the catalytic domains. In support of such a concept of "trans" regulation of sGC activity by the H-NOX domains our results indicate that the domains within sGC are organized in a way that allows for direct interaction of the amino-terminal regulatory domains with the carboxy-terminal catalytic region. In addition, we constructed "fluorescent-conjoined" sGC's by fusion of the alpha amino-terminus to the beta1 carboxy-terminus leading to a

  20. Cytokines and intestinal inflammation.

    Science.gov (United States)

    Bamias, Giorgos; Cominelli, Fabio

    2016-11-01

    Cytokines of the intestinal microenvironment largely dictate immunological responses after mucosal insults and the dominance of homeostatic or proinflammatory pathways. This review presents important recent studies on the role of specific cytokines in the pathogenesis of intestinal inflammation. The particular mucosal effects of cytokines depend on their inherent properties but also the cellular origin, type of stimulatory antigens, intermolecular interactions, and the particular immunological milieu. Novel cytokines of the interleukin-1 (IL-1) family, including IL-33 and IL-36, have dominant roles in mucosal immunity, whereas more established ones such as IL-18 are constantly enriched with unique properties. Th17 cells are important mucosal constituents, although their profound plasticity, makes the specific set of cytokines they secrete more important than their mere numbers. Finally, various cytokines, such as tumor necrosis factor-α, IL-6, tumor necrosis factor-like cytokine 1A, and death receptor, 3 demonstrate dichotomous roles with mucosa-protective function in acute injury but proinflammatory effects during chronic inflammation. The role of cytokines in mucosal health and disease is increasingly revealed. Such information not only will advance our understanding of the pathogenesis of gut inflammation, but also set the background for development of reliable diagnostic and prognostic biomarkers and cytokine-specific therapies.

  1. GUANYLYL CYCLASE/NATRIURETIC PEPTIDES RECEPTOR-A SIGNALING ANTAGONIZES PHOSPHOINOSITIDE HYDROLYSIS, Ca2+ RELEASE, AND ACTIVATION OF PROTEIN KINASE C

    Directory of Open Access Journals (Sweden)

    Kailash N Pandey

    2014-08-01

    Full Text Available Thus far, three related natriuretic peptides (NPs and three distinct sub-types of cognate NP receptors have been identified and characterized based on the specific ligand binding affinities, guanylyl cyclase activity, and generation of intracellular cGMP. Atrial and brain natriuretic peptides (ANP and BNP specifically bind and activate guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA, and C-type natriuretic peptide (CNP shows specificity to activate guanylyl cyclase/natriuretic peptide receptor-B (GC-B/NPRB. All three NPs bind to natriuretic peptide receptor-C (NPRC, which is also known as clearance or silent receptor. The NPRA is considered the principal biologically active receptor of NP family; however, the molecular signaling mechanisms of NP receptors are not well understood. The activation of NPRA and NPRB produces the intracellular second messenger cGMP, which serves as the major signaling molecule of all three NPs. The activation of NPRB in response to CNP also produces the intracellular cGMP; however, at lower magnitude than that of NPRA, which is activated by ANP and BNP. In addition to enhanced accumulation of intracellular cGMP in response to all three NPs, the levels of cAMP, Ca2+ and inositol triphosphate (IP3 have also been reported to be altered in different cells and tissue types. Interestingly, ANP has been found to lower the concentrations of cAMP, Ca2+, and IP3; however, NPRC has been proposed to increase the levels of these metabolic signaling molecules. The mechanistic studies of decreased and/or increased levels of cAMP, Ca2+, and IP3 in response to NPs and their receptors have not yet been clearly established. This review focuses on the signaling mechanisms of ANP/NPRA and their biological effects involving an increased level of intracellular accumulation of cGMP and a decreased level of cAMP, Ca2+, and IP3 in different cells and tissue systems.

  2. Intestinal pseudo-obstruction

    Science.gov (United States)

    Primary intestinal pseudo-obstruction; Acute colonic ileus; Colonic pseudo-obstruction; Idiopathic intestinal pseudo-obstruction; Ogilvie syndrome; Chronic intestinal pseudo-obstruction; Paralytic ileus - pseudo-obstruction

  3. Intestinal myiasis

    Directory of Open Access Journals (Sweden)

    U S Udgaonkar

    2012-01-01

    Full Text Available Purpose: Intestinal myiasis is a condition when the fly larvae inhabit the gastrointestinal tract and are passed out in faeces. This type of infestation results when eggs or larvae of the fly, deposited on food are inadvertently taken by man. They survive the unfavourable conditions within the gastrointestinal tract and produce disturbances, which may vary from mild to severe. The condition is not uncommon and is often misdiagnosed as pinworm infestation. Correct diagnosis by the clinical microbiologist is important to avoid unnecessary treatment. Materials and Methods: We had 7 cases of intestinal myiasis. In 2 cases the larvae were reared to adult fly in modified meat and sand medium (developed by Udgaonkar. This medium is simple and can be easily prepared in the laboratory. Results: Of the 7 larvae, 5 were Sarcophaga haemorrhoidalis, 1 Megaselia species and 1 was identified as Muscina stabulans. Conclusions: S. haemorrhoidalis was the commonest maggot involved. A high index of suspicion is required for clinical diagnosis when the patient complains of passing wriggling worms in faeces for a long period without any response to antihelminthics. The reason for long duration of illness and recurrence of infestation is baffling. The nearest to cure was colonic wash. We feel prevention is of utmost importance, which is to avoid eating food articles with easy access to flies.

  4. Intestinal Failure (Short Bowel Syndrome)

    Science.gov (United States)

    Intestinal Failure (Short Bowel Syndrome) What is intestinal failure? Intestinal failure occurs when a significant portion of the small ... intestine does. Who is at risk for intestinal failure? N Babies (usually premature) who have had surgery ...

  5. Blood carbonyl protein measurement as a specific oxidative stress biomarker after intestinal reperfusion in rats Dosagem da proteína carbonilada sanguínea como biomarcador específico do estresse oxidativo após reperfusão intestinal em ratos

    Directory of Open Access Journals (Sweden)

    Márcio José Jamel

    2010-02-01

    Full Text Available PURPOSE: An experimental study was performed to investigate the use of protein carbonyl group as a specific biological marker for oxidative stress in a rat model of intestinal ischaemia-reperfusion. METHODS: Twenty four male Wistar rats were randomly distributed into three groups with eight animals each: Group 1 - Control group; Group 2 - Sham; Group 3 - Intestinal ischaemia by clamping ileal branches of the superior mesenteric artery for one hour, followed by another hour of reperfusion. Blood samples were taken in order to analyze the protein carbonyl level by Slot blotting assay. RESULTS: In group 3 a significant increase of protein carbonyl level was observed if compared to the homogenous levels of groups 1 and 2. CONCLUSION: From the results it may be concluded that the protein carbonylation may be used as a specific marker for measuring oxidative stress in rat intestinal reperfusion model.OBJETIVO: Realizou-se um estudo experimental com a finalidade de investigar o uso da proteína carbonilada como um marcador biológico específico do estresse oxidativo em um modelo de isquemia e reperfusão intestinal, em ratos. MÉTODOS: Vinte e quarto ratos da linhagem Wistar, machos foram distribuídos, aleatoriamente, em três grupos compostos por oito animais cada: Grupo 1 - Controle; Grupo 2 - Simulação e Grupo 3 - Submetido à isquemia, mediante clampeamento de ramos ileais da artéria mesentérica superior por uma hora, seguida de reperfusão, por igual período. Amostras sanguíneas obtidas foram utilizadas para analise dos níveis de proteína carbonilada, através do método Slot blotting. RESULTADOS: No grupo 3 houve uma elevação significante da concentração de proteína carbonilada sérica se comparada aos níveis sanguíneos homogêneos encontrados nos grupos 1 e 2. CONCLUSÃO: Fundamentado nos resultados é possível concluir que, a carbonilação protéica pode ser utilizada como um marcador específico para a mensuração do

  6. Absorption and Emission Spectroscopic Investigation of Thermal Dynamics and Photo-Dynamics of the Rhodopsin Domain of the Rhodopsin-Guanylyl Cyclase from the Nematophagous Fungus Catenaria anguillulae

    Directory of Open Access Journals (Sweden)

    Alfons Penzkofer

    2017-10-01

    Full Text Available The rhodopsin-guanylyl cyclase from the nematophagous fungus Catenaria anguillulae belongs to a recently discovered class of enzymerhodopsins and may find application as a tool in optogenetics. Here the rhodopsin domain CaRh of the rhodopsin-guanylyl cyclase from Catenaria anguillulae was studied by absorption and emission spectroscopic methods. The absorption cross-section spectrum and excitation wavelength dependent fluorescence quantum distributions of CaRh samples were determined (first absorption band in the green spectral region. The thermal stability of CaRh was studied by long-time attenuation measurements at room temperature (20.5 °C and refrigerator temperature of 3.5 °C. The apparent melting temperature of CaRh was determined by stepwise sample heating up and cooling down (obtained apparent melting temperature: 62 ± 2 °C. The photocycle dynamics of CaRh was investigated by sample excitation to the first inhomogeneous absorption band of the CaRhda dark-adapted state around 590 nm (long-wavelength tail, 530 nm (central region and 470 nm (short-wavelength tail and following the absorption spectra development during exposure and after exposure (time resolution 0.0125 s. The original protonated retinal Schiff base PRSBall-trans in CaRhda photo-converted reversibly to protonated retinal Schiff base PRSBall-trans,la1 with restructured surroundings (CaRhla1 light-adapted state, slightly blue-shifted and broadened first absorption band, recovery to CaRhda with time constant of 0.8 s and deprotonated retinal Schiff base RSB13-cis (CaRhla2 light-adapted state, first absorption band in violet to near ultraviolet spectral region, recovery to CaRhda with time constant of 0.35 s. Long-time light exposure of light-adapted CaRhla1 around 590, 530 and 470 nm caused low-efficient irreversible degradation to photoproducts CaRhprod. Schemes of the primary photocycle dynamics of CaRhda and the secondary photocycle dynamics of CaRhla1 are developed.

  7. Nitric oxide-soluble guanylyl cyclase-cyclic GMP signaling in the striatum: New targets for the treatment of Parkinson's disease?

    Directory of Open Access Journals (Sweden)

    Anthony R West

    2011-06-01

    Full Text Available Striatal nitric oxide (NO-producing interneurons play an important role in the regulation of corticostriatal synaptic transmission and motor behavior. Striatal NO synthesis is driven by concurrent activation of NMDA and dopamine (DA D1 receptors. NO diffuses into the dendrites of medium-sized spiny neurons (MSNs which contain high levels of NO receptors called soluble guanylyl cyclases (sGC. NO-mediated activation of sGC leads to the synthesis of the second messenger cGMP. In the intact striatum, transient elevations in intracellular cGMP primarily act to increase neuronal excitability and to facilitate glutamatergic corticostriatal transmission. NO-cGMP signaling also functionally opposes the inhibitory effects of DA D2 receptor activation on corticostriatal transmission. Not surprisingly, abnormal striatal NO-sGC-cGMP signaling becomes apparent following striatal DA depletion, an alteration thought to contribute to pathophysiological changes observed in basal ganglia circuits in Parkinson’s disease (PD. Here, we discuss recent developments in the field which have shed light on the role of NO-sGC-cGMP signaling pathways in basal ganglia dysfunction and motor symptoms associated with PD and L-DOPA-induced dyskinesias.

  8. Differentiation of cGMP-dependent and -independent nitric oxide effects on platelet apoptosis and reactive oxygen species production using platelets lacking soluble guanylyl cyclase.

    Science.gov (United States)

    Rukoyatkina, N; Walter, U; Friebe, A; Gambaryan, S

    2011-11-01

    Platelet activation is an irreversible process resulting in platelet apoptosis and necrosis, and circulating platelets contain many components of the apoptotic machinery. Cyclic guanosine monophosphate (cGMP) generated by nitric oxide (NO) activated soluble guanylyl cyclase (sGC) plays a crucial role in preventing platelet activation. However, in addition to activation of sGC, cGMP-independent NO effects in platelets have been described. To differentiate between cGMP-dependent and -independent NO effects on platelet apoptosis and reactive oxygen species (ROS) production, we generated platelet-specific sGC-deficient mice (PS-GCKO). Platelet apoptosis was induced by a combination of thrombin/convulxin (Thr/Cvx) and assessed by phosphatidylserine (PS) surface exposure, and loss of the mitochondrial membrane potential. NO-induced inhibition of PS externalisation was mediated only by cGMP-dependent mechanisms. Inhibition of the mitochondrial membrane potential decrease at low NO concentration was also cGMP-dependent but became cGMP-independent at high NO concentrations. In contrast, inhibition of ROS formation at any NO concentration was mediated by cGMP-independent mechanisms, very likely due to direct radical scavenging. NO inhibits platelet apoptosis by cGMP-dependent mechanisms and ROS production by cGMP-independent mechanisms. The PS-GCKO mouse model is an important tool for the differentiation of cGMP-dependent and -independent NO effects on platelets.

  9. The arabidopsis wall associated kinase-like 10 gene encodes a functional guanylyl cyclase and is co-expressed with pathogen defense related genes

    KAUST Repository

    Meier, Stuart

    2010-01-26

    Background: Second messengers have a key role in linking environmental stimuli to physiological responses. One such messenger, guanosine 3?,5?-cyclic monophosphate (cGMP), has long been known to be an essential signaling molecule in many different physiological processes in higher plants, including biotic stress responses. To date, however, the guanylyl cyclase (GC) enzymes that catalyze the formation of cGMP from GTP have largely remained elusive in higher plants. Principal Findings: We have identified an Arabidopsis receptor type wall associated kinase-like molecule (AtWAKL10) as a candidate GC and provide experimental evidence to show that the intracellular domain of AtWAKL10431-700 can generate cGMP in vitro. Further, we also demonstrate that the molecule has kinase activity indicating that AtWAKL10 is a twin-domain catalytic protein. A co-expression and stimulus-specific expression analysis revealed that AtWAKL10 is consistently coexpressed with well characterized pathogen defense related genes and along with these genes is induced early and sharply in response to a range of pathogens and their elicitors. Conclusions: We demonstrate that AtWAKL10 is a twin-domain, kinase-GC signaling molecule that may function in biotic stress responses that are critically dependent on the second messenger cGMP. © 2010 Meier et al.

  10. Intestinal microbiome landscaping

    NARCIS (Netherlands)

    Shetty, Sudarshan A.; Hugenholtz, Floor; Lahti, Leo; Smidt, Hauke; Vos, de Willem M.

    2017-01-01

    High individuality, large complexity and limited understanding of the mechanisms underlying human intestinal microbiome function remain the major challenges for designing beneficial modulation strategies. Exemplified by the analysis of intestinal bacteria in a thousand Western adults, we discuss

  11. Small Intestine Cancer Treatment

    Science.gov (United States)

    ... all of an organ that contains cancer. The resection may include the small intestine and nearby organs (if the cancer has spread). The doctor may remove the section of the small intestine that contains cancer and perform an anastomosis (joining the cut ends of the intestine together). ...

  12. Prolonged exposure of chromaffin cells to nitric oxide down-regulates the activity of soluble guanylyl cyclase and corresponding mRNA and protein levels

    Directory of Open Access Journals (Sweden)

    Torres Magdalena

    2002-09-01

    Full Text Available Abstract Background Soluble guanylyl cyclase (sGC is the main receptor for nitric oxide (NO when the latter is produced at low concentrations. This enzyme exists mainly as a heterodimer consisting of one α and one β subunit and converts GTP to the second intracellular messenger cGMP. In turn, cGMP plays a key role in regulating several physiological processes in the nervous system. The aim of the present study was to explore the effects of a NO donor on sGC activity and its protein and subunit mRNA levels in a neural cell model. Results Continuous exposure of bovine adrenal chromaffin cells in culture to the nitric oxide donor, diethylenetriamine NONOate (DETA/NO, resulted in a lower capacity of the cells to synthesize cGMP in response to a subsequent NO stimulus. This effect was not prevented by an increase of intracellular reduced glutathione level. DETA/NO treatment decreased sGC subunit mRNA and β1 subunit protein levels. Both sGC activity and β1 subunit levels decreased more rapidly in chromaffin cells exposed to NO than in cells exposed to the protein synthesis inhibitor, cycloheximide, suggesting that NO decreases β1 subunit stability. The presence of cGMP-dependent protein kinase (PKG inhibitors effectively prevented the DETA/NO-induced down regulation of sGC subunit mRNA and partially inhibited the reduction in β1 subunits. Conclusions These results suggest that activation of PKG mediates the drop in sGC subunit mRNA levels, and that NO down-regulates sGC activity by decreasing subunit mRNA levels through a cGMP-dependent mechanism, and by reducing β1 subunit stability.

  13. Gaseous ligand selectivity of the H-NOX sensor protein from Shewanella oneidensis and comparison to those of other bacterial H-NOXs and soluble guanylyl cyclase.

    Science.gov (United States)

    Wu, Gang; Liu, Wen; Berka, Vladimir; Tsai, Ah-Lim

    2017-09-01

    To delineate the commonalities and differences in gaseous ligand discrimination among the heme-based sensors with Heme Nitric oxide/OXygen binding protein (H-NOX) scaffold, the binding kinetic parameters for gaseous ligands NO, CO, and O 2 , including K D , k on , and k off , of Shewanella oneidensis H-NOX (So H-NOX) were characterized in detail in this study and compared to those of previously characterized H-NOXs from Clostridium botulinum (Cb H-NOX), Nostoc sp. (Ns H-NOX), Thermoanaerobacter tengcongensis (Tt H-NOX), Vibrio cholera (Vc H-NOX), and human soluble guanylyl cyclase (sGC), an H-NOX analogue. The K D (NO) and K D (CO) of each bacterial H-NOX or sGC follow the "sliding scale rule"; the affinities of the bacterial H-NOXs for NO and CO vary in a small range but stronger than those of sGC by at least two orders of magnitude. On the other hand, each bacterial H-NOX exhibits different characters in the stability of its 6c NO complex, reactivity with secondary NO, stability of oxyferrous heme and autoxidation to ferric heme. A facile access channel for gaseous ligands is also identified, implying that ligand access has only minimal effect on gaseous ligand selectivity of H-NOXs or sGC. This comparative study of the binding parameters of the bacterial H-NOXs and sGC provides a basis to guide future new structural and functional studies of each specific heme sensor with the H-NOX protein fold. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  14. Chemostimuli for guanylyl cyclase-D-expressing olfactory sensory neurons promote the acquisition of preferences for foods adulterated with the rodenticide warfarin

    Directory of Open Access Journals (Sweden)

    Kevin Robert Kelliher

    2015-07-01

    Full Text Available Many animals have the ability to acquire food preferences from conspecifics via social signals. For example, the coincident detection of a food odor by canonical olfactory sensory neurons (OSNs and agonists of the specialized OSNs expressing the receptor guanylyl cyclase GC-D (GC-D+ OSNs will promote a preference in recipient rodents for similarly odored foods. It has been hypothesized that these preferences are acquired and maintained regardless of the palatability or quality of the food. We assessed whether mice could acquire and maintain preferences for food that had been adulterated with the anticoagulant rodenticide warfarin. After olfactory investigation of a saline droplet containing either cocoa (2%, w/w or cinnamon (1%, w/w along with a GC-D+ OSN-specific chemostimulus (either of the guanylin-family peptides uroguanylin and guanylin; 1–50 nM, C57BL/6J mice exhibited robust preferences for unadulterated food containing the demonstrated odor. The peptide-dependent preference was observed even when the food contained warfarin (0.025% w/w. Repeated ingestion of warfarin-containing food over four days did not disrupt the preference, even though mice were not re-exposed to the peptide stimulus. Surprisingly, mice continued to prefer warfarin-adulterated food containing the demonstrated odor when presented with a choice of warfarin-free food containing a novel odor. Our results indicate that olfactory-mediated food preferences can be acquired and maintained for warfarin-containing foods and suggest that guanylin peptides may be effective stimuli for promoting the ingestion of foods or other edibles with low palatability or potential toxicity.

  15. Biomarkers in Veterinary Medicine.

    Science.gov (United States)

    Myers, Michael J; Smith, Emily R; Turfle, Phillip G

    2017-02-08

    This article summarizes the relevant definitions related to biomarkers; reviews the general processes related to biomarker discovery and ultimate acceptance and use; and finally summarizes and reviews, to the extent possible, examples of the types of biomarkers used in animal species within veterinary clinical practice and human and veterinary drug development. We highlight opportunities for collaboration and coordination of research within the veterinary community and leveraging of resources from human medicine to support biomarker discovery and validation efforts for veterinary medicine.

  16. Combination of biomarkers

    DEFF Research Database (Denmark)

    Thurfjell, Lennart; Lötjönen, Jyrki; Lundqvist, Roger

    2012-01-01

    The New National Institute on Aging-Alzheimer's Association diagnostic guidelines for Alzheimer's disease (AD) incorporate biomarkers in the diagnostic criteria and suggest division of biomarkers into two categories: Aβ accumulation and neuronal degeneration or injury.......The New National Institute on Aging-Alzheimer's Association diagnostic guidelines for Alzheimer's disease (AD) incorporate biomarkers in the diagnostic criteria and suggest division of biomarkers into two categories: Aβ accumulation and neuronal degeneration or injury....

  17. Aberrant intestinal microbiota in individuals with prediabetes

    DEFF Research Database (Denmark)

    Allin, Kristine H.; Tremaroli, Valentina; Caesar, Robert

    2018-01-01

    Aims/hypothesis: Individuals with type 2 diabetes have aberrant intestinal microbiota. However, recent studies suggest that metformin alters the composition and functional potential of gut microbiota, thereby interfering with the diabetes-related microbial signatures. We tested whether specific gut...... microbiota profiles are associated with prediabetes (defined as fasting plasma glucose of 6.1–7.0 mmol/l or HbA1c of 42–48 mmol/mol [6.0–6.5%]) and a range of clinical biomarkers of poor metabolic health. Methods: In the present case–control study, we analysed the gut microbiota of 134 Danish adults...... impaired glucose regulation in recipient mice. Conclusions/interpretation: Collectively, our data show that individuals with prediabetes have aberrant intestinal microbiota characterised by a decreased abundance of the genus Clostridium and the mucin-degrading bacterium A. muciniphila. Our findings...

  18. New sepsis biomarkers

    Directory of Open Access Journals (Sweden)

    Dolores Limongi

    2016-06-01

    Full Text Available Sepsis remains a leading cause of death in the intensive care units and in all age groups worldwide. Early recognition and diagnosis are key to achieving improved outcomes. Therefore, novel biomarkers that might better inform clinicians treating such patients are surely needed. The main attributes of successful biomarkers would be high sensitivity, specificity, possibility of bedside monitoring and financial accessibility. A panel of sepsis biomarkers along with currently used laboratory tests will facilitate earlier diagnosis, timely treatment and improved outcome may be more effective than single biomarkers. In this review, we summarize the most recent advances on sepsis biomarkers evaluated in clinical and experimental studies.

  19. Gastric and intestinal surgery.

    Science.gov (United States)

    Fossum, Theresa W; Hedlund, Cheryl S

    2003-09-01

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

  20. Intestinal parasites and tuberculosis

    Directory of Open Access Journals (Sweden)

    Anuar Alonso Cedeño-Burbano

    2017-10-01

    Conclusions: The available evidence was insufficient to affirm that intestinal parasites predispose to developing tuberculous. The studies carried out so far have found statistically insignificant results.

  1. Cenderitide: structural requirements for the creation of a novel dual particulate guanylyl cyclase receptor agonist with renal-enhancing in vivo and ex vivo actions.

    Science.gov (United States)

    Lee, Candace Y W; Huntley, Brenda K; McCormick, Daniel J; Ichiki, Tomoko; Sangaralingham, S Jeson; Lisy, Ondrej; Burnett, John C

    2016-04-01

    Cenderitide is a novel dual natriuretic peptide (NP) receptor chimeric peptide activator, which targets the particulate guanylyl cyclase B (pGC-B) receptor and pGC-A unlike native NPs. Cenderitide was engineered to retain the anti-fibrotic properties of C-type natriuretic peptide (CNP)/pGC-B with renal-enhancing actions facilitated by fusion to the carboxyl terminus of Dendroaspis NP (DNP), a pGC-A agonist, to CNP. Here, we address significance of the DNP carboxyl terminus in dual pGC receptor activation and actions of cenderitide compared with CNP on renal function and cyclic guanosine monophosphate (cGMP) in vivo and ex vivo in normal canines. In vitro, only cenderitide and not CNP or three CNP-based variants was a potent dual pGC-A/pGC-B activator of cGMP production (from 5 to 237 pmol/mL) in human embryonic kidney (HEK) 293 cells overexpressing human pGC-A while in pGC-B overexpressing cells cenderitide increased cGMP production (from 4 to 321 pmol/mL) while the three CNP-based variants were weak agonists. Based upon our finding that the DNP carboxyl terminus is a key structural requirement for dual pGC-A/pGC-B activation, we defined in vivo the renal-enhancing actions of cenderitide compared with CNP. Cenderitide increased urinary cGMP excretion (from 989 to 5977 pmol/mL), net generation of renal cGMP (821-4124 pmol/min), natriuresis (12-242 μEq/min), and glomerular filtration rate (GFR) (37-51 mL/min) while CNP did not. We then demonstrated the transformation of CNP ex vivo into a renal cGMP-activating peptide which increased cGMP in freshly isolated glomeruli eight-fold greater than CNP. The current study establishes that dual pGC-A and pGC-B activation with CNP requires the specific carboxyl terminus of DNP. In normal canines in vivo and in glomeruli ex vivo, the carboxyl terminus of DNP transforms CNP into a natriuretic and GFR-enhancing peptide. Future studies of cenderitide are warranted in cardiorenal disease states to explore its efficacy in overall

  2. Plasma biomarker of dietary phytosterol intake.

    Directory of Open Access Journals (Sweden)

    Xiaobo Lin

    Full Text Available Dietary phytosterols, plant sterols structurally similar to cholesterol, reduce intestinal cholesterol absorption and have many other potentially beneficial biological effects in humans. Due to limited information on phytosterol levels in foods, however, it is difficult to quantify habitual dietary phytosterol intake (DPI. Therefore, we sought to identify a plasma biomarker of DPI.Data were analyzed from two feeding studies with a total of 38 subjects during 94 dietary periods. DPI was carefully controlled at low, intermediate, and high levels. Plasma levels of phytosterols and cholesterol metabolites were assessed at the end of each diet period. Based on simple ordinary least squares regression analysis, the best biomarker for DPI was the ratio of plasma campesterol to the endogenous cholesterol metabolite 5-α-cholestanol (R2 = 0.785, P 0.600; P < 0.01.The ratio of plasma campesterol to the coordinately regulated endogenous cholesterol metabolite 5-α-cholestanol is a biomarker of dietary phytosterol intake. Conversely, plasma phytosterol levels alone are not ideal biomarkers of DPI because they are confounded by large inter-individual variation in absorption and turnover of non-cholesterol sterols. Further work is needed to assess the relation between non-cholesterol sterol metabolism and associated cholesterol transport in the genesis of coronary heart disease.

  3. adhesive intestinal obstruction

    African Journals Online (AJOL)

    2006-06-01

    Jun 1, 2006 ... ABSTRACT. Background: Adhesions after abdominal and pelvic surgery are a major cause of intestinal obstruction in the western world and the pathology is steadily gaining prominence in our practice. Objective: To determine the magnitude of adhesive intestinal obstruction; to determine the types.

  4. Intestinal Barrier and Behavior.

    Science.gov (United States)

    Julio-Pieper, M; Bravo, J A

    2016-01-01

    The intestinal barrier function contributes to gut homeostasis by modulating absorption of water, electrolytes, and nutrients from the lumen into the circulation while restricting the passage of noxious luminal substances and microorganisms. Chronic conditions such as rheumatoid arthritis, inflammatory bowel disease, and celiac disease are associated to intestinal barrier dysfunction. Here, the hypothesis is that a leaky intestinal wall allowing for indiscriminate passage of intraluminal compounds to the vascular compartment could in turn lead to systemic inflammation. An increasing number of studies are now investigating the association between gut permeability and CNS disorders, under the premise that translocation of intestinal luminal contents could affect CNS function, either directly or indirectly. Still, it is unknown whether disruption of intestinal barrier is a causative agent or a consequence in these situations. Here, we discuss the latest evidence pointing to an association between increased gut permeability and disrupted behavioral responses. © 2016 Elsevier Inc. All rights reserved.

  5. Intestinal Permeability Biomarker Zonulin is Elevated in Healthy Aging.

    Science.gov (United States)

    Qi, YanFei; Goel, Ruby; Kim, Seungbum; Richards, Elaine M; Carter, Christy S; Pepine, Carl J; Raizada, Mohan K; Buford, Thomas W

    2017-09-01

    Increased gut permeability ("leaky gut") has been proposed as a potential contributor to age-related inflammation and gut dysbiosis. However, information on the relationship between a leaky gut and inflammation and physical frailty during aging are limited. To investigate the hypothesis that an aging-associated leaky gut is linked to the age-related inflammation and frailty. Two cohorts of healthy adults were studied: young (18-30 years old, n = 19) and older (≥70 years old, n = 18). Serum concentrations of the tumor necrosis factor (TNF)-α and interleukin (IL)-6, zonulin (a marker for leaky gut), and high-mobility group box protein (HMGB1, a nuclear protein triggering inflammation) were measured. Correlations of serum levels of zonulin and HMGB1 with strength of plantar flexor muscles and number of steps taken per day were analyzed. Serum concentration of zonulin and HMGB1 were 22% (P = .005) and 16% (P = .010) higher in the older versus young adults. Serum zonulin was positively associated with concentrations of TNF-α (r = 0.357, P = .032) and IL-6 (r = 0.345, P = .043). Importantly, both zonulin and HMGB1 were negatively correlated with skeletal muscle strength (zonulin: r = -0.332, P = .048; HMGB1: r = -0.383, P = .023), and habitual physical activity (zonulin: r = -0.410, P = .016; HMGB1: r = -0.483, P = .004). Serum zonulin was associated with both systemic inflammation and 2 key indices of physical frailty. These data suggest that a leaky gut may play a critical role in the development of age-related inflammation and frailty. Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

  6. Cardiac biomarkers in Neonatology

    OpenAIRE

    Vijlbrief, D.C.

    2015-01-01

    In this thesis, the role for cardiac biomarkers in neonatology was investigated. Several clinically relevant results were reported. In term and preterm infants, hypoxia and subsequent adaptation play an important role in cardiac biomarker elevation. The elevated natriuretic peptides are indicative of abnormal function; elevated troponins are suggestive for cardiomyocyte damage. This methodology makes these biomarkers of additional value in the treatment of newborn infants, separate or as a co...

  7. Mycotoxins and the intestine

    Directory of Open Access Journals (Sweden)

    Leon Broom

    2015-12-01

    Full Text Available Fungal biochemical pathways can yield various compounds that are not considered to be necessary for their growth and are thus referred to as secondary metabolites. These compounds have been found to have wide ranging biological effects and include potent poisons (mycotoxins. Mycotoxins invariably contaminate crops and (thus animal feeds. The intestine is the key link between ingested mycotoxins and their detrimental effects on the animal. Effects on the intestine, or intestinal environment, and immune system have been reported with various mycotoxins. These effects are almost certainly occurring across species. Most, if not all, of the reported effects of mycotoxins are negative in terms of intestinal health, for example, decreased intestinal cell viability, reductions in short chain fatty acid (SCFA concentrations and elimination of beneficial bacteria, increased expression of genes involved in promoting inflammation and counteracting oxidative stress. This challenge to intestinal health will predispose the animal to intestinal (and systemic infections and impair efficient digestion and absorption of nutrients, with the associated effect on animal productivity.

  8. Intestinal solute carriers

    DEFF Research Database (Denmark)

    Steffansen, Bente; Nielsen, Carsten Uhd; Brodin, Birger

    2004-01-01

    A large amount of absorptive intestinal membrane transporters play an important part in absorption and distribution of several nutrients, drugs and prodrugs. The present paper gives a general overview on intestinal solute carriers as well as on trends and strategies for targeting drugs and...... membrane transporters in the small intestine in order to increase oral bioavailabilities of drug or prodrug, the major influence on in vivo pharmacokinetics is suggested to be dose-dependent increase in bioavailability as well as prolonged blood circulation due to large capacity facilitated absorption...

  9. Intestinal solute carriers

    DEFF Research Database (Denmark)

    Steffansen, Bente; Nielsen, Carsten Uhd; Brodin, Birger

    2004-01-01

    membrane transporters in the small intestine in order to increase oral bioavailabilities of drug or prodrug, the major influence on in vivo pharmacokinetics is suggested to be dose-dependent increase in bioavailability as well as prolonged blood circulation due to large capacity facilitated absorption......A large amount of absorptive intestinal membrane transporters play an important part in absorption and distribution of several nutrients, drugs and prodrugs. The present paper gives a general overview on intestinal solute carriers as well as on trends and strategies for targeting drugs and...

  10. Biomarkers of Diabetic Retinopathy.

    Science.gov (United States)

    Ting, Daniel Shu Wei; Tan, Kara-Anne; Phua, Val; Tan, Gavin Siew Wei; Wong, Chee Wai; Wong, Tien Yin

    2016-12-01

    Diabetic retinopathy (DR), a leading cause of acquired vision loss, is a microvascular complication of diabetes. While traditional risk factors for diabetic retinopathy including longer duration of diabetes, poor blood glucose control, and dyslipidemia are helpful in stratifying patient's risk for developing retinopathy, many patients without these traditional risk factors develop DR; furthermore, there are persons with long diabetes duration who do not develop DR. Thus, identifying biomarkers to predict DR or to determine therapeutic response is important. A biomarker can be defined as a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. Incorporation of biomarkers into risk stratification of persons with diabetes would likely aid in early diagnosis and guide treatment methods for those with DR or with worsening DR. Systemic biomarkers of DR include serum measures including genomic, proteomic, and metabolomics biomarkers. Ocular biomarkers including tears and vitreous and retinal vascular structural changes have also been studied extensively to prognosticate the risk of DR development. The current studies on biomarkers are limited by the need for larger sample sizes, cross-validation in different populations and ethnic groups, and time-efficient and cost-effective analytical techniques. Future research is important to explore novel DR biomarkers that are non-invasive, rapid, economical, and accurate to help reduce the incidence and progression of DR in people with diabetes.

  11. Chemoresistive Gas Sensors for the Detection of Colorectal Cancer Biomarkers

    OpenAIRE

    Malagù, Cesare; Fabbri, Barbara; Gherardi, Sandro; Giberti, Alessio; Guidi, Vincenzo; Landini, Nicolò; Zonta, Giulia

    2014-01-01

    Numerous medical studies show that tumor growth is accompanied by protein changes that may lead to the peroxidation of the cell membrane with consequent emission of volatile organic compounds (VOCs) by breath or intestinal gases that should be seen as biomarkers for colorectal cancer (CRC). The analysis of VOCs represents a non-invasive and potentially inexpensive preliminary screening technique. An array of chemoresistive gas sensors based on screen-printed metal oxide semiconducting films h...

  12. Zonulin: A Potential Marker of Intestine Injury in Newborns

    Directory of Open Access Journals (Sweden)

    Anna Tarko

    2017-01-01

    Full Text Available Introduction. Zonulin (ZO, a new diagnostic biomarker of intestinal permeability, was tested in newborns presenting symptoms of infection and/or inflammation of the gut or being at risk of intestinal pathology. Material and Methods. Serum ZO was assessed in 81 newborns diagnosed with sepsis, necrotizing enterocolitis (NEC, rotavirus infection, and gastroschisis, also in extremely low gestational age babies, and in controls (healthy newborns. ZO concentration was compared to C-reactive protein (CRP and procalcitonin (PCT values, leucocyte and platelet count, basic demographic data, and the value of the Neonatal Therapeutic Intervention Scoring System (NTISS. Results. Median values of ZO were markedly higher in groups with rotavirus infection and gastroschisis (36.0 (1-3Q: 26.0–43.2 and 20.3 (1-3Q: 17.7–28.2 ng/ml, resp. versus controls (3.5 (1-3Q: 2.7–4.8 ng/ml. Its concentration in the NEC group was twice as high as in controls but did not reach statistical significance. ZO levels were not related to NTISS, CRP, and PCT. Conclusions. Zonulin is a promising biomarker of intestinal condition, markedly elevated in rotavirus infections. Its role in defining the severity of necrotizing enterocolitis and the risk for perforation is not well described and needs further evaluation. An increase in zonulin may not be parallel to the release of inflammatory markers, and low CRP should not exclude an injury to neonatal intestine.

  13. Zonulin: A Potential Marker of Intestine Injury in Newborns.

    Science.gov (United States)

    Tarko, Anna; Suchojad, Anna; Michalec, Marta; Majcherczyk, Małgorzata; Brzozowska, Aniceta; Maruniak-Chudek, Iwona

    2017-01-01

    Zonulin (ZO), a new diagnostic biomarker of intestinal permeability, was tested in newborns presenting symptoms of infection and/or inflammation of the gut or being at risk of intestinal pathology. Serum ZO was assessed in 81 newborns diagnosed with sepsis, necrotizing enterocolitis (NEC), rotavirus infection, and gastroschisis, also in extremely low gestational age babies, and in controls (healthy newborns). ZO concentration was compared to C-reactive protein (CRP) and procalcitonin (PCT) values, leucocyte and platelet count, basic demographic data, and the value of the Neonatal Therapeutic Intervention Scoring System (NTISS). Median values of ZO were markedly higher in groups with rotavirus infection and gastroschisis (36.0 (1-3Q: 26.0-43.2) and 20.3 (1-3Q: 17.7-28.2) ng/ml, resp.) versus controls (3.5 (1-3Q: 2.7-4.8) ng/ml). Its concentration in the NEC group was twice as high as in controls but did not reach statistical significance. ZO levels were not related to NTISS, CRP, and PCT. Zonulin is a promising biomarker of intestinal condition, markedly elevated in rotavirus infections. Its role in defining the severity of necrotizing enterocolitis and the risk for perforation is not well described and needs further evaluation. An increase in zonulin may not be parallel to the release of inflammatory markers, and low CRP should not exclude an injury to neonatal intestine.

  14. Plasma biomarker of dietary phytosterol intake.

    Science.gov (United States)

    Lin, Xiaobo; Racette, Susan B; Ma, Lina; Wallendorf, Michael; Spearie, Catherine Anderson; Ostlund, Richard E

    2015-01-01

    Dietary phytosterols, plant sterols structurally similar to cholesterol, reduce intestinal cholesterol absorption and have many other potentially beneficial biological effects in humans. Due to limited information on phytosterol levels in foods, however, it is difficult to quantify habitual dietary phytosterol intake (DPI). Therefore, we sought to identify a plasma biomarker of DPI. Data were analyzed from two feeding studies with a total of 38 subjects during 94 dietary periods. DPI was carefully controlled at low, intermediate, and high levels. Plasma levels of phytosterols and cholesterol metabolites were assessed at the end of each diet period. Based on simple ordinary least squares regression analysis, the best biomarker for DPI was the ratio of plasma campesterol to the endogenous cholesterol metabolite 5-α-cholestanol (R2 = 0.785, P 0.600; P phytosterol intake. Conversely, plasma phytosterol levels alone are not ideal biomarkers of DPI because they are confounded by large inter-individual variation in absorption and turnover of non-cholesterol sterols. Further work is needed to assess the relation between non-cholesterol sterol metabolism and associated cholesterol transport in the genesis of coronary heart disease.

  15. Biomarkers in Airway Diseases

    Directory of Open Access Journals (Sweden)

    Janice M Leung

    2013-01-01

    Full Text Available The inherent limitations of spirometry and clinical history have prompted clinicians and scientists to search for surrogate markers of airway diseases. Although few biomarkers have been widely accepted into the clinical armamentarium, the authors explore three sources of biomarkers that have shown promise as indicators of disease severity and treatment response. In asthma, exhaled nitric oxide measurements can predict steroid responsiveness and sputum eosinophil counts have been used to titrate anti-inflammatory therapies. In chronic obstructive pulmonary disease, inflammatory plasma biomarkers, such as fibrinogen, club cell secretory protein-16 and surfactant protein D, can denote greater severity and predict the risk of exacerbations. While the multitude of disease phenotypes in respiratory medicine make biomarker development especially challenging, these three may soon play key roles in the diagnosis and management of airway diseases.

  16. amphibian_biomarker_data

    Data.gov (United States)

    U.S. Environmental Protection Agency — Amphibian metabolite data used in Snyder, M.N., Henderson, W.M., Glinski, D.G., Purucker, S. T., 2017. Biomarker analysis of american toad (Anaxyrus americanus) and...

  17. Diagnosis of intestinal and extra intestinal amoebiasis

    International Nuclear Information System (INIS)

    Lopez, Myriam Consuelo; Quiroz, Damian Arnoldo; Pinilla, Analida Elizabeth

    2007-01-01

    The objective is to carry out a review of the national and international literature as of the XXth century in order to update the advances for the diagnosis of complex odd Entamoeba histolytic / Entamoeba dispar and that of intestinal and extra intestinal amoebiasis that may be of use to the scientific community. As well as to unify the diagnostic criteria of this parasitosis known as a public health problem, and as a consequence of that, optimize the quality of population care. Data source: there was a systematic search for the scientific literature Publisher in Spanish and English since 1960 until today, this selection started on the first semester of 2006 until 2007, in the development of the line on intestinal and extra-intestinal amoebiasis of the Medical School of the National University of Colombia. A retrospective search process was carried out, systematically reviewing the most relevant articles as well as the products of this research line. In deciding how to make this article, there was a continuous search in different data bases such as Medline, SciELO and other bases in the library of the National University of Colombia, as well as other classical books related to the subject. For that purpose the terms amoebiasis, odd Entamoeba histolytic, Entamoeba, diagnosis, epidemiology, dysentery, amoebic liver abscess, were used. Studies selection: titles and abstracts were reviewed to select the original publications and the most representative ones related to this article's subject. Data extraction: the articles were classified according to the subject, the chronology and the authors according to the scientific contribution to solve the problem. Synthesis of the data: in the fi rst instance, a chronological critical analysis was carried out to order and synthesize the progress made in the diagnosis until confirmation of the experts' agreements in the field of amoebiasis was obtained throughout the world. Conclusion: this article summarizes what has taken place

  18. Advancing Alcohol Biomarkers Research

    OpenAIRE

    Bearer, Cynthia F.; Bailey, Shannon M.; Hoek, Jan B.

    2010-01-01

    Biomarkers to detect past alcohol use and identify alcohol-related diseases have long been pursued as important tools for research into alcohol use disorders as well as for clinical and treatment applications and other settings. The National Institute on Alcohol Abuse and Alcoholism (NIAAA) sponsored a workshop titled “Workshop on Biomarkers for Alcohol-Induced Disorders” in June 2008. The intent of this workshop was to review and discuss recent progress in the development and implementation ...

  19. Biomarkers in rare diseases.

    Science.gov (United States)

    Ferlini, A; Scotton, C; Novelli, G

    2013-01-01

    Nowadays 7,000 rare diseases (RDs) have been identified with a prevalence less than 5/10,000. Despite of the enormous effort the European Union (EU) has already invested in this field, still 4,000 RDs remain orphan of genetic diagnosis and causative gene identification. The genetic definition of RDs represents a prerequisite for being diagnosed, for having a robust prevention, for entering in a specific standard of care, and ultimately, for being included in clinical trials, often via personalized medicine. It is well established that biomarkers can offer a way to speed up research by understanding the pathophysiological mechanisms of diseases. In particular, biomarkers will offer an invaluable tool for monitoring disease progression, prognosis and response to drug treatment. In this review, we summarize the different types of biomarkers and their importance as well as their translational applications in RDs. We have reviewed the current knowledge on biomarkers state-of-the-art via literature data, specific websites and EU sources regarding past, pending and current projects. Here we provide a comprehensive scenario of biomarkers research, its applications in clinical practice, with special emphasis on translational research applicable to diagnostic and clinical trials. The experience of the EU project BIO-NMD is also mentioned. Biomarkers represent key features in both diagnostics and research on rare diseases and will encounter wide exploitation in translational and personalized medicine. © 2013 S. Karger AG, Basel

  20. 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.

  1. Intestinal failure: a review

    Science.gov (United States)

    Allan, Philip; Lal, Simon

    2018-01-01

    Intestinal failure (IF) is the inability of the gut to absorb necessary water, macronutrients (carbohydrate, protein, and fat), micronutrients, and electrolytes sufficient to sustain life and requiring intravenous supplementation or replacement. Acute IF (types 1 and 2) is the initial phase of the illness and may last for weeks to a few months, and chronic IF (type 3) from months to years. The challenge of caring for patients with IF is not merely the management of the underlying condition leading to IF or the correct provision of appropriate nutrition or both but also the prevention of complications, whether thromboembolic phenomenon (for example, venous occlusion), central venous catheter-related bloodstream infection, IF-associated liver disease, or metabolic bone disease. This review looks at recent questions regarding chronic IF (type 3), its diagnosis and management, the role of the multidisciplinary team, and novel therapies, including hormonal treatment for short bowel syndrome but also surgical options for intestinal lengthening and intestinal transplant. PMID:29399329

  2. Small intestine diverticuli

    International Nuclear Information System (INIS)

    Pomakov, P.; Risov, A.

    1991-01-01

    The routine method of contrast matter passage applied to 850 patients with different gastrointestinal diseases proved inefficient to detect any small-intestinal diverticuli. The following modiffications of the method have been tested in order to improve the diagnostic possibilities of the X-ray: study at short intervals, assisted passage, enteroclysm, pharmacodynamic impact, retrograde filling of the ileum by irrigoscopy. Twelve diverticuli of the small-intestinal loops were identified: 5 Meckel's diverticuli, 2 solitary of which one of the therminal ileum, 2 double diverticuli and 1 multiple diverticulosis of the jejunum. The results show that the short interval X-ray examination of the small intestines is the method of choice for identifying local changes in them. The solitary diverticuli are not casuistic scarcity, its occurrence is about 0.5% at purposeful X-ray investigation. The assisted passage method is proposed as a method of choice for detection of the Meckel's diverticulum. 5 figs., 3 tabs. 18 refs

  3. Chronic intestinal pseudoobstruction syndrome

    International Nuclear Information System (INIS)

    Yeon, Kyung Mo; Seo, Jeong Kee; Lee, Yong Seok

    1992-01-01

    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. Small Intestinal Infections.

    Science.gov (United States)

    Munot, Khushboo; Kotler, Donald P

    2016-06-01

    Small intestinal infections are extremely common worldwide. They may be bacterial, viral, or parasitic in etiology. Most are foodborne or waterborne, with specific etiologies differing by region and with diverse pathophysiologies. Very young, very old, and immune-deficient individuals are the most vulnerable to morbidity or mortality from small intestinal infections. There have been significant advances in diagnostic sophistication with the development and early application of molecular diagnostic assays, though these tests have not become mainstream. The lack of rapid diagnoses combined with the self-limited nature of small intestinal infections has hampered the development of specific and effective treatments other than oral rehydration. Antibiotics are not indicated in the absence of an etiologic diagnosis, and not at all in the case of some infections.

  5. 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.

  6. Fækal calprotectin er en klinisk anvendelig markør for intestinal inflammation

    DEFF Research Database (Denmark)

    Theede, Klaus; Kiszka-Kanowitz, Marianne; Nordgaard-Lassen, Inge

    2014-01-01

    Faecal calprotectin is a biomarker for inflammation in the intestinal mucosa. Faecal calprotectin has the ability to detect inflammatory causes of gastrointestinal symptoms and to distinguish these from irritable bowel syndrome. The test is very sensitive but not specific to any particular...

  7. Intestinal microbiota and ulcerative colitis.

    Science.gov (United States)

    Ohkusa, Toshifumi; Koido, Shigeo

    2015-11-01

    There is a close relationship between the human host and the intestinal microbiota, which is an assortment of microorganisms, protecting the intestine against colonization by exogenous pathogens. Moreover, the intestinal microbiota play a critical role in providing nutrition and the modulation of host immune homeostasis. Recent reports indicate that some strains of intestinal bacteria are responsible for intestinal ulceration and chronic inflammation in inflammatory bowel diseases (IBD) such as ulcerative colitis (UC) and Crohn's disease (CD). Understanding the interaction of the intestinal microbiota with pathogens and the human host might provide new strategies treating patients with IBD. This review focuses on the important role that the intestinal microbiota plays in maintaining innate immunity in the pathogenesis and etiology of UC and discusses new antibiotic therapies targeting the intestinal microbiota. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  8. Small intestine aspirate and culture

    Science.gov (United States)

    ... ency/article/003731.htm Small intestine aspirate and culture To use the sharing features on this page, please enable JavaScript. Small intestine aspirate and culture is a lab test to check for infection ...

  9. The intestinal microbiome in type 1 diabetes.

    Science.gov (United States)

    Dunne, J L; Triplett, E W; Gevers, D; Xavier, R; Insel, R; Danska, J; Atkinson, M A

    2014-07-01

    Few concepts in recent years have garnered more disease research attention than that of the intestinal (i.e. 'gut') microbiome. This emerging interest has included investigations of the microbiome's role in the pathogenesis of a variety of autoimmune disorders, including type 1 diabetes (T1D). Indeed, a growing number of recent studies of patients with T1D or at varying levels of risk for this disease, as well as in animal models of the disorder, lend increasing support to the notion that alterations in the microbiome precede T1D onset. Herein, we review these investigations, examining the mechanisms by which the microbiome may influence T1D development and explore how multi-disciplinary analysis of the microbiome and the host immune response may provide novel biomarkers and therapeutic options for prevention of T1D. © 2014 British Society for Immunology.

  10. Stages of Small Intestine Cancer

    Science.gov (United States)

    ... all of an organ that contains cancer. The resection may include the small intestine and nearby organs (if the cancer has spread). The doctor may remove the section of the small intestine that contains cancer and perform an anastomosis (joining the cut ends of the intestine together). ...

  11. Intestinal inflammatory myofibroblastic tumour

    African Journals Online (AJOL)

    abdominal X-ray of patients 1, 3 and 4 demonstrated dilated small bowel loops with fluid levels in keeping with intestinal ... myxoid/vascular pattern characterised by a variable admixture of capillary-calibre blood vessels, .... in the present study had a past history of abdominal trauma or surgery. Ancillary histopathological ...

  12. Small intestine and microbiota.

    Science.gov (United States)

    Cotter, Paul D

    2011-03-01

    To highlight the recent studies which have enhanced our appreciation of the composition of the microbiota in the human small intestine and its relevance to the health of the host. In the past number of years, the composition of the microorganisms present in our small intestines has been the subject of greater scrutiny than ever before. These investigations have been possible as a consequence of the development and utilization of new molecular tools which have revolutionized the field of microbial ecology and have focused predominantly on the small intestinal microbiota associated with pediatric celiac disease, inflammatory bowel disease, irritable bowel syndrome and pouchitis. The impact of invasive procedures, such as small bowel transplant, ileostomy and ileal pouch anal anastomosis, on the ileal microbiota has also been investigated. The ever greater appreciation of the link between the small intestinal microbiota and the health status of the host has the potential to lead to the development of new strategies to alter this microbiota in a targeted way to prevent or treat specific disorders.

  13. Intestinal obstruction repair

    Science.gov (United States)

    ... Ileostomy and your diet Ileostomy - caring for your stoma Ileostomy - changing your pouch Ileostomy - discharge Ileostomy - what to ask your doctor Intestinal or bowel obstruction - discharge Low-fiber diet Surgical wound care - open Types of ileostomy When you have nausea ...

  14. adhesive intestinal obstruction

    African Journals Online (AJOL)

    2006-06-01

    Jun 1, 2006 ... obstruction. Brit. I. Surg. 1998; 85: 1071-1074. The acute abdomen: Intestinal obstruction. In: Primary surgery, Vol. 1. Edited by Maurice King et al. Oxford. Med. PubL, Oxford. 1990; 142-169. Fluids and electrolyte management. In: Essentials of pediatric surgery. Edited by Marc Rowe et al. Mosby,. St. Louis ...

  15. Intestinal Complications of IBD

    Science.gov (United States)

    ... localized pocket of pus caused by infection from bacteria. More common in Crohn’s than in colitis, an abscess may form in the intestinal wall—sometimes causing it to bulge out. Visible abscesses, such as those around the anus, look like boils and treatment often involves lancing. Symptoms of ...

  16. Intestinal failure in childhood

    African Journals Online (AJOL)

    Short bowel syndrome (SBS) was one of the first recognised conditions of protracted IF. With the increasing and successful use of long-term PN during the last three decades, several other causes of IF have emerged. Long-term PN and home-PN are the mainstay of therapy, independent of the nature of “Intestinal failure” ...

  17. Biomarkers of sepsis

    Science.gov (United States)

    2013-01-01

    Sepsis is an unusual systemic reaction to what is sometimes an otherwise ordinary infection, and it probably represents a pattern of response by the immune system to injury. A hyper-inflammatory response is followed by an immunosuppressive phase during which multiple organ dysfunction is present and the patient is susceptible to nosocomial infection. Biomarkers to diagnose sepsis may allow early intervention which, although primarily supportive, can reduce the risk of death. Although lactate is currently the most commonly used biomarker to identify sepsis, other biomarkers may help to enhance lactate’s effectiveness; these include markers of the hyper-inflammatory phase of sepsis, such as pro-inflammatory cytokines and chemokines; proteins such as C-reactive protein and procalcitonin which are synthesized in response to infection and inflammation; and markers of neutrophil and monocyte activation. Recently, markers of the immunosuppressive phase of sepsis, such as anti-inflammatory cytokines, and alterations of the cell surface markers of monocytes and lymphocytes have been examined. Combinations of pro- and anti-inflammatory biomarkers in a multi-marker panel may help identify patients who are developing severe sepsis before organ dysfunction has advanced too far. Combined with innovative approaches to treatment that target the immunosuppressive phase, these biomarkers may help to reduce the mortality rate associated with severe sepsis which, despite advances in supportive measures, remains high. PMID:23480440

  18. Mass spectrometry for biomarker development

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Chaochao; Liu, Tao; Baker, Erin Shammel; Rodland, Karin D.; Smith, Richard D.

    2015-06-19

    Biomarkers potentially play a crucial role in early disease diagnosis, prognosis and targeted therapy. In the past decade, mass spectrometry based proteomics has become increasingly important in biomarker development due to large advances in technology and associated methods. This chapter mainly focuses on the application of broad (e.g. shotgun) proteomics in biomarker discovery and the utility of targeted proteomics in biomarker verification and validation. A range of mass spectrometry methodologies are discussed emphasizing their efficacy in the different stages in biomarker development, with a particular emphasis on blood biomarker development.

  19. Biomarkers for sepsis.

    Science.gov (United States)

    Henriquez-Camacho, Cesar; Losa, Juan

    2014-01-01

    Bloodstream infections are a major concern because of high levels of antibiotic consumption and of the increasing prevalence of antimicrobial resistance. Bacteraemia is identified in a small percentage of patients with signs and symptoms of sepsis. Biomarkers are widely used in clinical practice and they are useful for monitoring the infectious process. Procalcitonin (PCT) and C-reactive protein (CRP) have been most widely used, but even these have limited abilities to distinguish sepsis from other inflammatory conditions or to predict outcome. PCT has been used to guide empirical antibacterial therapy in patients with respiratory infections and help to determine if antibacterial therapy can be stopped. New biomarkers such as those in this review will discuss the major types of biomarkers of bloodstream infections/sepsis, including soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), soluble urokinase-type plasminogen receptor (suPAR), proadrenomedullin (ProADM), and presepsin.

  20. Inflammatory biomarkers and cancer

    DEFF Research Database (Denmark)

    Rasmussen, Line Jee Hartmann; Schultz, Martin; Gaardsting, Anne

    2017-01-01

    In Denmark, patients with serious nonspecific symptoms and signs of cancer (NSSC) are referred to the diagnostic outpatient clinics (DOCs) where an accelerated cancer diagnostic program is initiated. Various immunological and inflammatory biomarkers have been associated with cancer, including...... soluble urokinase plasminogen activator receptor (suPAR) and the pattern recognition receptors (PRRs) pentraxin-3, mannose-binding lectin, ficolin-1, ficolin-2 and ficolin-3. We aimed to evaluate these biomarkers and compare their diagnostic ability to classical biomarkers for diagnosing cancer...... in patients with NSSC. Patients were included from the DOC, Department of Infectious Diseases, Copenhagen University Hospital Hvidovre. Patients were given a final diagnosis based on the combined results from scans, blood work and physical examination. Weight loss, Charlson score and previous cancer were...

  1. Biomarkers of the Dementia

    Directory of Open Access Journals (Sweden)

    Mikio Shoji

    2011-01-01

    Full Text Available Recent advances in biomarker studies on dementia are summarized here. CSF Aβ40, Aβ42, total tau, and phosphorylated tau are the most sensitive biomarkers for diagnosis of Alzheimer's disease (AD and prediction of onset of AD from mild cognitive impairment (MCI. Based on this progress, new diagnostic criteria for AD, MCI, and preclinical AD were proposed by National Institute of Aging (NIA and Alzheimer's Association in August 2010. In these new criteria, progress in biomarker identification and amyloid imaging studies in the past 10 years have added critical information. Huge contributions of basic and clinical studies have established clinical evidence supporting these markers. Based on this progress, essential therapy for cure of AD is urgently expected.

  2. I-FABP as biomarker for the early diagnosis of acute mesenteric ischemia and resultant lung injury.

    Directory of Open Access Journals (Sweden)

    Rachel G Khadaroo

    Full Text Available Acute mesenteric ischemia (AMI is a life-threatening condition that can result in multiple organ injury and death. A timely diagnosis and treatment would have a significant impact on the morbidity and mortality in high-risk patient population. The purpose of this study was to investigate if intestinal fatty acid binding protein (I-FABP and α-defensins can be used as biomarkers for early AMI and resultant lung injury. C57BL/6 mice were subjected to intestinal ischemia by occlusion of the superior mesenteric artery. A time course of intestinal ischemia from 0.5 to 3 h was performed and followed by reperfusion for 2 h. Additional mice were treated with N-acetyl-cysteine (NAC at 300 mg/kg given intraperitoneally prior to reperfusion. AMI resulted in severe intestinal injury characterized by neutrophil infiltrate, myeloperoxidase (MPO levels, cytokine/chemokine levels, and tissue histopathology. Pathologic signs of ischemia were evident at 1 h, and by 3 h of ischemia, the full thickness of the intestine mucosa had areas of coagulative necrosis. It was noted that the levels of α-defensins in intestinal tissue peaked at 1 h and I-FABP in plasma peaked at 3 h after AMI. Intestinal ischemia also resulted in lung injury in a time-dependent manner. Pretreatment with NAC decreased the levels of intestinal α-defensins and plasma I-FABP, as well as lung MPO and cytokines. In summary, the concentrations of intestinal α-defensins and plasma I-FABP predicted intestinal ischemia prior to pathological evidence of ischemia and I-FABP directly correlated with resultant lung injury. The antioxidant NAC reduced intestinal and lung injury induced by AMI, suggesting a role for oxidants in the mechanism for distant organ injury. I-FABP and α-defensins are promising biomarkers, and may guide the treatment with antioxidant in early intestinal and distal organ injury.

  3. Gastro-intestinal involvement in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Saurabh Kedia

    2017-01-01

    Full Text Available The gastrointestinal (GI tract can be involved in up to 90% of patients with systemic sclerosis (SSc and is the leading cause of morbidity and third most common cause of mortality in these patients. The GI involvement can occur in the absence of cutaneous manifestations in 10% of patients. Vasculopathy, cellular and humoral immunity, and diffuse fibrosis are the principal pathogenetic mechanisms in SSc and begin with autoantibody-mediated neuronal damage followed by muscular damage and fibrosis. This leads to progressive dysmotility of the entire GI tract from mouth to anus and is responsible for the clinical manifestations including gastroesophageal reflux disease and dysphagia due to esophageal involvement, gastroparesis, small intestinal bacterial overgrowth and chronic intestinal pseudo-obstruction, and constipation due to colonic and fecal incontinence due to anorectal involvement. The clinical features resulting from the involvement of these organs often overlap and multiple areas may be involved simultaneously. The treatment remains mostly symptomatic because effective disease-modifying therapies are lacking. These patients are at a risk of malnutrition and nutritional screening, and thus rehabilitation is very important. Refractory cases require nutritional support in the form of enteral nutrition and/or home parenteral nutrition. Future research is needed in the pathogenesis, development of biomarkers for early identification of GI involvement at the asymptomatic stage, and targeted disease-modifying therapies, which can alter/halt the disease progression.

  4. Small intestinal transplantation.

    LENUS (Irish Health Repository)

    Quigley, E M

    2012-02-03

    The past few years have witnessed a considerable shift in the clinical status of intestinal transplantation. A great deal of experience has been gained at the most active centers, and results comparable with those reported at a similar stage in the development of other solid-organ graft programs are now being achieved by these highly proficient transplant teams. Rejection and its inevitable associate, sepsis, remain ubiquitous, and new immunosuppressant regimes are urgently needed; some may already be on the near horizon. The recent success of isolated intestinal grafts, together with the mortality and morbidity attendant upon the development of advanced liver disease related to total parenteral nutrition, has prompted the bold proposal that patients at risk for this complication should be identified and should receive isolated small bowel grafts before the onset of end-stage hepatic failure. The very fact that such a suggestion has begun to emerge reflects real progress in this challenging field.

  5. Biomarkers of diseases in medicine

    Indian Academy of Sciences (India)

    phases (phase I, phase II and phase III), research on biomarkers has largely been guided by intui- tion and experience. In 2002, the National Can- cer Institute's 'Early Detection Research Network' developed a five-phase approach to systematic dis- covery and evaluation of biomarkers. In general, biomarker development ...

  6. Validation of New Cancer Biomarkers

    DEFF Research Database (Denmark)

    Duffy, Michael J; Sturgeon, Catherine M; Söletormos, Georg

    2015-01-01

    BACKGROUND: Biomarkers are playing increasingly important roles in the detection and management of patients with cancer. Despite an enormous number of publications on cancer biomarkers, few of these biomarkers are in widespread clinical use. CONTENT: In this review, we discuss the key steps in ad...

  7. Biomarkers for anorexia nervosa

    DEFF Research Database (Denmark)

    Sjøgren, Jan Magnus

    2017-01-01

    Biomarkers for anorexia nervosa (AN) which reflect the pathophysiology and relate to the aetiology of the disease, are warranted and could bring us one step closer to targeted treatment of AN. Some leads may be found in the biochemistry which often is found disturbed in AN, although normalization...

  8. Emerging Biomarkers in Glioblastoma

    Energy Technology Data Exchange (ETDEWEB)

    McNamara, Mairéad G.; Sahebjam, Solmaz; Mason, Warren P., E-mail: warren.mason@uhn.ca [Pencer Brain Tumor Centre, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, Ontario M5G 2M9 (Canada)

    2013-08-22

    Glioblastoma, the most common primary brain tumor, has few available therapies providing significant improvement in survival. Molecular signatures associated with tumor aggressiveness as well as with disease progression and their relation to differences in signaling pathways implicated in gliomagenesis have recently been described. A number of biomarkers which have potential in diagnosis, prognosis and prediction of response to therapy have been identified and along with imaging modalities could contribute to the clinical management of GBM. Molecular biomarkers including O(6)-methlyguanine-DNA-methyltransferase (MGMT) promoter and deoxyribonucleic acid (DNA) methylation, loss of heterozygosity (LOH) of chromosomes 1p and 19q, loss of heterozygosity 10q, isocitrate dehydrogenase (IDH) mutations, epidermal growth factor receptor (EGFR), epidermal growth factor, latrophilin, and 7 transmembrane domain-containing protein 1 on chromosome 1 (ELTD1), vascular endothelial growth factor (VEGF), tumor suppressor protein p53, phosphatase and tensin homolog (PTEN), p16INK4a gene, cytochrome c oxidase (CcO), phospholipid metabolites, telomerase messenger expression (hTERT messenger ribonucleic acid [mRNA]), microRNAs (miRNAs), cancer stem cell markers and imaging modalities as potential biomarkers are discussed. Inclusion of emerging biomarkers in prospective clinical trials is warranted in an effort for more effective personalized therapy in the future.

  9. Biomarkers of cell senescence

    Science.gov (United States)

    Dirmi, Goberdhan P.; Campisi, Judith; Peacocke, Monica

    1996-01-01

    The present invention provides a biomarker system for the in vivo and in vitro assessment of cell senescence. In the method of the present invention, .beta.-galactosidase activity is utilized as a means by which cell senescence may be assessed either in in vitro cell cultures or in vivo.

  10. Biomarkers in atopic dermatitis

    NARCIS (Netherlands)

    Thijs, J.L.

    2017-01-01

    Main findings of this thesis · A meta-analysis including 222 studies showed that serum TARC level is the best biomarker for disease severity currently available (chapter 2). · Immunoglobulin free light chains have been shown to correlate with disease severity in paediatric AD. However, they do not

  11. Emerging Biomarkers in Glioblastoma

    Directory of Open Access Journals (Sweden)

    Warren P. Mason

    2013-08-01

    Full Text Available Glioblastoma, the most common primary brain tumor, has few available therapies providing significant improvement in survival. Molecular signatures associated with tumor aggressiveness as well as with disease progression and their relation to differences in signaling pathways implicated in gliomagenesis have recently been described. A number of biomarkers which have potential in diagnosis, prognosis and prediction of response to therapy have been identified and along with imaging modalities could contribute to the clinical management of GBM. Molecular biomarkers including O(6-methlyguanine-DNA-methyltransferase (MGMT promoter and deoxyribonucleic acid (DNA methylation, loss of heterozygosity (LOH of chromosomes 1p and 19q, loss of heterozygosity 10q, isocitrate dehydrogenase (IDH mutations, epidermal growth factor receptor (EGFR, epidermal growth factor, latrophilin, and 7 transmembrane domain-containing protein 1 on chromosome 1 (ELTD1, vascular endothelial growth factor (VEGF, tumor suppressor protein p53, phosphatase and tensin homolog (PTEN, p16INK4a gene, cytochrome c oxidase (CcO, phospholipid metabolites, telomerase messenger expression (hTERT messenger ribonucleic acid [mRNA], microRNAs (miRNAs, cancer stem cell markers and imaging modalities as potential biomarkers are discussed. Inclusion of emerging biomarkers in prospective clinical trials is warranted in an effort for more effective personalized therapy in the future.

  12. The Role of Biomarkers in Diverticular Disease.

    Science.gov (United States)

    Gallo, Antonella; Ianiro, Gianluca; Montalto, Massimo; Cammarota, Giovanni

    2016-10-01

    Diverticulosis of the colon is a common condition in western countries. Acute diverticulitis may occur in 10% to 25% of the patients, sometimes associated with the presence of complications such as abscess, fistula, and perforation. Early diagnosis and accurate assessment of acute diverticulitis are necessary to start an efficacious treatment promptly, either conservatively or by surgery. The clinical picture may mimic other abdominal conditions; therefore, imaging techniques such as ultrasound or computed tomography are usually recommended, although they are expensive, examiner dependent, and potentially harmful. Recently, there has been increasing interest about the role of biological markers in diverticular disease as noninvasive, reliable, and inexpensive tools, conceivably able to support physicians in the diagnosis, the assessment of activity, and the monitoring of acute diverticulitis. By a MEDLINE search, most of the relevant data derived from C-reactive protein showed that it strongly supported the diagnosis of acute diverticulitis at values of >50 mg/L. It also represents a stronger marker compared with other serum biomarkers, able to correlate with the histologic severity in acute diverticulitis, the risk of perforation, and the response to therapy. Regarding fecal biomarkers, an interesting role has been reported for fecal calprotectin. It significantly correlates with inflammatory infiltrate. More relevantly, it correlates with the response to therapy and may predict the recurrence of colonic diverticulitis, as it is reliable in detecting subclinical intestinal inflammation, as reported already for inflammatory bowel disease. These represent encouraging results, but need to be confirmed in further larger studies.

  13. Small intestinal cytochromes P450.

    Science.gov (United States)

    Kaminsky, L S; Fasco, M J

    1991-01-01

    Small intestinal cytochromes P450 (P450) provide the principal, initial source of biotransformation of ingested xenobiotics. The consequences of such biotransformation are detoxification by facilitating excretion, or toxification by bioactivation. P450s occur at highest concentrations in the duodenum, near the pylorus, and at decreasing concentrations distally--being lowest in the ileum. Highest concentrations occur from midvillus to villous tip, with little or none occurring in the crypts of Lieberkuehn. Microsomal P4503A, 2C8-10, and 2D6 forms have been identified in human small intestine, and P450s 2B1, possibly 2B2, 2A1, and 3A1/2 were located in endoplasmic reticulum of rodent small intestine, while P4502B4 has been purified to electrophoretic homogeneity from rabbit intestine. Some evidence indicates a differential distribution of P450 forms along the length of the small intestine and even along the villus. Rat intestinal P450s are inducible by xenobiotics--with phenobarbital (PB) inducing P4502B1, 3-methylcholanthrene (3-MC) inducing P4501A1, and dexamethasone inducing two forms of P4503A. Induction is most effectively achieved by oral administration of the agents, and is rapid--aryl hydrocarbon hydroxylase (AHH) was increased within 1 h of administration of, for example, 3-MC. AHH, 7-ethoxycoumarin O-deethylase (ECOD), and 7-ethoxyresorufin O-deethylase (EROD) have been used most frequently as substrates to characterize intestinal P450s. Dietary factors affect intestinal P450s markedly--iron restriction rapidly decreased intestinal P450 to beneath detectable values; selenium deficiency acted similarly but was less effective; Brussels sprouts increased intestinal AHH activity 9.8-fold, ECOD activity 3.2-fold, and P450 1.9-fold; fried meat and dietary fat significantly increased intestinal EROD activity; a vitamin A-deficient diet increased, and a vitamin A-rich diet decreased intestinal P450 activities; and excess cholesterol in the diet increased intestinal

  14. Mechanism underlying methyl eugenol attenuation of intestinal ischemia/reperfusion injury.

    Science.gov (United States)

    Saleh, Hanan; El-Shorbagy, Haidan M

    2017-10-01

    Intestinal ischemia/reperfusion (I/R) injury is associated with a high risk of mortality in the clinical situation. Many factors are involved in I/R, including reactive oxygen species, cytokine release, and apoptosis. We aimed to determine whether a pure methyl eugenol (ME) given before intestinal ischemia, protects against intestinal I/R injury and the possible mechanism involved in this protection. Rat received ME (100 mg/kg) for 30 days then underwent intestinal I/R with 30 min ischemia and 60 min reperfusion. Serum lactate dehydrogenase (LDH) level, tissue malondialdehyde (MDA), as well as some antioxidant biomarkers were assessed, while the serum level of tumor necrosis factor alpha (TNF-α) was determined by ELISA. The change in TNF-α and interleukin 6 (IL-6) gene expressions were evaluated and confirmed by assessing protein level of TNF-α in the intestinal tissue by immunohistochemistry. Apoptosis was evaluated using DNA-laddering assay and by detecting caspase-3 immunohistochemically. Administration of ME prior to I/R injury resulted in a modulation of the production of MDA, LDH, and nitric oxide and restoration of the tested oxidative stress biomarkers. Pretreatment with ME downregulated messenger RNA of TNF-α and IL-6 inflammatory cytokines and their protein expressions in I/R rats. Marked inhibition of the apoptotic DNA and improvement of the architectures of small intestine were observed after pretreatment with ME. ME exhibits a protective effect against intestinal I/R via amelioration of the oxidative stress and inflammatory cytokines gene expression. Therefore, the supplementation of ME prior to intestinal I/R might be helpful in the attenuation of I/R complications.

  15. Lipo sarcoma in small intestine

    International Nuclear Information System (INIS)

    Rodriguez Iglesias, J.; Pineyro Gutierrez, A.; Taroco Medeiros, L.; Fein Kolodny, C.; Navarrete Pedocchi, H.

    1987-01-01

    A case is presented by primitive liposarcoma in small intestine , an extensive bibliographical review foreigner and national in this case. It detach the exceptional of the intestinal topography of the liposarcomas; and making stress in the relative value of the computerized tomography and ultrasonography in the diagnose of the small intestine tumors . As well as in the sarcomas of another topography, chemo and radiotherapy associated to the exeresis surgery, it can be of benefit [es

  16. Towards Improved Biomarker Research

    DEFF Research Database (Denmark)

    Kjeldahl, Karin

    This thesis takes a look at the data analytical challenges associated with the search for biomarkers in large-scale biological data such as transcriptomics, proteomics and metabolomics data. These studies aim to identify genes, proteins or metabolites which can be associated with e.g. a diet......, disease (e.g. cancer), drug response or physiological status. The value of these omics studies has to some extent been questioned as it is often observed that the validity of claimed biomarkers has been very difficult to verify in other studies. On the other hand, in many studies it is difficult...... is investigated and followed by some suggestions which can potentially improve the chances of a successful outcome of an omics study. A method widely applied in the analysis of omics studies is Partial Least Squares (PLS) regression which is one of the work horses within the chemometrics tool box; a method which...

  17. Novel biomarkers for sepsis

    DEFF Research Database (Denmark)

    Larsen, Frederik Fruergaard; Petersen, J Asger

    2017-01-01

    BACKGROUND: Sepsis is a prevalent condition among hospitalized patients that carries a high risk of morbidity and mortality. Rapid recognition of sepsis as the cause of deterioration is desirable, so effective treatment can be initiated rapidly. Traditionally, diagnosis was based on presence of two...... or more positive SIRS criteria due to infection. However, recently published sepsis-3 criteria put more emphasis on organ dysfunction caused by infection in the definition of sepsis. Regardless of this, no gold standard for diagnosis exist, and clinicians still rely on a number of traditional and novel...... biomarkers to discriminate between patients with and without infection, as the cause of deterioration. METHOD: Narrative review of current literature. RESULTS: A number of the most promising biomarkers for diagnoses and prognostication of sepsis are presented. CONCLUSION: Procalcitonin, presepsin, CD64, su...

  18. Hereditary intestinal polyposis syndromes.

    Science.gov (United States)

    Dean, P A

    1996-01-01

    Colorectal cancer is one of the most common cancers in the world, with overall mortality exceeding 40% even with treatment. Effective efforts for screening and prevention are most likely to succeed in patient groups identified as high risk for colorectal cancer, most notably the hereditary intestinal polyposis syndromes. In these syndromes, benign polyps develop throughout the intestinal tract prior to the development of colorectal cancer, marking the patient and associated family for precancer diagnosis followed by either close surveillance or preventive treatment. This review article was undertaken to discuss the most recent developments in the knowledge of hereditary intestinal polyposis syndromes, emphasizing the clinical approach to diagnosis and treatment relative to preventing the development of cancer. The most common of the hereditary polyposis syndromes is familial adenomatous polyposis (FAP), which is characterized by the development of hundreds to thousands of adenomatous polyps in the colon followed at an early age by colorectal cancer. Colorectal cancer can be prevented in this autosomal dominant condition by prophylactic colectomy, though a risk for other tumors, including periampullary cancers, remains throughout life. Variant of FAP associated with fewer and smaller polyps (hereditary flat adenoma syndrome), or even CNS tumors (Turcot's syndrome) also carry this high risk of colorectal cancer. Hereditary hamartomatous polyposis syndromes such as juvenile polyposis and Peutz-Jeghers syndrome (also autosomal dominant) are characterized by less frequent polyps. Though these are generally benign polyps, they are also associated with a significant risk of colorectal and other cancers. Other polyposis syndromes, including neurofibromatosis and Cowden's disease, do not carry this increased risk of colorectal cancer, and therefore affect different treatment strategies. Analysis of genetic factors responsible for these and other hereditary syndromes with

  19. Decreased leukocyte recruitment by inorganic nitrate and nitrite in microvascular inflammation and NSAID-induced intestinal injury.

    Science.gov (United States)

    Jädert, Cecilia; Petersson, Joel; Massena, Sara; Ahl, David; Grapensparr, Liza; Holm, Lena; Lundberg, Jon O; Phillipson, Mia

    2012-02-01

    Nitric oxide (NO) generated by vascular NO synthases can exert anti-inflammatory effects, partly through its ability to decrease leukocyte recruitment. Inorganic nitrate and nitrite, from endogenous or dietary sources, have emerged as alternative substrates for NO formation in mammals. Bioactivation of nitrate is believed to require initial reduction to nitrite by oral commensal bacteria. Here we investigated the effects of inorganic nitrate and nitrite on leukocyte recruitment in microvascular inflammation and in NSAID-induced small-intestinal injury. We show that leukocyte emigration in response to the proinflammatory chemokine MIP-2 is reduced by 70% after 7 days of dietary nitrate supplementation as well as by acute intravenous nitrite administration. Nitrite also reduced leukocyte adhesion to a similar extent and this effect was inhibited by the soluble guanylyl cyclase inhibitor ODQ, whereas the effect on emigrated leukocytes was not altered by this treatment. Further studies in TNF-α-stimulated endothelial cells revealed that nitrite dose-dependently reduced the expression of ICAM-1. In rats and mice subjected to a challenge with diclofenac, dietary nitrate prevented the increase in myeloperoxidase and P-selectin levels in small-intestinal tissue. Antiseptic mouthwash, which eliminates oral nitrate reduction, markedly blunted the protective effect of dietary nitrate on P-selectin levels. Despite attenuation of the acute immune response, the overall ability to clear an infection with Staphylococcus aureus was not suppressed by dietary nitrate as revealed by noninvasive IVIS imaging. We conclude that dietary nitrate markedly reduces leukocyte recruitment to inflammation in a process involving attenuation of P-selectin and ICAM-1 upregulation. Bioactivation of dietary nitrate requires intermediate formation of nitrite by oral nitrate-reducing bacteria and then probably further reduction to NO and other bioactive nitrogen oxides in the tissues. Copyright

  20. Biomarkers of Selenium Status

    Directory of Open Access Journals (Sweden)

    Gerald F. Combs, Jr.

    2015-03-01

    Full Text Available The essential trace element, selenium (Se, has multiple biological activities, which depend on the level of Se intake. Relatively low Se intakes determine the expression of selenoenzymes in which it serves as an essential constituent. Higher intakes have been shown to have anti-tumorigenic potential; and very high Se intakes can produce adverse effects. This hierarchy of biological activities calls for biomarkers informative at different levels of Se exposure. Some Se-biomarkers, such as the selenoproteins and particularly GPX3 and SEPP1, provide information about function directly and are of value in identifying nutritional Se deficiency and tracking responses of deficient individuals to Se-treatment. They are useful under conditions of Se intake within the range of regulated selenoprotein expression, e.g., for humans <55 μg/day and for animals <20 μg/kg diet. Other Se-biomarkers provide information indirectly through inferences based on Se levels of foods, tissues, urine or feces. They can indicate the likelihood of deficiency or adverse effects, but they do not provide direct evidence of either condition. Their value is in providing information about Se status over a wide range of Se intake, particularly from food forms. There is need for additional Se biomarkers particularly for assessing Se status in non-deficient individuals for whom the prospects of cancer risk reduction and adverse effects risk are the primary health considerations. This would include determining whether supranutritional intakes of Se may be required for maximal selenoprotein expression in immune surveillance cells. It would also include developing methods to determine low molecular weight Se-metabolites, i.e., selenoamino acids and methylated Se-metabolites, which to date have not been detectable in biological specimens. Recent analytical advances using tandem liquid chromatography-mass spectrometry suggest prospects for detecting these metabolites.

  1. Urinary Protein Biomarker Analysis

    Science.gov (United States)

    2017-10-01

    associated protein biomarkers were identified by transcriptomic comparison of cancer cells vs. normal luminal cells; cancer-associated stromal cells vs...analysis; (C) correction with PSA, P = 0.012); (D) ROC curve analysis. 4-1. Use of PSA levels for marker level normalization Other organs along the...Copyright: Shi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which

  2. Chemoresistive Gas Sensors for the Detection of Colorectal Cancer Biomarkers

    Directory of Open Access Journals (Sweden)

    Cesare Malagù

    2014-10-01

    Full Text Available Numerous medical studies show that tumor growth is accompanied by protein changes that may lead to the peroxidation of the cell membrane with consequent emission of volatile organic compounds (VOCs by breath or intestinal gases that should be seen as biomarkers for colorectal cancer (CRC. The analysis of VOCs represents a non-invasive and potentially inexpensive preliminary screening technique. An array of chemoresistive gas sensors based on screen-printed metal oxide semiconducting films has been selected to discriminate gases of oncological interest, e.g., 1-iodononane and benzene, widely assumed to be biomarkers of colorectal cancer, from those of interference in the gut, such as methane and nitric oxide.

  3. Intestinal parasites : associations with intestinal and systemic inflammation

    NARCIS (Netherlands)

    Zavala, Gerardo A; García, Olga P; Camacho, Mariela; Ronquillo, Dolores; Campos-Ponce, Maiza; Doak, Colleen; Polman, Katja; Rosado, Jorge L

    2018-01-01

    AIMS: Evaluate associations between intestinal parasitic infection with intestinal and systemic inflammatory markers in school-aged children with high rates of obesity. METHODS AND RESULTS: Plasma concentrations of CRP, leptin, TNF-α, IL-6 and IL-10 were measured as systemic inflammation markers and

  4. Farnesoid X Receptor Activation Attenuates Intestinal Ischemia Reperfusion Injury in Rats.

    Directory of Open Access Journals (Sweden)

    Laurens J Ceulemans

    Full Text Available The farnesoid X receptor (FXR is abundantly expressed in the ileum, where it exerts an enteroprotective role as a key regulator of intestinal innate immunity and homeostasis, as shown in pre-clinical models of inflammatory bowel disease. Since intestinal ischemia reperfusion injury (IRI is characterized by hyperpermeability, bacterial translocation and inflammation, we aimed to investigate, for the first time, if the FXR-agonist obeticholic acid (OCA could attenuate intestinal ischemia reperfusion injury.In a validated rat model of intestinal IRI (laparotomy + temporary mesenteric artery clamping, 3 conditions were tested (n = 16/group: laparotomy only (sham group; ischemia 60min+ reperfusion 60min + vehicle pretreatment (IR group; ischemia 60min + reperfusion 60min + OCA pretreatment (IR+OCA group. Vehicle or OCA (INT-747, 2*30mg/kg was administered by gavage 24h and 4h prior to IRI. The following end-points were analyzed: 7-day survival; biomarkers of enterocyte viability (L-lactate, I-FABP; histology (morphologic injury to villi/crypts and villus length; intestinal permeability (Ussing chamber; endotoxin translocation (Lipopolysaccharide assay; cytokines (IL-6, IL-1-β, TNFα, IFN-γ IL-10, IL-13; apoptosis (cleaved caspase-3; and autophagy (LC3, p62.It was found that intestinal IRI was associated with high mortality (90%; loss of intestinal integrity (structurally and functionally; increased endotoxin translocation and pro-inflammatory cytokine production; and inhibition of autophagy. Conversely, OCA-pretreatment improved 7-day survival up to 50% which was associated with prevention of epithelial injury, preserved intestinal architecture and permeability. Additionally, FXR-agonism led to decreased pro-inflammatory cytokine release and alleviated autophagy inhibition.Pretreatment with OCA, an FXR-agonist, improves survival in a rodent model of intestinal IRI, preserves the gut barrier function and suppresses inflammation. These results turn

  5. Ghrelin and melatonin as biomarkers in patients with giardiasis

    Directory of Open Access Journals (Sweden)

    Saleem Khteer Al-Hadraawy

    2016-05-01

    Full Text Available Giardia is the most frequently reported intestinal parasite worldwide. The aim of this study was to investigate the ghrelin, melatonin, glucose and cholesterol concentration in male patients infected with Giardia lamblia. We enrolled 66 patients with Giardiasis and the control groups consisted of healthy subjects (n = 30. The results demonstrated that there was a significant decrease (P < 0.05 in ghrelin levels, while the melatonin, glucose and cholesterol levels were significantly increased (P < 0.05 in giardiasis patients as compared to the healthy group. The obtained results suggest that ghrelin and melatonin could serve as biomarkers in patients infected with G. lamblia.

  6. Immunoproteomic to Identify Antigens in the Intestinal Mucosa of Crohn's Disease Patients

    Science.gov (United States)

    Gu, Guosheng; Wang, Gefei; Wu, Wenyong; Zhang, Changle; Ren, Jianan

    2013-01-01

    Incidences of Crohn disease (CD) have increased significantly in the last decade. Immunoproteomics are a promising method to identify biomarkers of different diseases. In the present study, we used immunoproteomics to study proteins of intestinal mucosal lesions and neighboring normal intestinal mucosa of 8 CD patients. Reactive proteins were validated by Western blotting. Approximately 50 protein spots localized in the 4 to 7 pI range were detected on two-dimensional electrophoresis gels, and 6 differentially expressed protein spots between 10 and 100 kDa were identified. Reactive proteins were identified as prohibitin, calreticulin, apolipoprotein A-I, intelectin-1, protein disulfide isomerase, and glutathione s-transferase Pi. Western blotting was conducted on the intestinal mucosa of another 4 CD patients to validate the reactive proteins. We found that intestinal mucosal lesions had high levels of prohibitin expression. Glutathione s-transferase expression was detected in 100% of the intestinal mucosa examined. Thus, we report 6 autoantigens of CD, including 3 new and 3 previously reported autoantigens. Intelectin-1, protein disulfide isomerase, and glutathione-s-transferases may be used as biomarkers for CD pathogenesis. PMID:24358121

  7. Biomarkers in Diabetic Retinopathy

    Science.gov (United States)

    Jenkins, Alicia J.; Joglekar, Mugdha V.; Hardikar, Anandwardhan A.; Keech, Anthony C.; O'Neal, David N.; Januszewski, Andrzej S.

    2015-01-01

    There is a global diabetes epidemic correlating with an increase in obesity. This coincidence may lead to a rise in the prevalence of type 2 diabetes. There is also an as yet unexplained increase in the incidence of type 1 diabetes, which is not related to adiposity. Whilst improved diabetes care has substantially improved diabetes outcomes, the disease remains a common cause of working age adult-onset blindness. Diabetic retinopathy is the most frequently occurring complication of diabetes; it is greatly feared by many diabetes patients. There are multiple risk factors and markers for the onset and progression of diabetic retinopathy, yet residual risk remains. Screening for diabetic retinopathy is recommended to facilitate early detection and treatment. Common biomarkers of diabetic retinopathy and its risk in clinical practice today relate to the visualization of the retinal vasculature and measures of glycemia, lipids, blood pressure, body weight, smoking, and pregnancy status. Greater knowledge of novel biomarkers and mediators of diabetic retinopathy, such as those related to inflammation and angiogenesis, has contributed to the development of additional therapeutics, in particular for late-stage retinopathy, including intra-ocular corticosteroids and intravitreal vascular endothelial growth factor inhibitors ('anti-VEGFs') agents. Unfortunately, in spite of a range of treatments (including laser photocoagulation, intraocular steroids, and anti-VEGF agents, and more recently oral fenofibrate, a PPAR-alpha agonist lipid-lowering drug), many patients with diabetic retinopathy do not respond well to current therapeutics. Therefore, more effective treatments for diabetic retinopathy are necessary. New analytical techniques, in particular those related to molecular markers, are accelerating progress in diabetic retinopathy research. Given the increasing incidence and prevalence of diabetes, and the limited capacity of healthcare systems to screen and treat

  8. Hippo signalling directs intestinal fate

    DEFF Research Database (Denmark)

    le Bouteiller, Marie Catherine M; Jensen, Kim Bak

    2015-01-01

    Hippo signalling has been associated with many important tissue functions including the regulation of organ size. In the intestinal epithelium differing functions have been proposed for the effectors of Hippo signalling, YAP and TAZ1. These are now shown to have a dual role in the intestinal epit...

  9. MDCT in blunt intestinal trauma

    Energy Technology Data Exchange (ETDEWEB)

    Romano, Stefania [Department of Diagnostic Imaging, ' A.Cardarelli' Hospital, 80131 Naples (Italy)]. E-mail: stefromano@libero.it; Scaglione, Mariano [Department of Diagnostic Imaging, ' A.Cardarelli' Hospital, 80131 Naples (Italy); Tortora, Giovanni [Department of Diagnostic Imaging, ' A.Cardarelli' Hospital, 80131 Naples (Italy); Martino, Antonio [Trauma Center, ' A.Cardarelli' Hospital, 80131 Naples (Italy); Di Pietto, Francesco [Department of Diagnostic Imaging, ' A.Cardarelli' Hospital, 80131 Naples (Italy); Romano, Luigia [Department of Diagnostic Imaging, ' A.Cardarelli' Hospital, 80131 Naples (Italy); Grassi, Roberto [Department ' Magrassi-Lanzara' , Section of Radiology, Second University of Naples, 80138 Naples (Italy)

    2006-09-15

    Injuries to the small and large intestine from blunt trauma represent a defined clinical entity, often not easy to correctly diagnose in emergency but extremely important for the therapeutic assessment of patients. This article summarizes the MDCT spectrum of findings in intestinal blunt lesions, from functional disorders to hemorrhage and perforation.

  10. MDCT in blunt intestinal trauma

    International Nuclear Information System (INIS)

    Romano, Stefania; Scaglione, Mariano; Tortora, Giovanni; Martino, Antonio; Di Pietto, Francesco; Romano, Luigia; Grassi, Roberto

    2006-01-01

    Injuries to the small and large intestine from blunt trauma represent a defined clinical entity, often not easy to correctly diagnose in emergency but extremely important for the therapeutic assessment of patients. This article summarizes the MDCT spectrum of findings in intestinal blunt lesions, from functional disorders to hemorrhage and perforation

  11. Biomarkers of Environmental Enteropathy, Inflammation, Stunting, and Impaired Growth in Children in Northeast Brazil.

    Directory of Open Access Journals (Sweden)

    Richard L Guerrant

    Full Text Available Critical to the design and assessment of interventions for enteropathy and its developmental consequences in children living in impoverished conditions are non-invasive biomarkers that can detect intestinal damage and predict its effects on growth and development. We therefore assessed fecal, urinary and systemic biomarkers of enteropathy and growth predictors in 375 6-26 month-old children with varying degrees of malnutrition (stunting or wasting in Northeast Brazil. 301 of these children returned for followup anthropometry after 2-6m. Biomarkers that correlated with stunting included plasma IgA anti-LPS and anti-FliC, zonulin (if >12m old, and intestinal FABP (I-FABP, suggesting prior barrier disruption; and with citrulline, tryptophan and with lower serum amyloid A (SAA (suggesting impaired defenses. In contrast, subsequent growth was predicted in those with higher fecal MPO or A1AT and also by higher L/M, plasma LPS, I-FABP and SAA (showing intestinal barrier disruption and inflammation. Better growth was predicted in girls with higher plasma citrulline and in boys with higher plasma tryptophan. Interactions were also seen with fecal MPO and neopterin in predicting subsequent growth impairment. Biomarkers clustered into markers of 1 functional intestinal barrier disruption and translocation, 2 structural intestinal barrier disruption and inflammation and 3 systemic inflammation. Principle components pathway analyses also showed that L/M with %L, I-FABP and MPO associate with impaired growth, while also (like MPO associating with a systemic inflammation cluster of kynurenine, LBP, sCD14, SAA and K/T. Systemic evidence of LPS translocation associated with stunting, while markers of barrier disruption or repair (A1AT and Reg1 with low zonulin associated with fecal MPO and neopterin. We conclude that key noninvasive biomarkers of intestinal barrier disruption, LPS translocation and of intestinal and systemic inflammation can help elucidate how

  12. Predictive Biomarkers for Asthma Therapy.

    Science.gov (United States)

    Medrek, Sarah K; Parulekar, Amit D; Hanania, Nicola A

    2017-09-19

    Asthma is a heterogeneous disease characterized by multiple phenotypes. Treatment of patients with severe disease can be challenging. Predictive biomarkers are measurable characteristics that reflect the underlying pathophysiology of asthma and can identify patients that are likely to respond to a given therapy. This review discusses current knowledge regarding predictive biomarkers in asthma. Recent trials evaluating biologic therapies targeting IgE, IL-5, IL-13, and IL-4 have utilized predictive biomarkers to identify patients who might benefit from treatment. Other work has suggested that using composite biomarkers may offer enhanced predictive capabilities in tailoring asthma therapy. Multiple biomarkers including sputum eosinophil count, blood eosinophil count, fractional concentration of nitric oxide in exhaled breath (FeNO), and serum periostin have been used to identify which patients will respond to targeted asthma medications. Further work is needed to integrate predictive biomarkers into clinical practice.

  13. Ca 2+ signaling by plant Arabidopsis thaliana Pep peptides depends on AtPepR1, a receptor with guanylyl cyclase activity, and cGMP-activated Ca 2+ channels

    KAUST Repository

    Qia, Zhi

    2010-11-18

    A family of peptide signaling molecules (AtPeps) and their plasma membrane receptor AtPepR1 are known to act in pathogendefense signaling cascades in plants. Little is currently known about the molecular mechanisms that link these signaling peptides and their receptor, a leucine-rich repeat receptor-like kinase, to downstream pathogen-defense responses. We identify some cellular activities of these molecules that provide the context for a model for their action in signaling cascades. AtPeps activate plasma membrane inwardly conducting Ca 2+ permeable channels in mesophyll cells, resulting in cytosolic Ca 2+ elevation. This activity is dependent on their receptor as well as a cyclic nucleotide-gated channel (CNGC2). We also show that the leucine-rich repeat receptor- like kinase receptor AtPepR1 has guanylyl cyclase activity, generating cGMP from GTP, and that cGMP can activate CNGC2- dependent cytosolic Ca 2+ elevation. AtPep-dependent expression of pathogen-defense genes (PDF1.2, MPK3, and WRKY33) is mediated by the Ca 2+ signaling pathway associated with AtPep peptides and their receptor. The work presented here indicates that extracellular AtPeps, which can act as danger-associated molecular patterns, signal by interaction with their receptor, AtPepR1, a plasma membrane protein that can generate cGMP. Downstream from AtPep and AtPepR1 in a signaling cascade, the cGMP-activated channel CNGC2 is involved in AtPep- and AtPepR1-dependent inward Ca 2+ conductance and resulting cytosolic Ca 2+ elevation. The signaling cascade initiated by AtPeps leads to expression of pathogen- defense genes in a Ca 2+-dependent manner.

  14. Biomarker Identification Using Text Mining

    Directory of Open Access Journals (Sweden)

    Hui Li

    2012-01-01

    Full Text Available Identifying molecular biomarkers has become one of the important tasks for scientists to assess the different phenotypic states of cells or organisms correlated to the genotypes of diseases from large-scale biological data. In this paper, we proposed a text-mining-based method to discover biomarkers from PubMed. First, we construct a database based on a dictionary, and then we used a finite state machine to identify the biomarkers. Our method of text mining provides a highly reliable approach to discover the biomarkers in the PubMed database.

  15. Modulation of Intestinal Microbiome Prevents Intestinal Ischemic Injury

    Directory of Open Access Journals (Sweden)

    Alessandra Bertacco

    2017-12-01

    Full Text Available Background: Butyrate protects against ischemic injury to the small intestine by reducing inflammation and maintaining the structure of the intestinal barrier, but is expensive, short-lived, and cannot be administered easily due to its odor. Lactate, both economical and more palatable, can be converted into butyrate by the intestinal microbiome. This study aimed to assess in a rat model whether lactate perfusion can also protect against intestinal ischemia.Materials and Methods: Rat intestinal segments were loaded in an in vitro bowel perfusion device, and water absorption or secretion was assessed based on fluorescence of FITC-inulin, a fluorescent marker bound to a biologically inert sugar. Change in FITC concentration was used as a measure of ischemic injury, given the tendency of ischemic cells to retain water. Hematoxylin and eosin-stained sections at light level microscopy were examined to evaluate intestinal epithelium morphology. Comparisons between the data sets were paired Student t-tests or ANOVA with p < 0.05 performed on GraphPad.Results: Lactate administration resulted in a protective effect against intestinal ischemia of similar magnitude to that observed with butyrate. Both exhibited approximately 1.5 times the secretion exhibited by control sections (p = 0.03. Perfusion with lactate and methoxyacetate, a specific inhibitor of lactate-butyrate conversion, abolished this effect (p = 0.09. Antibiotic treatment also eliminated this effect, rendering lactate-perfused sections similar to control sections (p = 0.72. Perfusion with butyrate and methoxyacetate did not eliminate the observed increased secretion, which indicates that ischemic protection was mediated by microbial conversion of lactate to butyrate (p = 0.71.Conclusions: Lactate's protective effect against intestinal ischemia due to microbial conversion to butyrate suggests possible applications in the transplant setting for reducing ischemic injury and ameliorating intestinal

  16. Hepcidin- A Burgeoning Biomarker

    Directory of Open Access Journals (Sweden)

    Hemkant Manikrao Deshmukh

    2017-10-01

    Full Text Available The discovery of hepcidin has triggered a virtual ignition of studies on iron metabolism and related disorders. The peptide hormone hepcidin is a key homeostatic regulator of iron metabolism. The synthesis of hepcidin is induced by systemic iron levels and by inflammatory stimuli. Several human diseases are associated with variations in hepcidin concentrations. The evaluation of hepcidin in biological fluids is therefore a promising device in the diagnosis and management of medical situations in which iron metabolism is affected. Thus, it made us to recapitulate role of hepcidin as biomarker.

  17. [Biomarkers in multiple sclerosis].

    Science.gov (United States)

    Fernández, Óscar; Arroyo-González, Rafael; Rodríguez-Antigüedad, Alfredo; García-Merino, Juan A; Comabella, Manuel; Villar, Luisa M; Izquierdo, Guillermo; Tintoré, Mar; Oreja-Guevara, Celia; Álvarez-Cermeño, José C; Meca-Lallana, José E; Prieto, José M; Ramió-Torrentà, Lluís; Martínez-Yélamos, Sergio; Montalban, Xavier

    2013-04-01

    Multiple sclerosis is the most frequent disabling neurological disease in young adults. Its development includes independent processes of inflammation, demyelination, neurodegeneration, gliosis and repair, which are responsible for the heterogeneity and individual variability in the expression of the disease, its prognosis and response to treatment. As part of personalised medicine, the progress made in the search for new biomarkers has identified promising candidates that may be useful for the early diagnosis of the disease, for detecting prognostic and developmental profiles of the disease, and for monitoring the response to treatment. Unfortunately, few of them have been validated adequately, which prevents them from being applied in clinical practice. In view of the latest findings, the experts recommend orienting research in another direction, not so much towards the discovery of new molecules or imaging techniques, but instead towards a clinical validation of these markers, with the aim of fostering translational research. This review offers an update on the information about the biomarkers in multiple sclerosis that have currently been validated and are thus potential candidates, as well as looking at their value in the diagnosis, prognosis, evaluation of the development of the disability caused by the disease and the response to therapy.

  18. Biomarkers in Vasculitis

    Science.gov (United States)

    Monach, Paul A.

    2014-01-01

    Purpose of review Better biomarkers are needed for guiding management of patients with vasculitis. Large cohorts and technological advances had led to an increase in pre-clinical studies of potential biomarkers. Recent findings The most interesting markers described recently include a gene expression signature in CD8+ T cells that predicts tendency to relapse or remain relapse-free in ANCA-associated vasculitis, and a pair of urinary proteins that are elevated in Kawasaki disease but not other febrile illnesses. Both of these studies used “omics” technologies to generate and then test hypotheses. More conventional hypothesis-based studies have indicated that the following circulating proteins have potential to improve upon clinically available tests: pentraxin-3 in giant cell arteritis and Takayasu’s arteritis; von Willebrand factor antigen in childhood central nervous system vasculitis; eotaxin-3 and other markers related to eosinophils or Th2 immune responses in eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome); and MMP-3, TIMP-1, and CXCL13 in ANCA-associated vasculitis. Summary New markers testable in blood and urine have the potential to assist with diagnosis, staging, assessment of current disease activity, and prognosis. However, the standards for clinical usefulness, in particular the demonstration of either very high sensitivity or very high specificity, have yet to be met for clinically relevant outcomes. PMID:24257367

  19. Megacystis microcolon intestinal hypoperistalsis syndrome

    Science.gov (United States)

    Hiradfar, Mehran; Shojaeian, Reza; Dehghanian, Paria; Hajian, Sara

    2013-01-01

    Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a multisystemic disorder in which impaired intestinal motor activity causes recurrent symptoms of intestinal obstruction in the absence of mechanical occlusion, associated with bladder distention without distal obstruction of the urinary tract. MMIHS and prune belly syndrome may overlap in most of the clinical features and discrimination of these two entities is important because the prognosis, management and consulting with parents are completely different. MMIHS outcome is very poor and in this article we present two neonates with MMIHS that both died in a few days. PMID:23729700

  20. INFANTS’ INTESTINAL COLICS. MODERN DATA

    Directory of Open Access Journals (Sweden)

    N.I. Ursova

    2011-01-01

    Full Text Available The article analyzes modern data on infants’ intestinal colics. Peculiarities of nutrition, intestinal microbiocenose in healthy infants, methods of colcs’ correction are discussed. Author describes the principles of probiotics choice based on their clinical effectiveness in infants. Milk formula «Nan Comfort» can be useful in prophylaxis and treatment of functional disorders of gastrointestinal tract in children.Key words: infants, gastrointestinal tract, anatomy, physiology, intestinal colics, nutrition, probiotics.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2011; 10 (2: 125–131

  1. Which biomarkers reveal neonatal sepsis?

    Directory of Open Access Journals (Sweden)

    Kun Wang

    Full Text Available We address the identification of optimal biomarkers for the rapid diagnosis of neonatal sepsis. We employ both canonical correlation analysis (CCA and sparse support vector machine (SSVM classifiers to select the best subset of biomarkers from a large hematological data set collected from infants with suspected sepsis from Yale-New Haven Hospital's Neonatal Intensive Care Unit (NICU. CCA is used to select sets of biomarkers of increasing size that are most highly correlated with infection. The effectiveness of these biomarkers is then validated by constructing a sparse support vector machine diagnostic classifier. We find that the following set of five biomarkers capture the essential diagnostic information (in order of importance: Bands, Platelets, neutrophil CD64, White Blood Cells, and Segs. Further, the diagnostic performance of the optimal set of biomarkers is significantly higher than that of isolated individual biomarkers. These results suggest an enhanced sepsis scoring system for neonatal sepsis that includes these five biomarkers. We demonstrate the robustness of our analysis by comparing CCA with the Forward Selection method and SSVM with LASSO Logistic Regression.

  2. Disorders of the Small Intestine

    Science.gov (United States)

    ... that move down the intestine in a peristaltic fashion (Phase III). Phase III represents a continuation of ... Activities, Legislative & Regulatory Research Leadership Contact us News Industry Treatment News Medical News Legislative & Regulatory News Press ...

  3. Defence Mechanisms during Intestinal Infection

    Directory of Open Access Journals (Sweden)

    André Buret

    1991-01-01

    Full Text Available This review examines and compares host defence mechanisms during intestinal infection with three types of organisms: a virus, a bacterium and a nematode parasite (ie, transmissible gastroenteritis virus [TGEV], Helicobacter jejuni and Trichinella spiralis. Diarrhea is commonly associated with all of these infections. It appears that T spiralis initiates the most elaborate defence system of the three organisms, involving full range humoral and cellular immunity, as well as mucus hypersecretion, epithelial alterations, altered gut motility and parasite impairment (morphological and physiological. In contrast, intestinal defence against H jejuni and TGEV involves fewer components. The latter seems to initiate the most rudimentary host response. Despite such differences, these mechanisms exhibit many similarities, thus further illustrating the relatively limited repertoire of defence systems that the intestine can mount. The mediators translating the insult of any intestinal pathogen into a common response deserve further investigation.

  4. INTESTINAL INTUSSUSCEPTION DUE TO CONCURRENT ...

    African Journals Online (AJOL)

    Administrator

    Hymenolepis nana and Dentostomella ... worms (H. nana and D. translucida) were observed in the lumen of the intestine with severe cellular infiltration .... helminthosis and Balantidosis in Red monkey (Erythrocebus patas) in Ibadan Nigeria Nigerian ...

  5. [Autoantibodies as biomarkers].

    Science.gov (United States)

    Tron, François

    2014-01-01

    Activation and differentiation of autoreactive B-lymphocytes lead to the production of autoantibodies, which are thus the direct consequence of the autoimmune process. They often constitute biomarkers of autoimmune diseases and are measured by tests displaying various diagnosis sensitivity and specificity. Autoantibody titers can be correlated to the disease activity and certain autoantibody populations associated with particular clinical manifestations or tissue lesions. The demonstration that autoantibodies appear years before the onset of autoimmune diseases indicates that their presence in healthy individuals may be a predictive marker of the occurrence of disease. Certain autoantibodies could also be predictive markers of a therapeutic response to biologics and of the occurrence of side effects as well. Thus, autoantibodies are useful tools in the diagnosis and the management of patients with organ specific or non-organ specific autoimmune diseases at different steps of the autoimmune process. Copyright © 2013. Published by Elsevier Masson SAS.

  6. Biomarkers of adverse drug reactions.

    Science.gov (United States)

    Carr, Daniel F; Pirmohamed, Munir

    2018-02-01

    Adverse drug reactions can be caused by a wide range of therapeutics. Adverse drug reactions affect many bodily organ systems and vary widely in severity. Milder adverse drug reactions often resolve quickly following withdrawal of the casual drug or sometimes after dose reduction. Some adverse drug reactions are severe and lead to significant organ/tissue injury which can be fatal. Adverse drug reactions also represent a financial burden to both healthcare providers and the pharmaceutical industry. Thus, a number of stakeholders would benefit from development of new, robust biomarkers for the prediction, diagnosis, and prognostication of adverse drug reactions. There has been significant recent progress in identifying predictive genomic biomarkers with the potential to be used in clinical settings to reduce the burden of adverse drug reactions. These have included biomarkers that can be used to alter drug dose (for example, Thiopurine methyltransferase (TPMT) and azathioprine dose) and drug choice. The latter have in particular included human leukocyte antigen (HLA) biomarkers which identify susceptibility to immune-mediated injuries to major organs such as skin, liver, and bone marrow from a variety of drugs. This review covers both the current state of the art with regard to genomic adverse drug reaction biomarkers. We also review circulating biomarkers that have the potential to be used for both diagnosis and prognosis, and have the added advantage of providing mechanistic information. In the future, we will not be relying on single biomarkers (genomic/non-genomic), but on multiple biomarker panels, integrated through the application of different omics technologies, which will provide information on predisposition, early diagnosis, prognosis, and mechanisms. Impact statement • Genetic and circulating biomarkers present significant opportunities to personalize patient therapy to minimize the risk of adverse drug reactions. ADRs are a significant heath issue

  7. Parenteral Nutrition and Intestinal Failure.

    Science.gov (United States)

    Bielawska, Barbara; Allard, Johane P

    2017-05-06

    Severe short bowel syndrome (SBS) is a major cause of chronic (Type 3) intestinal failure (IF) where structural and functional changes contribute to malabsorption and risk of micronutrient deficiencies. Chronic IF may be reversible, depending on anatomy and intestinal adaptation, but most patients require long-term nutritional support, generally in the form of parenteral nutrition (PN). SBS management begins with dietary changes and pharmacologic therapies taking into account individual anatomy and physiology, but these are rarely sufficient to avoid PN. New hormonal therapies targeting intestinal adaptation hold promise. Surgical options for SBS including intestinal transplant are available, but have significant limitations. Home PN (HPN) is therefore the mainstay of treatment for severe SBS. HPN involves chronic administration of macronutrients, micronutrients, fluid, and electrolytes via central venous access in the patient's home. HPN requires careful clinical and biochemical monitoring. Main complications of HPN are related to venous access (infection, thrombosis) and metabolic complications including intestinal failure associated liver disease (IFALD). Although HPN significantly impacts quality of life, outcomes are generally good and survival is mostly determined by the underlying disease. As chronic intestinal failure is a rare disease, registries are a promising strategy for studying HPN patients to improve outcomes.

  8. [Biomarkers in endocrinology].

    Science.gov (United States)

    d'Herbomez, Michèle; Bauters, Catherine; Cortet-Rudelli, Christine; Dewailly, Didier; Docao, Christine; Wémeau, Jean-Louis

    2014-01-01

    TSH assay is the best parameter of the thyroid function. For adults, the normal interval of TSH concentrations range from 0.4 to 4 mUI/L. At the first trimester of pregnancy, TSH levels must be <2.5 mUI/L. Normal TSH levels increase with aging and obesity. The biological diagnosis relies on the identification of excessive secretion of the metanephrines which are more sensitive and specific than those of catecholamines. The concentrations of the free plasmatic metanephrines reflect the ongoing production of tumor. Plasma methoxytyramine is a novel biomarker of metastatic pheochromocytomas and paragangliomas. Serum IGF1 is a reliable measure of integrated GH concentrations in patients with acromegaly. Accurate assessment of IGF1 concentrations requires age and sex-matched control values. IGF1 is a sensitive tool for the diagnosis of acromegaly and efficacy of therapies. Serum AMH assay is more sensitive, more specific and more reproducible that counting of ovarian follicles by ultrasound. AMH level above 5 ng/mL (35 pmol/L) could be chosen as one of the diagnostic criteria for the polycystic ovary syndrome. In early or "incipiens" ovarian failure, the decrease in serum AMH is far ahead of the increase in FSH. Thyroglobulin (TG) and calcitonin (CT) are the sensitive and specific markers of respectively well-differentiated thyroid cancers of follicular origin and of the medullary thyroid cancers. The same tumour marker assay should be used to monitor a given patient. Chromogranin A (CgA) is a highly efficient biomarker for diagnosis and follow-up of various endocrine tumours. Despite the lack of international standardisation, some CgA assays are reliable. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  9. Biomarkers of manganese intoxication.

    Science.gov (United States)

    Zheng, Wei; Fu, Sherleen X; Dydak, Ulrike; Cowan, Dallas M

    2011-01-01

    Manganese (Mn), upon absorption, is primarily sequestered in tissue and intracellular compartments. For this reason, blood Mn concentration does not always accurately reflect Mn concentration in the targeted tissue, particularly in the brain. The discrepancy between Mn concentrations in tissue or intracellular components means that blood Mn is a poor biomarker of Mn exposure or toxicity under many conditions and that other biomarkers must be established. For group comparisons of active workers, blood Mn has some utility for distinguishing exposed from unexposed subjects, although the large variability in mean values renders it insensitive for discriminating one individual from the rest of the study population. Mn exposure is known to alter iron (Fe) homeostasis. The Mn/Fe ratio (MIR) in plasma or erythrocytes reflects not only steady-state concentrations of Mn or Fe in tested individuals, but also a biological response (altered Fe homeostasis) to Mn exposure. Recent human studies support the potential value for using MIR to distinguish individuals with Mn exposure. Additionally, magnetic resonance imaging (MRI), in combination with noninvasive assessment of γ-aminobutyric acid (GABA) by magnetic resonance spectroscopy (MRS), provides convincing evidence of Mn exposure, even without clinical symptoms of Mn intoxication. For subjects with long-term, low-dose Mn exposure or for those exposed in the past but not the present, neither blood Mn nor MRI provides a confident distinction for Mn exposure or intoxication. While plasma or erythrocyte MIR is more likely a sensitive measure, the cut-off values for MIR among the general population need to be further tested and established. Considering the large accumulation of Mn in bone, developing an X-ray fluorescence spectroscopy or neutron-based spectroscopy method may create yet another novel non-invasive tool for assessing Mn exposure and toxicity. Copyright © 2010 Elsevier Inc. All rights reserved.

  10. Haemorrhage and intestinal lymphoma

    Directory of Open Access Journals (Sweden)

    Attilia M. Pizzini

    2013-04-01

    Full Text Available Background: The prevalence of coeliac disease is around 1% in general population but this is often unrecognised. The classical presentation of adult coeliac disease is characterized by diarrhoea and malabsorption syndrome, but atypical presentations are probably more common and are characterized by iron deficiency anaemia, weight loss, fatigue, infertility, arthralgia, peripheral neuropathy and osteoporosis. Unusual are the coagulation disorders (prevalence 20% and these are due to vitamin K malabsorption (prolonged prothrombin time. Clinical case: A 64-year-old man was admitted to our Department for an extensive spontaneous haematoma of the right leg. He had a history of a small bowel resection for T-cell lymphoma, with a negative follow-up and he didn’t report any personal or familiar history of bleeding. Laboratory tests showed markedly prolonged prothrombin (PT and partial-thromboplastin time (PTT, corrected by mixing studies, and whereas platelet count and liver tests was normal. A single dose (10 mg of intravenous vitamin K normalized the PT. Several days before the patient had been exposed to a superwarfarin pesticide, but diagnostic tests for brodifacoum, bromadiolone or difenacoum were negative. Diagnosis of multiple vitamin K-dependent coagulationfactor deficiencies (II, VII, IX, X due to intestinal malabsorption was made and coeliac disease was detected. Therefore the previous lymphoma diagnosis might be closely related to coeliac disease. Conclusions: A gluten free diet improves quality of life and restores normal nutritional and biochemical status and protects against these complications.

  11. [Malaria and intestinal protozoa].

    Science.gov (United States)

    Rojo-Marcos, Gerardo; Cuadros-González, Juan

    2016-03-01

    Malaria is life threatening and requires urgent diagnosis and treatment. Incidence and mortality are being reduced in endemic areas. Clinical features are unspecific so in imported cases it is vital the history of staying in a malarious area. The first line treatments for Plasmodium falciparum are artemisinin combination therapies, chloroquine in most non-falciparum and intravenous artesunate if any severity criteria. Human infections with intestinal protozoa are distributed worldwide with a high global morbid-mortality. They cause diarrhea and sometimes invasive disease, although most are asymptomatic. In our environment populations at higher risk are children, including adopted abroad, immune-suppressed, travelers, immigrants, people in contact with animals or who engage in oral-anal sex. Diagnostic microscopic examination has low sensitivity improving with antigen detection or molecular methods. Antiparasitic resistances are emerging lately. Copyright © 2016 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  12. Adult intestinal failure

    Energy Technology Data Exchange (ETDEWEB)

    Davidson, J., E-mail: Jdavidson@doctors.org.u [Salford Royal Hospital, Salford (United Kingdom); Plumb, A.; Burnett, H. [Salford Royal Hospital, Salford (United Kingdom)

    2010-05-15

    Intestinal failure (IF) is the inability of the alimentary tract to digest and absorb sufficient nutrition to maintain normal fluid balance, growth, and health. It commonly arises from disease affecting the mesenteric root. Although severe IF is usually managed in specialized units, it lies at the end of a spectrum with degrees of nutritional compromise being widely encountered, but commonly under-recognized. Furthermore, in the majority of cases, the initial enteric insult occurs in non-specialist IF centres. The aim of this article is to review the common causes of IF, general principles of its management, some commoner complications, and the role of radiology in the approach to a patient with severe IF. The radiologist has a crucial role in helping provide access for feeding solutions (both enteral and parenteral) and controlling sepsis (via drainage of collections) in an initial restorative phase of treatment, whilst simultaneously mapping bowel anatomy and quality, and searching for disease complications to assist the clinicians in planning a later, restorative phase of therapy.

  13. [Intestinal failure: from adaptation to transplantation].

    Science.gov (United States)

    Messing, B; Corcos, O; Amiot, A; Joly, F

    2009-01-01

    Optimised Home Parenteral Nutrition is still, after 35 years of progress, the of benign but chronic Intestinal Failure. A better recognition of chronic Intestinal Failure, in its multiple facets, is warranted for a better approach of associated treatment to Home Parenteral Nutrition, i.e., intestinal trophic factors (growth hormone, Glucagon Like Peptide-2), rehabilitative surgery (reestablishment of colonic continuity, reverse jejunal segment in severe short gut type II) and/or reconstructive surgery (intestinal transplantation for end stage intestinal failure patients). Boundaries of permanent, judged irreversible, intestinal failure will be certainly modified in the following years by combining the various and effective therapies which optimise management by ameliorating absorption of the remnant short gut. The work done on short bowel syndrome in the past 20 years should be done in the next years for chronic-intestinal - pseudo-obstruction patients presenting with intestinal failure on a large European scale because chronic-intestinal - pseudo-obstruction is a group of heterogeneous but rare intestinal diseases. Intestinal transplantation is now a mature therapy with formal indication especially in case of Home Parenteral Nutrition failure (mainly Home Parenteral Nutrition-associated severe liver disease) where combined Liver-intestine transplantation is indicated before end-stage liver failure occurs. For high-risk patients, "preemptive" indication for intestinal transplantation alone will be discussed before home parenteral nutrition complications occur. No doubt that, for improving overall outcome in intestinal failure patients, reference centres should have in expert hands the whole spectrum of medicosurgical therapies for intestinal failure.

  14. Homeostasis of the gut barrier and potential biomarkers

    Science.gov (United States)

    Brummer, Robert J.; Derrien, Muriel; MacDonald, Thomas T.; Troost, Freddy; Cani, Patrice D.; Theodorou, Vassilia; Dekker, Jan; Méheust, Agnes; de Vos, Willem M.; Mercenier, Annick; Nauta, Arjen; Garcia-Rodenas, Clara L.

    2017-01-01

    The gut barrier plays a crucial role by spatially compartmentalizing bacteria to the lumen through the production of secreted mucus and is fortified by the production of secretory IgA (sIgA) and antimicrobial peptides and proteins. With the exception of sIgA, expression of these protective barrier factors is largely controlled by innate immune recognition of microbial molecular ligands. Several specialized adaptations and checkpoints are operating in the mucosa to scale the immune response according to the threat and prevent overreaction to the trillions of symbionts inhabiting the human intestine. A healthy microbiota plays a key role influencing epithelial barrier functions through the production of short-chain fatty acids (SCFAs) and interactions with innate pattern recognition receptors in the mucosa, driving the steady-state expression of mucus and antimicrobial factors. However, perturbation of gut barrier homeostasis can lead to increased inflammatory signaling, increased epithelial permeability, and dysbiosis of the microbiota, which are recognized to play a role in the pathophysiology of a variety of gastrointestinal disorders. Additionally, gut-brain signaling may be affected by prolonged mucosal immune activation, leading to increased afferent sensory signaling and abdominal symptoms. In turn, neuronal mechanisms can affect the intestinal barrier partly by activation of the hypothalamus-pituitary-adrenal axis and both mast cell-dependent and mast cell-independent mechanisms. The modulation of gut barrier function through nutritional interventions, including strategies to manipulate the microbiota, is considered a relevant target for novel therapeutic and preventive treatments against a range of diseases. Several biomarkers have been used to measure gut permeability and loss of barrier integrity in intestinal diseases, but there remains a need to explore their use in assessing the effect of nutritional factors on gut barrier function. Future studies

  15. [Interaction between humans and intestinal bacteria as a determinant for intestinal health : intestinal microbiome and inflammatory bowel diseases].

    Science.gov (United States)

    Haller, Dirk; Hörmannsperger, G

    2015-02-01

    Recent scientific results underline the importance of the intestinal microbiome, the totality of all intestinal microbes and their genes, for the health of the host organism. The intestinal microbiome can therefore be considered as a kind of "external organ". It has been shown that the intestinal microbiota is a complex and dynamic ecosystem that influences host immunity and metabolism beyond the intestine. The composition and functionality of the intestinal microbiota is of major importance for the development and maintenance of intestinal functions. Inflammatory bowel diseases (IBD) are characterized by dysregulated interactions between the host and its microbiota.The present contribution summarizes current knowledge of the composition and development of the intestinal microbiome and gives an overview of the bidirectional interaction between host and microbiota. The contribution informs about insights regarding the role of the intestinal microbiota in IBD and finally discusses the protective potential of microbial therapies in the context of IBD.

  16. Biomarkers for Detecting Mitochondrial Disorders

    Directory of Open Access Journals (Sweden)

    Josef Finsterer

    2018-01-01

    Full Text Available (1 Objectives: Mitochondrial disorders (MIDs are a genetically and phenotypically heterogeneous group of slowly or rapidly progressive disorders with onset from birth to senescence. Because of their variegated clinical presentation, MIDs are difficult to diagnose and are frequently missed in their early and late stages. This is why there is a need to provide biomarkers, which can be easily obtained in the case of suspecting a MID to initiate the further diagnostic work-up. (2 Methods: Literature review. (3 Results: Biomarkers for diagnostic purposes are used to confirm a suspected diagnosis and to facilitate and speed up the diagnostic work-up. For diagnosing MIDs, a number of dry and wet biomarkers have been proposed. Dry biomarkers for MIDs include the history and clinical neurological exam and structural and functional imaging studies of the brain, muscle, or myocardium by ultrasound, computed tomography (CT, magnetic resonance imaging (MRI, MR-spectroscopy (MRS, positron emission tomography (PET, or functional MRI. Wet biomarkers from blood, urine, saliva, or cerebrospinal fluid (CSF for diagnosing MIDs include lactate, creatine-kinase, pyruvate, organic acids, amino acids, carnitines, oxidative stress markers, and circulating cytokines. The role of microRNAs, cutaneous respirometry, biopsy, exercise tests, and small molecule reporters as possible biomarkers is unsolved. (4 Conclusions: The disadvantages of most putative biomarkers for MIDs are that they hardly meet the criteria for being acceptable as a biomarker (missing longitudinal studies, not validated, not easily feasible, not cheap, not ubiquitously available and that not all MIDs manifest in the brain, muscle, or myocardium. There is currently a lack of validated biomarkers for diagnosing MIDs.

  17. Biomarker in archaeological soils

    Science.gov (United States)

    Wiedner, Katja; Glaser, Bruno; Schneeweiß, Jens

    2015-04-01

    The use of biomarkers in an archaeological context allow deeper insights into the understanding of anthropogenic (dark) earth formation and from an archaeological point of view, a completely new perspective on cultivation practices in the historic past. During an archaeological excavation of a Slavic settlement (10th/11th C. A.D.) in Brünkendorf (Wendland region in Northern Germany), a thick black soil (Nordic Dark Earth) was discovered that resembled the famous terra preta phenomenon. For the humid tropics, terra preta could act as model for sustainable agricultural practices and as example for long-term CO2-sequestration into terrestrial ecosystems. The question was whether this Nordic Dark Earth had similar properties and genesis as the famous Amazonian Dark Earth in order to find a model for sustainable agricultural practices and long term CO2-sequestration in temperate zones. For this purpose, a multi-analytical approach was used to characterize the sandy-textured Nordic Dark Earth in comparison to less anthropogenically influenced soils in the adjacent area in respect of ecological conditions (e.g. amino sugar), input materials (faeces) and the presence of stable soil organic matter (black carbon). Amino sugar analyses showed that Nordic Dark Earth contained higher amounts of microbial residues being dominated by soil fungi. Faecal biomarkers such as stanols and bile acids indicated animal manure from omnivores and herbivores but also human excrements. Black carbon content of about 30 Mg ha-1 in the Nordic Dark Earth was about four times higher compared to the adjacent soil and in the same order of magnitude compared to terra preta. Our data strongly suggest parallels to anthropogenic soil formation in Amazonia and in Europe by input of organic wastes, faecal material and charred organic matter. An obvious difference was that in terra preta input of human-derived faecal material dominated while in NDE human-derived faecal material played only a minor role

  18. Biomarkers of latent TB infection

    DEFF Research Database (Denmark)

    Ruhwald, Morten; Ravn, Pernille

    2009-01-01

    For the last 100 years, the tuberculin skin test (TST) has been the only diagnostic tool available for latent TB infection (LTBI) and no biomarker per se is available to diagnose the presence of LTBI. With the introduction of M. tuberculosis-specific IFN-gamma release assays (IGRAs), a new area...... of in vitro immunodiagnostic tests for LTBI based on biomarker readout has become a reality. In this review, we discuss existing evidence on the clinical usefulness of IGRAs and the indefinite number of potential new biomarkers that can be used to improve diagnosis of latent TB infection. We also present...... early data suggesting that the monocyte-derived chemokine inducible protein-10 may be useful as a novel biomarker for the immunodiagnosis of latent TB infection....

  19. Emergence of biomarkers in nephropharmacology.

    Science.gov (United States)

    Khan, Enver; Batuman, Vecihi; Lertora, Juan J L

    2010-12-01

    Blood-urea nitrogen, serum creatinine and urine output have long been used as markers of kidney function despite their known limitations. In the past few years, a number of novel biomarkers have been identified in the urine and blood that can detect kidney injury early. Although, to date, none of these biomarkers are in clinical use, many have been validated as reliable and sensitive, allowing detection of kidney injury before serum creatinine levels rise and urine output drops. These markers have been evaluated in great detail in animal models and to a lesser extent in humans in postcardiopulmonary bypass and sepsis. There is relatively scarse data on the use of these biomarkers in the detection of kidney injury associated with the use of pharmacologic agents. The purpose of this article is to summarize these data and highlight the potential utility of these biomarkers in nephropharmacology.

  20. Biomarkers in localized prostate cancer

    Science.gov (United States)

    Ferro, Matteo; Buonerba, Carlo; Terracciano, Daniela; Lucarelli, Giuseppe; Cosimato, Vincenzo; Bottero, Danilo; Deliu, Victor M; Ditonno, Pasquale; Perdonà, Sisto; Autorino, Riccardo; Coman, Ioman; De Placido, Sabino; Di Lorenzo, Giuseppe; De Cobelli, Ottavio

    2016-01-01

    Biomarkers can improve prostate cancer diagnosis and treatment. Accuracy of prostate-specific antigen (PSA) for early diagnosis of prostate cancer is not satisfactory, as it is an organ- but not cancer-specific biomarker, and it can be improved by using models that incorporate PSA along with other test results, such as prostate cancer antigen 3, the molecular forms of PSA (proPSA, benign PSA and intact PSA), as well as kallikreins. Recent reports suggest that new tools may be provided by metabolomic studies as shown by preliminary data on sarcosine. Additional molecular biomarkers have been identified by the use of genomics, proteomics and metabolomics. We review the most relevant biomarkers for early diagnosis and management of localized prostate cancer. PMID:26768791

  1. Urinary Biomarkers of Brain Diseases

    Directory of Open Access Journals (Sweden)

    Manxia An

    2015-12-01

    Full Text Available Biomarkers are the measurable changes associated with a physiological or pathophysiological process. Unlike blood, urine is not subject to homeostatic mechanisms. Therefore, greater fluctuations could occur in urine than in blood, better reflecting the changes in human body. The roadmap of urine biomarker era was proposed. Although urine analysis has been attempted for clinical diagnosis, and urine has been monitored during the progression of many diseases, particularly urinary system diseases, whether urine can reflect brain disease status remains uncertain. As some biomarkers of brain diseases can be detected in the body fluids such as cerebrospinal fluid and blood, there is a possibility that urine also contain biomarkers of brain diseases. This review summarizes the clues of brain diseases reflected in the urine proteome and metabolome.

  2. Procalcitonine als biomarker voor infecties

    NARCIS (Netherlands)

    de Jonge, J C; de Lange, D W; Bij de Vaate, E A; van Leeuwen, H; Arends, J E

    2016-01-01

    - Inappropriate use of antibiotics in patients without bacterial infection contributes significantly to worldwide antibiotic resistance.- The goal of this review is to summarise evidence from randomised trials investigating the value of the biomarker procalcitonin (PCT) in patients with symptoms of

  3. Intestinal circulation during inhalation anesthesia

    International Nuclear Information System (INIS)

    Tverskoy, M.; Gelman, S.; Fowler, K.C.; Bradley, E.L.

    1985-01-01

    This study was designed to evaluate the influence of inhalational agents on the intestinal circulation in an isolated loop preparation. Sixty dogs were studied, using three intestinal segments from each dog. Selected intestinal segments were pumped with aortic blood at a constant pressure of 100 mmHg. A mixture of 86 Rb and 9-microns spheres labeled with 141 Ce was injected into the arterial cannula supplying the intestinal loop, while mesenteric venous blood was collected for activity counting. A very strong and significant correlation was found between rubidium clearance and microsphere entrapment (r = 0.97, P less than 0.0001). Nitrous oxide anesthesia was accompanied by a higher vascular resistance (VR), lower flow (F), rubidium clearance (Cl-Rb), and microspheres entrapment (Cl-Sph) than pentobarbital anesthesia, indicating that the vascular bed in the intestinal segment was constricted and flow (total and nutritive) decreased. Halothane, enflurane, and isoflurane anesthesia were accompanied by a much lower arteriovenous oxygen content difference (AVDO 2 ) and oxygen uptake than pentobarbital or nitrous oxide. Compared with pentobarbital, enflurane anesthesia was not accompanied by marked differences in VR, F, Cl-Rb, and Cl-Sph; halothane at 2 MAC decreased VR and increased F and Cl-Rb while isoflurane increased VR and decreased F. alpha-Adrenoceptor blockade with phentolamine (1 mg . kg-1) abolished isoflurane-induced vasoconstriction, suggesting that the increase in VR was mediated via circulating catecholamines

  4. Modeling intestinal disorders using zebrafish.

    Science.gov (United States)

    Zhao, X; Pack, M

    2017-01-01

    Although the zebrafish was initially developed as a model system to study embryonic development, it has gained increasing attention as an advantageous system to investigate human diseases, including intestinal disorders. Zebrafish embryos develop rapidly, and their digestive system is fully functional and visible by 5days post fertilization. There is a large degree of homology between the intestine of zebrafish and higher vertebrate organisms in terms of its cellular composition and function as both a digestive and immune organ. Furthermore, molecular pathways regulating injury and immune responses are highly conserved. In this chapter, we provide an overview of studies addressing developmental and physiological processes relevant to human intestinal disease. These studies include those related to congenital disorders, host-microbiota interactions, inflammatory diseases, motility disorders, and intestinal cancer. We also highlight the utility of zebrafish to functionally validate candidate genes identified through mutational analyses and genome-wide association studies, and discuss methodologies to investigate the intestinal biology that are unique to zebrafish. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Isotopic identification of intestinal strangulation

    International Nuclear Information System (INIS)

    Anderson, M.C.; Selby, J.B.

    1982-01-01

    A small series of eleven dogs prepared with a strangulating segment of jejunum demonstrated that a radionuclide, 99 mTc-labelled albumin, concentrates in the lumen and bowel wall of the affected intestinal segment. Modern scanning equipment accurately localized the strangulating loop. This technique has the potential of identifying patients with intestinal obstruction, in whom strangulation is a factor, prior to the development of impaired arterial inflow and frank gangrene. These findings confirmed earlier obstructions that were reported when nuclear scanning instrumentation was less sophisticated. Identification of patients at risk for intestinal strangulation requires a high index of suspicion. Excruciating cramping abdominal pain out of proportion to physical findings, roentgenogram evidence, and laboratory studies should alert the physician to the possibility of intestinal ischemia and closed loop obstruction. Radionuclide scanning in such cases may be of assistance in defining or excluding the diagnosis of a strangulating mechanism. The test is simple, relatively economical, and represents a low risk procedure to patients. It would have no place when the classic physical and laboratory findings of intestinal infarction are present

  6. Isotopic identification of intestinal strangulation

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, M.C.; Selby, J.B.

    1982-12-01

    A small series of eleven dogs prepared with a strangulating segment of jejunum demonstrated that a radionuclide, /sup 99/mTc-labelled albumin, concentrates in the lumen and bowel wall of the affected intestinal segment. Modern scanning equipment accurately localized the strangulating loop. This technique has the potential of identifying patients with intestinal obstruction, in whom strangulation is a factor, prior to the development of impaired arterial inflow and frank gangrene. These findings confirmed earlier obstructions that were reported when nuclear scanning instrumentation was less sophisticated. Identification of patients at risk for intestinal strangulation requires a high index of suspicion. Excruciating cramping abdominal pain out of proportion to physical findings, roentgenogram evidence, and laboratory studies should alert the physician to the possibility of intestinal ischemia and closed loop obstruction. Radionuclide scanning in such cases may be of assistance in defining or excluding the diagnosis of a strangulating mechanism. The test is simple, relatively economical, and represents a low risk procedure to patients. It would have no place when the classic physical and laboratory findings of intestinal infarction are present.

  7. Analysis of biomarker data a practical guide

    CERN Document Server

    Looney, Stephen W

    2015-01-01

    A "how to" guide for applying statistical methods to biomarker data analysis Presenting a solid foundation for the statistical methods that are used to analyze biomarker data, Analysis of Biomarker Data: A Practical Guide features preferred techniques for biomarker validation. The authors provide descriptions of select elementary statistical methods that are traditionally used to analyze biomarker data with a focus on the proper application of each method, including necessary assumptions, software recommendations, and proper interpretation of computer output. In addition, the book discusses

  8. Urinary Biomarkers in Lupus Nephritis

    Science.gov (United States)

    Reyes-Thomas, Joyce; Blanco, Irene

    2010-01-01

    Renal involvement in patients with systemic lupus erythematosus in the form of severe lupus nephritis is associated with a significant burden of morbidity and mortality. Conventional laboratory biomarkers in current use have not been very successful in anticipating disease flares, predicting renal histology, or decreasing unwanted outcomes. Since early treatment is associated with improved clinical results, it is thus essential to identify new biomarkers with substantial predictive power to reduce the serious sequelae of this difficult to control lupus manifestation. Indeed, considerable efforts and progress have been made over the last few years in the search for novel biomarkers. Since urinary biomarkers are more easily obtainable with much less risk to the patient than repeat renal biopsies, and these may more accurately discern between renal disease and other organ manifestations than their serum counterparts, there has been tremendous interest in studying new candidate urine biomarkers. Below, we review several promising urinary biomarkers under investigation, including total proteinuria and microalbuminuria, urinary proteomic signatures, and the individual inflammatory mediators interleukin-6, vascular cell adhesion molecule-1, CXCL16, IP-10, and tumor necrosis factor-like weak inducer of apoptosis. PMID:20127204

  9. Clinical biomarkers in metabolic syndrome.

    Science.gov (United States)

    Barazzoni, Rocco; Silva, Veronica; Singer, Pierre

    2014-04-01

    A biomarker can be defined as a measurable variable that may be used as an indicator of a given biological state or condition. Biomarkers have been used in health and disease for diagnostic purposes, as tools to assess effectiveness of nutritional or drug intervention, or as risk markers to predict the development of certain diseases. In nutrition studies, selecting appropriate biomarkers is important to assess compliance, or incidence of a particular dietary component in the biochemistry of the organism, and in the diagnosis and prognosis of nutrition-related diseases. Metabolic syndrome is a cluster of cardiovascular risk factors that occur simultaneously in the same individual, and it is associated with systemic alterations that may involve several organs and tissues. Given its close association with obesity and the increasing prevalence of obesity worldwide, identifying obese individuals at risk for metabolic syndrome is a major clinical priority. Biomarkers for metabolic syndrome are therefore potential important tools to maximize the effectiveness of treatment in subjects who would likely benefit the most. Choice of biomarkers may be challenging due to the complexity of the syndrome, and this article will mainly focus on nutrition biomarkers related to the diagnosis and prognosis of the metabolic syndrome.

  10. Tubulointerstitial Biomarkers for Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Bancha Satirapoj

    2018-01-01

    Full Text Available Patients with diabetic nephropathy have a higher risk of mortality, mostly from cardiovascular complications. Standard biomarkers including serum creatinine, estimated glomerular filtration rate, and albuminuria are imprecise, do not directly measure renal tissue injury, and are relatively insensitive to small changes in renal function. Thus, availability of novel biomarkers that are sensitive, specific, and precise as well as able to detect kidney injury and predict clinically significant outcomes would be widely useful in diabetic nephropathy. Novel biomarkers of the processes that induce tubulointerstitial changes may ultimately prove to better predict renal progression and prognosis in type 2 diabetes. Recently, certain biomarkers, which were initially identified in acute kidney injury, also have been reported to confer value in evaluating patients with chronic kidney disease. Biomarkers such as cystatin C, kidney injury molecule-1 (KIM-1, neutrophil gelatinase-associated lipocalin (NGAL, angiotensinogen, periostin, and monocyte chemoattractant protein-1 (MCP-1 reflect tubular injury. In this article, we focused on the potential applications of these biomarkers in diabetic nephropathy.

  11. Antral atrophy, intestinal metaplasia, and pre-neoplastic markers in Mexican children with Helicobacter pylori-positive and negative gastritis

    Science.gov (United States)

    Villarreal-Calderon, Rodolfo; Luévano-González, Arturo; Aragón-Flores, Mariana; Zhu, Hongtu; Yuan, Ying; Xiang, Qun; Yan, Benjamin; Stoll, Kathryn Anne; Cross, Janet V.; Iczkowski, Kenneth A.; Mackinnon, Alexander Craig

    2015-01-01

    Chronic inflammation and infection are major risk factors for gastric carcinogenesis in adults. As chronic gastritis is common in Mexican children, diagnosis of Helicobacter pylori and other causes of gastritis are critical for the identification of children who would benefit from closer surveillance. Antral biopsies from 82 Mexican children (mean age 8.3±4.8y) with chronic gastritis (36 H. pylori +, 46 H. pylori -) were examined for gastritis activity, atrophy, intestinal metaplasia, and immunohistochemical expression of gastric carcinogenesis biomarkers CDX2, ephrin type-B receptor 4, matrix metalloproteinase 3 (MMP3), macrophage migration inhibitory factor (MIF), p53, β-catenin, and E-cadherin. Atrophy was diagnosed in 7/82 (9%) and intestinal metaplasia in 5/82 (6%) by routine histology, while 6 (7%) additional children (3 H. pylori +) exhibited aberrant CDX2 expression without intestinal metaplasia. Significant positive correlations were seen between EphB4, MMP3, and MIF (p<0.0001). Atrophy and follicular pathology were more frequent in H. pylori + biopsies (p<0.0001), while intestinal metaplasia and CDX2 expression showed no significant correlation with H. pylori status. Antral biopsies demonstrating atrophy, intestinal metaplasia, and/or aberrant CDX2 expression were seen in 21.95 % (18/82) of the children, potentially identifying those who would benefit from closer surveillance and preventive dietary strategies. Biomarkers CDX2, EphB4, MMP3, and MIF may be useful in the work-up of pediatric gastritis. PMID:24656654

  12. Galanin and vasoactive intestinal polypeptide

    DEFF Research Database (Denmark)

    Harling, H; Messell, T; Poulsen, Steen Seier

    1991-01-01

    By immunohistochemistry and double staining technique, almost complete coexistence of galanin-like immunoreactivity (GAL-LI) and vasoactive intestinal polypeptide-like immunoreactivity (VIP-LI) was demonstrated in submucosal ganglionic cells and mucosal nerve fibers of the porcine ileum. The rele......By immunohistochemistry and double staining technique, almost complete coexistence of galanin-like immunoreactivity (GAL-LI) and vasoactive intestinal polypeptide-like immunoreactivity (VIP-LI) was demonstrated in submucosal ganglionic cells and mucosal nerve fibers of the porcine ileum...

  13. Intestinal Microbiota Influences Non-intestinal Related Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Maria C. Opazo

    2018-03-01

    Full Text Available The human body is colonized by millions of microorganisms named microbiota that interact with our tissues in a cooperative and non-pathogenic manner. These microorganisms are present in the skin, gut, nasal, oral cavities, and genital tract. In fact, it has been described that the microbiota contributes to balancing the immune system to maintain host homeostasis. The gut is a vital organ where microbiota can influence and determine the function of cells of the immune system and contributes to preserve the wellbeing of the individual. Several articles have emphasized the connection between intestinal autoimmune diseases, such as Crohn's disease with dysbiosis or an imbalance in the microbiota composition in the gut. However, little is known about the role of the microbiota in autoimmune pathologies affecting other tissues than the intestine. This article focuses on what is known about the role that gut microbiota can play in the pathogenesis of non-intestinal autoimmune diseases, such as Grave's diseases, multiple sclerosis, type-1 diabetes, systemic lupus erythematosus, psoriasis, schizophrenia, and autism spectrum disorders. Furthermore, we discuss as to how metabolites derived from bacteria could be used as potential therapies for non-intestinal autoimmune diseases.

  14. Collagen fragment biomarkers as serological biomarkers of lean body mass

    DEFF Research Database (Denmark)

    Nedergaard, A.; Dalgas, U.; Primdahl, H.

    2015-01-01

    ) or change therein in head and neck cancer patients in the Danish Head and Neck Cancer Group(DAHANCA) 25B cohort subjected to resistance training as well as in an age-matched and gender-matched control group. Methods Blood samples and dual X-ray absorptiometry data were measured at baseline, after 12 and 24...... derived from the dual X-ray absorptiometry scans. Results We were not able to show any correlation between biomarkers and LBM or C6M and anabolic response to exercise in recovering head and neck cancer patients. However, we did find that the biomarkers IC6, IC6/C6M, and ProC3 are biomarkers of LBM...... in the control group subjects (R2/P of 0.249/0.035, 0.416/0.007 and 0.178 and P = 0.057, respectively), Conclusion In conclusion, the IC6, ProC3, and IC6/C6M biomarkers are indeed biomarkers of LBM in healthy individuals of both genders, but not in HNSCC patients....

  15. Gintonin absorption in intestinal model systems

    Directory of Open Access Journals (Sweden)

    Byung-Hwan Lee

    2018-01-01

    Conclusion: The present study shows that gintonin could be absorbed in the intestine through transcellular and paracellular diffusion, and active transport. In addition, the lipid component of gintonin might play a key role in its intestinal absorption.

  16. Microbiota, intestinal immunity, and mouse bustle

    OpenAIRE

    Kruglov, A.; Nedospasov, S.

    2014-01-01

    The composition of the intestinal microbiota is regulated by the immune system. This paper discusses the role of cytokines and innate immunity lymphoid cells in the intestinal immune regulation by means of IgA.

  17. Treatment Option Overview (Small Intestine Cancer)

    Science.gov (United States)

    ... all of an organ that contains cancer. The resection may include the small intestine and nearby organs (if the cancer has spread). The doctor may remove the section of the small intestine that contains cancer and perform an anastomosis (joining the cut ends of the intestine together). ...

  18. General Information about Small Intestine Cancer

    Science.gov (United States)

    ... all of an organ that contains cancer. The resection may include the small intestine and nearby organs (if the cancer has spread). The doctor may remove the section of the small intestine that contains cancer and perform an anastomosis (joining the cut ends of the intestine together). ...

  19. Abdominal tuberculosis presenting as intestinal obstruction- Case ...

    African Journals Online (AJOL)

    One of the complications of abdominal tuberculosis is intestinal obstruction, which can be acute, chronic or acute on chronic. Other complications include intestinal haemorrhage, perforation of the intestine (rare), faecal fistula, cold abscess formation, mal-absorption syndrome and dissemination of the tuberculosis to other ...

  20. Exercise and the gastro-intestinal tract

    African Journals Online (AJOL)

    on perfonnance and me value of cardiovascular training in improving performance in aerobic sports is well recognised. The role of me gastro-intestinal tracr, bom as a limiting and sustaining facror in aerobic exercises, is less well appreciared. Gastro-intestinal symptoms. The spectrum of gastro-intestinal effecrs of exercise ...

  1. Childhood intestinal obstruction in Northwestern Nigeria

    African Journals Online (AJOL)

    of childhood intestinal obstruction in this study agrees with those reportedis'gi m3 from other parts of the coun- try. Mortality from childhood intestinal obstruction is still high in our environment. References. 1. Otu AA. Tropical surgical abdominal emergencies: acute intestinal obstruction. Postgrad. Doctor (Afr) 1992; 14: 51. 2.

  2. Protein malnutrition and metronidazole induced intestinal bacterial ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-09-17

    Sep 17, 2008 ... The gastrointestinal tract serves as a potent barrier that prevents luminal bacteria from entering the host. This barrier function is maintained by a well-balanced intestinal flora, an unaltered perme- ability of the intestinal mucosa, and a normal functioning immune system. Furthermore, the intestinal mucosa, in.

  3. Childhood intestinal obstruction in Northwestern Nigeria | Uba ...

    African Journals Online (AJOL)

    Background: Intestinal obstruction is a common cause of childhood surgical emergency in the tropics. The aim of this paper was to assess the pattern and the outcome of mangement of intestinal obstruction in Nigerian children. Study design: The clinical reccords of all the cases of childhood intestinal obstructions managed ...

  4. The TNO gastro-intestinal model (TIM)

    NARCIS (Netherlands)

    Minekus, M.

    2015-01-01

    The TNO Gastro–Intestinal Model (TIM) is a multi–compartmental model, designed to realistically simulate conditions in the lumen of the gastro–intestinal tract. TIM is successfully used to study the gastro–intestinal behavior of a wide variety of feed, food and pharmaceutical products. Experiments

  5. Dunnione ameliorates cisplatin-induced small intestinal damage by modulating NAD{sup +} metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Pandit, Arpana; Kim, Hyung-Jin; Oh, Gi-Su; Shen, AiHua; Lee, Su-Bin; Khadka, Dipendra; Lee, SeungHoon [Center for Metabolic Function Regulation & Department of Microbiology, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Shim, Hyeok; Yang, Sei-Hoon; Cho, Eun-Young [Department of Internal Medicine, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Kwon, Kang-Beom [Department of Oriental Medical Physiology, School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Kwak, Tae Hwan [PAEAN Biotechnology, 160 Techno-2 Street, Yuseong-gu, Daejeon 305-500 (Korea, Republic of); Choe, Seong-Kyu; Park, Raekil [Center for Metabolic Function Regulation & Department of Microbiology, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); So, Hong-Seob, E-mail: jeanso@wku.ac.kr [Center for Metabolic Function Regulation & Department of Microbiology, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of)

    2015-11-27

    Although cisplatin is a widely used anticancer drug for the treatment of a variety of tumors, its use is critically limited because of adverse effects such as ototoxicity, nephrotoxicity, neuropathy, and gastrointestinal damage. Cisplatin treatment increases oxidative stress biomarkers in the small intestine, which may induce apoptosis of epithelial cells and thereby elicit damage to the small intestine. Nicotinamide adenine dinucleotide (NAD{sup +}) is a cofactor for various enzymes associated with cellular homeostasis. In the present study, we demonstrated that the hyper-activation of poly(ADP-ribose) polymerase-1 (PARP-1) is closely associated with the depletion of NAD{sup +} in the small intestine after cisplatin treatment, which results in downregulation of sirtuin1 (SIRT1) activity. Furthermore, a decrease in SIRT1 activity was found to play an important role in cisplatin-mediated small intestinal damage through nuclear factor (NF)-κB p65 activation, facilitated by its acetylation increase. However, use of dunnione as a strong substrate for the NADH:quinone oxidoreductase 1 (NQO1) enzyme led to an increase in intracellular NAD{sup +} levels and prevented the cisplatin-induced small intestinal damage correlating with the modulation of PARP-1, SIRT1, and NF-κB. These results suggest that direct modulation of cellular NAD{sup +} levels by pharmacological NQO1 substrates could be a promising therapeutic approach for protecting against cisplatin-induced small intestinal damage. - Highlights: • NAD{sup +} acts as a cofactor for numerous enzymes including Sirtuins and PARP. • Up-regulation of SIRT1 could attenuate the cisplatin-induced intestinal damage. • Modulation of the cellular NAD{sup +} could be a promising therapeutic approach.

  6. Exhaled breath and fecal volatile organic biomarkers of chronic kidney disease.

    Science.gov (United States)

    Meinardi, Simone; Jin, Kyu-Bok; Barletta, Barbara; Blake, Donald R; Vaziri, Nosratola D

    2013-03-01

    While much is known about the effect of chronic kidney disease (CKD) on composition of body fluids little is known regarding its impact on the gases found in exhaled breath or produced by intestinal microbiome. We have recently shown significant changes in the composition of intestinal microbiome in humans and animals with CKD. This study tested the hypothesis that uremia-induced changes in cellular metabolism and intestinal microbiome may modify the volatile organic metabolites found in the exhaled breath or generated by intestinal flora. SD rats were randomized to CKD (5/6 nephrectomy) or control (sham operation) groups. Exhaled breath was collected by enclosing each animal in a glass chamber flushed with clean air, then sealed for 45 min and the trapped air collected. Feces were collected, dissolved in pure water, incubated at 37 degrees C in glass reactors for 24 h and the trapped air collected. Collected gases were analyzed by gas chromatography. Over 50 gases were detected in the exhaled breath and 36 in cultured feces. Four gases in exhaled breath and 4 generated by cultured feces were significantly different in the two groups. The exhaled breath in CKD rats showed an early rise in isoprene and a late fall in linear aldehydes. The CKD animals' cultured feces released larger amounts of dimethyldisulfide, dimethyltrisulfide, and two thioesters. CKD significantly changes the composition of exhaled breath and gaseous products of intestinal flora. Analysis of breath and bowel gases may provide useful biomarkers for detection and progression of CKD and its complications.

  7. Entomoftoromicose intestinal: relato de caso

    Directory of Open Access Journals (Sweden)

    Fábia Aparecida Carvalho

    1997-02-01

    Full Text Available Os autores relatam um caso de entomoftoromicose intestinal causada por Entomophthorales, em indivíduo de 19 anos, agricultor e sem doença associada. O paciente foi submetido a ressecção intestinal e o diagnóstico foi feito após análise da peça cirúrgica. Após revisão da literatura, são discutidos a evolução clínica, as características clinicopatológicas, as dificuldades no diagnóstico e o tratamento dessa entidade rara.A case of intestinal entomophthoramycosis caused by Entomophthorales in a man with 19 years-old, farmer and without associated disease. The patient was submitted to a intestinal ressection and diagnosis was carried through after analisys of the surgical specimen. After a review of the literature, the clinical evolution, clinico-pathologic features, difficulties in diagnosis and treatment are discussed.

  8. Diversity of insect intestinal microflora

    Czech Academy of Sciences Publication Activity Database

    Mrázek, Jakub; Štrosová, Lenka; Fliegerová, Kateřina; Kott, T.; Kopečný, Jan

    2008-01-01

    Roč. 53, č. 3 (2008), s. 229-233 ISSN 0015-5632 R&D Projects: GA ČR GA303/06/0974 Institutional research plan: CEZ:AV0Z50450515 Keywords : insect intestinal microflora Subject RIV: EE - Microbiology, Virology Impact factor: 1.172, year: 2008

  9. Circadian disorganization alters intestinal microbiota.

    Science.gov (United States)

    Voigt, Robin M; Forsyth, Christopher B; Green, Stefan J; Mutlu, Ece; Engen, Phillip; Vitaterna, Martha H; Turek, Fred W; Keshavarzian, Ali

    2014-01-01

    Intestinal dysbiosis and circadian rhythm disruption are associated with similar diseases including obesity, metabolic syndrome, and inflammatory bowel disease. Despite the overlap, the potential relationship between circadian disorganization and dysbiosis is unknown; thus, in the present study, a model of chronic circadian disruption was used to determine the impact on the intestinal microbiome. Male C57BL/6J mice underwent once weekly phase reversals of the light:dark cycle (i.e., circadian rhythm disrupted mice) to determine the impact of circadian rhythm disruption on the intestinal microbiome and were fed either standard chow or a high-fat, high-sugar diet to determine how diet influences circadian disruption-induced effects on the microbiome. Weekly phase reversals of the light:dark (LD) cycle did not alter the microbiome in mice fed standard chow; however, mice fed a high-fat, high-sugar diet in conjunction with phase shifts in the light:dark cycle had significantly altered microbiota. While it is yet to be established if some of the adverse effects associated with circadian disorganization in humans (e.g., shift workers, travelers moving across time zones, and in individuals with social jet lag) are mediated by dysbiosis, the current study demonstrates that circadian disorganization can impact the intestinal microbiota which may have implications for inflammatory diseases.

  10. Milk products and intestinal health

    NARCIS (Netherlands)

    Van der Meer, R; Bovee-Oudenhoven, IMJ; Sesink, ALA; Kleibeuker, JH

    Milk products may improve intestinal health by means of the cytoprotective effects of their high calcium phosphate (CaPi) content. We hypothesized that this cytoprotection may increase host defenses against bacterial infections as well as decrease colon cancer risk. This paper summarizes our studies

  11. [Chronic intestinal pseudo-obstruction].

    Science.gov (United States)

    Joly, Francisca; Amiot, Aurélien; Coffin, Benoît; Lavergne-Slove, Anne; Messing, Bernard; Bouhnik, Yoram

    2006-01-01

    Chronic intestinal pseudo-obstruction (CIPO) is a disease characterized by episodes resembling mechanical obstruction in the absence of organic, systemic, or metabolic disorders. Pseudo-obstruction is an uncommon condition and can result from primary (40%) or secondary (60%) causes. The most common symptoms are nausea, vomiting, abdominal distension, abdominal pain and constipation or diarrhea. These symptoms are usually present many years before CIPO diagnosis. They can lead to severe electrolyte disorders and malnutrition. Principles for management of patients with CIPO are: to establish a correct clinical diagnosis in excluding mechanical obstruction; to perform a symptomatic and physiologic assessment of the gastrointestinal tract involved; to look for extra-intestinal manifestations, especially for myopathy and neuropathy; to discuss in some cases a surgery for full-thickness intestinal biopsies, and/or a neuromuscular biopsy in case of mitochondrial cytopathy suspicion. The management is primarily focused on symptom control and nutritional support to prevent weight loss and malnutrition. Treatment of CIPO includes prokinetic agents which may help to reduce gastrointestinal symptoms Courses of antibiotics may be needed in patients with symptoms suggestive of bacterial overgrowth. When necessary, enteral nutrition is preferred. In carefully selected patients, feeding jejunostomy with or without decompression gastrostomy may be tried. Long term parenteral nutrition should be reserved for patients who can not tolerate enteral nutrition. Intestinal transplantation can be discussed in selected patients.

  12. INTESTINAL PERMEABILITY IN PEDIATRIC GASTROENTEROLOGY

    NARCIS (Netherlands)

    VANELBURG, RM; UIL, JJ; DEMONCHY, JGR; HEYMANS, HSA

    1992-01-01

    The role of the physiologic barrier function of the small bowel and its possible role in health and disease has attracted much attention over the past decade. The intestinal mucosal barrier for luminal macromolecules and microorganism is the result of non-immunologic and immunologic defense

  13. Microcontainers for Intestinal Drug Delivery

    DEFF Research Database (Denmark)

    Tentor, Fabio; Mazzoni, Chiara; Keller, Stephan Sylvest

    Among all the drug administration routes, the oral one is the most preferred by the patients being less invasive, faster and easier. Oral drug delivery systems designed to target the intestine are produced by powder technology and capsule formulations. Those systems including micro- and nano...

  14. Hypersaline Microbial Mat Lipid Biomarkers

    Science.gov (United States)

    Jahnke, Linda L.; Embaye, Tsegereda; Turk, Kendra A.; Summons, Roger E.

    2002-01-01

    Lipid biomarkers and compound specific isotopic abundances are powerful tools for studies of contemporary microbial ecosystems. Knowledge of the relationship of biomarkers to microbial physiology and community structure creates important links for understanding the nature of early organisms and paleoenvironments. Our recent work has focused on the hypersaline microbial mats in evaporation ponds at Guerrero Negro, Baja California Sur, Mexico. Specific biomarkers for diatoms, cyanobacteria, archaea, green nonsulfur (GNS), sulfate reducing, sulfur oxidizing and methanotrophic bacteria have been identified. Analyses of the ester-bound fatty acids indicate a highly diverse microbial community, dominated by photosynthetic organisms at the surface. The delta C-13 of cyanobacterial biomarkers such as the monomethylalkanes and hopanoids are consistent with the delta C-13 measured for bulk mat (-10%o), while a GNS biomarker, wax esters (WXE), suggests a more depleted delta C-13 for GNS biomass (-16%o). This isotopic relationship is different than that observed in mats at Octopus Spring, Yellowstone National Park (YSNP) where GNS appear to grow photoheterotrophic ally. WXE abundance, while relatively low, is most pronounced in an anaerobic zone just below the cyanobacterial layer. The WXE isotope composition at GN suggests that these bacteria utilize photoautotrophy incorporating dissolved inorganic carbon (DIC) via the 3-hydroxypropionate pathway using H2S or H2.

  15. Biomarkers in acute heart failure.

    Science.gov (United States)

    Mallick, Aditi; Januzzi, James L

    2015-06-01

    The care of patients with acutely decompensated heart failure is being reshaped by the availability and understanding of several novel and emerging heart failure biomarkers. The gold standard biomarkers in heart failure are B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide, which play an important role in the diagnosis, prognosis, and management of acute decompensated heart failure. Novel biomarkers that are increasingly involved in the processes of myocardial injury, neurohormonal activation, and ventricular remodeling are showing promise in improving diagnosis and prognosis among patients with acute decompensated heart failure. These include midregional proatrial natriuretic peptide, soluble ST2, galectin-3, highly-sensitive troponin, and midregional proadrenomedullin. There has also been an emergence of biomarkers for evaluation of acute decompensated heart failure that assist in the differential diagnosis of dyspnea, such as procalcitonin (for identification of acute pneumonia), as well as markers that predict complications of acute decompensated heart failure, such as renal injury markers. In this article, we will review the pathophysiology and usefulness of established and emerging biomarkers for the clinical diagnosis, prognosis, and management of acute decompensated heart failure. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  16. Biomarkers of spontaneous preterm birth

    DEFF Research Database (Denmark)

    Polettini, Jossimara; Cobo, Teresa; Kacerovsky, Marian

    2017-01-01

    predictors of pregnancy outcome. This systematic review was conducted to synthesize the knowledge on PTB biomarkers identified using multiplex analysis. Three electronic databases (PubMed, EMBASE and Web of Science) were searched for studies in any language reporting the use of multiplex assays for maternal......Despite decades of research on risk indicators of spontaneous preterm birth (PTB), reliable biomarkers are still not available to screen or diagnose high-risk pregnancies. Several biomarkers in maternal and fetal compartments have been mechanistically linked to PTB, but none of them are reliable......) followed by MIP-1β, GM-CSF, Eotaxin, and TNF-RI (two studies) were reported more than once in maternal serum. However, results could not be combined due to heterogeneity in type of sample, study population, assay, and analysis methods. By this systematic review, we conclude that multiplex assays...

  17. Quantitative Imaging Biomarkers of NAFLD

    Science.gov (United States)

    Kinner, Sonja; Reeder, Scott B.

    2016-01-01

    Conventional imaging modalities, including ultrasonography (US), computed tomography (CT), and magnetic resonance (MR), play an important role in the diagnosis and management of patients with nonalcoholic fatty liver disease (NAFLD) by allowing noninvasive diagnosis of hepatic steatosis. However, conventional imaging modalities are limited as biomarkers of NAFLD for various reasons. Multi-parametric quantitative MRI techniques overcome many of the shortcomings of conventional imaging and allow comprehensive and objective evaluation of NAFLD. MRI can provide unconfounded biomarkers of hepatic fat, iron, and fibrosis in a single examination—a virtual biopsy has become a clinical reality. In this article, we will review the utility and limitation of conventional US, CT, and MR imaging for the diagnosis NAFLD. Recent advances in imaging biomarkers of NAFLD are also discussed with an emphasis in multi-parametric quantitative MRI. PMID:26848588

  18. Biomarkers of replicative senescence revisited

    DEFF Research Database (Denmark)

    Nehlin, Jan

    2016-01-01

    Biomarkers of replicative senescence can be defined as those ultrastructural and physiological variations as well as molecules whose changes in expression, activity or function correlate with aging, as a result of the gradual exhaustion of replicative potential and a state of permanent cell cycle...... arrest. The biomarkers that characterize the path to an irreversible state of cell cycle arrest due to proliferative exhaustion may also be shared by other forms of senescence-inducing mechanisms. Validation of senescence markers is crucial in circumstances where quiescence or temporary growth arrest may...... be triggered or is thought to be induced. Pre-senescence biomarkers are also important to consider as their presence indicate that induction of aging processes is taking place. The bona fide pathway leading to replicative senescence that has been extensively characterized is a consequence of gradual reduction...

  19. Imaging Biomarkers for Adult Medulloblastomas

    DEFF Research Database (Denmark)

    Keil, V C; Warmuth-Metz, M; Reh, C

    2017-01-01

    BACKGROUND AND PURPOSE: The occurrence of medulloblastomas in adults is rare; nevertheless, these tumors can be subdivided into genetic and histologic entities each having distinct prognoses. This study aimed to identify MR imaging biomarkers to classify these entities and to uncover differences...... in MR imaging biomarkers identified in pediatric medulloblastomas. MATERIALS AND METHODS: Eligible preoperative MRIs from 28 patients (11 women; 22-53 years of age) of the Multicenter Pilot-study for the Therapy of Medulloblastoma of Adults (NOA-7) cohort were assessed by 3 experienced neuroradiologists......-WNT/non-SHH medulloblastomas (in adults, Group 4), and histologic entities were correlated with the imaging criteria. These MR imaging biomarkers were compared with corresponding data from a pediatric study. RESULTS: There were 19 SHH TP53 wild type (69%), 4 WNT-activated (14%), and 5 Group 4 (17%) medulloblastomas. Six...

  20. Biomarkers for human radiation exposure.

    Science.gov (United States)

    Chaudhry, M Ahmad

    2008-09-01

    There is a concern over the potential use of radioactive isotopes as a weapon of terror. The detonation of a radiation dispersal device, the so-called "dirty bomb" can lead to public panic. In order to estimate risks associated with radiation exposure, it is important to understand the biological effects of radiation exposure. Based on this knowledge, biomarkers to monitor potentially exposed populations after a radiological accident can be developed and would be extremely valuable for emergency response. While the traditional radiation exposure biomarkers based on cytogenetic assays serve as standard, the development of rapid and noninvasive tests for radiation exposure is needed. The genomics based knowledge is providing new avenues for investigation. The examination of gene expression after ionizing radiation exposure could serve as a potential molecular marker for biodosimetry. Microarray based studies are identifying new radiation responsive genes that could potentially be used as biomarkers of human exposure to radiation after an accident.

  1. Exosomes in urine biomarker discovery.

    Science.gov (United States)

    Huebner, Alyssa R; Somparn, Poorichaya; Benjachat, Thitima; Leelahavanichkul, Asada; Avihingsanon, Yingyos; Fenton, Robert A; Pisitkun, Trairak

    2015-01-01

    Nanovesicles present in urine the so-called urinary exosomes have been found to be secreted by every epithelial cell type lining the urinary tract system in human. Urinary exosomes are an appealing source for biomarker discovery as they contain molecular constituents of their cell of origin, including proteins and genetic materials, and they can be isolated in a non-invasive manner. Following the discovery of urinary exosomes in 2004, many studies have been performed using urinary exosomes as a starting material to identify biomarkers in various renal, urogenital, and systemic diseases. Here, we describe the discovery of urinary exosomes and address the issues on the collection, isolation, and normalization of urinary exosomes as well as delineate the systems biology approach to biomarker discovery using urinary exosomes.

  2. Pathogenesis and biomarkers of carcinogenesis in ulcerative colitis

    DEFF Research Database (Denmark)

    Thorsteinsdottir, Sigrun; Gudjonsson, Thorkell; Nielsen, Ole Haagen

    2011-01-01

    One of the most serious complications of ulcerative colitis is the development of colorectal cancer. Screening patients with ulcerative colitis by standard histological examination of random intestinal biopsy samples might be inefficient as a method of cancer surveillance. This Review focuses...... on the current understanding of the pathogenesis of ulcerative colitis-associated colorectal cancer and how this knowledge can be transferred into patient management to assist clinicians and pathologists in identifying patients with ulcerative colitis who have an increased risk of colorectal cancer. Inflammation....... Although progress has been made in the understanding of inflammation-driven carcinogenesis, markers based on these findings possess insufficient sensitivity or specificity to be usable as reliable biomarkers for risk of colorectal cancer development in patients with ulcerative colitis. However, screening...

  3. Intestinal epithelium in inflammatory bowel disease

    DEFF Research Database (Denmark)

    Coskun, Mehmet

    2014-01-01

    homeostasis. Therefore, dysregulation within the epithelial layer can increase intestinal permeability, lead to abnormalities in interactions between IECs and immune cells in underlying lamina propria, and disturb the intestinal immune homeostasis, all of which are linked to the clinical disease course......The intestinal epithelium has a strategic position as a protective physical barrier to luminal microbiota and actively contributes to the mucosal immune system. This barrier is mainly formed by a monolayer of specialized intestinal epithelial cells (IECs) that are crucial in maintaining intestinal...

  4. Biomarkers in scleroderma: Current status

    Directory of Open Access Journals (Sweden)

    Latika Gupta

    2017-01-01

    Full Text Available Scleroderma is an autoimmune disease characterized by indolent obliterative vasculopathy and widespread fibrosis. The two main morphological manifestations of the disease overlap and may make it difficult to separate activity from damage. Many patients, especially those with the limited subset of the disease, have an indolent course without clear-cut inflammatory manifestations. There is a felt need for validated biomarkers, which can differentiate activity from damage, and yet be sensitive to change with therapy. Multiplex arrays of biomarkers have ushered an era of targeted or personalized medicine based on phenotypic characteristics in an individual.

  5. Biomarkers in Neonatal Posthemorrhagic Hydrocephalus

    Science.gov (United States)

    Merhar, Stephanie

    2011-01-01

    Posthemorrhagic hydrocephalus (PHH) is a rare but serious outcome among premature babies in the NICU, with consequences including mortality and severe neurodevelopmental disabilities. The causes of PHH are still not entirely understood, and its prevention and treatment are controversial. Various cerebrospinal fluid biomarkers have been studied in infants with PHH in order to recognize the causes, diagnose brain injury, and predict neurodevelopmental outcomes. This systematic review summarizes studies on biomarkers of extracellular matrix activity, fibrinolysis/coagulation, hypoxia/cell death, and inflammation in the cerebrospinal fluid of infants with PHH. PMID:21791933

  6. Exploring a Possible Link between the Intestinal Microbiota and Feed Efficiency in Pigs.

    Science.gov (United States)

    McCormack, Ursula M; Curião, Tânia; Buzoianu, Stefan G; Prieto, Maria L; Ryan, Tomas; Varley, Patrick; Crispie, Fiona; Magowan, Elizabeth; Metzler-Zebeli, Barbara U; Berry, Donagh; O'Sullivan, Orla; Cotter, Paul D; Gardiner, Gillian E; Lawlor, Peadar G

    2017-08-01

    that, although microbial diversity did not differ among animals of varying FE, specific intestinal microbes could potentially be linked with porcine FE. However, as the factors impacting FE are still not fully understood, intestinal microbiota composition may not be a major factor determining differences in FE. Nonetheless, this work has provided a potential set of microbial biomarkers for FE in pigs. Although culturability could be a limiting factor and intervention studies are required, these taxa could potentially be targeted in the future to manipulate the intestinal microbiome so as to improve FE in pigs. If successful, this has the potential to reduce both production costs and the environmental impact of pig production. Copyright © 2017 American Society for Microbiology.

  7. Exploring a Possible Link between the Intestinal Microbiota and Feed Efficiency in Pigs

    Science.gov (United States)

    McCormack, Ursula M.; Buzoianu, Stefan G.; Prieto, Maria L.; Ryan, Tomas; Varley, Patrick; Crispie, Fiona; Magowan, Elizabeth; Metzler-Zebeli, Barbara U.; Berry, Donagh; O'Sullivan, Orla; Cotter, Paul D.; Lawlor, Peadar G.

    2017-01-01

    that, although microbial diversity did not differ among animals of varying FE, specific intestinal microbes could potentially be linked with porcine FE. However, as the factors impacting FE are still not fully understood, intestinal microbiota composition may not be a major factor determining differences in FE. Nonetheless, this work has provided a potential set of microbial biomarkers for FE in pigs. Although culturability could be a limiting factor and intervention studies are required, these taxa could potentially be targeted in the future to manipulate the intestinal microbiome so as to improve FE in pigs. If successful, this has the potential to reduce both production costs and the environmental impact of pig production. PMID:28526795

  8. A etiological factors in mechanical intestinal obstruction

    International Nuclear Information System (INIS)

    Asad, S.; Khan, H.; Khan, I.A.; Ghaffar, S.; Rehman, Z.U.

    2012-01-01

    Background: Intestinal obstruction occurs when the normal flow of intestinal contents is interrupted. The most frequent causes of intestinal obstruction are postoperative adhesions and hernias, which cause extrinsic compression of the intestine. Less frequently, tumours or strictures of the bowel can cause intrinsic blockage. Objective of the study was to find out the various a etiological factors of mechanical intestinal obstruction and to evaluate the morbidity and mortality in adult patients presenting to Surgical 'A' unit of Ayub teaching hospital with mechanical intestinal obstruction. Methods: This cross-sectional study was conducted from March 2009 to September, 2009. All patients presenting with intestinal obstruction and were above the age of 12 years were included in the study. Patients with non-mechanical obstruction were excluded from the study and those who responded to conservative measures were also excluded. Results: A total of 36 patients with age ranging from 12 to 80 years (Mean age 37.72+-19.74 years) and male to female ratio of 1.77:1, were treated for mechanical intestinal obstruction. The most common cause for mechanical intestinal obstruction was adhesions (36.1%). Intestinal tuberculosis was the second most common cause (19.4%), while hernias and sigmoid volvulus affected 13.9% patients each. Malignancies were found in 5.6% cases. Conclusion: Adhesions and Tuberculosis are the leading causes of mechanical intestinal obstruction in Pakistan. Although some patients can be treated conservatively, a substantial portion requires immediate surgical intervention. (author)

  9. Intestinal Epithelial Sirtuin 1 Regulates Intestinal Inflammation During Aging in Mice by Altering the Intestinal Microbiota.

    Science.gov (United States)

    Wellman, Alicia S; Metukuri, Mallikarjuna R; Kazgan, Nevzat; Xu, Xiaojiang; Xu, Qing; Ren, Natalie S X; Czopik, Agnieszka; Shanahan, Michael T; Kang, Ashley; Chen, Willa; Azcarate-Peril, M Andrea; Gulati, Ajay S; Fargo, David C; Guarente, Leonard; Li, Xiaoling

    2017-09-01

    Intestinal epithelial homeostasis is maintained by complex interactions among epithelial cells, commensal gut microorganisms, and immune cells. Disruption of this homeostasis is associated with disorders such as inflammatory bowel disease (IBD), but the mechanisms of this process are not clear. We investigated how Sirtuin 1 (SIRT1), a conserved mammalian NAD + -dependent protein deacetylase, senses environmental stress to alter intestinal integrity. We performed studies of mice with disruption of Sirt1 specifically in the intestinal epithelium (SIRT1 iKO, villin-Cre+, Sirt1 flox/flox mice) and control mice (villin-Cre-, Sirt1 flox/flox ) on a C57BL/6 background. Acute colitis was induced in some mice by addition of 2.5% dextran sodium sulfate to drinking water for 5-9 consecutive days. Some mice were given antibiotics via their drinking water for 4 weeks to deplete their microbiota. Some mice were fed with a cholestyramine-containing diet for 7 days to sequester their bile acids. Feces were collected and proportions of microbiota were analyzed by 16S rRNA amplicon sequencing and quantitative PCR. Intestines were collected from mice and gene expression profiles were compared by microarray and quantitative PCR analyses. We compared levels of specific mRNAs between colon tissues from age-matched patients with ulcerative colitis (n=10) vs without IBD (n=8, controls). Mice with intestinal deletion of SIRT1 (SIRT1 iKO) had abnormal activation of Paneth cells starting at the age of 5-8 months, with increased activation of NF-κB, stress pathways, and spontaneous inflammation at 22-24 months of age, compared with control mice. SIRT1 iKO mice also had altered fecal microbiota starting at 4-6 months of age compared with control mice, in part because of altered bile acid metabolism. Moreover, SIRT1 iKO mice with defective gut microbiota developed more severe colitis than control mice. Intestinal tissues from patients with ulcerative colitis expressed significantly lower

  10. Intestinal perfusion in the study of intestinal absorption

    International Nuclear Information System (INIS)

    Baker, S.J.

    1976-01-01

    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)

  11. Biodiversity of Intestinal Lactic Acid Bacteria in the Healthy Population.

    Science.gov (United States)

    Mikelsaar, Marika; Sepp, Epp; Štšepetova, Jelena; Songisepp, Epp; Mändar, Reet

    2016-01-01

    The complex ecosystem of the gastrointestinal tract involves tight interrelations among host cells, diet, and billions of microbes, both beneficial and opportunistic pathogens. In spite of advanced genomic, metagenomic, and metabonomic approaches, knowledge is still quite limited regarding the biodiversity of beneficial microbiota, including Lactobacillus spp., and its impact on the main biomarkers of general health. In this paper, Lactobacillus biodiversity is demonstrated through its taxonomy, function, and host-microbial interactions. Its prevalence, composition, abundance, intertwined metabolic properties, and relation to host age, genotype, and socioeconomic factors are reviewed based on the literature and original research experience. The species richness, e.g., the biodiversity of gut microbiota, provides the host with a variety of metabolically active species and strains that predict their response for different health conditions and extrinsic interventions. Metabolically active and safe Lactobacillus species and specific strains with particular functional properties increase the biodiversity of the whole intestinal microbiota. The elaborated principles for effective application of probiotics are discussed, aimed at regulating the composition of microbiota simultaneously with blood and urine biomarkers at the borderline of normality. This approach targets the impact of probiotic strains to maintenance of health with anti-infectious, cardiovascular, and metabolic support.

  12. Intestinal proteomics in pig models of necrotising enterocolitis, short bowel syndrome and intra-uterine growth restriction

    DEFF Research Database (Denmark)

    Jiang, Pingping; Sangild, Per Torp

    2014-01-01

    are also affected by SBS and IUGR. Parallel changes in some plasma and urinary proteins (e.g., haptoglobin, globulins, complement proteins, fatty acid binding proteins) may mirror the intestinal responses and pave the way to biomarker discovery. Explorative non-targeted proteomics provide ideas about......, but only supplement, classical hypothesis-driven research that investigate disease mechanisms using a single or few endpoints. This article is protected by copyright. All rights reserved....

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

    Science.gov (United States)

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

    2017-02-10

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

  14. Bias in Peripheral Depression Biomarkers

    DEFF Research Database (Denmark)

    Carvalho, André F; Köhler, Cristiano A; Brunoni, André R

    2016-01-01

    sizes has been conducted. METHODS: Here, we performed a comprehensive review of meta-analyses of peripheral nongenetic biomarkers that could discriminate individuals with MDD from nondepressed controls. PubMed/MEDLINE, EMBASE, and PsycINFO databases were searched through April 10, 2015. RESULTS: From 15...

  15. Biomarkers of satiation and satiety

    NARCIS (Netherlands)

    Graaf, C. de; Blom, W.A.M.; Smeets, P.A.M.; Stafleu, A.; Hendriks, H.F.J.

    2004-01-01

    This review's objective is to give a critical summary of studies that focused on physiologic measures relating to subjectively rated appetite, actual food intake, or both. Biomarkers of satiation and satiety may be used as a tool for assessing the satiating efficiency of foods and for understanding

  16. Electrochemical Genosensing of Circulating Biomarkers

    Science.gov (United States)

    Campuzano, Susana; Yáñez-Sedeño, Paloma; Pingarrón, José Manuel

    2017-01-01

    Management and prognosis of diseases requires the measurement in non- or minimally invasively collected samples of specific circulating biomarkers, consisting of any measurable or observable factors in patients that indicate normal or disease-related biological processes or responses to therapy. Therefore, on-site, fast and accurate determination of these low abundance circulating biomarkers in scarcely treated body fluids is of great interest for health monitoring and biological applications. In this field, electrochemical DNA sensors (or genosensors) have demonstrated to be interesting alternatives to more complex conventional strategies. Currently, electrochemical genosensors are considered very promising analytical tools for this purpose due to their fast response, low cost, high sensitivity, compatibility with microfabrication technology and simple operation mode which makes them compatible with point-of-care (POC) testing. In this review, the relevance and current challenges of the determination of circulating biomarkers related to relevant diseases (cancer, bacterial and viral infections and neurodegenerative diseases) are briefly discussed. An overview of the electrochemical nucleic acid–based strategies developed in the last five years for this purpose is given to show to both familiar and non-expert readers the great potential of these methodologies for circulating biomarker determination. After highlighting the main features of the reported electrochemical genosensing strategies through the critical discussion of selected examples, a conclusions section points out the still existing challenges and future directions in this field. PMID:28420103

  17. Biomarkers of diseases in medicine

    Indian Academy of Sciences (India)

    Biomarkers have gained immense scientific and clinical value and interest in the practise of medicine. .... extent and characteristics of the disease detected ..... marker for cancer. In colon cancer, the tumour suppressor genes CDKN2A, MGMT and MLH1, as well as other genes (e.g., TIMP-3, p14ARF,. APC, MINT31, MINT2 ...

  18. The intestinal microenvironment in sepsis.

    Science.gov (United States)

    Fay, Katherine T; Ford, Mandy L; Coopersmith, Craig M

    2017-10-01

    The gastrointestinal tract has long been hypothesized to function as "the motor" of multiple organ dysfunction syndrome. The gastrointestinal microenvironment is comprised of a single cell layer epithelia, a local immune system, and the microbiome. These three components of the intestine together play a crucial role in maintaining homeostasis during times of health. However, the gastrointestinal microenvironment is perturbed during sepsis, resulting in pathologic changes that drive both local and distant injury. In this review, we seek to characterize the relationship between the epithelium, gastrointestinal lymphocytes, and commensal bacteria during basal and pathologic conditions and how the intestinal microenvironment may be targeted for therapeutic gain in septic patients. Published by Elsevier B.V.

  19. Drug Transporters in the Intestine

    DEFF Research Database (Denmark)

    Steffansen, Bente

    2016-01-01

    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...

  20. [Chronic gastritis and intestinal metaplasia].

    Science.gov (United States)

    Castillo, T; Navarrete, J; Celestina, A

    1989-01-01

    Much has been written about gastric mucosae behavior and the occurrence of intestinal metaplasia. The aim of this paper is to learn something more about these matters in peruvian population. We selected 100 patients with endoscopically no localized lesions between 30 to 70 years of age. We took 8 samples of gastric mucosae in each patient which were carefully examined for the presence of inflammatory changes, settle the line type between antral and fundic mucosae and the frequency of intestinal metaplasia finding. The results showed disagreement between endoscopic and histological findings, so we conclude it is better to diagnose chronic gastritis on the basis of histological parameters. The line between antral and fundic mucosae was of the close type one found in 87% of all cases and it advanced proximally with increasing age. Intestinal metaplasia was present in 46% of the whole number of patients and the rate of occurrence increased in 50% over 50 years age. These findings will let us compare future investigations of gastric mucosae behavior with localized benign or malign lesions.

  1. Radiological manifestations of intestinal tuberculosis

    International Nuclear Information System (INIS)

    Im, Jae Hoon

    1974-01-01

    Radiological findings of 87 cases of intestinal tuberculosis are analyzed and presented. The diagnosis was based on histopathology in 29 cases, and on clinical ground and radiological findings in 58 cases. The radio of male and female patients was 4:6, and peak incidence is between 10 and 30. Abdominal pain, diarrhea, weight loss, fever and general weakness are frequent symptoms, and tenderness of abdomen, ascites with abdominal distension, malnutrition and emaciation are frequent signs of the patients. Laboratory investigation reveal anemia, raised ESR, hypoalbuminaemia and positive occult blood reaction in the stool in most of the patients. Chest film show activity pulmonary tuberculosis in only 1/3 patients. There is no pathognomonic radiological findings in intestinal tuberculosis and their manifestations are protean, and differentiation from other inflammatory diseases and malignant tumors in gastrointestinal tract is very difficult on radiological ground alone. However, in patients with complaining vague abdominal symptoms and signs, the radiological diagnosis is most certain means in the decision of existence of organic lesion and suggestion of tuberculosis in the gastrointestinal tract and its extent as yet. Multiplicity of the lesion, involvement of adjacent organ such as peritoneum or mesenteric lymph nodes, typical nodularity or irregularity of mesenteric border and existence of active pulmonary tuberculosis are the suggestive findings of intestinal tuberculosis. In the diagnosis of inflammatory disease or malignant tumor of gastrointestinal tract, the possibility of tuberculosis should be borne in mind, and vice versa

  2. [Intestinal parasitic diseases in children].

    Science.gov (United States)

    Mare, Anca; Man, A; Toma, Felicia; Székely, Edit; Lôrinczi, Lilla; Sipoş, Anca

    2007-01-01

    To compare the incidence of intestinal parasitosis between children with residence in urban and rural areas: to compare the efficacy of parasitologic diagnostic methods. In our study we included two lots of children. The first lot consisted in 74 children from rural areas from which we collected 44 samples of feces and 55 samples for the "Scotch tape" test. The second lot consisted in 214 children from urban areas from which we collected 44 samples of feces. We examined each sample of feces by three different methods. The study was performed between April to June 2006. The incidence of intestinal parasitosis increases in children from urban areas towards rural areas, and in children between 5 and 10 years. Ascariasis is the most frequent disease in both urban and rural areas. By examination of each fecal sample by three different methods, the number of positive cases increased. The residence in rural areas and age between 5 to 10 years are risk factors for intestinal parasitosis. The "Scotch tape" test was more efficient in Enterobius vermicularis infection than the methods performed from feces. We recommend using at the same time three diagnostic methods for feces examination to improve the diagnostic sensibility.

  3. Colon in acute intestinal infection.

    Science.gov (United States)

    Guarino, Alfredo; Buccigrossi, Vittoria; Armellino, Carla

    2009-04-01

    The colon is actively implicated in intestinal infections not only as a target of enteric pathogens and their products but also as a target organ for treatment. In the presence of diarrhea, both of osmotic and secretory nature, the colon reacts with homeostatic mechanisms to increase ion absorption. These mechanisms can be effectively exploited to decrease fluid discharge. A model of intestinal infections using rotavirus (RV) in colonic cells was set up and used to define a dual model of secretory and osmotic diarrhea in sequence. Using this model, antidiarrheal drugs were tested, namely zinc and the enkephalinase inhibitor racecadotril. Zinc was able to decrease the enterotoxic activity responsible for secretory diarrhea. It also inhibited the cytotoxic effect of RV. The mechanism of zinc was related at least in part to the activation of MAPK activity, but also a direct antiviral effect was observed. Racecadotril showed a potent and selective inhibition of active secretion, being particularly effective in the first phase of RV diarrhea. The use of drugs active at the colonic level, therefore, offers effective options to treat intestinal infections in childhood. In addition, the colon is the natural site of colonic microflora, a target of probiotic therapy, which is the first line of approach recommended by the European Society for Paediatric Gastroenterology, Hepatology and Nutrition to treat infectious diarrhea.

  4. Urinary biomarkers in pediatric appendicitis.

    Science.gov (United States)

    Salö, Martin; Roth, Bodil; Stenström, Pernilla; Arnbjörnsson, Einar; Ohlsson, Bodil

    2016-08-01

    The diagnosis of pediatric appendicitis is still a challenge, resulting in perforation and negative appendectomies. The aim of this study was to evaluate novel biomarkers in urine and to use the most promising biomarkers in conjunction with the Pediatric Appendicitis Score (PAS), to see whether this could improve the accuracy of diagnosing appendicitis. A prospective study of children with suspected appendicitis was conducted with assessment of PAS, routine blood tests, and measurements of four novel urinary biomarkers: leucine-rich α-2-glycoprotein (LRG), calprotectin, interleukin 6 (IL-6), and substance P. The biomarkers were blindly determined with commercial ELISAs. Urine creatinine was used to adjust for dehydration. The diagnosis of appendicitis was based on histopathological analysis. Forty-four children with suspected appendicitis were included, of which twenty-two (50 %) had confirmed appendicitis. LRG in urine was elevated in children with appendicitis compared to children without (p appendicitis compared to those with phlegmonous appendicitis (p = 0.003). No statistical significances between groups were found for calprotectin, IL-6 or substance P. LRG had a receiver operating characteristic area under the curve of 0.86 (95 % CI 0.79-0.99), and a better diagnostic performance than all routine blood tests. LRG in conjunction with PAS showed 95 % sensitivity, 90 % specificity, 91 % positive predictive value, and 95 % negative predictive value. LRG, adjusted for dehydration, is a promising novel urinary biomarker for appendicitis in children. LRG in combination with PAS has a high diagnostic performance.

  5. Systems biology and biomarker discovery

    Energy Technology Data Exchange (ETDEWEB)

    Rodland, Karin D.

    2010-12-01

    Medical practitioners have always relied on surrogate markers of inaccessible biological processes to make their diagnosis, whether it was the pallor of shock, the flush of inflammation, or the jaundice of liver failure. Obviously, the current implementation of biomarkers for disease is far more sophisticated, relying on highly reproducible, quantitative measurements of molecules that are often mechanistically associated with the disease in question, as in glycated hemoglobin for the diagnosis of diabetes [1] or the presence of cardiac troponins in the blood for confirmation of myocardial infarcts [2]. In cancer, where the initial symptoms are often subtle and the consequences of delayed diagnosis often drastic for disease management, the impetus to discover readily accessible, reliable, and accurate biomarkers for early detection is compelling. Yet despite years of intense activity, the stable of clinically validated, cost-effective biomarkers for early detection of cancer is pathetically small and still dominated by a handful of markers (CA-125, CEA, PSA) first discovered decades ago. It is time, one could argue, for a fresh approach to the discovery and validation of disease biomarkers, one that takes full advantage of the revolution in genomic technologies and in the development of computational tools for the analysis of large complex datasets. This issue of Disease Markers is dedicated to one such new approach, loosely termed the 'Systems Biology of Biomarkers'. What sets the Systems Biology approach apart from other, more traditional approaches, is both the types of data used, and the tools used for data analysis - and both reflect the revolution in high throughput analytical methods and high throughput computing that has characterized the start of the twenty first century.

  6. Immunogenetic control of the intestinal microbiota.

    Science.gov (United States)

    Marietta, Eric; Rishi, Abdul; Taneja, Veena

    2015-07-01

    All vertebrates contain a diverse collection of commensal, symbiotic and pathogenic microorganisms, such as bacteria, viruses and fungi, on their various body surfaces, and the ecological community of these microorganisms is referred to as the microbiota. Mucosal sites, such as the intestine, harbour the majority of microorganisms, and the human intestine contains the largest community of commensal and symbiotic bacteria. This intestinal community of bacteria is diverse, and there is a significant variability among individuals with respect to the composition of the intestinal microbiome. Both genetic and environmental factors can influence the diversity and composition of the intestinal bacteria with the predominant environmental factor being diet. So far, studies have shown that diet-dependent differences in the composition of intestinal bacteria can be classified into three groups, called enterotypes. Other environmental factors that can influence the composition include antibiotics, probiotics, smoking and drugs. Studies of monozygotic and dizygotic twins have proven that genetics plays a role. Recently, MHC II genes have been associated with specific microbial compositions in human infants and transgenic mice that express different HLA alleles. There is a growing list of genes/molecules that are involved with the sensing and monitoring of the intestinal lumen by the intestinal immune system that, when genetically altered, will significantly alter the composition of the intestinal microflora. The focus of this review will be on the genetic factors that influence the composition of the intestinal microflora. © 2015 John Wiley & Sons Ltd.

  7. Immediate postconditioning during reperfusion attenuates intestinal injury.

    Science.gov (United States)

    Liu, Ke-Xuan; Li, Yun-Sheng; Huang, Wen-Qi; Chen, Shu-Qing; Wang, Zhong-Xin; Liu, Jia-Xin; Xia, Zhengyuan

    2009-05-01

    To test the hypothesis that immediate but not delayed ischemic postconditioning (IPo) during reperfusion attenuates intestinal injury, and that ischemic preconditioning (IPC) and IPo may confer synergy in intestinal protection. Prospective laboratory animal study with concurrent control. Adult Sprague-Dawley rats. Intestinal ischemia/reperfusion (II/R) injury in rats was produced by clamping superior mesenteric artery for 60 min followed by 60 min reperfusion; IPC was elicited by 10 min ischemia and 10 min reperfusion before index ischemia; IPo was performed by three cycles of 30 s reperfusion and 30 s ischemia initiated either immediately at the onset of reperfusion (IPo) or after reperfusion for 3 min (delayed-IPo). Combination of IPC and IPo was performed by combining both protocols. Intestinal ischemia/reperfusion resulted in significant intestinal injury evidenced as significant increase in Chiu's scores and wet-to-dry intestine weight ratio accompanied with increases in plasma levels of tumor necrosis factor-alpha and interleukin-6, as well as increases in the intestinal tissue lipid peroxidation product malonediadehyde and myeloperoxidase activity as compared to control animals (all P IPo or their combination (P IPo (P > 0.05). IPC and IPo showed synergistic protection compared with either protocol alone. Ischemic postconditioning reduces intestinal injury, in part, by inhibiting oxidative injury, neutrophils filtration and proinflammatory response. The early period of reperfusion is critical to intestinal protection by IPo, and intestinal protection with IPo can be enhanced by IPC.

  8. Intestinal microcirculatory dysfunction and neonatal necrotizing enterocolitis.

    Science.gov (United States)

    Zhang, Hong-yi; Wang, Fang; Feng, Jie-xiong

    2013-01-01

    Based on the observation that coagulation necrosis occurs in the majority of neonatal necrotizing enterocolitis (NEC) patients, it is clear that intestinal ischemia is a contributing factor to the pathogenesis of NEC. However, the published studies regarding the role of intestinal ischemia in NEC are controversial. The aim of this paper is to review the current studies regarding intestinal microcirculatory dysfunction and NEC, and try to elucidate the exact role of intestinal microcirculatory dysfunction in NEC. The studies cited in this review were mainly obtained from articles listed in Medline and PubMed. The search terms used were "intestinal microcirculatory dysfunction" and "neonatal necrotizing enterocolitis". Mainly original milestone articles and critical reviews written by major pioneer investigators in the field were selected. Immature regulatory control of mesentery circulation makes the neonatal intestinal microvasculature vulnerable. When neonates are subjected to stress, endothelial cell dysfunction occurs and results in vasoconstriction of arterioles, inflammatory cell infiltration and activation in venules, and endothelial barrier disruption in capillaries. The compromised vasculature increases circulation resistance and therefore decreases intestinal perfusion, and may eventually progress to intestinal necrosis. Intestinal ischemia plays an important role through the whole course of NEC. New therapeutic agents targeting intestinal ischemia, like HB-EGF, are promising therapeutic agents for the treatment of NEC.

  9. Ketogenesis contributes to intestinal cell differentiation.

    Science.gov (United States)

    Wang, Qingding; Zhou, Yuning; Rychahou, Piotr; Fan, Teresa W-M; Lane, Andrew N; Weiss, Heidi L; Evers, B Mark

    2017-03-01

    The intestinal epithelium undergoes a continual process of proliferation, differentiation and apoptosis. Previously, we have shown that the PI3K/Akt/mTOR pathway has a critical role in intestinal homeostasis. However, the downstream targets mediating the effects of mTOR in intestinal cells are not known. Here, we show that the ketone body β-hydroxybutyrate (βHB), an endogenous inhibitor of histone deacetylases (HDACs) induces intestinal cell differentiation as noted by the increased expression of differentiation markers (Mucin2 (MUC2), lysozyme, IAP, sucrase-isomaltase, KRT20, villin, Caudal-related homeobox transcription factor 2 (CDX2) and p21 Waf1 ). Conversely, knockdown of the ketogenic mitochondrial enzyme hydroxymethylglutaryl CoA synthase 2 (HMGCS2) attenuated spontaneous differentiation in the human colon cancer cell line Caco-2. Overexpression of HMGCS2, which we found is localized specifically in the more differentiated portions of the intestinal mucosa, increased the expression of CDX2, thus further suggesting the contributory role of HMGCS2 in intestinal differentiation. In addition, mice fed a ketogenic diet demonstrated increased differentiation of intestinal cells as noted by an increase in the enterocyte, goblet and Paneth cell lineages. Moreover, we showed that either knockdown of mTOR or inhibition of mTORC1 with rapamycin increases the expression of HMGCS2 in intestinal cells in vitro and in vivo, suggesting a possible cross-talk between mTOR and HMGCS2/βHB signaling in intestinal cells. In contrast, treatment of intestinal cells with βHB or feeding mice with a ketogenic diet inhibits mTOR signaling in intestinal cells. Together, we provide evidence showing that HMGCS2/βHB contributes to intestinal cell differentiation. Our results suggest that mTOR acts cooperatively with HMGCS2/βHB to maintain intestinal homeostasis.

  10. Brain caspase-3 and intestinal FABP responses in preterm and term rats submitted to birth asphyxia

    Directory of Open Access Journals (Sweden)

    R.L. Figueira

    2016-01-01

    Full Text Available Neonatal asphyxia can cause irreversible injury of multiple organs resulting in hypoxic-ischemic encephalopathy and necrotizing enterocolitis (NEC. This injury is dependent on time, severity, and gestational age, once the preterm babies need ventilator support. Our aim was to assess the different brain and intestinal effects of ischemia and reperfusion in neonate rats after birth anoxia and mechanical ventilation. Preterm and term neonates were divided into 8 subgroups (n=12/group: 1 preterm control (PTC, 2 preterm ventilated (PTV, 3 preterm asphyxiated (PTA, 4 preterm asphyxiated and ventilated (PTAV, 5 term control (TC, 6 term ventilated (TV, 7 term asphyxiated (TA, and 8 term asphyxiated and ventilated (TAV. We measured body, brain, and intestine weights and respective ratios [(BW, (BrW, (IW, (BrW/BW and (IW/BW]. Histology analysis and damage grading were performed in the brain (cortex/hippocampus and intestine (jejunum/ileum tissues, as well as immunohistochemistry analysis for caspase-3 and intestinal fatty acid-binding protein (I-FABP. IW was lower in the TA than in the other terms (P<0.05, and the IW/BW ratio was lower in the TA than in the TAV (P<0.005. PTA, PTAV and TA presented high levels of brain damage. In histological intestinal analysis, PTAV and TAV had higher scores than the other groups. Caspase-3 was higher in PTAV (cortex and TA (cortex/hippocampus (P<0.005. I-FABP was higher in PTAV (P<0.005 and TA (ileum (P<0.05. I-FABP expression was increased in PTAV subgroup (P<0.0001. Brain and intestinal responses in neonatal rats caused by neonatal asphyxia, with or without mechanical ventilation, varied with gestational age, with increased expression of caspase-3 and I-FABP biomarkers.

  11. Benign Lesions in Mucosa Adjacent to Intestinal-Type Sinonasal Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Blanca Vivanco

    2011-01-01

    Full Text Available Occupational exposure to wood dust is a strong risk factor for the development of intestinal-type sinonasal adenocarcinoma (ITAC; however, knowledge on possible precursor lesions or biomarkers is limited. Fifty-one samples of tumor-adjacent mucosa and 19 control samples of mucosa from the unaffected fossa of ITAC patients were evaluated for histological changes and p53 protein expression. Mild dysplasia was observed in 14%, cuboidal metaplasia in 57%, intestinal metaplasia in 8%, squamous metaplasia in 24%, and cylindrocellular hyperplasia in 53% of cases. P53 immunopositivity was generally weak occurring most frequently in squamous metaplasia. Wood dust etiology did not appear of influence on the histological changes, but p53 showed a tendency for higher positivity. Dysplasia adjacent to tumor was indicative of subsequent development of recurrence. In conclusion, precursor lesions do occur in mucosa adjacent to ITAC. This is clinically important, because it may justify the screening of high-risk individuals such as woodworkers.

  12. Implementation of proteomic biomarkers: making it work.

    Science.gov (United States)

    Mischak, Harald; Ioannidis, John P A; Argiles, Angel; Attwood, Teresa K; Bongcam-Rudloff, Erik; Broenstrup, Mark; Charonis, Aristidis; Chrousos, George P; Delles, Christian; Dominiczak, Anna; Dylag, Tomasz; Ehrich, Jochen; Egido, Jesus; Findeisen, Peter; Jankowski, Joachim; Johnson, Robert W; Julien, Bruce A; Lankisch, Tim; Leung, Hing Y; Maahs, David; Magni, Fulvio; Manns, Michael P; Manolis, Efthymios; Mayer, Gert; Navis, Gerjan; Novak, Jan; Ortiz, Alberto; Persson, Frederik; Peter, Karlheinz; Riese, Hans H; Rossing, Peter; Sattar, Naveed; Spasovski, Goce; Thongboonkerd, Visith; Vanholder, Raymond; Schanstra, Joost P; Vlahou, Antonia

    2012-09-01

    While large numbers of proteomic biomarkers have been described, they are generally not implemented in medical practice. We have investigated the reasons for this shortcoming, focusing on hurdles downstream of biomarker verification, and describe major obstacles and possible solutions to ease valid biomarker implementation. Some of the problems lie in suboptimal biomarker discovery and validation, especially lack of validated platforms with well-described performance characteristics to support biomarker qualification. These issues have been acknowledged and are being addressed, raising the hope that valid biomarkers may start accumulating in the foreseeable future. However, successful biomarker discovery and qualification alone does not suffice for successful implementation. Additional challenges include, among others, limited access to appropriate specimens and insufficient funding, the need to validate new biomarker utility in interventional trials, and large communication gaps between the parties involved in implementation. To address this problem, we propose an implementation roadmap. The implementation effort needs to involve a wide variety of stakeholders (clinicians, statisticians, health economists, and representatives of patient groups, health insurance, pharmaceutical companies, biobanks, and regulatory agencies). Knowledgeable panels with adequate representation of all these stakeholders may facilitate biomarker evaluation and guide implementation for the specific context of use. This approach may avoid unwarranted delays or failure to implement potentially useful biomarkers, and may expedite meaningful contributions of the biomarker community to healthcare. © 2012 The Authors. European Journal of Clinical Investigation © 2012 Stichting European Society for Clinical Investigation Journal Foundation.

  13. Mammalian intestinal epithelial cells in primary culture: a mini-review.

    Science.gov (United States)

    Kaeffer, Bertrand

    2002-03-01

    Epithelial cells lining the digestive tract represent a highly organized system built up by multipotent stem cells. A process of asymmetric mitosis produces a population of proliferative cells that are rapidly renewed and migrate along the crypt-villus axis, differentiating into functional mature cells before dying and exfoliating into the intestinal lumen. Isolated crypts or epithelial cells retaining high viability can be prepared within a few h after tissue sampling. After cells are cultured in serum-free media, short-term studies (16-48 h) can be conducted for endocrinology, energy metabolism, or programmed cell death. However, long-term primary culture of intestinal cells (up to 10 d) is still difficult despite progress in isolation methodologies and manipulation of the cell microenvironment. The main problem in developing primary culture is the lack of structural markers specific to the stem cell compartment. The design of a microscopic multidimensional analytic system to record the expression profiles of biomarkers all along the living intestinal crypt should improve basic knowledge of the survival and growth of adult crypt stem cells, and the selection of totipotent embryonic stem cells capable of differentiating into intestinal tissues should facilitate studies of the genomic basis of endodermal tissue differentiation.

  14. Degree of neutrophil, atrophy, and metaplasia intestinal were associate with malondialdehyde level in gastritis patients

    Science.gov (United States)

    Siregar, G. A.; Sari, D. K.; Sungkar, T.

    2018-03-01

    The main pathogenesis of gastritis is inflammation that closely related to free radicals. Malondialdehyde (MDA) is a free radical biomarker and is found to increase in gastritis patients. However, these studies are generally performed on experimental animals as well as MDA examination in gastric mucosa. This study aim was to determine the association of degrees of gastritis (degree of lymphocyte infiltration, neutrophil activity, atrophy, and intestinal metaplasia) with plasma MDA level. A cross-sectional study of 80 consecutive gastritis patients who came to an endoscopic unit of Adam Malik General Hospital in Medan, Indonesia, from May–September 2017. Assessed for severity of chronic inflammatory, neutrophil activity, atrophy, and intestinal metaplasia refers to Updated Sydney System. Plasma MDA levels were examined using an HPLC MDA kit. Univariate analysis, bivariate (chi-square and Fisher exact test), and multivariate (binary logistic regression test) were programmed with SPSS version 22. There was no significant association between degree of lymphocyte infiltration with MDA level. There were significant associations between degree of neutrophil activity, atrophy, and intestinal metaplasia with MDA level (p=0.039, 0.003, 0.021; respectively). The moderate+severe degree of neutrophil activity, atrophy, and intestinal metaplasia were associated with high level of MDA.

  15. Intraintestinal administration of ulinastatin protects against sepsis by relieving intestinal damage.

    Science.gov (United States)

    Yang, Bingchang; Gao, Min; Wang, Kangkai; Jiang, Yu; Peng, Yue; Zhang, Huali; Yang, Mingshi; Xiao, Xianzhong

    2017-05-01

    Intravenous administration of ulinastatin (UTI), a broad spectral protease inhibitor, has been used on an experimental basis with severe sepsis patients in Asia. However, the effects of intraintestinal administration of UTI on intestinal and multiple organ damage in sepsis have not been reported. In this study, we established a sepsis model in rats using cecal ligation and puncture and compared the effects of intraintestinal administration of UTI through an artificial fistula of duodenum and intraperitoneal administration of UTI on the pathophysiological changes of sepsis. It was found that intraintestinal administration of UTI (1) significantly improved the survival of septic rats, (2) significantly reduced the serum levels of tumor necrosis factor-α, interleukin-1β, interleukin-6 as well as intestinal injury biomarkers diamine oxidase, D-lactic acid, and fluorescein isothiocyanate-dextran 4, and (3) significantly reduced intestinal microscopic and ultrastructural damage of septic rats. In addition, the protective effects of intraintestinal administration of UTI were significantly better than those of intraperitoneal administration of UTI. Overall, the present study for the first time revealed that intraintestinal administration of protease inhibitor UTI could reduce systemic inflammatory responses and multiple organ dysfunction in rats with sepsis by inhibiting autodigestion of intestinal wall due to proteases and provided new research ideas and experimental evidences for treatment of sepsis by intraintestinal administration of UTI. Copyright © 2016. Published by Elsevier Inc.

  16. Meeting Report--NASA Radiation Biomarker Workshop

    Energy Technology Data Exchange (ETDEWEB)

    Straume, Tore; Amundson, Sally A,; Blakely, William F.; Burns, Frederic J.; Chen, Allen; Dainiak, Nicholas; Franklin, Stephen; Leary, Julie A.; Loftus, David J.; Morgan, William F.; Pellmar, Terry C.; Stolc, Viktor; Turteltaub, Kenneth W.; Vaughan, Andrew T.; Vijayakumar, Srinivasan; Wyrobek, Andrew J.

    2008-05-01

    A summary is provided of presentations and discussions from the NASA Radiation Biomarker Workshop held September 27-28, 2007, at NASA Ames Research Center in Mountain View, California. Invited speakers were distinguished scientists representing key sectors of the radiation research community. Speakers addressed recent developments in the biomarker and biotechnology fields that may provide new opportunities for health-related assessment of radiation-exposed individuals, including for long-duration space travel. Topics discussed include the space radiation environment, biomarkers of radiation sensitivity and individual susceptibility, molecular signatures of low-dose responses, multivariate analysis of gene expression, biomarkers in biodefense, biomarkers in radiation oncology, biomarkers and triage following large-scale radiological incidents, integrated and multiple biomarker approaches, advances in whole-genome tiling arrays, advances in mass-spectrometry proteomics, radiation biodosimetry for estimation of cancer risk in a rat skin model, and confounding factors. Summary conclusions are provided at the end of the report.

  17. Epidermal Growth Factor and Intestinal Barrier Function

    Directory of Open Access Journals (Sweden)

    Xiaopeng Tang

    2016-01-01

    Full Text Available Epidermal growth factor (EGF is a 53-amino acid peptide that plays an important role in regulating cell growth, survival, migration, apoptosis, proliferation, and differentiation. In addition, EGF has been established to be an effective intestinal regulator helping to protect intestinal barrier integrity, which was essential for the absorption of nutrients and health in humans and animals. Several researches have demonstrated that EGF via binding to the EGF receptor and subsequent activation of Ras/MAPK, PI3K/AKT, PLC-γ/PKC, and STATS signal pathways regulates intestinal barrier function. In this review, the relationship between epidermal growth factor and intestinal development and intestinal barrier is described, to provide a better understanding of the effects of EGF on intestine development and health.

  18. Intestinal epithelium in inflammatory bowel disease

    Directory of Open Access Journals (Sweden)

    Mehmet eCoskun

    2014-08-01

    Full Text Available The intestinal epithelium has a strategic position as a protective physical barrier to luminal microbiota and actively contributes to the mucosal immune system. This barrier is mainly formed by a monolayer of specialized intestinal epithelial cells (IECs that are crucial in maintaining intestinal homeostasis. Therefore, dysregulation within the epithelial layer can increase intestinal permeability, lead to abnormalities in interactions between IECs and immune cells in underlying lamina propria, and disturb the intestinal immune homeostasis, all of which are linked to the clinical disease course of inflammatory bowel disease (IBD. Understanding the role of the intestinal epithelium in IBD pathogenesis might contribute to an improved knowledge of the inflammatory processes and the identification of potential therapeutic targets.

  19. Cinnamon polyphenols regulate multiple metabolic pathways involved in intestinal lipid metabolism of primary small intestinal enterocytes

    Science.gov (United States)

    Increasing evidence suggests that dietary factors may affect the expression of multiple genes and signaling pathways including those that regulate intestinal lipoprotein metabolism. The small intestine is actively involved in the regulation of dietary lipid absorption, intracellular transport and me...

  20. 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

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

    International Nuclear Information System (INIS)

    Ogawa, Eiichi; Hosokawa, Masaya; Harada, Norio; Yamane, Shunsuke; Hamasaki, Akihiro; Toyoda, Kentaro; Fujimoto, Shimpei; Fujita, Yoshihito; Fukuda, Kazuhito; Tsukiyama, Katsushi; Yamada, Yuichiro; Seino, Yutaka; Inagaki, Nobuya

    2011-01-01

    Research highlights: → Exogenous GIP inhibits intestinal motility through a somatostatin-mediated pathway. → Exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility. → The GIP-receptor-mediated action in intestine does not involve in GLP-1-mediated pathway. -- Abstract: Gastric inhibitory polypeptide (GIP) is released from the small intestine upon meal ingestion and increases insulin secretion from pancreatic β cells. Although the GIP receptor is known to be expressed in small intestine, the effects of GIP in small intestine are not fully understood. This study was designed to clarify the effect of GIP on intestinal glucose absorption and intestinal motility. Intestinal glucose absorption in vivo was measured by single-pass perfusion method. Incorporation of [ 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 [ 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

  2. Differentiated thyroid carcinoma and intestinal polyposis syndromes.

    Science.gov (United States)

    Triggiani, Vincenzo; Angelo Giagulli, Vito; Tafaro, Angela; Resta, Francesco; Sabba, Carlo; Licchelli, Brunella; Guastamacchia, Edoardo

    2012-12-01

    Familial Adenomatous Polyposis, Cowden's Syndrome, and Peutz-Jeghers Syndrome are well known as Intestinal Polyposis Syndromes, inherited conditions characterized by the development of polyps of the gastro-intestinal tract in association with extra-intestinal manifestations, in particular malignant tumors at different sites. Thyroid carcinoma is sometimes a part of the clinical picture of these syndromes. The aim of this paper is to review the literature dealing with the association between differentiated thyroid carcinomas and Intestinal Polyposis Syndromes in order to point out peculiar aspects, providing suggestions for the screening and the management of thyroid tumors in these patients.

  3. Sonographic diagnosis of intestinal polyps in children.

    Science.gov (United States)

    Parra, Dimitri A; Navarro, Oscar M

    2008-06-01

    Although colonoscopy is the modality of choice for the diagnosis of intestinal polyps, sonography may be the first diagnostic modality in the evaluation of children with this pathology. Graded compression sonography of the small and large bowel may be useful in diagnosing intestinal polyps. A specific diagnosis is possible in many cases as most polyps have a characteristic appearance. Although sonography is not intended to replace endoscopy in the diagnostic work-up of intestinal polyps, it is important for radiologists to be aware of this appearance as they can be the first in making the diagnosis of intestinal polyps using sonography.

  4. Intestinal absorption of fluorescently labeled nanoparticles.

    Science.gov (United States)

    Simovic, Spomenka; Song, Yunmei; Nann, Thomas; Desai, Tejal A

    2015-07-01

    Characterization of intestinal absorption of nanoparticles is critical in the design of noninvasive anticancer, protein-based, and gene nanoparticle-based therapeutics. Here we demonstrate a general approach for the characterization of the intestinal absorption of nanoparticles and for understanding the mechanisms active in their processing within healthy intestinal cells. It is generally accepted that the cellular processing represents a major drawback of current nanoparticle-based therapeutic systems. In particular, endolysosomal trafficking causes degradation of therapeutic molecules such as proteins, lipids, acid-sensitive anticancer drugs, and genes. To date, investigations into nanoparticle processing within intestinal cells have studied mass transport through Caco-2 cells or everted rat intestinal sac models. We developed an approach to visualize directly the mechanisms of nanoparticle processing within intestinal tissue. These results clearly identify a mechanism by which healthy intestinal cells process nanoparticles and point to the possible use of this approach in the design of noninvasive nanoparticle-based therapies. Advances in nanomedicine have resulted in the development of new therapies for various diseases. Intestinal route of administration remains the easiest and most natural. The authors here designed experiments to explore and characterize the process of nanoparticle transport across the intestinal tissue. In so doing, further insights were gained for future drug design. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Bile acids in regulation of intestinal physiology.

    LENUS (Irish Health Repository)

    Keating, Niamh

    2009-10-01

    In addition to their roles in facilitating lipid digestion and absorption, bile acids are recognized as important regulators of intestinal function. Exposure to bile acids can dramatically influence intestinal transport and barrier properties; in recent years, they have also become appreciated as important factors in regulating cell growth and survival. Indeed, few cells reside within the intestinal mucosa that are not altered to some degree by exposure to bile acids. The past decade saw great advances in the knowledge of how bile acids exert their actions at the cellular and molecular levels. In this review, we summarize the current understanding of the role of bile acids in regulation of intestinal physiology.

  6. Intestinal myiasis caused by Muscina stabulans

    Directory of Open Access Journals (Sweden)

    Shivekar S

    2008-01-01

    Full Text Available Intestinal maggots were isolated from a patient, who had reported to the Department of General Medicine of Sri Manakula Vinayagar Medical College, Puducherry, in southern India with complaints of abdominal distress, bloating of abdomen and intestinal hurry following a meal. He was diagnosed as a case of intestinal myiasis. Maggots obtained from his stool were identified to be Muscina stabulans based on characteristic patterns of posterior spiracles. He was treated with purgatives and albendazole. This intestinal myiasis case caused by M. stabulans is reported here because of its rare occurrence and the need to establish a correct diagnosis.

  7. Ischemia-reperfusion and neonatal intestinal injury.

    Science.gov (United States)

    Young, Christopher M; Kingma, Sandra D K; Neu, Josef

    2011-02-01

    We review research relating ischemia/reperfusion to injury in the neonatal intestine. Epidemiologic evidence suggests that the most common form of necrotizing enterocolitis is not triggered by a primary hypoxic-ischemic event. Its late occurrence, lack of preceding ischemic events, and evidence for microbial and inflammatory processes preclude a major role for primary hypoxic ischemia as the sentinel pathogenic event. However, term infants, especially those with congenital heart disease who have development of intestinal necrosis, and those preterm infants with spontaneous intestinal perforations, are more likely to have intestinal ischemia as a primary component of their disease pathogenesis. Copyright © 2011 Mosby, Inc. All rights reserved.

  8. Chronic Obstructive Pulmonary Disease Biomarkers

    Directory of Open Access Journals (Sweden)

    Tatsiana Beiko

    2016-04-01

    Full Text Available Despite significant decreases in morbidity and mortality of cardiovascular diseases (CVD and cancers, morbidity and cost associated with chronic obstructive pulmonary disease (COPD continue to be increasing. Failure to improve disease outcomes has been related to the paucity of interventions improving survival. Insidious onset and slow progression halter research successes in developing disease-modifying therapies. In part, the difficulty in finding new therapies is because of the extreme heterogeneity within recognized COPD phenotypes. Novel biomarkers are necessary to help understand the natural history and pathogenesis of the different COPD subtypes. A more accurate phenotyping and the ability to assess the therapeutic response to new interventions and pharmaceutical agents may improve the statistical power of longitudinal clinical studies. In this study, we will review known candidate biomarkers for COPD, proposed pathways of pathogenesis, and future directions in the field.

  9. Glycoscience aids in biomarker discovery

    Directory of Open Access Journals (Sweden)

    Serenus Hua1,2 & Hyun Joo An1,2,*

    2012-06-01

    Full Text Available The glycome consists of all glycans (or carbohydrates within abiological system, and modulates a wide range of important biologicalactivities, from protein folding to cellular communications.The mining of the glycome for disease markers representsa new paradigm for biomarker discovery; however, this effortis severely complicated by the vast complexity and structuraldiversity of glycans. This review summarizes recent developmentsin analytical technology and methodology as applied tothe fields of glycomics and glycoproteomics. Mass spectrometricstrategies for glycan compositional profiling are described, as arepotential refinements which allow structure-specific profiling.Analytical methods that can discern protein glycosylation at aspecific site of modification are also discussed in detail.Biomarker discovery applications are shown at each level ofanalysis, highlighting the key role that glycoscience can play inhelping scientists understand disease biology.

  10. Effects of digested onion extracts on intestinal gene expression: an interspecies comparison using different intestine models

    NARCIS (Netherlands)

    Hulst, M.M.; Meulen, van der J.; Hoekman, A.J.W.; Smits, M.A.

    2016-01-01

    Applicability of in vitro (human Caco-2 cells) and ex vivo intestine models (rat precision cut intestine slices and the pig in-situ small intestinal segment perfusion (SISP) technique) to study the effect of food compounds. In vitro digested yellow (YOd) and white onion extracts (WOd) were used as

  11. Intestinal Microbiota Signatures Associated With Histological Liver Steatosis in Pediatric-Onset Intestinal Failure

    NARCIS (Netherlands)

    Korpela, K.; Mutanen, A.; Salonen, A.; Savilahti, E.; Vos, de W.M.; Pakarinen, M.P.

    2017-01-01

    BACKGROUND: Intestinal failure (IF)-associated liver disease (IFALD) is the major cause of mortality in IF. The link between intestinal microbiota and IFALD is unclear. METHODS: We compared intestinal microbiota of patients with IF (n = 23) with healthy controls (n = 58) using culture-independent

  12. Inflammatory mediators and intestinal injury.

    Science.gov (United States)

    Caplan, M S; MacKendrick, W

    1994-06-01

    Although the causes of necrotizing enterocolitis (NEC) are not well understood, there is compelling evidence to suggest that the inflammatory mediators play an important role in the pathophysiology of the disease. This article examines the role of platelet-activating factor (PAF) and other mediators on the development of NEC, and attempts to explain the association of the putative NEC risk factors with altered mediator production and subsequent intestinal injury. The authors hypothesize that PAF is a key mediator in the final common pathway leading to NEC.

  13. Intestinal Lymphangiectasia Secondary to Neuroblastoma

    Directory of Open Access Journals (Sweden)

    RM Reifen

    1994-01-01

    Full Text Available An eight month-old infant presented with a 10-day history of vomiting and diarrhea, and a one-week history of swelling of the lower extremities. Laboratory evaluations revealed hypoproteinemia and lymphocytopenia due to protein-losing enteropathy. Peroral small bowel biopsy showed intestinal lymphangiectasia. Subsequent onset of unexplained ecchymosis and obstructive jaundice resulted in additional studies which revealed an omental neuroblastoma as the underlying etiology of the infant’s symptoms. This report emphasizes the importance of considering secondary, obstructive causes for lymphangiectasia and protein-losing enteropathy.

  14. Dietary biomarkers: advances, limitations and future directions

    Directory of Open Access Journals (Sweden)

    Hedrick Valisa E

    2012-12-01

    Full Text Available Abstract The subjective nature of self-reported dietary intake assessment methods presents numerous challenges to obtaining accurate dietary intake and nutritional status. This limitation can be overcome by the use of dietary biomarkers, which are able to objectively assess dietary consumption (or exposure without the bias of self-reported dietary intake errors. The need for dietary biomarkers was addressed by the Institute of Medicine, who recognized the lack of nutritional biomarkers as a knowledge gap requiring future research. The purpose of this article is to review existing literature on currently available dietary biomarkers, including novel biomarkers of specific foods and dietary components, and assess the validity, reliability and sensitivity of the markers. This review revealed several biomarkers in need of additional validation research; research is also needed to produce sensitive, specific, cost-effective and noninvasive dietary biomarkers. The emerging field of metabolomics may help to advance the development of food/nutrient biomarkers, yet advances in food metabolome databases are needed. The availability of biomarkers that estimate intake of specific foods and dietary components could greatly enhance nutritional research targeting compliance to national recommendations as well as direct associations with disease outcomes. More research is necessary to refine existing biomarkers by accounting for confounding factors, to establish new indicators of specific food intake, and to develop techniques that are cost-effective, noninvasive, rapid and accurate measures of nutritional status.

  15. Prematurity reduces functional adaptation to intestinal resection in piglets

    DEFF Research Database (Denmark)

    Aunsholt, Lise; Thymann, Thomas; Qvist, Niels

    2015-01-01

    Background: Necrotizing enterocolitis and congenital gastrointestinal malformations in infants often require intestinal resection, with a subsequent risk of short bowel syndrome (SBS). We hypothesized that immediate intestinal adaptation following resection of the distal intestine with placement ...

  16. The Adaptive Response to Intestinal Oxidative Stress in Mammalian Hibernation

    National Research Council Canada - National Science Library

    Carey, Hannah V

    2006-01-01

    .... Specific Aim 2 examines consequences of intestinal oxidative stress during hibernation including seasonal changes in NF-kB activation in intestine, seasonal changes in the intestinal mucosal immune...

  17. Lymphoma Caused by Intestinal Microbiota

    Directory of Open Access Journals (Sweden)

    Mitsuko L. Yamamoto

    2014-09-01

    Full Text Available The intestinal microbiota and gut immune system must constantly communicate to maintain a balance between tolerance and activation: on the one hand, our immune system should protect us from pathogenic microbes and on the other hand, most of the millions of microbes in and on our body are innocuous symbionts and some can even be beneficial. Since there is such a close interaction between the immune system and the intestinal microbiota, it is not surprising that some lymphomas such as mucosal-associated lymphoid tissue (MALT lymphoma have been shown to be caused by the presence of certain bacteria. Animal models played an important role in establishing causation and mechanism of bacteria-induced MALT lymphoma. In this review we discuss different ways that animal models have been applied to establish a link between the gut microbiota and lymphoma and how animal models have helped to elucidate mechanisms of microbiota-induced lymphoma. While there are not a plethora of studies demonstrating a connection between microbiota and lymphoma development, we believe that animal models are a system which can be exploited in the future to enhance our understanding of causation and improve prognosis and treatment of lymphoma.

  18. Intestinal histoplasmosis in immunocompetent adults.

    Science.gov (United States)

    Zhu, Lin-Lin; Wang, Jin; Wang, Zi-Jing; Wang, Yi-Ping; Yang, Jin-Lin

    2016-04-21

    To present a retrospective analysis of clinical and endoscopic features of 4 cases of immunocompetent hosts with intestinal histoplasmosis (IH). Four immunocompetent adults were diagnosed with IH between October 2005 and March 2015 at West China Hospital of Sichuan University. Clinical and endoscopic characteristics were summarized and analyzed retrospectively. GMS (Gomori methenamine silver), PAS (periodic acid-Schiff) and Giemsa staining technique were used to confirm Histoplasma capsulatum(H. capsulatum). The symptoms, signs, endoscopic presentations, radiographic imaging, pathological stain results and follow-up are presented as tables and illustrations. The cases were male patients, ranging from 33 to 61 years old, and primarily presented with non-specific symptoms such as irregular fever, weight loss, abdominal pain and distention. Hepatosplenomegaly and lymphadenopathy were the most common signs. Endoscopic manifestations were localized or diffuse congestion, edema, ulcers, and polypoid nodules with central erosion involving the terminal ileum, ascending colon, transverse colon, descending colon, sigmoid colon and rectum, similar to intestinal tuberculosis, tumor, and inflammatory bowel disease. Numerous yeast-like pathogens testing positive for PAS and GMS stains but negative for Giemsa were detected in the cytoplasm of the histiocytes, which were highly suggestive of H. capsulatum. Immunocompetent individuals suffering from histoplasmosis are rarely reported. It is necessary that gastroenterologists and endoscopists consider histoplasmosis as a differential diagnosis, even in immunocompetent patients.

  19. Megacystis microcolon intestinal hypoperistalsis syndrome: a report ...

    African Journals Online (AJOL)

    The prognosis is poor and most patients die early because of sepsis or total parental nutrition-related complications. This report describes a new case of megacystis microcolon intestinal hypoperistalsis syndrome associated with meconium ileus, dilated stomach, and megaesophagus. Keywords: intestinal hypoperistalsis ...

  20. Intestinal cholesterol secretion: future clinical implications

    NARCIS (Netherlands)

    Jakulj, L.; Besseling, J.; Stroes, E. S. G.; Groen, A. K.

    2013-01-01

    Together with the liver, the intestine serves as a homeostatic organ in cholesterol metabolism. Recent evidence has substantiated the pivotal role of the intestine in reverse cholesterol transport (RCT). RCT is a fundamental antiatherogenic pathway, mediating the removal of cholesterol from tissues

  1. Intestinal cholesterol secretion : future clinical implications

    NARCIS (Netherlands)

    Jakulj, L.; Besseling, J.; Stroes, E. S. G.; Groen, A. K.

    2013-01-01

    Together with the liver, the intestine serves as a homeostatic organ in cholesterol metabolism. Recent evidence has substantiated the pivotal role of the intestine in reverse cholesterol transport (RCT). RCT is a fundamental antiatherogenic pathway, mediating the removal of cholesterol from tissues

  2. Alkaline Phosphatases From Camel Small Intestine | Fahmy ...

    African Journals Online (AJOL)

    Camel intestinal alkaline phosphatase have been purified and characterized. The purification was carried out by chromatography on DEAE-cellulose. Five intestinal alkaline phosphatase isoenzymes (IAP1 to IAP5) were obtained. IAP2 and IAP5 with the highest activity levels were purified to homogeneity by Sephacryl ...

  3. Megacystis microcolon intestinal hypoperistalsis syndrome: a report ...

    African Journals Online (AJOL)

    intestinal peristalsis. The prognosis is poor and most patients die early because of sepsis or total parental nutrition-related complications. This report describes a new case of megacystis microcolon intestinal hypoperistalsis syndrome associated with meconium ileus, dilated stomach, and megaesophagus. Ann Pediatr Surg.

  4. Is nonoperative management of adhesive intestinal obstruction ...

    African Journals Online (AJOL)

    Background: Nonoperative management of adhesive intestinal obstruction gives good results in adults but there are scant studies on its outcome in children. This study reports outcomes and experiences with nonoperative and operative management of adhesive intestinal obstruction in children in a resource-poor country.

  5. Laparoscopic Treatment of Intestinal Malrotation in Children

    NARCIS (Netherlands)

    Ooms, N.; Matthyssens, L.E.; Draaisma, J.M.T.; Blaauw, I. de; Wijnen, M.H.

    2016-01-01

    Purpose Intestinal malrotation is a congenital intestinal rotation anomaly, which can be treated by either laparotomy or laparoscopy. Our hypothesis is that laparoscopic treatment leads to less small bowel obstruction because of the fewer adhesions in comparison to laparotomy, without increasing the

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

    African Journals Online (AJOL)

    Intestinal parasitic infections constitute a global health burden causing clinical morbidity. Parasitic protozoa and helminthes are responsible for some of the most devastating and prevalent diseases of human. The study was conducted to determine the prevalence of intestinal parasites among patients attending Federal ...

  7. Ectoparasites and intestinal helminths of speckled pigeon ...

    African Journals Online (AJOL)

    Ectoparasites and intestinal helminths of speckled pigeon ( Columba guinea Hartlaub and Finsch 1870) in Zaria, Nigeria. ... Science World Journal ... A total of 30 (20 males and 10 females) Speckled Pigeons trapped from the wild in Zaria and its environs, Nigeria, were examined for ectoparasites and intestinal helminths, ...

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

    African Journals Online (AJOL)

    ADOWIE PERE

    ABSTRACT: Intestinal parasitic infections constitute a global health burden causing clinical morbidity. Parasitic protozoa and helminthes are responsible for some of the most devastating and prevalent diseases of human. The study was conducted to determine the prevalence of intestinal parasites among patients attending ...

  9. Intestinal radiation syndrome: sepsis and endotoxin

    International Nuclear Information System (INIS)

    Geraci, J.P.; Jackson, K.L.; Mariano, M.S.

    1985-01-01

    Rats were whole-body irradiated with 8-MeV cyclotron-produced neutrons and 137 Cs γ rays to study the role of enteric bacteria and endotoxin in the intestinal radiation syndrome. Decrease in intestinal weight was used as an index of radiation-induced breakdown of the mucosa. Neutron and γ-ray doses that were sublethal for intestinal death resulted in a dose-dependent decrease in intestinal weight, reaching minimal values 2 to 3 days after exposure, followed by recovery within 5 days after irradiation. Neutron and photon doses that caused intestinal death resulted in greater mucosal breakdown with little or no evidence of mucosal recovery. The presence of fluid in the intestine and diarrhea, but not bacteremia or endotoxemia, were related to mucosal breakdown and recovery. Neither sepsis nor endotoxin could be detected in liver samples taken at autopsy from animals which died a short time earlier from intestinal injury. These results suggest that overt sepsis and endotoxemia do not play a significant role in the intestinal radiation syndrome

  10. Biomarkers: A Challenging Conundrum in Cardiovascular Disease.

    Science.gov (United States)

    Libby, Peter; King, Kevin

    2015-12-01

    The use of biomarkers has proven utility in cardiovascular medicine and holds great promise for future advances, but their application requires considerable rigor in thinking and methodology. Numerous confounding factors can cloud the clinical and investigative uses of biomarkers. Yet, the thoughtful and critical use of biomarkers can doubtless aid discovery of new pathogenic pathways, identify novel therapeutic targets, and provide a bridge between the laboratory and the clinic. Biomarkers can provide diagnostic and prognostic tools to the practitioner. The careful application of biomarkers can also help design and guide clinical trials required to establish the efficacy of novel interventions to improve patient outcomes. Point of care testing, technological advances, such as microfluidic and wearable devices, and the power of omics approaches all promise to elevate the potential contributions of biomarkers to discovery science, translation, clinical trials, and the practice of cardiovascular medicine. © 2015 American Heart Association, Inc.

  11. Circulating Biomarkers for Duchenne Muscular Dystrophy.

    Science.gov (United States)

    Aartsma-Rus, Annemieke; Spitali, Pietro

    2015-07-22

    Duchenne muscular dystrophy is the most common form of muscular dystrophy. Genetic and biochemical research over the years has characterized the cause, pathophysiology and development of the disease providing several potential therapeutic targets and/or biomarkers. High throughput - omic technologies have provided a comprehensive understanding of the changes occurring in dystrophic muscles. Murine and canine animal models have been a valuable source to profile muscles and body fluids, thus providing candidate biomarkers that can be evaluated in patients. This review will illustrate known circulating biomarkers that could track disease progression and response to therapy in patients affected by Duchenne muscular dystrophy. We present an overview of the transcriptomic, proteomic, metabolomics and lipidomic biomarkers described in literature. We show how studies in muscle tissue have led to the identification of serum and urine biomarkers and we highlight the importance of evaluating biomarkers as possible surrogate endpoints to facilitate regulatory processes for new medicinal products.

  12. Cardiovascular disease biomarkers across autoimmune diseases.

    Science.gov (United States)

    Ahearn, Joseph; Shields, Kelly J; Liu, Chau-Ching; Manzi, Susan

    2015-11-01

    Cardiovascular disease is increasingly recognized as a major cause of premature mortality among those with autoimmune disorders. There is an urgent need to identify those patients with autoimmune disease who are at risk for CVD so as to optimize therapeutic intervention and ultimately prevention. Accurate identification, monitoring and stratification of such patients will depend upon a panel of biomarkers of cardiovascular disease. This review will discuss some of the most recent biomarkers of cardiovascular diseases in autoimmune disease, including lipid oxidation, imaging biomarkers to characterize coronary calcium, plaque, and intima media thickness, biomarkers of inflammation and activated complement, genetic markers, endothelial biomarkers, and antiphospholipid antibodies. Clinical implementation of these biomarkers will not only enhance patient care but also likely accelerate the pharmaceutical pipeline for targeted intervention to reduce or eliminate cardiovascular disease in the setting of autoimmunity. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Regulation of intestinal calcium absorption by luminal calcium content: role of intestinal alkaline phosphatase.

    Science.gov (United States)

    Brun, Lucas R; Brance, María L; Lombarte, Mercedes; Lupo, Maela; Di Loreto, Verónica E; Rigalli, Alfredo

    2014-07-01

    Intestinal alkaline phosphatase is a brush border enzyme that is stimulated by calcium. Inhibition of intestinal alkaline phosphatase increases intestinal calcium absorption. We hypothesized that intestinal alkaline phosphatase acts as a minute-to-minute regulatory mechanism of calcium entry. The aim of this study was to evaluate the mechanism by which intestinal luminal calcium controls intestinal calcium absorption. We performed kinetic studies with purified intestinal alkaline phosphatase and everted duodenal sacs and showed that intestinal alkaline phosphatase modifies the luminal pH as a function of enzyme concentration and calcium luminal content. A decrease in pH occurred simultaneously with a decrease in calcium absorption. The inhibition of intestinal alkaline phosphatase by l-phenylalanine caused an increase in calcium absorption. This effect was also confirmed in calcium uptake experiments with isolated duodenal cells. Changes in luminal pH arising from intestinal alkaline phosphatase activity induced by luminal calcium concentration modulate intestinal calcium absorption. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Relationship between intestinal microflora imbalance and nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    MA Ruijuan

    2015-01-01

    Full Text Available The intestinal microecosystem is composed of natural microflora, intestinal epithelial cells, and intestinal mucosal immune system. Nonalcoholic fatty liver disease (NAFLD is a metabolic stress-induced liver injury associated with insulin resistance and genetic susceptibility. In recent years, there has been increasing evidence showing the involvement of imbalanced intestinal microflora in the pathogenesis of NAFLD. Overgrowth of intestinal microflora, increased permeability of intestinal mucosa, intestinal endotoxemia, and production of inflammatory cytokines play important roles in the development of NAFLD. Further studies on the relationship between intestinal microflora imbalance and the pathogenesis of NAFLD may shed light on the treatment and prevention of NAFLD.

  15. Phospholipids as Biomarkers for Excessive Alcohol Use

    Science.gov (United States)

    2015-10-01

    2015 2. REPORT TYPE Annual 3. DATES COVERED 15Sept2014 - 14Sep2015 4. TITLE AND SUBTITLE Phospholipids as Biomarkers for Excessive Alcohol Use 5a...of potential biomarkers to monitor abstinence from alcohol abuse . Electrophoresis. 2015 Feb;36(4):556-63. doi: 10.1002/elps.201400319. Epub 2015 Jan...AWARD NUMBER: W81XWH-12-1-0497 TITLE: Phospholipids as Biomarkers for Excessive Alcohol Use PRINCIPAL INVESTIGATOR: Suthat Liangpunsakul

  16. Gallstone ileus resulting in strong intestinal obstruction

    Directory of Open Access Journals (Sweden)

    Israel Szajnbok

    Full Text Available Mechanic intestinal obstruction, caused by the passage of biliary calculus from vesicle to intestine, through fistulization, although not frequent, deserve study due to the morbi-mortality rates. Incidence in elder people explains the association with chronic degenerative diseases, increasing complexity in terms of therapy decision. Literature discusses the need and opportunity for the one or two-phase surgical attack of the cholecystenteric fistule, in front of the resolution on the obstructive urgency and makes reference to Gallstone Ileus as an exception for strong intestinal obstruction. The more frequent intestinal obstruction observed is when it occurs a Gallstone Ileus impacting in terms of ileocecal valve. The authors submit a Gallstone Ileus manifestation as causing strong intestinal obstruction, discussing aspects regarding diagnostic and treatment.

  17. Multispectral tissue characterization for intestinal anastomosis optimization

    Science.gov (United States)

    Cha, Jaepyeong; Shademan, Azad; Le, Hanh N. D.; Decker, Ryan; Kim, Peter C. W.; Kang, Jin U.; Krieger, Axel

    2015-10-01

    Intestinal anastomosis is a surgical procedure that restores bowel continuity after surgical resection to treat intestinal malignancy, inflammation, or obstruction. Despite the routine nature of intestinal anastomosis procedures, the rate of complications is high. Standard visual inspection cannot distinguish the tissue subsurface and small changes in spectral characteristics of the tissue, so existing tissue anastomosis techniques that rely on human vision to guide suturing could lead to problems such as bleeding and leakage from suturing sites. We present a proof-of-concept study using a portable multispectral imaging (MSI) platform for tissue characterization and preoperative surgical planning in intestinal anastomosis. The platform is composed of a fiber ring light-guided MSI system coupled with polarizers and image analysis software. The system is tested on ex vivo porcine intestine tissue, and we demonstrate the feasibility of identifying optimal regions for suture placement.

  18. ACUTE INTESTINAL INFECTIONS: THERAPEUTICAL TACTICS IN CHILDREN

    Directory of Open Access Journals (Sweden)

    A.N. Surkov

    2011-01-01

    Full Text Available Acute intestinal infections are quite common among children. Their clinical presentations include intoxication syndrome (drowsiness, low appetite, fever etc, infectious toxic syndrome (toxicosis with exicosis, neurotoxicosi, hypovolemic or infectious-toxic shockand diarrhea syndrome. Sometimes intestinal infections can be quite severe and even lethal. However disease duration and outcome depend on timelines and adequacy of prescribed treatment. Main guidelines of intestinal infections treatment include probiotics. That is why the right choice of probiotics is important for a pediatrician. The article contains basic information upon etiopathogenesis, classification, diagnostic criteria and acute pediatric intestinal infections treatment guidelines.Key words: acute intestinal infections, etiopathogenesis, diagnostic criteria, treatment, probiotics, children. (Voprosy sovremennoi pediatrii — Current Pediatrics. — 2011; 10 (6: 141–147

  19. Regional specialization within the intestinal immune system

    DEFF Research Database (Denmark)

    Mowat, Allan M.; Agace, William Winston

    2014-01-01

    The intestine represents the largest compartment of the immune system. It is continually exposed to antigens and immunomodulatory agents from the diet and the commensal microbiota, and it is the port of entry for many clinically important pathogens. Intestinal immune processes are also increasingly...... implicated in controlling disease development elsewhere in the body. In this Review, we detail the anatomical and physiological distinctions that are observed in the small and large intestines, and we suggest how these may account for the diversity in the immune apparatus that is seen throughout...... the intestine. We describe how the distribution of innate, adaptive and innate-like immune cells varies in different segments of the intestine and discuss the environmental factors that may influence this. Finally, we consider the implications of regional immune specialization for inflammatory disease...

  20. Mining the human intestinal microbiota for biomarkers associated with metabolic disorders

    NARCIS (Netherlands)

    Hermes, Gerben

    2016-01-01

    After birth, our gastrointestinal (GI) tract is colonized by a highly complex assemblage of microbes, collectively termed the GI microbiota, that develop intimate interactions with our body. Recent evidence indicates that the GI microbiota and its products may contribute to the development of

  1. Necrotizing enterocolitis: a clinical review on diagnostic biomarkers and the role of the intestinal microbiota

    NARCIS (Netherlands)

    Niemarkt, Hendrik J.; de Meij, Tim G. J.; van de Velde, Mirjam E.; van der Schee, Marc P.; van Goudoever, Johannes B.; Kramer, Boris W.; Andriessen, Peter; de Boer, Nanne K. H.

    2015-01-01

    Necrotizing enterocolitis (NEC) remains one of the most frequent gastrointestinal diseases in the neonatal intensive care unit, with a continuing unacceptable high mortality and morbidity rates. Up to 20% to 40% of infants with NEC will need surgical intervention at some point. Although the exact

  2. Biomarker qualification via public-private partnerships.

    Science.gov (United States)

    Eck, S L; Paul, S M

    2010-01-01

    Biomarkers linked to patient outcomes (safety and efficacy) have an increasingly important role in drug development. Consequently, validation and qualification of such biomarkers are essential, often requiring large data sets from well-controlled randomized clinical trials. In the December 2009 issue of Clinical Pharmacology & Therapeutics, investigators utilizing data from four pharmaceutical companies and working under the auspices of the Biomarkers Consortium described the utility of adiponectin as an early predictor of glycemic control in diabetic patients taking peroxisome proliferator-activated receptor (PPAR) agonists. This work illustrates the advantages of large public-private partnerships for biomarker qualification.

  3. [Neovagina with intestine: 13 cases].

    Science.gov (United States)

    Parente, A; Molina, E; Cerdá, J; Cañizo, A; Rodriguez, A; Laín, A; Fanjul, M; Vázquez, J

    2008-01-01

    The absence or hipoplasia vaginal can turn out to be isolated, associated with ambiguous genitalia, or as anatomical variant in a syndrome of sewer. The fundamental aim in the creation of a new vagina is: to obtain a good aesthetic result, to fulfil functional criteria (elasticity, sensibility, physiological inclination) and to improve the quality of life of the patients avoiding the use of molds and minimizing the morbidity of the zones donors. In this work let's sense beforehand our experience in the accomplishment of neovaginas with intestine. We analyze the clinical record of 13 patients treated surgically in the last ten years. We differentiate two groups according to the age, the diagnosis and the type of surgery: a) the first group of 8 patients present syndrome of insensibility to the androgens (4), syndrome of Rokitansky (2), extrofia of sewer (1) and mixed gonadal disgenesia (1). This group of patients were controlled in the adolescence by an average of age of 19 years (11-35 years), they fulfilling a neovagina with sigma; b) the second group of 5 patients with sewer (3), extrofia of sewer (1) and congenital suprarrenal hiperplasia (1). This group was controlled prematurely by a middle ages of one year (4 months-3 years). The intestinal segment used as neovagina was sigma (2), ileon (2) and rectum (1), and was performed during the surgical correction of her congenital malformation. Two patients have presented intestinal obstruction in the postoperatory immediate one. Four patients have needed removal of a small vaginal prolapse, and three have needed vaginal transitory expansions for introit stenosis. The long-term evolution has been favorable with an excellent aesthetic aspect. Four patients recount sexual fully satisfactory relations. We believe that the neovagina with sigma is at present the best option in patients with absence or hipoplasia vaginal. The advantages are the possibility of precocious and one time correction, a neovagina of dimensions and

  4. Synergistic effect of aluminum and ionizing radiation upon ultrastructure, oxidative stress and apoptotic alterations in Paneth cells of rat intestine.

    Science.gov (United States)

    Eltahawy, N A; Elsonbaty, S M; Abunour, S; Zahran, W E

    2017-03-01

    Environmental and occupational exposure to aluminum along with ionizing radiation results in serious health problems. This study was planned to investigate the impact of oxidative stress provoked by exposure to ionizing radiation with aluminum administration upon cellular ultra structure and apoptotic changes in Paneth cells of rat small intestine . Animals received daily aluminum chloride by gastric gavage at a dose 0.5 mg/Kg BW for 4 weeks. Whole body gamma irradiation was applied at a dose 2 Gy/week up to 8 Gy. Ileum malondialdehyde, advanced oxidative protein products, protein carbonyl and tumor necrosis factor-alpha were assessed as biomarkers of lipid peroxidation, protein oxidation and inflammation respectively along with superoxide dismutase, catalase, and glutathione peroxidase activities as enzymatic antioxidants. Moreover, analyses of cell cycle division and apoptotic changes were evaluated by flow cytometry. Intestinal cellular ultra structure was investigated using transmission electron microscope.Oxidative and inflammatory stresses assessment in the ileum of rats revealed that aluminum and ionizing radiation exposures exhibited a significant effect upon the increase in oxidative stress biomarkers along with the inflammatory marker tumor necrosis factor-α accompanied by a significant decreases in the antioxidant enzyme activities. Flow cytometric analyses showed significant alterations in the percentage of cells during cell cycle division phases along with significant increase in apoptotic cells. Ultra structurally, intestinal cellular alterations with marked injury in Paneth cells at the sites of bacterial translocation in the crypt of lumens were recorded. The results of this study have clearly showed that aluminum and ionizing radiation exposures induced apoptosis with oxidative and inflammatory disturbance in the Paneth cells of rat intestine, which appeared to play a major role in the pathogenesis of cellular damage. Furthermore, the

  5. [Intestinal endometriosis - a case report].

    Science.gov (United States)

    Krzemiński, Sławomir

    2017-03-21

    Endometriosis intestines due to its non-specific symptoms can pose diagnostic problems, a lack of or incorrect treatment worsens the quality of life, sometimes leading to serious complications. The differential diagnosis of abdominal pain, especially in patients of reproductive age should be taken disease into account. Often abdominal pain in young women are classified as a functional gastrointestinal disorder, and only carefully collected intelligence allows you to focus on the diagnosis of endometriosis, especially if the symptoms significantly impair quality of life. A woman 32 year old who was admitted to the department of gastroenterology because of increasing pain in the abdomen. Due to the deteriorating condition of the patient, the characteristics of mechanical obstruction on imaging studies was transferred to the surgical ward with suspected Crohn's disease. She was treated surgically. Histopathological examination found endometriosis. Endometriosis outside the sex system can lead to serious complications.

  6. Kaposiform hemangioendothelioma causing intestinal obstruction

    Directory of Open Access Journals (Sweden)

    Bassel Salman

    2018-01-01

    Full Text Available A previously healthy toddler with bilious vomiting and erythematous gluteal rash over 2 weeks had intermittent pain, constipation and decreased appetite. All labs were negative with the exception of fecal occult blood. Abdominal x-ray and ultrasound revealed dilated air-filled loops of bowel and partial small bowel obstruction. After persistent worsening abdominal pain and vomiting a CT scan with IV contrast (Fig. 1 suggested small bowel obstruction. Emergent surgery was performed and diagnostic laparoscopy revealed about 61 cm of necrotic bowel causing stricture formation and mesenteric shortening in the distal small bowel. 56 cm of inflamed bowel was resected with end-to-end anastomosis. Final pathology report indicated diffuse intestinal angiomatosis with transmural involvement and focal erosion consistent with KHE (Fig. 2. Presentation is varied, consists of cutaneous lesion, retroperitoneal mass, intestinal obstruction, jaundice, intussusception, or multifocal neoplasms. Complete surgical resection with wide margins is the best therapeutic option and has achieved the best outcomes. If not treated in sufficient time, KHE has a relatively high mortality rate of 30%, with most deaths occurring due to its locally invasive effects [5]. There are limited reports of identifying features of KHE on imaging. Of 165 cases of KHE none were presented in the small bowel [5]. We report the unique case of KHE presenting as a hypervascular mass causing obstruction in the distal small bowel. Although extremely rare, KHE should be considered as a reason for severe GI stricture or obstruction in infants and children in obscure cases and included in the differential.

  7. The significance of intestinal apoptosis

    International Nuclear Information System (INIS)

    Potten, C.S.

    1997-01-01

    Apoptosis occurs at a low level spontaneously in the small intestine (SI). The levels can be raised by a variety of cytotoxic agents including radiation. The apoptosis induced by radiation, and some drugs and the spontaneous apoptosis, show some specificity for the stem cells in the small intestinal crypt. In the colon, these agents target transit cells in the mid crypt. p53 expression is elevated at the same time as apoptosis in the SI but not in the cells undergoing apoptosis. The expression of bcl-2, a survival gene, is largely absent in the SI, but is expressed, albeit weakly, in the stem cells in the colon. Spontaneous apoptosis is observed in p53 null mice which also develop normally suggesting that spontaneous and developmental apoptosis are p53 independent and that spontaneous apoptosis is part of the homeostatic mechanisms maintaining stem cell numbers. Radiation induced apoptosis is completely absent at these early times post-irradiation in p53 nulls. In bel-2 null mice, the levels of spontaneous and radiation induced apoptosis are elevated in the colon. Bax, a death gene, is expressed on the villus and inter-crypt table in the colon suggesting that cells at the end of their lifespan initiate apoptosis. It has been suggested that apoptosis in the SI is a protective mechanism against carcinogenesis in the stem cells of the SI which rarely develops cancer. Cells that possess genetic damage detected. In the large bowel, this mechanism is not effective due to the action of bcl-2. Thus stem cells may persist in this tissue with genetic damage resulting in a higher cancer risk. Furthermore, the lack of spontaneous apoptosis in the colon may result in a gradual increase of the stem cells with time resulting in more ells at risk. (author)

  8. Alpha-ketoglutarate (AKG) lowers body weight and affects intestinal innate immunity through influencing intestinal microbiota.

    Science.gov (United States)

    Chen, Shuai; Bin, Peng; Ren, Wenkai; Gao, Wei; Liu, Gang; Yin, Jie; Duan, Jielin; Li, Yinghui; Yao, Kang; Huang, Ruilin; Tan, Bie; Yin, Yulong

    2017-06-13

    Alpha-ketoglutarate (AKG), a precursor of glutamate and a critical intermediate in the tricarboxylic acid cycle, shows beneficial effects on intestinal function. However, the influence of AKG on the intestinal innate immune system and intestinal microbiota is unknown. This study explores the effect of oral AKG administration in drinking water (10 g/L) on intestinal innate immunity and intestinal microbiota in a mouse model. Mouse water intake, feed intake and body weight were recorded throughout the entire experiment. The ileum was collected for detecting the expression of intestinal proinflammatory cytokines and innate immune factors by Real-time Polymerase Chain Reaction. Additionally, the ileal luminal contents and feces were collected for 16S rDNA sequencing to analyze the microbial composition. The intestinal microbiota in mice was disrupted with an antibiotic cocktail. The results revealed that AKG supplementation lowered body weight, promoted ileal expression of mammalian defensins of the alpha subfamily (such as cryptdins-1, cryptdins-4, and cryptdins-5) while influencing the intestinal microbial composition (i.e., lowering the Firmicutes to Bacteroidetes ratio). In the antibiotic-treated mouse model, AKG supplementation failed to affect mouse body weight and inhibited the expression of cryptdins-1 and cryptdins-5 in the ileum. We concluded that AKG might affect body weight and intestinal innate immunity through influencing intestinal microbiota.

  9. [Effect of perioperative intestinal probiotics on intestinal flora and immune function in patients with colorectal cancer].

    Science.gov (United States)

    Zhu, Dajian; Chen, Xiaowu; Wu, Jinhao; Ju, Yongle; Feng, Jing; Lu, Guangsheng; Ouyang, Manzhao; Ren, Baojun; Li, Yong

    2012-08-01

    To investigate the effect of perioperative application of intestinal probiotics to substitute oral intestinal antimicrobial agents on intestinal flora and immune function in surgical patients with colorectal cancer. Sixty patients with colorectal cancer undergoing elective laparoscopic radical surgery were randomized to receive preoperative bowel preparation using oral intestinal antimicrobial agents (n=20) or using oral intestinal probiotics (Jinshuangqi Tablets, 2.0 g, 3 times daily) since the fifth day before the operation and at 24 h after the operation for 7 consecutive days. Upon admission and 7 days after the operation, fecal samples and fasting peripheral venous blood were collected from the patients to examine the intestinal flora and serum levels of interleukin-2 (IL-2), IgA, IgG, and IgM, NK cell activity, T lymphocytes subsets CD3(+), CD4(+), CD8(+) and CD4(+)/CD8(+) ratio. At 7 days after the operation, the patients receiving probiotics showed significantly increased counts of intestinal Bifidobacterium, Lactobacillus, and Enterococcus (Pprobiotics group compared with those in patients with conventional intestinal preparation (Pprobiotics to replace preoperative oral intestinal antimicrobial agents can effectively correct intestinal flora imbalance and improve the immune function of surgical patients with colorectal cancer.

  10. Diffused and sustained inhibitory effects of intestinal electrical stimulation on intestinal motility mediated via sympathetic pathway.

    Science.gov (United States)

    Zhao, Xiaotuan; Yin, Jieyun; Wang, Lijie; Chen, Jiande D Z

    2014-06-01

    The aims were to investigate the energy-dose response effect of intestinal electrical stimulation (IES) on small bowel motility, to compare the effect of forward and backward IES, and to explore the possibility of using intermittent IES and mechanism of IES on intestinal motility. Five dogs implanted with a duodenal cannula and one pair of intestinal serosal electrodes were studied in five sessions: 1) energy-dose response study; 2) forward IES; 3) backward IES; 4) intermittent IES vs. continuous IES; 5) administration of guanethidine. The contractile activity and tonic pressure of the small intestine were recorded. The duration of sustained effect after turning off IES was manually calculated. 1) IES with long pulse energy dose dependently inhibited contractile activity and tonic pressure of the small intestine (p intestine depended on the energy of IES delivered (p intestine. 5) Guanethidine blocked the inhibitory effect of IES on intestinal motility. IES with long pulses inhibits small intestinal motility; the effect is energy-dose dependent, diffused, and sustained. Intermittent IES has the same efficacy as the continuous IES in inhibiting small intestinal motility. Forward and backward IES have similar inhibitory effects on small bowel motility. This IES-induced inhibitory effect is mediated via the sympathetic pathway. © 2013 International Neuromodulation Society.

  11. Vitamin D and intestinal calcium absorption.

    Science.gov (United States)

    Christakos, Sylvia; Dhawan, Puneet; Porta, Angela; Mady, Leila J; Seth, Tanya

    2011-12-05

    The principal function of vitamin D in calcium homeostasis is to increase calcium absorption from the intestine. Calcium is absorbed by both an active transcellular pathway, which is energy dependent, and by a passive paracellular pathway through tight junctions. 1,25Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) the hormonally active form of vitamin D, through its genomic actions, is the major stimulator of active intestinal calcium absorption which involves calcium influx, translocation of calcium through the interior of the enterocyte and basolateral extrusion of calcium by the intestinal plasma membrane pump. This article reviews recent studies that have challenged the traditional model of vitamin D mediated transcellular calcium absorption and the crucial role of specific calcium transport proteins in intestinal calcium absorption. There is also increasing evidence that 1,25(OH)(2)D(3) can enhance paracellular calcium diffusion. The influence of estrogen, prolactin, glucocorticoids and aging on intestinal calcium absorption and the role of the distal intestine in vitamin D mediated intestinal calcium absorption are also discussed. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  12. Prospective of ischemic stroke biomarkers

    Directory of Open Access Journals (Sweden)

    Szewczak Krzysztof

    2017-06-01

    Full Text Available Methods currently used in brain vascular disorder diagnostics are neither fast enough nor clear-out; thus, there exists a necessity of finding new types of testing which could enlarge and complete the actual panel of diagnostics or be an alternative to current methods. The discovery of sensitive and specific biomarkers of ischemic brain stroke will improve the effects of treatment and will help to assess the progress or complications of the disease. The relevant diagnosis of ischemic stroke (IS within the first 4.5 hours after the initial symptoms allows for the initiation of treatment with recombinant tissue plasminogen activators which limits the magnitude of negative changes in the brain and which enhance the final effectiveness of therapy. The potential biomarkers which are under investigation are substances involved in the processes of coagulation and fibrinolysis, and are of molecules released from damaged vascular endothelial cells and from nerves and cardiac tissue. The analyzed substances are typical of oxidative stress, apoptosis, excitotoxicity and damage of the blood brain barrier.

  13. Intestinal lineage commitment of embryonic stem cells.

    Science.gov (United States)

    Cao, Li; Gibson, Jason D; Miyamoto, Shingo; Sail, Vibhavari; Verma, Rajeev; Rosenberg, Daniel W; Nelson, Craig E; Giardina, Charles

    2011-01-01

    Generating lineage-committed intestinal stem cells from embryonic stem cells (ESCs) could provide a tractable experimental system for understanding intestinal differentiation pathways and may ultimately provide cells for regenerating damaged intestinal tissue. We tested a two-step differentiation procedure in which ESCs were first cultured with activin A to favor formation of definitive endoderm, and then treated with fibroblast-conditioned medium with or without Wnt3A. The definitive endoderm expressed a number of genes associated with gut-tube development through mouse embryonic day 8.5 (Sox17, Foxa2, and Gata4 expressed and Id2 silent). The intestinal stem cell marker Lgr5 gene was also activated in the endodermal cells, whereas the Msi1, Ephb2, and Dcamkl1 intestinal stem cell markers were not. Exposure of the endoderm to fibroblast-conditioned medium with Wnt3A resulted in the activation of Id2, the remaining intestinal stem cell markers and the later gut markers Cdx2, Fabp2, and Muc2. Interestingly, genes associated with distal gut-associated mesoderm (Foxf2, Hlx, and Hoxd8) were also simulated by Wnt3A. The two-step differentiation protocol generated gut bodies with crypt-like structures that included regions of Lgr5-expressing proliferating cells and regions of cell differentiation. These gut bodies also had a smooth muscle component and some underwent peristaltic movement. The ability of the definitive endoderm to differentiate into intestinal epithelium was supported by the vivo engraftment of these cells into mouse colonic mucosa. These findings demonstrate that definitive endoderm derived from ESCs can carry out intestinal cell differentiation pathways and may provide cells to restore damaged intestinal tissue. Copyright © 2010 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

  14. 18F-FDG as an inflammation biomarker for imaging dengue virus infection and treatment response.

    Science.gov (United States)

    Chacko, Ann-Marie; Watanabe, Satoru; Herr, Keira J; Kalimuddin, Shirin; Tham, Jing Yang; Ong, Joanne; Reolo, Marie; Serrano, Raymond M F; Cheung, Yin Bun; Low, Jenny G H; Vasudevan, Subhash G

    2017-05-04

    Development of antiviral therapy against acute viral diseases, such as dengue virus (DENV), suffers from the narrow window of viral load detection in serum during onset and clearance of infection and fever. We explored a biomarker approach using 18F-fluorodeoxyglucose (18F-FDG) PET in established mouse models for primary and antibody-dependent enhancement infection with DENV. 18F-FDG uptake was most prominent in the intestines and correlated with increased virus load and proinflammatory cytokines. Furthermore, a significant temporal trend in 18F-FDG uptake was seen in intestines and selected tissues over the time course of infection. Notably, 18F-FDG uptake and visualization by PET robustly differentiated treatment-naive groups from drug-treated groups as well as nonlethal from lethal infections with a clinical strain of DENV2. Thus, 18F-FDG may serve as a novel DENV infection-associated inflammation biomarker for assessing treatment response during therapeutic intervention trials.

  15. Imaging biomarker roadmap for cancer studies

    NARCIS (Netherlands)

    O'Connor, James P. B.; Aboagye, Eric O.; Adams, Judith E.; Aerts, Hugo J. W. L.; Barrington, Sally F.; Beer, Ambros J.; Boellaard, Ronald; Bohndiek, Sarah E.; Brady, Michael; Brown, Gina; Buckley, David L.; Chenevert, Thomas L.; Clarke, Laurence P.; Collette, Sandra; Cook, Gary J.; Desouza, Nandita M.; Dickson, John C.; Dive, Caroline; Evelhoch, Jeffrey L.; Faivre-Finn, Corinne; Gallagher, Ferdia A.; Gilbert, Fiona J.; Gillies, Robert J.; Goh, Vicky; Griffiths, J. R.; Groves, Ashley M.; Halligan, Steve; Harris, Adrian L.; Hawkes, David J.; Hoekstra, Otto S.; Huang, Erich P.; Hutton, Brian F.; Jackson, Edward F.; Jayson, Gordon C.; Jones, Andrew; Koh, Dow-Mu; Lacombe, Denis; Lambin, Philippe; Lassau, Nathalie; Leach, Martin O.; Lee, Ting-Yim; Leen, Edward L.; Lewis, Jason S.; Liu, Yan; Lythgoe, Mark F.; Manoharan, Prakash; Maxwell, Ross J.; Miles, Kenneth A.; Morgan, Bruno; Morris, Steve; Ng, Tony; Padhani, Anwar R.; Parker, Geoff J. M.; Partridge, Mike; Pathak, Arvind P.; Peet, Andrew C.; Punwani, Shonit; Reynolds, Andrew R.; Robinson, Simon P.; Shankar, Lalitha K.; Sharma, Ricky A.; Soloviev, Dmitry; Stroobants, Sigrid G.; Sullivan, Daniel C.; Taylor, Stuart A.; Tofts, Paul S.; Tozer, Gillian M.; van Herk, Marcel B.; Walker-Samuel, Simon; Wason, James; Williams, Kaye J.; Workman, Paul; Yankeelov, Thomas E.; Brindle, Kevin M.; McShane, Lisa M.; Jackson, Alan; Waterton, John C.

    Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and

  16. Proteomic Biomarkers for Spontaneous Preterm Birth

    DEFF Research Database (Denmark)

    Kacerovsky, Marian; Lenco, Juraj; Musilova, Ivana

    2014-01-01

    This review aimed to identify, synthesize, and analyze the findings of studies on proteomic biomarkers for spontaneous preterm birth (PTB). Three electronic databases (Medline, Embase, and Scopus) were searched for studies in any language reporting the use of proteomic biomarkers for PTB published...

  17. Cytokines as Biomarkers in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Agata Burska

    2014-01-01

    Full Text Available RA is a complex disease that develops as a series of events often referred to as disease continuum. RA would benefit from novel biomarker development for diagnosis where new biomarkers are still needed (even if progresses have been made with the inclusion of ACPA into the ACR/EULAR 2010 diagnostic criteria and for prognostic notably in at risk of evolution patients with autoantibody-positive arthralgia. Risk biomarkers for rapid evolution or cardiovascular complications are also highly desirable. Monitoring biomarkers would be useful in predicting relapse. Finally, predictive biomarkers for therapy outcome would allow tailoring therapy to the individual. Increasing numbers of cytokines have been involved in RA pathology. Many have the potential as biomarkers in RA especially as their clinical utility is already established in other diseases and could be easily transferable to rheumatology. We will review the current knowledge’s relation to cytokine used as biomarker in RA. However, given the complexity and heterogeneous nature of RA, it is unlikely that a single cytokine may provide sufficient discrimination; therefore multiple biomarker signatures may represent more realistic approach for the future of personalised medicine in RA.

  18. Fluid biomarkers in multiple system atrophy

    DEFF Research Database (Denmark)

    Laurens, Brice; Constantinescu, Radu; Freeman, Roy

    2015-01-01

    Despite growing research efforts, no reliable biomarker currently exists for the diagnosis and prognosis of multiple system atrophy (MSA). Such biomarkers are urgently needed to improve diagnostic accuracy, prognostic guidance and also to serve as efficacy measures or surrogates of target engagem...

  19. DNA Methylation Biomarkers: Cancer and Beyond

    Directory of Open Access Journals (Sweden)

    Thomas Mikeska

    2014-09-01

    Full Text Available Biomarkers are naturally-occurring characteristics by which a particular pathological process or disease can be identified or monitored. They can reflect past environmental exposures, predict disease onset or course, or determine a patient’s response to therapy. Epigenetic changes are such characteristics, with most epigenetic biomarkers discovered to date based on the epigenetic mark of DNA methylation. Many tissue types are suitable for the discovery of DNA methylation biomarkers including cell-based samples such as blood and tumor material and cell-free DNA samples such as plasma. DNA methylation biomarkers with diagnostic, prognostic and predictive power are already in clinical trials or in a clinical setting for cancer. Outside cancer, strong evidence that complex disease originates in early life is opening up exciting new avenues for the detection of DNA methylation biomarkers for adverse early life environment and for estimation of future disease risk. However, there are a number of limitations to overcome before such biomarkers reach the clinic. Nevertheless, DNA methylation biomarkers have great potential to contribute to personalized medicine throughout life. We review the current state of play for DNA methylation biomarkers, discuss the barriers that must be crossed on the way to implementation in a clinical setting, and predict their future use for human disease.

  20. Stable isotopes and biomarkers in microbial ecology

    NARCIS (Netherlands)

    Boschker, H.T.S.; Middelburg, J.J.

    2002-01-01

    The use of biomarkers in combination with stable isotope analysis is a new approach in microbial ecology and a number of papers on a variety of subjects have appeared. We will first discuss the techniques for analysing stable isotopes in biomarkers, primarily gas chromatography-combustion-isotope

  1. Cytokines as Biomarkers in Rheumatoid Arthritis

    Science.gov (United States)

    Burska, Agata; Boissinot, Marjorie; Ponchel, Frederique

    2014-01-01

    RA is a complex disease that develops as a series of events often referred to as disease continuum. RA would benefit from novel biomarker development for diagnosis where new biomarkers are still needed (even if progresses have been made with the inclusion of ACPA into the ACR/EULAR 2010 diagnostic criteria) and for prognostic notably in at risk of evolution patients with autoantibody-positive arthralgia. Risk biomarkers for rapid evolution or cardiovascular complications are also highly desirable. Monitoring biomarkers would be useful in predicting relapse. Finally, predictive biomarkers for therapy outcome would allow tailoring therapy to the individual. Increasing numbers of cytokines have been involved in RA pathology. Many have the potential as biomarkers in RA especially as their clinical utility is already established in other diseases and could be easily transferable to rheumatology. We will review the current knowledge's relation to cytokine used as biomarker in RA. However, given the complexity and heterogeneous nature of RA, it is unlikely that a single cytokine may provide sufficient discrimination; therefore multiple biomarker signatures may represent more realistic approach for the future of personalised medicine in RA. PMID:24733962

  2. Transcriptome changes during intestinal cell differentiation

    DEFF Research Database (Denmark)

    Tadjali, Mehrdad; Seidelin, Jakob B; Olsen, Jørgen Lillelund

    2002-01-01

    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....

  3. Recreating Intestinal Peristalsis in the Petri Dish.

    Science.gov (United States)

    Espinosa-Luna, Rosa; Barajas-Espinosa, Alma R; Ochoa-Cortez, Fernando; Barajas-López, Carlos

    2018-01-01

    Here we describe a culture technique of cells dissociated from the external muscularis of the guinea pig small intestine, which allows us to maintain all the elements involved in the intestinal peristaltic reflex. After a few days in culture, these cells reorganize to form a small group of cells that permit the generation of pacemaker activity, spontaneous contractions, and the development of inhibitory and excitatory junction potentials in the petri dish, all elements involved in the peristaltic reflex. Therefore, these co-cultures are suitable to study the cellular and molecular aspects related to the development, maintenance, and modulation of motor intestinal functions.

  4. Intestinal lengthening: an experimental and clinical review.

    Science.gov (United States)

    Bianchi, A

    1984-01-01

    Small intestinal lengthening by the Bianchi procedure has now had successful clinical application in children and neonates with the short-bowel syndrome. This paper reviews the background experimental work and clinical cases so far treated. A personal case of intestinal lengthening in a 7-week-old baby with 35 cm jejunum is described in detail. Intestinal lengthening appears to reduce dependence on parenteral nutrition, thus allowing earlier establishment of total enteral alimentation. The procedure may therefore have a useful place in the overall management of the short-bowel syndrome. Images Figure 3. A Figure 3. B Figure 3. C Figure 3. D PMID:6471060

  5. Bias in emerging biomarkers for bipolar disorder

    DEFF Research Database (Denmark)

    Carvalho, A F; Köhler, C A; Fernandes, B S

    2016-01-01

    BACKGROUND: To date no comprehensive evaluation has appraised the likelihood of bias or the strength of the evidence of peripheral biomarkers for bipolar disorder (BD). Here we performed an umbrella review of meta-analyses of peripheral non-genetic biomarkers for BD. METHOD: The Pubmed/Medline, E......BACKGROUND: To date no comprehensive evaluation has appraised the likelihood of bias or the strength of the evidence of peripheral biomarkers for bipolar disorder (BD). Here we performed an umbrella review of meta-analyses of peripheral non-genetic biomarkers for BD. METHOD: The Pubmed....../Medline, EMBASE and PsycInfo electronic databases were searched up to May 2015. Two independent authors conducted searches, examined references for eligibility, and extracted data. Meta-analyses in any language examining peripheral non-genetic biomarkers in participants with BD (across different mood states...

  6. Early-Phase Studies of Biomarkers

    DEFF Research Database (Denmark)

    Pepe, Margaret S.; Janes, Holly; Li, Christopher I.

    2016-01-01

    BACKGROUND: Many cancer biomarker research studies seek to develop markers that can accurately detect or predict future onset of disease. To design and evaluate these studies, one must specify the levels of accuracy sought. However, justified target levels are rarely available. METHODS: We describe...... a way to calculate target levels of sensitivity and specificity for a biomarker intended to be applied in a defined clinical context. The calculation requires knowledge of the prevalence or incidence of cases in the clinical population and the ratio of benefit associated with the clinical consequences...... for ovarian cancer. CONCLUSIONS: It is feasible to specify target levels of biomarker performance that enable evaluation of the potential clinical impact of biomarkers in early-phase studies. Nevertheless, biomarkers meeting the criteria should still be tested rigorously in studies that measure the actual...

  7. Diagnostic and prognostic epigenetic biomarkers in cancer.

    Science.gov (United States)

    Costa-Pinheiro, Pedro; Montezuma, Diana; Henrique, Rui; Jerónimo, Carmen

    2015-01-01

    Growing cancer incidence and mortality worldwide demands development of accurate biomarkers to perfect detection, diagnosis, prognostication and monitoring. Urologic (prostate, bladder, kidney), lung, breast and colorectal cancers are the most common and despite major advances in their characterization, this has seldom translated into biomarkers amenable for clinical practice. Epigenetic alterations are innovative cancer biomarkers owing to stability, frequency, reversibility and accessibility in body fluids, entailing great potential of assay development to assist in patient management. Several studies identified putative epigenetic cancer biomarkers, some of which have been commercialized. However, large multicenter validation studies are required to foster translation to the clinics. Herein we review the most promising epigenetic detection, diagnostic, prognostic and predictive biomarkers for the most common cancers.

  8. The Indian Consensus Document on cardiac biomarker

    Directory of Open Access Journals (Sweden)

    I. Satyamurthy

    2014-01-01

    Full Text Available Despite recent advances, the diagnosis and management of heart failure evades the clinicians. The etiology of congestive heart failure (CHF in the Indian scenario comprises of coronary artery disease, diabetes mellitus and hypertension. With better insights into the pathophysiology of CHF, biomarkers have evolved rapidly and received diagnostic and prognostic value. In CHF biomarkers prove as measures of the extent of pathophysiological derangement; examples include biomarkers of myocyte necrosis, myocardial remodeling, neurohormonal activation, etc. In CHF biomarkers act as indicators for the presence, degree of severity and prognosis of the disease, they may be employed in combination with the present conventional clinical assessments. These make the biomarkers feasible options against the present expensive measurements and may provide clinical benefits.

  9. Biomarkers for colitis-associated colorectal cancer

    Science.gov (United States)

    Chen, Ru; Lai, Lisa A; Brentnall, Teresa A; Pan, Sheng

    2016-01-01

    Patients with extensive ulcerative colitis (UC) of more than eight years duration have an increased risk of colorectal cancer. Molecular biomarkers for dysplasia and cancer could have a great clinical value in managing cancer risk in these UC patients. Using a wide range of molecular techniques - including cutting-edge OMICS technologies - recent studies have identified clinically relevant biomarker candidates from a variety of biosamples, including colonic biopsies, blood, stool, and urine. While the challenge remains to validate these candidate biomarkers in multi-center studies and with larger patient cohorts, it is certain that accurate biomarkers of colitis-associated neoplasia would improve clinical management of neoplastic risk in UC patients. This review highlights the ongoing avenues of research in biomarker development for colitis-associated colorectal cancer. PMID:27672285

  10. Biomarkers: in medicine, drug discovery, and environmental health

    National Research Council Canada - National Science Library

    Vaidya, Vishal S; Bonventre, Joseph V

    2010-01-01

    ... Identification Using Mass Spectrometry Sample Preparation Protein Quantitation Examples of Biomarker Discovery and Evaluation Challenges in Proteomic Biomarker Discovery The Road Forward: Targeted ...

  11. Peptidases Compartmentalized to the Ascaris suum Intestinal Lumen and Apical Intestinal Membrane

    Science.gov (United States)

    Rosa, Bruce A.

    2015-01-01

    The nematode intestine is a tissue of interest for developing new methods of therapy and control of parasitic nematodes. However, biological details of intestinal cell functions remain obscure, as do the proteins and molecular functions located on the apical intestinal membrane (AIM), and within the intestinal lumen (IL) of nematodes. Accordingly, methods were developed to gain a comprehensive identification of peptidases that function in the intestinal tract of adult female Ascaris suum. Peptidase activity was detected in multiple fractions of the A. suum intestine under pH conditions ranging from 5.0 to 8.0. Peptidase class inhibitors were used to characterize these activities. The fractions included whole lysates, membrane enriched fractions, and physiological- and 4 molar urea-perfusates of the intestinal lumen. Concanavalin A (ConA) was confirmed to bind to the AIM, and intestinal proteins affinity isolated on ConA-beads were compared to proteins from membrane and perfusate fractions by mass spectrometry. Twenty-nine predicted peptidases were identified including aspartic, cysteine, and serine peptidases, and an unexpectedly high number (16) of metallopeptidases. Many of these proteins co-localized to multiple fractions, providing independent support for localization to specific intestinal compartments, including the IL and AIM. This unique perfusion model produced the most comprehensive view of likely digestive peptidases that function in these intestinal compartments of A. suum, or any nematode. This model offers a means to directly determine functions of these proteins in the A. suum intestine and, more generally, deduce the wide array functions that exist in these cellular compartments of the nematode intestine. PMID:25569475

  12. Pathogen invasion changes the intestinal microbiota composition and induces innate immune responses in the zebrafish intestine.

    Science.gov (United States)

    Yang, Hui-Ting; Zou, Song-Song; Zhai, Li-Juan; Wang, Yao; Zhang, Fu-Miao; An, Li-Guo; Yang, Gui-Wen

    2017-12-01

    Numerous bacteria are harbored in the animal digestive tract and are impacted by several factors. Intestinal microbiota homeostasis is critical for maintaining the health of an organism. However, how pathogen invasion affects the microbiota composition has not been fully clarified. The mechanisms for preventing invasion by pathogenic microorganisms are yet to be elucidated. Zebrafish is a useful model for developmental biology, and studies in this organism have gradually become focused on intestinal immunity. In this study, we analyzed the microbiota of normal cultivated and infected zebrafish intestines, the aquarium water and feed samples. We found that the predominant bacteria in the zebrafish intestine belonged to Gammaproteobacteria (67%) and that feed and environment merely influenced intestinal microbiota composition only partially. Intestinal microbiota changed after a pathogenic bacterial challenge. At the genus level, the abundance of some pathogenic intestinal bacteria increased, and these genera included Halomonas (50%), Pelagibacterium (3.6%), Aeromonas (2.6%), Nesterenkonia (1%), Chryseobacterium (3.4‰), Mesorhizobium (1.4‰), Vibrio (1‰), Mycoplasma (0.7‰) and Methylobacterium (0.6‰) in IAh group. However, the abundance of some beneficial intestinal bacteria decreased, and these genera included Nitratireductor (0.8‰), Enterococcus (0.8‰), Brevundimonas (0.7‰), Lactococcus (0.7‰) and Lactobacillus (0.4‰). Additionally, we investigated the innate immune responses after infection. ROS levels in intestine increased in the early stages after a challenge and recovered subsequently. The mRNA levels of antimicrobial peptide genes lectin, hepcidin and defensin1, were upregulated in the intestine after pathogen infection. These results suggested that the invasion of pathogen could change the intestinal microbiota composition and induce intestinal innate immune responses in zebrafish. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Apple-peel intestinal atresia: enteroplasty for intestinal lengthening and primary anastomosis.

    Science.gov (United States)

    Onofre, Luciano Silveira; Maranhão, Renato Frota de Albuquerque; Martins, Elaine Cristina Soares; Fachin, Camila Girardi; Martins, Jose Luiz

    2013-06-01

    Apple-peel atresia (or Type-IIIb intestinal atresia) is an unusual type of jejunoileal atresia. They present with jejunal atresia near the ligament of Treitz and a foreshortened small bowel. Many surgical options have been used, but the optimal method of repair remains unclear. We present a case of a newborn with apple-peel intestinal atresia managed by enteroplasty for intestinal lengthening and primary anastomosis. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Intestinal Leiomyositis: A Cause of Chronic Intestinal Pseudo?Obstruction in 6 Dogs

    OpenAIRE

    Zacuto, A.C.; Pesavento, P.A.; Hill, S.; McAlister, A.; Rosenthal, K.; Cherbinsky, O.; Marks, S.L.

    2015-01-01

    Background Intestinal leiomyositis is a suspected autoimmune disorder affecting the muscularis propria layer of the gastrointestinal tract and is a cause of chronic intestinal pseudo?obstruction in humans and animals. Objective To characterize the clinical presentation, histopathologic features, and outcome of dogs with intestinal leiomyositis in an effort to optimize treatment and prognosis. Animals Six client?owned dogs. Methods Retrospective case series. Medical records were reviewed to de...

  15. Interactions between the intestinal microbiota and innate lymphoid cells.

    Science.gov (United States)

    Chen, Vincent L; Kasper, Dennis L

    2014-01-01

    The mammalian intestine must manage to contain 100 trillion intestinal bacteria without inducing inappropriate immune responses to these microorganisms. The effects of the immune system on intestinal microorganisms are numerous and well-characterized, and recent research has determined that the microbiota influences the intestinal immune system as well. In this review, we first discuss the intestinal immune system and its role in containing and maintaining tolerance to commensal organisms. We next introduce a category of immune cells, the innate lymphoid cells, and describe their classification and function in intestinal immunology. Finally, we discuss the effects of the intestinal microbiota on innate lymphoid cells.

  16. Methodological issues in the study of intestinal microbiota in irritable bowel syndrome.

    Science.gov (United States)

    Taverniti, Valentina; Guglielmetti, Simone

    2014-07-21

    Irritable bowel syndrome (IBS) is an intestinal functional disorder with the highest prevalence in the industrialized world. The intestinal microbiota (IM) plays a role in the pathogenesis of IBS and is not merely a consequence of this disorder. Previous research efforts have not revealed unequivocal microbiological signatures of IBS, and the experimental results are contradictory. The experimental methodologies adopted to investigate the complex intestinal ecosystem drastically impact the quality and significance of the results. Therefore, to consider the methodological aspects of the research on IM in IBS, we reviewed 29 relevant original research articles identified through a PubMed search using three combinations of keywords: "irritable bowel syndrome + microflora", "irritable bowel syndrome + microbiota" and "irritable bowel syndrome + microbiome". For each study, we reviewed the quality and significance of the scientific evidence obtained with respect to the experimental method adopted. The data obtained from each study were compared with all considered publications to identify potential inconsistencies and explain contradictory results. The analytical revision of the studies referenced in the present review has contributed to the identification of microbial groups whose relative abundance significantly alters IBS, suggesting that these microbial groups could be IM signatures for this syndrome. The identification of microbial biomarkers in the IM can be advantageous for the development of new diagnostic tools and novel therapeutic strategies for the treatment of different subtypes of IBS.

  17. Experiencing sexuality after intestinal stoma

    Directory of Open Access Journals (Sweden)

    Maria Angela Boccara de Paula

    2012-06-01

    Full Text Available OBJECTIVE: Identify the Social Representations (SR of ostomized people in terms of sexuality after the stoma. METHODS: An exploratory, descriptive, qualitative study using the Social Representation Theory with 15 ostomized people (8 females, mean age of 57.9 years, between August and September 2005. Data obtained from transcribed interviews were submitted to content analysis, resulting in the thematic unit "Giving new meaning to sexuality" and subthemes. RESULTS: The study demonstrated that the intestinal stoma interferes in the sexuality experience, showing that the meanings attributed to this experience are based on individual life stories, quality of personal relationships established in practice and perception of sexuality, despite the stoma. CONCLUSIONS: The Social Representations, in terms of experiencing sexuality after the stoma, are based on meanings attributed to the body, associated with daily life and present in the social imaginary. It is influenced by other factors, such as physiological changes resulting from the surgery and the fact of having or not a partner. Care taken during sexual practices provide greater security and comfort in moments of intimacy, resembling the closest to what ostomized people experienced before the stoma. The self-irrigation technique associated or not with the use of artificial occluder, has been attested by its users as a positive element that makes a difference in sexual practice after the stoma. The support to ostomized people should be comprehensive, not limited to technical care and disease, which are important, but not sufficient. The interdisciplinary health team should consider all aspects of the person, seeking a real meeting between subjects.OBJETIVO: Identificar as Representações Sociais (RS da pessoa estomizada intestinal sobre vivência da sexualidade após confecção do estoma. MÉTODOS: Estudo exploratório, descritivo, qualitativo do ponto de vista do referencial da Representa

  18. Congenital central hypoventilation syndrome and intestinal ...

    African Journals Online (AJOL)

    ... hypoventilation syndrome (CCHS), also called 'Ondine's curse', is characterised by an abnormal ventilatory response to progressive hypercapnia and sustained hypoxaemia. Neonates with this condition experience hypoventilation or apnoea while asleep. Patients may also have congenital intestinal aganglionosis (CIA), ...

  19. Intestinal perforation secondary to metastasic lung carcinoma

    Directory of Open Access Journals (Sweden)

    M. C. Álvarez Sánchez

    2014-11-01

    Full Text Available Secondary symptomatic gastrointestinal metastases from lung primary tumor are rare. They can cause a variety of clinical conditions such as perforation, obstruction and bleeding. Intestinal perforations of intestinal metastases have a very poor prognosis. We present a case of a patient with metastatic lung cancer who presents with intestinal perforation and pneumoperitoneum. A 67 year old male, immunosuppressed and smoker is diagnosed with acute abdomen secondary to perforation of a tumor of the terminal ileum, as well as three other similar injuries. Resection and anastomosis. The patient died two months after surgery. The final pathological diagnosis supports epidermoidide poorly differentiated lung carcinoma. It was concluded that given an intestinal perforation in a patient diagnosed with lung carcinoma, it shouldn´t be excluded the metastases origen . Surgery is a purely palliative procedure.

  20. Intestinal Colonization Dynamics of Vibrio cholerae

    Science.gov (United States)

    Almagro-Moreno, Salvador; Pruss, Kali; Taylor, Ronald K.

    2015-01-01

    To cause the diarrheal disease cholera, Vibrio cholerae must effectively colonize the small intestine. In order to do so, the bacterium needs to successfully travel through the stomach and withstand the presence of agents such as bile and antimicrobial peptides in the intestinal lumen and mucus. The bacterial cells penetrate the viscous mucus layer covering the epithelium and attach and proliferate on its surface. In this review, we discuss recent developments and known aspects of the early stages of V. cholerae intestinal colonization and highlight areas that remain to be fully understood. We propose mechanisms and postulate a model that covers some of the steps that are required in order for the bacterium to efficiently colonize the human host. A deeper understanding of the colonization dynamics of V. cholerae and other intestinal pathogens will provide us with a variety of novel targets and strategies to avoid the diseases caused by these organisms. PMID:25996593

  1. [Acute intestinal infections: current and upcoming vaccines].

    Science.gov (United States)

    Erlich, Paul; Sansonetti, Philippe J

    2013-01-01

    Currently, only a few licensed vaccines against intestinal infections are available. Existing vaccines have shown good efficacy when used by travelers in industrialized countries. However, these vaccines have lower efficacy in endemic areas with high prevalence of enteric pathogens. Current vaccines are too expensive to be efficiently distributed in endemic countries. Immune correlates of protection are not well defined for current licensed vaccines. A better understanding of protection mechanisms at the intestinal mucosal surfaces should allow the development of more efficient vaccines. Gut physiology and microbial composition play an important role in both physical integrity and immunological status of the gastro-intestinal tract. These parameters can partially explain the disparities observed in current vaccines efficiency. Several next-generation vaccines combined or not with adjuvant able to promote a strong mucosal response in the intestine, are under preclinical and clinical investigations. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  2. [THE INTESTINAL BARRIER, THE MICROBIOTA, MICROBIOME].

    Science.gov (United States)

    Mar'yanovich, A T

    2016-01-01

    The review examined modern condition of development directions physiology of digestion, like structure and function of the intestinal barrier, the microbiota of the digestive tract in its relations with the microorganism.

  3. Diversity and functions of intestinal mononuclear phagocytes

    DEFF Research Database (Denmark)

    Joeris, Thorsten; Müller-Luda, K; Agace, William Winston

    2017-01-01

    The intestinal lamina propria (LP) contains a diverse array of mononuclear phagocyte (MNP) subsets, including conventional dendritic cells (cDC), monocytes and tissue-resident macrophages (mφ) that collectively play an essential role in mucosal homeostasis, infection and inflammation. In the curr......The intestinal lamina propria (LP) contains a diverse array of mononuclear phagocyte (MNP) subsets, including conventional dendritic cells (cDC), monocytes and tissue-resident macrophages (mφ) that collectively play an essential role in mucosal homeostasis, infection and inflammation....... In the current review we discuss the function of intestinal cDC and monocyte-derived MNP, highlighting how these subsets play several non-redundant roles in the regulation of intestinal immune responses. While much remains to be learnt, recent findings also underline how the various populations of MNP adapt...

  4. Inflammasome in Intestinal Inflammation and Cancer

    Directory of Open Access Journals (Sweden)

    Tiago Nunes

    2013-01-01

    Full Text Available The activation of specific cytosolic pathogen recognition receptors, the nucleotide-binding-oligomerization-domain- (NOD- like receptors (NLRs, leads to the assembly of the inflammasome, a multimeric complex platform that activates caspase-1. The caspase-1 pathway leads to the upregulation of important cytokines from the interleukin (IL-1 family, IL-1β, and IL-18, with subsequent activation of the innate immune response. In this review, we discuss the molecular structure, the mechanisms behind the inflammasome activation, and its possible role in the pathogenesis of inflammatory bowel diseases and intestinal cancer. Here, we show that the available data points towards the importance of the inflammasome in the innate intestinal immune response, being the complex involved in the maintenance of intestinal homeostasis, correct intestinal barrier function and efficient elimination of invading pathogens.

  5. Upper intestinal and biliary tract endoprosthesis

    NARCIS (Netherlands)

    Tytgat, G. N.; Bartelsman, J. F.; den Hartog Jager, F. C.; Huibregtse, K.; Mathus-Vliegen, E. M.

    1986-01-01

    The endoscopic insertion of an endoprosthesis is now a standard procedure in the ultimate palliation of malignant obstructing upper gastrointestinal and biliary malignancy. The commercially available prostheses and introducing devices are adequate for the majority of upper intestinal cancers. For

  6. Epidemiology of small intestinal atresia in Europe

    DEFF Research Database (Denmark)

    Best, Kate E; Tennant, Peter W G; Addor, Marie-Claude

    2012-01-01

    The epidemiology of congenital small intestinal atresia (SIA) has not been well studied. This study describes the presence of additional anomalies, pregnancy outcomes, total prevalence and association with maternal age in SIA cases in Europe....

  7. Intestinal microbiota and HIV-1 infection

    Directory of Open Access Journals (Sweden)

    E. B. S. M. Trindade

    2007-01-01

    Full Text Available The intestinal microbiota consists of a qualitatively and quantitatively diverse range of microorganisms dynamically interacting with the host. It is remarkably stable with regard to the presence of microorganisms and their roles which, however, can be altered due to pathological conditions, diet composition, gastrointestinal disturbances and/or drug ingestion. The present review aimed at contributing to the discussion about changes in the intestinal microbiota due to HIV-1 infection, focusing on the triad infection-microbiota-nutrition as factors that promote intestinal bacterial imbalance. Intestinal microbiota alterations can be due to the HIV-1 infection as a primary factor or the pharmacotherapy employed, or they can be one of the consequences of the disease.

  8. Molecular characterization of intestinal protozoan parasites from ...

    African Journals Online (AJOL)

    Koffi Mathurin

    2014-02-17

    AJEST. African Journal of Environmental Science and. Technology. Full Length Research Paper. Molecular characterization of intestinal protozoan parasites from children facing diarrheal disease and associated risk factors in ...

  9. PET Metabolic Biomarkers for Cancer

    Directory of Open Access Journals (Sweden)

    Etienne Croteau

    2016-01-01

    Full Text Available The body's main fuel sources are fats, carbohydrates (glucose, proteins, and ketone bodies. It is well known that an important hallmark of cancer cells is the overconsumption of glucose. Positron emission tomography (PET imaging using the glucose analog 18 F-fluorodeoxyglucose ( 18 F-FDG has been a powerful cancer diagnostic tool for many decades. Apart from surgery, chemotherapy and radiotherapy represent the two main domains for cancer therapy, targeting tumor proliferation, cell division, and DNA replication–-all processes that require a large amount of energy. Currently, in vivo clinical imaging of metabolism is performed almost exclusively using PET radiotracers that assess oxygen consumption and mechanisms of energy substrate consumption. This paper reviews the utility of PET imaging biomarkers for the detection of cancer proliferation, vascularization, metabolism, treatment response, and follow-up after radiation therapy, chemotherapy, and chemotherapy-related side effects.

  10. Non-Meckel Small Intestine Diverticulitis

    Directory of Open Access Journals (Sweden)

    Shamim Ejaz

    2017-08-01

    Full Text Available Non-Meckel small intestine diverticulitis can have many manifestations and its management is not well-defined. We report 4 unselect cases of small intestine diverticulitis; all patients were seen by the same physician at the Emergency Center at The University of Texas MD Anderson Cancer Center between 1999 and 2014. The median age at diagnosis of these patients was 82 years (range, 76–87 years. All 4 patients presented with acute onset of abdominal pain, and computed tomography scans showed characteristics of small intestine diverticulitis unrelated to cancer. Most of the diverticula were found in the region of the duodenum and jejuno-ileal segments of the small intestine. The patients, even those with peripancreatic inflammation and localized perforation, were treated conservatively. Non-Meckel diverticulitis can be overlooked in the initial diagnosis because of the location of the diverticulosis, the age of the patient, and the rarity of the disease. Because patients with non-Meckel small intestine diverticulitis can present with acute abdominal pain, non-Meckel small intestine diverticulitis should be considered in the differential diagnosis of patients with acute abdominal pain, and computed tomography scans can help identify the condition. Because of the rarity of non-Meckel small intestine diverticulitis, few studies have been published, and the data are inconclusive about how best to approach these patients. Our experience with these 4 elderly patients indicates that non-Meckel small intestine diverticulitis can be treated conservatively, which avoids the potential morbidity and mortality of a surgical approach.

  11. Neuroimmune regulation during intestinal development and homeostasis.

    Science.gov (United States)

    Veiga-Fernandes, Henrique; Pachnis, Vassilis

    2017-02-01

    Interactions between the nervous system and immune system are required for organ function and homeostasis. Evidence suggests that enteric neurons and intestinal immune cells share common regulatory mechanisms and can coordinate their responses to developmental challenges and environmental aggressions. These discoveries shed light on the physiology of system interactions and open novel perspectives for therapy designs that target underappreciated neurological-immunological commonalities. Here we highlight findings that address the importance of neuroimmune cell units (NICUs) in intestinal development, homeostasis and disease.

  12. Intestinal angina. Report on two operated cases.

    Science.gov (United States)

    Solheim, K; Rosseland, A; Lund, B L

    1977-01-01

    In spite of the fact that the concept of intestinal angina is more than 70 years old, it is not generally accepted and only 400 cases of elective revascularization of the celiac/mesenteric arteries are reported in the literature. Two typical cases of intestinal angina treated with elective revascularization are presented and the pertinent literature is reviewed. An aggresive approach to the problem, followed by adequate reconstruction, is recommended.

  13. DIAGNOSIS AND MANAGEMENT OF SUBACUTE INTESTINAL OBSTRUCTION: A PROSPECTIVE STUDY

    OpenAIRE

    Amit; Anjani; Shaleen; Vikram; Prasheel

    2014-01-01

    Intestinal obstruction can be defined as impairment to the abnormal passage of intestinal contents that may be due to either mechanical obstruction or failure of normal intestinal motility in the absence of an obstructing lesion. Intestinal obstruction is the most common surgical disorder of the small intestine. SAIO implies incomplete obstruction. It has been defined in a number of ways and there are many gray zones in the treatment protocols. It is characterized by conti...

  14. Interactions between the intestinal microbiota and innate lymphoid cells

    OpenAIRE

    Chen, Vincent L; Kasper, Dennis L

    2013-01-01

    The mammalian intestine must manage to contain 100 trillion intestinal bacteria without inducing inappropriate immune responses to these microorganisms. The effects of the immune system on intestinal microorganisms are numerous and well-characterized, and recent research has determined that the microbiota influences the intestinal immune system as well. In this review, we first discuss the intestinal immune system and its role in containing and maintaining tolerance to commensal organisms. We...

  15. Functions and Signaling Pathways of Amino Acids in Intestinal Inflammation

    OpenAIRE

    Fang He; Chenlu Wu; Pan Li; Nengzhang Li; Dong Zhang; Quoqiang Zhu; Wenkai Ren; Yuanyi Peng

    2018-01-01

    Intestine is always exposed to external environment and intestinal microorganism; thus it is more sensitive to dysfunction and dysbiosis, leading to intestinal inflammation, such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and diarrhea. An increasing number of studies indicate that dietary amino acids play significant roles in preventing and treating intestinal inflammation. The review aims to summarize the functions and signaling mechanisms of amino acids in intestin...

  16. Thoracic surface temperature rhythms as circadian biomarkers for cancer chronotherapy

    Science.gov (United States)

    Roche, Véronique Pasquale; Mohamad-Djafari, Ali; Innominato, Pasquale Fabio; Karaboué, Abdoulaye; Gorbach, Alexander; Lévi, Francis Albert

    2014-01-01

    The disruption of the temperature circadian rhythm has been associated with cancer progression, while its amplification resulted in cancer inhibition in experimental tumor models. The current study investigated the relevance of skin surface temperature rhythms as biomarkers of the Circadian Timing System (CTS) in order to optimize chronotherapy timing in individual cancer patients. Baseline skin surface temperature at four sites and wrist accelerations were measured every minute for 4 days in 16 patients with metastatic gastro-intestinal cancer before chronotherapy administration. Temperature and rest-activity were recorded, respectively, with wireless skin surface temperature patches (Respironics, Phillips) and an actigraph (Ambulatory Monitoring). Both variables were further monitored in 10 of these patients during and after a 4-day course of a fixed chronotherapy protocol. Collected at baseline, during and after therapy longitudinal data sets were processed using Fast Fourier Transform Cosinor and Linear Discriminant Analyses methods. A circadian rhythm was statistically validated with a period of 24 h (p|0.7|; p<0.05). Individual circadian acrophases at baseline were scattered from 15:18 to 6:05 for skin surface temperature, and from 12:19 to 15:18 for rest-activity, with respective median values of 01:10 (25–75% quartiles, 22:35–3:07) and 14:12 (13:14–14:31). The circadian patterns in skin surface temperature and rest-activity persisted or were amplified during and after fixed chronotherapy delivery for 5/10 patients. In contrast, transient or sustained disruption of these biomarkers was found for the five other patients, as indicated by the lack of any statistically significant dominant period in the circadian range. No consistent correlation (r<|0.7|, p ≥ 0.05) was found between paired rest-activity and temperature time series during fixed chronotherapy delivery. In conclusion, large inter-patient differences in circadian amplitudes and acrophases of

  17. Intestinal perforation by an ingested foreign body

    Directory of Open Access Journals (Sweden)

    Gabriel Cleve Nicolodi

    Full Text Available Abstract Objective: To identify the computed tomography findings suggestive of intestinal perforation by an ingested foreign body. Materials and Methods: This was a retrospective study of four cases of surgically proven intestinal perforation by a foreign body, comparing the computed tomography findings with those described in the literature. Results: None of the patients reported having ingested a foreign body, all were over 60 years of age, three of the four patients used a dental prosthesis, and all of the foreign bodies were elongated and sharp. In all four patients, there were findings indicative of acute abdomen. None of the foreign bodies were identified on conventional X-rays. The computed tomography findings suggestive of perforation were thickening of the intestinal walls (in all four cases, increased density of mesenteric fat (in all four cases, identification of the foreign body passing through the intestinal wall (in three cases, and gas in the peritoneal cavity (in one case. Conclusion: In cases of foreign body ingestion, intestinal perforation is more common when the foreign body is elongated and sharp. Although patients typically do not report having ingested such foreign bodies, the scenario should be suspected in elderly individuals who use dental prostheses. A computed tomography scan can detect foreign bodies, locate perforations, and guide treatment. The findings that suggest perforation are thickening of the intestinal walls, increased mesenteric fat density, and, less frequently, gas in the peritoneal cavity, often restricted to the point of perforation.

  18. Intestinal perforation by an ingested foreign body*

    Science.gov (United States)

    Nicolodi, Gabriel Cleve; Trippia, Cesar Rodrigo; Caboclo, Maria Fernanda F. S.; de Castro, Francisco Gomes; Miller, Wagner Peitl; de Lima, Raphael Rodrigues; Tazima, Leandro; Geraldo, Jamylle

    2016-01-01

    Objective To identify the computed tomography findings suggestive of intestinal perforation by an ingested foreign body. Materials and Methods This was a retrospective study of four cases of surgically proven intestinal perforation by a foreign body, comparing the computed tomography findings with those described in the literature. Results None of the patients reported having ingested a foreign body, all were over 60 years of age, three of the four patients used a dental prosthesis, and all of the foreign bodies were elongated and sharp. In all four patients, there were findings indicative of acute abdomen. None of the foreign bodies were identified on conventional X-rays. The computed tomography findings suggestive of perforation were thickening of the intestinal walls (in all four cases), increased density of mesenteric fat (in all four cases), identification of the foreign body passing through the intestinal wall (in three cases), and gas in the peritoneal cavity (in one case). Conclusion In cases of foreign body ingestion, intestinal perforation is more common when the foreign body is elongated and sharp. Although patients typically do not report having ingested such foreign bodies, the scenario should be suspected in elderly individuals who use dental prostheses. A computed tomography scan can detect foreign bodies, locate perforations, and guide treatment. The findings that suggest perforation are thickening of the intestinal walls, increased mesenteric fat density, and, less frequently, gas in the peritoneal cavity, often restricted to the point of perforation. PMID:27818542

  19. Intestinal perforation by an ingested foreign body

    International Nuclear Information System (INIS)

    Nicolodi, Gabriel Cleve; Trippia, Cesar Rodrigo; Caboclo, Maria Fernanda F.S.; Castro, Francisco Gomes de; Miller, Wagner Peitl; Lima, Raphael Rodrigues de; Tazima, Leandro; Geraldo, Jamylle

    2016-01-01

    Objective: To identify the computed tomography findings suggestive of intestinal perforation by an ingested foreign body. Materials and Methods: This was a retrospective study of four cases of surgically proven intestinal perforation by a foreign body, comparing the computed tomography findings with those described in the literature. Results: None of the patients reported having ingested a foreign body, all were over 60 years of age, three of the four patients used a dental prosthesis, and all of the foreign bodies were elongated and sharp. In all four patients, there were findings indicative of acute abdomen. None of the foreign bodies were identified on conventional X-rays. The computed tomography findings suggestive of perforation were thickening of the intestinal walls (in all four cases), increased density of mesenteric fat (in all four cases), identification of the foreign body passing through the intestinal wall (in three cases), and gas in the peritoneal cavity (in one case). Conclusion: In cases of foreign body ingestion, intestinal perforation is more common when the foreign body is elongated and sharp. Although patients typically do not report having ingested such foreign bodies, the scenario should be suspected in elderly individuals who use dental prostheses. A computed tomography scan can detect foreign bodies, locate perforations, and guide treatment. The findings that suggest perforation are thickening of the intestinal walls, increased mesenteric fat density, and, less frequently, gas in the peritoneal cavity, often restricted to the point of perforation. (author)

  20. Intestinal perforation by an ingested foreign body.

    Science.gov (United States)

    Nicolodi, Gabriel Cleve; Trippia, Cesar Rodrigo; Caboclo, Maria Fernanda F S; de Castro, Francisco Gomes; Miller, Wagner Peitl; de Lima, Raphael Rodrigues; Tazima, Leandro; Geraldo, Jamylle

    2016-01-01

    To identify the computed tomography findings suggestive of intestinal perforation by an ingested foreign body. This was a retrospective study of four cases of surgically proven intestinal perforation by a foreign body, comparing the computed tomography findings with those described in the literature. None of the patients reported having ingested a foreign body, all were over 60 years of age, three of the four patients used a dental prosthesis, and all of the foreign bodies were elongated and sharp. In all four patients, there were findings indicative of acute abdomen. None of the foreign bodies were identified on conventional X-rays. The computed tomography findings suggestive of perforation were thickening of the intestinal walls (in all four cases), increased density of mesenteric fat (in all four cases), identification of the foreign body passing through the intestinal wall (in three cases), and gas in the peritoneal cavity (in one case). In cases of foreign body ingestion, intestinal perforation is more common when the foreign body is elongated and sharp. Although patients typically do not report having ingested such foreign bodies, the scenario should be suspected in elderly individuals who use dental prostheses. A computed tomography scan can detect foreign bodies, locate perforations, and guide treatment. The findings that suggest perforation are thickening of the intestinal walls, increased mesenteric fat density, and, less frequently, gas in the peritoneal cavity, often restricted to the point of perforation.

  1. 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.

  2. Intestinal perforation by an ingested foreign body

    Energy Technology Data Exchange (ETDEWEB)

    Nicolodi, Gabriel Cleve; Trippia, Cesar Rodrigo; Caboclo, Maria Fernanda F.S.; Castro, Francisco Gomes de; Miller, Wagner Peitl; Lima, Raphael Rodrigues de; Tazima, Leandro; Geraldo, Jamylle, E-mail: gabrielnicolodi@gmail.com [Hospital Sao Vicente - Funef, Curitiba, PR (Brazil)

    2016-09-15

    Objective: To identify the computed tomography findings suggestive of intestinal perforation by an ingested foreign body. Materials and Methods: This was a retrospective study of four cases of surgically proven intestinal perforation by a foreign body, comparing the computed tomography findings with those described in the literature. Results: None of the patients reported having ingested a foreign body, all were over 60 years of age, three of the four patients used a dental prosthesis, and all of the foreign bodies were elongated and sharp. In all four patients, there were findings indicative of acute abdomen. None of the foreign bodies were identified on conventional X-rays. The computed tomography findings suggestive of perforation were thickening of the intestinal walls (in all four cases), increased density of mesenteric fat (in all four cases), identification of the foreign body passing through the intestinal wall (in three cases), and gas in the peritoneal cavity (in one case). Conclusion: In cases of foreign body ingestion, intestinal perforation is more common when the foreign body is elongated and sharp. Although patients typically do not report having ingested such foreign bodies, the scenario should be suspected in elderly individuals who use dental prostheses. A computed tomography scan can detect foreign bodies, locate perforations, and guide treatment. The findings that suggest perforation are thickening of the intestinal walls, increased mesenteric fat density, and, less frequently, gas in the peritoneal cavity, often restricted to the point of perforation. (author)

  3. The intestinal microbiome of fish under starvation.

    Science.gov (United States)

    Xia, Jun Hong; Lin, Grace; Fu, Gui Hong; Wan, Zi Yi; Lee, May; Wang, Le; Liu, Xiao Jun; Yue, Gen Hua

    2014-04-05

    Starvation not only affects the nutritional and health status of the animals, but also the microbial composition in the host's intestine. Next-generation sequencing provides a unique opportunity to explore gut microbial communities and their interactions with hosts. However, studies on gut microbiomes have been conducted predominantly in humans and land animals. Not much is known on gut microbiomes of aquatic animals and their changes under changing environmental conditions. To address this shortcoming, we determined the microbial gene catalogue, and investigated changes in the microbial composition and host-microbe interactions in the intestine of Asian seabass in response to starvation. We found 33 phyla, 66 classes, 130 orders and 278 families in the intestinal microbiome. Proteobacteria (48.8%), Firmicutes (15.3%) and Bacteroidetes (8.2%) were the three most abundant bacteria taxa. Comparative analyses of the microbiome revealed shifts in bacteria communities, with dramatic enrichment of Bacteroidetes, but significant depletion of Betaproteobacteria in starved intestines. In addition, significant differences in clusters of orthologous groups (COG) functional categories and orthologous groups were observed. Genes related to antibiotic activity in the microbiome were significantly enriched in response to starvation, and host genes related to the immune response were generally up-regulated. This study provides the first insights into the fish intestinal microbiome and its changes under starvation. Further detailed study on interactions between intestinal microbiomes and hosts under dynamic conditions will shed new light on how the hosts and microbes respond to the changing environment.

  4. Genomic Biomarkers for Breast Cancer Risk

    Science.gov (United States)

    Walsh, Michael F.; Nathanson, Katherine L.; Couch, Fergus J.

    2016-01-01

    Clinical risk assessment for cancer predisposition includes a three-generation pedigree and physical examination to identify inherited syndromes. Additionally genetic and genomic biomarkers may identify individuals with a constitutional basis for their disease that may not be evident clinically. Genomic biomarker testing may detect molecular variations in single genes, panels of genes, or entire genomes. The strength of evidence for the association of a genomic biomarker with disease risk may be weak or strong. The factors contributing to clinical validity and utility of genomic biomarkers include functional laboratory analyses and genetic epidemiologic evidence. Genomic biomarkers may be further classified as low, moderate or highly penetrant based on the likelihood of disease. Genomic biomarkers for breast cancer are comprised of rare highly penetrant mutations of genes such as BRCA1 or BRCA2, moderately penetrant mutations of genes such as CHEK2, as well as more common genomic variants, including single nucleotide polymorphisms, associated with modest effect sizes. When applied in the context of appropriate counseling and interpretation, identification of genomic biomarkers of inherited risk for breast cancer may decrease morbidity and mortality, allow for definitive prevention through assisted reproduction, and serve as a guide to targeted therapy. PMID:26987529

  5. Predicting Clinical Outcomes Using Molecular Biomarkers

    Directory of Open Access Journals (Sweden)

    Harry B. Burke

    2016-01-01

    Full Text Available Over the past 20 years, there has been an exponential increase in the number of biomarkers. At the last count, there were 768,259 papers indexed in PubMed.gov directly related to biomarkers. Although many of these papers claim to report clinically useful molecular biomarkers, embarrassingly few are currently in clinical use. It is suggested that a failure to properly understand, clinically assess, and utilize molecular biomarkers has prevented their widespread adoption in treatment, in comparative benefit analyses, and their integration into individualized patient outcome predictions for clinical decision-making and therapy. A straightforward, general approach to understanding how to predict clinical outcomes using risk, diagnostic, and prognostic molecular biomarkers is presented. In the future, molecular biomarkers will drive advances in risk, diagnosis, and prognosis, they will be the targets of powerful molecular therapies, and they will individualize and optimize therapy. Furthermore, clinical predictions based on molecular biomarkers will be displayed on the clinician's screen during the physician–patient interaction, they will be an integral part of physician–patient-shared decision-making, and they will improve clinical care and patient outcomes.

  6. Fecal markers of intestinal inflammation and intestinal permeability are elevated in Parkinson's disease.

    Science.gov (United States)

    Schwiertz, Andreas; Spiegel, Jörg; Dillmann, Ulrich; Grundmann, David; Bürmann, Jan; Faßbender, Klaus; Schäfer, Karl-Herbert; Unger, Marcus M

    2018-02-12

    Intestinal inflammation and increased intestinal permeability (both possibly fueled by dysbiosis) have been suggested to be implicated in the multifactorial pathogenesis of Parkinson's disease (PD). The objective of the current study was to investigate whether fecal markers of inflammation and impaired intestinal barrier function corroborate this pathogenic aspect of PD. In a case-control study, we quantitatively analyzed established fecal markers of intestinal inflammation (calprotectin and lactoferrin) and fecal markers of intestinal permeability (alpha-1-antitrypsin and zonulin) in PD patients (n = 34) and controls (n = 28, group-matched for age) by enzyme-linked immunosorbent assay. The study design controlled for potential confounding factors. Calprotectin, a fecal marker of intestinal inflammation, and two fecal markers of increased intestinal permeability (alpha-1-antitrypsin and zonulin) were significantly elevated in PD patients compared to age-matched controls. Lactoferrin, as a second fecal marker of intestinal inflammation, showed a non-significant trend towards elevated concentrations in PD patients. None of the four fecal markers correlated with disease severity, PD subtype, dopaminergic therapy, or presence of constipation. Fecal markers reflecting intestinal inflammation and increased intestinal permeability have been primarily investigated in inflammatory bowel disease so far. Our data indicate that calprotectin, alpha-1-antitrypsin and zonulin could be useful non-invasive markers in PD as well. Even though these markers are not disease-specific, they corroborate the hypothesis of an intestinal inflammation as contributing factor in the pathogenesis of PD. Further investigations are needed to determine whether calprotectin, alpha-1-antitrypsin and zonulin can be used to define PD subgroups and to monitor the effect of interventions in PD. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Biomarkers in DILI: one more step forward

    Directory of Open Access Journals (Sweden)

    Mercedes Robles-Díaz

    2016-08-01

    Full Text Available Despite being relatively rare, drug-induced liver injury (DILI is a serious condition, both for the individual patient due to the risk of acute liver failure, and for the drug development industry and regulatory agencies due to associations with drug development attritions, black box warnings and postmarketing withdrawals. A major limitation in DILI diagnosis and prediction is the current lack of specific biomarkers. Despite refined usage of traditional liver biomarkers in DILI, reliable disease outcome predictions are still difficult to make. These limitations have driven the growing interest in developing new more sensitive and specific DILI biomarkers, which can improve early DILI prediction, diagnosis and course of action. Several promising DILI biomarker candidates have been discovered to date, including mechanistic-based biomarker candidates such as glutamate dehydrogenase, high-mobility group box 1 protein and keratin-18, which can also provide information on the injury mechanism of different causative agents. Furthermore, microRNAs have received much attention lately as potential non-invasive DILI biomarker candidates, in particular miR-122. Advances in omics technologies offer a new approach for biomarker exploration studies. The ability to screen a large number of molecules (for example metabolites, proteins or DNA simultaneously enables the identification of ‘toxicity signatures’, which may be used to enhance preclinical safety assessments and disease diagnostics. Omics-based studies can also provide information on the underlying mechanisms of distinct forms of DILI that may further facilitate the identification of early diagnostic biomarkers and safer implementation of personalized medicine. In this review we summarize recent advances in the area of DILI biomarker studies.

  8. Cardiac Biomarkers and Cycling Race

    Directory of Open Access Journals (Sweden)

    Caroline Le Goff, Jean-François Kaux, Sébastien Goffaux, Etienne Cavalier

    2015-06-01

    Full Text Available In cycling as in other types of strenuous exercise, there exists a risk of sudden death. It is important both to understand its causes and to see if the behavior of certain biomarkers might highlight athletes at risk. Many reports describe changes in biomarkers after strenuous exercise (Nie et al., 2011, but interpreting these changes, and notably distinguishing normal physiological responses from pathological changes, is not easy. Here we have focused on the kinetics of different cardiac biomarkers: creatin kinase (CK, creating kinase midbrain (CK-MB, myoglobin (MYO, highly sensitive troponin T (hs-TnT and N-terminal brain natriuretic peptide (NT-proBNP. The population studied was a group of young trained cyclists participating in a 177-km cycling race. The group of individuals was selected for maximal homogeneity. Their annual training volume was between 10,000 and 16,000 kilometers. The rhythm of races is comparable and averages 35 km/h, depending on the race’s difficulty. The cardiac frequency was recorded via a heart rate monitor. Three blood tests were taken. The first blood test, T0, was taken approximately 2 hours before the start of the race and was intended to gather values which would act as references for the following tests. The second blood test, T1, was realized within 5 minutes of their arrival. The third and final blood test, T3, was taken 3 hours following their arrival. The CK, CK-MB, MYO, hs-TnT and NT-proBNP were measured on the Roche Diagnostic modular E (Manhein, Germany. For the statistical analysis, an ANOVA and post hoc test of Scheffé were calculated with the Statistica Software version 9.1. We noticed an important significant variation in the cardiac frequency between T0 and T1 (p < 0.0001, T0 and T3 (p < 0.0001, and T1 and T3 (p < 0.01. Table 1 shows the results obtained for the different biomarkers. CK and CK-MB showed significant variation between T0-T1 and T0-T3 (p < 0.0001. Myoglobin increased significantly

  9. Rapid biosensing tools for cancer biomarkers.

    Science.gov (United States)

    Ranjan, Rajeev; Esimbekova, Elena N; Kratasyuk, Valentina A

    2017-01-15

    The present review critically discusses the latest developments in the field of smart diagnostic systems for cancer biomarkers. A wide coverage of recent biosensing approaches involving aptamers, enzymes, DNA probes, fluorescent probes, interacting proteins and antibodies in vicinity to transducers such as electrochemical, optical and piezoelectric is presented. Recent advanced developments in biosensing approaches for cancer biomarker owes much credit to functionalized nanomaterials due to their unique opto-electronic properties and enhanced surface to volume ratio. Biosensing methods for a plenty of cancer biomarkers has been summarized emphasizing the key principles involved. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Biomarkers of Lung Injury in Cardiothoracic Surgery

    Science.gov (United States)

    Engels, Gerwin Erik; van Oeveren, Willem

    2015-01-01

    Diagnosis of pulmonary dysfunction is currently almost entirely based on a vast series of physiological changes, but comprehensive research is focused on determining biomarkers for early diagnosis of pulmonary dysfunction. Here we discuss the use of biomarkers of lung injury in cardiothoracic surgery and their ability to detect subtle pulmonary dysfunction in the perioperative period. Degranulation products of neutrophils are often used as biomarker since they have detrimental effects on the pulmonary tissue by themselves. However, these substances are not lung specific. Lung epithelium specific proteins offer more specificity and slowly find their way into clinical studies. PMID:25866435

  11. Molecular aspects of intestinal calcium absorption.

    Science.gov (United States)

    Diaz de Barboza, Gabriela; Guizzardi, Solange; Tolosa de Talamoni, Nori

    2015-06-21

    Intestinal Ca(2+) absorption is a crucial physiological process for maintaining bone mineralization and Ca(2+) homeostasis. It occurs through the transcellular and paracellular pathways. The first route comprises 3 steps: the entrance of Ca(2+) across the brush border membranes (BBM) of enterocytes through epithelial Ca(2+) channels TRPV6, TRPV5, and Cav1.3; Ca(2+) movement from the BBM to the basolateral membranes by binding proteins with high Ca(2+) affinity (such as CB9k); and Ca(2+) extrusion into the blood. Plasma membrane Ca(2+) ATPase (PMCA1b) and sodium calcium exchanger (NCX1) are mainly involved in the exit of Ca(2+) from enterocytes. A novel molecule, the 4.1R protein, seems to be a partner of PMCA1b, since both molecules co-localize and interact. The paracellular pathway consists of Ca(2+) transport through transmembrane proteins of tight junction structures, such as claudins 2, 12, and 15. There is evidence of crosstalk between the transcellular and paracellular pathways in intestinal Ca(2+) transport. When intestinal oxidative stress is triggered, there is a decrease in the expression of several molecules of both pathways that inhibit intestinal Ca(2+) absorption. Normalization of redox status in the intestine with drugs such as quercetin, ursodeoxycholic acid, or melatonin return intestinal Ca(2+) transport to control values. Calcitriol [1,25(OH)₂D₃] is the major controlling hormone of intestinal Ca(2+) transport. It increases the gene and protein expression of most of the molecules involved in both pathways. PTH, thyroid hormones, estrogens, prolactin, growth hormone, and glucocorticoids apparently also regulate Ca(2+) transport by direct action, indirect mechanism mediated by the increase of renal 1,25(OH)₂D₃ production, or both. Different physiological conditions, such as growth, pregnancy, lactation, and aging, adjust intestinal Ca(2+) absorption according to Ca(2+) demands. Better knowledge of the molecular details of intestinal Ca(2

  12. Intestinal ischemia-reperfusion injury augments intestinal mucosal injury and bacterial translocation in jaundiced rats.

    Science.gov (United States)

    Yüksek, Yunus Nadi; Kologlu, Murat; Daglar, Gül; Doganay, Mutlu; Dolapci, Istar; Bilgihan, Ayse; Dolapçi, Mete; Kama, Nuri Aydin

    2004-01-01

    The aim of this study was to evaluate local effects and degree of bacterial translocation related with intestinal ischemia-reperfusion injury in a rat obstructive jaundice model. Thirty adult Sprague-Dawley rats (200-250 g) were divided into three groups; including Group 1 (jaundice group), Group 2 (jaundice-ischemia group) and Group 3 (ischemia group). All rats had 2 laparotomies. After experimental interventions, tissue samples for translocation; liver and ileum samples for histopathological examination, 25 cm of small intestine for mucosal myeloperoxidase and malondialdehyde levels and blood samples for biochemical analysis were obtained. Jaundiced rats had increased liver enzyme levels and total and direct bilirubin levels (p<0.05). Intestinal mucosal myeloperoxidase and malondialdehyde levels were found to be high in intestinal ischemia-reperfusion groups (p<0.05). Intestinal mucosal damage was more severe in rats with intestinal ischemia-reperfusion after bile duct ligation (p<0.05). Degree of bacterial translocation was also found to be significantly high in these rats (p<0.05). Intestinal mucosa is disturbed more severely in obstructive jaundice with the development of ischemia and reperfusion. Development of intestinal ischemia-reperfusion in obstructive jaundice increases bacterial translocation.

  13. Plasma intestinal fatty acid binding protein (I-FABP) concentrations increase following intestinal ischemia in pigs

    NARCIS (Netherlands)

    Niewold, T.A.; Meinen, M.; Meulen, van der J.

    2004-01-01

    Intestinal fatty acid binding protein (I-FABP) is an intracellular epithelial protein in the intestinal mucosa of many animals. IFABP appears in the circulation following epithelial damage, and in humans, is proven to be a parameter for damage to the mucosa. In this paper, an ELISA test designed for

  14. Intestinal rehabilitation for children with intestinal failure is cost-effective : a simulation study

    NARCIS (Netherlands)

    Groen, Henk; Neelis, Esther G; Poley, Marten J; Olieman, Joanne F; Scheenstra, René; Krabbe, Paul Fm; Dijkstra, Gerard; Rings, Edmond Hhm

    2017-01-01

    BACKGROUND: Children with intestinal failure (IF) depend on parenteral nutrition (PN). The goal in the treatment of IF is to wean children off PN through intestinal rehabilitation (IR). Although the healthcare burden of IF is enormous, to our knowledge there has been no previous cost-effectiveness

  15. Intestinal rehabilitation for children with intestinal failure is cost-effective : a simulation study

    NARCIS (Netherlands)

    Groen, Henk; Neelis, Esther G.; Poley, Marten J.; Olieman, Joanne F.; Scheenstra, Rene; Krabbe, Paul F. M.; Dijkstra, Gerard; Rings, Edmond H. H. M.

    Background: Children with intestinal failure (IF) depend on parenteral nutrition (PN). The goal in the treatment of IF is to wean children off PN through intestinal rehabilitation (IR). Although the healthcare burden of IF is enormous, to our knowledge there has been no previous cost-effectiveness

  16. [Myosin B ATPase activity of the intestinal smooth muscle in intestinal obstruction].

    Science.gov (United States)

    Takamatsu, H

    1983-06-01

    Intestinal smooth myosin B was prepared from muscle layers around the lesion in dogs with experimental colonic stenosis and in patients with congenital intestinal obstruction. Mg2+-ATPase activity of the myosin B was compared between the proximal dilated segment and distal segment to obstruction. Experimental colonic stenosis: In early period after surgery, proximal colons showed higher activity of myosin B ATPase than distal colons, decreasing to less than distal colon as time passed. Congenital intestinal obstruction: In three cases, whose atresia might have occurred at earlier period of gestation, proximal bowels showed less activity of myosin B ATPase than distal bowels. However, in two cases, whose atresia might have occurred at later period of gestation, and two cases with intestinal stenosis, proximal bowels indicated higher activity of myosin B ATPase than distal bowels. These data suggested that the contractibility of the proximal intestine was depending on the duration of obstruction, and it was depressed in the former patients and was accelerated in the latter patients. These results suggested that the extensive resection of dilated proximal bowel in the congenital atresia is not always necessary to obtain good postoperative intestinal dynamics at the operation of the atresial lesions which may be induced at later period of gestation. They also suggested that surgery for intestinal obstruction should be performed before the depression of intestinal contractibility to get good bowel function.

  17. Molecular characterization of the intestinal microbiota in patients with and without abdominal bloating.

    Science.gov (United States)

    Ringel-Kulka, Tamar; Benson, Andrew K; Carroll, Ian M; Kim, Jaehyoung; Legge, Ryan M; Ringel, Yehuda

    2016-03-15

    Recent studies have demonstrated differences in the intestinal microbiota between patients with irritable bowel syndrome (IBS) and healthy controls (HC), suggesting a role for the intestinal microbiota in the pathogenesis of IBS. Alterations in the microbiota have also been implicated in the pathogenesis of abdominal bloating, a commonly reported symptom in IBS. We investigated the relationship between the intestinal microbiota, abdominal bloating, and altered bowel patterns in a cohort of patients with IBS and HC. The 16S rRNA gene from fresh fecal samples was amplified and pyrosequenced by using Roche-454 Titanium chemistry. A Core Measurable Microbiome (CMM) was generated for Operational Taxonomic Unit (OTU) detected in >75% of all samples and compositional features of CMM were compared between groups by Linear Discriminant Analysis (LDA). IBS differentiated from HC by LDA using continuous variation in the species/OTUs or the CMM genera. When subcategorized based on bloating symptoms and bowel characteristics, the same subjects were also well differentiated from one another and from HC. ANOVA analysis showed quantitative species/OTU differences between the subgroups including IBS with and without bloating, and subtypes based on bowel characteristics. The clear LDA differentiation and the significant microbial taxa differences between the groups imply a significant association of the microbiota with bloating symptoms and bowel characteristics in IBS. These changes in the microbiota may serve as a biomarker for IBS and its clinical subtypes and suggest a role for the intestinal microbiota in the pathogenesis of the main symptoms of the disorder. Copyright © 2016 the American Physiological Society.

  18. Markers of intestinal injury are associated with endotoxemia in successfully resuscitated patients.

    Science.gov (United States)

    Grimaldi, D; Guivarch, E; Neveux, N; Fichet, J; Pène, F; Marx, J-S; Chiche, J-D; Cynober, L; Mira, J-P; Cariou, A

    2013-01-01

    Gut dysfunction is suspected to play a major role in the pathophysiology of post-resuscitation disease through an increase in intestinal permeability and endotoxin release. However this dysfunction often remains occult and is poorly investigated. The aim of this pilot study was to explore intestinal failure biomarkers in post-cardiac arrest patients and to correlate them with endotoxemia. Following resuscitation after cardiac arrest, 21 patients were prospectively studied. Urinary intestinal fatty acid-binding protein (IFABP), which marks intestinal permeability, plasma citrulline, which reflects the functional enterocyte mass, and whole blood endotoxin were measured at admission, days 1-3 and 6. We explored the kinetics of release and the relationship between IFABP, citrulline and endotoxin values. IFABP was extremely high at admission and normalized at D3 (6668 pg/mL vs 39 pg/mL, p=0.01). Lowest median of citrulline (N=20-40 μmol/L) was attained at D2 (11 μmol/L at D2 vs 24 μmol/L at admission, p=0.01) and tended to normalize at D6 (21 μmol/L). During ICU stay, 86% of patients presented a detectable endotoxemia. Highest endotoxin level was positively correlated with highest IFABP level (R(2)=0.31, p=0.01) and was inversely correlated with lowest plasma citrulline levels (R(2)=0.55, pintestinal injury are altered after cardiac arrest and are associated with endotoxemia. This could worsen post-resuscitation shock and organ failure. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  19. Boswellia serrata Preserves Intestinal Epithelial Barrier from Oxidative and Inflammatory Damage.

    Directory of Open Access Journals (Sweden)

    Daniela Catanzaro

    Full Text Available Aminosalicylates, corticosteroids and immunosuppressants are currently the therapeutic choices in inflammatory bowel diseases (IBD, however, with limited remission and often serious side effects. Meanwhile complementary and alternative medicine (CAM use is increasing, particularly herbal medicine. Boswellia serrata is a traditional Ayurvedic remedy with anti-inflammatory properties, of interest for its usefulness in IBDs. The mechanism of this pharmacological potential of Boswellia serrata was investigated in colonic epithelial cell monolayers exposed to H2O2 or INF-γ+TNF-α, chosen as in vitro experimental model of intestinal inflammation. The barrier function was evaluated by the transepithelial electrical resistance (TEER and paracellular permeability assay, and by the tight junction proteins (zonula occludens-1, ZO-1 and occludin immunofluorescence. The expression of phosphorylated NF-κB and reactive oxygen species (ROS generation were determined by immunoblot and cytofluorimetric assay, respectively. Boswellia serrata oleo-gum extract (BSE and its pure derivative acetyl-11-keto-β-boswellic acid (AKBA, were tested at 0.1-10 μg/ml and 0.027 μg/ml, respectively. BSE and AKBA safety was demonstrated by no alteration of intestinal cell viability and barrier function and integrity biomarkers. H2O2 or INF-γ+TNF-α treatment of Caco-2 cell monolayers significantly reduced TEER, increased paracellular permeability and caused the disassembly of tight junction proteins occludin and ZO-1. BSE and AKBA pretreatment significantly prevented functional and morphological alterations and also the NF-κB phosphorylation induced by the inflammatory stimuli. At the same concentrations BSE and AKBA counteracted the increase of ROS caused by H2O2 exposure. Data showed the positive correlation of the antioxidant activity with the mechanism involved in the physiologic maintenance of the integrity and function of the intestinal epithelium. This study

  20. Coagulation of sheep intestinal and prefemoral lymph.

    Science.gov (United States)

    Hanley, C A; Johnston, M G; Nelson, W

    1988-06-01

    We have determined the most suitable method for the automated analysis of the clotting parameters in sheep intestinal and prefemoral lymph as defined by the Activated Partial Thromboplastin Times (APTT; measure of intrinsic coagulation pathway) and the Prothrombin Times (PT; measure of extrinsic coagulation pathway). As opposed to optical density systems, the use of a Fibro-System Fibrometer was found to provide the most consistent assessment of coagulation with the endpoint being the time to fibrin strand formation. We measured APTT in sheep intestinal and prefemoral lymph of 59.78 +/- 7.69 seconds and 51.03 +/- 10.49 seconds respectively. These values were more prolonged than those obtained from sheep blood plasma but only in the case of intestinal lymph were the differences significant (p less than 0.025). Human blood APTT values were significantly less than both sheep blood (p less than 0.05) and sheep intestinal (p less than 0.001) and prefemoral lymph (p less than 0.01). PT values were found to be 21.56 +/- 1.14 seconds in intestinal and 22.00 +/- 1.88 seconds in prefemoral lymph. These values were also significantly greater than those obtained from sheep blood (both p less than 0.001). Human blood PTs were significantly less than both sheep blood (p less than 0.001) and intestinal and prefemoral lymph (both p less than 0.001). Measurement of APTT and PT values in intestinal lymph and PT determinations in prefemoral lymph were not affected by storage in the refrigerator or freezer. There was some indication that APTT values in prefemoral samples were susceptible to storage artifacts; however, the differences in coagulation times were not significant.

  1. Neonatal intestinal obstruction in Benin, Nigeria

    Directory of Open Access Journals (Sweden)

    Osifo Osarumwense

    2009-01-01

    Full Text Available Background: Intestinal obstruction is a life threatening condition in the newborn, with attendant high mortality rate especially in underserved subregion. This study reports the aetiology, presentation, and outcome of intestinal obstruction management in neonates. Materials and Methods: A prospective study of neonatal intestinal obstruction at the University of Benin Teaching Hospital, Benin, Nigeria, between January 2006-June 2008. Data were collated on a structured proforma and analysed for age, sex, weight, presentation, type/date of gestation/delivery, aetiology, clinical presentation, associated anomaly, treatment, and outcome. Results: There were 71 neonates, 52 were males and 19 were females (2.7:1. Their age range was between 12 hours and 28 days (mean, 7.9 ± 2.7 days and they weighed between 1.8 and 5.2 kg (average, 3.2 kg. The causes of intestinal obstruction were: Anorectal anomaly, 28 (39.4%; Hirschsprung′s disease, 8 (11.3%′ prematurity, 3 (4.2%; meconeum plug, 2 (2.8%; malrotation, 6 (8.5%; intestinal atresia, 8 (11.3%; necrotising enterocolitis (NEC, 4 (5.6%; obstructed hernia, 4 (5.6%; and spontaneous gut perforation, 3 (4.2%. Also, 27 (38% children had colostomy, 24 (33.8% had laparotomy, 9 (12.8% had anoplasty, while 11 (15.4% were managed nonoperatively. A total of 41 (57.7% neonates required incubator, 26 (36.6% needed total parenteral nutrition, while 15 (21.1% require d paediatric ventilator. Financial constraint, late presentation, presence of multiple anomalies, aspiration, sepsis, gut perforation, and bowel gangrene were the main contributors to death. Neonates with lower obstructions had a better outcome compared to those having upper intestinal obstruction ( P < 0.0001. Conclusion: Outcomes of intestinal obstruction are still poor in our setting; late presentation, financial constraints, poor parental motivation and lack of basic facilities were the major determinants of mortality.

  2. CT evaluation of mechanical intestinal obstruction

    Energy Technology Data Exchange (ETDEWEB)

    Han, Sung Tag; Kim, Ho Kyun; Jeon, Jeong Dong; Kim, Young Tong [Gollege of Medicine, Inje University, Seoul (Korea, Republic of)

    1994-11-15

    To evaluate the usefulness of CT for the diagnosis and treatment planning of mechanical intestinal obstruction. We retrospectively reviewed 38 patients who were clinically suspected of mechanical intestinal obstruction and had undergone abdominal CT. The CT scans were evaluated for the absence or presence, severity, cause and site of intestinal obstruction. CT findings were compared with the results of laparotomy, barium study and clinical course. The absence or presence and severity of intestinal obstruction were classified into no obstruction, partial obstruction, complete obstruction. Diagnosis was established by means of laparotomy in 20 cases, barium study in 9 cases and clinical course in 9 cases. Of 38 cases, 7(18.4%) showed no obstruction, 22(57.9%) showed partial obstruction, and 9(23.7%) showed complete obstruction. The presence or absence and severity on CT scans were correctly predicted in 36 of 38 cases (sensitivity 95 %, specificity 97 %, accuracy 96 %) (in case of no obstruction: sensitivity 100 %, specificity 94%, accuracy 95%; in case of partial obstruction : sensitivity 91%, specificity 100%, accuracy 95%; in case of complete obstruction : sensitivity 100%, specificity 100%, accuracy 100%). All 9 cases with complete obstruction underwent prompt and immediate laparotomy. 13 cases, excluding those with mass around the site of transition and adhesion with strangulation, with partial obstruction improved with conservative treatment without laparotomy. The causes of obstruction were adhesion in 13, hernia in 6, primary cancer in 5, metastatic cancer in 3, abscess in 2, intestinal tbc in 1, and Crohn's disease in 1. The cause of obstruction on CT scans were correctly predicted in 27 of 31 cases (87.1 %). The sites of obstruction on CT scans were correctly predicted in 22 of 26 cases (84.6%). CT is valuable in the evaluation of absence or presence, severity, cause and site of intestinal obstruction, and is considered to be helpful in treatment

  3. Integrative assessment of biomarker responses in teleostean fishes exposed to glyphosate-based herbicide (Excel Mera 71

    Directory of Open Access Journals (Sweden)

    Sukhendu Dey

    2016-12-01

    Full Text Available Present study deals with the effects of glyphosate-based herbicide, Excel Mera 71 on Anabas testudineus, Heteropnestes fossilis and Oreochromis niloticus in field conditions (1.85 kg/ha based on anti-oxidative, metabolic and digestive responses. For this study following biomarkers viz., acetylcholinesterase (AChE, lipid peroxidation (LPO, catalase (CAT, glutathione-S-transferase (GST, alkaline phosphatase (ALP, aspartate aminotransferase (AST, alanine aminotransferase (ALT, amylase, lipase and protease were investigated in gill, stomach, intestine, liver, kidney, brain, muscle and spinal cord of the concerned fish species. Enzyme activities were significantly altered by glyphosate exposure after 30 days, these activities were tissue as well as species specific. The results suggested that these biomarkers could be used to assess the ecological risks of glyphosate on fish. Bioaccumulation factor (BAF studied in different aquatic natural macrophytes showed order of Alternanthera philoxeroides > Azolla pinnata > Lemna sp. (Minor > Lemna sp. (Major > Pistia stratiotes, while transfer factor (TF showed the order of Pistia stratiotes > Alternanthera philoxeroides > Lemna sp. Bioconcentration factor (BCF study showed maximum accumulation of glyphosate in liver, kidney or intestine, and minimum either in bone or stomach irrespective of fish species. An integrated biomarker response (IBR, which uses a battery of biomarkers to calculate the standardized scores for each biomarker responses ranging from physiological to biochemical/molecular responses, was evaluated by combining the multiple biomarkers into a single value to evaluate quantitatively the toxicological effects of glyphosate. In general, the multiple indices exhibited variations and A. testudineus was more affected than other fish species; maximum IBR value was observed for LPO and minimum in case of ALT. The order of integrated biomarkers caused by glyphosate treatment was

  4. Have biomarkers made their mark? A brief review of dental biomarkers

    Directory of Open Access Journals (Sweden)

    Mohammed Kaleem Sultan

    2014-01-01

    Full Text Available Biomarkers are substances that are released into the human body by tumor cells or by other cells in response to tumor. A high level of a tumor marker is considered a sign of certain cancer, which makes biomarker the subject of many testing methods for the diagnosis of cancers. In recent times, these biomarkers have been successfully isolated to diagnose dental-related tumors, benign and malignant conditions. This article is a brief review of literature for various biomarkers used in the field of dentistry.

  5. Relationship between Testosterone, Oxidative Stress Biomarkers ...

    African Journals Online (AJOL)

    Hypogonadism attributable to males with metabolic syndrome was also observed in automechanics occupationally exposed to mixed chemicals accompanied by oxidative stress (OS). We evaluated associations among testosterone, OS biomarkers, enzymatic and non-enzymatic antioxidants in normal weight ...

  6. The development and applications of biomarkers

    International Nuclear Information System (INIS)

    Normandy, J.; Peeters, J.

    1994-01-01

    This report is a compilation of submitted abstracts of scientific papers presented at the second Department of Energy-supported workshop on the use and applications of biomarkers held in Santa Fe, New Mexico, from April 26--29, 1994. The abstracts present a synopsis of the latest scientific developments in biomarker research and how these developments meet with the practical needs of the occupational physician as well as the industrial hygienist and the health physicist. In addition to considering the practical applications and potential benefits of this promising technology, the potential ethical and legal ramifications of using biomarkers to monitor workers are discussed. The abstracts further present insights on the present benefits that can be derived from using biomarkers as well as a perspective on what further research is required to fully meet the needs of the medical community

  7. The development and applications of biomarkers

    Energy Technology Data Exchange (ETDEWEB)

    Normandy, J.; Peeters, J. [eds.

    1994-04-15

    This report is a compilation of submitted abstracts of scientific papers presented at the second Department of Energy-supported workshop on the use and applications of biomarkers held in Santa Fe, New Mexico, from April 26--29, 1994. The abstracts present a synopsis of the latest scientific developments in biomarker research and how these developments meet with the practical needs of the occupational physician as well as the industrial hygienist and the health physicist. In addition to considering the practical applications and potential benefits of this promising technology, the potential ethical and legal ramifications of using biomarkers to monitor workers are discussed. The abstracts further present insights on the present benefits that can be derived from using biomarkers as well as a perspective on what further research is required to fully meet the needs of the medical community.

  8. Dietary and health biomarkers - time for an update

    DEFF Research Database (Denmark)

    Dragsted, Lars Ove; Gao, Qian; Pratico, Giulia

    2017-01-01

    for these biomarker classes, and no recent systematic review of all proposed biomarkers for food intake. While advanced databases exist for the human and food metabolomes, additional tools are needed to curate and evaluate current data on dietary and health biomarkers. The Food Biomarkers Alliance (FoodBAll) under......In the dietary and health research area, biomarkers are extensively used for multiple purposes. These include biomarkers of dietary intake and nutrient status, biomarkers used to measure the biological effects of specific dietary components, and biomarkers to assess the effects of diet on health....... The implementation of biomarkers in nutritional research will be important to improve measurements of dietary intake, exposure to specific dietary components, and of compliance to dietary interventions. Biomarkers could also help with improved characterization of nutritional status in study volunteers and to provide...

  9. 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.

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

    Science.gov (United States)

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

    2015-10-12

    Short bowel syndrome (SBS) is characterized by poor nutrient absorption due to a deficit of healthy intestine. Current treatment practices rely on providing supportive medical therapy with parenteral nutrition; while life saving, such interventions are not curative and are still associated with significant co-morbidities. As approaches to lengthen remaining intestinal tissue have been met with only limited success and intestinal transplants have poor survival outcomes, new approaches to treating SBS are necessary. Human intestine derived from embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs), called human intestinal organoids (HIOs), have the potential to offer a personalized and scalable source of intestine for regenerative therapies. However, given that HIOs are small three-dimensional structures grown in vitro, methods to generate usable HIO-derived constructs are needed. We investigated the ability of hESCs or HIOs to populate acellular porcine intestinal matrices and artificial polyglycolic/poly L lactic acid (PGA/PLLA) scaffolds, and examined the ability of matrix/scaffolds to thrive when transplanted in vivo. Our results demonstrate that the acellular matrix alone is not sufficient to instruct hESC differentiation towards an endodermal or intestinal fate. We observed that while HIOs reseed acellular porcine matrices in vitro, the HIO-reseeded matrices do not thrive when transplanted in vivo. In contrast, HIO-seeded PGA/PLLA scaffolds thrive in vivo and develop into tissue that looks nearly identical to adult human intestinal tissue. Our results suggest that HIO-seeded PGA/PLLA scaffolds are a promising avenue for developing the mucosal component of tissue engineered human small intestine, which need to be explored further to develop them into fully functional tissue. © 2015. Published by The Company of Biologists Ltd.

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

    Directory of Open Access Journals (Sweden)

    Stacy R. Finkbeiner

    2015-11-01

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

  12. Intestinal Leiomyositis: A Cause of Chronic Intestinal Pseudo-Obstruction in 6 Dogs.

    Science.gov (United States)

    Zacuto, A C; Pesavento, P A; Hill, S; McAlister, A; Rosenthal, K; Cherbinsky, O; Marks, S L

    2016-01-01

    Intestinal leiomyositis is a suspected autoimmune disorder affecting the muscularis propria layer of the gastrointestinal tract and is a cause of chronic intestinal pseudo-obstruction in humans and animals. To characterize the clinical presentation, histopathologic features, and outcome of dogs with intestinal leiomyositis in an effort to optimize treatment and prognosis. Six client-owned dogs. Retrospective case series. Medical records were reviewed to describe signalment, clinicopathologic and imaging findings, histopathologic diagnoses, treatment, and outcome. All biopsy specimens were reviewed by a board-certified pathologist. Median age of dogs was 5.4 years (range, 15 months-9 years). Consistent clinical signs included vomiting (6/6), regurgitation (2/6), and small bowel diarrhea (3/6). Median duration of clinical signs before presentation was 13 days (range, 5-150 days). Diagnostic imaging showed marked gastric distension with dilated small intestines in 4/6 dogs. Full-thickness intestinal biopsies were obtained in all dogs by laparotomy. Histopathology of the stomach and intestines disclosed mononuclear inflammation, myofiber degeneration and necrosis, and fibrosis centered within the region of myofiber loss in the intestinal muscularis propria. All dogs received various combinations of immunomodulatory and prokinetic treatment, antimicrobial agents, antiemetics, and IV fluids, but none of the dogs showed a clinically relevant improvement with treatment. Median survival was 19 days after diagnosis (range, 3-270 days). Intestinal leiomyositis is a cause of intestinal pseudo-obstruction and must be diagnosed by full-thickness intestinal biopsy. This disease should be considered in dogs with acute and chronic vomiting, regurgitation, and small bowel diarrhea. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  13. Serum biomarkers in periprosthetic joint infections.

    Science.gov (United States)

    Saleh, A; George, J; Faour, M; Klika, A K; Higuera, C A

    2018-01-01

    The diagnosis of periprosthetic joint infection (PJI) is difficult and requires a battery of tests and clinical findings. The purpose of this review is to summarize all current evidence for common and new serum biomarkers utilized in the diagnosis of PJI. We searched two literature databases, using terms that encompass all hip and knee arthroplasty procedures, as well as PJI and statistical terms reflecting diagnostic parameters. The findings are summarized as a narrative review. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were the two most commonly published serum biomarkers. Most evidence did not identify other serum biomarkers that are clearly superior to ESR and CRP. Other serum biomarkers have not demonstrated superior sensitivity and have failed to replace CRP and ESR as first-line screening tests. D-dimer appears to be a promising biomarker, but more research is necessary. Factors that influence serum biomarkers include temporal trends, stage of revision, and implant-related factors (metallosis). Our review helped to identify factors that can influence serum biomarkers' level changes; the recognition of such factors can help improve their diagnostic utility. As such, we cannot rely on ESR and CRP alone for the diagnosis of PJI prior to second-stage reimplantation, or in metal-on-metal or corrosion cases. The future of serum biomarkers will likely shift towards using genomics and proteomics to identify proteins transcribed via messenger RNA in response to infection and sepsis. Cite this article: Bone Joint Res 2018;7:85-93. © 2018 Saleh et al.

  14. Biomarkers in Multiple Sclerosis: Role of Antibodies

    OpenAIRE

    Berger, Thomas; Reindl, Markus

    2006-01-01

    The first international workshop on “Biomarkers in Multiple Sclerosis” was organized by B. Bielekova, R. Hohlfeld, R. Martin and U. Utz from April 14–16, 2004, in Washington, DC. The workshop intended to discuss the current status and potential applicability of biological markers for the understanding of the pathogenesis, diagnosis, and therapy of multiple sclerosis. The present review summarizes the presentation on the potential role of antibodies as biomarkers for diagnosis, disease activit...

  15. Shotgun Proteomics and Biomarker Discovery

    Directory of Open Access Journals (Sweden)

    W. Hayes McDonald

    2002-01-01

    Full Text Available Coupling large-scale sequencing projects with the amino acid sequence information that can be gleaned from tandem mass spectrometry (MS/MS has made it much easier to analyze complex mixtures of proteins. The limits of this “shotgun” approach, in which the protein mixture is proteolytically digested before separation, can be further expanded by separating the resulting mixture of peptides prior to MS/MS analysis. Both single dimensional high pressure liquid chromatography (LC and multidimensional LC (LC/LC can be directly interfaced with the mass spectrometer to allow for automated collection of tremendous quantities of data. While there is no single technique that addresses all proteomic challenges, the shotgun approaches, especially LC/LC-MS/MS-based techniques such as MudPIT (multidimensional protein identification technology, show advantages over gel-based techniques in speed, sensitivity, scope of analysis, and dynamic range. Advances in the ability to quantitate differences between samples and to detect for an array of post-translational modifications allow for the discovery of classes of protein biomarkers that were previously unassailable.

  16. Quality assurance in biomarker measurement.

    Science.gov (United States)

    Aitio, A; Apostoli, P

    1995-05-01

    Quality assurance (QA) concerns the validity of all the analytical processes (from collection of the samples to interpretation of the results). It is not an abstract concept but must be adapted to the different situations such as the different exposure levels, the different analytical methods, and the context of use (risk assessment procedures, research, routine determinations). The main requirements in QA programmes regard the control of all the known sources of preanalytical and analytical variations, while the instruments with which adequate QA can be implemented are the certified materials and the quality control programmes (quality manual, internal and external quality controls). Another important concept in QA is that measurements must be placed a different metrological levels: at the highest there are the methods (definitive, reference) to be used for assessing accuracy of routine methods. QA programmes should enable a grading of biomarkers (from experimental only to full evaluated) and of the laboratories in order to identify the significance of the test and to assess the level at which a laboratory could operate.

  17. Intestinal parasitic infections in renal transplant recipients.

    Science.gov (United States)

    Azami, Mehdi; Sharifi, Mehran; Hejazi, Sayed Hossein; Tazhibi, Mehdi

    2010-01-01

    The impact of intestinal parasitic infection in renal transplant recipients requires careful consideration in the developing world. However, there have been very few studies addressing this issue in Iran. This study was conducted to determine the prevalence of intestinal parasitic infections in renal transplant recipients in Iran. Stool specimens from renal transplant recipients and control groups were obtained between June 2006 and January 2007. The samples screened for intestinal parasitic infections using direct smear, formalin-ether sedimentation, Sheather's flotation and modified Ziehl-Neelsen staining methods. Out of 150 renal transplant recipients, 33.3% (50), and out of 225 control group, 20% (45) were infected with one or more type of intestinal parasites. The parasites detected among patients included Entamoeba coli (10.6%), Endolimax nana (8.7%), Giardia lamblia (7.4%), Blastocystis spp. (4.7%), Iodamoeba butschlii (0.7%), Chilomastix mesnili (0.7%) and Ascaris lumbricoides (0.7%). Multiple infections were more common among renal transplant recipients group (p < 0.05). This study highlights the importance of testing for intestinal parasites among Iranian renal transplant recipients. Routine examinations of stool samples for parasites would significantly benefit the renal transplant recipients by contributing to reduce severe infections.

  18. Macrophages in intestinal homeostasis and inflammation

    Science.gov (United States)

    Bain, Calum C; Mowat, Allan McI

    2014-01-01

    The intestine contains the largest pool of macrophages in the body which are essential for maintaining mucosal homeostasis in the face of the microbiota and the constant need for epithelial renewal but are also important components of protective immunity and are involved in the pathology of inflammatory bowel disease (IBD). However, defining the biological roles of intestinal macrophages has been impeded by problems in defining the phenotype and origins of different populations of myeloid cells in the mucosa. Here, we discuss how multiple parameters can be used in combination to discriminate between functionally distinct myeloid cells and discuss the roles of macrophages during homeostasis and how these may change when inflammation ensues. We also discuss the evidence that intestinal macrophages do not fit the current paradigm that tissue-resident macrophages are derived from embryonic precursors that self-renew in situ, but require constant replenishment by blood monocytes. We describe our recent work demonstrating that classical monocytes constantly enter the intestinal mucosa and how the environment dictates their subsequent fate. We believe that understanding the factors that drive intestinal macrophage development in the steady state and how these may change in response to pathogens or inflammation could provide important insights into the treatment of IBD. PMID:24942685

  19. Glutamine and Its Effects on the Intestine

    Directory of Open Access Journals (Sweden)

    Paul E Hardy

    1991-01-01

    Full Text Available Glutamine, an amino acid, is the principal energy substrate for small intestinal cells. It also acts as a nitrogen carrier through its amide nitrogen. Arterial glutamine is supported by net synthesis in skeletal muscle. Glutamine is rapidly metabolized by the intestine, whether supplied from the lumen or from the arterial circulation. Intestinal uptake of glutamine increases after trauma and operative stress. The consumption of glutamine by the gut may in large part be dependent on mucosal glutaminase activity and on enterocyte glutamine transport. Glutaminc has been shown to improve gut morphology and outcome in animal models of encerocolitis. It may play a similar role in aiding repair of human intestinal injury in persons with sufficient glutamine in their diet compared to those who arc glutamine deficient. Glutamine may have a positive effect on the immune function of the intestinal mucosal-associated lymphoid tissue. Glutamine is not currently available in nutritional preparations for routine clinical use, yet it has recently been shown to benefit maintenance of nitrogen balance in humans. Due to the instability and low solubility of glutamine, dipeptides have been studied. L-alanyl-L-glutamine seems to be the most promising glutamine precursor for parenteral use in humans, as it is safe and rapidly hydrolyzed in vivo to release free glutamine. The exact role of glutamine as a therapeutic agent to promote intetitinal well-being has yet to be determined. However, preliminary evidence suggests that glutaminc will be helpful in a variety of clinical scenarios.

  20. Intestinal parasitic infections in renal transplant recipients

    Directory of Open Access Journals (Sweden)

    Mehdi Azami

    Full Text Available The impact of intestinal parasitic infection in renal transplant recipients requires careful consideration in the developing world. However, there have been very few studies addressing this issue in Iran. This study was conducted to determine the prevalence of intestinal parasitic infections in renal transplant recipients in Iran. Stool specimens from renal transplant recipients and control groups were obtained between June 2006 and January 2007. The samples screened for intestinal parasitic infections using direct smear, formalin-ether sedimentation, Sheather's flotation and modified Ziehl-Neelsen staining methods. Out of 150 renal transplant recipients, 33.3% (50, and out of 225 control group, 20% (45 were infected with one or more type of intestinal parasites. The parasites detected among patients included Entamoeba coli (10.6%, Endolimax nana (8.7%, Giardia lamblia (7.4%, Blastocystis spp. (4.7%, Iodamoeba butschlii (0.7%, Chilomastix mesnili (0.7% and Ascaris lumbricoides (0.7%. Multiple infections were more common among renal transplant recipients group (p < 0.05. This study highlights the importance of testing for intestinal parasites among Iranian renal transplant recipients. Routine examinations of stool samples for parasites would significantly benefit the renal transplant recipients by contributing to reduce severe infections.

  1. Small Intestinal Obstruction Caused by Anisakiasis

    Directory of Open Access Journals (Sweden)

    Yuichi Takano

    2013-01-01

    Full Text Available Small intestinal anisakiasis is a rare disease that is very difficult to diagnose, and its initial diagnosis is often surgical. However, it is typically a benign disease that resolves with conservative treatment, and unnecessary surgery can be avoided if it is appropriately diagnosed. This case report is an example of small intestinal obstruction caused by anisakiasis that resolved with conservative treatment. A 63-year-old man admitted to our department with acute abdominal pain. A history of raw fish (sushi ingestion was recorded. Abdominal CT demonstrated small intestinal dilatation with wall thickening and contrast enhancement. Ascitic fluid was found on the liver surface and in the Douglas pouch. His IgE (RIST was elevated, and he tested positive for the anti-Anisakis antibodies IgG and IgA. Small intestinal obstruction by anisakiasis was highly suspected and conservative treatment was performed, ileus tube, fasting, and fluid replacement. Symptoms quickly resolved, and he was discharged on the seventh day of admission. Small intestinal anisakiasis is a relatively uncommon disease, the diagnosis of which may be difficult. Because it is a self-limiting disease that usually resolves in 1-2 weeks, a conservative approach is advisable to avoid unnecessary surgery.

  2. Tissue response after radiation exposure. Intestine

    International Nuclear Information System (INIS)

    Otsuka, Kensuke; Tomita, Masanori; Yamauchi, Motohiro; Iwasaki, Toshiyasu

    2014-01-01

    Gastrointestinal syndrome followed by 'gut death' is due to intestinal disorders. This syndrome is induced by high-dose (>10 Gy) of ionizing radiation. Recovery from the gastrointestinal syndrome would depend on the number of survived clonogens and regeneration capability of crypts. These tissue alterations can be observed by high-dose radiation, however, cellular dynamics in crypts can be affected by low-dose radiation. For example, Potten et al. found that low-dose radiation induce apoptosis of intestinal stem cells, which produce all differentiated function cells. Recently, intestinal stem cells are characterized by molecular markers such as Lgr5. Since intestinal adenomas can be induced by deletion of Apc gene in Lgr5 + stem cells, it is widely recognized that Lgr5 + stem cells are the cell-of-origin of cancer. Duodenal Lgr5 + stem cells are known as radioresistant cells, however, we found that ionizing radiation significantly induces the turnover of colonic Lgr5 + stem cells. Combined with the knowledge of other radioresistant markers, stem-cell dynamics in tissue after irradiation are becoming clear. The present review introduces the history of gastrointestinal syndrome and intestinal stem cells, and discusses those future perspectives. (author)

  3. Intestinal endocrine cells in radiation enteritis

    International Nuclear Information System (INIS)

    Pietroletti, R.; Blaauwgeers, J.L.; Taat, C.W.; Simi, M.; Brummelkamp, W.H.; Becker, A.E.

    1989-01-01

    In this study, the intestinal endocrine cells were investigated in 13 surgical specimens affected by radiation enteritis. Endocrine cells were studied by means of Grimelius' silver staining and immunostaining for chromogranin, a general marker of endocrine cells. Positively stained cells were quantified by counting their number per unit length of muscularis mucosa. Results in radiation enteritis were compared with matched control specimens by using Student's t test. Chromogranin immunostaining showed a statistically significant increase of endocrine cells in radiation enteritis specimens compared with controls both in small and large intestine (ileum, 67.5 +/- 23.5 cells per unit length of muscularis mucosa in radiation enteritis versus 17.0 +/- 6.1 in controls; colon, 40.9 +/- 13.7 cells per unit length of muscularis mucosa in radiation enteritis versus 9.5 +/- 4.1 in controls--p less than 0.005 in both instances). Increase of endocrine cells was demonstrated also by Grimelius' staining; however, without reaching statistical significance. It is not clear whether or not the increase of endocrine cells in radiation enteritis reported in this study is caused by a hyperplastic response or by a sparing phenomenon. We should consider that increased endocrine cells, when abnormally secreting their products, may be involved in some of the clinical features of radiation enteropathy. In addition, as intestinal endocrine cells produce trophic substances to the intestine, their increase could be responsible for the raised risk of developing carcinoma of the intestine in long standing radiation enteritis

  4. AIDBD: AUTOIMMUNE AND INFLAMMATORY DISEASES BIOMARKER DATABASE

    Directory of Open Access Journals (Sweden)

    Kulwinder Singh

    2016-09-01

    Full Text Available One of the major challenges facing the healthcare industry is how to personalize, or tailor healthcare products and services to individuals’ unique genetic and biomarker make-ups. Biomarkers provide information about normal or patho-physiological processes to detect or define disease progression or to predict or quantify therapeutic responses. Once these footprints have been identified and measured, they can then be used to personalize or tailor treatment plans, products and services to each individual’s unique makeup and background. Autoimmune and Inflammatory Diseases Biomarker Database (AIDBD is one of the first efforts to build an easily accessible and comprehensive literature-derived database covering information on known autoimmune and inflammatory diseases, biomarkers and available medications. It allows users to link autoimmune and inflammatory diseases to protein or gene biomarkers through its user interface. Currently, AIDBD integrates 206 biomarkers for 21 autoimmune and inflammatory diseases and data on 516 launched drugs for the treatment these diseases. The database is freely accessible at http://www.aidbd.in/.

  5. Biomarkers in T cell therapy clinical trials

    Directory of Open Access Journals (Sweden)

    Kalos Michael

    2011-08-01

    Full Text Available Abstract T cell therapy represents an emerging and promising modality for the treatment of both infectious disease and cancer. Data from recent clinical trials have highlighted the potential for this therapeutic modality to effect potent anti-tumor activity. Biomarkers, operationally defined as biological parameters measured from patients that provide information about treatment impact, play a central role in the development of novel therapeutic agents. In the absence of information about primary clinical endpoints, biomarkers can provide critical insights that allow investigators to guide the clinical development of the candidate product. In the context of cell therapy trials, the definition of biomarkers can be extended to include a description of parameters of the cell product that are important for product bioactivity. This review will focus on biomarker studies as they relate to T cell therapy trials, and more specifically: i. An overview and description of categories and classes of biomarkers that are specifically relevant to T cell therapy trials, and ii. Insights into future directions and challenges for the appropriate development of biomarkers to evaluate both product bioactivity and treatment efficacy of T cell therapy trials.

  6. Potential Blood-based Biomarkers for Concussion.

    Science.gov (United States)

    Papa, Linda

    2016-09-01

    Mounting research in the field of sports concussion biomarkers has led to a greater understanding of the effects of brain injury from sports. A recent systematic review of clinical studies examining biomarkers of brain injury following sports-related concussion established that almost all studies have been published either in or after the year 2000. In an effort to prevent chronic traumatic encephalopathy and long-term consequences of concussion, early diagnostic and prognostic tools are becoming increasingly important; particularly in sports and in military personnel, where concussions are common occurrences. Early and tailored management of athletes following a concussion with biomarkers could provide them with the best opportunity to avoid further injury. Should blood-based biomarkers for concussion be validated and become widely available, they could have many roles. For instance, a point-of-care test could be used on the field by trained sport medicine professionals to help detect a concussion. In the clinic or hospital setting, it could be used by clinicians to determine the severity of concussion and be used to screen players for neuroimaging (computed tomography and/or magnetic resonance imaging) and further neuropsychological testing. Furthermore, biomarkers could have a role in monitoring progression of injury and recovery and in managing patients at high risk of repeated injury by being incorporated into guidelines for return to duty, work, or sports activities. There may even be a role for biomarkers as surrogate measures of efficacy in the assessment of new treatments and therapies for concussion.

  7. Allergic asthma biomarkers using systems approaches

    Directory of Open Access Journals (Sweden)

    Gaurab eSircar

    2014-01-01

    Full Text Available Asthma is characterized by lung inflammation caused by complex interaction between the immune system and environmental factors such as allergens and inorganic pollutants. Recent research in this field is focused on discovering new biomarkers associated with asthma pathogenesis. This review illustrates updated research associating biomarkers of allergic asthma and their potential use in systems biology of the disease. We focus on biomolecules with altered expression, which may serve as inflammatory, diagnostic and therapeutic biomarkers of asthma discovered in human or experimental asthma model using genomic, proteomic and epigenomic approaches for gene and protein expression profiling. These include high-throughput technologies such as state of the art microarray and proteomics Mass Spectrometry (MS platforms. Emerging concepts of molecular interactions and pathways may provide new insights in searching potential clinical biomarkers. We summarized certain pathways with significant linkage to asthma pathophysiology by analyzing the compiled biomarkers. Systems approaches with this data can identify the regulating networks, which will eventually identify the key biomarkers to be used for diagnostics and drug discovery.

  8. Single Domain Antibodies as New Biomarker Detectors

    Science.gov (United States)

    Fischer, Katja; Leow, Chiuan Yee; Chuah, Candy; McCarthy, James

    2017-01-01

    Biomarkers are defined as indicators of biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention. Biomarkers have been widely used for early detection, prediction of response after treatment, and for monitoring the progression of diseases. Antibodies represent promising tools for recognition of biomarkers, and are widely deployed as analytical tools in clinical settings. For immunodiagnostics, antibodies are now exploited as binders for antigens of interest across a range of platforms. More recently, the discovery of antibody surface display and combinatorial chemistry techniques has allowed the exploration of new binders from a range of animals, for instance variable domains of new antigen receptors (VNAR) from shark and variable heavy chain domains (VHH) or nanobodies from camelids. These single domain antibodies (sdAbs) have some advantages over conventional murine immunoglobulin owing to the lack of a light chain, making them the smallest natural biomarker binders thus far identified. In this review, we will discuss several biomarkers used as a means to validate diseases progress. The potential functionality of modern singe domain antigen binders derived from phylogenetically early animals as new biomarker detectors for current diagnostic and research platforms development will be described. PMID:29039819

  9. Single Domain Antibodies as New Biomarker Detectors

    Directory of Open Access Journals (Sweden)

    Chiuan Herng Leow

    2017-10-01

    Full Text Available Biomarkers are defined as indicators of biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention. Biomarkers have been widely used for early detection, prediction of response after treatment, and for monitoring the progression of diseases. Antibodies represent promising tools for recognition of biomarkers, and are widely deployed as analytical tools in clinical settings. For immunodiagnostics, antibodies are now exploited as binders for antigens of interest across a range of platforms. More recently, the discovery of antibody surface display and combinatorial chemistry techniques has allowed the exploration of new binders from a range of animals, for instance variable domains of new antigen receptors (VNAR from shark and variable heavy chain domains (VHH or nanobodies from camelids. These single domain antibodies (sdAbs have some advantages over conventional murine immunoglobulin owing to the lack of a light chain, making them the smallest natural biomarker binders thus far identified. In this review, we will discuss several biomarkers used as a means to validate diseases progress. The potential functionality of modern singe domain antigen binders derived from phylogenetically early animals as new biomarker detectors for current diagnostic and research platforms development will be described.

  10. Measures to minimize small intestine injury in the irradiated pelvis

    International Nuclear Information System (INIS)

    Green, N.; Iba, G.; Smith, W.R.

    1975-01-01

    Small intestine injury causes long-term suffering and high mortality. Five of 187 of our patients had developed serious small intestine injury. Four patients had corrective surgery. Three patients died. All were women. Subsequently, all patients who received definitive pelvic irradiation had small intestine roentgenograms to determine its location and mobility. Female patients, thin patients, and elderly patients had larger amounts of small intestine in the whole pelvis, a deeper cul de sac, and a greater incidence of relatively immobile small intestine. Patients with relatively immobile small intestine in the treatment field may be predisposed to injury. There was no relationship of the incidence of relatively immobile small intestine to prior pelvic surgery. We used the findings from the small intestine roentgenograms to modify individually the radiotherapy regimen so as to minimize the risk for small intestine injury. Patients were placed in the prone position to displace the small intestine out of the treatment fields used for booster dose irradiation. The treatment field was modified to exclude the small intestine. The total tumor dose delivered was determined by expectations for cure vs complications. To date, none of the patients in this study group has developed small intestine injury. Cadaver studies showed the feasibility of elective shortening of the pelvic cul de sac. The small intestine can be displaced away from the bladder, prostate, or cervix. (U.S.)

  11. Small Bowel Obstruction due to Intestinal Xanthomatosis

    Directory of Open Access Journals (Sweden)

    L. E. Barrera-Herrera

    2015-01-01

    Full Text Available Vast majority of bowel obstruction is due to postoperative adhesions, malignancy, intestinal inflammatory disease, and hernias; however, knowledge of other uncommon causes is critical to establish a prompt treatment and decrease mortality. Xanthomatosis is produced by accumulation of cholesterol-rich foamy macrophages. Intestinal xanthomatosis is an uncommon nonneoplastic lesion that may cause small bowel obstruction and several cases have been reported in the English literature as obstruction in the jejunum. We report a case of small intestinal xanthomatosis occurring in a 51-year-old female who presented with one day of copious vomiting and intermittent abdominal pain. Radiologic images revealed jejunal loop thickening and inflammatory changes suggestive of foreign body obstruction, diagnostic laparoscopy found two strictures at the jejunum, and a pathologic examination confirmed a segmental small bowel xanthomatosis. This case illustrates that obstruction even without predisposing factors such as hyperlipidemia or lymphoproliferative disorders.

  12. Radiodiagnosis of early radiation intestinal changes

    International Nuclear Information System (INIS)

    Volodina, G.I.; Abdulkhakova, D.A.

    1987-01-01

    X-ray examination of the colon in 102 patients and of the small intestine in 62 was performed during combined radiation therapy of cervical cancer and at different time after its discontinuation. Early radiation functional and morphological changes in the ileum and colon were detected. Radiation changes in the ileac mucosa were noted in 52% of the patients, changes of various degree in the rectal, sigmoid and cecal mucosa were noted in 41.2%. Moderate radiation changes in the ascending, descending and horizontal parts of the colon were noted in 10.7%. Early radiation intestinal injuries in the form of erosions and ulcers were revealed in 5.8% of the patients. In most of the patients radiation intestinal changes were without noticeable clinical manifestations. All these patients could be defined as a group at risk of developing late radiation changes

  13. Recent Advances in Intestinal Stem Cells.

    Science.gov (United States)

    McCabe, Laura R; Parameswaran, Narayanan

    2017-09-01

    The intestine is a dynamic organ with rapid stem cell division generating epithelial cells that mature and apoptose in 3-5 days. Rapid turnover maintains the epithelial barrier and homeostasis. Current insights on intestinal stem cells (ISCs) and their regulation are discussed here. The Lgr5+ ISCs maintain intestinal homeostasis by dividing asymmetrically, but also divide symmetrically to extinguish or replace ISCs. Following radiation or mucosal injury, reserve BMI1+ ISCs as well as other crypt cells can de-differentiate into Lgr5+ ISCs. ISC niche cells, including Paneth, immune and myofibroblast cells secrete factors that regulate ISC proliferation. Finally, several studies indicate that the microbiome metabolites regulate ISC growth. ISC cells can be plastic and integrate a complexity of environmental/niche cues to trigger or suppress proliferation as needed.

  14. Intestinal infarction: A complication of endovascular therapy

    Energy Technology Data Exchange (ETDEWEB)

    England, Andrew [Department of Radiology, South Manchester University Hospitals NHS Trust, Southmoor Road, Wythenshawe, Manchester M23 9LT (United Kingdom)]. E-mail: andrew.england@smtr.nhs.uk; Butterfield, John S. [Department of Radiology, South Manchester University Hospitals NHS Trust, Southmoor Road, Wythenshawe, Manchester M23 9LT (United Kingdom); Sukumar, Sathi [Department of Radiology, South Manchester University Hospitals NHS Trust, Southmoor Road, Wythenshawe, Manchester M23 9LT (United Kingdom); Thompson, David [Department of Radiology, South Manchester University Hospitals NHS Trust, Southmoor Road, Wythenshawe, Manchester M23 9LT (United Kingdom); Roulson, Jo-An [Department of Histopathology, South Manchester University Hospitals NHS Trust, Southmoor Road, Wythenshawe, Manchester M23 9LT (United Kingdom); Pritchard, Susan [Department of Histopathology, South Manchester University Hospitals NHS Trust, Southmoor Road, Wythenshawe, Manchester M23 9LT (United Kingdom); Ashleigh, Raymond J. [Department of Radiology, South Manchester University Hospitals NHS Trust, Southmoor Road, Wythenshawe, Manchester M23 9LT (United Kingdom)

    2007-08-15

    This report presents a rare case of intestinal infarction following endovascular therapy. A female patient who had undergone an internal carotid artery stenting procedure presented suddenly with abdominal pain. Radiological and clinical examinations at the time suggested a picture of intestinal ischaemia, in view of the patient's general conditions and co-existing morbidities surgical intervention was not considered to be an option. The patient died 4 days after the carotid stenting procedure, post-mortem examination revealed infarction of the ileum and caecum. The learning outcomes are if performing endovascular therapy in a patient with diffuse atherosclerotic disease early consideration of intestinal ischaemia should be given to any patient who presents with acute post-procedural abdominal pain.

  15. Intestinal infarction: A complication of endovascular therapy

    International Nuclear Information System (INIS)

    England, Andrew; Butterfield, John S.; Sukumar, Sathi; Thompson, David; Roulson, Jo-An; Pritchard, Susan; Ashleigh, Raymond J.

    2007-01-01

    This report presents a rare case of intestinal infarction following endovascular therapy. A female patient who had undergone an internal carotid artery stenting procedure presented suddenly with abdominal pain. Radiological and clinical examinations at the time suggested a picture of intestinal ischaemia, in view of the patient's general conditions and co-existing morbidities surgical intervention was not considered to be an option. The patient died 4 days after the carotid stenting procedure, post-mortem examination revealed infarction of the ileum and caecum. The learning outcomes are if performing endovascular therapy in a patient with diffuse atherosclerotic disease early consideration of intestinal ischaemia should be given to any patient who presents with acute post-procedural abdominal pain

  16. Seronegative Intestinal Villous Atrophy: A Diagnostic Challenge

    Directory of Open Access Journals (Sweden)

    Cláudio Martins

    2016-01-01

    Full Text Available Celiac disease is the most important cause of intestinal villous atrophy. Seronegative intestinal villous atrophy, including those that are nonresponsive to a gluten-free diet, is a diagnostic challenge. In these cases, before establishing the diagnosis of seronegative celiac disease, alternative etiologies of atrophic enteropathy should be considered. Recently, a new clinical entity responsible for seronegative villous atrophy was described—olmesartan-induced sprue-like enteropathy. Herein, we report two uncommon cases of atrophic enteropathy in patients with arterial hypertension under olmesartan, who presented with severe chronic diarrhea and significant involuntary weight loss. Further investigation revealed intestinal villous atrophy and intraepithelial lymphocytosis. Celiac disease and other causes of villous atrophy were ruled out. Drug-induced enteropathy was suspected and clinical improvement and histologic recovery were verified after olmesartan withdrawal. These cases highlight the importance for clinicians to maintain a high index of suspicion for olmesartan as a precipitant of sprue-like enteropathy.

  17. Viability of the vascularly perfused, recirculating rat intestine and intestine-liver preparations

    Energy Technology Data Exchange (ETDEWEB)

    Hirayama, H.; Xu, X.; Pang, K.S. (Univ. of Toronto, Ontario (Canada))

    1989-08-01

    Function and stability of vascularly perfused, recirculating in situ rat intestine (I) and intestine-liver (IL) preparations were evaluated in fasted and nonfasted rats because these techniques may be readily applied in drug metabolism studies. The rat intestine was perfused with blood medium (7.5 ml/min) via the superior mesenteric artery, with the venous outflow draining into the portal vein, which, together with hepatic arterial flow (2.5 ml/min), constituted the total blood flow (10 ml/min) to the liver. Maintenance of intestinal membrane integrity was observed. Rapid ({sup 14}C)glucose absorption against a concentration gradient and a lack of ({sup 3}H)-polyethylene glycol 4000 (PEG 4000, less than 4%) and Evans blue absorption by the recirculating I and IL preparations resulted after bolus injections of these markers into the pyloric end of the duodenum. Other indexes that revealed stable intestinal and liver functions were the following: preservation of reservoir perfusate volume, constancy in perfusion pressure, bile flow, and hemoglobin concentrations, evidence of intestinal glucose utilization and liver glucose production, and a lack of significant leakage of serum glutamic oxalic transaminase. The intestine and liver consumed oxygen at relatively constant rates, but the consumption rates for the fasted tissues (I or L) were significantly higher than those for nonfasted tissues. These results indicate that the vascularly perfused I and IL preparations were maintained in a viable and stable state for a 2-h perfusion period.

  18. Radiologic study on differential diagnosis of intestinal tuberculosis and intestinal Behcet's disease

    International Nuclear Information System (INIS)

    Kim, Jong Chul; Kim, Young Goo; Kim, Sang Joon; Choi, Byung Ihn; Park, Jae Hyung

    1986-01-01

    Radiologic findings in 30 patients with intestinal tuberculosis and 10 patients with intestinal Behcet's disease, who had been diagnosed at Seoul National University Hospital during the recent 5 years, were analysed retrospectively to evaluate the radiologic differential diagnosis of the two diseases. Intestinal tuberculosis severely involved the cecum, the ileocecal valve, the distal ileum and colons, but Behcet's disease mainly involved the distal ileum and infrequently the ileocecal valve and the cecum. The ulcers in tuberculosis were usually multiple small barium collected areas among pseudopolyps, on the contrary, those in Behcet's disease were multiple, discrete, well marinated, geographic, ring-like deep penetrating or collar-button shaped. Intestinal tuberculosis tended to involved long segments of intestines, with severer mucosal irregularity and deformity of the ileocecal valve and the ascending colon in comparison with Behcet's disease. Mesenteric and/or peritoneal involvement were accompanied in 1/3 cases of intestinal tuberculosis, and active pulmonary tuberculosis or pleural effusion also in 1/3 cases of intestinal tuberculosis.

  19. Intestinal Microbiota Signatures Associated With Histological Liver Steatosis in Pediatric-Onset Intestinal Failure.

    Science.gov (United States)

    Korpela, Katri; Mutanen, Annika; Salonen, Anne; Savilahti, Erkki; de Vos, Willem M; Pakarinen, Mikko P

    2017-02-01

    Intestinal failure (IF)-associated liver disease (IFALD) is the major cause of mortality in IF. The link between intestinal microbiota and IFALD is unclear. We compared intestinal microbiota of patients with IF (n = 23) with healthy controls (n = 58) using culture-independent phylogenetic microarray analysis. The microbiota was related to histological liver injury, fecal markers of intestinal inflammation, matrix metalloproteinase 9 and calprotectin, and disease characteristics. Overabundance of Lactobacilli, Proteobacteria, and Actinobacteria was observed in IF, whereas bacteria related to Clostridium clusters III, IV, and XIVa along with overall diversity and richness were reduced. Patients were segregated into 3 subgroups based on dominating bacteria: Clostridium cluster XIVa, Proteobacteria, and bacteria related to Lactobacillus plantarum. In addition to liver steatosis and fibrosis, Proteobacteria were associated with prolonged current parenteral nutrition (PN) as well as liver and intestinal inflammation. Lactobacilli were related to advanced steatosis and fibrosis mostly after weaning off PN without associated inflammation. In multivariate permutational analysis of variance, liver steatosis, bowel length, PN calories, and antibiotic treatment best explained the microbiota variation among patients with IF. Intestinal microbiota composition was associated with liver steatosis in IF and better predicted steatosis than duration of PN or length of the remaining intestine. Our results may be explained by a model in which steatosis is initiated during PN in response to proinflammatory lipopolysaccharides produced by Proteobacteria and progresses after weaning off PN, as the L plantarum group Lactobacilli becomes dominant and affects lipid metabolism by altering bile acid signaling.

  20. Neural regulation of intestinal nutrient absorption.

    Science.gov (United States)

    Mourad, Fadi H; Saadé, Nayef E

    2011-10-01

    The nervous system and the gastrointestinal (GI) tract share several common features including reciprocal interconnections and several neurotransmitters and peptides known as gut peptides, neuropeptides or hormones. The processes of digestion, secretion of digestive enzymes and then absorption are regulated by the neuro-endocrine system. Luminal glucose enhances its own absorption through a neuronal reflex that involves capsaicin sensitive primary afferent (CSPA) fibres. Absorbed glucose stimulates insulin release that activates hepatoenteric neural pathways leading to an increase in the expression of glucose transporters. Adrenergic innervation increases glucose absorption through α1 and β receptors and decreases absorption through activation of α2 receptors. The vagus nerve plays an important role in the regulation of diurnal variation in transporter expression and in anticipation to food intake. Vagal CSPAs exert tonic inhibitory effects on amino acid absorption. It also plays an important role in the mediation of the inhibitory effect of intestinal amino acids on their own absorption at the level of proximal or distal segment. However, chronic extrinsic denervation leads to a decrease in intestinal amino acid absorption. Conversely, adrenergic agonists as well as activation of CSPA fibres enhance peptides uptake through the peptide transporter PEPT1. Finally, intestinal innervation plays a minimal role in the absorption of fat digestion products. Intestinal absorption of nutrients is a basic vital mechanism that depends essentially on the function of intestinal mucosa. However, intrinsic and extrinsic neural mechanisms that rely on several redundant loops are involved in immediate and long-term control of the outcome of intestinal function. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Bacteria, bile salts, and intestinal monosaccharide malabsorption

    Science.gov (United States)

    Gracey, Michael; Burke, Valerie; Oshin, Ademola; Barker, Judith; Glasgow, Eric F.

    1971-01-01

    Intestinal monosaccharide transport was studied in a series of rats with a self-filling jejunal blind loop using 3mM arbutin (p-hydroxyphenyl-B-glucoside) or 1mM D-fructose as substrate in vitro and 10 mM arbutin or 5mM D-fructose in vivo. These results were compared with changes in the bacterial flora and state of conjugation of intraluminal bile salts in those animals. Observations were also made of the microscopic and ultrastructural appearances of the small-intestinal epithelium. In the small intestine of blind-loop rats intestinal monosaccharide transport is impaired, and in vitro is most marked in the blind loop, less so in the efferent jejunum, and not significantly altered in the afferent jejunum. A similar pattern of disturbed monosaccharide absorption was demonstrated by perfusions in vivo. The degree of the transport defect correlates closely with the luxuriance of the anaerobic flora, which averaged 108 per millilitre in the blind loop, 107 in the efferent jejunum, and 106 in the afferent jejunum. A similar pattern of abnormality of bile salt conjugation occurred. In the blind loop the ratio of free to conjugated bile salts was grossly abnormal; this disturbance was somewhat less marked in the efferent jejunum and considerably less in the intraluminal contents of the afferent jejunum. An irregularly distributed lesion, consisting of swelling and vacuolation of microvilli and intracellular organelles, was demonstrated in the small-intestinal epithelium of blind-loop animals. Impaired absorption of monosaccharides is a further consequence of bacterial contamination of the upper gut. It is suggested that this defect is caused by the presence of high levels of deconjugated bile salts produced by an abnormal anaerobic bacterial flora in the small intestine. ImagesFig. 3Fig. 4 PMID:4329096

  2. The effect of fucoidan on intestinal flora and intestinal barrier function in rats with breast cancer.

    Science.gov (United States)

    Xue, Meilan; Ji, Xinqiang; Liang, Hui; Liu, Ying; Wang, Bing; Sun, Lingling; Li, Weiwei

    2018-02-21

    Recent research studies have shown that the intestinal flora are related to the occurrence and progress of breast cancer. This study investigates the effect of fucoidan on intestinal flora and intestinal barrier function in rats with 7,12-dimethylbenz[a]anthracene (DMBA)-induced breast cancers. Sixty female Sprague-Dawley rats were randomly assigned to the control group, the model group, and the F1 and F2 groups, which were fed fucoidan at concentrations of 200 and 400 mg per kg bw (body weight), respectively. Intestinal histopathological analysis was performed and 16S rDNA high-throughput sequencing was used to provide an overview of the intestinal flora composition. The contents of d-lactic acid (d-LA), diamine oxidase (DAO) and endotoxin in plasma were detected by ELISA. Expression levels of the tight junction (TJ) proteins, phosphorylated p38 MAPK and ERK1/2 were measured using western blotting. Our results suggested that the intestinal wall of the model group was damaged. However, after fucoidan intervention, the villi were gradually restored. ELISA showed that the levels of plasma endotoxin, d-LA and DAO decreased in the F1 and F2 groups compared to those in the model group. Fucoidan treatment also increased the expressions of ZO-1, occludin, claudin-1 and claudin-8. Furthermore, the expression levels of phosphorylated p38 MAPK and ERK1/2 were upregulated in fucoidan treatment groups. The results of 16S rDNA high-throughput sequencing indicated that fucoidan increased the diversity of the intestinal microbiota and induced changes in microbial composition, with the increased Bacteroidetes/Firmicutes phylum ratio. In conclusion, the supplement of fucoidan could improve the fecal microbiota composition and repair the intestinal barrier function. The study suggested the use of fucoidan as an intestinal flora modulator for potential prevention of breast cancer.

  3. Persistently increased intestinal fraction of alkaline phosphatase

    DEFF Research Database (Denmark)

    Nathan, E; Baatrup, G; Berg, H

    1984-01-01

    Persistent elevation of the intestinal fraction of the alkaline phosphatase (API) as an isolated finding has to our knowledge not been reported previously. It was found in a boy followed during a period of 5.5 years. The only symptom was transient periodic fatigue observed at home, but not apparent...... during hospitalization. His blood type was O, RH+, Le (a-, b+) and he was a secretor of H-substance, which may be associated with rising API activity after fat-loading. In this case API was unchanged after fat-loading. Neither intestinal nor liver diseases were found, and no other cause for the elevated...

  4. Relationships between intestinal parasitosis and handedness.

    Science.gov (United States)

    Uslu, Hakan; Dane, Senol; Uyanik, M Hamidullah; Ayyildiz, Ahmet

    2010-07-01

    The aim of the study was to investigate if there is a possible relation between intestinal parasitosis and handedness in patients with suspected intestinal parasitosis. Hand preference was assessed on the Edinburgh Handedness Inventory. Stool samples were examined microscopically for the presence of parasite. In the present study right-handers had many more helminth infections and left-handers had many more protozoon infections. Lower rate of helminth infections in the present study, and higher asthma incidences in the left-handed population in literature, may be associated with different immune machinery in left-handed people than in right-handed ones.

  5. Translational control of an intestinal microvillar enzyme

    DEFF Research Database (Denmark)

    Danielsen, E M; Cowell, G M; Sjöström, H

    1986-01-01

    The rates of biosynthesis of adult and foetal pig small-intestinal aminopeptidase N (EC 3.4.11.2) were compared to determine at which level the expression of the microvillar enzyme is developmentally controlled. In organ-cultured explants, the rate of biosynthesis of foetal aminopeptidase N is only...... about 3% of the adult rate. The small amount synthesized occurs in a high-mannose-glycosylated, membrane-bound, form that is processed to the mature, complex-glycosylated, form at a markedly slower rate than that of the adult enzyme. Extracts of total RNA from adult and foetal intestine contained...

  6. Verification of chronic intestinal ischemia by angiography

    Energy Technology Data Exchange (ETDEWEB)

    Stolze, T.; Sandmann, W.

    1982-06-25

    With chronical occlusion of an intestianal artery (coeliac artery, superior and inferior mesenteric artery) functionally acting and organ-supplying collateral circulations may develop. When this collateral circulation provides a sufficient blood supply, uncharacteristic (10) and absent or minor clinical symptomatology (21) result and therefore in many cases such vascular occlusions are not detected in older people. Consequently, the possible existence of an intestinal ischaemia should be taken into consideration when indefinite complaints occur in older patients, particularly in those cases, where arterial occlusions exist in the lower extremities. With chronical intestinal (arteriosclerotic) ischaemia an acute thrombo-embolism has always to be regarded as a possible complication.

  7. Transcriptome changes during intestinal cell differentiation

    DEFF Research Database (Denmark)

    Tadjali, Mehrdad; Seidelin, Jakob B; Olsen, Jørgen

    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 transc......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...

  8. Intestinal tuberculosis sometimes mimics Crohn's disease.

    Directory of Open Access Journals (Sweden)

    Esfandiar Shojaei

    2013-11-01

    Full Text Available Intestinal tuberculosis is an uncommon presentation of tuberculosis (TB and has clinicopathological similarities with Crohn's disease. In regions where TB is endemic clinicians must aware of this condition and fully evaluate their patients when Crohn's disease is diagnosed. We recommend all pathologic specimens be evaluate effectively for TB.Smear,culture and PCR for Mycobacterium.tuberculosis from samples aside the pathological reviews help for better diagnosis. Here we present a case of intestinal tuberculosis which initially diagnosed as Crohn's disease but after starting immunosuppressive agents he presented with disseminated tuberculosis.

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

    Science.gov (United States)

    Westerhout, Joost; van de Steeg, Evita; Grossouw, Dimitri; Zeijdner, Evelijn E; Krul, Cyrille A M; Verwei, Miriam; Wortelboer, Heleen M

    2014-10-15

    A reliable prediction of the oral bioavailability in humans is crucial and of high interest for pharmaceutical and food industry. The predictive value of currently used in silico methods, in vitro cell lines, ex vivo intestinal tissue and/or in vivo animal studies for human intestinal absorption, however, is often insufficient, especially when food-drug interactions are evaluated. Ideally, for this purpose healthy human intestinal tissue is used, but due to its limited availability there is a need for alternatives. The aim of this study was to evaluate the applicability of healthy porcine intestinal tissue mounted in a newly developed InTESTine™ system to predict human intestinal absorption of compounds with different chemical characteristics, and within biorelevant matrices. To that end, first, a representative set of compounds was chosen of which the apparent permeability (Papp) data in both Caco-2 cells and human intestinal tissue mounted in the Ussing chamber system, and absolute human oral bioavailability were reported. Thereafter, Papp values of the subset were determined in both porcine jejunal tissue and our own Caco-2 cells. In addition, the feasibility of this new approach to study regional differences (duodenum, jejunum, and ileum) in permeability of compounds and to study the effects of luminal factors on permeability was also investigated. For the latter, a comparison was made between the compatibility of porcine intestinal tissue, Caco-2 cells, and Caco-2 cells co-cultured with the mucin producing HT29-MTX cells with biorelevant samples as collected from an in vitro dynamic gastrointestinal model (TIM). The results demonstrated that for the paracellularly transported compounds atenolol, cimetidine, mannitol and ranitidine porcine Papp values are within 3-fold difference of human Papp values, whereas the Caco-2 Papp values are beyond 3-fold difference. Overall, the porcine intestinal tissue Papp values are more comparable to human Papp values (9 out

  10. Pseudo-obstrucción intestinal crónica Chronic intestinal pseudo-obstruction

    OpenAIRE

    M. T. Muñoz; J. A. Solís Herruzo

    2007-01-01

    El síndrome de pseudo-obstrucción intestinal crónica se caracteriza por la presencia de cuadros clínicos recidivantes que simulan una obstrucción intestinal pero en ausencia de proceso obstructivo anatómico. Es poco frecuente pero determina una alta morbilidad. Se origina como consecuencia de una alteración de la motilidad intestinal que no puede hacer progresar su contenido debido a la afectación de su componente muscular, neurológico o de ambos. Son más frecuentes los casos secundarios a un...

  11. Sodium recirculation and isotonic transport in toad small intestine

    DEFF Research Database (Denmark)

    Nedergaard, Signe Nielsen; Larsen, Erik Hviid; Ussing, Hans H.

    1999-01-01

    Small intestine; leaky epithelia; solute-coupled water transport; Na*O+ recirculation; lateral intercellular space; flux ratio analysi......Small intestine; leaky epithelia; solute-coupled water transport; Na*O+ recirculation; lateral intercellular space; flux ratio analysi...

  12. Diversity of human small intestinal Streptococcus and Veillonella populations

    NARCIS (Netherlands)

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

    2013-01-01

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

  13. Surgical management and autologous intestinal reconstruction in short bowel syndrome

    NARCIS (Netherlands)

    Hommel, Matthijs J.; van Baren, Robertine; Haveman, Jan Willem

    Short bowel syndrome (SBS) is a serious condition with considerable morbidity and mortality. When treatment with parenteral nutrition fails and life-threatening complications occur, autologous intestinal reconstruction (AIR) should be considered before intestinal transplantation (ITx). Single or

  14. Plasmodium berghei ANKA causes intestinal malaria associated with dysbiosis.

    Science.gov (United States)

    Taniguchi, Tomoyo; Miyauchi, Eiji; Nakamura, Shota; Hirai, Makoto; Suzue, Kazutomo; Imai, Takashi; Nomura, Takahiro; Handa, Tadashi; Okada, Hiroko; Shimokawa, Chikako; Onishi, Risa; Olia, Alex; Hirata, Jun; Tomita, Haruyoshi; Ohno, Hiroshi; Horii, Toshihiro; Hisaeda, Hajime

    2015-10-27

    Gastrointestinal symptoms, such as abdominal pain and diarrhea, are frequently observed in patients with Plasmodium falciparum malaria. However, the correlation between malaria intestinal pathology and intestinal microbiota has not been investigated. In the present study, infection of C57BL/6 mice with P. berghei ANKA (PbA) caused intestinal pathological changes, such as detachment of epithelia in the small intestines and increased intestinal permeability, which correlated with development with experimental cerebral malaria (ECM). Notably, an apparent dysbiosis occurred, characterized by a reduction of Firmicutes and an increase in Proteobacteria. Furthermore, some genera of microbiota correlated with parasite growth and/or ECM development. By contrast, BALB/c mice are resistant to ECM and exhibit milder intestinal pathology and dysbiosis. These results indicate that the severity of cerebral and intestinal pathology coincides with the degree of alteration in microbiota. This is the first report demonstrating that malaria affects intestinal microbiota and causes dysbiosis.

  15. Surgical aspects of intestinal tuberculosis in children: Our experience

    African Journals Online (AJOL)

    constrained countries. Intestinal TB is especially notorious as a number of cases have to be dealt surgically, which too have morbidity and mortality. This study was conducted to identify various presentations of intestinal TB necessitating surgical ...

  16. Diversity of human small intestinal Streptococcus and Veillonella populations

    NARCIS (Netherlands)

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

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

  17. Dimethyloxalylglycine preserves the intestinal microvasculature and protects against intestinal injury in a neonatal mouse NEC model: role of VEGF signaling.

    Science.gov (United States)

    Bowker, Rakhee M; Yan, Xiaocai; Managlia, Elizabeth; Liu, Shirley X L; Marek, Catherine; Tan, Xiao-Di; De Plaen, Isabelle G

    2018-02-01

    BackgroundNecrotizing enterocolitis (NEC) is a devastating neonatal disease characterized by intestinal necrosis. Hypoxia-inducible factor-1α (HIF-1α) has a critical role in cellular oxygen homeostasis. Here, we hypothesized that prolyl hydroxylase (PHD) inhibition, which stabilizes HIF-1α, protects against NEC by promoting intestinal endothelial cell proliferation and improving intestinal microvascular integrity via vascular endothelial growth factor (VEGF) signaling.MethodsTo assess the role of PHD inhibition in a neonatal mouse NEC model, we administered dimethyloxalylglycine (DMOG) or vehicle to pups before or during the NEC protocol, and determined mortality and incidence of severe intestinal injury. We assessed intestinal VEGF by western blot analysis and quantified endothelial cell and epithelial cell proliferation following immunofluorescence.ResultsDMOG decreased mortality and incidence of severe NEC, increased intestinal VEGF expression, and increased intestinal villus endothelial and epithelial cell proliferation in experimental NEC. Inhibiting VEGFR2 signaling eliminated DMOG's protective effect on intestinal injury severity, survival, and endothelial cell proliferation while sparing DMOG's protective effect on intestinal epithelial cell proliferation.ConclusionDMOG upregulates intestinal VEGF, promotes endothelial cell proliferation, and protects against intestinal injury and mortality in experimental NEC in a VEGFR2 dependent manner. DMOG's protective effect on the neonatal intestinal mucosa may be mediated via VEGFR2 dependent improvement of the intestinal microvasculature.

  18. Commensal Bacteria and Epithelial Cross Talk in the Developing Intestine

    OpenAIRE

    Rautava, Samuli; Walker, W. Allan

    2007-01-01

    Indigenous intestinal microbes have co-evolved with the intestinal immune system to form a symbiotic ecosystem. In the postnatal period, intestinal microbes provide the developing gut with stimuli that are necessary for healthy maturation of the intestinal immune system. Cross talk between the host and commensal microbes is an essential component of gut homeostasis mechanisms also in later life. During recent years, innovative research has shed light on the molecular mechanisms of these inter...

  19. Intestinal sclerosis with pseudo-obstruction in three dogs.

    Science.gov (United States)

    Moore, R; Carpenter, J

    1984-04-01

    Intestinal sclerosis causing chronic intestinal pseudo-obstruction was diagnosed in 3 dogs. The pseudo-obstruction was characterized by vomiting and weight loss of 2 weeks' to 3 months' duration. A patent intestinal lumen was determined by contrast radiography and verified at surgery. Intestinal biopsy revealed diffuse atrophy, fibrosis, and mononuclear cell infiltration of the tunica muscularis. Each dog was euthanatized because of a progressive, deteriorating clinical course.

  20. Microdialysis in the assessment of regional intestinal ischemia

    DEFF Research Database (Denmark)

    Sommer, Thorbjørn

     The Ph.D.thesis “Microdialysis in the assessment of regional intestinal ischemia” is based on three scientific papers. The diagnosis of intestinal ischemia remains a diagnostic challenge, since no technique has been able to monitor the intestinal perfusion continuously with a high sensitivity an...

  1. Intestinal failure in childhood | Goulet | South African Journal of ...

    African Journals Online (AJOL)

    Intestinal failure (IF) requires the use of parenteral nutrition (PN) for as long as it persists and in case of irreversible IF may be an indication for intestinal transplantation (ITx). Biological evaluation of IF is becoming possible with the use of plasma citrulline as a marker of intestinal mass. Short bowel syndrome (SBS) is the ...

  2. Effects of Radiation on the Microbiota and Intestinal Inflammatory Disease

    Science.gov (United States)

    2016-09-01

    evaluating the effects of these changes on intestinal susceptibility to inflammatory disease. 15. SUBJECT TERMS Radiation, microbiome , mycobiome...immune cells associated with the intestine and their interactions with the normal microbial contents of the gut. 2. KEYWORDS Radiation, microbiome ... microbiome following TBI. At the end of the experiment, we also harvested the intestines and mesenteric lymph nodes for multiparametric flow cytometry and

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

    NARCIS (Netherlands)

    Bogert, van den B.

    2013-01-01

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

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

    NARCIS (Netherlands)

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

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

  5. Asymptomatic Intestinal Parasites in School Children at Ota, Ogun ...

    African Journals Online (AJOL)

    Asymptomatic Intestinal Parasites in School Children at Ota, Ogun State. ... This study thus advocates routine periodic screening even of the healthy pupils for intestinal parasitosis to minimize morbidity and mortality and improve ... Key Words: intestinal parasites, Giardia lamblia, Entamoeba histolytica, School, Nigeria ...

  6. Prevalence of intestinal parasites and bacteria among food handlers ...

    African Journals Online (AJOL)

    No intestinal parasites were detected from fingernail contents. Forty six (23%) stool specimens were positive for intestinal para¬sites. Giardia lamblia 18 (9%) was most frequent among the 10 different types of detected intestinal parasites followed by Entamoeba histolytica 9 (4.5%). No pathogenic bacteria were detected in ...

  7. Observations on the origin of congenital intestinal atresia

    African Journals Online (AJOL)

    The article by Louw and Barnard entitled 'Congenital intestinal atresia – observations on its origin' published in The Lancet in. 19951 was a landmark paper that elucidated the pathogenesis of intestinal atresia and radically altered the surgical treatment of the condition. As a result of a review of cases of intestinal atresia at.

  8. Pattern Of Intestinal Obstruction In A Semiurban Nigerian Hospital ...

    African Journals Online (AJOL)

    Adhesive intestinal obstruction is the commonest cause in this semi-urban population which was studied. Obstructed hernia is becoming increasingly less common as a cause of intestinal obstruction. Keywords: Pattern, Intestinal Obstruction, Semiurban Hospital. Nigerian Journal of Clinical Practice Vol. 11 (4) 2008: pp.

  9. Novel biomarkers for cardiovascular risk prediction.

    Science.gov (United States)

    Wang, Juan; Tan, Guo-Juan; Han, Li-Na; Bai, Yong-Yi; He, Miao; Liu, Hong-Bin

    2017-02-01

    Cardiovascular disease (CVD) is the leading cause of death and disability worldwide. The primary prevention of CVD is dependent upon the ability to identify high-risk individuals long before the development of overt events. This highlights the need for accurate risk stratification. An increasing number of novel biomarkers have been identified to predict cardiovascular events. Biomarkers play a critical role in the definition, prognostication, and decision-making regarding the management of cardiovascular events. This review focuses on a variety of promising biomarkers that provide diagnostic and prognostic information. The myocardial tissue-specific biomarker cardiac troponin, high-sensitivity assays for cardiac troponin, and heart-type fatty acid binding proteinall help diagnose myocardial infarction (MI) in the early hours following symptoms. Inflammatory markers such as growth differentiation factor-15, high-sensitivity C-reactive protein, fibrinogen, and uric acid predict MI and death. Pregnancy-associated plasma protein A, myeloperoxidase, and matrix metalloproteinases predict the risk of acute coronary syndrome. Lipoprotein-associated phospholipase A2 and secretory phospholipase A2 predict incident and recurrent cardiovascular events. Finally, elevated natriuretic peptides, ST2, endothelin-1, mid-regional-pro-adrenomedullin, copeptin, and galectin-3 have all been well validated to predict death and heart failure following a MI and provide risk stratification information for heart failure. Rapidly developing new areas, such as assessment of micro-RNA, are also explored. All the biomarkers reflect different aspects of the development of atherosclerosis.

  10. Biomarkers for wound healing and their evaluation.

    Science.gov (United States)

    Patel, S; Maheshwari, A; Chandra, A

    2016-01-01

    A biological marker (biomarker) is a substance used as an indicator of biological state. Advances in genomics, proteomics and molecular pathology have generated many candidate biomarkers with potential clinical value. Research has identified several cellular events and mediators associated with wound healing that can serve as biomarkers. Macrophages, neutrophils, fibroblasts and platelets release cytokines molecules including TNF-α, interleukins (ILs) and growth factors, of which platelet-derived growth factor (PDGF) holds the greatest importance. As a result, various white cells and connective tissue cells release both matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs). Studies have demonstrated that IL-1, IL-6, and MMPs, levels above normal, and an abnormally high MMP/TIMP ratio are often present in non-healing wounds. Clinical examination of wounds for these mediators could predict which wounds will heal and which will not, suggesting use of these chemicals as biomarkers of wound healing. There is also evidence that the application of growth factors like PDGF will alleviate the recuperating process of chronic, non-healing wounds. Finding a specific biomarker for wound healing status would be a breakthrough in this field and helping treat impaired wound healing.

  11. [Circulating proteinic biomarkers and breast cancer].

    Science.gov (United States)

    Mathelin, C; Koehl, C; Rio, M-C

    2006-01-01

    Circulating proteinic biomarkers are secreted by tumor cells or by their environmental cells and they have a variable specificity. In case of breast cancer, carcino-embryonic antigen (CEA) was for a long time the only circulating biomarker used. Nowadays, the most useful biomarkers measure circulating levels of fragments of MUC1-polymorphic epithelial mucin (MUC1-PEM): cancer antigen (CA) 15.3, mucin-like carcinoma-associated antigen (MCA), CA 27-29, CA 549... They are useful for general disease follow-up. Other circulating markers belonging to keratins (tissue polypeptide antigen, TPA, TPS or Cyfra 21.1) are correlated with proliferative activity of breast tumors. More recently, the measure of the c-erb B2 circulating part (extra cellular domain, ECD) was proposed as a prognostic biomarker for breast tumors with c-erb B2 overexpression. Moreover, the determination of urinary level of trefoil factor1 (PS2-TFF1) might be useful for the follow-up of hormonodependent breast cancers. The present review describes the clinical interest of these different circulating biomarkers in case of breast cancer, emphasizing their biological characteristics.

  12. Computational Analyses for Transplant Biomarker Discovery

    Directory of Open Access Journals (Sweden)

    Anyou eWang

    2015-09-01

    Full Text Available Translational medicine offers a rich promise for improved diagnostics and drug discovery for biomedical research in the field of transplantation, where continued unmet diagnostic and therapeutic needs persist. Current advent of genomics and proteomics profiling called omics provides new resources to develop novel biomarkers for clinical routine. Establishing such a marker system heavily depends on appropriate applications of computational algorithms and software, which are basically based on mathematical theories and models. Understanding these theories would help to apply appropriate algorithms to ensure biomarker systems successful. Here, we review the key advances in theories and mathematical models relevant to transplant biomarker developments. Advantages and limitations inherent inside these models are discussed. The principles of key computational approaches for selecting efficiently the best subset of biomarkers from high dimensional omics data are highlighted. Prediction models are also introduced and the integration of multi-microarray data is also discussed. Appreciating these key advances would help to accelerate the development of clinically reliable biomarker systems.

  13. Are self-reported gastrointestinal symptoms among older adults associated with increased intestinal permeability and psychological distress?

    Science.gov (United States)

    Ganda Mall, John-Peter; Östlund-Lagerström, Lina; Lindqvist, Carl Mårten; Algilani, Samal; Rasoal, Dara; Repsilber, Dirk; Brummer, Robert J; V Keita, Åsa; Schoultz, Ida

    2018-03-20

    Despite the substantial number of older adults suffering from gastrointestinal (GI) symptoms little is known regarding the character of these complaints and whether they are associated with an altered intestinal barrier function and psychological distress. Our aim was to explore the relationship between self-reported gut health, intestinal permeability and psychological distress among older adults. Three study populations were included: 1) older adults with GI symptoms (n = 24), 2) a group of older adults representing the general elderly population in Sweden (n = 22) and 3) senior orienteering athletes as a potential model of healthy ageing (n = 27). Questionnaire data on gut-health, psychological distress and level of physical activity were collected. Intestinal permeability was measured by quantifying zonulin in plasma. The level of systemic and local inflammation was monitored by measuring C-reactive protein (CRP), hydrogen peroxide in plasma and calprotectin in stool samples. The relationship between biomarkers and questionnaire data in the different study populations was illustrated using a Principal Component Analysis (PCA). Older adults with GI symptoms displayed significantly higher levels of both zonulin and psychological distress than both general older adults and senior orienteering athletes. The PCA analysis revealed a separation between senior orienteering athletes and older adults with GI symptoms and showed an association between GI symptoms, psychological distress and zonulin. Older adults with GI symptoms express increased plasma levels of zonulin, which might reflect an augmented intestinal permeability. In addition, this group suffer from higher psychological distress compared to general older adults and senior orienteering athletes. This relationship was further confirmed by a PCA plot, which illustrated an association between GI symptoms, psychological distress and intestinal permeability.

  14. Intestinal and Circulating MicroRNAs in Coeliac Disease.

    Science.gov (United States)

    Felli, Cristina; Baldassarre, Antonella; Masotti, Andrea

    2017-09-06

    MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression at the post-transcriptional level and play a key role in the pathogenesis of autoimmune and gastrointestinal diseases. Previous studies have revealed that miRNAs are dysregulated in intestinal biopsies of patients affected by coeliac disease (CD). Combined bioinformatics analyses of miRNA expression profiles and mRNA target genes as classified by Gene Ontology, are powerful tools to investigate the functional role of miRNAs in coeliac disease. However, little is still known about the function of circulating miRNAs, their expression level compared to tissue miRNAs, and whether the mechanisms of post-transcriptional regulation are the same of tissue miRNAs. In any case, if we assume that a cell-cell communication process has to occur, and that circulating miRNAs are delivered to recipient cells, we can derive useful information by performing target predictions. Interestingly, all of the mRNA targets of dysregulated miRNAs reported in the literature (i.e., miR-31-5p, miR-192, miR-194, miR-449a and miR-638) belong to several important biological processes, such as Wnt signaling, cell proliferation and differentiation, and adherens junction pathways. Although we think that these predictions have to be necessarily confirmed by "wet-lab" data, the miRNAs dysregulated during the development of CD could be potentially involved in the pathogenesis of coeliac disease and their correlation with circulating miRNAs offers new possibilities to use them as disease biomarkers.

  15. Intestinal schistosomiasis associated with intussusception: a case ...

    African Journals Online (AJOL)

    Abstract: We report a case of intestinal schistosomiasis associated with iliocaecal intussusception resulting from obstructions of the terminal part of the ileum by schistosome egg-induced fibrosis. A 7- year-old boy presented with the history of abdominal pain and difficulties in passing stool for two months. Ultrasound ...

  16. Intestinal perforation caused by multiple magnet ingestion

    Directory of Open Access Journals (Sweden)

    Nergul Corduk

    2014-01-01

    Full Text Available Multiple magnet ingestion is rare, but can cause serious gastrointestinal complications. We report a case of 7-year-old girl with multiple intestinal perforations caused by multiple magnet ingestion. The aim of this report is to draw attention to magnetic toys, results of magnet ingestion and the importance of timing of operation.

  17. Performance, Nutrient Utilization and Intestinal Environment of ...

    African Journals Online (AJOL)

    The performance, nutrient utilization and intestinal environment of weaned rabbits fed diets supplemented with organic acids (acetic acid, citric acid and formic acid) were investigated with 24 (6-week old) rabbits in a completely randomized design. The control diet was not supplemented while others were supplemented ...

  18. Colonoscopic features of early intestinal tuberculosis

    African Journals Online (AJOL)

    1991-03-02

    Mar 2, 1991 ... resembled sessile polyps. They occurred ... the colonoscopic diagnosis of intestinal tuberculosis has, until recently ... Transverse colon. Ascending colon. Rectum. Caecum. Transverse colon. Caecum and ascending colon. Caecum and transverse colon*. Caecum, ascending and transverse colon*. Caecum ...

  19. Repairing organs : lessons from intestine and liver

    NARCIS (Netherlands)

    Gehart, Helmuth; Clevers, Hans

    The concept of organ regeneration has fascinated humanity from ancient mythology to modern science fiction. Recent advances offer the potential to soon bring such technology within the grasp of clinical medicine. Rapidly expanding insights into the intrinsic repair processes of the intestine and

  20. Repairing organs : lessons from intestine and liver

    NARCIS (Netherlands)

    Gehart, Helmuth; Clevers, Hans

    2015-01-01

    The concept of organ regeneration has fascinated humanity from ancient mythology to modern science fiction. Recent advances offer the potential to soon bring such technology within the grasp of clinical medicine. Rapidly expanding insights into the intrinsic repair processes of the intestine and

  1. Rage mediated DAMP signaling in intestinal tumorigenesis

    NARCIS (Netherlands)

    Heijmans, Jarom; Büller, Nikè V. J. A.; Muncan, Vanesa; van den Brink, Gijs R.

    2012-01-01

    In the intestine, a large variety of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) can instigate innate immune responses, which have been shown to promote colorectal carcinogenesis. We have recently demonstrated an important role for the receptor for

  2. Congenital Central Hypoventilation Syndrome And Intestinal

    African Journals Online (AJOL)

    to progressive hypercapnia and sustained hypoxaemia. Neonates with this condition experience hypoventilation or apnoea while asleep. Patients may also have congenital intestinal aganglionosis (CIA), aganglionic megacolon or Hirschsprung's disease, suggesting an aberrant phenotype arising from a defect of migration ...

  3. characterization of intestinal microbiota in celiac children

    African Journals Online (AJOL)

    F. Lahcene1*, A. Tir Touil Meddah1, K. Bouziane-Nedjadi2, B. Meddah1, A. Leke3

    2016-09-01

    Sep 1, 2016 ... In this study, 13 Samples of intestinal biopsy, ... Research Article. Journal of Fundamental and Applied Sciences is licensed under a Creative Commons Attribution-NonCommercial 4.0. International License. ... disease are caused by several factors among, the ingestion of gluten, and it has been suggested.

  4. Postoperative Adhesive Intestinal Obstruction from Gossypiboma ...

    African Journals Online (AJOL)

    We report a case of 41.year.old female admitted with features of intestinal obstruction and had a previous history of hysterectomy performed 2 months back at another hospital. Pathologists must be aware of this entity and its proper reporting as the cases are liable to go to court. Surgeons must recognize the risk factors that ...

  5. Intestinal amino acid metabolism in neonates

    NARCIS (Netherlands)

    van Goudoever, Johannes B.; van der Schoor, Sophie R. D.; Stoll, Barbara; Burrin, Douglas G.; Wattimena, Darcos; Schierbeek, Henk; Schaart, Maaike W.; Riedijk, Maaike A.; van der Lugt, Jasper

    2006-01-01

    The portal-drained viscera (stomach, intestine, pancreas and spleen) have a much higher rate of both energy expenditure and protein synthesis than can be estimated on the basis of their weight. A high utilization rate of dietary nutrients by the portal-drained viscera might result in a low systemic

  6. Unusual cause of neonatal intestinal obstruction | Zikavska ...

    African Journals Online (AJOL)

    There are many causes of intestinal obstruction in the neonatal age. The most common types are mechanical and result from congenital malformations of the gastrointestinal tract. However, functional disorders also occur. In some cases, diagnosis can be made prenatally but in others manifestation occurs after birth. The aim ...

  7. Pig models on intestinal development and therapeutics.

    Science.gov (United States)

    Yin, Lanmei; Yang, Huansheng; Li, Jianzhong; Li, Yali; Ding, Xueqing; Wu, Guoyao; Yin, Yulong

    2017-12-01

    The gastrointestinal tract plays a vital role in nutrient supply, digestion, and absorption, and has a crucial impact on the entire organism. Much attention is being paid to utilize animal models to study the pathogenesis of gastrointestinal diseases in response to intestinal development and health. The piglet has a body size similar to that of the human and is an omnivorous animal with comparable anatomy, nutritional requirements, and digestive and associated inflammatory processes, and displays similarities to the human intestinal microbial ecosystem, which make piglets more appropriate as an animal model for human than other non-primate animals. Therefore, the objective of this review is to summarize key attributes of the piglet model with which to study human intestinal development and intestinal health through probing into the etiology of several gastrointestinal diseases, thus providing a theoretical and hopefully practical, basis for further studies on mammalian nutrition, health, and disease, and therapeutics. Given the comparable nutritional requirements and strikingly similar brain developmental patterns between young piglets and humans, the piglet has been used as an important translational model for studying neurodevelopmental outcomes influenced by pediatric nutrition. Because of similarities in anatomy and physiology between pigs and mankind, more emphasises are put on how to use the piglet model for human organ transplantation research.

  8. Peritoneal drainage for newborn intestinal perforation: primary ...

    African Journals Online (AJOL)

    Keywords: intestinal perforation in newborn, necrotizing enterocolitis, primary peritoneal drainage. Department of Surgery, Paul L. Foster School of Medicine, Texas Tech University. HSC, El Paso, Texas, USA. Correspondence to Donald E. Meier, MD, Department of Surgery, Paul L. Foster. School of Medicine, Texas Tech ...

  9. Genetics Home Reference: intestinal pseudo-obstruction

    Science.gov (United States)

    ... branching network of filaments that make up the cytoskeleton , which gives structure to cells and allows them to change shape and move. ... 2 actin protein is found in smooth muscle cells of the intestinal and urinary ... filaments in the cytoskeleton and reduce the ability of smooth muscles in ...

  10. Intestinal Parasites of the Grasscutter (Thryonomys swinderianus ...

    African Journals Online (AJOL)

    The intestinal content of the animals were examined with the aid of a hand lens, a microscope and direct smear method. The parasites identified include helminthes such as Ancylostoma sp., Trichuris sp., Ascaris sp., Hymenolepis sp. and Schistosoma haematobium, and protozoans such as Giardia sp. and Entamoeba sp.

  11. What's new in Osmosin and intestinal perforation?

    Science.gov (United States)

    Laidler, P; Maslin, S C; Gilhome, R W

    1985-07-01

    New formulations of drugs may have unexpected side effects. Osmosin is a new osmotic-pump controlled-release formulation of Indomethacin, designed to prevent gastrointestinal irritation. However, in a small number of cases the use of Osmosin has coincided with perforation of the small and large intestine, probably because passage of the tablet through the gastrointestinal tract was impeded.

  12. Prevalence of opportunistic intestinal parasites and associated ...

    African Journals Online (AJOL)

    Therefore, frequent assessment of the magnitude and associated factors for intestinal parasitosis is essential for the management of HIV/AIDS patients. Methods: A hospital based cross-sectional study was conducted among patients attending Arba Minch Hospital Antiretroviral Therapy (ART) Clinic from March to June 2016.

  13. Intestinal obstruction secondary to infantile polyarteritis nodosa ...

    African Journals Online (AJOL)

    Polyarteritis Nodosa (PAN) is a rare systemic necrotising vasculitis of medium and small-sized arteries. Patients typically present with systemic symptoms. Obstructive intestinal symptoms are described but usually resolve with treatment of the underlying vascular disease. We report a case of a one year old boy with multiple ...

  14. Assessment of intestinal peristalsis in vitro.

    Science.gov (United States)

    Pozzoli, Cristina; Poli, Enzo

    2012-11-01

    The protocol detailed in this unit is designed to assess intestinal peristaltic motility in the isolated small intestine in vitro and to measure the effects of drugs able to interfere with gut propulsive activity. The procedure is based on Trendelenburg's classic technique, described at the beginning of the 20th century in the isolated guinea pig ileum and, later on, extended to other intestinal preparations from the same animal and other animal species. This unit illustrates the basic procedures for setting up the intestinal preparation, recording peristalsis under near-physiologic conditions, and testing the pharmaco-toxicological effects of drugs and pollutants on the contractile behavior of the gut wall. The protocol allows evaluating the action of drugs affecting sensory and/or motor neurons of the enteric nervous system and how these neurons control the development of the motor program of the gut wall. This model can be exploited to investigate novel compounds undergoing preclinical development and both inhibitors and stimulants of gastrointestinal peristaltic activity, as well as environmental or alimentary pollutants, like xenobiotics and naturally-occurring toxins, endowed with noxious activity with regard to digestive functions.

  15. Schistosomiasis and intestinal helminth infections in Sengerema

    African Journals Online (AJOL)

    Abstract: Schistosomiasis and intestinal helminth infections are common health problems among the people of Lake. Victoria basin particularly in Mwanza ... these infections is largely lacking and that biomedical studies give only a partial ... sampling procedure was such that in each sub-village. ' Correspondence: Joseph R.

  16. Periarrest intestinal bacterial translocation and resuscitation outcome.

    Science.gov (United States)

    Chalkias, Athanasios; Scheetz, Marc H; Gulati, Anil; Xanthos, Theodoros

    2016-02-01

    During the periarrest period, intestinal ischemia may result in barrier dysfunction and bacterial translocation, which has clear mechanistic links to inflammation and cascade stimulation, especially in patients who are treated with therapeutic hypothermia. Despite optimal management, periarrest bacterial translocation may worsen the outcome of cardiac arrest victims. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Intestinal helminth infections among pregnant Cameroonian women ...

    African Journals Online (AJOL)

    Objectives: To investigate the prevalence and intensity of intestinal helminth infections in pregnant Cameroonian women and assess their anaemic status. Design: Longitudinal study. Setting: Buea Integrated Health Centre, Muea Health Centre, Mutengene Integrated Health Centre and the University of Buea Life Sciences ...

  18. Intestinal intussusception due to concurrent infections with ...

    African Journals Online (AJOL)

    The rat was anorexic and depressed with rough hair coat, and died before the commencement of the experiment. Grossly, the intussusception was 7 cm in length and 27 cm caudal to the stomach and 81cm to the ileo-caecal junction. The affected part of the small intestine was moderately distended with worms and the ...

  19. Knowledge based assessment of intestinal parasitic Infections ...

    African Journals Online (AJOL)

    There is an apparent lack of information on the risk and clinical symptoms of Intestinal Parasitic Infections (IPIs) among students attending boarding secondary schools in Ebonyi State, Nigeria. This questionnaire-based survey attempts to assess some behavioural habits, possible risk factor(s) as well as clinical symptoms ...

  20. intestinal helminthiasis among malnourished school age children

    African Journals Online (AJOL)

    Government Area to determine the prevalence rate of intestinal hjelminth infection among malnourished school children. Stool samples and finger prick blood .... in both male and female school children compared with a marked depreciation clue to the .... -rnalnutrition among India children. He submitted that control of such ...

  1. Intestinal Infarctus following Dilatation and Uterine Curettage

    Directory of Open Access Journals (Sweden)

    N.M. Ngowe

    2007-03-01

    Full Text Available We present a case of intestinal infarctus through the vagina. This was a consequence of induced abortion done clandestinely. The main objective was to point out the surgical complications of uterine dilatation and curettage by means of this rare case.

  2. Therapeutic hypothermia reduces intestinal ischemia/reperfusion ...

    African Journals Online (AJOL)

    To investigate the effects of therapeutic hypothermia (TH) on the morphology and function of intestine after cardiac arrest and resuscitation, 45 male rats were randomly assigned into three groups: (1) normothermia group, animals underwent ventricular fibrillation (VF) and cardiopulmonary resuscitation (CPR) with the rectal ...

  3. Mucin dynamics in intestinal bacterial infection.

    Directory of Open Access Journals (Sweden)

    Sara K Lindén

    Full Text Available Bacterial gastroenteritis causes morbidity and mortality in humans worldwide. Murine Citrobacter rodentium infection is a model for gastroenteritis caused by the human pathogens enteropathogenic Escherichia coli and enterohaemorrhagic E. coli. Mucin glycoproteins are the main component of the first barrier that bacteria encounter in the intestinal tract.Using Immunohistochemistry, we investigated intestinal expression of mucins (Alcian blue/PAS, Muc1, Muc2, Muc4, Muc5AC, Muc13 and Muc3/17 in healthy and C. rodentium infected mice. The majority of the C. rodentium infected mice developed systemic infection and colitis in the mid and distal colon by day 12. C. rodentium bound to the major secreted mucin, Muc2, in vitro, and high numbers of bacteria were found in secreted MUC2 in infected animals in vivo, indicating that mucins may limit bacterial access to the epithelial surface. In the small intestine, caecum and proximal colon, the mucin expression was similar in infected and non-infected animals. In the distal colonic epithelium, all secreted and cell surface mucins decreased with the exception of the Muc1 cell surface mucin which increased after infection (p<0.05. Similarly, during human infection Salmonella St Paul, Campylobacter jejuni and Clostridium difficile induced MUC1 in the colon.Major changes in both the cell-surface and secreted mucins occur in response to intestinal infection.

  4. intestinal helminth infections among pregnant cameroonian women

    African Journals Online (AJOL)

    East African Medical Journal Vol. 88 No. 11 November 2011. INTESTINAL HELMINTH ... The pregnant women received mebendazole and iron tablets on the day of enrollment at the antenatal clinic to control helminth ... malnutrition, vitamin A deficiency, diarrhoea and iron-deficiency anaemia (3,1). Pregnant women and.

  5. Metabolic complications in the small intestine syndrome

    International Nuclear Information System (INIS)

    Mora, Rafael; Orozco, Reynaldo

    2000-01-01

    Metabolic complications in the syndrome of small intestine is presented in a patient of masculine sex, 27 years old, who consulted for a square of inflammation gingival, migraine, fever, anorexia and adinamia for three days, followed by maculopapular-eritematose eruption for 8 days, coincident with the ampicillin ingestion, and later on severe abdominal pain and diarrhea

  6. Therapeutic hypothermia reduces intestinal ischemia/reperfusion ...

    African Journals Online (AJOL)

    Jane

    2011-07-25

    Jul 25, 2011 ... diamine oxidase (DAO) and apoptosis rate of intestinal epithelial cells were tested by ELISA and flow cytometry, respectively. ... The interruption and restoration of blood flow, induced by. *Corresponding author. ... intubated with a 14-gauge cannula (Abbocath-T, Abbott Hospital. Products Division; North ...

  7. Temporary intestinal ischemia for radiation protection

    International Nuclear Information System (INIS)

    Lote, K.

    1983-01-01

    The most important determinant of cellular radiosensivity is the tissue oxygen content at the time of irradiation. The purpose of the present experimental work was to assess a new iscemia-inducing method in order to reduce normal tissue radiation damage during radiotherapy. Temporary ischemia was induced in a cat small intestine by degraded starch microspheres. Regional arterial and tissue blod flow immediately fell by 85% with subsequent normalization within 26 minutes after microsphere injection. No tendency of small vessel thrombosis caused by starch sphere embolization in combination with previous or current intestinal irradiation was detected. Starch sphere remenants were rapidly engulfed by, and persisted within tissue macrophages for 14 days without causing intestinal inflammatory reactions. In vitro studies showed that human platelets neither adhered to nor were aggregated by starch microspheres. The new method, wich occlude arteriolar vessels distal to the mesentric arterial arcades and thus largely excludes collateral blood flow, seems suited to provide effictive and selective feline small intestinal hypoxic radiation protection. This conclusion may also be valid in man

  8. Faecalibacterium prausnitzii and human intestinal health

    NARCIS (Netherlands)

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

    2013-01-01

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

  9. Intestinal colonisation, microbiota and future probiotics

    NARCIS (Netherlands)

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

    2006-01-01

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

  10. Intestinal obstruction in germ-free dogs.

    Science.gov (United States)

    Heneghan, J B; Robinson, J W; Menge, H; Winistörfer, B

    1981-08-01

    Mechanical occlusions were created in the intestines of four germ-free dogs. At the time of the operation, a control loop of mid-intestine was perfused in vivo and then excised for examinations in vitro, which included the determination of the equilibrium uptake of phenylalanine and of beta-methyl-glucoside, the influx kinetics of phenylalanine and morphometric analysis of the mucosa by microdissection and stereological techniques. Seven days after establishment of the occlusion the abdomen was reopened, and loops above and below the occlusion were perfused, and then excised for the same tests in vitro. Unlike occluded loops of conventional dogs, the intestine of the germ-free animal above the occlusion does not secrete water and electrolytes into the lumen. Its transport properties in vitro do not differ from those of the control loop, and the morphometric analyses reveal only slight changes in villus structure. The loop below the obstruction undergoes marked atrophy, as has been observed in conventional dogs. The results suggest that the copious secretion that occurs above an intestinal obstruction in normal animals is due to the presence of an abundant bacterial population in the obstruction fluid.

  11. Temporal changes in the intestinal growth promoting effects of glucagon-like peptide 2 following intestinal resection

    DEFF Research Database (Denmark)

    Kaji, Tatsuru; Tanaka, Hiroaki; Redstone, Heather

    2008-01-01

    BACKGROUND: We investigated the effects of variations in the postresection timing of glucagon-like peptide-2 (GLP-2) administration on intestinal morphology and activity. METHODS: A rat model of 90% intestinal resection (SBR) with exclusively parenteral nutritional (TPN) was used. Early versus late...... that the intestinal adaptive and growth promoting actions of GLP-2 may be mediated by non-neuronal effector pathways. Although further studies are required, early treatment with GLP-2 following resection may maximize intestinal growth....

  12. Effects of Digested Onion Extracts on Intestinal Gene Expression: An Interspecies Comparison Using Different Intestine Models.

    Directory of Open Access Journals (Sweden)

    Nicole J W de Wit

    Full Text Available Human intestinal tissue samples are barely accessible to study potential health benefits of nutritional compounds. Numbers of animals used in animal trials, however, need to be minimalized. Therefore, we explored the applicability of in vitro (human Caco-2 cells and ex vivo intestine models (rat precision cut intestine slices and the pig in-situ small intestinal segment perfusion (SISP technique to study the effect of food compounds. In vitro digested yellow (YOd and white onion extracts (WOd were used as model food compounds and transcriptomics was applied to obtain more insight into which extent mode of actions depend on the model. The three intestine models shared 9,140 genes which were used to compare the responses to digested onions between the models. Unsupervised clustering analysis showed that genes up- or down-regulated by WOd in human Caco-2 cells and rat intestine slices were similarly regulated by YOd, indicating comparable modes of action for the two onion species. Highly variable responses to onion were found in the pig SISP model. By focussing only on genes with significant differential expression, in combination with a fold change > 1.5, 15 genes showed similar onion-induced expression in human Caco-2 cells and rat intestine slices and 2 overlapping genes were found between the human Caco-2 and pig SISP model. Pathway analyses revealed that mainly processes related to oxidative stress, and especially the Keap1-Nrf2 pathway, were affected by onions in all three models. Our data fit with previous in vivo studies showing that the beneficial effects of onions are mostly linked to their antioxidant properties. Taken together, our data indicate that each of the in vitro and ex vivo intestine models used in this study, taking into account their limitations, can be used to determine modes of action of nutritional compounds and can thereby reduce the number of animals used in conventional nutritional intervention studies.

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

    Science.gov (United States)

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

    2013-04-11

    Food can have a significant impact on the pharmacokinetics of orally administered drugs, as it may affect drug solubility as well as permeability. Since fed state conditions cannot easily be implemented in the presently available permeability tools, including the frequently used Caco-2 system, exploring food effects during drug development can be quite challenging. In this study, we investigated the effect of fasted and fed state conditions on the intestinal absorption of the HIV protease inhibitor indinavir using simulated and human intestinal fluids in the in situ intestinal perfusion technique in mice. Although the solubility of indinavir was 6-fold higher in fed state human intestinal fluids (FeHIF) as compared to fasted state HIF (FaHIF), the intestinal permeation of indinavir was 22-fold lower in FeHIF as compared to FaHIF. Dialysis experiments showed that only a small fraction of indinavir is accessible for absorption in FeHIF due to micellar entrapment, possibly explaining its low intestinal permeation. The presence of ritonavir, a known P-gp inhibitor, increased the intestinal permeation of indinavir by 2-fold in FaHIF, while there was no increase when using FeHIF. These data confirm that drug-food interactions form a complex interplay between solubility and permeability effects. The use of HIF in in situ intestinal perfusions holds great promise for biorelevant absorption evaluation as it allows to directly explore this complex solubility/permeability interplay on drug absorption. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Fish oil enhances recovery of intestinal microbiota and epithelial integrity in chronic rejection of intestinal transplant.

    Directory of Open Access Journals (Sweden)

    Qiurong Li

    Full Text Available BACKGROUND: The intestinal chronic rejection (CR is the major limitation to long-term survival of transplanted organs. This study aimed to investigate the interaction between intestinal microbiota and epithelial integrity in chronic rejection of intestinal transplantation, and to find out whether fish oil enhances recovery of intestinal microbiota and epithelial integrity. METHODS/PRINCIPAL FINDINGS: The luminal and mucosal microbiota composition of CR rats were characterized by DGGE analysis at 190 days after intestinal transplant. The specific bacterial species were determined by sequence analysis. Furthermore, changes in the localization of intestinal TJ proteins were examined by immunofluorescent staining. PCR-DGGE analysis revealed that gut microbiota in CR rats had a shift towards Escherichia coli, Bacteroides spp and Clostridium spp and a decrease in the abundance of Lactobacillales bacteria in the intestines. Fish oil supplementation could enhance the recovery of gut microbiota, showing a significant decrease of gut bacterial proportions of E. coli and Bacteroides spp and an increase of Lactobacillales spp. In addition, CR rats showed pronounced alteration of tight junction, depicted by marked changes in epithelial cell ultrastructure and redistribution of occuldin and claudins as well as disruption in TJ barrier function. Fish oil administration ameliorated disruption of epithelial integrity in CR, which was associated with an improvement of the mucosal structure leading to improved tight junctions. CONCLUSIONS/SIGNIFICANCE: Our study have presented novel evidence that fish oil is involved in the maintenance of epithelial TJ integrity and recovery of gut microbiota, which may have therapeutic potential against CR in intestinal transplantation.

  15. Effects of Digested Onion Extracts on Intestinal Gene Expression: An Interspecies Comparison Using Different Intestine Models.

    Science.gov (United States)

    de Wit, Nicole J W; Hulst, Marcel; Govers, Coen; van der Meulen, Jan; van Hoef, Angeline; Stoopen, Geert; Hamers, Astrid; Hoekman, Arjan; de Vos, Ric; Bovee, Toine F H; Smits, Mari; Mes, Jurriaan J; Hendriksen, Peter J M

    2016-01-01

    Human intestinal tissue samples are barely accessible to study potential health benefits of nutritional compounds. Numbers of animals used in animal trials, however, need to be minimalized. Therefore, we explored the applicability of in vitro (human Caco-2 cells) and ex vivo intestine models (rat precision cut intestine slices and the pig in-situ small intestinal segment perfusion (SISP) technique) to study the effect of food compounds. In vitro digested yellow (YOd) and white onion extracts (WOd) were used as model food compounds and transcriptomics was applied to obtain more insight into which extent mode of actions depend on the model. The three intestine models shared 9,140 genes which were used to compare the responses to digested onions between the models. Unsupervised clustering analysis showed that genes up- or down-regulated by WOd in human Caco-2 cells and rat intestine slices were similarly regulated by YOd, indicating comparable modes of action for the two onion species. Highly variable responses to onion were found in the pig SISP model. By focussing only on genes with significant differential expression, in combination with a fold change > 1.5, 15 genes showed similar onion-induced expression in human Caco-2 cells and rat intestine slices and 2 overlapping genes were found between the human Caco-2 and pig SISP model. Pathway analyses revealed that mainly processes related to oxidative stress, and especially the Keap1-Nrf2 pathway, were affected by onions in all three models. Our data fit with previous in vivo studies showing that the beneficial effects of onions are mostly linked to their antioxidant properties. Taken together, our data indicate that each of the in vitro and ex vivo intestine models used in this study, taking into account their limitations, can be used to determine modes of action of nutritional compounds and can thereby reduce the number of animals used in conventional nutritional intervention studies.

  16. Effects of zeolite supplementation on parameters of intestinal barrier integrity, inflammation, redoxbiology and performance in aerobically trained subjects.

    Science.gov (United States)

    Lamprecht, Manfred; Bogner, Simon; Steinbauer, Kurt; Schuetz, Burkhard; Greilberger, Joachim F; Leber, Bettina; Wagner, Bernhard; Zinser, Erwin; Petek, Thomas; Wallner-Liebmann, Sandra; Oberwinkler, Tanja; Bachl, Norbert; Schippinger, Gert

    2015-01-01

    Zeolites are crystalline compounds with microporous structures of Si-tetrahedrons. In the gut, these silicates could act as adsorbents, ion-exchangers, catalysts, detergents or anti-diarrheic agents. This study evaluated whether zeolite supplementation affects biomarkers of intestinal wall permeability and parameters of oxidation and inflammation in aerobically trained individuals, and whether it could improve their performance. In a randomized, double-blinded, placebo controlled trial, 52 endurance trained men and women, similar in body fat, non-smokers, 20-50 years, received 1.85 g of zeolite per day for 12 weeks. Stool samples for determination of intestinal wall integrity biomarkers were collected. From blood, markers of redox biology, inflammation, and DNA damage were determined at the beginning and the end of the study. In addition, VO2max and maximum performance were evaluated at baseline and after 12 weeks of treatment. For statistical analyses a 2-factor ANOVA was used. At baseline both groups showed slightly increased stool zonulin concentrations above normal. After 12 weeks with zeolite zonulin was significantly (p zonulin. This was accompanied by mild anti-inflammatory effects in this cohort of aerobically trained subjects. Further research is needed to explore mechanistic explanations for the observations in this study.

  17. Transplante de intestino delgado Small intestine transplantation

    Directory of Open Access Journals (Sweden)

    Flávio Henrique Ferreira Galvão

    2003-06-01

    Full Text Available RACIONAL: Avanços da biotecnologia e o desenvolvimento de novas drogas imunossupressoras melhoraram os resultados do transplante de intestino delgado. Esse transplante é atualmente indicado para casos especiais da falência intestinal. OBJETIVO: A presente revisão realça os recentes desenvolvimentos na área do transplante de intestino delgado. MATERIAL E MÉTODO: Mais de 600 publicações de transplante de intestino delgado foram revisadas. O desenvolvimento da pesquisa, novas estratégias de imunossupressão, monitorização do enxerto e do receptor, e avanços na técnica cirúrgica são discutidos. RESULTADOS: Realizaram-se cerca de 700 transplante de intestino delgado em 55 centros: 44% intestino-fígado, 41% enxerto intestinal isolado e 15% transplante multivisceral. Rejeição e infecção são as principais limitações desse transplante. Sobrevida de 5 anos na experiência internacional é de 46% para o transplante de intestino isolado, 43% para o intestino-fígado e de cerca de 30% para o transplante multivisceral. Sobrevidas prolongadas são mais freqüentes nos centros com maior experiência. Em série de 165 transplantes intestinais na Universidade de Pittsburgh, PA, EUA, foi relatada sobrevida do paciente maior do que 75% no primeiro ano, 54% em 5 anos e 42% em 10 anos. Mais de 90% desses pacientes assumem dieta oral irrestrita. CONCLUSÃO: O transplante de intestino delgado evoluiu de estratégia experimental para uma alternativa viável no tratamento da falência intestinal permanente. Promover o refinamento da terapia imunossupressora, do manejo e prevenção de infecções, da técnica cirúrgica e da indicação e seleção adequada dos pacientes é crucial para melhorar a sobrevida desse transplante.BACKGROUND: Significant progress has been made in clinical small bowel transplantation over the last decade mainly due advances in biotechnology and new immunosuppressive regiments. This transplantation has now been indicated

  18. [The complications of intestinal stoma in children].

    Science.gov (United States)

    Minaev, S V; Bykov, N I; Isaeva, A V; Kachanov, A V; Tovkan, E A; Filip'yeva, N V; Gerasimenko, I N

    To investigate the complications of intestinal stoma in children and to develop measures for decrease of their incidence. The study included 152 children with congenital and acquired gastrointestinal pathology requiring surgical treatment with the imposition of intestinal stoma. Atresia of intestinal tube was observed in 28 (18.4%) children, meconium ileus - in 10 (6.6%) cases, Hirschsprung's disease - in 11 (7.2%)cases, anorectal malformations - in 39 (25.7%) cases, multiple malformations - in 11 (7.2%) patients, necrotic enterocolitis - in 56 (36.8%) patients, other reasons - in 7 (4.6%) cases. The average age of patients was 12,3±7,2 days. There were 93 (61.2%) boys and 59 (38.8%) girls. Ileostomy, ileocolostomy and colostomy were made in 37 (24.3%), 46 (30.3%) and 69 (45.4%) cases respectively. Time of intestinal stoma function was 18-217 days. Early complications were dehiscence in the area of stoma in 4 (2.6%) children, evagination in 7 (4.6%) patients, marginal necrosis of stoma in 2 (1.3%) cases, retraction of stomy into abdominal cavity in 1 (0.6%) child and abdominal skin maceration in 8 (5.2%) patients. Remote complications included dermatitis around stomy in 35 (23.1%) children, stenosis of stoma in 9 (5.9%) cases, evagination of stoma in 12 (7.9%) patients. Also, 5 patients were unable to use the colostomy bag due to vicious overlaying of intestinal stoma. Using the colostomy bags «Coloplast» and skin care products around the stoma significantly reduced (pstoma depends on not only technical aspects but also obligatory care performance with timely correction of complications.

  19. Role of Smooth Muscle in Intestinal Inflammation

    Directory of Open Access Journals (Sweden)

    Stephen M Collins

    1996-01-01

    Full Text Available The notion that smooth muscle function is altered in inflammation is prompted by clinical observations of altered motility in patients with inflammatory bowel disease (IBD. While altered motility may reflect inflammation-induced changes in intrinsic or extrinsic nerves to the gut, changes in gut hormone release and changes in muscle function, recent studies have provided in vitro evidence of altered muscle contractility in muscle resected from patients with ulcerative colitis or Crohn’s disease. In addition, the observation that smooth muscle cells are more numerous and prominent in the strictured bowel of IBD patients compared with controls suggests that inflammation may alter the growth of intestinal smooth muscle. Thus, inflammation is associated with changes in smooth muscle growth and contractility that, in turn, contribute to important symptoms of IBD including diarrhea (from altered motility and pain (via either altered motility or stricture formation. The involvement of smooth muscle in this context may be as an innocent bystander, where cells and products of the inflammatory process induce alterations in muscle contractility and growth. However, it is likely that intestinal muscle cells play a more active role in the inflammatory process via the elaboration of mediators and trophic factors, including cytokines, and via the production of collagen. The concept of muscle cells as active participants in the intestinal inflammatory process is a new concept that is under intense study. This report summarizes current knowledge as it relates to these two aspects of altered muscle function (growth and contractility in the inflamed intestine, and will focus on mechanisms underlying these changes, based on data obtained from animal models of intestinal inflammation.

  20. Determination of Intestine Inflammation Markers in Diagnostic Search in Children with Intestinal Diseases

    Directory of Open Access Journals (Sweden)

    N.V. Pavlenko

    2016-08-01

    Full Text Available Introduction. Prevalence of bowel diseases in children is the second, trailing only the diseases of gastroduodenal zone and growing in recent years. Actual one is the problem of differential diagnosis of functional and inflammatory intestinal diseases using non-invasive methods on the prehospital stage and as a screening. Objective. Comparative analysis of fecal markers of the bowel inflammation (lactoferrine and calprotectine with endoscopy and morphology of intestinal mucosa in children. Matherials and methods. 49 children aged 6–18 years were examined. All patients underwent endoscopic and morphological study of the intestine, coprotest, determination of fecal markers of bowel inflammation (lactoferrin and calprotectine. Results. It is shown that in young children, the intestinal mucosa mainly hadn’t endoscopic changes, coprotest and morphological examination didn’t reveal the signs of inflammation, fecal intestinal inflammation markers were negative (p < 0.05. In the group of older children, moderate or marked catarrhal changes were found endoscopically, coprotest results were typical of inflammation in the intestines, it was morphologically proved the presence of chronic inflammation of the mucous membrane of the colon with signs of atrophy, the results of lactoferrin and calprotectine determination were positive (p < 0.05. Conclusion. The findings suggest that the evaluation of calprotectine and lactoferrin can be used in pediatric patients because of its non-invasiveness as diagnostic screening for the selection of patients for the further endoscopic examination and diagnostic search.

  1. Epigenetics as biomarkers in autoimmune diseases.

    Science.gov (United States)

    Wu, Haijing; Liao, Jieyue; Li, Qianwen; Yang, Ming; Zhao, Ming; Lu, Qianjin

    2018-03-21

    Autoimmune diseases are immune system disorders in which immune cells cannot distinguish self-antigens from foreign ones. The current criteria for autoimmune disease diagnosis are based on clinical manifestations and laboratory tests. However, none of these markers shows both high sensitivity and specificity. In addition, some autoimmune diseases, for example, systemic lupus erythematosus (SLE), are highly heterogeneous and often exhibit various manifestations. On the other hand, certain autoimmune diseases, such as Sjogren's syndrome versus SLE, share similar symptoms and autoantibodies, which also causes difficulties in diagnosis. Therefore, biomarkers that have both high sensitivity and high specificity for diagnosis, reflect disease activity and predict drug response are necessary. An increasing number of publications have proposed the abnormal epigenetic modifications as biomarkers of autoimmune diseases. Therefore, this review will comprehensively summarize the epigenetic progress in the pathogenesis of autoimmune disorders and unearth potential biomarkers that might be appropriate for disease diagnosis and prediction. Copyright © 2018. Published by Elsevier Inc.

  2. Chromogranin A as biomarker in diabetes

    DEFF Research Database (Denmark)

    Broedbaek, Kasper; Hilsted, Linda

    2016-01-01

    Chromogranin A (CgA) is an established plasma marker of neuroendocrine tumors and has been suggested to also have a role as biomarker in other diseases. Whether CgA has any role as biomarker in diabetes is, however, unresolved, but its widespread distribution in the secretory granules in endocrine...... tissues including β cells and α cells in pancreas, and the metabolic effects of its peptide fragments suggest that CgA may play a pathophysiological role in diabetes, and thus also be a potential diabetes biomarker. In this review, we summarize the available information on CgA and some of its functional...... post-translational cleavage products in diabetes, followed by a discussion of its potential as a plasma marker in diabetes and the methodological concerns involved....

  3. Using Aptamers for Cancer Biomarker Discovery

    Directory of Open Access Journals (Sweden)

    Yun Min Chang

    2013-01-01

    Full Text Available Aptamers are single-stranded synthetic DNA- or RNA-based oligonucleotides that fold into various shapes to bind to a specific target, which includes proteins, metals, and molecules. Aptamers have high affinity and high specificity that are comparable to that of antibodies. They are obtained using iterative method, called (Systematic Evolution of Ligands by Exponential Enrichment SELEX and cell-based SELEX (cell-SELEX. Aptamers can be paired with recent advances in nanotechnology, microarray, microfluidics, and other technologies for applications in clinical medicine. One particular area that aptamers can shed a light on is biomarker discovery. Biomarkers are important in diagnosis and treatment of cancer. In this paper, we will describe ways in which aptamers can be used to discover biomarkers for cancer diagnosis and therapeutics.

  4. Biomarkers in pancreatic adenocarcinoma: current perspectives.

    Science.gov (United States)

    Swords, Douglas S; Firpo, Matthew A; Scaife, Courtney L; Mulvihill, Sean J

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5-year survival rate of 7.7%. Most patients are diagnosed at an advanced stage not amenable to potentially curative resection. A substantial portion of this review is dedicated to reviewing the current literature on carbohydrate antigen (CA 19-9), which is currently the only guideline-recommended biomarker for PDAC. It provides valuable prognostic information, can predict resectability, and is useful in decision making about neoadjuvant therapy. We also discuss carcinoembryonic antigen (CEA), CA 125, serum biomarker panels, circulating tumor cells, and cell-free nucleic acids. Although many biomarkers have now been studied in relation to PDAC, significant work still needs to be done to validate their usefulness in the early detection of PDAC and management of patients with PDAC.

  5. Advances in biomarkers of major depressive disorder.

    Science.gov (United States)

    Huang, Tiao-Lai; Lin, Chin-Chuen

    2015-01-01

    Major depressive disorder (MDD) is characterized by mood, vegetative, cognitive, and even psychotic symptoms and signs that can cause substantial impairments in quality of life and functioning. Biomarkers are measurable indicators that could help diagnosing MDD or predicting treatment response. In this chapter, lipid profiles, immune/inflammation, and neurotrophic factor pathways that have long been implicated in the pathogenesis of MDD are discussed. Then, pharmacogenetics and epigenetics of serotonin transport and its metabolism pathway, brain-derived neurotrophic factor, and abnormality of hypothalamo-pituitary-adrenocortical axis also revealed new biomarkers. Lastly, new techniques, such as proteomics and metabolomics, which allow researchers to approach the studying of MDD with new directions and make new discoveries are addressed. In the future, more data are needed regarding pathophysiology of MDD, including protein levels, single nucleotide polymorphism, epigenetic regulation, and clinical data in order to better identify reliable and consistent biomarkers for diagnosis, treatment choice, and outcome prediction. © 2015 Elsevier Inc. All rights reserved.

  6. Current early diagnostic biomarkers of prostate cancer

    Directory of Open Access Journals (Sweden)

    Min Qu

    2014-08-01

    Full Text Available Prostate cancer (PCa has become to have the highest incidence and the second mortality rate in western countries, affecting men's health to a large extent. Although prostate-specific antigen (PSA was discovered to help diagnose the cancer in an early stage for decades, its specificity is relative low, resulting in unnecessary biopsy for healthy people and over-treatment for patients. Thus, it is imperative to identify more and more effective biomarkers for early diagnosis of PCa in order to distinguish patients from healthy populations, which helps guide an early treatment to lower disease-related mortality by noninvasive or minimal invasive approaches. This review generally describes the current early diagnostic biomarkers of PCa in addition to PSA and summarizes the advantages and disadvantages of these biomarkers.

  7. Biomarkers for CNS involvement in pediatric lupus

    Science.gov (United States)

    Rubinstein, Tamar B; Putterman, Chaim; Goilav, Beatrice

    2015-01-01

    CNS disease, or central neuropsychiatric lupus erythematosus (cNPSLE), occurs frequently in pediatric lupus, leading to significant morbidity and poor long-term outcomes. Diagnosing cNPSLE is especially difficult in pediatrics; many current diagnostic tools are invasive and/or costly, and there are no current accepted screening mechanisms. The most complicated aspect of diagnosis is differentiating primary disease from other etiologies; research to discover new biomarkers is attempting to address this dilemma. With many mechanisms involved in the pathogenesis of cNPSLE, biomarker profiles across several modalities (molecular, psychometric and neuroimaging) will need to be used. For the care of children with lupus, the challenge will be to develop biomarkers that are accessible by noninvasive measures and reliable in a pediatric population. PMID:26079959

  8. Precision cut intestinal slices are an appropriate ex vivo model to study NSAID-induced intestinal toxicity in rats

    NARCIS (Netherlands)

    Niu, Xiaoyu; de Graaf, Inge A. M.; van der Bij, Hendrik A.; Groothuis, Geny M. M.

    2014-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used therapeutic agents, however, they are associated with a high prevalence of intestinal side effects. In this investigation, rat precision cut intestinal slices (PCIS) were evaluated as an ex vivo model to study NSAID-induced intestinal

  9. Alternative Functional In Vitro Models of Human Intestinal Epithelia

    Directory of Open Access Journals (Sweden)

    Amanda L Kauffman

    2013-07-01

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

  10. Molecular biomarker analyses using circulating tumor cells.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Punnoose

    2010-09-01

    Full Text Available Evaluation of cancer biomarkers from blood could significantly enable biomarker assessment by providing a relatively non-invasive source of representative tumor material. Circulating Tumor Cells (CTCs isolated from blood of metastatic cancer patients hold significant promise in this regard.Using spiked tumor-cells we evaluated CTC capture on different CTC technology platforms, including CellSearch and two biochip platforms, and used the isolated CTCs to develop and optimize assays for molecular characterization of CTCs. We report similar performance for the various platforms tested in capturing CTCs, and find that capture efficiency is dependent on the level of EpCAM expression. We demonstrate that captured CTCs are amenable to biomarker analyses such as HER2 status, qRT-PCR for breast cancer subtype markers, KRAS mutation detection, and EGFR staining by immunofluorescence (IF. We quantify cell surface expression of EGFR in metastatic lung cancer patient samples. In addition, we determined HER2 status by IF and FISH in CTCs from metastatic breast cancer patients. In the majority of patients (89% we found concordance with HER2 status from patient tumor tissue, though in a subset of patients (11%, HER2 status in CTCs differed from that observed in the primary tumor. Surprisingly, we found CTC counts to be higher in ER+ patients in comparison to HER2+ and triple negative patients, which could be explained by low EpCAM expression and a more mesenchymal phenotype of tumors belonging to the basal-like molecular subtype of breast cancer.Our data suggests that molecular characterization from captured CTCs is possible and can potentially provide real-time information on biomarker status. In this regard, CTCs hold significant promise as a source of tumor material to facilitate clinical biomarker evaluation. However, limitations exist from a purely EpCAM based capture system and addition of antibodies to mesenchymal markers could further improve CTC

  11. Biomarkers of lipid peroxidation in clinical material.

    Science.gov (United States)

    Niki, Etsuo

    2014-02-01

    Free radical-mediated lipid peroxidation has been implicated in a number of human diseases. Diverse methods have been developed and applied to measure lipid peroxidation products as potential biomarkers to assess oxidative stress status in vivo, discover early indication of disease, diagnose progression of disease, and evaluate the effectiveness of drugs and antioxidants for treatment of disease and maintenance of health, respectively. However, standardized methods are not yet established. Characteristics of various lipid peroxidation products as biomarkers are reviewed on the basis of mechanisms and dynamics of their formation and metabolism and also on the methods of measurement, with an emphasis on the advantages and limitations. Lipid hydroxides such as hydroxyoctadecadienoic acids (HODE), hydroxyeicosatetraenoic acids (HETE), and hydroxycholesterols may be recommended as reliable biomarkers. Notably, the four HODEs, 9-cis,trans, 9-trans,trans, 13-cis,trans, and 13-trans,trans-HODE, can be measured separately by LC-MS/MS and the trans,trans-forms are specific marker of free radical mediated lipid peroxidation. Further, isoprostanes and neuroprostanes are useful biomarker of lipid peroxidation. It is important to examine the distribution and temporal change of these biomarkers. Despite the fact that lipid peroxidation products are non-specific biomarkers, they will enable to assess oxidative stress status, disease state, and effects of drugs and antioxidants. This article is part of a Special Issue entitled Current methods to study reactive oxygen species - pros and cons and biophysics of membrane proteins. Guest Editor: Christine Winterbourn. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Biomarkers in Multiple Sclerosis: Role of Antibodies

    Directory of Open Access Journals (Sweden)

    Thomas Berger

    2006-01-01

    Full Text Available The first international workshop on “Biomarkers in Multiple Sclerosis” was organized by B. Bielekova, R. Hohlfeld, R. Martin and U. Utz from April 14–16, 2004, in Washington, DC. The workshop intended to discuss the current status and potential applicability of biological markers for the understanding of the pathogenesis, diagnosis, and therapy of multiple sclerosis. The present review summarizes the presentation on the potential role of antibodies as biomarkers for diagnosis, disease activity, classification and prediction of clinical courses in multiple sclerosis.

  13. Biomarkers and Targeted Therapy in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Fataneh Karandish

    2016-01-01

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC constitutes 90% of pancreatic cancers. PDAC is a complex and devastating disease with only 1%–3% survival rate in five years after the second stage. Treatment of PDAC is complicated due to the tumor microenvironment, changing cell behaviors to the mesenchymal type, altered drug delivery, and drug resistance. Considering that pancreatic cancer shows early invasion and metastasis, critical research is needed to explore different aspects of the disease, such as elaboration of biomarkers, specific signaling pathways, and gene aberration. In this review, we highlight the biomarkers, the fundamental signaling pathways, and their importance in targeted drug delivery for pancreatic cancers.

  14. WONOEP appraisal: Imaging biomarkers in epilepsy.

    Science.gov (United States)

    van Vliet, Erwin A; Dedeurwaerdere, Stefanie; Cole, Andrew J; Friedman, Alon; Koepp, Matthias J; Potschka, Heidrun; Immonen, Riikka; Pitkänen, Asla; Federico, Paolo

    2017-03-01

    Neuroimaging offers a wide range of opportunities to obtain information about neuronal activity, brain inflammation, blood-brain barrier alterations, and various molecular alterations during epileptogenesis or for the prediction of pharmacoresponsiveness as well as postoperative outcome. Imaging biomarkers were examined during the XIII Workshop on Neurobiology of Epilepsy (XIII WONOEP) organized in 2015 by the Neurobiology Commission of the International League Against Epilepsy (ILAE). Here we present an extended summary of the discussed issues and provide an overview of the current state of knowledge regarding the biomarker potential of different neuroimaging approaches for epilepsy. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

  15. Biomarkers of secondhand smoke exposure in automobiles.

    Science.gov (United States)

    Jones, Ian A; St Helen, Gideon; Meyers, Matthew J; Dempsey, Delia A; Havel, Christopher; Jacob, Peyton; Northcross, Amanda; Hammond, S Katharine; Benowitz, Neal L

    2014-01-01

    The objectives of this study were: (1) to characterise the exposure of non-smokers exposed to secondhand smoke (SHS) in a vehicle using biomarkers, (2) to describe the time course of the biomarkers over 24 h, and (3) to examine the relationship between tobacco biomarkers and airborne concentrations of SHS markers. Eight non-smokers were individually exposed to SHS in cars with fully open front windows and closed back windows over an hour from a smoker who smoked three cigarettes at 20 min intervals. The non-smokers sat in the back seat on the passenger side, while the smoker sat in the driver's seat. Plasma cotinine and urine cotinine, 3-hydroxycotinine (3HC) and 4-(methylnitrosoamino)-(3-pyridyl)-1-butanol (NNAL) were compared in samples taken at baseline (BL) and several time-points after exposure. Nicotine, particulate matter (PM2.5) and carbon monoxide (CO) were measured inside and outside the vehicle and ventilation rates in the cars were measured. Average plasma cotinine and the molar sum of urine cotinine and 3HC (COT+3HC) increased four-fold, urine cotinine increased six-fold and urine NNAL increased ∼27 times compared to BL biomarker levels. Plasma cotinine, urine COT+3HC and NNAL peaked at 4-8 h post-exposure while urine cotinine peaked within 4 h. Plasma cotinine was significantly correlated to PM2.5 (Spearman correlation rs=0.94) and CO (rs=0.76) but not to air nicotine. The correlations between urine biomarkers, cotinine, COT+3HC and NNAL, and air nicotine, PM2.5 and CO were moderate but non-significant (rs range =  0.31-0.60). Brief SHS exposure in cars resulted in substantial increases in levels of tobacco biomarkers in non-smokers. For optimal characterisation of SHS exposure, tobacco biomarkers should be measured within 4-8 h post-exposure. Additional studies are needed to better describe the relationship between tobacco biomarkers and environmental markers of SHS.

  16. Diagnostic and Research Aspects of Small Intestinal Disaccharidases in Coeliac Disease

    Directory of Open Access Journals (Sweden)

    Tanja Šuligoj

    2017-01-01

    Full Text Available Disaccharidases (DS are brush border enzymes embedded in the microvillous membrane of small intestinal enterocytes. In untreated coeliac disease (CD, a general decrease of DS activities is seen. This manuscript reviews different aspects of DS activities in CD: their utility in the diagnosis and their application to in vitro toxicity testing. The latter has never been established in CD research. However, with the recent advances in small intestinal organoid techniques, DS might be employed as a biomarker for in vitro studies. This includes establishment of self-renewing epithelial cells raised from tissue, which express differentiation markers, including the brush border enzymes. Determining duodenal DS activities may provide additional information during the diagnostic workup of CD: (i quantify the severity of the observed histological lesions, (ii provide predictive values for the grade of mucosal villous atrophy, and (iii aid diagnosing CD where minor histological changes are seen. DS can also provide additional information to assess the response to a gluten-free diet as marked increase of their activities occurs four weeks after commencing it. Various endogenous and exogenous factors affecting DS might also be relevant when considering investigating the role of DS in other conditions including noncoeliac gluten sensitivity and DS deficiencies.

  17. [Brief lecture on cardiovascular biomarkers based on the pathophysiology].

    Science.gov (United States)

    Shimada, Toshio

    2011-10-01

    Living organisms on the earth live dependent on the sun. Human beings are unexceptional. Plants with chlorophyll on the earth capture energy radiated from the sun and produce carbohydrate and oxygen from carbon dioxide and water using the energy from the sun. Herbivorous animals eat plants, carnivorous ones eat herbivorous ones and human beings eat both with a small amount of vitamins and minerals. Food including carbohydrate, protein and lipid which is digested by the gastroenteric system and mainly absorbed through the small intestine. Finally, nutrients from the digestive system and oxygen from the lungs are brought to the cells or the tissue through the cardiovascular system. Acetyl-CoA from food and oxygen from the lungs are chemically burned in the mitochondria to produce a lot of ATP. On the way of ATP production, unfavorable free radicals are inevitably produced to result in cancer and/or atherosclerosis. Cardiovascular system delivers oxygen and nutrients to the tissue or the cells. Literally, it is a pipe line for life support and then we must maintain cardiovascular system well to live long in good health. And therefore, it is essential to find cardiovascular abnormality as early as possible. Cardiovascular biomarkers such as BNP and NT-proBNP for screening for heart failure, RemL-C for screening for metabolic syndrome, cystatin C for screening for renal impairment and high sensitive troponin I, T for screening for ischemic myocardial damage have been greatly expected as tools to find early cardiovascular disorders for long survival in health examination and clinical practice.

  18. (Very) Early technology assessment and translation of predictive biomarkers in breast cancer

    NARCIS (Netherlands)

    Miquel-Cases, Anna; Schouten, Philip C; Steuten, Lotte M G; Retèl, Valesca P; Linn, Sabine C; van Harten, Wim H

    Predictive biomarkers can guide treatment decisions in breast cancer. Many studies are undertaken to discover and translate these biomarkers, yet few biomarkers make it to practice. Before use in clinical decision making, predictive biomarkers need to demonstrate analytical validity, clinical

  19. (Very) Early technology assessment and translation of predictive biomarkers in breast cancer

    NARCIS (Netherlands)

    Miquel-Cases, Anna; Schouten, Philip C.; Steuten, Lotte M.G.; Retèl, Valesca P.; Linn, Sabine C.; van Harten, Wim H.

    2017-01-01

    Predictive biomarkers can guide treatment decisions in breast cancer. Many studies are undertaken to discover and translate these biomarkers, yet few biomarkers make it to practice. Before use in clinical decision making, predictive biomarkers need to demonstrate analytical validity, clinical

  20. Intestinal Cgi-58 deficiency reduces postprandial lipid absorption.

    Science.gov (United States)

    Xie, Ping; Guo, Feng; Ma, Yinyan; Zhu, Hongling; Wang, Freddy; Xue, Bingzhong; Shi, Hang; Yang, Jian; Yu, Liqing

    2014-01-01

    Comparative Gene Identification-58 (CGI-58), a lipid droplet (LD)-associated protein, promotes intracellular triglyceride (TG) hydrolysis in vitro. Mutations in human CGI-58 cause TG accumulation in numerous tissues including intestine. Enterocytes are thought not to store TG-rich LDs, but a fatty meal does induce temporary cytosolic accumulation of LDs. Accumulated LDs are eventually cleared out, implying existence of TG hydrolytic machinery in enterocytes. However, identities of proteins responsible for LD-TG hydrolysis remain unknown. Here we report that intestine-specific inactivation of CGI-58 in mice significantly reduces postprandial plasma TG concentrations and intestinal TG hydrolase activity, which is associated with a 4-fold increase in intestinal TG content and large cytosolic LD accumulation in absorptive enterocytes during the fasting state. Intestine-specific CGI-58 knockout mice also display mild yet significant decreases in intestinal fatty acid absorption and oxidation. Surprisingly, inactivation of CGI-58 in intestine significantly raises plasma and intestinal cholesterol, and reduces hepatic cholesterol, without altering intestinal cholesterol absorption and fecal neutral sterol excretion. In conclusion, intestinal CGI-58 is required for efficient postprandial lipoprotein-TG secretion and for maintaining hepatic and plasma lipid homeostasis. Our animal model will serve as a valuable tool to further define how intestinal fat metabolism influences the pathogenesis of metabolic disorders, such as obesity and type 2 diabetes.