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Found 7 results

  1. Great Smokies Diagnostic Laboratory (GSDL), a private, rapid-growth Functional Medicine Clinical laboratory, announced today receipt of 510(K) market clearance from the Food and Drug Administration (FDA) for its Intestinal Permeability test kit, utilizing the lactulose-mannitol challenge drink. Used in the non-invasive assessment of intestinal permeability, the test demonstrated its superior sensitivity as compared to the existing d-xylose test in measuring intestinal permeability, a measurement used in the diagnosis of gastrointestinal malabsorption syndromes, such as celiac disease, colitis, Crohns disease, and Irritable Bowel Syndrome. What is intestinal permeability? Intestinal permeability refers to impairment of the intestinal mucosal barrier, which is central to healthy absorption of nutrients and protection against bacterial and toxin translocation from the gastrointestinal (GI) tract to the blood stream. Disturbances in mucosal barrier function can lead to malnourishment and increased permeability (leaky gut) which can cause or contribute to disease conditions throughout the body as diverse as asthma, arthritis, and food allergies. What are gastrointestinal malabsorption syndromes? Although the Centers for Disease Control (celiac disease) has not gathered statistics specifically for malabsorption itself, tens of millions of Americans suffer from related gut mucosal integrity conditions responsible for enormous healthcare expense. Arthritis, for example, strikes over 43 million annually at a cost of more than $65 million (celiac disease), while functional gastrointestinal disorders are responsible for an estimated 2.5 to 3.5 million visits to doctors every year and some $40 million in medication expenditures (University of North Carolina Functional Gastrointestinal Disorders Center). The incidence of these health disorders and other intestinal permeability related- conditions continues to grow at an alarming rate. The growing use of non-steroidal anti-inflammatory drugs (NSAIDS), which can irritate the mucosal lining, has contributed significantly to an increase intestinal permeability worldwide. Intestinal Permeability Assessment can be used to monitor treatment of NSAID-related damage to the mucosal barrier and intestinal permeability-related to other irritants in the GI tract. An estimated 20% or more of patients taking NSAIDS develop systematic or endoscopic gastrointestinal toxicity with incidence increasing among the elderly, who account for 40-60% of NSAID users (Canadian Medical Association Journal 1996; 155: 77-88). Inflammatory and detoxification disorders, impaired healing following surgery, failure to thrive, and complications from radiation and chemotherapy for cancer have all been linked to intestinal permeability. Recent research has consistently underscored the value of Intestinal Permeability Assessment in GI disorders such as Crohns and Irritable Bowel Syndrome, as well as traumatic care, geriatric interventions, adjunctive AIDS therapy, and pediatric care, especially in the treatment of allergies and immune disorders. GSDL is the first commercial laboratory to offer Intestinal permeability testing. Utilizing state-of-the art technology, GSDL has developed a comprehensive range of functional assessments in the areas of gastroenterology, endocrinology, cardiology, nutrition/metabolism, and immunology. The laboratory conducts aggressive, ongoing research and development for innovative functional assessments.
  2. Celiac.com 12/12/2012 - In duodenal biopsy samples from people with active celiac disease, the transferrin receptor, CD71, is up-regulated, and promotes retro-transport of secretory immunoglobulin A (SIgA)-gliadin complexes. To better understand how interactions between SIgA and CD71 promote transepithelial transport of gliadin peptides, a team of researchers set out to determine if interactions among secretory immunoglobulin A, CD71, and transglutaminase-2 affect permeability of intestinal epithelial cells to gliadin peptides. The research team included C. Lebreton, S. Ménard, J. Abed, I.C. Moura, R. Coppo, C. Dugave, R.C. Monteiro, A. Fricot, M.G. Traore, M. Griffin, C. Cellier, G. Malamut, N. Cerf-Bensussan, and M. Heyman. They are affiliated with the Mixed Research Unit 989 of the National Institute of Health and Medical Research (INSERM UMR989) in Paris, France. For their study, the team evaluated duodenal biopsy specimens from 8 adults and 1 child with active celiac disease. The team used fluorescence-labeled small interfering RNAs against CD71 to transfect Caco-2 and HT29-19A epithelial cell lines. They used flow cytometry, immunoprecipitation, and confocal microscopy to assess interactions among IgA, CD71, and transglutaminase 2 (Tgase2). They then assessed transcytosis of SIgA-CD71 complexes and intestinal permeability to the gliadin 3H-p31-49 peptide in polarized monolayers of Caco-2 cells. To assess physical interplay between SIgA and CD71 or CD71 and Tgase2 at the apical surface of enterocytes in biopsy samples and monolayers of Caco-2 cells, the team used fluorescence resonance energy transfer and in situ proximity ligation assays. They co-precipitated CD71 and Tgase2 with SIgA, bound to the surface of Caco-2 cells. They found that SIgA-CD71 complexes were internalized and localized in early endosomes and recycling compartments, but not in lysosomes. In the presence of celiac IgA or SIgA against p31-49, transport of intact 3H-p31-49 increased significantly across Caco-2 monolayers, while soluble CD71 or Tgase2 inhibitors interfered with transport. Once it binds to apical CD71, SIgA (with or without gliadin peptides) enters a recycling pathway and avoids lysosomal degradation; this process allows apical-basal transcytosis of bound peptides. This mechanism is assisted by Tgase2 and might be involved in the pathogenesis of celiac disease. Source: Gastroenterology. 2012 Sep;143(3):698-707.e1-4. doi: 10.1053/j.gastro.2012.05.051.
  3. Celiac.com 07/03/2009 - A new study provides demonstrates that small intestinal bacterial overgrowth and increased intestinal permeability are both associated with non-alcoholic fatty liver disease (NAFLD). Previous studies have suggested that bacteria from the intestine might play a role in NAFLD, which is the hepatic component of the Metabolic Syndrome. NAFLD can worsen to nonalcoholic steatohepatitis, and some experts have wondered if this progression might be promoted by liver exposure to gut bacteria. A team of researchers, led by Antonio Grieco of Rome, set out to answer this question by investigating gut permeability in patients with NAFLD and comparing the results to patients with untreated celiac disease and known susceptibility to this condition, and with healthy volunteers. The research team included Luca Miele, Venanzio Valenza, Giuseppe La Torre, Massimo Montalto, Giovanni Cammarota, Riccardo Ricci, Roberta Masciana, Alessandra Forgione, Maria Gabrieli, Germano Perotti, Fabio Vecchio, Gian Ludovico Rapaccini, Giovanni Gasbarrini, Christopher Day, and Antonio Grieco. They studied 35 patients with biopsy-confirmed NAFLD, 27 with celiac disease and 24 healthy volunteers. For each participant, the research team checked levels of small intestinal bacterial overgrowth using a glucose breath test. They evaluated intestinal permeability by examining urinary excretion of Cr-EDTA. They then assessed the integrity of tight junctions within the gut via duodenal biopsy. "The main findings of this study are that both intestinal permeability and the prevalence of small intestinal bacterial overgrowth are increased in patients with NAFLD and correlate with the severity of steatosis," the authors report. "Disruption of tight junction integrity may explain the increased permeability in these patients." The authors hypothesize that small intestinal bacterial overgrowth and/or the associated increase in gut permeability may cause steatosis. This hypothesis is supported by studies on mice, and by reports that probiotics can improve steatosis resulting from a high fat diet. One important note was that the study showed no connection between either small intestinal bacterial overgrowth or intestinal permeability and steatohepatitis or fibrosis, which suggests gut bacteria do not play a role in the transformation of NAFLD to more serious liver disease. "In conclusion," the authors write, "we have demonstrated that NAFLD is associated with increased intestinal permeability and small intestinal bacterial overgrowth and that these factors are associated with the severity of hepatic steatosis." More study is needed to nail down the exact causal relationship, which, once understood, could help scientists develop new therapies for NAFLD that incorporate the microbiome of the gut.'' According to colleagues Elisabetta Bugianesi and Ester Vanni of the University of Turin, "The study...raises the possibility that gut microbiota and intestine permeability are important mediators of diet-induced metabolic disturbances in NAFLD." Bugianesi and Vanni add that lifestyle-focused therapy would likely present the best treatment for NAFLD, but suggest that influencing gut flora by antibiotics, prebiotics, and probiotics might help offset the effects of unbalanced diets on metabolic conditions. Article: "Increased Intestinal Permeability and Tight Junction Alterations in Non-Alcoholic Fatty Liver Disease (NAFLD)." Editorial: "The Gut-Liver Axis in Nonalcoholic Fatty Liver Disease (NAFLD): Another Pathway to Insulin Resistance?" Bugianesi, Elisabetta; Vanni, Ester. Hepatology; June 2009. Hepatology. 2009 Jun;49(6):1877-87.
  4. Dig Dis Sci. 2005 Apr;50(4):785-90. Celiac.com 05/09/2005 – To determine the effect a long-term gluten-free diet has on intestinal permeability in those with celiac disease, Canadian researchers divided celiac disease patients into three groups based on the length of time on a gluten-free diet: Group A less than 1 month; Group B, 1 month-1 year; Group C more than 1 year. Groups B and C were tested three times over the course of 12 weeks for lactulose/mannitol intestinal permeability, endomysial antibody, and 3-day food record. These results were compared to that of Group A and control subjects. The researchers found that intestinal permeability was elevated in those newly diagnosed with celiac disease and in those who were on a gluten-free diet for less than one year. They also found that it increased in those on a gluten-free diet for more than one year in those whose diets were contaminated with gluten. The researchers conclude that intestinal permeability normalizes in most people with celiac disease on a gluten-free diet, and gluten ingestion as determined by a 3 day food record correlates with intestinal permeability measurements. Further studies need to be done on the role of intestinal permeability testing in the follow-up care of those with celiac disease.
  5. Celiac.com 07/01/2006 - With the likelihood that increased intestinal permeability in celiacs caused by gluten damage to the intestinal mucosa leads to a high prevalance of liver damage as well as an increase in food allergy and possible other medical conditions, emphasis on healing the intestinal mucosa should be given an elevated priority. Simply going on a gluten-free diet and waiting months or years for the intestine to heal may not be enough. Friendly commensal gut bacteria are an important part of the intestinal barrier, and thus probiotics, such as yogurt, kefir, or supplemental probiotic capsules, do help diminish the amount of endotoxins released by pathogenic gut bacteria getting through the barrier. Liver disease studies confirm the benefit of probiotics by reducing inflammation and infection. However, to date, there is no product currently available which can enhance the repair and regeneration process of the mucosal epithelia. Undergoing current clinical studies in Crohns patients, Teduglutide may enhance mucosal healing, but requires multiple daily injections: Cell Prolif. 2004 Dec;37(6):385-400. Teduglutide ([Gly2]GLP-2) protects small intestinal stem cells from radiation damage. Booth C, Booth D, Williamson S, Demchyshyn LL, Potten CS. Abstract: http://www.blackwell-synergy.com/doi/abs/10.1111/j.1365-2184.2004.00320.x New Crohns Disease Drug Induces Remission Through Mucosal Healing By Martha Kerr (Free article, free Medscape registration may be required.) http://www.medscape.com/viewarticle/533109 A while back I posted an abstract about a protein called R-spondin1 which is "a specific and potent stimulator of the human epithelial cells that line the gastrointestinal tract and mouth." R-spondin1 is a product being developed by Nuvelo, Inc. of San Carlos, CA designated as NU206. The press release describing NU206 is: Nuvelo Announces NU206 Publication in Science (August 18, 2005) http://www.corporate-ir.net/ireye/ir_site.zhtml?ticker=NUVO&script=410&item_id=744876 An article discussing the discovery and potentials of R-spondin1 is available in the New England Journal of Medicine, and free full text of that article is available at the address below: NEJM.-Volume 353:2297-2299 November 24, 2005 Number 21 Inducing Intestinal Growth Clara Abraham, M.D., and Judy H. Cho, M.D. Free Full Text Reprint of NEJM article: http://www.e-medicum.com/newsletters/medicinaInterna/verNoticia.php?noticia=51479 Nuvelo has recently announced plans for the "initiation of a Phase 1 study of NU206, which is being developed for the treatment of cancer therapy-induced mucositis in the second half of 2006." Obviously the benefits of NU206 go beyond that of cancer therapy. Healing the epithelial tissues of celiacs with NU206 may rapidly eliminate increased intestinal permeability and other associated conditions. Nuvelo had a live webcast of its annual shareholder meeting this Wednesday, May 24, at 11:00 am PDT. No new information on NU206 was provided at the meeting other than that plans to initiate the NU206 Phase 1 study are proceding. Replay of Nuvelo Webcast: http://www.corporate-ir.net/ireye/ir_site.zhtml?ticker=NUVO&script=1010&item_id=1234084
  6. Celiac.com 11/08/2005 - Today a team of scientists at Alba Therapeutics Corporation (Alba) and the University of Maryland School of Medicine reported a direct link between gluten-induced intestinal permeability and zonulin in tissues from patients with celiac disease. The investigators were able to successfully prevent gluten-induced intestinal tissue leak with the administration of the zonulin antagonist FZI/0 (AT-1001). AT-1001 is an orally administered peptide currently under development for the treatment of celiac disease. Published in the November issue of the Scandinavian Journal of Gastroenterology, these results describe the role that leaky gut plays in celiac disease and the role that zonulin plays in establishing the leak. These results are another milestone towards understanding the role of zonulin in celiac disease, says Alessio Fasano, M.D., lead author of the paper, professor of pediatrics, medicine and physiology at the University of Maryland School of Medicine and director of its Center for Celiac Research. These results reinforce our conviction that AT-1001 has great therapeutic potential and we look forward to confirming these observations in celiac patients soon, stated Alba CEO Dr. Blake M. Paterson. About Zonulin Zonulin is a signaling protein that transiently and reversibly opens the tight junctions (tj) between the cells of epithelial and endothelial tissues such as the intestinal mucosa, blood brain barrier and pulmonary epithelia. Zonulin appears to be involved in many diseases in which leakage occurs via paracellular transport across epithelial and endothelial tight junctions (tj), and thus may play an important potential role in the treatment of autoimmune diseases. About Celiac Disease Celiac disease is a T-cell mediated auto-immune disease that occurs in genetically susceptible individuals and is characterized by small intestinal inflammation, injury and intolerance to gluten. According to the National Institutes of Health, celiac disease affects approximately 3 million Americans, although the diagnosis is rarely made. The only treatment for celiac disease is complete elimination of gluten from the diet, which results in remission for some patients. About Alba Alba Therapeutics Corporation is a privately held biopharmaceutical company based in Baltimore, Maryland. Alba is dedicated to commercializing disease-modifying therapeutics and drug delivery adjuvants based on the zonulin pathway. Albas lead molecule, AT-1001, is targeted towards the treatment of celiac disease and other auto-immune illnesses. Contact: Dr. Blake Paterson Alba Therapeutics Corporation (410) 522-8708
  7. This was posted to the Celiac Listserv by Don Wiss. Testing for intestinal permeability is a sensitive and accurate way to screen for celiac disease, with fewer false positive and false negative results than other commonly used screens. Intestinal permeability reflects the ability of the intestinal lining to absorb nutrients while keeping undesirable chemical substances out of the body. In patients with celiac disease who are consuming gluten, even small amounts of damage to the intestine will allow certain large chemical molecules to leak into the bloodstream, from which they may be excreted by the kidneys into the urine. The available permeability test requires that the individual drink a solution which contains two sugars, neither of which is metabolized or changed in the body. One sugar is usually mannitol, which is readily absorbed from the intestine and excreted in the urine. The other sugar is lactulose, which is hardly absorbed at all under normal conditions. Any lactulose that is absorbed is excreted unchanged in the urine within 5 to 6 hours. Both sugars are safe to be taken, even by small children. When a person with celiac disease drinks the lactulose/mannitol mixture, an excessive amount of lactulose will appear in the urine, unless the person is on a strict gluten-free diet. If the person has enough celiac disease to create malabsorption, then the mannitol level in urine will be low. The ratio of lactulose to mannitol in urine is the most sensitive index of active celiac disease. An elevated lactulose to mannitol ratio in urine may be due to conditions other than celiac disease, such as intestinal infection, severe food allergy or Crohns disease, but a normal ratio indicates either that the person does not have celiac disease or is in complete remission due to strict adherence to a gluten-free diet. Information about this test can be obtained from the one laboratory that presently offers it, Great Smokies Diagnostic Laboratory in Asheville, NC. Their number is 1-800-522-4762.
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