Effects of Epithelial IL-13Rα2 Expression in Inflammatory Bowel Disease

Background: Mucosal IL-13 Receptor alpha 2 (IL13RA2) mRNA expression is one of the best predictive markers for primary non-responsiveness to infliximab therapy in patients with inflammatory bowel disease (IBD). The objective of this study was to understand how IL-13Rα2, a negative regulator of IL-13 signaling, can contribute to IBD pathology.Methods:IL13RA2 knockout (KO) and wild type (WT) mice were exposed to dextran sodium sulfate (DSS) in drinking water to induce colitis. Furthermore, mucosal biopsies and resection specimen of healthy individuals and IBD patients before the start of anti-tumor necrosis factor (anti-TNF) therapy were obtained for immunohistochemistry and gene expression analysis.Results: After induction of DSS colitis, IL13RA2 KO mice had similar disease severity, but recovered more rapidly than WT animals. Goblet cell numbers and mucosal architecture were also more rapidly restored in IL13RA2 KO mice. In mucosal biopsies of active IBD patients, immunohistochemistry revealed that IL-13Rα2 protein was highly expressed in epithelial cells, while expression was restricted to goblet cells in healthy controls. Mucosal IL13RA2 mRNA negatively correlated with mRNA of several goblet cell-specific and barrier genes, and with goblet cell numbers.Conclusions: The data suggest that IL-13Rα2 on epithelial cells contributes to IBD pathology by negatively influencing goblet cell recovery, goblet cell function and epithelial restoration after injury. Therefore, blocking IL-13Rα2 could be a promising target for restoration of the epithelial barrier in IBD

Studies on inflammation and fibrosis in a model of chronic inflammatory colitis

Crohn s disease is in essence a transmural disease in which chronic intestinal inflammation leads to perforating ulcers (due to insufficient mucosal healing) and intestinal wall fibrosis (due to excessive healing). Despite the clinical importance of fibrosis in IBD, until now, there is no clue about the time course, the pathophysiology or the treatment, nor are there good markers of fibrosis in serum, imaging tools or good animal models to study fibrosis. Therefore, the general aim of this study was to develop a chronic model of relapsing murine colitis mimicking human disease in order to acquire in depth knowledge on the mechanisms responsible for intestinal fibrosis. Next, we aimed to search for non-invasive imaging tools to assess intestinal inflammation and fibrosis. We have set up a reliable chronic colitis model in mice by exposing them to repeated cycles of administration of DSS followed by a recovery period. In this chronic model of inflammatory colitis which pathologically mimics human CD, we showed that the adaptive immune system is activated with induction of Th1 and Th17 cells in MLNs. This effect is progressive with an increasing number of cycles of administration of DSS. Inhibition of T cell associated cytokines IFN-gamma and IL-17F during the chronic phase of inflammation did not alter the deposition of collagen. Anti-IL-17A slightly promoted fibrosis. Next, we showed that fibrosis can be induced by chronic DSS colitis in RAG-1 deficient mice on the C57BL/6 background, suggesting that the adaptive immune system is not crucial for fibrogenesis in chronic DSS colitis. Furthermore, transcriptomic analysis of colonic gene expression in the different phases of inflammation and fibrosis, provided information on the differential regulation of genes during inflammation, fibrosis and recovery. During prolonged recovery after the induction of fibrosis, an upregulation of keratins was observed. A type I IFN-related gene signature could be identified in chronic colitis in RAG-1 KO mice as compared to WT mice. Finally, we showed that in vivo T2 relaxometry is a promising non-invasive assessment tool of inflammation and fibrosis of the bowel wall in murine colitis. Furthermore, in a clinical setting, MRI T2 relaxometry of the pelvis was feasible in patients with IBD and a histogram shift compared to healthy volunteers reminiscent of chronic DSS colitis was observed.nrpages: 177status: publishe

Voedselallergie en -intolerantie

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Abdominal pain of the right upper quadrant

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Progress Report M2S-LCC-R.2009-1 - Evaluation of the potential application of zeolites as a sorption sink for selected radionuclides in cementitious aqueous solutions

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Exafs and DFT: Evidence for the [Tc=O]2+ core

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EXAFS and DFT: Evidence for the [TcO]2+ core

Technetium, an unusual element whereof only radioactive isotopes exist, is characterised by a very rich redox (-1 to +7) and coordination chemistry. Due to its importance for nuclear medicine and the considerable amount of Tc present in high level radioactive waste as a fission product from U it has been the focus of many studies for several decades.1-5 In absence of stabilising ligands Tc(VII) and Tc(IV) are the main, stable oxidation states in oxygenated and reducing conditions, respectively. In spite of the research efforts invested in this element, some important gaps in the basic Tc chemistry remain. The pH dependent speciation of dissolved Tc(IV) in aqueous solutions is thermodynamically described by the series TcO2+, TcOOH+, TcO(OH)2 and TcO(OH)3-. Nevertheless, the molecular structure of these Tc(IV) hydrolysis species is uncertain because of the difficulties to distinguish between oxy- and hydroxy- coordination in these sparingly soluble Tc(IV) species (solubility of TcO2.xH2O = 3x10-8 M). The description of hydrolyzed Tc(IV) species as TcO(OH)n2−n(aq) rather than Tc(OH)m4−m(aq) was mainly due to the observation that the charge of Tc(IV) species never exceeded +2 even at pH = 0.6 To our knowledge the existence of the TcO2+ core has not been detected spectroscopically in either hydrolyzed Tc(IV) species or in any other Tc(IV) coordination compound. In this contribution, XAS evidence for its existence will be provided using a strategy based on the combined use of X-ray Absorption Spectroscopy (XAS) and Density Functional methods (DFT). Using this methodology, detailed structural information can be obtained for non-crystalline and crystalline components in virtually all experimental conditions.status: publishe

An abdominal pain syndrome in a lupus patient

Systemic lupus erythematosus can be complicated by the antiphospholipid syndrome (APS). The clinical manifestations of this syndrome most often documented thus far are recurrent deep venous thrombosis, recurrent spontaneous abortions, and cerebral vascular accidents. Abdominal ischemic events have received relatively little attention in prior reports. We report on a lupus patient with lupus anticoagulant positivity who presented with abdominal pain, anorexia, and weight loss who was subsequently diagnosed with gastric ulcers and pancreatitis. Computerized tomography of the abdomen in addition revealed splenic and kidney infarcts. We conclude that this patient had (ischemic) chronic pancreatitis with pseudocysts and splenic and renal infarcts probably due to secondary APS.status: publishe

Invited: Impact of Cations on (Un)desirable Zeolite Transformations at High pH

High alumina zeolites are typically synthesized hydrothermally in hyperalkaline conditions. Postsynthetic alkaline treatment induces partial or complete dissolution, followed by nucleation and growth of new (zeolite) products. Major factors controlling such zeolite transformations are temperature, alkalinity and the presence of specific cations in the zeolite and the alkaline medium. While material scientists exploit zeolite transformations to design novel zeolite materials, zeolite stability in hyperalkaline media is of high interest to geoscientists, evaluating long-term stability of natural zeolites used as reactive barrier in concrete based disposal strategies for nuclear waste. This contribution discusses the role of alkali metal cations on FAU (faujasite) type zeolite transformations in 1 M hydroxide solutions under autogeneous pressure at 95°C or lower. Liquid and solid phase analysis was performed as function of contact time, with ICP-AES, NMR, SEM and XRD. Although exposure of FAU to KOH nowadays is a standard recipe to synthesize chabazite (CHA), few studies dealing with the transformation mechanism and kinetics are available. Our systematic study revealed, among others, that the presence of K+ ions is crucial for the conversion of FAU to CHA. Identical transformation conditions yielded ABW, FAU, MER and ANA frameworks by substituting KOH with LiOH, NaOH, RbOH, and CsOH respectively. [1] In addition to cation identity, other important variables determining the outcome of the transformations were the Si/Al ratio of the initial FAU framework, and the solid/liquid ratio. Furthermore, CHA was obtained by contacting FAU with K+ rich young cement water (YPW, pH 13.5) at 60°C, illustrating its potential use in such hyperalkaline conditions. In these conditions, a minor fraction of zeolite with MER (merlinoite) topology was detected in addition to CHA. The MER framework has buckled 8-rings of MER that form a perfect nest for K+ .[2] Currently, the relationship between CHA and MER formation, starting from FAU, is investigated and compared to direct syntheses from amorphous sources. The hypothesis is explored that the FAU framework structure directs the CHA formation, as CHA was observed to nucleate on the FAU (111) crystal faces. [1] Van Tendeloo et al (2013) Chem. Commun. 49, 11737- 11739 [2] Skofteland et al (2001) Microporous Mesoporous Mater. 43, 61-71status: publishe