Strategies for the identification and prevention of coeliac disease

Coeliac disease is an autoimmune disorder of the small intestine which occurs in genetically predisposed individuals. CD is caused by an inflammatory T-cell response to the protein gluten and the treatment is a lifelong gluten-free diet. CD may be identified by non-invasive tests which measure the specific coeliac antibodies and HLA-DQ2/DQ8 genotypes, and by an invasive test the small bowel biopsies. The aim of this thesis is to evaluate different methods used in the identification (Chapter 2 shows improvements of serological mass screening programs for CD and chapter 3 adds knowledge to the relation between geno-phenotype of CD), diagnosis (Chapter 4 illustrates a diagnostic scoremodel that could prevent 58% of the usually performed small bowel biopsies) and follow-up of childhood CD (Chapter 5 investigates the decline and normalization of specific coeliac antibodies when being on a glutenfree diet). Furthermore, new strategies for the prevention of the disease are explored (in chapter 7 the rationale behind the primary prevention of CD is outlined, which is based on adjusting factors that contribute to the disorder might improve tolerance to the food allergens gluten). And chapter 8 describes a European multicenter study PreventCD that investigates whether it is possible to induce tolerance to gluten by introducing small quantities of gluten to infants, preferably whilst they are breastfed.Euro Diagnostica, Nutricia Nederland BV Phadia now Thermo Fisher Scientific Zorgverzekeraar VGZ, Nederlandse coeliakie vereniging, Leiden University Medical Center Celiac disease consortiumUBL - phd migration 201

Electrochemical anionic polymerization of 4‐vinylpyridine in pyridine

The preparation of poly‐4‐vinylpyridine (poly‐4VP) by electrochemical polymerization of 4‐vinylpyridine (4VP) in pyridine containing sodium tetraphenylboron (NaBPh 4 ) is described. Information on the influence of monomer concentration, current density, polymerization rate, molecular weight, and electrochemical efficiency is presented. The polymerizations were performed under conditions of constant electrolysis current. Polymer formed in the cathodic compartment only, where a red‐orange solution developed after about 15 min of electrolysis time. The optical absorption spectra of these colored solutions were studied. Cyclic voltammograms of 4VP in pyridine and NaBPh 4 are also reported, and the influence of the scan rate upon peak current is described. The results indicate that the polymerization was anionic and nonterminating. The characteristics of the electrochemical polymerization of 4VP in pyridine are compared with those of the same monomer in liquid NH 3 . In the former case, the catholyte was homogeneous, and polymer growth occurred in the liquid phase, while in the latter growth took place in a heterogeneous environment. Kinetic consequences of these physical differences are pointed out. Suggestions for the mechanism of this electrochemical initiation are advanced.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/100167/1/150080121_ftp.pd

Adult Lysophosphatidic Acid Receptor 1-Deficient Rats with Hyperoxia-Induced Neonatal Chronic Lung Disease Are Protected against Lipopolysaccharide-Induced Acute Lung Injury

Developmen

Bone Morphogenetic Protein 9 Protects against Neonatal Hyperoxia-Induced Impairment of Alveolarization and Pulmonary Inflammation.

Aim: Effective treatment of premature infants with bronchopulmonary dysplasia (BPD) is lacking. We hypothesize that bone morphogenetic protein 9 (BMP9), a ligand of the TGF-β family that binds to the activin receptor-like kinase 1 (ALK1)-BMP receptor type 2 (BMPR2) receptor complex, may be a novel therapeutic option for BPD. Therefore, we investigated the cardiopulmonary effects of BMP9 in neonatal Wistar rats with hyperoxia-induced BPD. Methods: Directly after birth Wistar rat pups were exposed to 100% oxygen for 10 days. From day 2 rat pups received BMP9 (2.5 μg/kg, twice a day) or 0.9% NaCl by subcutaneous injection. Beneficial effects of BMP9 on aberrant alveolar development, lung inflammation and fibrosis, and right ventricular hypertrophy (RVH) were investigated by morphometric analysis and cytokine production. In addition, differential mRNA expression of BMP9 and its receptor complex: ALK1, BMPR2, and Endoglin, and of the ALK1 downstream target transmembrane protein 100 (TMEM100) were studied during the development of experimental BPD. Expression of the BMP9 receptor complex and TMEM100 was studied in human endothelial and epithelial cell cultures and the effect of BMP9 on inflammatory cytokine production and TMEM100 expression was studied in endothelial cell cultures. Results:ALK1, ALK2, BMPRII, TMEM100, and Endoglin were differentially expressed in experimental BPD, suggesting a role for BMP9-dependent signaling in the development of (experimental) BPD. TMEM100 was expressed in the wall of blood vessels, showing an elastin-like expression pattern in arterioles. Expression of TMEM100 mRNA and protein was decreased after exposure to hyperoxia. BMP9 treatment of rat pups with hyperoxia-induced experimental BPD reduced alveolar enlargement, lung septal thickness and fibrosis, and prevented inflammation, but did not attenuate vascular remodeling and RVH. The anti-inflammatory effect of BMP9 was confirmed in vitro. Highest expression of ALK1, BMPR2, and TMEM100 was observed in human endothelial cell cultures. Stimulation of human endothelial cell cultures with BMP9 reduced their pro-inflammatory cytokine response and induced TMEM100 expression in pulmonary arterial endothelial cells. Conclusion: BMP9 protects against neonatal hyperoxia-induced BPD by improving aberrant alveolar development, inflammation and fibrosis, demonstrating its therapeutic potential for premature infants with severe BPD