Megan Vitko, Dana M. Valerio, Philip D. Rye, Edvar Onsøyen, Astrid H

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A novel guluronate oligomer improves intestinal transit and survival in cystic fibrosis mice  Megan Vitko, Dana M. Valerio, Philip D. Rye, Edvar Onsøyen, Astrid H. Myrset, Arne Dessen, Mitchell L. Drumm, Craig A. Hodges  Journal of Cystic Fibrosis  Volume 15, Issue 6, Pages 745-751 (November 2016) DOI: 10.1016/j.jcf.2016.06.005 Copyright © 2016 European Cystic Fibrosis Society. Terms and Conditions

Fig. 1 Intestinal transit time in WT and CF mice. (A) Examples of rhodamine-labeled dextran (bright white areas) in the small intestines of fasted WT and CF mice on regular water or OligoG. All intestines are oriented with the duodenum at the top and ileum at the bottom. Two examples of CF mice on OligoG(1 and 2) are shown to illustrate the improvement in CF intestinal transit on OligoG treatment. GCF for each displayed animal was WT=5.3, CF=2.9, CF on OligoG(1)=4.7 and CF on OligoG(2)=8.5. (B) Average GCF value for WT and CF mice on regular water or OligoG. n≥8. *P=0.001 vs. WT. Journal of Cystic Fibrosis 2016 15, 745-751DOI: (10.1016/j.jcf.2016.06.005) Copyright © 2016 European Cystic Fibrosis Society. Terms and Conditions

Fig. 2 Survival of WT and CF mice on regular water or OligoG for 25days after weaning. n≥17. *P<0.001 compared to WT or CF on OligoG. Journal of Cystic Fibrosis 2016 15, 745-751DOI: (10.1016/j.jcf.2016.06.005) Copyright © 2016 European Cystic Fibrosis Society. Terms and Conditions

Fig. 3 Intestinal histology and assessment of relative intestinal mucus amount in WT and CF mice on regular water or OligoG. (A) Intestinal sections from WT, CF and CF mice on OligoG are shown stained with nuclear fast red (red) to stain cells and alcian blue (blue) to stain mucus (first column). Assessment of blue stained mucus was made between pairs of villi (second column). The space between villi was indicated within the software which then pseudo-colored mucus green and empty space black (third column) to calculate percent of space between the villi that contained mucus. Scale bar=50μm. (B) Percentage of area between villi that is mucus filled from intestinal sections in WT, WT on OligoG, CF and CF mice on OligoG. n≥10; *P<0.05. Journal of Cystic Fibrosis 2016 15, 745-751DOI: (10.1016/j.jcf.2016.06.005) Copyright © 2016 European Cystic Fibrosis Society. Terms and Conditions

Fig. 4 Growth of WT and CF mice on regular water or OligoG. (A) Weight of WT, WT on OligoG, CF and CF mice on OligoG was measured from weaning (day 0) to 25days post-weaning. WT mice were significantly heavier at all time points measured P<0.05. Equal numbers of males and females were included. (B) Weight of WT, WT on OligoG, CF and CF mice on OligoG at 25days post-weaning separated by sex. *P<0.05 compared to WT. n≥10. Journal of Cystic Fibrosis 2016 15, 745-751DOI: (10.1016/j.jcf.2016.06.005) Copyright © 2016 European Cystic Fibrosis Society. Terms and Conditions