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Results: 4

1.
Figure 2

Figure 2. From: Computational repositioning of the anticonvulsant topiramate for inflammatory bowel disease.

Gross clinical evaluation of IBD severity between treatment groups by percent of animals with diarrhea within each group. Both the topiramate treated group and the prednisolone treated group show reduced proportions of animals with diarrhea relative to the disease-induced group receiving only vehicle. (n=12 animals per group)

Joel T. Dudley, et al. Sci Transl Med. 2011 August 17;3(96):96ra76-96ra76.
2.
Figure 1

Figure 1. From: Computational repositioning of the anticonvulsant topiramate for inflammatory bowel disease.

Significant drug-disease scores for Crohn’s disease. The names of the drugs are placed along the bottom axis, and the vertical bars above the drug name indicate the computationally predicted therapeutic score for the drug based on comparison of the gene expression signature of the drug with the gene expression signature of Crohn’s disease. A positive score indicates that the drug exhibits an expression pattern that is synergistic with the disease, while a negative score indicates that the drug exhibits an expression pattern that is oppositional to the disease. Drugs are sorted from left-to-right starting with those predicted to be most efficacious for the disease. Green bars indicate drugs that are discussed in the text. The red triangle points towards the anticonvulsant drug topiramate, which was selected for experimental validation.

Joel T. Dudley, et al. Sci Transl Med. 2011 August 17;3(96):96ra76-96ra76.
3.
Figure 3

Figure 3. From: Computational repositioning of the anticonvulsant topiramate for inflammatory bowel disease.

Pathological assessment of IBD severity between treatment groups. A) Clinical endoscopy captured from live animals on day 7 of the study. B) Gross pathology score. C) Pictomicrographs of H&E stained colon tissues showing microscopic damage to the mucosal and epithelial layers of the colon wall between treatment groups. D) Macroscopic damage score assessed from light microscopy of fixed colon tissues. Data graphs represent the mean and SEM estimated from three independent experiments. (n=12 rats per group) (* = P<0.05, ****=P<0.00005; Mann Whitney U test).

Joel T. Dudley, et al. Sci Transl Med. 2011 August 17;3(96):96ra76-96ra76.
4.
Figure 4

Figure 4. From: Computational repositioning of the anticonvulsant topiramate for inflammatory bowel disease.

Evaluation and comparison of gene expression signatures for the drug compound topiramate and Crohn’s disease. A) Comparison of the Crohn’s disease signature (right) to the topiramate gene expression profile (left) showing a generally anti-correlated pattern, with genes at the top- and bottom-most ends of the expression pattern showing generally oppositional expression patterns. Genes that are up regulated are shown in green. Genes that are down regulated are shown in red. The pathways and functional groups significantly enriched (enrichment P-value < 0.05) in the top- and bottom 25% of genes are shown on the right hand side. B) qPCR results showing that gene transcripts for TRPV1 and IFI30 have oppositional gene expression levels in the disease condition (TNBS+vehicle) relative to the drug treated condition (TNBS+topiramate) in colon tissues collected from the animal validation study, which corroborates their expected oppositional relationship from initial comparison of the topiramate and Crohn’s expression signatures. (n=12 rats per group) (*=P<0.05, **=P<0.005; Mann Whitney U test; Error bars=SEM)

Joel T. Dudley, et al. Sci Transl Med. 2011 August 17;3(96):96ra76-96ra76.

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