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Figure 1.

Prasugrel increases the clinical and pathological manifestations of PG-PS-induced arthritis.

(A) Daily measurements of ankle joint diameter. Values represent the change of hind paw diameter in millimetres (n = 16 measurements [8 rats] per group). Values plotted are the mean ± SEM of the measurements. *p<0.05 and ***p<0.001 between PG-PS+prasugrel vs. PG-PS groups. (B) Macroscopic images of paw and ankle joint of the animals at day 21. Increase joint diameter associated with visible signs of inflammation.

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Figure 2.

Differences observed in the PG-PS-induced erosive arthritis after prasugrel treatment.

Histological examination of ankle joints of rats from different groups of sections stained with H&E at 2X and 10× magnifications (A and B, respectively). Sections from untreated animals (not shown) and prasugrel alone revealed no histopathological signs of inflammation. (C) CTGF expression was assessed with fluorescence microscopy (green – FITC). Images are representative of 4 different animals per group. Lower and right photographs underneath are representative of the control isotype stainings. (D) Histopathological score. Values plotted are the mean of the measurements ± SEM, (n = 4 per group) **p<0.01. b, bone; ss, synovial space; p, pannus.

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Figure 3.

Increase in liver granuloma formation in the prasugrel treated PG-PS-induced animals.

Photographs of liver tissue, stained with H&E, showing the formation of granulomas in the hepatic tissue. Upper panel photographs represent hepatic tissue at 2× magnification (A) and middle panel photographs are magnifications of granulomas (10X) (B) with the presence of giant cells (40X) (C). Images are representative of 4 animals per group. Percentage of granuloma area in the liver (**p<0.01) (D) and the presence of giant cells at the granuloma (*p<0.05) (E) were measured and plotted. Values represent the mean ± SEM, (n = 6).

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Figure 4.

Hematology cell counts following prasugrel treatment in PG-PS- induced arthritis model.

White blood cells (WBC) (A), differential (B) and platelet (C) blood counts at day 21. Cell counts are 103/µL. Values are mean ± SEM, (n = 6), **p<0.01, ***p<0.001.

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Figure 5.

Platelet aggregation studies using 2MeSADP.

Effect of 2MeSADP (100 nM) on platelet aggregation in washed platelets isolated from the blood of the rats. Traces are representative (n = 3) of each of the groups of the study.

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Table 1.

Cytokine profile.

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Table 1 Expand