Both local and systemic routes selleck chemical Wortmannin of ad ministration were tested and, in the case of i. a, a dose effect for UCX cells was also evaluated. The treatment schedule and UCX dosage are shown in Figure 6. Arth ritis was induced in the sub plantar area of right hind paws and the onset of arthritic manifestations was observed at day 13, when arthritis became established. Figure 7 depicts % variations related to naive animals Inhibitors,Modulators,Libraries in both, volume of posterior right hind paw and ankle circumference, for systemic and local administration groups. In all experimental groups, animals typically lost near to 20% body weight during the acute phase of the disease, between days 13 and 20 after induction. Body weight recovery between days 20 and 55 was accompanied by regression of hind paw inflammation in all experimental groups.
However, UCX i. a. administration proved to be highly effective in ameliorating local inflammatory sig nals when compared to UCX i. p. administration. Inhibitors,Modulators,Libraries While UCX i. p. administration has shown no improvements in local inflammation, Inhibitors,Modulators,Libraries when compared to the Sham control, UCX i. a. administration promoted a significantly faster regression of both hind paw volume Inhibitors,Modulators,Libraries and hind paw circumference, from days 20 to 55. The promotion of hind paw volume regression caused by UCX cells was shown to be dose dependent, with the highest UCX cell dose reaching an average of nearly 80% volume recovery at day 55. When all local and systemic parameters were taken together, as a measure of the arthritic index, the positive effect of UCX treatment became clear.
As it can be seen in Figure 8A and 8C the severity of AIA was rapidly attenuated overtime in UCX treated mice, as compared with both control untreated Inhibitors,Modulators,Libraries and vehicle treated groups. As observed in Figure 8A, the Sham group reached a maximum AI score of 7. 6 while i. p. UCX treated animals reached a maximum of 5 after arthritis induction. In the case of local treat ment, the Sham group reached a maximum AI of 6 at day 32 after induction and significant lower values were obtained for treated groups, in a dose dependent fashion. The Sham group presented a decrease in AI values following the same trend as treated groups but with higher severity index. This can pos sibly be interpreted as either a local wash away effect, reducing the infection locally, or a decompressing effect due to i. a. injection that released pus, thereby reducing hind paw volume. Just like the promotion of volume and paw circumference regression before, the reduction of AI scores during the follow up of i. a. administration was shown to be UCX dose dependent. The AI scores were representative of the relative AIA severity and were clearly better supported by ma croscopic observations.