LY2940680 is prepared using saline Solution as a vehicle injection

For further details of the LY2940680 policy, if you pla t contact Procter & Gamble. The induction of arthritis iodoacetate-induced arthritis was induced by a single intraarticular Re injection of iodoacetate into the knee joint of anaesthetized rats with CO2/O2. A 10 mg / ml concentration of monosodium iodoacetate is prepared using saline Solution as a vehicle injection. After ad Quate to Anesthesia, each rat was placed on the back and the left leg was flexed 90 degrees at the knee. The patellar ligament was palpated below the patella and the injection was made in this area. Each rat re 0.025 u ml intraarticular re In the left knee using a gas with a glass syringe needle gauge sealed 27 1/2 inches. Care was taken, the needle is not too far ahead in the Kreuzb Direction.
After injection of rats were orally treated with vehicle offers iodoacetate, VX 745 or SB203580 as a suspension in 0.5% carboxymethylcellulose / 0.5% Tween 20 for 3 weeks. There were 15 rats in each treatment group. After completion of the study, Avasimibe the left knee were eingeschl Disarticulated tert animals and the tibial plateau mapped using an image analyzer Optima. The tibial tray has been used for image analysis, because it is a relatively flat surface che Provided with respect to the femoral condyles, such that the device t Of image analysis on the entire surface Surface to concentrate the cartilage. The severity of the Sch In the enlarged Erten images were independently by three-Dependent observers blinded manner using a scale of increasing severity, as described above rated.
Hargraeve hyperalgesia model sm MALE Sprague-Dawley rats weighing 100 150 g were two per K Housed in fig bo Shoe you health, animals ventilated with the temperature controlled Lee, humidity and lighting regularly Strength were used. Rodent and water were allowed ad libitum. The animals were acclimated for one week before use. The first day of the study, each animal was weight Hnt to test equipment, and thermal hyperalgesia was tested using the Hargreaves plantar Ger t establish reference values paw withdrawal latency. The reference values were calculated as an average of 2 PWL pre dose. Animals were fasted overnight before dosing. Animals following day, orally administered with a compound vehicle, indomethacin or test. Three moderately minutes after administration of each animal was bet Ubt with CO2/O2 and re U intra-plantar injection of 0.
100 ml of 1.2% carrageenan Viscarin GP 109 and returned to his K Recover fig. Four hours after the injection, the left hind leg of the rat was evaluated for thermal hyperalgesia. The animals were again placed in the Hargreaves plantar to the response to the stimulus of W Determine warmth. Three responses were recorded, and the last two were averaged to determine the response to the end of the study. The statistical analysis Change in paw volume withdrawal latency treatment groups of vehicles and drugs in the assay Hargraeve s was calculated. Statistical comparisons between the treatment groups were compared using analysis of covariance. The percentage reduction iodoacetate induced knee degeneration in rats, the animals were compared with vehicle and analyzed using the Cochran Mantel Haenszel. Results 745 SB 203580 and VX are potent inhibitors of p38.

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