P38␣ is a protein kinase that regulates the expression of inflammatory cytokines, suggesting a role in the pathogenesis of diseases such as rheumatoid arthritis (RA) or systemic lupus erythematosus. Here, we describe the preclinical pharmacology of pamapimod, a novel p38 mitogen-activated protein kinase inhibitor. Pamapimod inhibited p38␣ and p38 enzymatic activity, with IC 50 values of 0.014 Ϯ 0.002 and 0.48 Ϯ 0.04 M, respectively. There was no activity against p38␦ or p38␥ isoforms. When profiled across 350 kinases, pamapimod bound only to four kinases in addition to p38. Cellular potency was assessed using phosphorylation of heat shock protein-27 and c-Jun as selective readouts for p38 and c-Jun NH 2 -terminal kinase (JNK), respectively. Pamapimod inhibited p38 (IC 50 , 0.06 M), but inhibition of JNK was not detected. Pamapimod also inhibited lipopolysaccharide (LPS)-stimulated tumor necrosis factor (TNF) ␣ production by monocytes, interleukin (IL)-1 production in human whole blood, and spontaneous TNF␣ production by synovial explants from RA patients. LPS-and TNF␣-stimulated production of TNF␣ and IL-6 in rodents also was inhibited by pamapimod. In murine collagen-induced arthritis, pamapimod reduced clinical signs of inflammation and bone loss at 50 mg/kg or greater. In a rat model of hyperalgesia, pamapimod increased tolerance to pressure in a dose-dependent manner, suggesting an important role of p38 in pain associated with inflammation. Finally, an analog of pamapimod that has equivalent potency and selectivity inhibited renal disease in lupus-prone MRL/lpr mice. Our study demonstrates that pamapimod is a potent, selective inhibitor of p38␣ with the ability to inhibit the signs and symptoms of RA and other autoimmune diseases.
The thermal degradation behavior of indium tin oxide (ITO) thin films coated on glass substrates using radio frequency (rf) magnetron sputtering was investigated over the temperature range of 100–400 °C in air. The resistivity of ITO films increases abruptly after the thermal degradation temperature of 250 °C is reached, with a slight increase from 200 to 250 °C. The x-ray photoelectron spectrometry intensity ratio of O/(In + Sn) in thermally degraded ITO films is higher than that in normal films. The carrier concentration gradually decreases up to 200 °C, sharply drops between 200 and 250 °C with increasing temperature, and then saturates from 275 °C. The Hall mobility drops suddenly at 275 °C. The diffusion of oxygen into oxygen interstitials and oxygen vacancies and the chemisorption of oxygen into grain boundaries decrease the carrier concentration and the Hall mobility, respectively. The former mainly affects the resistivity of ITO films below 250 °C, and the later above 250 °C.
Purpose: The purpose of this study was to investigate the effects of combined training using proprioceptive neuromuscular facilitation (PNF) patterns and treadmills on the balance and walking ability of stroke patients. Methods: Twenty-three stroke patients were randomized into a control group (n= 11), receiving only treadmill training and an experimental group (n= 12) receiving combined training. The use of both PNF exercise and treadmill were implemented in the combined training. Interventions were performed 5 times a week for 6 weeks. Balance ability was measured by a timed up and go (TUG) test. Walking ability was measured by a 10-meter walk test (10MWT) and a 6-minute walk test (6MWT). A paired t-test was used to compare differences between pre-and post-intervention and independent t-tests were used to compare between groups. Results: Changes in TUG, 10MWT, and 6MWT before and after interventions were significantly different for both the experimental group and the control group (p< 0.05). In addition, within-group changes in the TUG, 10MWT, and 6MWT were more effective in the experimental group than in the control group (p< 0.05). Conclusion: Combined training using PNF techniques and treadmills may be useful in improving the balance and walking ability of stroke patients.
[Purpose] This study aimed to investigate the effects of horse-riding exercise on
balance, gait, and activities of daily living (ADLs) in stroke patients. [Subjects] Among
20 participants with stroke, 10 were randomly assigned to the experimental group, and 10
were randomly assigned to the control group. The experimental group participated in
horse-riding exercise for 30 minutes per day, 5 days a week for 6 weeks. Balance was
tested with the Berg Balance Scale (BBS). Gait was measured using the 10-Meter Walk Test
(10MWT). ADLs were tested with the Modified Barthel Index (MBI). Differences between pre-
and post-experiment values within the two groups were compared using paired t-tests.
Between-group differences were compared using independent t-tests. [Results] The
experimental group showed significant improvements in balance, gait, and ADLs following
horse-riding exercise. Additionally, the experimental group showed significant differences
in balance, gait, and ADLs compared with in the control group. [Conclusion] These results
support that horse-riding exercise enhances balance, gait, and ADLs in stroke patients.
This study supports the need for further research on horse-riding exercise programs.
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