The serine/threonine kinase p38 is a ubiquitous, highly conserved, stress responsive, signal-transducing enzyme. It regulates the production of proinflammatory mediators and is the target of the cytokine synthesis inhibitory pyridinylimidazoles. We have expressed human p38 in Drosophila S2 cells and characterized preparations of mixed unphosphorylated/monophosphorylated (inactive) and homogeneously diphosphorylated (active) forms of the enzyme. We observed that only the active preparation of the enzyme has significant kinase activity when assayed using an ATF2-GST fusion protein as the substrate. We determined that the value of KM[ATP] in this reaction is 25 microM and that the pyridinylimidazole inhibitor of p38 kinase activity, SB203580, competes with ATP. We have found that a tritiated pyridinylimidazole, SB202190, has an equal affinity for both the active and inactive forms of the enzyme and that SB203580 competes with it equally well for binding to either form of the enzyme. However, ATP can compete with the tritiated inhibitor for binding to only the active form of the enzyme. Further, we demonstrate in vivo that at concentrations consistent with its IC50 as a cytokine inhibitor, SB203580 can inhibit stimulus-induced phosphorylation of p38 at the Thr-Gly-Tyr activation motif. Our observations suggest that pyridinylimidazoles may block the biological activity of p38 kinase by binding to the inactive form of p38 and reducing its rate of activation. Under these conditions, ATP would not effectively compete with the inhibitors in vivo.

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Mobile populations are vulnerable to contracting HIV. The present study aims to evaluate the relative efficacy of the voluntary counseling and testing plus information dissemination (VCT-ID) approach versus the information dissemination (ID) approach for promoting HIV preventive behaviors in a mobile population, cross-border truck drivers. A total of 301 adult male cross-border truck drivers who self-reported having had sex with female sex workers (FSW) or non-regular sex partners (NRPs) in mainland China in the last 12 months were recruited and randomized into the VCT-ID intervention group (Group I) or ID control group (Group C). Anonymous structured questionnaires, administered through a computer-assisted method, were used to collect data. At the follow-up survey (about 8-9 weeks since the baseline survey), Group I participants, as compared to Group C participants, were more likely to be consistent condom users when having sex with FSW (85.5% versus 68.5%, p<0.05) and with NRP (54.8% versus 36.4%, p<0.1), more knowledgeable about HIV, and were less likely to have contracted sexually transmitted diseases (STD) in the last two months. The VCT-ID approach is shown to be more efficacious than the ID approach in promoting safer sex and HIV-related knowledge among local cross-border truck drivers. Feasibility of providing voluntary counseling and testing (VCT) services at locations which are convenient to the target population is demonstrated. It also shows that VCT services can be used as a means of HIV prevention. The findings of this study resulted in up-scaled VCT services for the local target population.