“Salmonella enterica Gallinarum (SG) causes fowl typhoid (FT), a septicemic disease in avian species. We constructed deletion mutants lacking the stress sigma factor RpoS, the nitric oxide (NO)-detoxifying flavohemoglobin PFTα mouse Hmp, and the SsrA/SsrB regulator to confirm the functions of these factors in SG. All gene products were fully functional in wild-type (WT) SG whereas mutants harboring single mutations or a combination of rpoS,hmp, and
ssrAB mutations showed hypersusceptibility to H2O2, loss of NO metabolism, and absence of Salmonella pathogenicity island (SPI)-2 expression, respectively. Atriple-deletion mutant, SG Delta 3 (SG Delta rpoS Delta hmp Delta ssrAB), was evaluated for attenuated virulence and protection efficacy in two-week-old Lohmann layer chickens. The SG Delta 3 mutant did not cause any mortality after inoculation with either 1 x 10(6) or 1 x 10(8) colony-forming units (CFUs) of bacteria. Significantly lower numbers of salmonellae were recovered from the liver and spleen of chickens inoculated with the SG Delta 3 mutant compared to chickens inoculated with WT SG. Vaccination with the SG Delta 3 mutant conferred complete protection against challenge with virulent SG on the chickens comparable
to the group vaccinated with a conventional vaccine see more strain, SG9R. Overall, these results indicate that SG Delta 3 could be a promising candidate for a live Salmonella vaccine against FT.”
“The present study examined the antihyperalgesic effect of a specific inhibitor of Glycogen
Synthase Kinase 3 (GSK3), AR-A014418, on the partial ligation of the sciatic nerve (PSNL), a neuropathic pain model in mice and investigated some mechanisms of action. AR-A014418 (0.01-1 mg/kg) administered by intraperitoneal route (i.p.) inhibited mechanical hyperalgesia. This action started 30 min after i.p. administration and remained significant up to 2 h. When administered daily for Sotrastaurin chemical structure 5 days, AR-A014418 (0.3 mg/kg, i.p.) significantly reduced the mechanical hyperalgesia caused by PSNL. Intraperitoneal (i.p.) treatment with AR-A014418 (0.3 mg/kg) also significantly inhibited cold hyperalgesia induced by PSNL. Pre-administration of PCPA (100 mg/kg, i.p., inhibitor of serotonin synthesis) and AMPT (100 mg/kg, i.p., inhibitor of tyrosine hydroxylase), but not L-arginine (600 mg/kg, i.p., a nitric oxide precursor), significantly reduced the mechanical hyperalgesia elicited by AR-A014418. Furthermore, the administration of AR-A014418 significantly prevented the increase of TNF-alpha (inhibition of 76 +/- 8%) and IL-1 beta (inhibition of 62 +/- 10%), but did not alter lumbar spinal cord IL1-ra and IL-10 levels. Finally, intraperitoneal administration of AR-A014418 did not affect locomotor activity in the open-field test.