Generalized estimation equations were used to examine HPA axis activity (plasma ACTH and cortisol), immune activation (plasma IL-6), and depressive symptoms (Hamilton Depression Rating Scale (HDRS) Cell Cycle inhibitor score). Tolerance of IL-2 treatment (concomitant medications required) and adherence (number of IL-2 doses received) were also assessed. Both the groups (ESC (n = 9), placebo (n = 11)) exhibited significant IL-2-induced increases in plasma cortisol, IL-6,
and depressive symptoms (p<0.05), as well as a temporal trend for increases in plasma ACTH (p = 0.054); the effects of age and treatment were not significant. Higher plasma ACTH concentrations were associated with higher depressive symptoms during cycles 1-3 of IL-2 therapy (p<0.01). Although ESC had no significant effects on ACTH, cortisol, IL-6, tolerance of, or adherence to IL-2, ESC treatment was associated with lower depressive symptoms, ie, a maximal difference of similar to 3 points on the HDRS, which, though not statistically significant (in part, due to small sample size), represents a clinically significant difference according to the National Institute for Health and Clinical Excellence guidelines. A larger sample size will establish whether antidepressant pretreatment
can prevent IL-2-induced neurobehavioral changes.”
“A novel anti-varicella-zoster JQ-EZ-05 virus compound, a derivative of pyrazolo[1,5-c]1,3,5-triazin-4-one (coded as 35B2), was identified from a library of 9,600 random compounds. This compound inhibited both acyclovir (ACV)-resistant and -sensitive strains. In a plaque reduction assay under conditions in which the 50% effective concentration of ACV against the vaccine Oka strain (V-Oka) in human fibroblasts was 4.25 mu M, the 50% effective concentration of 35B2 was 0.75 mu M. The selective index of the compound
was more than 200. Treatment with 35B2 inhibited neither immediate-early gene Dorsomorphin supplier expression nor viral DNA synthesis. Twenty-four virus clones resistant to 35B2 were isolated, all of which had a mutation(s) in the amino acid sequence of open reading frame 40 (ORF40), which encodes the major capsid protein (MCP). Most of the mutations were located in the regions corresponding to the “”floor”" domain of the MCP of herpes simplex virus 1. Treatment with 35B2 changed the localization of MCP in the fibroblasts infected with V-Oka but not in the fibroblasts infected with the resistant clones, although it did not affect steady-state levels of MCP. Overexpression of the scaffold proteins restored the normal MCP localization in the 35B2-treated infected cells. The compound did not inhibit the scaffold protein-mediated translocation of MCP from the cytoplasm to the nucleus.