The histone acetyl transferases CBP and p300 regulate stress response pathways in synovial fibroblasts at transcriptional and functional levels.

The activation of stress response pathways in synovial fibroblasts (SF) is a hallmark of rheumatoid arthritis (RA). CBP and p300 are two highly homologous histone acetyl transferases and writers of activating histone 3 lysine 27 acetylation (H3K27ac) marks. Furthermore, they serve as co-factors for transcription factors and acetylate many non-histone proteins.

Individual functions of the histone acetyl transferases CBP and p300 in regulating the inflammatory response of synovial fibroblasts.

Chromatin remodeling, and a persistent histone 3 lysine 27 acetylation (H3K27ac) in particular, are associated with a sustained inflammatory response of synovial fibroblasts (SF) in rheumatoid arthritis (RA). Here we investigated individual functions of the writers of H3K27ac marks, the homologues histone acetyl transferases (HAT) CBP and p300, in controlling the constitutive and inflammatory gene expression in RA SF. We applied a silencing strategy, followed by RNA-sequencing and pathway analysis, complemented with the treatment of SF with inhibitors targeting the HAT (C646) or bromo domains (I-CBP) of CBP and p300.

Potency, duration of action and pA2 in man of intravenous naloxone measured by reversal of morphine-depressed respiration.

Placebo and morphine (5 and 10 mg) alone and in combination with naloxone (0.2, 0.4 and 0.

Respiratory depression of intravenous hydroxyzine in man: potency, duration, and lack of reversal by naloxone.

The effects of intravenous hydroxyzine and hydroxyzine with naloxone on respiration were determined in man. Drug effect was expressed as the shift in the 20-L intercept of the respiratory response curve measured by a rebreathing technique. The time-effect curve of hydroxyzine was found to be the same for hydroxyzine alone and in combination with naloxone, but significantly different from placebo or naloxone alone.