Anti-Morphine monoclonal antibody, clone N2800Nps4

Background: Environmentally induced epigenetic changes can lead to health problems or disease, but the mechanisms involved remain unclear. Morphine can pass through the placental barrier leading to abnormal embryo development. However, the mechanism by which morphine causes these effects and how they sometimes persist into adulthood is not well known. To unravel the morphine-induced chromatin alterations involved in aberrant embryo development, we explored the role of the H3K27me3/PRC2 repressive complex in gene expression and its transmission across cellular generations in response to morphine. Results: Using mouse embryonic stem cells as a model system, we found that chronic morphine treatment induces a global downregulation of the histone modification H3K27me3. Conversely, ChIP-Seq showed a remarkable increase in H3K27me3 levels at specific genomic sites, particularly promoters, disrupting selective target genes related to embryo development, cell cycle and metabolism. Through a self-regulatory mechanism, morphine downregulated the transcription of PRC2 components responsible for H3K27me3 by enriching high H3K27me3 levels at the promoter region. Downregulation of PRC2 components persisted for at least 48 h (4 cell cycles) following morphine removal, though promoter H3K27me3 levels returned to control levels. Conclusions: Morphine induces targeting of the PRC2 complex to selected promoters, including those of PRC2 components, leading to characteristic changes in gene expression and a global reduction in H3K27me3. Following morphine removal, enhanced promoter H3K27me3 levels revert to normal sooner than global H3K27me3 or PRC2 component transcript levels. We suggest that H3K27me3 is involved in initiating morphine-induced changes in gene expression, but not in their maintenance.

Background: We examined the disparities in emergency department (ED) pain treatment based on cognitive status in older adults with an acute hip fracture. Methods: Observational study in an academic ED in the Bronx, New York. One hundred forty-four adults aged 65 years and older with acute hip fracture were administered the Telephone Interview for Cognitive Status (TICS) while in the ED. The primary outcome was receipt of any parenteral analgesic. The risk factor of interest was cognitive impairment (TICS <= 25). Secondary outcomes included receipt of any opioid, receipt of any analgesic, total dose of analgesics in intravenous morphine equivalent units (MEQ), and time to receiving first analgesic. Results: Of the 87 (60%) study patients who were cognitively impaired, 60% received a parenteral analgesic compared to 79% of the 57 cognitively unimpaired patients (RR 0.76 [95% CI 0.61, 0.94]). The effect of cognitive impairment on receiving any opioids (RR: 0.81, 95% CI 0.67, 0.98) and any analgesic (RR: 0.85; 95% CI: 0.71, 1.01) was similar. The median analgesic dose in cognitively impaired patients was significantly lower than in cognitively unimpaired patients (4 MEQ vs 8 MEQ, p = .003). Conclusion: Among older adults presenting to the ED with acute hip fracture, cognitive impairment was independently associated with lower likelihood of receiving analgesia and lower amount of opioid analgesia.