Anti-Morphine monoclonal antibody, clone CDI919

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 The association of morphine ziconotide or sufentanil ziconotide was used to manage cancer pain. Moving these patients is sometimes difficult. In order to transport these syringes for pump refilling, it could be interesting to demonstrate the stability of the mixture and so to be able to ensure the best transport conditions of syringes. Materials and Methods A stability indicating UPLC-DAD method was developed and validated according to the ICH guidelines. Fur mixtures of each association have been stored in 5 +/- 3 degrees C and 25 +/- 2 degrees C and were evaluated for seven days and compared to the initial observed concentrations. Results The stability of these associations was demonstrated at 5 degrees C for seven days thanks to relative concentrations (95% confidence intervals of the mean of three samples) systematically positioned between 95% and 105%. No degradation product was observed during the stability study. Conclusion This study shows the stability of these association morphine ziconotide or sufentanil ziconotide at 5 degrees C for seven days in polypropylen syringes. This result will allow the transport of the preparation under optimal conditions. Advance preparations for intrathecal pump refills could also be feasible.