Introduction: Angioedema is a rare but potentially life-threatening adverse effect associated with the use of angiotensin-converting enzyme (ACE) inhibitors. Various therapies, including ecallantide, icatibant, complement-1 esterase inhibitors, and fresh frozen plasma, have been used for treatment with inconsistent results and significant adverse effects. Tranexamic acid (TXA) is used as an alternative for the treatment of hereditary angioedema and it may be an attractive option for the treatment of ACE inhibitor-induced angioedema (ACEi-AE) in the emergency department (ED). The purpose of this study was to evaluate the impact of TXA administration on rates of intubation in patients presenting to the ED with suspected ACEi-AE.Methods: This was an institutional review board-approved, retrospective cohort study conducted at a singlesite ED. All patients who received TXA for ACEi-AE in the ED between January 1, 2019 and March 31, 2021 were eligible for inclusion. The primary outcome was the proportion of patients who required intubation for suspected ACEi-AE.Results: A total of 16 patients received TXA in the ED for suspected ACEi-AE during the study timeframe. Of these, two patients were intubated prior to administration of TXA. The remaining 14 patients did not require intubation following TXA administration. Conclusion: Administration of TXA was associated with a low rate of adverse effects and did not contribute to further morbidity when added to standard care in patients presenting to the ED with suspected ACEi-AE.

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Colorectal cancer (CRC) is a common, and often incurable, form of cancer. Gene silencing by CpG island hypermethylation often plays a role in CRC progression. Certain regions of the genome, called high confidence differentially‐methylated regions (DMRs), are consistently hypermethylated across numerous patient samples. In this study, we used bisulfite PCR sequencing to investigate methylation levels at DMRs in the promoter region of CDKN2A, DKK3, EN1, MiR34b, SPG20, and TLX1 in HCT‐116 CRC cells. We observed that for all DMRs except CDKN2A, the demethylating agent decitabine significantly reduced CpG methylation. Using ENCODE project data, we observed that transcriptional activator binding inversely correlates with DNA methylation at all of these sites across diverse cancers and cell types. Our data increase resolution of the methylation status at the above DMRs, show the reversibility of methylation at these sites by decitabine, and the likely role of hypermethylation at these sites in gene silencing. In the future, we plan to test if DMR any specific gene silencing protects HCT116 cells.Support or Funding InformationThis work is supported by the Lake Forest College biochemistry and molecular biology program.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Background: Gene silencing by CpG island hypermethylation often plays a role in colorectal cancer (CRC) progression. Certain regions of the genome, called high confidence differentially-methylated regions (DMRs), are consistently hypermethylated across numerous patient samples. Methods: In this study, we used bioinformatics and bisulfite PCR sequencing of HCT-116 cells to investigate methylation levels at DMRs in the promoters of six genes: DKK3, EN1, MiR34b, SDC2, SPG20, and TLX1. We then investigated whether the anti-cancer drug decitabine, had a demethylating effect at these promoter regions. Results: We found that hypermethylation correlated with lack of transcriptional enhancer binding in these six regions. Importantly, we observed that for all DMRs, decitabine significantly reduced CpG methylation. Decitabine also reduced clonogenic survival, suggesting that there is a correlation between lower CpG island methylation levels and reduced cancerous properties. Conclusions: Our study provided single-nucleotide resolution and revealed hypermethylated CpG sites not shown by previous genome-wide methylation studies. In the future, we plan to perform experiments that demonstrate a causal link between promoter hypermethylation and carcinogenesis and that more accurately model treatments in CRC patients.