Incompatibility of drug and nutrient injections is clinically hazardous. Knowledge of products' chemical facts, organic acid-base equilibria in relation to ionization and nonionization and aqueous solubility, and ranges of pH and ingredient strength from United States Pharmacopeia monographs and product labeling is the foundation of expertise in drug incompatibility. Precipitation in injectable drug solutions should be suspected, particularly when oppositely charged drug salts are mixed in relatively strong concentrations and when pH values of dilutions create more than 1% of nonionized drug forms.
A brief review of pKa values and their uses in pharmacy practice is presented. Tables of pKa values for 400 medicinal compounds, of pH values of 18 body fluid sites, and of electron-inducing chemical substituents are provided. Adequate literature sources are included to permit further reference to the more detailed aspects of conditions associated with pKa value determinations or uses.
Background
Prior transcriptional studies of atrial fibrillation (AF) have been limited to specific transcripts, animal models, chronic AF, right atria, or small samples. We sought to characterize the left atrial transcriptome in human AF to distinguish changes related to AF susceptibility and persistence.
Methods and Results
Left atrial appendages from 239 patients stratified by coronary artery disease, valve disease and AF history (No AF history, AF history in sinus rhythm at surgery, AF history in AF at surgery) were selected for genome-wide mRNA microarray profiling. Transcripts were examined for differential expression with AF phenotype group. Enrichment in differentially expressed genes was examined in 3 gene set collections: A transcription factor (TF) collection, defined by shared conserved cis-regulatory motifs; a miRNA collection, defined by shared 3′UTR motifs; and a molecular function collection, defined by shared Gene-Ontology molecular function. AF susceptibility was associated with decreased expression of the targets of CREB/ATF family, HSF1, ATF6, SRF, and E2F1 TFs. Persistent AF activity was associated with decreased expression in genes and gene sets related to ion channel function consistent with reported functional changes.
Conclusions
AF susceptibility was associated with decreased expression of targets of several transcription factors related to inflammation, oxidation, and cellular stress responses. In contrast, changes in ion channel expression were associated with AF activity, but were limited in AF susceptibility. Our results suggest that significant transcriptional remodeling marks susceptibility to AF, while remodeling of ion channel expression occurs later in the progression or as a consequence of AF.
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