Azithromycin-Induced Liver Injury in Legionnaires' Disease.

Drug-induced liver injury (DILI) is the leading cause of acute liver failure in the United States. Azithromycin is a commonly used antibiotic for community-acquired pneumonia that causes liver injury in rare cases. Typically, cholestatic liver injury has been reported for azithromycin, but there have only been a few case reports addressing the association with direct hepatocellular liver injury. This is a case of a 66-year-old man, with no pre-existing liver disease, who was managed for Legionnaires' disease who sustained a hepatocellular pattern of liver injury associated with azithromycin. We report this case to highlight the importance of prompt recognition of these rare side effects associated with azithromycin and the discontinuation of the drug to facilitate rapid recovery.

Lack of Influence by CYP3A4 and CYP3A5 Genotypes on Pain Relief by Hydrocodone in Postoperative Cesarean Section Pain Management.

BACKGROUND: Genetic polymorphisms of cytochrome P450 are contributors to variability in individual response to drugs. Within the P450 family, CYP2D6 is responsible for metabolizing hydrocodone, a widely prescribed opioid for pain management. Alternatively, CYP3A4 and CYP3A5 can form norhydrocodone and dihydrocodeine. We have previously found that in a postcesarean section cohort, the rate of hydromorphone formation was dependent on the genotype of CYP2D6 and that plasma hydromorphone, not hydrocodone, was predictive of pain relief. METHOD: Blood was obtained from a postcesarean cohort that were surveyed for pain response and common side effects. Plasma samples were genotyped for CYP3A4/5, and their hydrocodone concentrations were measured by LC-MS. R statistical software was used to check for differences in the outcomes due to CYP3A4/5 and CYP2D6, and a multivariate regression model was fit to determine factors associated with pain score. RESULTS: Two-way ANOVA between CYP3A4/A5 and CYP2D6 phenotypes revealed that the former variants did not have a statistical significance on the outcomes, and only CYP2D6 phenotypes had a significant effect on total dosage (P = 0.041). Furthermore, a 3-way ANOVA analysis showed that CYP2D6 (P = 0.036) had a predictive effect on plasma hydromorphone concentrations, and CYP3A4/A5 did not have any effect on the measured outcomes. CONCLUSIONS: With respect to total dosages in a cesarean section population, these results confirm that CYP2D6 phenotypes are predictors for plasma hydromorphone concentration and pain relief, but CYP3A4/A5 phenotypes have no influence on pain relief or on side effects.

Long interspersed nuclear element-1 mobilization as a target in cancer diagnostics, prognostics and therapeutics.

Long Interspersed Nuclear Element-1 (LINE-1) are DNAs that compromise 17% of our genome. LINE-1 expression is triggered by environmental stressors and accomplished through its demethylation leading to genomic instability. Expression of LINE-1 is regulated in adult somatic tissues through several endogenous defensive mechanisms, but is found to be associated with tumorigenesis in several cancers. This finding, has inspired the use of different indicators of LINE-1 activation, as biomarkers in cancer diagnostics and even therapeutic targets in recent years. The objective of this review is to provide a critical examination of LINE-1 elements as companion cancer diagnostic/prognostic biomarkers and anti-cancer drug targets. In our view, there's great potential for LINE-1 serving at both forefronts, but there is a need for more mechanistic studies in the clinic as well as on the bench research to validate LINE-1 activation elements as cancer biomarkers or therapeutic targets; in different cancer types and/or stages of the disease. In this context, development of minimally invasive, reliable and sensitive diagnostic tools for LINE-1 activation elements for clinical use, is of priority.

Discovery of the Long Interspersed Nuclear Element-1 activation product [Open Reading Frame-1 (ORF1) protein] in human blood.

Long Interspersed Nuclear Element 1 is the only autonomous mobile DNA capable of self-propagation, and is an environmental biomarker that is activated upon an environmental trigger. We have developed an ELISA method to detect and measure Open Reading Frame-1 (ORF1) and have applied it to interrogate serum samples from men with equivocal prostate specific antigen (PSA) results. Polyclonal antibodies were developed using the first 14-amino acid peptide of N-terminal-ORF1 protein. Remnant serum samples from a total of 53 men, ages>50 yr, were analyzed for immunoreactive ORF1 (iORF1) and PSA concentrations; outcomes for the non-biopsied and biopsied groups were also recorded. The dynamic range of the ELISA was between (CV): 2.0 (14%) to 30 ng/mL (1.2%). The total imprecision (within-run/inter-day) was: QC3 = 2.7%/21%, QC6 = 1.1%/18%, and QC20 = 0.33%/11%. The median iORF1 concentration in the non-biopsy group was 14.7 ng/mL (Q1 - Q3: 10.5 - Q3:18.4), which was significantly lower than the Biopsy group at 25.0 ng/mL (Q1 - Q3: 20.0-33.1), P-value = .003. In conclusion, we have developed a competitive ELISA and discovered the presence of iORF1 in serum, which could be used to advance future studies involving ORF1 measurement from blood. In addition, iORF1 may be a complement with the PSA screen to better detect prostate cancer.