Storage conditions, sample integrity, interferences, and a decision tool for investigating unusual high-sensitivity cardiac troponin results.

The current definition of high-sensitivity cardiac troponin (hs-cTn) assays is laboratory-based and their analytical attributes and characteristics have drawn significant attention in the literature at least partly due to the lower concentration cut-offs and changes in concentrations (i.e., deltas) employed in different algorithms and pathways to manage patient care. We propose that pre-analytical conditions such as sample type, storage conditions, and other interferences may also have a significant impact on hs-cTn concentrations and clinical management. The purpose of this literature review is to provide a summary of important pre-analytical and interference studies affecting hs-cTn concentrations. A breakdown of the literature for the major diagnostic companies providing core laboratory instrumentation (i.e., Abbott, Beckman, Ortho, Roche, and Siemens) is also provided. Finally, three cases are highlighted where knowledge of pre-analytical factors aids the hs-cTn clinically discordant investigations. This review highlights the importance of pre-analytical variables, especially storage condition, sample handling, and blood tubes used (i.e., sample type) when interpreting hs-cTn assays. Additional studies are needed to further elaborate on pre-analytical variables (i.e., centrifugation, sample type, stability) and interferences for all hs-cTn assays in clinical use, as knowledge of these variables may aid in hs-cTn clinically discordant investigations.

Chemical Methods for Probing Virus-Host Proteomic Interactions.

Interactions between host and pathogen proteins constitute an important aspect of both infectivity and the host immune response. Different viruses have evolved complex mechanisms to hijack host-cell machinery and metabolic pathways to redirect resources and energy flow toward viral propagation. These interactions are often critical to the virus, and thus understanding these interactions at a molecular level gives rise to opportunities to develop novel antiviral strategies for therapeutic intervention. This review summarizes current advances in chemoproteomic methods for studying these molecular altercations between different viruses and their hosts.

6-Hydroxydopamine Inhibits the Hepatitis C Virus through Alkylation of Host and Viral Proteins and the Induction of Oxidative Stress.

Many viruses, including the hepatitis C virus (HCV), are dependent on the host RNA silencing pathway for replication. In this study, we screened small molecule probes, previously reported to disrupt loading of the RNA-induced silencing complex (RISC), including 6-hydroxydopamine (6-OHDA), suramin (SUR), and aurintricarboxylic acid (ATA), to examine their effects on viral replication. We found that 6-OHDA inhibited HCV replication; however, 6-OHDA was a less potent inhibitor of RISC than either SUR or ATA. By generating a novel chemical probe (6-OHDA-yne), we determined that 6-OHDA covalently modifies host and virus proteins. Moreover, 6-OHDA was shown to be an alkylating agent that is capable of generating adducts with a number of enzymes involved in the oxidative stress response. Furthermore, modification of viral enzymes with 6-OHDA and 6-OHDA-yne was found to inhibit their enzymatic activity. Our findings suggest that 6-OHDA is a probe for oxidative stress as well as protein alkylation, and these properties together contribute to the antiviral effects of this compound.