High-performance liquid chromatographic assay of 8-hydroxyquinoline sulfate and its stability in immunobiological preparations.

Because of the ability of 8-hydroxyquinoline sulfate (8-HQS) to irreversibly bind metals from rubber stoppers, the stability of 8-HQS in tuberculin solutions was investigated. For the determination of 8-HQS, a simple and sensitive reversed-phase HPLC method with detection at 240 nm was developed and validated. Rapid decreases in concentrations of 8-HQS were found in samples stored in original vials which were exposed to different temperatures and vial positions.

Hepatocyte lysis induced by environmental metal toxins may involve apoptotic death signals initiated by mitochondrial injury.

Addition of CdCl2, HgCl2 or K2Cr2O7 to isolated hepatocytes caused a rapid increase in reactive oxygen species ("ROS") formation and a decline in mitochondrial membrane potential. Later lipid peroxidation and cell lysis ensued. Cytotoxicity was prevented by "ROS" scavengers and various inhibitors of the mitochondrial permeability transition (MPT) eg. cyclosporin A, carnitine or trifluoperazine. Antioxidants prevented hepatocyte lysis induced by CdCl2, K2Cr2O7 but not HgCl2. Hepatocyte lysis was also prevented by various apoptosis inhibitors eg, cycloheximide, dactinomycin and a tetrapeptide caspase 3 inhibitor which suggests that metal induced hepatocyte lysis involves apoptotic death signals initiated by MPT and "ROS".

Psychiatric pharmacogenomics predicts health resource utilization of outpatients with anxiety and depression.

Antidepressants are among the most widely prescribed medications, yet only 35-45% of patients achieve remission following an initial antidepressant trial. The financial burden of treatment failures in direct treatment costs, disability claims, decreased productivity, and missed work may, in part, derive from a mismatch between optimal and actual prescribed medications. The present 1 year blinded and retrospective study evaluated eight direct or indirect health care utilization measures for 96 patients with a DSM-IV-TR diagnosis of depressive or anxiety disorder. The eight measures were evaluated in relation to an interpretive pharmacogenomic test and reporting system, designed to predict antidepressant responses based on DNA variations in cytochrome P450 genes (CYP2D6, CYP2C19, CYP2C9 and CYP1A2), the serotonin transporter gene (SLC6A4) and the serotonin 2A receptor gene (5HTR2A). All subjects had been prescribed at least one of 26 commonly prescribed antidepressant or antipsychotic medications. Subjects whose medication regimen included a medication identified by the gene-based interpretive report as most problematic for that patient and are in the 'red bin' (medication status of 'use with caution and frequent monitoring'), had 69% more total health care visits, 67% more general medical visits, greater than three-fold more medical absence days, and greater than four-fold more disability claims than subjects taking drugs categorized by the report as in the green bin ('use as directed') or yellow bin ('use with caution'). There were no correlations between the number of medications taken and any of the eight healthcare utilization measures. These results demonstrate that retrospective psychiatric pharmacogenomic testing can identify past inappropriate medication selection, which led to increased healthcare utilization and cost.