Search

Purpose: Biological contamination of insulin pens in a hospital setting was studied., Methods: This prospective study, conducted at two hospitals within a multihospital system, examined 125 insulin pens that had been returned to the inpatient pharmacies after patient discharge and were refrigerated for up to 48 hours before laboratory testing. Insulin was removed from the 125 pens and examined microscopically for the presence of nucleated cells and red blood cells (RBCs). Positive samples were examined by a pathologist to determine the cell types present. An immunochromatographic assay was used to determine the presence of free hemoglobin in the insulin. The 10 control samples were negative on microscopic examination., Results: Out of 125 insulin pens, 7 (5.6%) tested positive for cells or hemoglobin. Microscopic examination revealed six positive samples containing a total of nine cells, including macrophages, squamous cells, and an RBC. The sample containing the RBC was not the same sample that tested positive for hemoglobin. Based on findings of intact cells and hemoglobin in insulin pens after administration, the potential exists for transmission of infectious agents from patient to patient if a single pen cartridge is used to administer insulin to multiple patients, even if a new needle is used for each individual., Conclusion: Examination of 125 insulin pens used in hospitals revealed hemoglobin in 1 pen and at least one cell in another 6 pens. The nine detected cells consisted of four squamous epithelial cells, four macrophages, and one RBC.

The cJun N-terminal kinase (JNK)-signaling pathway is activated in response to a variety of stimuli, including environmental insults, and has been implicated in neuronal apoptosis. In this study, we investigated the role that the JNK pathway plays in neurotoxicity caused by thimerosal, an ethylmercury-containing preservative. SK-N-SH cells treated with thimerosal (0-10 microM) showed an increase in the phosphorylated (active) form of JNK and cJun with 5 and 10 microM thimerosal treatment at 2 and 4 h. To examine activator protein-1 (AP-1) transcription, cells were transfected with a pGL2 vector containing four AP-1 consensus sequences and then treated with thimerosal (0-2.5 microM) for 24 h. Luciferase studies showed an increase in AP-1 transcriptional activity upon thimerosal administration. To determine the components of the AP-1 complex, cells were transfected with a dominant negative to either cFos (A-Fos) or cJun (TAM67). Reporter analysis showed that TAM67, but not A-Fos, decreased AP-1 transcriptional activity, indicating a role for cJun in this pathway. To assess which components are essential to apoptosis, cells were treated with a cell-permeable JNK inhibitor II (SP600125) or transfected with TAM67, and the downstream effectors of apoptosis were analyzed. Cells pretreated with SP600125 showed decreases in activation of caspases 9 and 3, decreases in degradation of poly(ADP-ribose) polymerase (PARP), and decreased levels of proapoptotic Bim, in comparison to cells treated with thimerosal alone. However, cells transfected with TAM67 showed no changes in those same components. Taken together, these results indicate that thimerosal-induced neurotoxicity occurs through the JNK-signaling pathway, independent of cJun activation, leading ultimately to apoptotic cell death.

The distribution and sub-cellular localization of cytochrome P-450-dependent mono-oxygenase activity in the skin of adult hairless mice has been investigated using ethoxycoumarin, ethoxyresorufin and benzpyrene as substrates. Highest levels of mono-oxygenase activity per unit area of skin were found in the dermis, both before and after induction with benzanthracene. Subcellularly, mono-oxygenase activity was predominantly microsomal and, prior to induction, located entirely in the smooth microsomal fraction.

The effect of the topical application of clobetasol propionate on cutaneous ethoxycoumarin O'dealkylation (EOD) has been studied in various strains of mice. Clobetasol propionate markedly increased cutaneous EOD activity in adult hairless mice only. Similar treatment of adult haired C57BL/6J mice, or adult haired DBA/2J mice had no significant effect on cutaneous EOD activity. In contrast 3 methylcholanthrene induced cutaneous EOD activity in both hairless and C57 strains to a far greater extent than in the DBA strain. EOD activity in hairless mice non-responsive to polycyclic hydrocarbons, derived by selective breeding of hairless and DBA strains was induced by clobetasol propionate to a similar extent to that observed in responsive hairless strains. Hepatic EOD activity was not induced by clobetasol propionate in any of the strains tested. Strain differences in the induction of EOD by clobetasol propionate were not related to differences in either the concentration of cytosolic glucocorticoid receptor in the skin, the dissociation constant of the cytosolic receptor, or differences in percutaneous absorption. Polycyclic hydrocarbons did not compete with triaminolone acetonide for binding to the cytosolic glucocorticoid receptor. Strain differences in the induction of EOD activity by clobetasol propionate appear therefore not to be related to strain differences in either the Ah receptor of the glucocorticoid receptor, but to be regulated by the hr locus.

The effects of the topical application of glucocorticoid steroid creams used in clinical practice, on the activity of drug metabolising enzymes in the skin of adult hairless mice has been investigated. Treatment with hydrocortisone and fluandrenolone had no effect on the activity of ethoxycoumarin O'dealkylase (EOD) in the skin whereas all other fluorinated synthetic glucocorticoids tested, significantly induced cutaneous EOD activity. Fluincinolone acetonide, Fluincinonide , and Betamethasone Valertate increased enzyme activity 2-3-fold, and clobetasol propionate induced enzyme activity 6-fold. The ability of each steroid preparation to induce enzyme activity was related to its clinical potency, and induction of enzyme activity by clobetasol propionate was maximal at 0.05%, the concentration used in clinical practice. The effects of clobetasol propionate on cutaneous ethoxycoumarin and ethoxyresorufin dealkylase activities were different from those produced by 3 methycholanthrene , indicating that glucocorticoids may represent a class of inducing agents with different properties from the polycyclic hydrocarbons.