No abstract

Fluorescence spectroscopy revealed a dramatic difference between the intracellular distributions of doxorubicin (DOX) and its paramagnetic analogue, ruboxyl (Rb). Modification of the anthracyclin structure by introduction of a paramagnetic label at position 14 in the DOX molecule resulted in reduced DNA binding and enhanced partitioning into phospholipid membranes, as evidenced by the fluorescence-quenching experiments. Higher partitioning into cell membranes resulted in stronger intracellular fluorescence of Rb. In addition, a paramagnetic label on the Rb molecule provided a unique opportunity for an EPR investigation of the drug's intracellular distribution and dynamics. The observed changes in the EPR spectra of drug-containing cells during their life cycle suggested either a progressive release of the intercalated drug, cell membrane fluidization, or both.

Background/aims NAT is performed on blood collected in the United States allowing for the classification of HCV antibody positive donors into resolved and chronic hepatitis C infections. We report a case-control study of factors associated with HCV resolution. Methods Blood donors with resolved (HCV Ab+, RNA- defined as “cases”) or chronic (HCV Ab+, RNA+ defined as “controls”) based on their index donation HCV test results were enrolled. Participants completed a risk factor, symptoms and treatment questionnaire followed by HCV antibody, RNA and liver biochemical testing. Results We enrolled 100 cases and 202 controls. In a multivariate logistic regression model, significant independent effects for spontaneous viral clearance were observed for African American (inverse) (OR = 0.11, 95% CI: 0.01-0.87), autologous blood donation (OR = 4.70, 95% CI: 2.02-10.94), alcohol intake (OR=2.39, 95% CI: 1.13-5.03), and transfusion prior to May 1990 (inverse) (OR = 0.36, 95% CI: 0.14-0.91). Cases admitting injection drug use (IDU) had shorter time since first injection than did controls. Forty-nine index RNA+ controls received antiviral therapy and 25 (51%) were RNA- at enrollment; surprisingly several RNA- cases received liver biopsies and/or antiviral treatment. Conclusions We document the role donor screening plays in the identification, subsequent medical evaluation and treatment among individuals who presumable did not know they were at risk for HCV infection. Additionally, we confirmed race/ethnicity as a determinant of clearance and suggest infectious dose and route of infection may play a role in clearance.