Effects of chronic inhibition of Testosterone metabolism on cardiac remodeling after ischemia/reperfusion-induced myocardial damage in gonadectomized rats.

The effects of testosterone on cardiovascular homeostasis are still not well understood. The objective of this work was to evaluate the effects of testosterone in the absence or presence of inhibition of Aromatase (4-hydroxyandrostenedione) and/or 5α reductase (Finasteride) enzymatic activities on the myocardial remodeling 30 days after ischemia/reperfusion (I/R) injury in gonadectomized rats. Results showed that testosterone administration to ORX rats resulted in decreased myocardial damaged area, inflammatory infiltrates and reduced MMP-3 and 13 expressions. Interestingly, Finasteride administration resulted in a greater decrease in scar tissue, inflammatory infiltrates, along with a significant decrease in MMP-3 and 13 expressions. In contrast, 4-hydroxyandrostenedione administrations increased all parameters. Our results suggest that testosterone does not have a direct effect since simultaneous inhibition of aromatase and 5α-reductase did not induce significant changes in I/R induced myocardial injury.

A bacterial reporter system for the evaluation of antisense oligodeoxynucleotides directed against human papillomavirus type 16 (HPV-16).

BACKGROUND: Antisense oligodeoxynucleotides (AS-ODNs) are a promising alternative for the cure of many diseases because of their in vivo specificity and stability. However, AS-ODNs have a strong dependence on the target mRNA structure making necessary extensive in vivo testing. There is, therefore, a need to develop assays to rapidly evaluate in vivo ODN performance. METHODS: We report a simple and inexpensive bacterial reporter system for the rapid in vivo evaluation of AS-ODNs directed against human papillomavirus type 16 (HPV-16) based on the destruction of a chimeric CFP mRNA using the reported HPV-16 nt 410-445 target. RESULTS: In vitro RNaseH assays confirmed target RNA accessibility after AS-ODN treatment. Expression of CFP in Escherichia coli BL21(DE3) with pGST-TSd2-CFP plasmid containing HPV-16 nt 410-445 target linked to CFP was blocked by transformed antisense PS-ODNs but not by two different scrambled ODN controls. CONCLUSIONS: A correlation was observed between bacterial CFP downregulation with the HPV-16 E6/E7 mRNA downregulation and the inhibition of anchorage-independent growth of HPV-16 containing cells suggesting that inhibition of HPV-16 E6/E7 expression by AS-ODNs directed against 410-445 target in cervical tumor cells can be tested in bacterial models.