GcvA and Lrp are both necessary for activation of the gcv operon. The upstream GcvA-binding sites 3 and 2 were separated from the Lrp-binding region and the rest of the gcv control region. Moving these sites by 1 or 2 helical turns of DNA further from the gcv promoter reduces, but does not eliminate, either GcvA-mediated activation or repression of a gcvT::lacZ gene fusion. However, moving thes...

The present study was carried out to delineate the ocular pharmacokinetics of ganciclovir (GCV) following intravitreal administration. Another objective was to achieve sustained therapeutic concentrations of GCV in the vitreous over a prolonged period of time using its acyl monoester prodrugs (acetate, propionate, butyrate, and valerate). New Zealand albino male rabbits (2-2.5 kg) were kept und...

Human cytomegalovirus (HCMV) is a widespread pathogen that can cause severe disease in immunologically immature and immunocompromised patients. The current standard of therapy for the treatment of HCMV infections is ganciclovir (GCV). However, high incidence rates of adverse effects are prevalent and limit the use of this drug. Cyclopropavir (CPV) is 10-fold more effective against HCMV in vitro...

PURPOSE The purpose of this study was to investigate the effect of the antiviral drug ganciclovir (GCV) on Müller glia dedifferentiation and proliferation and the underlying cellular and molecular mechanisms in adult zebrafish. METHODS A Tg(1016tuba1a:GFP) transgenic line was generated to identify injury-induced dedifferentiation of Müller glia. Mechanical retinal damage was induced by a need...

PURPOSE To evaluate the intraocular safety and antiviral treatment efficacy of the sustained lipid prodrug of ganciclovir, 1-O-hexadecylpropanediol-3-phospho-ganciclovir (HDP-P-GCV), as an intravitreal injectable drug system for viral retinitis. METHODS HDP-P-GCV was synthesized by coupling 1-O-hexadecyl-propanediol-3-phosphate to either free hydroxyl of ganciclovir in pyridine with dicyclohe...

PURPOSE To evaluate the efficacy of a biodegradable scleral plug containing ganciclovir (GCV) in a rabbit model of human cytomegalovirus (HCMV) retinitis. METHODS To develop a rabbit model for HCMV retinitis, HCMV solution was injected once into the vitreous cavity of pigmented rabbits. The treated animals were divided into three groups: group A received no treatment, group B was treated once...

A study was carried out in mungbean Vigna radiata (L.) Wilczek) with eight ‘lines’ and four ‘testers’ crossed in a Line x Tester Genetic variability, heritability and genetic advance were estimated for marketable and its component yield traits in 48 lines of carrot (Daucus carota var. sativa L.). The study showed high ranges for total yield (3.15 -7.56 kg/plot), marketable yield (2.60 – 6.85 kg...

The ability of herpes simplex virus type 1 thymidine kinase (HSV-TK)-expressing cells incubated with ganciclovir (GCV) to induce cytotoxicity in neighboring HSV-TK-negative (bystander) cells has been well documented. Although it has been suggested that this bystander cell killing occurs through the transfer of phosphorylated GCV, there is little direct proof that bystander cells can accumulate ...

A new mutation in Escherichia coli, designated gcvA1, that results in noninducible expression of both gcv and a gcvT-lacZ gene fusion was isolated. A plasmid carrying the wild-type gcvA gene complemented the mutation and restored glycine-inducible gcv and gcvT-lacZ gene expression. These results suggest that gcvA encodes a positive-acting regulatory protein that acts in trans to increase expres...

BACKGROUND The summit of the left ventricle (LV) is the most superior portion of the epicardial LV bounded by an arc from the left anterior descending coronary artery, superior to the first septal perforating branch to the left circumflex coronary artery. Ventricular arrhythmias (VAs) originating from this region may present challenges for catheter ablation. METHODS AND RESULTS We studied 27 ...