ABSTRACT
The feasibility of ablating differentiated adipocytes and the mechanism of cell ablation with a suitable prodrug activating system is described. The system is based on the use of E. coli nitroreductase (NTR) enzyme that activates certain nitro compounds, such as the antitumor drug CB1954, into cytotoxic DNA interstrand cross-linking agents. Differentiated preadipocyte cells (3T3L1) transfected with an aP2 driven nitroreductase construct were efficiently killed after incubation with medium containing the prodrug CB1954, while untransfected cells were not affected. It was demonstrated that the mechanism of cell ablation is apoptosis and that the system has a bystander effect mediated by a toxic metabolite of the prodrug. The described system should provide a good alternative approach for gene therapy studies and a new inducible approach to manipulating the number of cells in tissues of transgenic animals and the ability to study the recovery of the tissue from cell damage or loss.
Subject(s)
Animals , Mice , Adipocytes/drug effects , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Aziridines/pharmacology , Escherichia coli Proteins/genetics , Genes, Transgenic, Suicide/drug effects , Cell Culture Techniques , Cell Differentiation , Feasibility Studies , Time Factors , Transfection/methodsABSTRACT
Binary ethyleneimine [BEI] was used to inactivate the local Egyptian strain of sheep pox virus. The inactivation process was applied using final concentrations of BEI at 0.5, 1, 2 and 3% for different incubation periods at 37 dgree C. The virus was completely inactivated after 7 hours incubation with by 2% BEI final concentration; the inactivated virus was adsorbed on aluminium hydroxide gel when incubated for 6 hours in a concentration 1:1. The antibody levels were estimated by virus neutralization test and ELISA. Specific antibodies appeared from the 1[st] week post vaccination and remained until the 4[th] week post challenge. The prepared vaccine was evaluated for safety, sterility and potency. The vaccine proved to be safe, sterile and inducing protection for the vaccinated lambs when challenged by the virulent sheep pox virus up to 6 months post vaccination
Subject(s)
Animals , Vaccines , Aziridines/pharmacologyABSTRACT
Bisazir, at a 0.5% solution induced sterility in males and at a 1.5% solution in female A. dirus. These sterilizing doses reduced P. falciparum infection in mosquitoes, however, they can still transmit malaria. It is concluded that by the concentration of 1.5 and 2.0% that induced complete sterility in males and females are not safe in sterile-male release programme for the control of A. dirus, unless all females were eliminated prior to release.