ABSTRACT
In the present work there are described some spectral characteristics in the ultraviolet and infrared region under various environment conditions for a series of synthetic analogues of deoxyguanosine, substances possessing antiviral properties. The study is performed on the Acyclovir compounds and on its Na, K and Li salts, synthetized in Romania, in comparison with the similar product Zovirax, of the "Wellcome" firm (England), used in the clinical practice for several years. The results show a very marked resemblance of the spectral behavior for all these products, a conclusion confirmed by the similar biological effects in the herpetic infection.
Subject(s)
Acyclovir/pharmacology , Antiviral Agents/pharmacology , Herpesvirus 1, Human/drug effects , Fluorescence , Humans , Spectrophotometry, UltravioletABSTRACT
The experimental results of the in vivo testing of an autochthonous pharmaceutical Acyclovir form prepared for the topical treatment of herpetic infections with a mucocutaneous location are shown in this paper. This testing on laboratory animals continues the in vivo performed investigations regarding the antiviral activity of this compound, which have proved that the efficacy of the inhibitory action exerted by the product on the Herpes simplex virus multiplication is comparable with the characteristics of the standard substance (Acyclovir-Zovirax Wellcome). By testing the therapeutic efficacy of the autochthonous Acyclovir preparation on an experimental model of cutaneous herpes infection in the newborn rat, it is demonstrated in a statistically significant manner that the product exerts a strong inhibitory action on the virus multiplication at the level of epidermis (proved by the lowering of virus production in the cutaneous tissue); the result is a drastic reduction of local herpes vesicles and of virus propagation in the neuraxis attended by the appearance of herpes meningo-encephalitis with a lethal course. The preparation is well tolerated (phenomena of local intolerance or remote toxicity were not observed). These in vivo positive results corroborated by those obtained in vitro complete the experimental argumentation necessary to support the proposal regarding the clinical trial of the product.
Subject(s)
Acyclovir/therapeutic use , Antiviral Agents/therapeutic use , Herpes Genitalis/drug therapy , Animals , Disease Models, Animal , Herpes Genitalis/pathology , Herpes Genitalis/physiopathology , Herpes Genitalis/virology , Humans , Ointments , Rats , Rats, Sprague-Dawley , Skin/pathology , Skin/virologyABSTRACT
In the present work, the preliminary results of a study regarding the pharmacokinetic properties of the autochthonous synthetic drug Acyclovir are shown. The in vitro and in vivo toxicologic test demonstrates a low toxicity of this product, the drug being well tolerated both by the laboratory animal and by the fibroblasts of the human embryo. The specific antiviral action of the product on the multiplication in vitro of the Herpes simplex virus types 1 and 2, appreciated by the lowering capacity of the infection titre and by the determination of the inhibitory concentration 50% (IC50), is significant and comparable with previous results obtained by the authors by testing the drug Zovirax of the Welcome firm.
Subject(s)
Acyclovir/pharmacology , Antiviral Agents/pharmacology , Acyclovir/chemistry , Acyclovir/toxicity , Animals , Antiviral Agents/chemistry , Antiviral Agents/toxicity , Cell Line , Herpesvirus 1, Human/drug effects , Herpesvirus 2, Human/drug effects , Humans , Male , Microbial Sensitivity Tests , Molecular Structure , Rats , Rats, WistarABSTRACT
The LDH cytotoxicity test is able to emphasize the stabilisation of human embryo fibroblast membranes, in vitro, by two amphiphilic drugs: the metomidate and the thymolol. The membrane stabilisation is emphasized by the reduced LDH externalization as compared with the untreated cells. The use of the LDH test for the selection of some natural complexes or synthetic drugs with membrane stabilising and potential antiviral activity is proposed. The inhibition of LDH by metomidate was recorded, as decreasing of the enzyme activity with increasing metomidate concentration. This fact explains the known lactic acid accumulation, under metomidate treatment of human subjects. The use of metomidate in classical cancer treatment potentiation is proposed instead of lactate externalization inhibitors, already used for this aim.
Subject(s)
Antineoplastic Agents/pharmacology , Antiviral Agents/pharmacology , Etomidate/analogs & derivatives , Fibroblasts/drug effects , Antineoplastic Agents/toxicity , Antiviral Agents/toxicity , Calcium Dobesilate/pharmacology , Calcium Dobesilate/toxicity , Cells, Cultured , Fibroblasts/enzymology , Humans , Imidazoles/pharmacology , Imidazoles/toxicity , L-Lactate Dehydrogenase/drug effects , Neutral Red , Structure-Activity Relationship , Timolol/pharmacology , Timolol/toxicityABSTRACT
As evaluated by light scattering at 90 degrees, natural organic oligocations such as putrescine, spermidine and spermine interfered with myxovirus aggregates which were induced by the histone H2A and strongly amplified by shaking during incubation. In contrast, the synthetic oligocation 1.7-diamino heptane itself aggregated the virus particles, its action being unmodified by adding polycationic H2A in abundance. When human chromosome preparations treated with protamine solution and shaked during incubation were covered with a stable polycationic molecular layer, the chromosomes had become unstainable by the Giemsa method even if the dye was used in excess. Nevertheless, the affinity of influenza virus particles for protamine was so high that they were able to dissociate the protamine molecules from the preformed complexes reconstituting the affinity of chromosome preparations to Giemsa stain. The virus-caused shift in the staining ability of chromosomes did not occur when bacterial suspension was added instead of the viral one. The model of oligocationic relaxation and of polycation condensation accounting for the modulatory effects of polyamines is discussed.
Subject(s)
Cations/pharmacology , Influenza A virus/drug effects , Parainfluenza Virus 1, Human/drug effects , Chromosomes/physiology , Histones/pharmacology , Light , Polyamines/pharmacology , Polyelectrolytes , Polymers/pharmacology , Scattering, RadiationABSTRACT
Chromosome alterations induced in human diploid cells by separate or mixed infection with measles and cytomegalic virus were analyzed. Chromosome changes characteristic of each virus could be made evident in the case of the mixed infection. Of particular interest are the cytogenetic alterations associated with syncytium formation, both in separate measles virus infection and in the mixed one. The cytogenetic consequences of premature chromosome condensation, of the synchronism in division of polykaryocyte nuclei, of chromosome contraction and pyknosis are discussed.
Subject(s)
Chromosome Aberrations , Chromosomes/ultrastructure , Cytomegalovirus/growth & development , Measles virus/growth & development , Cell Cycle , Cells, Cultured , Cytopathogenic Effect, Viral , Fibroblasts , Humans , Karyotyping , PloidiesABSTRACT
Alterations in chromosome number and structure could be detected in phytohemagglutin-stimulated leukocyte cultures from four patients with an ascertained diagnosis, of subacute sclerosing panencephalitis. Chromosome changes are polymorphous, involving most frequently the acrocentric group G or D chromosomes. It is suggested that chromosome damage might represent a diagnostic indication before the onset of neurologic symptoms.