ABSTRACT
Clinical isolates of the Herpes simplex virus had different susceptibility to acyclovir. Along with highly susceptible variants there were often isolated resistant variants and variants with intermediate susceptibility to the drug. All the clinical isolates were from the patients previously not treated with acyclovir. Therefore, it is possible to consider the drug resistance of the Herpes simplex virus to be natural. Two cultures of the virus differing in their susceptibility to acyclovir were simultaneously isolated from the affections of various localization in one patient. The study of the time course of the resistance development in the cell cultures showed that it depended on the drug dose and the subculture level. It is advisable to test the isolates of the Herpes simplex virus for their susceptibility to drugs used in the patient treatment. This will provide individual therapy of the patients with Herpes simplex.
Subject(s)
Acyclovir/pharmacology , Antiviral Agents/pharmacology , Herpes Simplex/drug therapy , Simplexvirus/drug effects , Adolescent , Adult , Cells, Cultured , Child , Child, Preschool , Drug Resistance , Humans , Infant , Kidney/cytology , Kidney/drug effects , Kidney/virology , Laboratories , Microbial Sensitivity Tests , Virus Replication/drug effectsABSTRACT
Interferon (IF) was synthesized in animals by diverse populations of immunocytes in response to induction by various low molecular weight aromatic hydrocarbons. The level of the involvement of either population of the immunocytes in IF production is determined by the chosen inductor. IF induction by acridanone L-1 was mainly observed in macrophages and B-lymphocytes. T-Cells actively participated in IF synthesis induced by amyxin, a representative of the fluorenone group. IF synthesized by lymphocytes of human peripheral blood in response to L-1 was completely neutralized by antiserum to alpha-IF while IF induced by amyxin in the same culture was a mixture of alpha- and beta-IFs at a ratio of 3:1.
Subject(s)
Acridines/pharmacology , B-Lymphocytes/metabolism , Interferon Inducers/pharmacology , Interferon-alpha/biosynthesis , Macrophages/metabolism , Models, Biological , T-Lymphocytes/metabolism , Tilorone/pharmacology , Animals , B-Lymphocytes/drug effects , Cattle , Culture Media , In Vitro Techniques , Macrophages/drug effects , Mice , Mice, Inbred CBA , T-Lymphocytes/drug effectsABSTRACT
The antiviral activity of a national analogue of virasol, ribamydil, with regard to RS virus infection was studied in tissue culture and in experimental animals. In L-41 cell cultures ribamydil in a dose of 60 micrograms/ml or more completely inhibited multiplication of RS virus strain Long, in a titre of 4.75 lg CPD50. The drug concentrations of 30, 15, and 7 micrograms/ml reduced the virus content by 3.75, 2.75 and 2.0 lg CPD50, respectively; ED50 of the drug was 7 micrograms/ml, the chemotherapeutic index was 71. In cotton rats, RS virus infection could be reproduced in 95%. Subcutaneous inoculation of the injection form of ribamydil in a dose of 100 mg/kg body weight prevented the development of infection with RS virus in 100% of the animals.
Subject(s)
Respiratory Syncytial Viruses , Respirovirus Infections/drug therapy , Ribavirin/therapeutic use , Animals , Cells, Cultured/drug effects , Cells, Cultured/microbiology , Drug Evaluation, Preclinical , Respiratory Syncytial Viruses/drug effects , Ribavirin/pharmacology , Sigmodontinae , Time Factors , Virus CultivationABSTRACT
Aromatic hydrocarbons are rightly considered to belong to most active synthetic interferon inducers among low molecular compounds. A comparative evaluation of L-1 (acridanon) and amixin (fluorenon) showed L-1 to have more marked interferon-inducing properties. Both compounds differed not only in the dynamics and levels of interferon synthesis in different organs which suggests the possibility of their employment in different diseases, but also in the efficacy of the modes of application. L-1 induced IF synthesis most actively after subcutaneous inoculation, amixin after oral administration.
Subject(s)
Interferon Inducers/pharmacology , Polycyclic Compounds/pharmacology , Acridines/administration & dosage , Acridines/pharmacology , Administration, Oral , Animals , Dose-Response Relationship, Drug , Injections, Intraperitoneal , Injections, Subcutaneous , Interferon Inducers/administration & dosage , Interferons/analysis , L Cells , Mice , Mice, Inbred CBA , Polycyclic Compounds/administration & dosage , Tilorone/administration & dosage , Tilorone/pharmacologyABSTRACT
Tolerance and interferon-inducing activity of amixine, an interferon inducer, was studied by the double-blind method clinically in healthy volunteers given tableted amixine orally in doses of 0.125-0.25 g by different schedules. According to clinical laboratory examinations and studies of indirect parameters of labor capacity amixine was found to be tolerable for man. The amount of interferon in the blood serum depended on the schedule of administration of the inducer, the optimal being 1-2 amixine tablets at least 2 days apart.
Subject(s)
Interferon Inducers/therapeutic use , Tilorone/analogs & derivatives , Adolescent , Adult , Double-Blind Method , Drug Tolerance , Humans , Interferons/blood , Male , Placebos , Psychological Tests/methods , Psychophysiology , Tablets , Tilorone/therapeutic use , Time FactorsSubject(s)
Arbovirus Infections/prevention & control , Arenaviridae Infections/prevention & control , Alphavirus , Animals , Antiviral Agents/therapeutic use , Arbovirus Infections/drug therapy , Arenaviridae Infections/drug therapy , Bunyaviridae Infections/drug therapy , Bunyaviridae Infections/prevention & control , Drug Evaluation , Drug Evaluation, Preclinical , Flavivirus , Humans , Togaviridae Infections/drug therapy , Togaviridae Infections/prevention & controlSubject(s)
Amphotericin B/analogs & derivatives , Influenza, Human/drug therapy , Multiple Sclerosis/drug therapy , Amphotericin B/pharmacology , Amphotericin B/therapeutic use , Amphotericin B/toxicity , Animals , Chick Embryo , Drug Evaluation , Drug Evaluation, Preclinical , Drug Therapy, Combination , Female , Humans , Influenza A virus/drug effects , Male , Mice , Rimantadine/therapeutic use , Tilorone/therapeutic use , Virus Replication/drug effectsSubject(s)
Interferon Inducers/pharmacology , Animals , Humans , Molecular Weight , Structure-Activity RelationshipABSTRACT
The latest data are reviewed on the molecular biology mechanisms of antiviral effect exhibited by the analogues of nucleic acids components. Main effects of preparations used in medicine and virology are analyzed. The data are presented in proof of the existence of different as well as common pathways for virus inhibiting effects of different preparations. The pathways include the analogue interference with virus specific DNA-polymerases, affecting the posttranscriptional processes, etc.
Subject(s)
Antiviral Agents , Nucleosides/pharmacology , Purine Nucleosides/pharmacology , Pyrimidine Nucleosides/pharmacologySubject(s)
Anti-Bacterial Agents/pharmacology , Antiviral Agents/pharmacology , Cephalosporins/pharmacology , DNA, Viral/antagonists & inhibitors , Dactinomycin/pharmacology , Drug Interactions , Interferon Inducers/pharmacology , Membrane Lipids/pharmacology , Polyenes/pharmacology , RNA, Viral/antagonists & inhibitors , Rifamycins/pharmacology , Streptovaricin/pharmacology , Structure-Activity Relationship , Viral Proteins/antagonists & inhibitors , Virion/drug effects , Virus Replication/drug effectsSubject(s)
Antiviral Agents/antagonists & inhibitors , Viruses/drug effects , Animals , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Dose-Response Relationship, Drug , Drug Resistance, Microbial , Humans , Mutation , Recombination, Genetic/drug effects , Structure-Activity Relationship , Virus Cultivation , Virus Diseases/drug therapy , Virus Replication/drug effects , Viruses/genetics , Viruses/metabolismABSTRACT
The results of the development of a nonfatal model of experimental infection induced by Pixuna alpha-virus and suitable for the evaluation of the effectiveness of antiviral drugs are described. The asymptomatic infection induced in white mice by intranasal inoculation of Pixuna virus is characterized by intensive virus multiplication in the brain and spleen of the animals. In these organs virus reproduction is observed early after infection and amplification of the agent reaches maximum titres within 72 h postinfection. With this model, the main criterion of the effectiveness of antiviral drugs would be their effect on virus reproduction in the spleen and brain.