Asunto(s)
Poli C/toxicidad , Poli G/toxicidad , Poli I-C/toxicidad , Polilisina/toxicidad , Polirribonucleótidos/toxicidad , Animales , Antivirales , Chlorocebus aethiops , Inductores de Interferón , Interferones/sangre , Dosificación Letal Mediana , Ratones , Poli C/farmacología , Poli G/farmacología , Poli I-C/farmacología , Polilisina/farmacología , Virus/efectos de los fármacosRESUMEN
The mutagenic activity of poly(I) . poly(C) and poly(G) . poly(C) complexes in somatic and generative cells of mice was tested. Both preparations exhibited mutagenic activity in both test-systems. The poly(I) . poly(C) complex in the three doses tested was found to be more active both in bone marrow cells and in sex cells of male mice. The maximum effectiveness of this complex was demonstrated upon treatment of postmeiotic cells of males in an intermediate dose of 2.5 mg/kg bw. The rate of induced dominant lethals was 19.1%. In bone marrow metaphases the subtoxic dose of this complex increased 10-fold the control value of structural aberrations. The activity of poly(G) . poly(C) was found to be slightly lower.
Asunto(s)
Inductores de Interferón/toxicidad , Mutágenos , Poli C/toxicidad , Poli G/toxicidad , Poli I-C/toxicidad , Polirribonucleótidos/toxicidad , Animales , Aberraciones Cromosómicas , Embrión de Mamíferos/efectos de los fármacos , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , EmbarazoRESUMEN
The results of studies of the antiviral and interferon-inducing activity of the synthetic interferon inducer polyguacyl in white mice as well as the results of the study of safety and tolerance of this drug given to human subjects as aerosol and intranasally are presented. Both modes of administration to mice induced production of endogenous interferon, although after intranasal inoculation high interferon titres in the blood serum of the animals were observed for longer periods of time, whereas after aerosol administration interferon disappeared more rapidly. Significant antiviral protection was achieved only by the intranasal administration of the inducer resulting in 84.0% survival of the animals challenged with the mouse-adapted influenza A/Aichi virus. Clinical trials of polyguacyl in human volunteers demonstrated the safety and good tolerance of this drug given both as aerosol and intranasally.
Asunto(s)
Inductores de Interferón/toxicidad , Poli C/toxicidad , Poli G/toxicidad , Polirribonucleótidos/toxicidad , Administración Intranasal , Adulto , Aerosoles , Animales , Relación Dosis-Respuesta a Droga , Evaluación de Medicamentos , Evaluación Preclínica de Medicamentos , Tolerancia a Medicamentos , Humanos , Virus de la Influenza A/efectos de los fármacos , Gripe Humana/tratamiento farmacológico , Inductores de Interferón/administración & dosificación , Inductores de Interferón/uso terapéutico , Ratones , Poli C/administración & dosificación , Poli C/uso terapéutico , Poli G/administración & dosificación , Poli G/uso terapéutico , Factores de Tiempo , Virus de la Estomatitis Vesicular Indiana/efectos de los fármacosRESUMEN
Acute experiments on mice and rats were made to determine the intraperitoneal lethal doses of the polyribonucleotide complexes poly (I).poly (C) and poly (G).poly (C) manufactured in this country. Changes in the function of cardiovascular, nervous, thermoregulatory and motor systems seen after injection of both complexes were shown to have some features in common but to differ in the rate and severity of poisoning. It was disclosed that the test polyribonucleotide complexes might be attributed to a group of substances that manifest the medium degree of cumulation.
Asunto(s)
Enfermedades Cardiovasculares/inducido químicamente , Enfermedades Gastrointestinales/inducido químicamente , Enfermedades del Sistema Nervioso/inducido químicamente , Poli C/toxicidad , Poli G/toxicidad , Poli I-C/toxicidad , Polirribonucleótidos/toxicidad , Animales , Temperatura Corporal , Dosificación Letal Mediana , Ratones , Actividad Motora , Poli C/metabolismo , Poli G/metabolismo , Poli I-C/metabolismo , Pulso Arterial , RatasRESUMEN
Poly(G).poly(C) inoculated intravenously to mice in a dose of 100 microgram induced interferon in the blood in amounts comparable to those induced by poly(I).poly (C). In contrast to rapid accumulation (within 2 hours after induction) and rapid disappearance of interferon in response to poly(I).poly(C) inoculation, the interferon induced by poly(G).poly(C) reached the maximum titer by 6 hours and remained at a high level for 24 hours after inoculation. When given to human volunteers intranasally in a dose of 6 mg, the poly(G).poly(C) complex induced interferon in the blood serum in 70% of the subjects in a titer of 85 units/ml within 24 hours.
Asunto(s)
Inductores de Interferón/farmacología , Interferones/biosíntesis , Poli C/farmacología , Poli G/farmacología , Polirribonucleótidos/farmacología , Administración Intranasal , Adolescente , Adulto , Animales , Humanos , Inyecciones Intravenosas , Ratones , Poli C/administración & dosificación , Poli C/toxicidad , Poli G/administración & dosificación , Poli G/toxicidad , Poli I-C/farmacología , Poli I-C/toxicidadRESUMEN
The poly(G).poly(C) complex has the same interferon-inducing and antiviral activity upon parenteral administration to white mice as poly(I).poly(C), but is considerably less toxic. Upon intravenous inoculation of poly(I).poly(C) to mice its LD50 is 15.8 mg/kg whereas poly(G).poly(C) is not toxic in doses up to 200 mg/kg. In rabbits inoculated with poly(I).ploy(C) intravenously its LD50 is 0.22 mg/kg, while poly(G).poly(C) is not toxic in doses of 1 mg/kg. Histological examinations of different organs of mice and rats revealed no pathomorphological changes after a single intravenous and intraperitoneal inoculation of poly(G).poly(C). It exerted no embryotoxic effect in mice in a dose of 5 mg/kg and was considerably less toxic than poly(I).poly(C) in continuous diploid cell cultures of human embryo lung cells.