RESUMEN
The efficacy of the antiviral agents nucleoside analogues manufactured in Russia and foreign countries against Bolivian hemorrhagic fever in the treatment and rapid prevention regimens was studied in guinea pigs. In rapid prevention and treatment of guinea pigs, the intraperitoneal injection of 1/10 of the equivalent dose of vero-ribavirin for this animal species was ascertained to protect 70% of the animals infected with Machupo virus strain Carvallo in doses 8 and 10 LD50.
Asunto(s)
Antivirales/uso terapéutico , Arenavirus del Nuevo Mundo/efectos de los fármacos , Fiebre Hemorrágica Americana/tratamiento farmacológico , Ribavirina/uso terapéutico , Administración Oral , Animales , Antivirales/administración & dosificación , Cápsulas , Modelos Animales de Enfermedad , Femenino , Cobayas , Inyecciones Intraperitoneales , Masculino , Ribavirina/administración & dosificación , Resultado del TratamientoRESUMEN
The metabolism of a continuous Ae. albopictus cell line (clone C6/36) was studied relative to the consumption of an environmental component by mammalian cells of the continuous lines Vero(B) and BNK-21 under steady-state cultivation conditions. The Ae. albopictus cells were found to utilize the amino acid glycine and on glycolysis they elaborated not more than (10...20)% of acid products (lactic acid) neutralized by sodium biocarbonate, suggesting that there were also other ways of using glucose. These features lead to the conclusion that the mosquito cells form an extracellular matrix. The findings were used to certify the culture of cells, to substantiate the composition of a cultivation medium, and to optimize the latter.
Asunto(s)
Aedes/citología , Aedes/metabolismo , Línea Celular/metabolismo , Animales , Técnicas de Cultivo de Célula , Glicina/metabolismo , Glucólisis , Ácido Láctico/metabolismoRESUMEN
The essence of studies was that the disease is simulated in 12-day albino mice subcutaneously infected with Hantaan virus, strain 76-118 in a dose of 10 LD50. As an efficiency index, the study of drugs uses major (death protection coefficient, mean animal lifetime) and auxiliary (virological: pathogen accumulation in the brain tissues of deceased animals) parameters, biochemical (the levels of creatinine, urea, alanine aminotransferase, aspartate aminotransferase, malonic dialdehyde), hematological (count of leukocytes, leukogram) ones; as well as interferon status (the levels of circulatory interferon, leukocytic production of alpha- and gamma-interferons). The procedure for simulating the disease caused by Hantaan virus on an experimental animal is used to choose effective drugs against the pathogen of hemorrhagic nephrosonephritis.
Asunto(s)
Modelos Animales de Enfermedad , Virus Hantaan , Fiebre Hemorrágica con Síndrome Renal , Ratones , Alanina Transaminasa/sangre , Animales , Animales Recién Nacidos , Antivirales/aislamiento & purificación , Antivirales/farmacología , Aspartato Aminotransferasas/sangre , Encéfalo/virología , Creatinina/sangre , Susceptibilidad a Enfermedades , Evaluación Preclínica de Medicamentos , Cobayas , Virus Hantaan/efectos de los fármacos , Fiebre Hemorrágica con Síndrome Renal/sangre , Fiebre Hemorrágica con Síndrome Renal/inmunología , Fiebre Hemorrágica con Síndrome Renal/virología , Interferones/biosíntesis , Dosificación Letal Mediana , Recuento de Leucocitos , Activación de Linfocitos , Linfocitos/inmunología , Malonatos/sangre , Conejos , Ratas , Urea/sangreRESUMEN
Experimental studies of arbidol and arbidol mesylate versus ribavirin suggest that insertion of these agents into the nutrient medium of the cultured cells GMK-AH-1 (D) after infection at concentrations of 50, 25, and 100 microg/ml, respectively, is effective in suppressing the reproduction of severe acute respiratory syndrome (SARS) virus. Arbidol and arbidol mesylate were shown to have a direct antiviral effect in early viral replication in the cultured cells. The promising antiviral agent is arbidol mesylate that is nearly 5 times as effective as arbidol in reducing the reproduction of SARS virus in the cultured cells. Insertion of arbidol, arbidol mesylate, and ribavirin into the nutrient medium 2 hours after infection of porcine embryonic renal cells caused a reduction in the accumulation of the pathogen by 2.5, 2.1, and 2.6 Ig, respectively.
Asunto(s)
Antivirales/farmacología , Indoles/farmacología , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/efectos de los fármacos , Animales , Línea Celular , Chlorocebus aethiops , Relación Dosis-Respuesta a Droga , Ribavirina/farmacología , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/fisiología , Replicación Viral/efectos de los fármacosRESUMEN
It is shown that primary screening of drugs against the pathogens of hemorrhagic fever with renal syndrome (HFV) may be performed, by using two approaches in estimating the suppression of plague formation and that of viral reproduction in the cultured cells. It is expedient to make a primary screening of interferon and its inductors to estimate the suppression of viral reproduction in the cultured Vero E6, PSEV, and CL-17 cells, the infection multiplicity should be hundredth parts of BOE/cell. Among the test agents, there are virazole and realdiron that are the most active drugs against Hantaan virus, 76-118 strain, which virually completely suppress the reproduction of the study causative agent, when used even at concentrations of 1-5 microg/ml and 100 U/ml, respectively.
Asunto(s)
Antivirales/farmacología , Virus Hantaan/efectos de los fármacos , Animales , Línea Celular , Chlorocebus aethiops , Relación Dosis-Respuesta a Droga , Virus Hantaan/crecimiento & desarrollo , Humanos , Inductores de Interferón/farmacología , Interferones/farmacología , Ratones , Compuestos Orgánicos/farmacología , Porcinos , Factores de Tiempo , Replicación Viral/efectos de los fármacosRESUMEN
The evaluation of the biological and epidemiological properties of Ebola, Marburg, Lassa, and Machupo viruses suggests that they are of social importance for health care authorities. The studies have created prerequisites to the development of reliable biosafety means against these pathogens. Particular emphasis is laid on the methods for infection diagnosis and on the studies to design specific protective agents--immunoglobulins and inactivated vaccines.
Asunto(s)
Arenavirus del Nuevo Mundo/patogenicidad , Brotes de Enfermedades , Ebolavirus/patogenicidad , Fiebre Hemorrágica Americana , Fiebres Hemorrágicas Virales , Virus Lassa/patogenicidad , Marburgvirus/patogenicidad , Animales , Especificidad de Anticuerpos/inmunología , Antígenos Virales/administración & dosificación , Antivirales/uso terapéutico , Arenavirus del Nuevo Mundo/inmunología , Ebolavirus/inmunología , Salud Global , Fiebre Hemorrágica Americana/epidemiología , Fiebre Hemorrágica Americana/patología , Fiebre Hemorrágica Americana/terapia , Fiebres Hemorrágicas Virales/epidemiología , Fiebres Hemorrágicas Virales/patología , Fiebres Hemorrágicas Virales/terapia , Caballos , Humanos , Inmunización , Inmunoglobulinas/inmunología , Inmunoglobulinas/uso terapéutico , Infección de Laboratorio/epidemiología , Virus Lassa/inmunología , Marburgvirus/inmunología , Ribavirina/uso terapéutico , Vacunas Virales/administración & dosificación , VirulenciaRESUMEN
The antiviral effectiveness of the combined and single use of superlow-dose amixine and virasole on the course of experimental hemorrhagic fever with renal syndrome was studied in sucking albino mice parenterally infected with their virus Hantaan. The co-administration of virasole and amixine was shown to protect 52% of the infected animals from death, which is superior to the effect of their monotherapy. The combined use of the drugs substantially prolongs the survival of albino mice after their infection and the level of brain viral reproduction suppression ( delta = 3.21 g) in the experimental group as compared to the controls and to the mice given only one of the drugs.
Asunto(s)
Antivirales/uso terapéutico , Virus Hantaan , Fiebre Hemorrágica con Síndrome Renal/tratamiento farmacológico , Ribavirina/uso terapéutico , Tilorona/uso terapéutico , Animales , Animales Lactantes , Antivirales/administración & dosificación , Encéfalo/virología , Esquema de Medicación , Evaluación Preclínica de Medicamentos , Quimioterapia Combinada , Fiebre Hemorrágica con Síndrome Renal/virología , Ribavirina/administración & dosificación , Tilorona/administración & dosificaciónRESUMEN
In the clinical trials of vaccine TEOVac in lower and reglamented doses under the conditions of remote vaccination, carried out on 11 volunteers, local reactions in the form of hyperemia, gingival edema (1 vaccinee), faucial hyperemia, enlargement of submaxillary lymph nodes (2 vaccinees) were registered in some of the vaccines; in one vaccinee systemic postvaccinal reaction of medium gravity was observed. Revaccination produced no negative effect on the hematological and biochemical characteristics of the blood, as well as on the urine characteristics. The study of the sensitizing vaccine to the antigens of the accumulation substrate (chick embryo), as well as its influence on the development of autoimmune reactions, revealed the absence of the allergic action of the preparation and its influence on autoimmune processes in the vaccines. The trial of the smallpox vaccine in tablets under the conditions of the primary immunization of adults was the topical and most promising trend in the improvement of smallpox vaccination, as the preparation TEOVac proved to be safe, in contrast to the traditional smallpox vaccine introduced by the scarification method, for both vaccines and nonimmunized persons having contacts with them.
Asunto(s)
Inmunización Secundaria/efectos adversos , Vacuna contra Viruela/efectos adversos , Viruela/prevención & control , Vacunación/efectos adversos , Administración Oral , Adulto , Edema/patología , Femenino , Encía/patología , Enfermedades de las Encías/inducido químicamente , Enfermedades de las Encías/patología , Humanos , Hiperemia/inducido químicamente , Ganglios Linfáticos , Linfadenitis/inducido químicamente , Masculino , Vacuna contra Viruela/administración & dosificación , Glándula Submandibular , Comprimidos , Factores de Tiempo , Vacunas Atenuadas/administración & dosificación , Vacunas Atenuadas/efectos adversosRESUMEN
Experimental research was undertaken to investigate the use of amixin in prevention, emergency prevention schemes and treatment of mice infected with West Nile fever (WNF) agent, strain Eg-101; the results are indicative of the drug efficiency both in its peroral and subcutaneous administrations. Amixin was shown to be most effective in the former case when administered, 10 mg/kg, in 96 hours before mice were infected as well as during the entire incubation period: lethality protection--46%. In the latter case, the drug was effective, when 3 administration schemes were in use, 10 mg/kg. The maximum degree of protection efficiency was registered with amixin administration according to the emergency prevention scheme: lethality protection--33%. The drug suppresses effectively the WNF virus reproduction in cerebral tissues.
Asunto(s)
Antivirales/uso terapéutico , Tilorona/uso terapéutico , Fiebre del Nilo Occidental/tratamiento farmacológico , Virus del Nilo Occidental , Administración Oral , Animales , Encéfalo/virología , Modelos Animales de Enfermedad , Inyecciones Subcutáneas , Interferones/sangre , Ratones , Fiebre del Nilo Occidental/sangre , Virus del Nilo Occidental/efectos de los fármacos , Virus del Nilo Occidental/aislamiento & purificaciónRESUMEN
The most promising trends of using monoclonal antibodies (Mabs) in virology research of the viral hemorrhagic-fevers' agents are related with studying viral antigen structure and with developing diagnostic preparations for indicating and identifying infectious agents of the mentioned pathologies. The methodological specificity of obtaining the Mabs to viral hemorrhagic-fevers' agents as well as data on its practical use are discussed.
Asunto(s)
Anticuerpos Monoclonales/inmunología , Anticuerpos Antivirales/inmunología , Antígenos Virales/análisis , Arenaviridae/aislamiento & purificación , Bunyaviridae/aislamiento & purificación , Filoviridae/aislamiento & purificación , Flaviviridae/aislamiento & purificación , Fiebres Hemorrágicas Virales/virología , Animales , Arenaviridae/inmunología , Bunyaviridae/inmunología , Filoviridae/inmunología , Flaviviridae/inmunología , Fiebres Hemorrágicas Virales/diagnóstico , Humanos , InvestigaciónRESUMEN
The experimental studies conducted on 2-week suckling mice infected with Hantaan virus, Strain 76-118) treated with oral and subcutaneous amoxine showed its prophylactic, therapeutical-and-prophylactic, and therapeutical efficiencies. Oral amoxine exhibited the highest efficiency when used in a dose of 10 mg/kg-1 96 hours before infection and throughout the incubation period. The protective efficiency was 61%. Subcutaneously, the agent was effective when three schemes for injection in a dose of 1 mg/kg-1. Its maximum effect was observed when amoxine was given by the therapeutical-and-prophylactic scheme. The death protection rate was 65%. The agent is effective in suppressing the reproduction of Hantaan virus in the brain tissue.
Asunto(s)
Antivirales/uso terapéutico , Infecciones por Hantavirus/tratamiento farmacológico , Infecciones por Hantavirus/prevención & control , Tilorona/uso terapéutico , Animales , Animales Lactantes , Antivirales/farmacología , Encéfalo/virología , Relación Dosis-Respuesta a Droga , Orthohantavirus/efectos de los fármacos , Orthohantavirus/fisiología , Ratones , Tilorona/farmacología , Replicación Viral/efectos de los fármacosRESUMEN
Hybridomas producing monoclonal antibodies (MAb) to Marburg virus glycoprotein were prepared by splicing of mouse myeloma cells (NSO and X.63-Ag6.653 strains) and splenocytes of immunized BALB/c mice. Cultural and MAb-producing properties of hybridomas were studied. The production of MAb during serial passages 15-30 was confirmed. MAb titers in culture fluids were 1:4096-1:8152, in immune ascitic fluids of BALB/c mice 1:409,600-1:638,400. The possibility of using MAbs as a component of ELISA test system was demonstrated. The sensitivity of ELISA-MAb method for Marburg virus was 1 x 10(3) PFU/mu.
Asunto(s)
Anticuerpos Monoclonales/biosíntesis , Hibridomas/inmunología , Marburgvirus/inmunología , Proteínas del Envoltorio Viral/inmunología , Proteínas Estructurales Virales/inmunología , Animales , Ensayo de Inmunoadsorción Enzimática , Ratones , Ratones Endogámicos BALB C , Pase SeriadoRESUMEN
Comparative assessment of the stability of Venezuelan equine encephalomyelitis virus cultured in BHK-21, Vero, 66-19(1)D, and developing chick embryo cells showed that an increase of the share of phosphatidylcholine and cholesterol in viral envelopes, caused by the conditions of culturing, improved the survival of the virus exposed to heating and some chemicals.
Asunto(s)
Virus de la Encefalitis Equina Venezolana/genética , Animales , Línea Celular , Embrión de Pollo , Virus de la Encefalitis Equina Venezolana/crecimiento & desarrollo , Calor , Fenotipo , Cultivo de Virus , Replicación ViralRESUMEN
A relationship between ribamydil concentration and the intensity of accumulation of peroxidation products was found while storing ribamydil-containing liposomes which indicated a significant pro-oxidant activity of ribamydil. Increasing lethality of guinea pigs and white mice infected with Venezuelan equine encephalomyelitis virus was shown while using liposomal ribamydil containing from 4.78 to 6.82 nmol. ml-1 malonic dialdehyde which appeared to be associated with disordered function of the antioxidant system of the experimental animals.
Asunto(s)
Encefalomielitis Equina Venezolana/tratamiento farmacológico , Peroxidación de Lípido/efectos de los fármacos , Ribavirina/farmacocinética , Fiebre del Valle del Rift/tratamiento farmacológico , Animales , Relación Dosis-Respuesta a Droga , Portadores de Fármacos , Evaluación Preclínica de Medicamentos , Encefalomielitis Equina Venezolana/metabolismo , Encefalomielitis Equina Venezolana/mortalidad , Radicales Libres , Cobayas , Liposomas , Malondialdehído/metabolismo , Ratones , Ratas , Ribavirina/administración & dosificación , Fiebre del Valle del Rift/metabolismo , Fiebre del Valle del Rift/mortalidadAsunto(s)
Antivirales/administración & dosificación , Liposomas , Animales , Portadores de Fármacos , HumanosRESUMEN
The comparative evaluation of R. prowazekii vaccine and virulent strains has revealed that strain Breinl possesses greater capacity for plaque formation than strain E. The possibility of using the plaque assay for differentiation of substrains 288 and 281 of strain E has been established.