RESUMEN
Four rhesus monkeys (Macaca mulatta) were inoculated with a homogenate of a cutaneous lepromatous leprosy lesion from a mangabey monkey (Cercocebus atys). One died of B-cell lymphoma, and another died of an immunodeficiency syndrome. Cell suspensions prepared from the tumor and spleen of the monkey with lymphoma induced lymphoma or an immunodeficiency syndrome when inoculated into additional young rhesus monkeys. The immunodeficiency syndrome was similar to simian acquired immunodeficiency syndrome and consisted of opportunistic infections, lymphoid hyperplasia or atrophy, wasting, and syncytial cell formation. Mitogen responses and percentages of T4- and T8-positive lymphocytes were normal until the animals were moribund. Lymphoblastoid cell lines became established in vitro from tumor cell suspensions. These cells were infected with a herpesvirus related to Epstein-Barr virus. In addition, a retrovirus morphologically similar to human T-cell lymphotrophic virus type III (HTLV-III) and simian T-lymphotrophic virus type III (STLV-III) was isolated from one of the lymphoblastoid cell lines (LCL). Type D retroviruses could not be demonstrated in the monkeys in the transmission study; however, a retrovirus similar to that in the LCL was isolated from 4 animals by coculture of peripheral blood lymphocytes with the human cell line H9. These results suggest that this retrovirus, STLV-III/Delta, may be associated with the immunodeficiency syndrome in these macaques and may be of mangabey origin.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/transmisión , Linfoma/transmisión , Infecciones Tumorales por Virus/transmisión , Síndrome de Inmunodeficiencia Adquirida/inmunología , Síndrome de Inmunodeficiencia Adquirida/microbiología , Animales , Anticuerpos Monoclonales , Línea Celular , Células Cultivadas , Cercopithecidae/microbiología , Efecto Citopatogénico Viral , Enzimas de Restricción del ADN , ADN Viral/análisis , Deltaretrovirus/inmunología , Femenino , Herpesvirus Humano 4/genética , Linfocitos/clasificación , Linfoma/inmunología , Linfoma/patología , Macaca mulatta , Masculino , Microscopía Electrónica , Infecciones por Retroviridae/transmisión , Virión/ultraestructuraRESUMEN
Acyclovir (9-(2-hydroxyethoxymethyl)guanine) administered as an intramuscular formulation twice daily at a dosage of 100 mg/kg per day prevented the development of disease in African green monkeys inoculated with simian varicella virus. Viremia, appearance of a vesicular rash, and elevations of serum transaminases, each indicative of infection, were suppressed by acyclovir treatment. Plasma concentrations of acyclovir were measured and showed rising levels after repeated intramuscular injection with a prolonged period of absorption of acyclovir into the plasma circulation. Investigation of antiviral efficacy after either intramuscular or intravenous acyclovir treatment showed both routes of administration to be effective in inhibiting simian varicella virus infection at the 100 mg/kg per day level. However, intravenous acyclovir 50 mg/kg twice daily did result in elevated values of blood urea nitrogen, creatinine, and serum transaminases.
Asunto(s)
Antivirales/uso terapéutico , Varicela/tratamiento farmacológico , Guanina/análogos & derivados , Aciclovir , Animales , Anticuerpos Antivirales/análisis , Antivirales/administración & dosificación , Chlorocebus aethiops , Evaluación Preclínica de Medicamentos , Guanina/administración & dosificación , Guanina/uso terapéutico , Herpesvirus Humano 3/inmunología , Inyecciones Intramusculares , Inyecciones Intravenosas , Viremia/tratamiento farmacológicoRESUMEN
Acyclovir inhibited the replication of a varicella-like simian virus (DHV-1) in cell culture (Vero cells) with an ED50 of 38 +/- 2 microM. The activation of acyclovir in this cell culture system was compared with that in the cell system with human varicella zoster virus (VZV). Extracts of cells infected with DHV-1 catalyzed the phosphorylation of acyclovir. The phosphorylation was inhibited by dThd, suggesting the catalyst was a dThd kinase. Electrophoresis of cytosol fractions on polyacrylamide gels corroborated the existence of a virus-associated dThd kinase. This enzyme copurified with an acyclovir-phosphorylating activity. The enzyme catalyzed the phosphorylation of acyclovir at a greater relative rate than that with the VZV enzyme, but with a higher apparent Km value for acyclovir. The relative efficiencies for the two enzymes with acyclovir were similar. Anabolic studies with cells infected with DHV-1 and incubated with [14C]acyclovir indicated that triphosphate of acyclovir did accumulate. The results indicate that acyclovir is activated in cells infected with DHV-1 in a manner similar to that in cells infected with VZV.
Asunto(s)
Antivirales/farmacología , Guanina/análogos & derivados , Herpesviridae/efectos de los fármacos , Aciclovir , Animales , Línea Celular , Chlorocebus aethiops , Guanina/metabolismo , Guanina/farmacología , Herpesviridae/enzimología , Herpesvirus Humano 3/efectos de los fármacos , Cinética , Fosforilación , Timidina Quinasa/metabolismoRESUMEN
Simian varicella virus (SVV) is closely related to human varicella-zoster virus (VZV) and induces a varicella-like disease in nonhuman primates. The SVV genome encodes a glycoprotein E (gE) which is homologous to the gE of VZV and other alphaherpesviruses. The SVV gE was expressed in Escherichia coli and rabbits were immunized with the recombinant gE fusion proteins to generate polyclonal gE antiserum. Immunofluorescence and immunoprecipitation analyses demonstrated that the SVV gE is expressed on the surface and within SVV-infected cells. The gE is also expressed on SVV virions as indicated by serum neutralization assay. The mature SVV gE is glycosylated and is similar in size ( approximately 100 kd) to the mature VZV gE. Immunohistochemical analysis detected gE within skin vesicles and lung tissue of SVV-infected monkeys. Analysis of the humoral immune response to gE in an SVV-infected monkey determined that anti-gE antibody is induced as early as day 9 postinfection and persists at high titer for longer than 4 months. The simian varicella model offers an opportunity to investigate the role of gE in viral pathogenesis and immunity and to evaluate its potential as a varicella vaccine.
Asunto(s)
Antígenos Virales/genética , Expresión Génica , Infecciones por Herpesviridae/virología , Glicoproteínas de Membrana/genética , Varicellovirus/genética , Proteínas del Envoltorio Viral/genética , Animales , Anticuerpos Antivirales/biosíntesis , Antígenos Virales/inmunología , Línea Celular , Chlorocebus aethiops , ARN Polimerasas Dirigidas por ADN/genética , Escherichia coli , Vectores Genéticos/genética , Haplorrinos , Infecciones por Herpesviridae/sangre , Infecciones por Herpesviridae/inmunología , Infecciones por Herpesviridae/patología , Glicoproteínas de Membrana/inmunología , Conejos , Virus Vaccinia/genética , Varicellovirus/inmunología , Varicellovirus/aislamiento & purificación , Proteínas del Envoltorio Viral/inmunología , Proteínas ViralesRESUMEN
1-beta-D-Arabinofuranosylthymine (ara-T) and 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil (BV-ara-U) were shown to have antiviral activity in vitro and in vivo against simian varicella virus. Both compounds successfully prevented clinical disease caused by inoculation of African green monkeys with simian varicella virus, eliminating the development of rash and substantially suppressing viremia. Ara-T treatment was effective by either intraperitoneal or oral routes of administration and BV-ara-U was active by both oral and intramuscular routes. Ara-T, however, was associated with the appearance of marked signs of neurotoxicity. Histologic examination of brain tissue demonstrated chromatolysis and pyknosis of neurons and pyknotic nuclei in glial cells. The neurologic impairment persisted in affected monkeys. This observation of central nervous system toxicity in monkeys is in contrast to studies in mice and rats where high doses of ara-T by multiple routes of administration were nontoxic. No apparent toxicity was observed in monkeys treated with BV-ara-U.
Asunto(s)
Arabinofuranosil Uracilo/análogos & derivados , Arabinonucleósidos/uso terapéutico , Varicela/tratamiento farmacológico , Infecciones por Herpesviridae/tratamiento farmacológico , Sistema Nervioso/efectos de los fármacos , Timidina/análogos & derivados , Uridina/análogos & derivados , Animales , Arabinofuranosil Uracilo/efectos adversos , Arabinofuranosil Uracilo/uso terapéutico , Arabinonucleósidos/efectos adversos , Chlorocebus aethiops , Neuronas/patología , Timidina/efectos adversos , Timidina/uso terapéuticoRESUMEN
1-(2-Deoxy-2-fluoro-1-beta-D-arabinofuranosyl)-5-ethyluracil (FEAU) has been shown to be a highly effective inhibitor of Simian varicella virus infection in African green monkeys. Administration of FEAU by either intravenous injection or gavage at doses as low as 1 mg/kg/day prevented the development of rash and reduced viremia. The effective dose could be further reduced to 0.2 mg/kg/day when administered in combination with a sub-effective dose of human recombinant interferon-beta. No evidence of toxicity was seen in monkeys treated for 10 days with FEAU doses of 10 mg/kg/day when they were monitored by hematology and clinical chemistry tests and by clinical observations.
Asunto(s)
Infecciones por Adenoviridae/prevención & control , Antivirales/farmacología , Arabinofuranosil Uracilo/análogos & derivados , Interferón Tipo I/farmacología , Uridina/análogos & derivados , Adenovirus de los Simios/efectos de los fármacos , Animales , Arabinofuranosil Uracilo/administración & dosificación , Arabinofuranosil Uracilo/farmacología , Chlorocebus aethiops , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Humanos , Inyecciones Intravenosas , Interferón Tipo I/administración & dosificación , Proteínas Recombinantes , Viremia/tratamiento farmacológicoRESUMEN
(S)-1-[3-Hydroxy-2-(phosphonylmethoxy)propyl]cytosine (S-HPMPC) was able to prevent simian varicella infection in African green monkeys inoculated intratracheally with virus. A dose of 50 mg/S-HPMPC/kg administered intravenously was shown to prevent the development of rash, reduce viremia and protect the monkeys from death. The 50 mg/kg dose was effective when treatments initiated on day 2 post-infection (p.i.) was given as ten daily doses of 5 mg/kg, as 10 mg/kg administered on five days on an alternate-day schedule, as two 25 mg/kg doses given on day 2 and on day 7 p.i., or as a single injection of 50 mg/kg on day 2. The single 50 mg/kg dose was also effective when treatment was delayed until four days p.i., but was ineffective when treatment was delayed until six days p.i. The 50 mg/kg dose was not effective when given orally by gavage. No evidence of toxicity was noted in daily clinical examinations, or in frequent hematology and clinical chemistry tests performed during the clinical evaluation of the infection.
Asunto(s)
Antivirales/administración & dosificación , Varicela/tratamiento farmacológico , Citosina/análogos & derivados , Herpesvirus Humano 3/efectos de los fármacos , Organofosfonatos , Compuestos Organofosforados/administración & dosificación , Administración Oral , Animales , Anticuerpos Antivirales/sangre , Antivirales/farmacología , Antivirales/uso terapéutico , Chlorocebus aethiops , Cidofovir , Citosina/administración & dosificación , Citosina/farmacología , Citosina/uso terapéutico , Herpesvirus Humano 3/inmunología , Inyecciones Intravenosas , Compuestos Organofosforados/farmacología , Compuestos Organofosforados/uso terapéutico , Viremia/tratamiento farmacológicoRESUMEN
A novel nucleoside analog BMS-181165 with potent activity against varicella-zoster virus was tested for efficacy in a simian varicella virus infection in African green monkeys. BMS-181165 was effective in preventing the development of a rash, decreasing the development of viremia and preventing death in infected monkeys when administered orally at 4, 16 or 64 mg/kg/day. The compound is well orally absorbed in monkeys, between 44 to 50% oral bioavailability, and may prove of value in therapy of varicella-zoster infections in humans.
Asunto(s)
Antivirales/farmacocinética , Infecciones por Herpesviridae/prevención & control , Herpesvirus Cercopitecino 1 , Uridina/análogos & derivados , Administración Oral , Animales , Antivirales/administración & dosificación , Antivirales/sangre , Disponibilidad Biológica , Chlorocebus aethiops , Modelos Animales de Enfermedad , Infecciones por Herpesviridae/complicaciones , Resultado del Tratamiento , Uridina/administración & dosificación , Uridina/sangre , Uridina/farmacocinética , Viremia/prevención & controlRESUMEN
6-Dimethylamino-9-(beta-D-arabinofuranosyl)-9H-purine (ara-DMAP) effectively prevented the development of rash and appreciably reduced viremia in simian varicella virus-infected monkeys. Doses of 100 and 50 mg/kg/day, administered orally, were highly effective. The lowest dose of 20 mg/kg/day was much less effective in preventing moderate viremia. However, the 20 mg/kg/day did prevent the development of rash in two of three monkeys. All three doses of ara-DMAP reduced liver infection as reflected by lower aspartate aminotransferase values in the sera of the African green monkeys. Orally administered ara-DMAP was rapidly absorbed. However, significant variation among individual monkeys in the AUC values, peak plasma levels, and plasma half-lives were observed.
Asunto(s)
Antivirales/farmacocinética , Varicela/tratamiento farmacológico , Vidarabina/análogos & derivados , Administración Oral , Animales , Animales Salvajes , Antivirales/sangre , Antivirales/uso terapéutico , Aspartato Aminotransferasas/sangre , Chlorocebus aethiops , Evaluación de Medicamentos , Semivida , Efectividad Biológica Relativa , Piel/patología , Resultado del Tratamiento , Vidarabina/administración & dosificación , Vidarabina/farmacocinética , Vidarabina/uso terapéutico , Viremia/tratamiento farmacológicoRESUMEN
The management of opportunistic infections is a significant problem in acquired immunodeficiency syndrome (AIDS) and the development of more effective chemotherapeutic agents is needed. We present the ocular manifestations of an AIDS-like disease in rhesus monkeys experimentally infected with simian immunodeficiency virus (SIV) at the Delta Regional Primate Research Center. These findings consisted of rubeosis in the anterior segment and retinitis, optic neuritis, choroiditis and panophthalmitis in the posterior segment of the eye. Investigation of the retinas by electron microscopy revealed SIV in both eyes of one animal and a herpes virus in two animals. Serology confirmed cytomegalovirus (CMV) as the likely agent. This primate model will prove useful for both further investigations of the possible interaction between immunosuppressive lentiviruses and CMV in ocular disease and antiviral drug testing.
Asunto(s)
Oftalmopatías/complicaciones , Síndrome de Inmunodeficiencia Adquirida del Simio/complicaciones , Virus de la Inmunodeficiencia de los Simios , Animales , Anticuerpos Antivirales/sangre , Antígenos Virales/inmunología , Citomegalovirus/inmunología , Modelos Animales de Enfermedad , Oftalmopatías/microbiología , Linfocitos/inmunología , Macaca mulatta , Retina/ultraestructura , Virus de la Inmunodeficiencia de los Simios/inmunología , Virus de la Inmunodeficiencia de los Simios/ultraestructura , Simplexvirus/inmunologíaRESUMEN
BACKGROUND AND PURPOSE: Spontaneous viral encephalitis is rare in the baboon; yet, during a 13-month period (1993-1994), eight juvenile baboons (Papio cynocephalus spp.) developed acute, progressive nonsuppurative meningoencephalomyelitis caused by an unknown agent. Clinical signs of disease included disorientation and truncal ataxia that rapidly progressed to hemiparesis or paraparesis. Clinicopathologic findings were not remarkable and appreciable gross lesions were not seen at necropsy. Microscopic examination revealed CNS lesions that were characterized by lymphoplasmacytic perivascular cuffing, microglial nodules, demyelination, axonal degeneration, vacuolization, and hemorrhage. Subsequently, a novel syncytium-inducing mammalian orthoreovirus was isolated from the brain tissue of five baboons with clinical signs of infection. METHODS: To confirm the etiologic role of the orthoreovirus, two juvenile baboons were inoculated with the virus, then were monitored for 6 weeks. RESULTS: Lesions similar to those seen in spontaneous cases were found in the CNS, and orthoreovirus was isolated from the brain of both animals. CONCLUSION: Analysis of the outbreak indicated juvenile baboons were most susceptible to disease and the virus had a possible incubation time of 46 to 66 days, but did not indicate a source of the virus or mode of transmission.
Asunto(s)
Animales de Laboratorio , Brotes de Enfermedades/veterinaria , Meningitis Viral/veterinaria , Meningoencefalitis/veterinaria , Enfermedades de los Monos/epidemiología , Orthoreovirus/aislamiento & purificación , Animales , Bioensayo , Encéfalo/patología , Encéfalo/ultraestructura , Encéfalo/virología , Chlorocebus aethiops , Femenino , Vivienda para Animales , Masculino , Meninges/patología , Meningitis Viral/diagnóstico , Meningitis Viral/virología , Meningoencefalitis/diagnóstico , Meningoencefalitis/virología , Ratones , Orthoreovirus/crecimiento & desarrollo , Orthoreovirus/inmunología , Orthoreovirus/ultraestructura , Papio , Ratas , Pruebas Serológicas , Médula Espinal/patología , Texas , Células Vero , Ensayo de Placa ViralRESUMEN
Two separate studies are described in this report. First, 5 Owl monkeys were inoculated intracerebrally (IC) with coronavirus JHM OMP1; this virus isolate was cultured from the brain of an animal inoculated with uncloned MHV JHM. Two of the animals became neurological impaired and were sacrificed; these animals had developed severe encephalomyelitis as previously described. Two of the remaining 3 healthy animals were inoculated IC again at 90 days post-inoculation (DPI) and all 3 were sacrificed approximately 5 months after the first virus inoculation. Despite the lack of detectable infectious virus, viral RNA and antigen, all 3 animals had significant white matter inflammation and areas of demyelination in the spinal cord. In the second study 4 Owl monkeys were inoculated intranasally (IN) and ocularly and 4 inoculated intravenously (i.v.) with JHM OMP1. The animals were sacrificed between 16 and 215 DPI with 2 IN and 2 i.v. animals receiving a second i.v. inoculum at 152 DPI. Viral RNA and/or antigen was detected in the brains of all animals and the distribution corresponded to areas of inflammation and edema. One of the animals that received the second inoculum developed neurological impairment and subsequent analysis of tissues showed viral antigen in both brain and spinal cord. Viral products were predominantly found in blood vessels suggesting hematogenous spread with entry into the central nervous system (CNS) through endothelium.
Asunto(s)
Aotidae/microbiología , Infecciones por Coronavirus/etiología , Coronavirus/patogenicidad , Enfermedades Desmielinizantes/microbiología , Encefalomielitis/microbiología , Administración Intranasal , Animales , Antígenos Virales/análisis , Astrocitos/microbiología , Encéfalo , Edema Encefálico/microbiología , Edema Encefálico/patología , Córnea , Coronavirus/aislamiento & purificación , Coronavirus/fisiología , Infecciones por Coronavirus/microbiología , Infecciones por Coronavirus/patología , Enfermedades Desmielinizantes/patología , Encefalomielitis/patología , Gliosis/microbiología , Gliosis/patología , Inyecciones , Inyecciones Intravenosas , Meningitis Viral/microbiología , Meningitis Viral/patología , ARN Viral/análisis , Médula Espinal/microbiología , Médula Espinal/patología , Viremia/microbiologíaRESUMEN
Lumbar sympathetic ganglionitis was found by light microscopy in 2 of 17 (12%) squirrel monkeys (Saimiri sciureus) experimentally infected with Coxsackievirus B4. This finding shows that viruses can cause ganglionitis which, in turn, must cause autonomic nervous system dysfunction. Such viral ganglionitis may explain some diseases, including cardiovascular ones, of poorly understood or unknown etiology which present with manifestations of dysfunction of the sympathetic nervous system.
Asunto(s)
Enfermedades del Sistema Nervioso Autónomo/etiología , Infecciones por Coxsackievirus/complicaciones , Animales , Enfermedades del Sistema Nervioso Autónomo/microbiología , Enfermedades Cardiovasculares/etiología , Enterovirus Humano B/aislamiento & purificación , Ganglios Simpáticos/microbiología , SaimiriRESUMEN
Enzyme-linked immunosorbent assay examination of sera from three nonhuman primate species demonstrated the presence of antibody reacting with simian rotavirus SA-11 and calf rotavirus C486. The occurrence of this antibody in sera from adult, wild-caught animals suggests natural rotovirus infection. The occurrence of antibody was highest in the chimpanzee and declined, respectively, in the rhesus macaque and in the squirrel monkey. Inoculation of three infant rhesus macaques, a nursery-reared chimpanzee, and a cesarian-derived nursery-reared baboon with SA-11 virus resulted in enteric infection, with virus excretion beginning 48 to 72 hours after oral administration of the virus. Clinical disease, as manifested by diarrhea, was observed only in the chimpanzee. Inoculation of ten squirrel monkeys, from 30 to 191 days old, induced infection only in the monkey inoculated at 30 days of age. This monkey became ill within 48 hours after viral administration and was euthanatized. Necropsy demonstrated a generalized infection, with virus recovered from lung, liver, kidney, spleen, and intestine. The remaining nine inoculated squirrel monkeys failed to develop enteric infection and did not respond with antibody to SA-11 virus.
Asunto(s)
Haplorrinos , Enfermedades de los Monos/etiología , Infecciones por Reoviridae/veterinaria , Animales , Anticuerpos Antivirales/análisis , Heces/microbiología , Macaca mulatta , Enfermedades de los Monos/microbiología , Pan troglodytes , Papio , Infecciones por Reoviridae/microbiología , Rotavirus/inmunología , Rotavirus/aislamiento & purificación , SaimiriRESUMEN
Encephalomyocarditis virus (EMCV), has caused the deaths of many species of animals in zoological parks and research institutions. The Audubon Park Zoo, (New Orleans, Louisiana, USA) attempted vaccination of several species with a killed EMCV vaccine with mixed results. This paper reports an attempt at vaccination against EMCV using a genetically engineered, live attenuated Mengo virus (vMC0) at the Audubon Park Zoo and Miami Metro Zoo, (Miami, Florida, USA) from December 1996 to June 1997. Several species of animals were vaccinated with vMC0, which is serologically indistinguishable from the field strain of EMCV. Serum samples were taken at the time of vaccination and again 21 days later, then submitted for serum neutralization titers against EMCV. The vaccinate species included red capped mangebey (Cercocebus torquatus), colobus (Colobus guereza), angolan colobus (Colobus angolensis), ruffed lemur (Lemur variegatus ruber and Lemur variegatus variegatus), back lemur (Lemur macaco), ring-tailed lemur (Lemur catta), siamang (Hylobates syndactylus), diana guenon (Cercopithicus diana), spider monkey (Ateles geoffroyi), common marmoset (Callithrix jacchus), talapoin monkey (Cercopithecus talapoin), Brazilian tapir (Tapirus terrestris), Baird's tapir (Tapirus bairdii), Malayan tapir (Tapirus indicus), dromedary camel (Camelus dromedarius), bactrian camel (Camelus bactrianus), gerenuk (Litocranius walleri), guanaco (Lama glama guanicoe), black duiker (Cephalophus niger), Vietnamese potbellied pig (Sus scrofa), babirusa (Babyrousa babyrussa), collard peccary (Tayass tajacu), and African crested porcupine (Hystrix africaeaustralis). The vaccine response was variable, with high virus neutralizing antibody titer responses in some primate species and mixed to poor responses for other species. No ill effects were seen with vaccination.
Asunto(s)
Animales de Zoológico , Infecciones por Cardiovirus/veterinaria , Mengovirus/inmunología , Vacunas Virales , Animales , Artiodáctilos , Infecciones por Cardiovirus/prevención & control , Ingeniería Genética , Células HeLa , Humanos , Mengovirus/genética , Perisodáctilos , Primates , Roedores , Vacunas Atenuadas/genética , Vacunas Sintéticas/genética , Vacunas Virales/genéticaRESUMEN
The free-ranging population of rhesus monkeys (Macaca mulatta) on Cayo Santiago was sero-surveyed for human measles, simian virus 40, B virus (Herpes simiae), rhesus cytomegalovirus, human and simian retroviruses and encephalomyocarditis virus to determine the prevalence of these viruses in the colony. The results of this study indicate that the colony is free of SV40, HTLVIII (HIV-1), STLVIII (SIV) and SRV1; has a low prevalence of measles and EMCV; and high prevalence rates for B virus, CMV and HTLVI.
Asunto(s)
Anticuerpos Antivirales/análisis , Macaca mulatta/inmunología , Macaca/inmunología , Enfermedades de los Monos/diagnóstico , Virosis/diagnóstico , Academias e Institutos , Factores de Edad , Animales , Citomegalovirus/inmunología , Anticuerpos Antideltaretrovirus/análisis , Virus de la Encefalomiocarditis/inmunología , Virus del Sarampión/inmunología , Enfermedades de los Monos/inmunología , Vigilancia de la Población , Puerto Rico , Virus de la Inmunodeficiencia de los Simios/inmunología , Virosis/inmunologíaAsunto(s)
Antivirales/uso terapéutico , Citosina/análogos & derivados , Infecciones por Herpesviridae/tratamiento farmacológico , Organofosfonatos , Compuestos Organofosforados/uso terapéutico , Animales , Antivirales/administración & dosificación , Antivirales/química , Línea Celular , Chlorocebus aethiops , Cidofovir , Infecciones por Citomegalovirus/tratamiento farmacológico , Citosina/uso terapéutico , Ratones , Estructura MolecularRESUMEN
The pharmacokinetics of recombinant human interferon-alpha I (rHuIFN-alphaI) were studied following a single 3 X 10(6) U/kg dose administered as a 30-min intravenous (iv) infusion and as an intramuscular (im) injection to four African green monkeys using a crossover design. Concentrations of rHuIFN-alpha I in serum were determined by bioassay. Serum rHuIFN-alpha I concentrations declined rapidly following an iv infusion. The elimination half-life ranged from 1.7 to 2.0 h. The volume of distribution at steady state and the total body clearance ranged from 0.42 to 2.4 L/kg and 28 to 233 ml/min, respectively. A protracted absorption profile was seen following im injection, with a highly variable bioavailability ranging from 16 to 680%, compared with the iv infusion. The overall disposition of rHuIFN-alpha I is comparable to that of rHuIFN-alpha A and other IFNs in monkeys.