RESUMEN
HSV-1 multiplication rates have been shown to vary in different tissues and the rate of multiplication may correlate with susceptibility to antiviral chemotherapy. Herpetic stromal keratitis is a necrotizing condition refractive to antiviral therapy and this lack of antiviral efficacy in stromal disease may be the result of very low rates of viral replication in the corneal stromal keratocytes. In this study, we investigated the efficacy of antiviral drugs in an in vitro system in which the virus multiplication rate is slow. In this system, the reduced rate of virus multiplication is achieved by a reduction in the incubation temperature. Vero cells were infected at one of several multiplicities of infection with McKrae strain HSV-1 and incubated for 24, 48, or 72 h at 26 or 36.5 degrees C in the presence or absence of trifluridine (50 micrograms/ml) or acyclovir (20 micrograms/ml). Both drugs suppressed viral replication at 36.5 degrees C. However, under some specific sets of conditions, trifluridine was not effective in suppressing viral replication in cells incubated at 26 degrees C. At this temperature, viral replication and cell metabolism are slowed to a pace which may be similar to that which occurs in corneal stromal keratocytes in vivo. Acyclovir significantly reduced HSV-1 replication under all conditions at 26 degrees C, indicating that the antiviral activity of this compound is effective in cells whose metabolic rate is slow and in which viral replication is taking place slowly.
Asunto(s)
Aciclovir/farmacología , Herpes Simple/tratamiento farmacológico , Simplexvirus/efectos de los fármacos , Trifluridina/farmacología , Replicación Viral/efectos de los fármacos , Animales , Simplexvirus/crecimiento & desarrollo , Células Vero/microbiología , Ensayo de Placa ViralRESUMEN
Adenosine-5'-monophosphate (AMP) was evaluated for efficacy in the prevention of spontaneous and induced herpes simplex virus type 1 (HSV-1) ocular shedding in latently infected rabbits with strain McKrae. Intraperitoneal injections (IP) of AMP (100 mg/kg) or NaCl (10 mg/kg) were given on postinoculation (PI) days 16-39. Spontaneous viral shedding was monitored by ocular tear film swabs on PI days 20-39. In the induced rabbits, one group received AMP (IP) and a second group received NaCl (IP) on PI days 66-77. In a third group, AMP (100 mg/kg) was given twice a day IP on PI days 66-77, and AMP was applied by iontophoresis to these eyes on PI days 68-74. In these three groups, ocular viral shedding was induced by ocular iontophoresis of 6-hydroxydopamine on PI day 70 followed by topical application of epinephrine for 5 days (PI days 70-74). HSV-1 ocular shedding was monitored on PI days 66-78. There were no significant differences in spontaneous or induced shedding patterns between the AMP (systemic or systemic plus ocular iontophoresis) and the NaCl groups. These results suggest that this dose of systemically administered AMP plus iontophoresis of AMP does not reduce ocular HSV-1 shedding in rabbits.
Asunto(s)
Adenosina Monofosfato/farmacología , Ojo/microbiología , Simplexvirus/aislamiento & purificación , Animales , Hidroxidopaminas/farmacología , Inyecciones Intraperitoneales , Iontoforesis , Oxidopamina , Conejos , Simplexvirus/inmunología , Cloruro de Sodio/farmacología , Lágrimas/microbiologíaRESUMEN
Several analogues of Met-enkephalin and beta-endorphin were tested for their analgesic properties after systemic injection. The latencies of mice to flick their tails away from a source of heat revealed that analogues of the opiate peptides can cause analgesia when injected by this route. In particular, compounds specifically designed to be more lipophilic or to possess additional binding sites were shown to be potent analgesic after peripheral administration.