|Budget Amount *help
¥1,900,000 (Direct Cost : ¥1,900,000)
Fiscal Year 1992 : ¥500,000 (Direct Cost : ¥500,000)
Fiscal Year 1991 : ¥1,400,000 (Direct Cost : ¥1,400,000)
At the time of the primary skin infection, herpes simplex virus (HSV) is transported by retrograde axoplasmic flow, and a long-term latent infection is established in sensory ganglionic neurons of humans and experimentally infected animals. The major morbidity in herpetic disease comes not from the primary infection, but from clinical recurrences that occur after reactivation of the latent infection, migration of virions back down the sensory axons, and replication of virus at skin or mucosal surfaces. Once it has been established, there has been no effective way to eliminate HSV latency. In our previous study, we selectivly destroyed ganglionic neurons by injecting the toxic lectin ricin into particular intradermal sites of latently infected mice (J.Inf.Dis.157.1270.1988). Although the ricin has been given intravenously to patients with advanced cancer (Cancer Res.44.862.1984), the treatment of recurrentherpes may not be recommended because of it's high toxicity.
Similar results for th
e elimination of ganglionic latency have been reported in a rat model of HSV latency after intraneural injection of adriamycin (doxorubicin), an antineoplastic drug that is transported in axons and is toxic to neurons (J.Virol.59.242.1986). In our previous study, however, suboutaneous (sc) injection of 0.1ml of doxorubicin (10mg/ml) failed to eliminate latency. We thought that peripheral nerve terminals did not take updoxorubicin in sufficient amounts and that intraneural injection of this drug is necessary for it to be effective. In the present study, we noted that decreasing of skin langerhans cell by sc injection of hypertonic saline solution (10%Nacl)was prerequisite for the elimination, ie, injected with 10% Nacl subcutaneously, 6-24h later, 10mg/ml of doxorubicin suspended in 10% Nacl was injected subcutaneowsly. Results that Ca.50-100% elimination of the latency were obtained. Explantation-cocultivation was used as a method for the study but polymerase chain reaction (PCR) was not available probably because of very small amount of HSV-genome in ganglia. Finally, the treatment may be available in case of genital herpes, especially occurred frequently, rather than exposured skin such as face, neck and head because there was skin defect at the injection site. Less