The 2'-fluorinated arabinosyl-pyrimidine nucleosides, 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine (FIAC) and 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-methyluracil (FMAU), are new antiviral compounds with in vitro inhibitory activity against the DNA polymerase of hepadnaviruses. Those compounds also induced permanent inhibition of viral replication in woodchucks chronically infected by woodchuck hepatitis virus. The effects of these antiviral compounds were assessed in ducks chronically infected by duck hepatitis B virus (DHBV). Following intraperitoneal administration for 5 days, FMAU (2 mg/kg/day) and FIAC (10 mg/kg/day) induced a transient decrease in DHBV replication, as shown by the decrease in both the serum and liver DHBV DNA level. After stopping therapy, DHBV replication rebounded immediately to the pretreatment level. The supercoiled form of liver viral DNA was found to be less affected by the therapy. By contrast, no obvious antiviral effect was observed with vidarabine monophosphate (ara-AMP) (80 mg/kg/day) therapy. No sign of toxicity was observed during the course of the treatment. These preliminary results confirmed in the DHBV model the higher efficacy of FIAC and FMAU as compared to ara-AMP. Pharmacokinetic studies are needed to explain the differences observed in viral replication in these 2 models of HBV infection.
Asthma is often preceded by atopic dermatitis (AD), a phenomenon known as 'atopic march'. It has been suggested that sensitization to common inhalant allergens, which is developed in a majority of patients with AD and often during the course of AD, may play a critical role in triggering the atopic march. Yet, what signal(s) delivered by AD skin could promote sensitization to inhalant allergens remains elusive. Here, by employing an experimental mouse asthma protocol, which is induced by airway sensitization and challenge to inhalant house dust mite (HDM), we demonstrate that the overproduction of cytokine thymic stromal lymphopoietin (TSLP) by AD skin promotes airway sensitization to HDM, thereby triggering subsequently an allergic asthma. Together, this study provides, for the first time, the experimental proof that TSLP represents an AD skin-delivered signal to promote sensitization to inhalant aeroallergen, which may account for one mechanism underlying the 'atopic march'.
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