RESUMO
This study investigated whether immunostimulatory DNA sequences (ISS) induce a transient or sustained inhibition of Th2 responses to inhaled antigen. We sensitized mice with subcutaneous injections to develop a Th2 response to ovalbumin (ova) and then administered a dose of ISS prior to ova inhalation challenge. Mice were then rechallenged with ova by inhalation a second time at varying time points after the first ova inhalation (1 to 8 weeks later) to determine whether the ISS dose administered prior to the first ova inhalation protected against a subsequent second ova inhalation challenge. A single dose of ISS inhibited the Th2 response to the first inhalation of ova antigen, as well as 4 weeks later to the second inhalation of ova. However, ISS did not inhibit a Th2 response to the second inhalation of ova 8 weeks later. The reversible inhibition of Th2 responses at 8 weeks suggests the need for repeated ISS administration at monthly intervals.
Assuntos
Adjuvantes Imunológicos/administração & dosagem , Asma/prevenção & controle , DNA/administração & dosagem , Células Th2/efeitos dos fármacos , Células Th2/imunologia , Animais , Asma/imunologia , Sequência de Bases , Hiper-Reatividade Brônquica/imunologia , Hiper-Reatividade Brônquica/prevenção & controle , Ilhas de CpG/imunologia , Citocinas/biossíntese , DNA/genética , DNA/imunologia , Modelos Animais de Doenças , Eosinófilos/efeitos dos fármacos , Eosinófilos/imunologia , Feminino , Imunoglobulina E/sangue , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/administração & dosagem , Ovalbumina/imunologia , Células Th1/efeitos dos fármacos , Células Th1/imunologiaRESUMO
Cisplatin was administered to 11 patients as a continuous infusion, 25 mg/m2/day for 1 to 4 days. Total and filterable platinum in plasma were monitored for 12 courses and a pharmacokinetic study was carried out in 7 patients by computerized nonlinear least-squares analysis. Following interruption of the infusion, the decrease of plasma filterable platinum was biphasic, with initial and terminal half-life of 21.6 +/- 11.4 min and 31.7 +/- 27.1 hr. Filterable platinum was still detectable in plasma 24 hours after the end of infusion. The total AUC exposure of filterable platinum for 24 hrs, 48 hrs and 96 hrs infusion were 3.67 micrograms.hr/ml, 13.68 micrograms.hr/ml and 14.75 micrograms.hr/ml, which were at least 3-fold higher than that observed for the short-term infusion of equal dose in literature. Gastrointestinal toxicity was evaluated and compared with short-term infusion of equal dose. In the continuous-infusion patients, the reduction of vomiting was observed but the duration of nausea was not shortened.