Modeling the Kinetic Behavior of Reactive Oxygen Species with Cerium Dioxide Nanoparticles.

The world of medicinal therapies has been historically, and remains to be, dominated by the use of elegant organic molecular structures. Now, a novel medical treatment is emerging based on CeO2 nano-crystals that are discrete clusters of a few hundred atoms. This development is generating a great deal of exciting and promising research activity, as evidenced by this Special Issue of Biomolecules. In this paper, we provide both a steady-state and time-dependent mathematical description of a sequence of reactions: superoxide generation, superoxide dismutase, and hydrogen peroxide catalase and ceria regeneration. This sequence describes the reactive oxygen species (ROS); superoxide, O2-, molecular oxygen, O2, hydroxide ion OH- and hydrogen peroxide, H2O2, interacting with the Ce3+, and Ce4+ surface cations of nanoparticle ceria, CeO2. Particular emphasis is placed on the predicted time-dependent role of the Ce3+/Ce4+ ratio within the crystal. The net reaction is succinctly described as: H2O2 + 2O2- + 2H+ → 2H2O + 2O2. The chemical equations and mathematical treatment appears to align well with several critical in vivo observations such as; direct and specific superoxide dismutase (SOD), ROS control, catalytic regeneration, ceria self-regulation and self-limiting behavior. However, in contrast to experimental observations, the model predicts that the 4+ ceric ion state is the key SOD agent. Future work is suggested based on these calculations.

Safety and immunogenicity of an inactivated Vero cell_derived Japanese encephalitis vaccine (IXIARO®, JESPECT®) in a pediatric population in JE non-endemic countries: An uncontrolled, open-label phase 3 study.

BACKGROUND: Young travelers to South-East Asia may be at risk for Japanese encephalitis (JE). METHODS: IXIARO® (0.25 ml or 0.5 ml, depending on age) were administrated to 100 travelers aged ≥ 2 months to < 18 years. Solicited AEs were collected for 7 days after each injection, unsolicited adverse events (AEs) for a total of 7 months. JE neutralizing antibodies were assessed in 64 subjects. RESULTS: The most common solicited local AEs were redness (3/12 subjects), induration and tenderness (both 1/12) with 0.25 ml IXIARO®, and tenderness (44/88) and pain (22/88) with 0.5 ml IXIARO®. Common solicited systemic AEs were diarrhea (2/12) and loss of appetite (1/12) with 0.25 ml IXIARO® and muscle pain (27/88) and excessive fatigue (10/88) with 0.5 ml IXIARO®. In total, up to day 56, AEs were reported by 10/12 (83.3%) of subjects who received the 0.25 ml dose and 67/88 (76.1%) of those vaccinated with the 0.5 ml dose. All subjects (62/62; 100%) developed protective levels of JE neutralizing antibodies by Day 56 and 31/34 (91.2%) retained protective titers at Month 7. CONCLUSIONS: IXIARO® was generally well tolerated in children, with an overall AE profile similar to adults. IXIARO® was highly immunogenic in both dose groups.