Pharmacokinetics of Beclomethasone Dipropionate in an Hydrofluoroalkane-134a Propellant System in Japanese Children with Bronchial Asthma

ABSTRACTBackgroundHydrofluoroalkane-134a (HFA) has been shown to be a safe replacement for chlorofluorocarbons (CFCs) as a pharmaceutical propellant, with the advantage that it has no ozone-depleting potential. This is the first report of the pharmacokinetics of beclomethasone dipropionate (BDP) delivered from a pressurized solution formulation using an HFA propellant system (HFA-BDP) in Japanese children with bronchial asthma.MethodsPlasma concentrations of beclomethasone 17-monopropionate (17-BMP), a major metabolite of BDP, following an inhaled dose of HFA-BDP (200 μg as four inhalations from 50 μg/actuation) in five Japanese children with bronchial asthma were quantified and analyzed by a non-compartmental analysis to obtain pharmacokinetic parameters.ResultsThe area under the concentration-time curve from time zero to the last quantifiable time (AUC0-t) was 1659 ± 850 pg • h/mL (arithmetic mean ± standard deviation (SD)), the maximum concentration observed (Cmax) was 825 ± 453 pg/mL and the apparent elimination half-life (t1/2) was 2.1 ± 0.7 hours. The time to reach Cmax (Tmax) was 0.5 hours in all patients. No special relationship was observed between these parameters and age or body weight. These parameters were compared with the previously reported parameters of American children with bronchial asthma. The Japanese/American ratio of the geometric means of each parameter was 1.36 for AUC0-t, 1.04 for Cmax and 1.4 for t1/2. The median of Tmax was 0.5 hours in American patients as well as Japanese patients.ConclusionsThe pharmacokinetics of HFA-BDP in Japanese children with bronchial asthma are reported for the first time and a similarity to those in American children is suggested

Phloem-Conducting Cells in Haustoria of the Root-Parasitic Plant Phelipanche aegyptiaca Retain Nuclei and Are Not Mature Sieve Elements

Phelipanche aegyptiaca parasitizes a wide range of plants, including important crops, and causes serious damage to their production. P. aegyptiaca develops a specialized intrusive organ called a haustorium that establishes connections to the host’s xylem and phloem. In parallel with the development of xylem vessels, the differentiation of phloem-conducting cells has been demonstrated by the translocation of symplasmic tracers from the host to the parasite. However, it is unclear yet whether haustorial phloem-conducting cells are sieve elements. In this study, we identified phloem-conducting cells in haustoria by the host-to-parasite translocation of green fluorescent protein (GFP) from AtSUC2pro::GFP tomato sieve tubes. Haustorial GFP-conducting cells contained nuclei but not callose-rich sieve plates, indicating that phloem-conducting cells in haustoria differ from conventional sieve elements. To ascertain why the nuclei were not degenerated, expression of the P. aegyptiaca homologs NAC-domain containing transcription factor (NAC45), NAC45/86-dependent exonuclease-domain protein 1 (NEN1), and NEN4 was examined. However, these genes were more highly expressed in the haustorium than in tubercle protrusion, implying that nuclear degradation in haustoria may not be exclusively controlled by the NAC45/86-NEN regulatory pathway. Our results also suggest that the formation of plasmodesmata with large size exclusion limits is independent of nuclear degradation and callose deposition

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Visualizing distribution of hydrogen peroxidein an aqueous gelatin sample irradiated by carbon ion beam

The spatial distribution of hydrogen peroxide (H2O2) generated in a solid gelatin sample irradiated by heavy-ion (carbon) beam was investigated. The detectable level of H2O2 was generated in water by relatively high-dose (~ 256 Gy) X-ray irradiation. Simultaneously, oxygen consumption was observed in water irradiated by X-ray. H2O2 generated in an aqueous solution of a nitroxyl radical, 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPOL), participated a reducing the nitroxyl radical during X-ray irradiation, since this reduction of nitroxyl radical was inhibited by catalase. H2O2 generation in the solid gelatin sample irradiated by carbon beam was analyzed using this reaction system.An aqueous solution of a nitroxyl radical, TEMPOL, was caked using gelatin to test depth-dependent redox reactions. The gelatin sample was irradiated with a 290 MeV/nucleon carbon ion beam up to a dose of 128 Gy. The detection of H2O2 in a sample irradiated by a carbon beam was performed by EPR spectroscopic and MRI methods. When gelatin samples were irradiated by several different linear energy transfer (LET) of carbon beam, the H2O2 generation profile in the gelatin sample was obtained based on H2O2-dependent EPR signal loss of TEMPOL in the sample. The oxygen consumption profile in the gelatin sample, measured with L-band EPR oxymetry, showed almost the same shape as the H2O2 profile. The H2O2 profile in one intact solid gelatin sample scanned by 7 T MRI showed a similar shape as a result of the EPR experiment. Micromolar level generation of H2O2 in a gelatin sample irradiated by carbon beam was observed from the surface to the beam end with an almost flat distribution, except for a slight peak just before the beam end. The MRI approach using nitroxyl based redox transformations shows feasibility of obtaining spatial profiles of H2O2 generation in a solid sample irradiated with high LET radiation.5th Joint Meeting of The Societies for Free Radical Research Australasia and Japa

Distribution of Hydrogen Peroxide-dependent Reaction in a Gelatin Sample Irradiated by Carbon Ion Beam

We investigated the amount and distribution of hydrogen peroxide (H2O2) generated in a solid gelatin sample irradiated by heavy ion (carbon) beam. We irradiated the gelatin sample, which contained a nitroxyl radical (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl, TEMPOL), with a 290-MeV/nucleon carbon beam (~128 Gy). To verify the distribution of H2O2 generation in the irradiated sample, we employed both electron paramagnetic resonance (EPR) spectroscopic and magnetic resonance (MR) imaging methods based on H2O2-dependent paramagnetic loss of TEMPOL. We obtained a distribution profile of the H2O2-dependent reaction in the gelatin sample when we irradiated gelatin samples with carbon beams with several different linear energy transfer (LET) values. Because the profiles of oxygen consumption in the gelatin sample measured by L-band EPR oxymetry and of the H2O2-dependent reaction have almost the same shape, the profile of the H2O2-dependent reaction can be used as an estimation of the profile of the generation of H2O2. The H2O2 profile in one intact gelatin sample scanned by 7-tesla MR imaging showed a similar shape as a result of the EPR experiment. We obtained several hundreds of micromolars of H2O2 generated in a gelatin sample irradiated by carbon beam when 200 Gy was given at the surface of the sample. H2O2 distribution was almost flat, with only a slight peak just before the end of the beam