Comparison of the changes of the antigenicities of a hen's egg albumin by a gamma and an electron beam irradiation

The study was conducted to compare the radiation types of a gamma ray and an electron beam for the inhibition and reduction of a food allergy. OVA (2 mg/ml) were irradiated at 3, 5, 7 and 10 kGy. Patterns detected by the SDS-PAGE and an immunoblot showed that the intact OVA band disappeared and that it was dependant upon the radiation doses regardless of the radiation types. Binding abilities of the irradiated OVA against the monoclonal IgG and the egg allergic patients’ IgE decreased due to a conformational change of the epitope, but differences from using the two different radiation types were not observed. The results indicate that both the radiation types can be used for an inhibition and a reduction of a food allergy regardless of the radiation types.     

Pharmacokinetics, tissue distribution and excretion of a new photodynamic drug deuxemether

Deuxemether was a new photodynamic drug effective for many kinds of solid tumor therapy, which was mainly composed of 3-(or 8-)-(1-methoxyethyl)-8-(or 3-)-(1-hydroxyethyl)-deutero-porphyrin IX (MHD) and 3,8-di(1-methoxyethyl)-deuteroporphyrin IX (DMD). The aims of this study were to elucidate its pharmacokinetic characteristics, tissue distribution, plasma protein binding and excretion properties and underlying mechanisms of deuxemether in rats based on the simultaneous determination of MHD and DMD. The pharmacokinetic profiles of both MHD and DMD in rats after intravenous doses were linear and best fitted to a two compartment model, characterized with a rapid distribution phase (MHD: t_1/2, 0.09–0.14 h; DMD: t_1/2, 0.07–0.11 h) and a relatively slow elimination phase (MHD: t_1/2β, 2.03–3.20 h; DMD: t_1/2β, 2.51–3.20 h). The tissue distributions of MHD and DMD in rats were rather limited as evidenced from their low distribution volume (0.75–1.70 L/kg) and the results of tissue distribution study. Protein binding of MHD and DMD were moderate (65.36–89.99% for MHD; 45.43–76.23% for DMD), independent of drug concentrations and similar between human and rat plasma over a concentration range of 0.50–50.0 μg/mL. Both MHD and DMD were predominantly (>74.1%) eliminated from rats as the parent drugs through the hepatobiliary systems and finally excreted into the feces. The multidrug resistance-associated proteins 2 (MRP2) inhibitors, bromosulfophthalein and probenecid, substantially inhibited the hepatobiliary elimination of MHD and DMD while the P-gp inhibitor digoxin had little effect, suggesting that MRP2 may contribute to the rapid and extensive hepatobiliary excretion of deuxemether. There were no significant differences between MHD and DMD for all pharmacokinetic characteristics studied. In conclusion, this study provided firstly the full pharmacokinetic characteristics and mechanisms of deuxemether, which would be helpful for its clinical regiment design.     

Metabolism linked synthesis of fluorinated anti-tumour drug the fluorine - deuterium gambit

Metabolism studies of the known anti-tumour agents 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (C C N u), 4-[4-bis(2-chloroethyl)amino phenyl]butyric acid (chloroambucil) and [2-bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2 oxazaphosphorine-2-oxide (cyclophosphamide) and their polydeuterio derivatives have led to an understanding of their mode of action, deactivation and ultimate excretion.In an attempt to modify or halt these processes, with the object of improving drug design and potency we have synthesised analogues of these drugs with fluorinated substituents in strategic positions within the molecules as indicated by metabolism data.The synthesis of each set of derivatives will be described with emphasis on the overcoming of problems of isomer distribution.Biological test results will be presented.