Evaluation of the Formation Conditions of a Spontaneous Emulsification Using Porous Silica Particles.

Emulsions are colloid dispersions which are attractive for use as drug carriers due to their simple structure and facile preparation. However, their low physicochemical stability has been problematic. In order to solve this problem, a spontaneous emulsification technique composed of porous silica particles has been developed. In this study, we investigated the conditions for effective formation of protein-encapsulated solid-in-oil-in-water (S/O/W) emulsions using this technique. Porous silica particles having a hydrophilic surface promoted the formation of a fine and uniform emulsion. It was found that the progression of emulsification was affected by electrolytes in aqueous solution. Moreover, it was confirmed that the S/O/W emulsion prepared using this method could successfully encapsulate protein.

PET imaging of nobiletin based on a practical total synthesis.

A practical synthesis of nobiletin, a polymethoxylated citrus flavone, was accomplished by utilizing our novel flavone synthesis. Synthetic nobiletin was labelled by selective demethylation and rapid incorporation of (11)C atom. Positron emission tomography images successfully visualized the brain distribution, which may provide therapeutic benefits in the treatment of Alzheimer's disease.

Concise synthesis of chafurosides A and B.

The regioselective synthesis of chafurosides A (1) and B (2) from the same methyl ketone 5 was accomplished using a novel protecting group strategy. Both flavone rings were constructed from beta-diketone intermediate 4, which was readily obtained by condensation of an acyl donor and ketone 5. Construction of the dihydrofuran ring was achieved via an intramolecular Mitsunobu reaction.

Identification and characterization of flavonoids as sialyltransferase inhibitors.

Sialyltransferases biosynthesize sialyl-glycoconjugates involved in many biological and pathological processes. We investigated and characterized synthetic flavonoid derivatives as sialyltransferase inhibitors. We first examined 54 compounds by solid-phase enzyme assay using beta-galactoside alpha2,6-sialyltransferase 1 (ST6Gal I) and beta-galactoside alpha2,3-sialyltransferase. Several compounds inhibited sialyltransferase enzyme activity regardless of sialyl-linkage reactions. Among them, two compounds showed inhibitory activity against ST6Gal I with IC(50) values less than 10 microM. Three characteristic features of flavonoids were determined by structure-inhibitory activity relationships. First, a double bond between C2-C3 linkages is required for the activity. Second, increasing hydrophilic properties on the B-ring markedly augmented the inhibitory effect. Third, a hydrophobic functional group introduced on the hydroxyl groups of the A-ring enhanced the inhibitory activity. Kinetic analysis using human ST6Gal I indicated a mixed inhibition mechanism of the compounds. In conclusion, the flavonoids identified could be applied for control of cellular expression of sialic acid.

[Atypical antipsychotic-associated impaired glucose tolerance].

Some reports of impaired glucose tolerance associated with olanzapine (OLZ) treatment have been published before OLZ was marketed in Japan. In Japan, we have been prohibited from using OLZ for patients with diabetes mellitus, since several cases with OLZ-associated impaired glucose tolerance including two deaths from diabetic coma have been reported. Here, we report four cases of OLZ-associated impaired glucose tolerance and review the points to consider in treatment with OLZ. Of our four cases, three cases were new-onset (non diabetes mellitus cases) and the other case was a diabetes mellitus-existent (diabetes mellitus case). In the non DM cases, the time to the onset of impaired glucose tolerance after initiating treatment with OLZ was 8-9 months, and the impaired glucose tolerance immediately improved after discontinuing treatment with OLZ and initiating treatment for diabetes mellitus. Therefore, it is necessary to continue long-term monitoring of the parameters of glucose metabolism for all patients treated with OLZ. Should impaired glucose tolerance develop during treatment with OLZ, treatment with OLZ should be discontinued immediately and treatment for diabetes mellitus should be started if necessary. Although the condition of diabetes mellitus was stable befor initiating treatment with OLZ in the DM case, hyperglycemia developed immediately after initiating treatment with OLZ and the condition remained unstable even after early treatment for diabetes mellitus. Therefore, it is necessary to check for a previous history of diabetes mellitus and hyperglycemia befor initiating treatment with OLZ. Correlations between weight gain and occurrence of impaired glucose tolerance are not clear, so it is necessary to monitor the occurrence of impaired glucose tolerance even in cases without weight gain.