The inhibitory effect of glabridin from licorice extracts on melanogenesis and inflammation.

Glabridin is the main ingredient in hydrophobic fraction of licorice extract affecting on skins. In this study, we investigated inhibitory effects of glabridin on melanogenesis and inflammation using cultured B16 murine melanoma cells and guinea pig skins. The results indicated that glabridin inhibits tyrosinase activity of these cells at concentrations of 0.1 to 1.0 microg/ml and had no detectable effect on their DNA synthesis. Combined analysis of SDS-polyacrylamide gel electrophoresis and DOPA staining on the large granule fraction of these cells disclosed that glabridin decreased specifically the activities of T1 and T3 tyrosinase isozymes. It was also shown that UVB-induced pigmentation and erythema in the skins of guinea pigs were inhibited by topical applications of 0.5% glabridin. Anti-inflammatory effects of glabridin in vitro were also shown by its inhibition of superoxide anion productions and cyclooxygenase activities. These data indicated that glabridin is a unique compound possessing more than one function; not only the inhibition of melanogenesis but also the inhibition of inflammation in the skins. By replacing each of hydroxyl groups of glabridin with others, it was revealed that the inhibitory effect of 2'-O-ethyl glabridin was significantly stronger than that of 4'-O-ethyl-glabridin on melanin synthesis in cultured B16 cells at the concentration of 1.0 mg/ml. With replacement of both of two hydroxyl groups, the inhibitory effect was totally lost. Based on these data, we concluded that two hydroxyl groups of glabridin are important for the inhibition of melanin synthesis and that the hydroxyl group at the 4' position of this compound is more closely related to melanin synthesis.

Thalamic experiential hallucinosis.

Two patients with an infarct limited to the thalamus developed auditory and visual experiential hallucinations. Neuropathological studies in one patient showed a small cavity in the right intralaminar nuclei surrounded by focal spongiform change, partly involving the right dorsomedial nucleus. Neuroradiological data in another patient indicated that the same nuclei in the left thalamus were also affected. It was concluded that a unilateral thalamic lesion could cause experiential hallucinations and the intralaminar and dorsomedial nuclei might be important structures to explain the phenomenon.

[Studies on drug release from anti-cancer drug suspended Lipiodol].

In case of an arterial infusion chemoembolization therapy for primary or metastatic liver cancer, gradual release of the anti-cancer drug from lipiodol is a very important factor for a higher drug concentration in the tumor and for longer contact. We studied basic points about what kind of drug form has a gradual drug release. We prepared 3 forms of drugs. (1) Powder form: Powder of ADM, MMC and CDDP was suspended in lipiodol with ultrasonic suspender. (2) URO form: ADM and MMC were dissolved with Urografin and mixed with lipiodol. (3) Surfactant form: ADM and MMC were dissolved with water and then mixed with lipiodol using surfactant. We put lipiodol suspension into physiological saline and then stirred water at 100 rpm with the paddle method, measuring drug release from the suspension or emulsion. Powder form had a lowest drug release. In clinical trials, we administered intra-arterially (1) ADM, MMC dissolved with physiological saline water as usually used (physiological saline water form) (2) Powder form; (3) URO from; (1) CDDP solution as usually used was administered; (2) Powder form. Then we studied the changes of serum concentration of ADM, MMC and CDDP. The results indicated that powder form had the lowest drug release. Thus, the water-soluble anti-cancer drugs ADM, MMC and CDDP should be used in powder form.