Effects of ascorbic acid on gingival melanin pigmentation in vitro and in vivo.

BACKGROUND: Gingival melanin pigmentation may cause esthetic concerns, even if no serious medical problem is present. As an inhibitor of melanin formation, ascorbic acid is often used to treat skin melanin pigmentation. Thus, the present study investigated the effects of ascorbic acid on gingival melanin pigmentation in vitro and in vivo. METHODS: The effects of ascorbic acid on melanin formation were evaluated in vitro in B16 mouse melanoma cells and three-dimensional human skin models. In addition, a clinical trial was performed to investigate the inhibitory effects of a gel containing ascorbic acid 2-glucoside (AS-G gel) on gingival melanin pigmentation. This study used a double-masked, split-mouth design on 73 subjects with symmetric gingival melanin pigmentation. AS-G gel was applied to one side of the gingiva for 12 weeks, whereas placebo gel was applied to the other side as a control. Luminance (L*)-value, which describes the lightness of gingiva, was determined by spectrophotometry to obtain an objective measure of melanin pigmentation every 4 weeks. RESULTS: Ascorbic acid significantly inhibited tyrosinase activity and melanin formation in B16 mouse melanoma cells (P <0.01 and P <0.05, respectively). The inhibitory effects of ascorbic acid on melanin formation were also significant in three-dimensional human skin models (P <0.01). Moreover, in the clinical trial, a significant relative change in pigmentation was seen after 4 weeks with the application of AS-G gel compared to placebo (L*-value ratio). CONCLUSION: Ascorbic acid (AS-G) has potential for the treatment of gingival melanin pigmentation.

[Remarkably reduced tumor marker SCC levels by combined chemotherapy of paclitaxel and S-1 in two cases of advanced cervical cancer].

Case 1: A-35-year-old woman was diagnosed as cervical cancer Stage IIIb. When admitted to the hospital, her tumor marker SCC level was 50 ng/mL. Concurrent chemoradiation therapy was started on November, 2005. The SCC level was reduced by 0.9 ng/mL in February, 2006. In April, tumor recurrence was found by PET, and chemotherapy was restarted, but the SCC level was increased. In September, paclitaxel/S-1 therapy was performed, and the tumor markers were again reduced remarkably (SCC 9.8--> 1.3 ng/mL). Case 2: A-78-year-old woman was diagnosed as cervical cancer Stage IIIb. In August, 2004, concurrent chemoradiation therapy was started, and tumor markers were reduced (SCC 25.4--> 1.8 ng/mL). However, tumor markers were increased soon after the therapy. Chemotherapy was started, but it could not be maintained because of the side effects. In April, 2006, paclitaxel/S-1 therapy was performed, and the tumor markers were reduced remarkably (SCC 120--> 10 ng/mL). However, that therapy could also not be maintained because of the side effect. In July, she died of the cancer.

Induction of apoptosis by rhapontin having stilbene moiety, a component of rhubarb (Rheum officinale Baillon) in human stomach cancer KATO III cells.

We have investigated the effects of rhapontin on proliferation and DNA of human stomach cancer KATO III cells. Growth inhibition and induction of apoptosis by rhapontin were observed in the KATO III cells. Morphological change showing apoptotic bodies was observed in the KATO III cells treated with rhapontin. The fragmentation of DNA by rhapontin to oligonucleosomal-sized fragments that is a characteristic of apoptosis was observed to be concentration- and time-dependent in the KATO III cells. N-acetyl-L-cysteine, an antioxidant, suppressed the DNA fragmentation caused by rhapontin. On the other hand, it was found that resveratrol having stilbene moiety as well as rhapontin induced apoptosis in the KATO III cells. So, it is considered that stilbene moiety in the molecule is essential for the induction of apoptosis. The data of the present study show that the suppression of KATO III cell-growth by rhapontin results from the induction of apoptosis by the compound, and that active oxygen is involved in the inductions of apoptosis caused by rhapontin in the KATO III cells.

Platform for "Chemical Metabolic Switching" to Increase Sesquiterpene Content in Plants.

The biosynthetic pathway of cytosolic isoprenoids bifurcates after farnesyl diphosphate into sesquiterpene and triterpene pathways. "Metabolic switching" has been used to increase sesquiterpene content in plants by suppressing the competitive triterpene pathway using transgenic technology. To develop "metabolic switching" without using transgenic technology, we developed a model system of "chemical metabolic switching" using inhibitors of the competitive pathway. Arabidopsis plants that overexpress the amorpha-4,11-diene synthase gene were treated with squalestatin, a squalene synthase inhibitor, or terbinafine, a squalene epoxidase inhibitor. We then analyzed total sterol content as major triterpenes and amorpha-4,11-diene in the plant. Plants treated with squalestatin showed decreased total sterol content and increased amorpha-4,11-diene content. In contrast, plants treated with terbinafine showed decreased total sterol content, but amorpha-4,11-diene accumulation was quite low. These results suggest that inhibition of the enzyme just below the branch point is more effective than inhibition of enzymes far from the branch point for "chemical metabolic switching". In addition, the activity of 3-hydroxy-3-methylglutaryl-CoA reductase, the rate-limiting enzyme of the cytosolic isoprenoid biosynthetic pathway, was upregulated in plants treated with squalestatin, suggesting that feedback regulation of 3-hydroxy-3-methylglutaryl-CoA reductase may contribute to amorpha-4,11-diene production. Here we demonstrated the effectiveness of "chemical metabolic switching" in plants.

A study on phase-noise reduction method in phase-locked loop systems.

Experimental studies are carried out on phase noise and the correlation coefficient between the phase and average current noises of voltage-controlled oscillator in phased-locked loop (PLL) systems. The precise phase stabilization technique is discussed, and new methods to reduce the phase noise are described in PLL systems, using the correlation.