Abstract.A new bleaching protocol for skin hyperpigmentation with a higher concentration of all-trans retinoic acid (atRA) aqueous gel than those commercially available is introduced. AtRA aqueous gel (0.1%) was applied topically twice a day along with 4% hydroquinone, 7% lactic acid ointment to oriental patients with hyperpigmented lesions such as senile lentigines, melasma, and postinflammatory hyperpigmentation. The clinical results of 39 patients treated with 0.1% atRA aqueous gel were compared to those of 22 patients treated with 0.1% atRA hydrophilic ointment. Better clinical results and subjective satisfaction were obtained through a significantly shorter period of treatment with 0.1% atRA aqueous gel than with 0.1% atRA hydrophilic ointment, although side effects such as erythema and irritation were seen at a higher frequency. It is suggested that our bleaching protocol with a high concentration of atRA aqueous gel in combination with hydroquinone and lactic acid has a strong bleaching ability and a potential as a standard therapy for various kinds of skin lesions with hyperpigmentation.

beta-adrenergic receptor blocking agents (beta-blocking agents) have been widely used clinically for the treatment of various cardiovascular conditions. However, beta-blocking agents are liable to cause sleep disturbance, such as vivid dreams, nightmares, increased waking, and insomnia. The mechanisms of the sleep disorders are not known, but several may conceivably be responsible for these CNS-related side effects. In the present study, we hypothesized that the sleep disorders are induced by the blockade of central or peripheral beta 2 receptors and/or central serotonin (5-HT) receptors. To verify the hypothesis, we retrospectively analyzed the relationships between the extent of the sleep disorders and the beta 1, beta 2, or 5-HT receptor occupancies for four beta-blocking agents (atenolol, metoprolol, pindolol, and propranolol). No significant correlations were observed among pharmacokinetic/physicochemical parameters (therapeutic dose, plasma concentration, plasma unbound concentration, cerebrospinal fluid concentration, and lipid solubility) and pharmacodynamic parameters (the scores of the sleep disorders such as the number of dreams). Furthermore, no significant relationship (correlation coefficient: r < 0.3) was observed between beta 1 receptor occupancies of the drugs and the number of dreams. On the other hand, good relationships (r > 0.95) were observed between central and peripheral beta 2 or central 5-HT receptor occupancies and the number of dreams. These findings suggest that beta 2 and/or 5-HT receptor occupancy is superior to beta 1 receptor occupancy as an index for the sleep disorders.

Cigarette smoking is one of the avoidable causes for diseases such as lung cancers, but biomarkers for health condition by cigarette cessation are expected. Biochemical data in plasma from 3053 Japanese in Tokyo were investigated who underwent an annual health check-up from 2003 to 2007 with amount and duration of cigarette smoking. Dose-dependent effects of cigarette smoking as indicated by Brinkman index (daily number of cigarettes × years) were observed on increased circulating white blood cell counts in men and women, red blood cell in women, and plasma triglycerides concentrations in men. Higher levels of hemoglobin and hematocrit in females were seen with ≤ 400 of Brinkman index, but these increases were observed in the male group with ≤ 800 of index. Decreased high-density lipoprotein cholesterol levels in blood were seen in men (> 800 of index). Decreased low-density lipoprotein cholesterol levels and enhanced glucose levels were only seen in a pooled heavy smoker group. Since increased ratios for the white blood cell counts in men and women by cigarette smoking were high among the markers tested in this study, the recovery of these parameters by cigarette cessation was investigated. The white blood cell counts were recovered time-dependently after quitting smoking for 1-3 years as evident with 38 other former smokers. These results suggest white blood cell counts would be sensitive biomarkers for smoking exposures and time-dependent recovery in hearty volunteers in monitoring and educating cigarette smoking and cessation.

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