Beta-cryptoxanthin, plentiful in Japanese mandarin orange, prevents age-related cognitive dysfunction and oxidative damage in senescence-accelerated mouse brain.

Increased oxidative stress is known to accelerate age-related pathologies. Beta-cryptoxanthin (ß-CRX, (3R)-ß,ß-caroten-3-ol) is a potent antioxidant that is highly rich in Satsuma mandarin orange (mandarin), which is the most popular fruit in Japan. We investigated the antioxidative and anti-aging effects of ß-CRX and mandarin using senescence-accelerated mice (SAMP10), which were characterized by a short lifespan, high generation of superoxide anions in the brain and poor learning ability with aging. ß-CRX (0.5-5.0 µg/ml) or mandarin juice (3.8-38.0%) was added to drinking water of SAMP10 one to 12 months of age. ß-CRX was dose-dependently incorporated into the cerebral cortex and the contents were similar to the concentration of ß-CRX in the human frontal lobe. These mice also had higher learning ability. The level of DNA oxidative damage was significantly lower in the cerebral cortex of mice that ingested ß-CRX and mandarin than control mice. In addition, the mice that ingested ß-CRX (>1.5 µg/ml) and mandarin (>11.3%) exhibited a higher survival when 12 month-old, the presenile age of SAMP10, than control mice. These results suggest that ß-CRX is incorporated into the brain and has an important antioxidative role and anti-aging effect.

Protection of brain and pancreas from high-fat diet: effects of catechin and caffeine.

To investigate the effect of a high-fat diet on brain and pancreas functions, we used SAMP10 mice that have characteristics of brain atrophy and cognitive dysfunction with aging. Simultaneously, we investigated the effect of green tea catechin consumption on high-fat diet feeding, because green tea catechin has been reported to improve brain atrophy, brain dysfunction and obesity. The body weight of mice fed a high-fat diet from 2 to 12 months was higher than that of the control, although the calorie intake was not. The high-fat diet also increased insulin secretion; however, the hypersecretion of insulin and obesity were suppressed when mice were fed a high-fat diet with green tea catechin and caffeine. Furthermore, brain atrophy was suppressed and the working memory, tested using Y-maze, improved in mice fed a high-fat diet containing green tea catechin and caffeine. The secretion of insulin might affect both obesity and brain function. A strong correlation was found between working memory and insulin release in mice fed a high-fat diet with green tea catechin and/or caffeine. The results indicate the protective effect of green tea catechin and caffeine on the functions of brain and pancreas in mice fed a high-fat diet.

Inhaled steroid therapy and hospitalization for bronchial asthma: trend in Tokushima University Hospital.

With the recognition that airway inflammation is present even in patients with mild bronchial asthma, therapy with inhaled corticosteroids is now indicated in various stages of patients. In the present article, we retrospectively examined the prescriptions for inhaled corticosteroids and other drugs for the treatment of outpatients with bronchial asthma at Tokushima University Hospital. We also analyzed asthma control in these patients, in terms of the incidence of emergency consultations and hospitalizations due to asthma exacerbations. To analyze the recent trend, the patients observed from 1998 to 2000 (recent years) were included, and for control purpose, those in 1990 and 1991 (earlier years) were also included. The percentage of patients treated with inhaled corticosteroids remarkably increased in recent years (mean; 81.3%) compared to earlier years (mean; 23.5%). In contrast, the usage of oral corticosteroids, oral xanthine derivatives, beta-adrenergic receptor agonists and anti-allergic agents tended to decrease in the 10 years period. After the introduction in 1995, considerable patients up to 25% have been treated with anti-leukotrienes. Emergency consultations decreased in recent years (mean; 0.18/patient/year) compared to earlier years (mean; 0.79/patient/year). Emergency hospitalizations also decreased in recent years (mean; 0.043/patient/year) compared to earlier years (mean; 0.23/patient/ year). In the present study, spread of inhaled corticosteroid therapy and decline in incidence of emergency consultation and hospitalization were simultaneously observed at Tokushima University Hospital, and the former has, at least in part, a contribution to the latter.

Further evidence regarding the effect of dietary protein on oral tolerance against beta-lactoglobulin through Th1-mediated immune response in mice.

Oral tolerance is a potential strategy for preventing or minimizing aberrant immune responses. Although, oral tolerance has been extensively studied, to date the effects of dietary protein on the induction of oral tolerance are poorly understood. We have previously shown that restricted dietary protein induces oral tolerance to ovalbumin. This study was designed to investigate whether or not such tolerance occurs with beta-lactoglobulin (BLG) instead of ovalbumin (OVA) and if the tolerance resulting from this feeding regimen involves Th1-mediated immune response. Female BALB/c mice fed either 20% or 5% dietary protein were given 5 mg BLG or water orally for four consecutive days and then immunized intraperitoneally (ip) twice with BLG at 3-wk intervals. Oral tolerance induction was compared in BLG-fed and water-fed mice by measuring total IgE, BLG-specific antibodies, footpad reactions, splenocyte proliferation, and cytokine production. When mice were given BLG orally before ip immunization, the Th1-mediated immune responses (production of IL-2, IFN-gamma, and IgG2a) were significantly reduced, whereas the Th2-mediated immune responses (production of IL-4 and IgG1) were unchanged. The Th1-mediated immune responses were markedly down-regulated in mice fed 5% protein as compared to those in mice fed 20% protein. Moreover, the production of total IgE, BLG-specific IgE, splenocyte proliferation, and footpad reactions were more reduced in mice fed 5% protein than those in mice fed 20% protein. The present study provides evidence that dietary protein plays an important role in the induction of oral tolerance against BLG as the result of, clear down-regulation of Th1 helper activity accompanied by a reduction in IgE.

Theanine intake improves the shortened lifespan, cognitive dysfunction and behavioural depression that are induced by chronic psychosocial stress in mice.

To evaluate the psychosocial effect on lifespan and cognitive function, this study investigated the effect of confrontational housing on mice because conflict among male mice is a psychosocial stress. In addition, it investigated the anti-stress effect of theanine (γ-glutamylethylamide), an amino acid in tea. Mice were housed under confrontation. That is, two male mice were separately housed in the same cage with a partition for establishing the territorial imperative in each mouse. Then, the partition was removed and mice were co-housed confrontationally (confront-housing) using a model mouse of accelerated-senescence (SAMP10) that exhibited cerebral atrophy and cognitive dysfunction with ageing. It was found that mice began to die earlier under confront-housing than group-housed control mice. Additionally, it was found that cerebral atrophy, learning impairment and behavioural depression were higher in mice under the stressed condition of confront-housing than age-matched mice under group-housing. Furthermore, the level of oxidative damage in cerebral DNA was higher in mice housed confrontationally than group-housed control mice. On the other hand, the consumption of purified theanine (20 µg/ml, 5-6 mg/kg) suppressed the shortened lifespan, cerebral atrophy, learning impairment, behavioural depression and oxidative damage in cerebral DNA. These results suggest that psychosocial stress accelerates age-related alterations such as oxidative damage, lifespan, cognitive dysfunction and behavioural depression. The intake of theanine might be a potential candidate for suppression of disadvantage under psychosocial stress.

Atomic beam-induced fluorination of polyimide and its application to site-selective Cu metallization.

Metallization methods of polyimide by hyperthermal atomic oxygen and atomic fluorine beams were developed. An atomic fluorine beam with a translational energy of 6.2 eV modified the wettability of polyimide surfaces to provide an advancing water contact angle of 132 degrees. It was confirmed that in-air storage for 2 months did not alter the hydrophobic property created by the atomic fluorine beam. This stable beam-induced surface fluorination technique was then applied to site-selective electroless Cu plating on polyimide. It was demonstrated that changing the exposure sequence could create both positive- and negative-type plating processes.