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Background Bronchial asthma is a chronic disease characterized by inflammation, obstruction, and hyperresponsiveness of the airways. There is currently no curative therapy for asthma. Type 2 helper T cell response plays a critical role in the pathogenesis of the disease. Protein S is a glycoprotein endowed with anticoagulant, anti-inflammatory, and anti-apoptotic properties. Whether protein S can suppress bronchial asthma and be useful for its therapy is unknown. Methods To address this question here we compared the development of allergen-associated bronchial asthma between wild type and protein S-overexpressing transgenic mice. Mice were sensitized and challenged with ovalbumin. We also evaluated the circulating levels of total and active protein S in patients with bronchial asthma and healthy controls. Results The circulating level of total protein S and of its active form was significantly decreased in patients with bronchial asthma compared to controls. Allergic protein S transgenic mice showed a significant reduction of airway hyperresponsiveness, lung tissue inflammatory cell infiltration, lung levels of Th2 cytokines and IgE compared to their wild-type counterparts. Administration of exogenous human protein S also decreased airway hyperresponsiveness and Th2-mediated lung inflammation in allergic wild-type mice compared with their untreated mouse counterparts. Human protein S significantly shifted the Th1/Th2 balance to Th1 and promoted the secretion of Th1 cytokines (IL-12, tumor necrosis factor-α) from dendritic cells. Conclusions These observations suggest the strong protective activity of protein S against the development of allergic bronchial asthma implicating its potential usefulness for the disease treatment.

The suprachiasmatic nuclei (SCN) are necessary and sufficient for the maintenance of circadian rhythms in primate and other mammalian species. The human dorsomedial SCN contains populations of non-species-specific vasopressin and species-specific neurotensin neurons. We made time-series recordings of core body temperature and locomotor activity in 19 elderly, male, end-stage dementia patients and 8 normal elderly controls. Following the death of the dementia patients, neuropathological diagnostic information and tissue samples from the hypothalamus were obtained. Hypothalamic tissue was also obtained from eight normal control cases that had not had activity or core temperature recordings previously. Core temperature was analysed for parametric, circadian features, and activity was analysed for non-parametric and parametric circadian features. These indices were then correlated with the degree of degeneration seen in the SCN (glia/neuron ratio) and neuronal counts from the dorsomedial SCN (vasopressin, neurotensin). Specific loss of SCN neurotensin neurons was associated with loss of activity and temperature amplitude without increase in activity fragmentation. Loss of SCN vasopressin neurons was associated with increased activity fragmentation but not loss of amplitude. Evidence for a circadian rhythm of vasopressinergic activity was seen in the dementia cases but no evidence was seen for a circadian rhythm in neurotensinergic activity. These results provide evidence that the SCN is necessary for the maintenance of the circadian rhythm in humans, information on the role of neuronal subpopulations in subserving this function and the utility of dementia in elaborating brain-behaviour relationships in the human.

The role of Airport during and after large earthquake is important as assist emergency medical service, stating special operation for transporting living necessities for suffers' daily life immediately and restarting commercial logistic operation to support the activities of the enterprises located around the airport. Full-scale experiment using controlled blasting was conducted in the Ishikari Bay New Port (Ishikariwan-shinko) in Hokkaido Island, Japan, to assess the performance of airport facilities subjected to the liquefaction. Airport facilities in this study included runway pavement with full specifications for B747 aircraft and apron pavement with/without countermeasures for liquefaction, air traffic control facilities such as the Glide Slope Antenna, the Localizer Antenna, drainage conduit and etc. This paper presents that the earthquake resistance improvement strategy and some of the test results while the measurement and investigation are progressing now.

Previously, we reported that morning bright light therapy improved sleep time and cognitive function in Alzheimer type of dementia. We conducted a double blind study to examine the effects of melatonin on the sleep-wake rhythm, cognitive and non-cognitive functions in Alzheimer type of dementia. The subjects were 9 persons given a placebo (PLA), and 11 given melatonin ( 3 mg)(MLT). The mean age was 79.2+/-6.4 (17 females and 3 males). The drugs were given at 20: 30 each day for 4 weeks. We checked sleep time and activity by Actigraph through one week before and the 4th week after drug administration. Cognitive and non-cognitive functions were evaluated with the clinical dementia rating scale (CDR), and Mini Mental State Examination (MMSE), and the Alzheimer's Disease Assessment Scale (ADAS). We successfully recorded Actigraph data from 18 patients (PLA8, MLT10). The mean sleep time change ratio and SD of the administration of PLA in the night was-0.2+/-13.7%, and MLT was 33.2+/-37.6%. The mean activity counts and SD of the administration of PLA in the night was 29.8+/-77.0%; in MLT it was-44.9+/-21.9%. Melatonin significantly prolonged the sleep time (p=0.017) and decreased activity (p=0.014) in the night (21: 00-6: 00) in the MLT group, although no significant difference in sleep time or activity in the daytime (6: 00-21: 00) was recognized between the two groups. In comparison with ADAS cognition score changes, the mean change and SD in the PLA was 0.3+/-3.7; in MLT it was-4.3+/-3.6 points. In comparison with ADAS non-cognition score, the mean change and SD in the PLA group was-0.8+/-1.0, in the MLT group it was-4.1+/-2.2 points. There were also significant differences between the PLA and the MLT groups in the comparison with the score improvement of ADAS cognition (p=0.017) and non-cognition (p=0.002), otherwise there was no significant difference in improvement of MMSE between both groups. Melatonin administration had effect to improve sleep time and night activity, but no significant effect to improve daytime naps and activity. Although melatonin administration might has less strong effect on circadian rhythm than morning bright light therapy we previously reported, cognitive and non-cognitive functions were improved. Melatonin seemed to be useful for care of the Alzheimer type of dementia patients.

In the present study, the effects of short-acting benzodiazepines on nocturnal sleep and the carryover effects of these drugs were studied. The study involved 10 young, healthy male subjects who had given their written informed consent to participate. Either a placebo (PLA), 0.125 mg triazolam (TRZ), 0.25 mg TRZ or 0.25 mg brotizolam (BRZ) was administered to the subjects in a double-blind crossover design by randomized allocation with a single oral administration at 23.00 h. A polysomnography (PSG) was recorded for each subject from 23.00 to 07.00 h the following day. Then, the Stanford Sleepiness Scale (SSS) and Kwansei Gakuin Sleepiness Scale (KSS) were checked between 07.55 and 08.00 h, and the sleep latency test (SLT) was performed between 08.00 and 08.20 h. Event-related potentials (ERPs) were then recorded with an oddball paradigm; the reaction time (RT) was measured simultaneously. According to the PSG, treatment with 0.25 mg TRZ resulted in a statistically significant increase in the percentage of stage 2 sleep (p < 0.05) and a reduction in the percentage of rapid eye movement sleep (p < 0.05) compared with PLA. None of the drugs had any effect on the percentage of slow-wave sleep compared with PLA. With regard to carryover effects, although none of the drugs had any effect on SSS, KSS, RT or ERPs, BRZ did cause a statistically significant decrease in sleep latency (p < 0.05) compared with PLA. TRZ (0.125 and 0.25 mg) and 0.25 mg BRZ exerted different effects on SLT. We suggest that these different effects are attributable to differences in the half-life of these hypnotics.

Twenty-seven patients with Alzheimer-type dementia (ATD) were treated with bright light therapy in the morning for four consecutive weeks. The cognitive state of each patient was evaluated with the Mini-Mental-State Examination (MMSE) and circadian rhythm with actigram before and after therapy for all of the patients and those of two groups divided by the severity criteria of the Clinical Dementia Rating. The therapy improved the circadian rhythm disturbances. Although the therapy caused no remarkable effects on dementia severity, it improved the MMSE scores, especially in the early stages of ATD. These results suggest that bright light therapy improved the circadian rhythm disturbances and then bettered the cognitive state in early-stage ATD.

Using polysomnography, sleep effect was studied, then the sleep latency test (SLT), Stanford Sleepiness Scale (SSS), and Kwansei Gakuin Sleepiness Scale (KSS) were studied the next morning after administration of either an inactive placebo (PL), 0.125 mg triazolam (TL), 0.25 mg triazolam (TH), or 0.25 mg brotizolam (BR). Ten healthy male volunteers were used for the double-blind crossover design. TL increased the percentage of stage 2 sleep significantly compared with PL, whereas TH decreased the number of stage shifts significantly. TH and BR increased the percentage of stage 2 sleep significantly and decreased the percentage of rapid eye movement sleep significantly. Although no drug had any effect on SSS and KSS, BR decreased the sleep latency in SLT significantly.

The present study investigated the effects of vitamin B12 (VB12) on circadian rhythm in Alzheimer-type dementia (ATD). Twenty-eight ATD patients were treated with bright light therapy (BLT) for 8 weeks. For the latter 4 weeks, half were treated with VB12 with BLT (BLT + VB12). We evaluated the cognitive state with Mini-Mental State Examination and the circadian rhythm with actigraphy after the fourth and eighth week. After the first 4 weeks BLT improved the circadian rhythm disturbances and cognitive state especially in the early stage of ATD. Although the latter 4 week-BLT caused no significant effects on the circadian rhythm; BLT + VB12 improved the vigilance level during the daytime. These results suggest that VB12 has some efficiency to enhance vigilance for ATD patients.