Association of sleep-disordered breathing and alcohol consumption with hypertension among Japanese male bus drivers.

There is limited evidence regarding the combined effects of sleep-disordered breathing (SDB) and alcohol consumption on hypertension. The aim of this study was to examine the combined effects of SDB and alcohol consumption on hypertension in Japanese male bus drivers. This cross-sectional study included 2525 Japanese male bus drivers aged 20-65 years. SDB was assessed using a single-channel airflow monitor, which measured the respiratory disturbance index (RDI) during overnight sleep at home. Alcohol consumption (g/day) was assessed by a self-administered questionnaire and calculated per unit of body weight. Hypertension was defined as systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg and/or use of antihypertensive medications. Multiple logistic regression analyses were performed to examine the association of the combined categories of RDI and alcohol consumption with hypertension. The multivariable-adjusted odds ratio (OR) and 95% confidence interval (95% CI) of hypertension for the alcohol consumption ≥1.0 g/day/kg and RDI ≥ 20 events/h group were 2.41 (1.45-4.00) compared with the alcohol consumption <1.0 g/day/kg and RDI < 10 events/h group. Our results suggest that Japanese male bus drivers with both SDB and excessive alcohol consumption are at higher risk of hypertension than those without SDB and excessive alcohol consumption, highlighting the importance of simultaneous management of SDB and excessive alcohol consumption to prevent the development of hypertension among bus drivers.

Sporadic Triple A (Allgrove) Syndrome with Novel Tandem Mutations.

In triple A (Allgrove) syndrome, motor neuron disease is a co-morbid condition. We herein report a 38-year-old Japanese man with triple A (Allgrove) syndrome and novel tandem mutations: a novel c.881delT deletion mutation and c.835C>T localized to the AAAS gene. A nerve conduction study revealed marked axonal damage in several motor nerves. Tandem mutations in the AAAS gene may be involved in co-morbid motor neuron disease and aberrant electrophysiological findings.

The association between asthma and anxiety in elementary school students in Japan.

BACKGROUND: Studies on the association between asthma and anxiety in Asian children are limited. Therefore, we aimed to evaluate the association between asthma and anxiety among Japanese elementary school students. METHODS: A cross-sectional study of the association between asthma and anxiety in primary school children in Matsuyama City was conducted in 2014. The questionnaires included inquiries on asthma, anxiety, and other demographic variables. After excluding missing values, 17 752 (51.5% male) children were included in the analysis. The presence of asthma (yes/no) was answered by guardians. A score of four or more on the emotional symptom subscale of the strengths and difficulties questionnaire was considered as having anxiety. A Rohrer index score of 145 or more was considered as overweight. We estimated the prevalence ratio (PR) of having anxiety in relation to the presence of asthma based on the Poisson regression model. RESULTS: The multivariate PR (95% confidence interval) of having anxiety in asthmatic boys compared with non-asthmatic boys was 1.56 (1.21-1.99). The association was more evident in older than younger boys, where PR = 1.32 (0.93-1.88) for younger versus 1.87(1.32-2.64) for older boys (P for interaction = .08); and in non-overweight boys than overweight, where PR = 1.64 (1.27-2.13) and 0.94 (0.41-2.19) (P for interaction = .22), respectively. Similar associations were not found for girls. CONCLUSION: Asthma was significantly associated with anxiety in boys, particularly in older boys.

Impact of sleep disordered breathing on performance in judo players.

OBJECTIVE: Previous studies have suggested that young sports players may suffer from sleep disordered breathing (SDB). It was hypothesised that SDB in heavy-class judo players was far more prevalent than expected and that it could reduce judo performance, which could be improved by appropriate therapies. To address this, the present study estimated the percentage of heavy-class judo players with SDB and investigated the effect of SDB treatment on judo performance. METHODS: We enrolled 19 young judo players from a university judo team with body weight >100 kg and/or body mass index >30 kg/m2. Both excessive daytime sleepiness (EDS) and respiratory disturbance index (RDI) were evaluated using the Epworth Sleepiness Scale (ESS) and an overnight type 3 sleep monitor. RESULTS: The percentages of young heavyweight-class judo players with EDS (ESS ≥11) and those with SDB (RDI ≥5) were both 63%, which was unexpectedly high for the age class. Seven of the participants underwent continuous positive airway pressure therapy, which improved both RDI and ESS scores (p<0.05 for each) and subsequently the sleep quality and judo performance of the participants. CONCLUSIONS: Our study indicates that young judo players might silently suffer from SDB, leading to poorer judo performance and to future cardiovascular diseases. Clinicians should be aware of the possible presence of SDB in young sports players and consider the application of diagnostic and therapeutic remedies.

Harmonizing work with the treatment and prevention of sleep disordered breathing in commercial motor vehicle drivers: implications for health and productivity management.

The desastrous traffic accidents to date have provided the relevance for promotion of harmonization of work with treatment and prevention of sleep disordered breathing (SDB) in transport sectors. SDB is highly prevalent in commercial motor vehicle (CMV) drivers and is one cause of cognitive impairment and consequent traffic accidents, potentially costing billions and leading to many deaths. Various screening, diagnostic, and therapeutic approaches, some well established, are explored in this paper. Although drivers with SDB need to be appropriately diagnosed and treated, some are reluctant to continue their treatment or never submit to screening because of a lack of information. Thus, CMV drivers need to be well informed and screened, in addition to being encouraged to continue the treatment. The harmonization of work with treatment and prevention aids these objectives, providing benefits not only for individual health but also for transport companies, and further being an essential step towards uptake of "health and productivity management" in the transport sectors.

Nocturnal enuresis and sleep disordered breathing in primary school children: Potential implications.

INTRODUCTION: The association between nocturnal enuresis (NE) and sleep disordered breathing (SDB) has been repeatedly reported, but has primarily been focused on clinical cohorts. The purpose of this study, was to assess whether SDB-related symptoms such as snoring and unrefreshing sleep in the morning are associated with NE in a large-scale community school-based survey. METHODS: A cross-sectional assessment using a standard questionnaire was conducted on nearly 20 000 primary school children (5-12 years old) in Matsuyama, Japan. Associations between NE and the frequencies of snoring and unrefreshing sleep were evaluated using multivariate logistic and regression analyses. RESULTS: Multivariate adjusted odds ratios (95% confidence intervals) for enuresis were 1.21 (1.04 to 1.40) and 1.36 (1.07 to 1.73) in boys who snored 1 or 2 nights per week and ≥3 nights per week, respectively (P for trend <0.0001). Those for enuresis were 1.67 (1.41 to 1.99) and 1.96 (1.63 to 2.36) in boys who showed unrefreshing sleep 1 or 2 nights per week and ≥3 nights per week, respectively (P for trend <0.0001). Significant associations between NE and snoring frequency emerged among children who did not report unrefreshing sleep (P-trend for boys and girls were <0.0001 and <0.01, respectively), while significant associations between NE and frequency of unrefreshing sleep were detected among children who snored ≥1 nights per week (P for trend >0.1). CONCLUSIONS: The pathogenic mechanisms linking snoring and unrefreshing sleep to increased risk of NE are unknown. However, snoring, a surrogate reporter of SDB, is associated with increased urine production, while unrefreshing sleep may result from disrupted sleep facilitating increased sleep pressure and elevated arousal thresholds. Thus, both SDB and unrefreshing sleep are potential independent risk factors of NE in school age children.

Determination of phenylalanine tRNA recognition sites by phenylalanyl-tRNA synthetase from hyperthermophilic archaeon, Aeropyrum pernix K1.

Phenylalanine tRNA identity has been determined in the bacteria and the eukaryote system, but remains unknown for the archaea system. To investigate the molecular recognition mechanism of phenylalanine tRNA by phenylalanyl-tRNA synthetase from hyperthermophilic and aerobic archaeon, Aeropyrum pernix K1, various mutant transcripts of phenylalanine tRNA prepared by an in vitro transcription system were examined by overexpressed A. pernix phenylalanyl tRNA synthetase. The results indicated that anticodon nucleotides G34, A35 and A36, discriminator base A73 and G20 in the variable pocket were base-specifically recognized by A. pernix phenylalanyl-tRNA synthetase.

Protective effect of donepezil in primary-cultured rat cortical neurons exposed to N-methyl-d-aspartate (NMDA) toxicity.

Donepezil has a neuroprotective effect against oxygen-glucose deprivation injury and glutamate toxicity in cultured cortical neurons. In this study, we further characterized the neuroprotective properties of donepezil in rat cortical cell cultures using glutamate receptor-specific agonists (N-methyl-d-aspartate (NMDA), alpha-amino-3-hydroxy-5-methylisoxazolepropionate (AMPA) and kainate). Pretreatment with donepezil (1 microM) for 12 h significantly decreased the lactate dehydrogenase (LDH) release in response to NMDA (100 microM) by 43.8%, and reduced the LDH release in response to kainate (100 microM) and AMPA (100 microM) by 11.9% and 7.5% (without statistical significance), respectively. Donepezil appeared to inhibit LDH release in a concentration-dependent manner at 0.1-10 microM. Cortical neurons exposed to NMDA retained a normal morphological appearance in the presence of 10 microM donepezil. In binding assay for glutamate receptors, donepezil at 100 microM only slightly inhibited binding to the glycine and polyamine sites on NMDA receptor complex. On the other hand, 12 h pretreatment with donepezil at 10 and 100 microM significantly decreased the NMDA-induced increase of intracellular calcium concentration ([Ca2+]i). In conclusion, our results show that donepezil has protective activity against NMDA toxicity in cortical neurons, and this neuroprotection seems to be partially mediated by inhibition of the increase of [Ca2+]i.

Comparison of donepezil and memantine for protective effect against amyloid-beta(1-42) toxicity in rat septal neurons.

Donepezil, a potent acetylcholinesterase (AChE) inhibitor and memantine, an N-methyl-d-aspartate (NMDA) receptor antagonist, have been used for the treatment of Alzheimer's disease (AD), and both of them have been shown to have neuroprotective action against glutamate excitotoxicity. However, it is not known whether donepezil and memantine similarly exert neuroprotective effects against amyloid-beta peptide(1-42) [Abeta(1-42)] toxicity in cholinergic neurons. Therefore, in the present study we compared the neuroprotective effects of donepezil and memantine against Abeta(1-42) toxicity in rat cultured septal cholinergic neurons, because deficit in cholinergic neurotransmission is a major feature in AD, and medial septal cholinergic neurons are known to degenerate in AD patients. Septal neuronal cells were cultured for 7 days and then 5 micromol/L of Abeta(1-42) was added to the medium for 48 h. Measurement of the efflux of lactate dehydrogenase (LDH) indicated that septal neuronal cells were highly susceptible to Abeta toxicity and relatively resistant to NMDA toxicity. Donepezil concentration-dependently reduced the LDH efflux induced by Abeta(1-42), and the effect was significant at 1 micromol/L and above. NMDA receptor antagonists, memantine and MK-801, did not show a significant neuroprotective effect against Abeta(1-42) toxicity. It is concluded that the neuroprotective effect of donepezil against Abeta(1-42) toxicity is not mediated by interference with the NMDA-mediated excitotoxic process, and that donepezil may be more effective than memantine against cholinergic neuronal damage induced by Abeta(1-42) exposure.

Protective effect of donepezil against Abeta(1-40) neurotoxicity in rat septal neurons.

Donepezil, a potent acetylcholinesterase (AChE) inhibitor used for the treatment of Alzheimer's disease (AD), is thought to have a neuroprotective effect in AD patients. Because a deficit in cholinergic neurotransmission is a major feature in AD, and amyloid-beta (Abeta) accumulation has been proposed as a possible causative phenomenon, we were interested to examine the effect of donepezil on Abeta(1-40) induced neurotoxicity in primary cultures of rat septal neurons. Using immunohistochemical staining, almost all the neurons were found to be positive for vesicular acetylcholine transporter (VAChT) in these septal cultures. Septal neuronal cells were cultured for 7 days and then 15 micromol/L of Abeta(1-40) was added to the cell medium for 48 h. The cultured septal neurons were highly susceptible to Abeta toxicity, as shown by morphological examination and lactate dehydrogenase (LDH) assay. Donepezil concentration-dependently reduced the LDH efflux induced by Abeta(1-40), and the effect was significant at 100 nmol/L and above. Donepezil decreased both the negative peak at around 215 nm in the circular dichroism (CD) spectrum and the fluorescence intensity of thioflavin T in the presence of Abeta(1-40). These results suggest that donepezil exerts a neuroprotective effect by reducing the amount of the toxic form of Abeta fibrils in septal neuron cultures. These findings support the idea that the clinical efficacy of donepezil in AD is due to not only activation of cholinergic transmission, but also attenuation of neuronal damage.

Synthesis of optically active methyl 7 beta-hydroxykaurenoate with potent neuroprotective activity.

(-)-Methyl 7 beta-hydroxykaurenoate (3) and its 4-demethyl acetate (-)-4 were both synthesized via methods that contained radical cyclization and intramolecular Diels-Alder reactions as key steps. Both compounds displayed potent neuroprotective activity against N-methyl-D-aspartate toxicity in cultured cortical neurons.

Protective effect of donepezil in a primary culture of rat cortical neurons exposed to oxygen-glucose deprivation.

Donepezil hydrochloride (donepezil: (+/-)-2-[(1-benzylpiperidin-4-yl)methyl]-5,6-dimethoxy-indan-1-one monohydrochloride) is a potent acetylcholinesterase inhibitor used for treatment of Alzheimer's disease. Although acetylcholinesterase inhibitors are used as a symptomatic treatment for Alzheimer's disease, it is not clear whether or not they are effective against progressive degeneration of neuronal cells. In this study, we investigated the neuroprotective effects of donepezil and other acetylcholinesterase inhibitors used for treatment of Alzheimer's disease, i.e., galantamine, rivastigmine, and tacrine. As a neurodegenerative model, we used rat cortical neurons exposed to oxygen-glucose deprivation. Lactate dehydrogenase (LDH) released into the culture medium was measured as a marker of neuronal cell damage. First, the effects of donepezil (10 microM) on three different treatment schedules (from 12 h before to 24 h after oxygen-glucose deprivation (pre-12 h), from 1 h before to 24 h after oxygen-glucose deprivation (pre-1 h) and from 1 h after to 24 h after oxygen-glucose deprivation (post-1 h)) were compared. The pre-12-h treatment most effectively inhibited LDH release. The protective effect of donepezil was confirmed morphologically. Next, the effects of donepezil and the other three acetylcholinesterase inhibitors were compared under the pre-12-h treatment condition. Donepezil (0.1, 1, and 10 microM) significantly decreased LDH release in a concentration-dependent manner. However, galantamine (1, 10, and 100 microM), tacrine (0.1, 1, and 10 microM), and rivastigmine (0.1, 1, and 10 microM) did not significantly decrease LDH release. The neuroprotective effect of donepezil was not antagonized by scopolamine or mecamylamine. These results demonstrate that donepezil has a protective effect against oxygen-glucose deprivation-induced injury to rat primary cultured cerebral cortical neurons. Besides, it is suggested that this effect of donepezil is independent of muscarinic cholinergic system and nicotinic cholinergic system. Thus, donepezil is expected to have a protective effect against progressive degeneration of brain neuronal cells in ischemic cerebrovascular disease and Alzheimer's disease.

Discovery of novel neuronal voltage-dependent calcium channel blockers based on emopamil left hand as a bioactive template.

A series of novel neuronal voltage-dependent calcium channel (VDCC) blockers, with inhibitory activity at low micromolar and moderate solubility in water, was discovered by constructing and screening a focused library based on emopamil (1) left hand (ELH) as a bioactive template.