Rika Aizawa

CSF hypocretin-1 (orexin-A) concentrations in narcolepsy with and without cataplexy and idiopathic hypersomnia

We measured cerebrospinal fluid (CSF) hypocretin‐1 levels in 11 patients with narcolepsy–cataplexy, five with narcolepsy without cataplexy and 12 with idiopathic hypersomnia (IHS). All patients were Japanese. As reported in Caucasian patients, undetectable or very low hypocretin‐1 levels were observed in most (9 out of 11) Japanese narcolepsy–cataplexy patients. Our hypocretin‐deficient narcoleptics included three prepubertal cases within few months after the disease onset. All nine hypocretin‐deficient patients were human leuckocyte antigen (HLA) DR2 positive, while two who had normal CSF hypocretin‐1 levels were HLA DR2 negative. In contrast, none of the narcolepsy without cataplexy and IHS subjects had undetectable low levels. Low CSF hypocretin‐1 is therefore very specific for HLA DR2 positive narcolepsy–cataplexy, and the deficiency is likely to be established at the early stage of the disease.

Inhibitory effects of natural carotenoids, α-carotene, β-carotene, lycopene and lutein, on colonic aberrant crypt foci formation in rats

Inhibitory effect of four carotenoids prevalent in human blood and tissues against the formation of colonic aberrant crypt foci was examined in Sprague-Dawley rats. They received three intrarectal doses of N-methylnitrosourea in week 1, and a daily gavage of de-escalated doses of carotenoids during weeks 2 and 5. Lycopene, lutein, α-carotene and palm carotenes (a mixture of α-carotene, β-carotene and lycopene) inhibited the development of aberrant crypt foci quantitated at week 6, but β-carotene did not. The results suggested that lycopene and lutein in small doses may potentially prevent colon carcinogenesis.

Chemoprevention by pravastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, of N-methyl-N-nitrosourea-induced colon carcinogenesis in F344 rats.

A potential chemopreventive action of pravastatin (Pr), a 3‐hydroxy‐3‐methylglutaryl‐coenzyme A redutase inhibitor, on colon carcinogenesis was evaluated in F344 rats. All rats at 7 weeks of age received an intrarectal dose of 2 mg of N‐methyl‐N‐nitrosourea 3 times weekly for 2 weeks in experiment I (2 groups of 16 rats each), and for 3 weeks in experiment II (4 groups of 30 rats each). They were given drinking water containing 0 ppm (control) or 200 ppm Pr during weeks 1 to 40 in experiment I, and containing 0 ppm (control), 25 ppm, 5 ppm and 1 ppm Pr during weeks 4 to 40 in experiment II. The body weight gains, and food and water intakes were similar in all the groups. The incidence of colon carcinomas at termination of the experiment at week 40 was not different in the 200 ppm Pr and control groups in experiment I (63% vs. 69%), while it was significantly lower in the 25 ppm and 5 ppm groups, but not in the 1 ppm Pr group, compared with the control group in experiment II (50%, 48%, and 77% vs. 80%). This inhibitory effect of Pr against colon carcinogenesis was not related to the cholesterol‐lowering effect of this agent. We postulate that Pr inhibits the promotion stage of colon carcinogenesis, perhaps through modulation of cholesterol synthesis in situ in the colonic mucosa, thereby suppressing farnesyl isoprenylation of growth‐regulating proteins such as p21 ras.

Effects of Yoku-kan-san-ka-chimpi-hange on the sleep of normal healthy adult subjects

Abstract Yoku‐kan‐san‐ka‐chimpi‐hange (YKCH) is a drug used for insomnia in Japanese traditional herbal medicine. The present study evaluated the effects of YKCH on sleep by all‐night polysomnography using the double‐blind method. Yoku‐kan‐san‐ka‐chimpi‐hange increased the total sleep time significantly, and tended to cause an increase in sleep efficiency and of stage 2 sleep, as well as a decrease of sleep latency and of stage 3 + 4 sleep. There was no apparent influence on rapid eye movement (REM) sleep. In terms of non‐REM sleep, the effects of YKCH exhibit a profile similar to those of benzodiazepines.

Diazepam reduces both arterial blood pressure and muscle sympathetic nerve activity in human.

It is known that benzodiazepines have a hypotensive effect, but the mechanism has not been well elucidated yet. To clarify whether this effect is due to central or peripheral mechanism, we administered 5 mg of diazepam or saline intravenously to healthy volunteers and assessed the change in blood pressure, heart rate, muscle sympathetic nerve activity and heart rate variability. After diazepam administration, systolic and mean blood pressure decreased significantly. Muscle sympathetic nerve activity was also significantly reduced but heart rate did not change, whereas the variables of spectral analysis of heart rate variability did not show significant change. We concluded that the hypotensive effect of diazepam in human is mainly due to the central mechanism.

The effects of oral melatonin on the autonomic function in healthy subjects.

We investigated the influence of melatonin on the human autonomic functions by measuring muscle sympathetic nerve activity (MSNA). Five healthy male volunteers took 3 mg of melatonin, and their plasma melatonin concentration, blood pressure, heart rate, and burst rate of MSNA were then recorded. The peak level of melatonin concentration showed a marked interindividual variation. Blood pressure was reduced significantly, while heart rate and burst rate of MSNA did not change significantly. These results indicate that melatonin has a hypotensive effect on blood pressure, and the central cardiovascular regulatory mechanism such as lowering of the baroreflex setpoint would be involved in the effect.

Hypocretin-1 (orexin-A) concentrations in cerebrospinal fluid are low in patients with Guillain-Barré syndrome

Abstract It is reported that cerebrospinal fluid (CSF) hypocretin‐1 (orexin‐A) concentrations in patients with narcolepsy are significantly low. Human narcolepsy is also known to be closely associated with a specific human histocompatibility leukocyte antigen (HLA), suggesting that autoimmunity is involved in the pathophysiology of the disease. Thus, it is important to know whether hypocretin changes are found in definite neuroimmunological diseases such as multiple sclerosis and Guillain–Barré syndrome (GBS). The results of the present study indicate that some patients with GBS have lower levels of CSF hypocretin‐1.

CSF hypocretin measures in patients with obstructive sleep apnea.

The majority of patients with narcolepsy‐cataplexy were reported to have very low cerebrospinal fluid (CSF) hypocretin‐1 (orexin‐A) levels. The hypocretin‐1 levels of secondary excessive daytime sleepiness (EDS) disorders are not known. In this study, we found that CSF hypocretin levels in the patients with obstructive sleep apnea syndrome were within the control range. The low hypocretin levels seem to reflect only the presence of cataplexy and DR2 positive in narcoleptics but not EDS itself.

Effects of donepezil (Aricept) on the rapid eye movement sleep of normal subjects

Abstract Donepezil (Aricept) is a therapeutic drug for the treatment of Alzheimer’s disease (AD). However, there have been only two reports describing the effects of donepezil on sleep as assessed by nocturnal polysomnography (PSG). With this in mind, the effects of donepezil on the sleep of healthy subjects was evaluated using PSG. The results indicated that the percentage of rapid eye movement sleep to total sleep time was increased significantly by a single dose of 5 mg of donepezil when given to healthy subjects immediately before retiring to bed.

Sleep habits of students attending elementary schools, and junior and senior high schools in Akita prefecture.

Abstract It is widely accepted that students in Japan sleep fewer hours than what they actually need. However, epidemiological data on sleep habits among students are scarce. The sleep habits and related problems among 1650 students in Akita prefecture were studied. The results revealed that schoolchildren attending elementary schools seemed to sleep for a sufficient number of hours, whereas students attending junior or senior high schools were not sleeping enough. In particular, approximately half of the students attending senior high schools answered that they slept 6 h or less on weekdays and nodded off during classes more than twice a week.