Biomedical subjects

M Okawa

Publications and source records attributed to M Okawa.

At least 73 records · Page 4Linked to original sources

PubMed1999

Melatonin rhythms in delayed sleep phase syndrome.

The aim of this study was to compare circadian and sleep characteristics between patients with delayed sleep phase syndrome (DSPS) and healthy controls. The authors studied 8 DSPS patients and 15 normal controls. Serum melatonin concentration was assessed every hour for 24 h under dim light conditions. The sleep phase and the melatonin rhythm in DSPS patients were significantly delayed compared to those in normal controls. Sleep length was significantly greater in DSPS patients compared to that in controls, but the duration of melatonin secretion did not differ between the two groups. The final awakening, relative to melatonin onset, melatonin midpoint, and melatonin offset, was significantly longer in DSPS patients than in controls. By contrast, the timing of sleep onset relative to melatonin rhythm did not differ between the two groups. The authors found a significant positive correlation between sleep phase markers and melatonin phase markers in DSPS. They postulate that a delayed circadian pacemaker may be responsible for delayed sleep phase syndrome. The alteration of phase angle between melatonin rhythm and sleep phase suggested that not only the delay of the circadian clock but also a functional disturbance of the sleep-wake mechanism underlies DSPS.

Adolescent↗

PubMed1999

Study of structure--hepatoprotective relationships of oleanene-type triterpenoidal glucuronides obtained from several fabaceous plants on rat primary hepatocyte cultures.

The protective effects of nine oleanene-type triterpenoidal glucuronides obtained from several fabaceous plants (Lupinus polyphyllus x arboreus Hybrid, Astragalus complanatus, Wistaria brachybotrys) on in vitro immunological liver injury in primary cultured rat hepatocytes were studied. Although all tested saponins showed hepatoprotective action, the levels of activity of the individual saponins differed. Structure-activity relationships for the sapogenol moiety suggested that the presence of the carbonyl group at C-22 would show a similar hepatoprotective effect to that of the hydroxyl group at C-22 while the presence of the hydroxyl group at C-30 would reduce the hepatoprotective action. This structure-activity relationship substantiated other recently obtained data. Furthermore, the beta-orientation of the hydroxyl group at C-21 is more effective than the alpha-configuration in regard to the hepatoprotection. Furthermore, structure-activity relationships for the sugar moiety substantiated previously obtained data that the hydroxyl group at C-5" enhances the hepatoprotective action.

Animals↗

PubMed1999

Hepatoprotective and hepatotoxic actions of oleanolic acid-type triterpenoidal glucuronides on rat primary hepatocyte cultures.

The protective effects of oleanolic acid-type saponins and their derivatives on in vitro immunological liver injury of primary cultured rat hepatocytes were studied. A known antihepatotoxic saponin (chikusetsusaponin IVa, 1) showed hepatoprotective activity in this model. Although a rhamnosyl derivative (2) of 1 similarly showed hepatoprotective activity, its prosapogenin (5) did not show any hepatoprotective activity. On the contrary, 5 exhibited cytotoxicity toward liver cells. In the absence of antiserum, monodesmosyl saponins showed hepatotoxicity, while the bisdesmosyl saponins except for 1, did not show such hepatotoxicity. In order to clarify the effects of the sugar residues at C-3 and C-28 responsible for hepatoprotective and hepatotoxic actions, oleanolic acid 3-O-glucuronide (2a) and oleanolic acid 28-O-glucoside (2b) were prepared and tested. 2b showed neither hepatoprotective action nor hepatotoxicity. In contrast, 2a was effective at 90 microM on hepatoprotection, although it showed strong hepatotoxicity. Oleanolic acid (2c) itself showed both hepatoprotective action and weak hepatotoxicity. Therefore, the hepatoprotective activity of these types of saponins could represent a balance between hepatoprotective action and hepatotoxicity.

Animals↗

PubMed1999

HPLC profile analysis of hepatoprotective oleanene-glucuronides in Puerariae Flos.

In order to confirm the constitution of hepatoprotective oleanene glucuronide (OG), HPLC profile analyses of the total OG fractions of both Puerariae Thomsonii Flos (the flowers of Pueraria thomsonii) and Puerariae Lobatae Flos (the flowers of P. lobata) were performed. No remarkable difference in the HPLC profiles with respect to OGs in the flowers was shown, in contrast to those of the roots. By repeated chromatography of the total OG fraction of Puerariae Thomsonii Flos, soyasaponin I (1), kaikasaponin III (2) and kakkasaponin I (3), which had been already isolated from Puerariae Lobatae Flos, were obtained. The hepatoprotective activity of 2 towards immunologically induced liver injury was significantly more effective than that of 1. This information supported previously obtained structure-hepatoprotective relationship data which was measured on another model. The structure-activity relationship information which suggested that the hydroxymethyl group of the galactosyl unit would enhance the hepatoprotective activity was also substantiated.

Animals↗

PubMed1998

Periodic fatigue symptoms due to desynchronization in a patient with non-24-h sleep-wake syndrome.

A 43-year-old man complaining of recurrent fatigue symptoms and sleep disorders occurring periodically every 4 weeks was studied. Using a wrist worn actigraphy and an ambulatory rectal temperature monitoring apparatus, his sleep-wake cycle and rectal temperature were measured continuously for 4 months, while diagnostic evaluation and therapeutic interventions were conducted. It was found that after he gave up an attempt to keep to a 24-h-day, a free-running sleep wake pattern appeared but his fatigue symptoms disappeared. An analysis of the relationship between his sleep-wake cycle and the rectal temperature rhythm found that his fatigue symptoms did not appear when both rhythms were synchronized with each other. Artificial bright light therapy entrained him to a 24-h day without relapsing of fatigue symptoms. Desynchronization between a 24-h sleep-wake schedule and his circadian pacemaker may have caused his periodically appearing fatigue symptoms.

Adult↗

PubMed1998

Circadian rhythm sleep disorders in adolescents: clinical trials of combined treatments based on chronobiology.

Delayed sleep phase syndrome (DSPS) and non-24-h sleep-wake rhythm are circadian rhythm sleep disorders that are common in adolescents. Most patients have difficulty adjusting to school life, poor class attendance or refuse to go to school. Since a treatment has not been established, the present paper is presented to propose a strategy for treating circadian rhythm sleep disorders in adolescents, based on our clinical studies. Twenty subjects (12 males and eight females, mean age 16.2+/-1.7 years) participated in the study. The onset of sleep disorder occurred between the ages of 11 and 17. The most common factors affecting the onset of disorders were changes in social environment. The subjects kept a sleep-log for the periods before and during treatments. The treatments were based on chronobiology: resetting the daily life schedule, chronotherapy, regulation of the lighting environment, methylcobalamin, and/or melatonin. Bright light exposure was successful in 10 patients, of whom four were treated with methylcobalamin. Melatonin treatment was successful in two patients (one with and one without chronotherapy). Thirteen of the 20 patients were successfully, treated with therapies based on chronobiology. After consideration of these results, a step-by-step procedure of combined treatments for the circadian rhythm sleep disorders is proposed.

Absenteeism↗

PubMed1998

Latent cerebral artery stenoses on magnetic resonance angiography in a patient diagnosed as probable Alzheimer disease.

A 65-year-old woman with hypertension developed slowly progressive memory disturbance and disorientation. She was diagnosed as having Alzheimer-type dementia according to clinical criteria. Later her cognitive deterioration was noted to fluctuate in parallel to her blood pressure. Magnetic resonance angiography and single photon emission computed tomography showed bilateral middle cerebral artery stenoses and middle cerebral artery watershed dominant hypoperfusion. It is postulated that the patient's cognitive disturbance may have originated from vascular lesions.

Aged↗

PubMed1998

Clinical characteristics of circadian rhythm sleep disorders.

From our practice at the sleep disorders clinic in Kohnodai Hospital, National Center of Neurology and Psychiatry (NCNP), we report the clinical characteristics of circadian sleep-wake rhythm disorders. Nearly 90% of circadian rhythm sleep disorders were diagnosed as delayed sleep phase syndrome (DSPS) or as non-24 sleep-wake syndrome (non-24). While DSPS was equally common in males and females, non-24 was more frequently seen in men. It was of psychiatric interest that a considerable number of patients had depressive states in the course of their circadian rhythm sleep disorders. Difficulty in adapting to social life was more severe in patients with non-24 than in those with DSPS.

Adult↗

PubMed1998

Continuous measurement of temperature in non-24 hour sleep-wake syndrome.

The onset of the low temperature (LT) zone which was defined as a period when the rectal temperature was below its daily mean is a convenient circadian phase marker. In this study, we document three cases of non-24 h sleep-wake syndrome in which identification of the LT zone as an evening circadian phase marker contributed to clinical judgments. We found that the LT zone was correlated well with dim light melatonin onset. Moreover, calculating the LT zone was useful in determining phase position in irregular sleep pattern and in determining the timing of bright light therapy.

Adult↗

PubMed1998

Human time production under constant routine.

Previous reports have suggested that human time production of several seconds fluctuates across the day. In order to test whether human time production was controlled by the circadian process or by the homeostatic process, we investigate diurnal fluctuation of human time production under constant routine conditions. We found a common circadian feature in time production tests of 10 s by calculating Z-score for each subject; afternoon troughs and morning peaks. These results may suggest that human time production was modulated by the circadian process.

Adult↗

PubMed1998

Twenty-four hour profiles of four hormones under constant routine.

We studied the circadian features of melatonin, cortisol, thyroid stimulating hormone (TSH), and growth hormone (GH) together with rectal temperature during 36 h continuous forced wakefulness without physical exercise under dim light condition (constant routine). Subjects consisted of four healthy men aged 22-24 years. Blood sampling was conducted hourly, and food and water were supplied bi-hourly during the constant routine. Melatonin, TSH and cortisol displayed clear circadian rhythms under constant routine condition. While GH secretion was unlikely to be driven solely by the circadian pacemaker, its suppression round BT nadir may indicate that GH secretion was modulated to some extent by circadian rhythm.

Adult↗

PubMed1998

Effects of evening light on body temperature.

Six healthy male subjects aged 21-35 years participated in the present study. The subjects were exposed to dim light (150 lux) or bright light (3000 lux) at eye level, from 19.00 to 21.30 h for 5 days. Rectal temperature and wrist activity were monitored throughout the study period. Rectal temperature nadir was delayed significantly after the bright light exposure. Ease in sleep initiation and overall sleep quality, measured by questionnaire, were aggravated significantly by the evening bright light exposure. These results suggest that strong illumination at night may disturb nocturnal sleep.

Adult↗

PubMed1998

Melatonin treatment for circadian rhythm sleep disorders.

We administered 1-3 mg melatonin to 11 patients (eight men, three women, aged 16-46 years) with circadian rhythm sleep disorders; nine with delayed sleep phase syndrome and two with non-24-hour sleep-wake syndrome. Sleep logs were recorded throughout the study periods and actigraph and rectal temperature were monitored during treatment periods. Melatonin was administered 1-2 h before the desirable bedtime for expected phase-shifting, or 0.5-1 h before habitual bedtime for gradual advance expecting an hypnotic effect of the melatonin. Melatonin treatments were successful in 6/11 patients. Timing and dose of melatonin administration, together with its pharmacological properties for circadian rhythm sleep disorders, should be further studied.

Adolescent↗

PubMed1998

Trials of bright light exposure and melatonin administration in a patient with non-24 hour sleep-wake syndrome.

We report a patient with non-24 h sleep-wake syndrome (non-24) whose free-running sleep-wake cycle was successfully treated with both scheduled bright light exposure and melatonin treatment. In the present study, morning bright light as well as evening melatonin phase-advanced sleep-wake cycles and melatonin rhythm. Both these procedures achieved appropriate entrainment to a 24 h day. However, the patient did not continue morning bright light therapy after the discharge. Rising at appropriate times in the morning for bright light therapy was difficult for him to continue. Melatonin treatment was better tolerated because of its ease of application.

Adult↗

PubMed1998

Partial hydrolysis of soyasaponin I and the hepatoprotective effects of the hydrolytic products. Study of the structure-hepatoprotective relationship of soyasapogenol B analogs.

As a part of our studies of hepatoprotective drugs, we prepared some soyasapogenol B analogs from soyasaponin I. We examined the hepatoprotective effects of these analogs, using immunologically-induced liver injury, in primary cultured rat hepatocytes. Soyasaponin III and soyasapogenol B monoglucuronide were more effective than soyasaponin I. Both compounds were significantly effective even at 30 microM. The action of soyasapogenol B was almost equal to that of soyasaponin I, although glucuronic acid did not show any activity even at the highest dose (500 microM). When the two compounds were mixed, the hepatoprotective action did not change, compared with soyasapogenol B. Therefore, we concluded that the linkage between glucuronic acid and soyasapogenol B could enhance the hepato-protective activity.

Animals↗

PubMed1998

Randomized, dim light controlled, crossover test of morning bright light therapy for rest-activity rhythm disorders in patients with vascular dementia and dementia of Alzheimer's type.

The authors compared the therapeutic effect of morning bright and dim light exposure on rest-activity (R-A) rhythm disorders in patients with vascular dementia (VD) and patients with dementia of Alzheimer's type (DAT). Participants in this study were 12 patients with VD (M/F = 5/7; average age = 81 years) and 10 patients with DAT (M/F = 4/6; average age = 78 years). They were exposed to 2 weeks of bright light (BL; 5000-8000 lux) and 2 weeks of dim light (DL; 300 lux) in the morning (09:00-11:00) in a randomized crossover design in which the 2-week treatment period took place between pretreatment (1 week) and posttreatment (1 week) periods. Continuous R-A monitoring was performed at 1-minute intervals throughout the study using an actigraph around the nondominant wrist. The BL exposure for 2 weeks induced a significant reduction in both nighttime activity and percentages of nighttime activity to total activity compared with the pretreatment period, as well as compared with the DL condition in the VD group, but not in the DAT group. These findings support the assumption that the therapeutic efficacies of morning BL exposure are prominent in VD patients and are mainly due to its photic effect rather than nonphotic effects such as the intensification of social interaction accompanying light therapy.

Activity Cycles↗

PubMed1998

[Effects of melatonin on circadian time keeping system].

This paper is intended to provide an overview of a physiological role of melatonin (MLT) in sleep-wake regulation. In human MLT studies, MLT has significantly increased sleepiness and fatigue during the daytime but not at night, which indicates time-dependent sleep-promoting effect of MLT. Op the other hand, MLT is known to have phase-shifting effect of biological clock. Phase response curve (PRC) for MLT administration was introduced in human studies. Successful melatonin treatments for circadian rhythm sleep-disorders based on PRC have been reported. MLT is known to decrease core body temperature. Effects of MLT on sleep-wake cycle may be mediated by a combination of sleep-promoting and phase-shifting actions and may involve the temperature lowering effect.

Animals↗

PubMed1997

Sleep and mood disorders.

Mood disorders are found in one-third to one-half of patients with chronic sleep problems. Likewise, most patients with mood disorders experience insomnia, but a minority obtain significantly increased amounts of sleep. Although mood disorders cause significant morbidity and mortality, they often go undiagnosed. Attention to sleep complaints could lead to better identification of mood disorders. Management of sleep problems in patients with mood disorders should focus on treating underlying mood disorders with attention to the nature of the sleep complaint. Patients with depression show characteristic abnormalities in sleep continuity, slow-wave sleep and REM sleep patterns. Differences in sleep patterns cannot reliably distinguish patients with depression from those with other psychiatric disorders, but sleep changes may provide a window on neurobiologieal abnormalities in depression.

Journal Article↗