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Biomedical subjects

Tatsushige Fukunaga

Publications and source records attributed to Tatsushige Fukunaga.

10 recordsLinked to original sources

Underlying factors for the rapid increase of suicide in Mie Prefecture, Japan.

The number of suicides in Japan increased from about 22,000 per year during the period 1988 to 1997 to over 30,000 since 1998. The number of suicides has also been increasing in Mie Prefecture. In the present study we examined the incidence and the circumstances for all suicidal cases during the seven-year period, 1996-2002, that were reported to Mie Prefectural Police Headquarters. In Mie Prefecture, the number of suicides per year averaged 421 cases: from a minimum of 319 in 1997 to a maximum of 501 in 1998. The most frequent month for suicides was July, while the lowest number occurred in February. Suicide was most common in the 50-59 year age group in men, and in the 70-79 year group in women. Regarding the means of suicide, hanging was the most frequent (61.6%) in both sexes. Psychiatric disorders were the most serious causative factors in all generations, accounting for 23.8% in general but being especially prevalent in the younger generation of people under 39 years. Further reasons for suicide were economic problems for the 40-64 age-group in men and suffering from illness for the elderly age-groups in both sexes. In order to prevent suicide, urgent strategies for effective medical treatments and improved working circumstances are required.

Adult↗

Menaquinone-7 regulates the expressions of osteocalcin, OPG, RANKL and RANK in osteoblastic MC3T3E1 cells.

Epidemiological studies show that dietary intake of natto, which contains significant amount of vitamin K(2), reduces the risk of bone formation loss. However, many confounding factors, such as calcium and isoflavone, are found in natto, because it is made from soybeans. In this study, the direct effects of MK-7, a vitamin K(2) analogue, were assessed in osteoblasts. Osteoblastic MC3T3E1 cells were cultured with or without MK-7 for 10 days and the number of cells was calculated. The cell count was not different between MK-7 treated cells and control cells for 1, 2, and 4 days. However, it was significantly suppressed in MK-7 treated cells at 10 days, suggesting that MK-7 suppressed cell proliferation. Real-time PCR analysis showed that mRNAs of osteocalcin (OC), osteoprotegerin (OPG), and the receptor activator of the NFkappaB ligand (RANKL) were induced after MK-7 administration to the culture medium. RANK mRNA expression was also enhanced by MK-7 administration. Immunocytochemical analysis showed that MK-7 increased the protein levels of OC and RANKL. RANK protein was also enhanced, but this induction was suppressed by anti-RANK antibody administration. This suppression was recovered when anti-RANK antibody and MK-7 were administered. These observations suggest that MK-7 may directly affect MC3T3E1 cells and stimulate osteoblastic differentiation, not proliferation.

Animals↗

Promotion of bone formation by fermented soybean (Natto) intake in premenopausal women.

A therapeutic agent of vitamin K2 is approved for the treatment of osteoporosis in Japan. However, little is known about the efficacy of dietary intake of vitamin K2 for bone health. We compared the effects of various levels of fermented soybeans (Natto) intake, which contains plenty of vitamin K2, on bone stiffness and bone turnover markers in healthy premenopausal women. Seventy-three healthy premenopausal women were randomly divided into four groups matched for age and parity categories. Natto was supplied as follows: Group 1 (no intake), Group 2 (once per month), Group 3 (once per week) and Group 4 (three times per week). Subjects took Natto at a lunch for 1 y, and the stiffness index by quantitative ultrasound and bone turnover markers were assessed at baseline, 6 mo and 1 y. There was no statistical difference in the stiffness index during the 1 y observation. However, bone specific alkaline phosphatase (BAP) in Group 4 was higher than that in Group 3 at 1 y and undercarboxylated osteocalcin (Glu) in Group 4 was significantly lower than those in Groups 1, 2 and 3 at 6 mo. Logistic regression analysis showed that the risk of reduction of bone formation markers declined to 0.07 in Group 4 based on that in Group 1. In premenopausal women who had to keep the stiffness index as high as possible before menopause, Natto intake may have contributed to the promotion of bone formation.

Adult↗

Inquest results on the aged: comparison between Mie Prefecture and three Medical Examiners' Offices in Japan.

In Japan, the medical examiner system was enforced only in three large cities, Tokyo metropolitan, Osaka and Kobe Cities. In other areas without this system, autopsy rates are much lower than in the areas with the system. Since the population of the aged (>/=65 years old) has been increasing recently, the subjects for medicolegal investigations seem to be also increasing. In the present study, between Mie Prefecture and those three Medical Examiner's Offices in Japan, the inquest results during the 5-year-period from 1996 to 2000, especially on the aged, were compared. The aged accounted for approximately 50% of all inquest cases in those areas. Autopsy rates for the aged were 16, 24 and 75% in Tokyo, Osaka and Kobe, respectively. Seventy-five to eighty percent was classified in deaths due to disease. Seventy to seventy-five percent of death due to disease was subclassified in circulatory diseases. The highest incidence of vascular diseases was observed in Kobe whose autopsy ratio was the highest. On the contrary, ambiguous causes of deaths, e.g. heart failure or unknown, were still frequent in Mie Prefecture.

Aged↗

Age-dependent changes in electroencephalographic responses to alcohol consumption in subjects with aldehyde dehydrogenase-2 genetic variations.

BACKGROUND: We have recently reported that alcohol consumption resulted in a significant increase in alpha power of the EEGs in aldehyde dehydrogenase-2 (ALDH2)-normal (NN) subjects but not in ALDH2-deficient heterozygote (ND) subjects. The purpose of the present study was to investigate interactive effects of individual factors such as age and ALDH2 genotype on alcohol-induced EEG changes. METHODS: We examined EEG power spectral changes induced by 0.4 ml/kg of alcohol ingestion in 53 NN and 21 ND subjects of two different age groups: younger and older groups. Blood ethanol and acetaldehyde levels were also determined in 17 NN and 13 ND subjects in separate studies. RESULTS: Alcohol consumption markedly increased EEG power in the NN subjects of the older group, especially in theta and slow alpha power, whereas only slight increases were noted in fast alpha and beta power in the NN subjects of the younger group. However, no such differences between the two age groups were observed in the ND subjects. It should be noted that there were no differences in blood ethanol and acetaldehyde level at 30 min after alcohol ingestion between the different age groups in both genotypes. However, there was a significant increase in frequency of alcohol intake in the older group of both genotype groups. The multiple regression analysis indicated that both alcohol use habits and genotype, as well as aging, significantly modulated EEG changes after alcohol ingestion. CONCLUSIONS: The results suggest that both ALDH2 genotype and age as well as alcohol use habits modify alcohol sensitivity in the central nervous system, resulting in greater increases in EEG energy in response to alcohol intake in the older group of the NN subjects.

Acetaldehyde↗

Effects of aldehyde dehydrogenase-2 genotype on cardiovascular and endocrine responses to alcohol in young Japanese subjects.

The present study was designed to investigate the effects of aldehyde dehydrogenase-2 (ALDH2) genotype on cardiovascular and endocrine responses to alcohol ingestion in young, healthy Japanese subjects. For this purpose, we monitored changes in the electrocardiogram (ECG), blood pressure (BP), finger blood flow (BF) and facial skin temperature (FST) during and after alcohol ingestion (0.4 ml/kg body weight). Spectral analyses of beat-to-beat variations of heart rate (HR), BP and BF were applied. Two major spectral components were examined at low frequency (LF: 0.04-0.15 Hz) and high frequency (HF: 0.15-10.4 Hz) bands for HR and BP variability (BPV). Significant effects for ALDH2 genotype were observed in HR variability (HRV) analysis; HF power of HRV was markedly depressed and the LF/HF ratio was significantly higher with alcohol in ALDH2-deficient (ND) subjects, while ALDH2-normal (NN) subjects did not display such changes. Analysis of BP variability showed increased LF and HF power after alcohol ingestion in the NN subjects, but there were no significant differences between genotypic groups. We also examined BF variability (BFV) in six major spectral components; power of the 0.8-2.2 Hz frequency band was significantly affected by genotype and higher power was observed in the ND subjects. Plasma concentrations of both epinephrine and norepinephrine increased after alcohol ingestion only in the ND subjects. Furthermore, plasma concentrations and urinary excretion of epinephrine, but not norepinephrine, were higher after alcohol ingestion in the ND than in the NN subjects. Blood acetaldehyde levels were about 10-fold higher in the ND than in the NN subjects although blood alcohol levels similarly increased in the ND and NN subjects. Our results also indicated that alcohol ingestion increased secretion of pituitary-adrenal hormones including ACTH, beta-endorphin and cortisol in the ND subjects. The present results along with previous studies suggest that alcohol-induced tachycardia in the ND subjects was probably mediated by acetaldehyde-induced rise in epinephrine secretion from the adrenal medulla and/or changes in the autonomic nervous system. Alcohol-induced relative predominance of cardiac sympathetic activity in the ND subjects might be ascribed partly to increased norepinephrine secretion from sympathetic nerve terminals. Effects of acetaldehyde on these cardiovascular and endocrine systems were discussed in terms of their effects on the central nervous system.

Adult↗

Effects of alcohol restriction on ambulatory blood pressure, heart rate, and heart rate variability in Japanese men.

We investigated the effects of alcohol restriction on ambulatory blood pressure (BP), heart rate, and heart rate variability in 33 Japanese male volunteers (37 +/- 1 years, mean +/- SE), who were all habitual drinkers. Subjects were told either to keep their usual drinking habits for 3 weeks (usual alcohol period), or to reduce alcohol intake by at least half of their usual drinking amount (reduced alcohol period). The ambulatory BP, heart rate, and electrocardiographic R-R intervals were measured during a 24-h period with a portable recorder on the last day of each period. A power spectral analysis of R-R intervals was performed to obtain the low-frequency (LF) and high-frequency (HF) components. The percentage of differences between adjacent normal R-R intervals >50 msec (pNN50) was also calculated. The amount of ethanol intake was significantly reduced from 70 +/- 5 mL/day in the usual alcohol period to 19 +/- 3 mL/day in the reduced alcohol period (P < .0001). The daytime systolic BP was significantly lower in the reduced alcohol period than in the usual alcohol period by 4 +/- 1 mm Hg (P < .05). The daytime and nighttime heart rate was significantly lower in the reduced alcohol period than in the usual alcohol (P < .001 for each). The pNN50 and the HF component were significantly higher in the reduced alcohol period than in the usual alcohol period (P < .0001 for each). The LF/HF ratio was significantly lower in the reduced period than in the usual period (P < .01). These results demonstrate that 3-week alcohol restriction produced reductions in ambulatory systolic BP, heart rate, and the index of sympathovagal balance, and augmentations of parasympathetic indices of heart rate variability in Japanese male drinkers.

Adult↗