Identification of a predictive biomarker for the beneficial effect of keishibukuryogan, a kampo (Japanese traditional) medicine, on patients with climacteric syndrome.

Keishibukuryogan (KBG; Guizhi-Fuling-Wan in Chinese) is one of the Kampo (Japanese traditional) medicines used to treat patients with climacteric syndrome. KBG can be used by patients who cannot undergo hormone replacement therapy due to a history of breast cancer. We evaluated whether cytosine-adenine (CA) repeat polymorphism of the estrogen receptor ß gene can be a predictor of the beneficial effect of KBG on climacteric syndrome. We also investigated the relationship between CA repeat polymorphism, the patients' profiles, and the therapeutic effect. We found that CA was an SS, SL, or LL genotype according to the number of repeats. We studied 39 consecutive patients with climacteric disorders who took KBG for 12 weeks. The diagnosis of climacteric disorders was made on the basis of the Kupperman index. KBG significantly improved the patients' climacteric symptoms (i.e., vasomotor symptoms in the patients with the LL genotype and melancholia in the patients with the SL genotype). No relationship between the patients' profiles and CA repeat polymorphism was recognized. CA repeat polymorphism could thus be a potential biomarker to predict the efficacy of KBG in climacteric syndrome, and its use will help to reduce the cost of treating this syndrome by focusing the administration of KBG on those most likely to benefit from it.

Acupuncture Alleviated the Nonmotor Symptoms of Parkinson's Disease including Pain, Depression, and Autonomic Symptoms.

A woman started to feel intractable pain on her lower legs when she was 76. At the age of 78, she was diagnosed as having Parkinson's disease (PD). The leg pain was suspected to be a symptom of PD after eliminating other causes. The patient also suffered from nonmotor symptoms, depression, anxiety, hot flashes, and paroxysmal sweating. Though the patient had received pharmacotherapy including levodopa for 5 years, she still suffered from the nonmotor symptoms and was referred to our department. We treated her with acupuncture based on the Chinese traditional medicine and electroacupuncture five times per week. After the 2-week treatment, the assessment for the symptoms was as follows; visual analogue scale (VAS) score of the leg pain was 16 mm (70 mm, before), Hamilton's rating scales for depression (HAM-D) score was 9 (18, before), timed 3 m Up and Go took 20 steps in 30 sec (24 steps in 38 sec, before), and the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part 1 score was 13 (21, before). Autonomic symptoms, hot flashes and paroxysmal sweating, were also alleviated. Acupuncture may be a good treatment modality for nonmotor symptoms in PD.

Alcohol consumption and abstention among pregnant Japanese women.

BACKGROUND: In order to clarify the alcohol consumption status of pregnant women in Japan and the characteristics of pregnant women who abstained from alcohol after their pregnancy had been confirmed, a nationwide questionnaire-based study of alcohol consumption behavior was performed. We also examined the factors associated with alcohol consumption during pregnancy and abstention after the confirmation of pregnancy. METHODS: After random sampling, 260 institutions participated in the survey; these were selected from a list of survey points fixed by the Japan Association of Obstetricians and Gynecologists. The study was conducted on pregnant women with confirmed pregnancies by using self-administered anonymous questionnaires during the period from February 1 through 14, 2002. RESULTS: Alcohol consumption during pregnancy was reported in 11.1% of the study participants, and abstention after the confirmation of pregnancy, in 76.9%. Significant associations were recognized between higher education and both alcohol consumption during pregnancy and abstention after pregnancy confirmation. Furthermore, alcohol consumption was significantly associated with parity, smoking, and shorter sleep duration, whereas abstention was significantly associated with less frequent alcohol consumption and knowledge regarding the risk of alcohol consumption. CONCLUSION: The results clarified the factors associated with alcohol consumption during pregnancy and abstention after the confirmation of pregnancy in Japan.

Smoking trends before, during, and after pregnancy among women and their spouses.

BACKGROUND: Pregnancy and childbirth can act as strong factors motivating parents to spontaneously quit smoking. The aim of the present survey was to establish smoking cessation guidelines for this group. The objectives were to clarify the smoking status of parents before, during and after pregnancy, as well as the factors associated with continuous smoking during pregnancy and post-partum smoking relapse among women who had stopped smoking during pregnancy. METHODS: A cross-sectional survey with self-administered questionnaires was conducted for the parents of the 908 infants who participated in the official medical and dental examination for 18-month-old infants in Itabashi ward, Tokyo, Japan. RESULTS: The prevalence of smoking among women before, during pregnancy, and at post-partum 18 months at 95% confidence intervals was 29.3% (23.3-35.3%), 9.8% (3.0-16.6%), and 23.1 (16.8%-29.4%), and among their spouses it was 64.3% (60.0-68.6%), 58.1% (53.4-62.7%), and 58.2% (53.5-62.8%), respectively. The positive factors associated with smoking among pregnant women were marriage to a smoker, less education, under stress, and part-time employment rather than unemployment. The positive factors associated with smoking relapse after childbirth among women were breast-feeding <6 months and age under 30 years. CONCLUSION: Compared with Western countries, the rate of smoking cessation during pregnancy was relatively high in Japan. It is necessary that smoking cessation intervention and support for men be initiated at the early stages of their spouses' pregnancies. These observations could influence the targeting and design of maternal smoking intervention.

Association between sleep duration and hemoglobin A1c level.

OBJECTIVE: The association between sleep habits and hemoglobin A1c (HbA1c) level has not been sufficiently examined. In the present study of residents in a local community, the associations between sleep duration and HbA1c level were examined. METHODS: Self-administered questionnaires were mailed to 1062 residents in a rural community in Japan, and completed questionnaires were collected. At the time of collection, the fasting plasma glucose and Hb(1c levels were measured using peripheral blood samples. For the analyses, values that were considered to represent high levels were a fasting plasma glucose level of 126mg/dl and a HbA1c level of 6.5%. Logistic regression analyses were performed to examine the associations between sleep duration and high fasting plasma glucose or high HbA1c levels. RESULTS: The prevalence of high fasting plasma glucose and high HbA1c levels was significantly high (p<0.01) in subjects with a short or a long sleep duration. Logistic regression analyses demonstrated a significant association between high HbA1c level and sleep duration. The adjusted odds ratios for a high HbA1c level showed high values with regard to both short and long sleep durations. CONCLUSIONS: HbA1c level showed a U-shaped association with sleep duration. These results suggest that there may be an appropriate range of sleep duration in individuals with glucose tolerance disorders. It is expected that the present findings will contribute to the treatment and prevention of diabetes mellitus.

Association between subjective well-being and sleep among the elderly in Japan.

OBJECTIVE: The purpose of this study was to examine the association between sleep and subjective quality of life in an elderly Japanese population. METHODS: Elderly people aged 70 years or more (n=1,769) were selected randomly from all areas of Japan. They were visited and interviewed in November 2003. Subjective well-being of the subjects was assessed using the Philadelphia Geriatric Center (PGC) Morale Scale. A logistic regression analysis was performed using sleep-related factors as explanatory variables. RESULTS: A positive linear association was observed between subjective sleep sufficiency and the mean PGC Morale Scale score. The crude and adjusted odds ratios for sleep disorders such as difficulty initiating sleep, excessive daytime sleepiness, and restless legs syndrome were significantly low. The mean score was highest for a sleep duration of 7-8h and became lower at sleep durations of <6 and 9h (inverted U-shaped association). However, the adjusted odds ratio for sleep duration did not show a significant reduction. CONCLUSIONS: In order to improve the subjective well-being of the elderly, better subjective sleep sufficiency and alleviation of sleep disorders are necessary. Different mechanisms may reduce subjective well-being in individuals who sleep less than 6h or who sleep 9h or more.

Use of alcohol and hypnotic medication as aids to sleep among the Japanese general population.

OBJECTIVE: The present study was conducted to clarify the prevalence of the use of alcohol and hypnotic medication as sleep aids, and associated factors, in the general population in Japan. METHODS: The survey was conducted in June 2000, using self-administered questionnaires, targeting a population that was selected randomly from among 300 communities throughout Japan. A total of 18,205 responses indicating alcohol use and 16,804 responses indicating hypnotic medication use were analyzed. RESULTS: The prevalence of alcohol use as a sleep aid one or more times per week was 48.3% among men and 18.3% among women. The prevalence of the use of hypnotic medication one or more times per week was 4.3% among men and 5.9% among women. The prevalence of alcohol used as a sleep aid increased gradually for men and women up to age 55-59 years and 40-44 years, respectively, and then declined with increasing age thereafter. The prevalence of the use of hypnotic medication among both men and women showed a trend toward a gradual increase with age. The use of alcohol as a sleep aid was associated with "difficulty maintaining sleep," but no such problem was associated with the use of hypnotic medication. CONCLUSIONS: Alcohol is a more popular sleep aid than hypnotic medication. The factors associated with the use of alcohol and of hypnotic medication are different.

Prevalence of smoking and associated factors among pregnant women in Japan.

OBJECTIVE: This study was conducted to estimate the prevalence of smoking among pregnant women living in Japan and to analyze the factors associated with their smoking behavior. METHOD: Five hundred institutions with maternity services were randomly sampled from a list of the Japan Association of Obstetricians and Gynecologists. Of these institutions, 260 participated in the survey which was conducted in February 2002. Using a self-reported anonymous questionnaire, a survey on smoking behavior, drinking behavior and sleep status was conducted on pregnant women. Chi-square tests and logistic regression analyses were used to examine the factors associated with their smoking behavior. RESULTS: Data were obtained from a total of 16,414 pregnant women. The prevalence of smoking during pregnancy was 9.9% [95% confidence interval (CI) 9.4%, 10.4%]. The quit rate of smoking among pregnant woman was 61.9% [95% CI 60.4%, 63.4%]. The odds ratios for smoking during pregnancy were significantly higher in women with relatively young age, less schooling, multiparous, exposure to passive smoking, short sleep duration and in women who drank. CONCLUSION: Smoking among pregnant women remains an important public health problem in Japan. It is necessary to promote antismoking measures based on the results of this study.

Signaling pathway of nitric oxide production induced by ginsenoside Rb1 in human aortic endothelial cells: a possible involvement of androgen receptor.

Ginsenosides have been shown to stimulate nitric oxide (NO) production in aortic endothelial cells. However, the signaling pathways involved have not been well studied in human aortic endothelial cells. The present study was designed to examine whether purified ginsenoside Rb1, a major active component of ginseng could actually induce NO production and to clarify the signaling pathway in human aortic endothelial cells. NO production was rapidly increased by Rb1. The rapid increase in NO production was abrogated by treatment with nitric oxide synthetase inhibitor, L-NAME. Rb1 stimulated rapid phosphorylation of Akt (Ser473), ERK1/2 (Thr202/Thr204) and eNOS (Ser1177). Rapid phosphorylation of eNOS (Ser1177) was prevented by SH-5, an Akt inhibitor or wortmannin, PI3-kinase inhibitor and partially attenuated by PD98059, an upstream inhibitor for ERK1/2. Interestingly, NO production and eNOS phosphorylation at Ser1177 by Rb1 were abolished by androgen receptor antagonist, nilutamide. The results suggest that PI3kinase/Akt and MEK/ERK pathways and androgen receptor are involved in the regulation of acute eNOS activation by Rb1 in human aortic endothelial cells.

Factors associated with exclusive breast-feeding in Japan: for activities to support child-rearing with breast-feeding.

BACKGROUND: Benefits of breast-feeding are not only limited to nutrition and sanitation in developing countries but also extend to cost-saving health care and alleviation of anxiety related to childrearing in developed countries. This study aims to elucidate factors associated with exclusive breast-feeding in Japan and use this information to achieve child-rearing support worldwide by promoting breast-feeding. METHODS: This cross-sectional study used data from a survey conducted by Ministry of Health, Labour and Welfare of the Japanese government, the First Longitudinal Survey of Babies in 21st Century. All subjects were infants (n=53,575) born in Japan in 2001 between January 10 and 17 and between July 10 and 17. According to the data, the exclusive breast-feeding rate in Japan during the first 6 months of life was 21.0%. We examined the factors associated with exclusive breast-feeding using univariate and multivariate logistic regression analyses. RESULTS: Among the factors examined, the adjusted odds ratio (OR) for exclusive breast-feeding was low for late childbearing, low birth weight infants, multiple births, smoking parents, living with grandparents, and feeling burdened by childrearing. The adjusted OR was high for factors that included sufficient childcare leave and consultation about childrearing with the spouse, a birth attendant and/or nurse, and a peer in a child-rearing circle. CONCLUSIONS: Exclusive breast-feeding is associated not only with medical factors but also with social factors. This study clarifies the necessity of social support to reduce the child rearing burden and a political system to promote paternal participation in childrearing and to improve the childcare leave system.

Epidemiological study on passive smoking among Japanese infants and smoking behavior of their respective parents: a nationwide cross-sectional survey.

BACKGROUND: Passive smoking is a well-known health hazard for infants. This study was conducted to: (1) estimate the prevalence of passive smoking among Japanese infants and (2) clarify the prevalence of indoor smoking and associating factors among parents having infants. METHODS: Subjects were all 53,575 infants born throughout Japan on January 10-17, 2001 or July 10-17, 2001. When the infants reached 6 months of age, the questionnaires were mailed to the homes. Family members answered questions that included information about the current smoking behavior of the parents. RESULTS: A total of 44,562 questionnaires (83.2%) were analyzed. The prevalence of smoking among the mothers and the fathers were 17.1% and 63.5%. The percentages of mothers and fathers who smoked indoors were 12.1% and 36.2%. The percentage of households where mothers and/or fathers smoked indoors was 37.5%. Multivariate logistic analysis indicated that young age, having a spouse who was a smoker, infants having many siblings, the mother not breast-feeding, and lower annual incomes had significantly higher odds ratios for both the mother's and the father's indoor smoking. CONCLUSIONS: Passive smoking is common among Japanese infants. To protect Japanese infants from passive smoking, further public health measures must be taken.

Hange-koboku-to, a Kampo medicine, modulates cerebral levels of 5-HT (5-hydroxytryptamine), NA (noradrenaline) and DA (dopamine) in mice.

Cerebral monoamine systems play important pathogenic roles in various psychiatric and neurologic diseases, such as depression, anxiety and swallowing disturbance. Hange-koboku-to, a Kampo (Japanese herbal) medicine, has been successfully used for the treatment of these disorders. To elucidate the mechanisms underlying its clinical efficacy for these disorders, the effects of Hange-koboku-to (500 mg/kg, p.o.) on the cerebral monoamine systems were examined. Regional levels of 5-HT (5-hydroxytryptamine), NA (noradrenaline), DA (dopamine) and their metabolites in mouse brain were measured using a high-performance liquid chromatography system. Hange-koboku-to increased the 5-HT and NA levels and decreased 5-HIAA (5-hydroxyindole-3-acetic acid), thus decreasing 5-HT and NA turnover (metabolites/monoamine ratio) in the hypothalamus. The levels of DA, DOPAC (3,4-dihydroxyphenylacetic acid) and HVA (4-hydroxy-3-methoxy-phenylacetic acid) were all increased, resulting in a decreased DA turnover in the striatum. Since decreased 5-HT turnover has been observed after administration of various antidepressants, Hange-koboku-to-mediated reduction of 5-HT turnover may be related to the clinical efficacy of this Kampo medicine on certain psychiatric disorders. Furthermore, the beneficial therapeutic effects of Hange-koboku-to on swallowing disturbance may be related to the increased cerebral DA level brought about by this Kampo medicine.

Excessive daytime sleepiness among the Japanese general population.

BACKGROUND: Excessive daytime sleepiness is one of the principal symptoms of sleep disturbances, and is often associated with serious consequences including traffic and industrial accidents, decreased productivity, and interpersonal problems. However, there are few epidemiologic studies on excessive daytime sleepiness in a large scale sample targeting Japanese general population. METHODS: The survey was performed using a self-administered questionnaire in June 2000, targeting a population randomly selected from among 300 communities throughout Japan. This questionnaire included information about sleep habits and sleep problems. Excessive daytime sleepiness measured according to a question "Do you fall asleep when you must not sleep (for example when you are driving a car)?" RESULTS: A total of 28,714 subjects completed the questionnaire. The prevalence of excessive daytime sleepiness was 2.5% (male=2.8% and female=2.2%). Backward elimination analysis showed that the following were associated with excessive daytime sleepiness: male sex, young age, short sleep duration, subjective insufficient sleep, loss of deep sleep, disagreeable sensations in the legs, interruption of sleep by snoring or dyspnea, and feeling psychological stress. Interruption of sleep by snoring or dyspnea was the strongest associated factor (adjusted odds ratio=2.46, 95% confidence interval=1.76-3.43) of excessive daytime sleepiness. CONCLUSIONS: These results suggest that excessive daytime sleepiness in Japanese is associated with several sleep problems. These findings may be useful in attempts to prevent excessive daytime sleepiness in the general population of Japan.

Mental health status, shift work, and occupational accidents among hospital nurses in Japan.

A questionnaire survey was conducted with questions from the 12-item General Health Questionnaire, among others, targeting 4,407 nurses in 8 general hospitals in Japan, in the hope of improving the work environment of nurses and to provide data that will allow a discussion of the measures necessary for preventing medical errors, thus improving occupational health. For each type of accident, the percentage of those who had made medical errors was significantly higher for the "mentally in poor health" group than for the "mentally in good health" group (p<0.0001). The percentage of nurses in the "mentally in good health" and "mentally in poor health" groups who had experienced occupational accidents over the past 12 months (i.e., whether they were "with errors" or "without errors") was calculated for each of the following four types of medical accident: (1) drug-administration errors, (2) incorrect operation of medical equipment, (3) errors in patient identification, and (4) needlestick injuries. For each type of accident, the percentage of those who had made medical errors was significantly higher for the "mentally in poor health" group than for the "mentally in good health" group (p<0.0001). Multiple logistic regression analyses revealed significant associations between experience of medical errors in the past 12 months and being mentally in poor health, with night or irregular shift work, and age.

[Relationships between finding of calcaneal quantitative ultrasound and lifestyle in Japanese college students].

PURPOSE: The actual situation regarding the lifestyle of college students in Japan cannot be said to be healthy and future reduction of bone mass is a possible matter for concern. However, there have been only a few reports about the relationship between lifestyle during this period and bone mass, and especially none focusing on males not affected by female hormones. The purpose of this study was thus to investigate the relationship between bone mass and lifestyle in college students of both sexes. METHODS: Seven hundred and sixty-six college students of both genders were enrolled in this study as subjects and underwent calcaneal quantitative ultrasound with an AOS-100 device (ALOKA). At the same time physical factors, lifestyle and nutrition were also examined with laboratory findings. RESULTS: Physical factors such as stature, weight, body mass index (BMI), percentage body fat and gripping power were more strongly related to calcaneal quantitative ultrasound among females than in male students. Multiple regression analysis using calcaneal Osteo Sono-Assessment Index (OSI) as the dependent variable, and physical factors, lifestyle and nutrition, and laboratory findings as the independent variables, indicated that regular physical activity was strongly related to OSI in both sexes. The OSI in the alcohol-consuming group was significantly higher than that in the non alcohol-consuming group in males, and demonstrated a significant negative correlation with liver function markers, i.e. ALT (GPT) IU/l. CONCLUSION: It is very necessary to undertake daily physical activity for primary prevention of osteoporosis in both males and females. Bone mass in the alcohol-consuming group was here found to be significantly higher than that in the non alcohol-consuming group, but the study suggested that if the amount of alcohol consumed reaches an extent where liver function markers are affected, bone mass may decrease.

Evaluation of immunological effects of hochu-ekki-to (TJ-41) prophylactic administration in mice.

We evaluated the immunological effects of a Kampo (Chinese) prescription Hochuekki-to (TJ-41) for 32 weeks and 1 week prophylactically in mice, The splenic natural killer cells (NK) of C57BL/6N mice prophylactically treated with TJ-41 for 32 weeks showed little enhanced cytotoxicity against NK-sensitive YAC-1 targets, but mice treated for 1 week showed significantly enhanced cytotoxicity. TJ-41 administration for 32 weeks increased the splenic NK cell population and CD4/CD8 significantly, but TJ-41 for 1 week was not affected. Further, there were no adverse effects of TJ-41 administration for 32 weeks. Whether or not that duration of administration can have the same beneficial effects on humans await further studies.