Liquid marbles as a micro-reactor for efficient radical alternating copolymerization of diene monomer and oxygen.

Liquid marbles have been shown to be a novel micro-reactor to synthesize polyperoxides by the radical alternating copolymerization of the 1,3-diene monomer with oxygen in a good yield. Oxygen gas is effectively absorbed as a comonomer by the large and permeable gas-liquid interface of the liquid marbles.

Similar in vitro effects and pulp regeneration in ectopic tooth transplantation by basic fibroblast growth factor and granulocyte-colony stimulating factor.

OBJECTIVES: Granulocyte-colony stimulating factor (G-CSF) has been shown to have combinatorial trophic effects with dental pulp stem cells for pulp regeneration. The aim of this investigation is to examine the effects of basic fibroblast growth factor (bFGF) in vitro and in vivo compared with those of G-CSF and to assess the potential utility of bFGF as an alternative to G-CSF for pulp regeneration. MATERIALS AND METHODS: Five different types of cells were examined in the in vitro effects of bFGF on cell migration, proliferation, anti-apoptosis, neurite outgrowth, angiogenesis, and odontogenesis compared with those of G-CSF. The in vivo regenerative potential of pulp tissue including vasculogenesis and odontoblastic differentiation was also compared using an ectopic tooth transplantation model. RESULTS: Basic fibroblast growth factor was similar to G-CSF in high migration, proliferation and anti-apoptotic effects and angiogenic and neurite outgrowth stimulatory activities in vitro. There was no significant difference between bFGF and G-CSF in the regenerative potential in vivo. CONCLUSIONS: The potential utility of bFGF for pulp regeneration is demonstrated as a homing/migration factor similar to the influence of G-CSF.

Association of a polymorphism of BTN2A1 with type 2 diabetes mellitus in Japanese individuals.

AIMS: We previously showed that the C→T polymorphism (rs6929846) of BTN2A1 was significantly associated with myocardial infarction in Japanese individuals by a genome-wide association study. Given that diabetes mellitus is an important risk factor for myocardial infarction, the association of rs6929846 of BTN2A1 with myocardial infarction might be attributable, at least in part, to its effect on susceptibility to diabetes. The purpose of this study was to examine the relation of rs6929846 of BTN2A1 to Type 2 diabetes mellitus. METHODS: A total of 8650 Japanese individuals from two independent subject panels were examined: Panel A comprised 1141 individuals with Type 2 diabetes and 3161 control subjects and panel B comprised 1664 individuals with Type 2 diabetes and 2684 control subjects. RESULTS: The chi-square test revealed that rs6929846 of BTN2A1 was significantly related to the prevalence of Type 2 diabetes in subject panel A (P = 0.0002) and subject panel B (P=0.006). Multivariable logistic regression analysis with adjustment for age, sex, body mass index and smoking status revealed that rs6929846 was significantly associated with Type 2 diabetes (P = 0.0006; odds ratio 1.25) in all individuals, with the T allele representing a risk factor for this condition. Multiple regression analysis with adjustment for age, sex and body mass index revealed that rs6929846 was significantly (P=0.04) related to blood glycosylated haemoglobin content in control subjects. CONCLUSIONS: BTN2A1 may be a susceptibility gene for Type 2 diabetes in Japanese individuals.

Cholesterol, coronary heart disease, and stroke in the Asia Pacific region.

BACKGROUND: Cholesterol levels in many Asian countries are rising. Predictions of the likely effects of this on the incidence of cardiovascular diseases have mostly relied on data from Western populations. Whether the associations between total cholesterol and cardiovascular diseases are similar in Asia is not established. METHODS: The Asia Pacific Cohort Studies Collaboration (APCSC) is an individual-participant data meta-analysis of prospective studies from the Asia-Pacific region. Cox models were applied to the combined data from 29 cohorts to estimate the region-, sex-, and age-specific hazard ratios of major cardiovascular diseases by the fifths of total cholesterol. RESULTS: At baseline, the age/sex-adjusted mean value of total cholesterol was higher in Australia and New Zealand (ANZ) (5.52 +/- 1.05 mmol/l) than in Asia (4.87 +/- 1.05 mmol/l). During 2 million person-years of follow-up among 352 033 individuals, 4841 cardiovascular deaths were recorded. The association of total cholesterol with coronary heart disease and stroke was similar in Asian and ANZ cohorts. Overall, each 1-mmol/l higher level of total cholesterol was associated with 35% (95% CI: 26-44%) increased risk of coronary death, 25% (95% CI: 13-40%) increased risk of fatal or non-fatal ischaemic stroke, and 20% (95% CI: 8-30%) decreased risk of fatal haemorrhagic stroke. CONCLUSIONS: In both Asian and non-Asian populations in the Asia-Pacific region, total cholesterol is similarly strongly associated with the risk of CHD and ischaemic, but not haemorrhagic, stroke. Rising population-wide levels of cholesterol would be expected to contribute to a substantial increase in the overall burden of cardiovascular diseases in this region.

Exercise-induced nausea is exaggerated by eating.

This study was conducted to determine whether and under what circumstances exercise causes nausea. Twelve healthy volunteers (20-37 years), including six athletes, participated in the study. Subjects were studied on seven occasions. Each subject performed low and high-intensity exercise without eating, immediately after eating a beef patty and 60 min after eating. Besides these exercise experiments, effect of meal on nausea was studied in each subject for 180 min without exercise. Exercise was done on a bicycle ergometer for 60 min at 40-50% maximal heart rate reserve and 20 min at 70-80% maximal heart rate reserve. Subjects were tested for nausea by visual analogue scales. Both low and high-intensity exercise caused nausea. Scores for nausea were greater during exercise at fasting state and immediately after eating than those without exercise (p<0.05 during low-intensity exercise, and p<0.01 during high-intensity exercise). Immediately after eating, scores for nausea were greater during high-intensity exercise than during low-intensity exercise (p<0.05). During high-intensity exercise, scores for nausea were greater immediately after eating than without eating (p<0.05). There were no differences in ratings for nausea between the sexes in any of the experimental conditions. Training did not decrease exercise-induced nausea. In conclusion, exercise causes nausea, the severity of which is related to exercise intensity and food intake, but not sex differences nor physical training.

Cold pain prolongs gastric emptying of liquid but not solid meal: an electrical impedance tomography (EIT) study.

Stressful stimuli are reported to affect gastric emptying. However, methods for measuring gastric emptying are, in themselves, stressful. Electrical impedance tomography (EIT) is a method for measuring gastric emptying noninvasively. We used EIT to measure gastric emptying of liquid and solid meals to determine the effect of cold pain stress on gastric emptying. EIT (DAS-01P APT system; University of Sheffield, UK) was carried out in six healthy women (age, 21.6 +/- 0.4 [mean +/- SD] years) who had ingested a liquid (potage, 263 g; 139 kcal) or solid (beef patty, 205 g; 435 kcal) test meal. Cold pain stimuli consisted of repeated immersions of the subject's non-dominant hand into ice water (4 degrees C) for 1 min, with a 15-s recovery period between immersions, for a total of 20 min. For the control stimulus, water at 37 degrees C was used. The cold pain stimulus was applied immediately after the ingestion of a test meal. All studies were carried out randomly in each subject at intervals of more than 1 week. With cold pain, the half emptying time of the liquid meal was significantly greater than that with the control stimulus (47.6 +/- 26.1 min vs 28.1 +/- 10.8 min, P < 0.05). For the solid meal, the half emptying time did not differ between stimuli (101.9 +/- 44.8 min with cold pain vs 92.6 +/- 30.5 min with control stimulus). There were no significant differences in lag time between the liquid and solid meals. Cold pain stress delayed gastric emptying of liquid but not solid meals.

Sleep patterns and total mortality: a 12-year follow-up study in Japan.

A population-based cohort study was conducted to assess the relationship between total mortality and self-reported sleep patterns as regards not only to sleep duration but also subjective sleep quality. A total of 5,322 inhabitants in Gifu Prefecture, Japan, completed a self-administered questionnaire on health status and lifestyles including habitual sleep patterns, and were followed-up for an average of 11.9 years. Relative risks were computed by using Cox proportional hazards models. Both longer and shorter sleep, compared to 7-8 hour-sleep, was related to significantly increased risk of total mortality in males (relative risk [RR] for > or = 10 hours = 1.94, and RR for < 7 hour = 1.90), but not in females. Females complaining of poor awakening state experienced a higher mortality risk compared to those who woke up normally (RR: 1.97). Males who usually fell asleep easily showed a marginally lower mortality risk compared to those who fell asleep normally (RR: 0.70). Female users of sleeping pills were at an elevated risk (RR: 1.89). These findings were almost unchanged after adjustment for sleep duration and other confounders. Poor self-reported quality of sleep seemed to be associated with an increased risk of mortality independently of sleep duration.

Current trend in prevalence of diabetes mellitus in Japan, 1964-1992.

Prevalence of diabetes mellitus in Japan was investigated through studying the published reports from 1964 to 1992 by searching the electronic data base and some leading Japanese journals following certain inclusion criteria. Out of total 74 retrieved reports, 14 were found eligible for review, some containing data of multiple community and/or periods and were converted into total of 40 reports following a predetermined criteria. Review analysis of only the prevalence of diabetes was done paying much attention to age range, survey methodology and response rate. Oral glucose tolerance test (OGTT) was done in 19 (47.5%) with and in 21 (52.5%) reports without initial urine and/or blood sugar screening. OGTT was done using 75, 50, or 100 grams glucose following either Japan Diabetes Society or WHO criteria. The recent prevalence was estimated ranging from 9.6-11.9% in both sexes of 40 years or over, 4.2-13.1% in men and 2.6-12.9% in women. The higher prevalences were found in and around 1990 and the lower values in and around 1970. Regression analysis shows the upward trend of the prevalence of diabetes 2.2% in men (p < 0.01), 1.6% in women (p < 0.01) by 10 years.

Analysis of serum lipid levels in Japanese men and women according to body mass index. Increase in risk of atherosclerosis in postmenopausal women. Research Group on Serum Lipid Survey 1990 in Japan.

Relatively low serum lipid levels are thought to be an important factor contributing to the low incidence of ischemic heart diseases (IHD) in Japanese. It has been proven that obesity or overweight constitutes a basal condition for several risk factors in atherosclerosis. The purpose of this study is to obtain data on serum lipids and lipoprotein profiles in relation to body mass index (BMI), which will enable us to compare the nature and weight of metabolic risk factors in atherosclerosis between Japanese and people in Western countries. Data of total serum cholesterol, triglyceride, and HDL-cholesterol levels of Japanese men and women obtained from a large-scale survey in 1990 were analysed according to BMI for different age groups. Apolipoprotein A-I and B and Lp(a) were also measured in randomly selected samples and their contribution as a risk factor was estimated especially in postmenopausal women. The subjects in two age groups of men (20-39 and 40 59 years) and women (20 39 and 50-69 years) were graded into quintiles according to the BMI. The middle grades of BMI were 21.9-23.3 and 22.4-23.6 for younger and older men, and 20.0-21.1 and 22.2-23.6 for younger and older women, respectively. These values are much lower than those in Western populations, the border between the IVth and the top quintile almost corresponding to the average for Americans. Total cholesterol showed a tendency to shift into higher ranges in all age groups in both men and women as BMI increased, with the highest distribution remaining in the range of 160-199 mg/dl (4.2-5.2 mmol/l). The average cholesterol levels for the top quintile of BMI were still lower than most of the average values in Western populations. The distribution of cholesterol in higher ranges was much greater and the difference according to BMI was smaller in older women than in men. In both men and women, whether younger or older, about 90% of the subjects in the lower quintiles of BMI had triglyceride levels lower than 150 mg/dl. The distribution in the higher range of triglyceride was small in women, not only at younger ages but also in postmenopausal women at the top quintile of BMI. About 85% of the younger women with a middle grade of BMI had an HDL-cholesterol level higher than 50 mg/dl. The values in postmenopausal women were still higher than in men aged 40-59 years. Shift of the distribution curves of HDL-cholesterol according to BMI was similar in all groups and more remarkable than the change in triglyceride. The average HDL-cholesterol levels at the top quintile were almost comparable to the average values in Western countries; the difference in HDL-cholesterol levels between the two populations can mostly be explained by the difference in BMI. Smokers showed a slightly lower total cholesterol and significantly (3-4 mg/dl) lower HDL-cholesterol levels, although there was no difference in distribution of BMI between smokers and non-smokers. Relatively low total cholesterol levels even in smokers has probably contributed to the low incidence of IHD in spite of the high frequency of smoking in Japanese population. Mean Lp(a) levels showed a tendency to increase after age 40 in women. BMI itself did not have a correlation with serum Lp(a) levels. The distribution curve of Lp(a) shifted to higher levels as total cholesterol increased and the tendency was most remarkable in women around or after the menopause. It was remarkable in older women that as the total cholesterol or apo B level increased there was also an increased prevalence of abnormal ECG with a pattern of myocardial ischemia. Postmenopausal women seem to have a great risk of atherosclerosis regarding the lipid and lipoprotein profile even in the Japanese population.

Changes in psychophysiological functions during night shift in nurses. Influence of changing from a full-day to a half-day work shift before night duty.

The effects of changing from a full-day to a half-day shift work before a night duty shift on physiological and psychological functions during the night shift were investigated in 12 healthy unmarried nurses working on the same ward of a university hospital. Three shift patterns, i.e., a day shift following a day shift, a night shift following a day shift, and a night shift following a half-day shift, were studied in terms of physical activity level, sympathetic and parasympathetic activity levels, cortisol, prolactin, NK cell activity, and changes in mood states. The change to the half-day shift increased the duration of sleep before night duty by about 86 min and brought wake-up times forward by about 1 h, resulting in increases in rest and time before work. In addition, the change was revealed to reduce the influence of reversed-phase circadian rhythms on autonomic nervous activity during the night shift. The score for sleepiness was significantly lower at 0500 hours following a half-day shift. There were some marginal but not significant differences in the scores reflecting the degree of vigor, tiredness and irritation during the night shift. Although the prolactin concentration was significantly decreased at the start of the night shift after the half-day shift, there was no difference in cortisol concentration or NK cell activity between the usual night shift after a day shift and the night shift after the half-day shift. The half-day shift was not observed to cause any marked change in the fixed biorhythms of these nurses. The cortisol and NK cell activity levels were low during the night shift, suggesting that the night shift itself is a high stress level, which is prejudicial to biodefense.

Determination of the absolute configuration of urothion.

In order to determine the absolute configuration of urothion (1), the CD spectra of tri-4-chlorobenzoyl derivatives of 2-amino-6-[(3R)-3,4-dihydroxybutyl]pteridin-4(3H)-one and its (3S) compound were compared with that of the tri-4-chlorobenzoyl derivative obtained from the natural product. R-Configuration was concluded for the secondary hydroxyl group on the side chain of 1, which is the same configuration as that of molybdopterin (2). This supports the view that 1 might be a urinary metabolite of 2.

pH-independent controlled-release microspheres using polyglycerol esters of fatty acids.

The release of a drug having low solubility in a certain pH range from controlled-release microspheres using tetraglycerol pentastearate and tetraglycerol monostearate in combination as the matrix base showed pH dependence. Trepibutone, an acidic drug having lower solubility in an acidic medium, was released pH-independently from the microspheres which incorporated magnesium oxide, a solid base. It might have resulted from the pH inside the matrix being kept in an optimum range for drug release due to the incorporation of a solid base. On the other hand, the addition of water soluble acidic or basic excipients was ineffective to achieve pH-independent release. For papaverine, a basic drug, pH-independent drug-release characteristics could be achieved by adding Eudragit L100-55, an enteric polymer. It is thought that the enteric polymer increased the pores for drug release by dissolving in a higher pH range, where the solubility of papaverine is low, and thereby made the release pH-independent. Further, selecting a polyglycerol ester of a fatty acid with an appropriate hydrophile-lipophile balance as the matrix could yield a drug with the desired release rate at any pH.

Anti-hypertensive effect of oral controlled-release microspheres containing an ACE inhibitor (delapril hydrochloride) in rats.

An oral controlled-release drug delivery system based on microspheres of polyglycerol esters of fatty acids (PGEFs), was applied to an anti-hypertensive, delapril hydrochloride. The in-vitro release profile was controlled by selecting a PGEF with an appropriate hydrophilic-lipophilic balance value for the matrix. The microspheres from which 80% of the drug was released in 6 h were orally administered to rats. The plasma concentration of the active metabolite was sustained after administration of the microspheres in comparison with administration of a solution. The in-vivo release profile was in good agreement with the in-vitro release profile. When the microspheres were administered, the pharmacological effect of delapril hydrochloride on the angiotensin I-induced pressor response was also sustained showing consistency with the plasma concentration-time curve.

The relationship between the ambulatory variability and the laboratory reactivity of blood pressure and heart rate.

We examined the relationship between the ambulatory variability and the laboratory reactivity of systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) in 21 male college students. The mean increase during the waking period from that during sleep was defined as variability 1, and the standard deviation of the ambulatory measurements during waking was defined as variability 2. The reactivity to laboratory tests was measured by the pretask-to-task increase in variables. The high SBP variability 1 group showed a significantly higher reactivity of SBP and noradrenaline in the bicycle exercise test (70w). This suggests the possibility that SBP variability 1, can be predicted by increased reactivity to a mild limb exercise test. The high HR variability 1 group, and the high SBP variability 2 group showed significantly lower reactivity of stroke volume (SV) and cardiac output (CO) in the cold face test. Thus, parasympathetic responses such as trigeminal-brainstem-vagal pathway function or baroreflex sensitivity seemed to be reduced in these groups. The high DBP variability 2 group showed significantly lower DBP reactivity in the cold face test, and low noradrenaline reactivity in the mental arithmetic test, which indicated a reduced alpha-adrenergic response in this group. No other significant differences in reactivity to the laboratory mental stress tests were found between the variability 1 and variability 2 groups.

Assessment of sympathetic nerve activity controlling blood pressure in the elderly using head-up tilt.

In order to assess age-related changes in sympathetic nerve activity controlling blood pressure, we recorded muscle sympathetic nerve activity, blood pressure, and heart rate during head-up tilt in 10 healthy elderly (69-75 years) and 16 healthy young (19-23 years) subjects. The elderly had significantly lower responsiveness of muscle sympathetic nerve activity to postural change than did the young subjects. In the elderly, marked rise in blood pressure without increase in muscle sympathetic nerve activity was observed in nearly upright position during head-up tilt, whereas this phenomenon was not observed in the young. We conclude that neural control function of blood pressure during head-up tilt in the elderly differs from that in the young, which may be due to age-related change in baroreflex function.

[Serum cholesterol levels as a risk factor of cardiovascular disease].

By summing up a series of epidemiological evidence a continuous elevation of total serum cholesterol, especially LDL-cholesterol, leads atherosclerosis and causes the narrowing or occlusion of coronary artery which introduces acute myocardial infarction or angina pectoris in the heart. In the brain, it is a risk factor for cerebral thrombosis. On the other hand, a lower level, 160 mg/dl or less of total serum cholesterol relates with the higher incidence of cerebral hemorrhage or subarachnoid hemorrhage, but still with the lower incidence of ischemic heart disease. It is concluded that the higher the total serum cholesterol level and the longer the period of continuous elevation is, the higher the incidence of ischemic heart disease. And there is a U-shape relationship between the level of serum cholesterol and cerebrovascular disease as a whole with a nadir around 160 to 200 mg/dl which means an optimal range of total serum cholesterol. A subject with total serum cholesterol over the optimal level may need some sort of modification in his daily life, in eating or physical exercise but not necessarily requires any pharmacological therapy.

[Relation of the difference between blood pressure before and after 5 minutes' rest to blood pressure status one year later in an epidemiological setting].

The relationship of the difference between blood pressures before and after 5 minutes' rest (before minus after) to resting blood pressures one year later was studied on 439 subjects, aged 35 to 44 years, not being treated for hypertension, in an epidemiological setting. Multiple regression analysis was applied to systolic (SBP) and diastolic blood pressure (DBP) separately. Both the resting SBP level and the SBP difference were significant predictors of the resting SBP one year later in both sexes. For resting DBP one year later, the resting DBP level and DBP difference were found to be significant in females. Multiple logistic analysis was used to identify the factors which predict development from normotension to above borderline hypertension one year later. The SBP difference as well as the resting DBP level were significant predictors in males. These findings suggest that BP difference between before and after 5 minutes' rest may be an important indicator of subsequent BP status, and therefore there would be value in measuring blood pressure before as well as after rest with particular attention to BP difference.

[Trends, risk factors, and prevention of ischemic heart disease in Japan].

The mortality from ischemic heart disease has increased steadily in most industrialized countries from the 19th century up to 1970. In some developed countries, such as the U.S.A. and Australia, it started to decrease in the nineteen seventies and accelerated recently. However, it has increased in some East European countries, such as Rumania, Poland and Hungary. The mortality had been extraordinarily low and the age standardized rate declined since the nineteen seventies in our country as in the U.S.A. These finding strongly suggests the possibility of prevention of ischemic heart disease worldwide. Among the risk factors, hypertension has gradually decreased due to treatment and lower intake salt in Japan. However, the compliance of antihypertensive treatment could be improved and the average intake of salt further decreased. The frequency of hypercholesterolemia was quite low for many years, but increased recently in Japan. However, the national average level of serum cholesterol is probably close to 200 mg/dl, and the new cholesterol level data will be revealed by the national survey in 1990. The world-famous high figure of smoking among Japanese men has been declining for these 20 years down to 61.2% in 1988, along with an exceptionally low rate for women in industrialized countries. The average figure of body weight by stature was in line with the desirable body weight for Japanese and the average intake of lipids has leveled off recently according to the National Nutrition Survey. After all it can be concluded that incidence of ischemic heart disease could be reduced further, even in Japan.