Prevention of hypercholesterolemia and atherosclerosis in the hyperlipidemia- and atherosclerosis-prone Japanese (LAP) quail by taurine supplementation.

The effects of taurine supplementation on the serum cholesterol levels and the progression of atherosclerosis were investigated in the hyperlipidemia- and atherosclerosis-prone Japanese (LAP) quail. The ingestion of a high-cholesterol diet containing 1% cholesterol by LAP quails for 60 days resulted in a marked elevation in serum non-HDL cholesterol and triglyceride, as well as severe aortic lesions with lipid droplets. An immunohistochemical study showed that the lesion consisted of mainly lipid-rich macrophages and T cells. Sixty-day taurine supplementation (1% in drinking tap water) to LAP quails fed high-cholesterol diet containing 1% cholesterol significantly reduced serum non-HDL cholesterol from 4,549 to 2,350 mg/dl. The serum triglyceride level also decreased after taurine supplementation from 703 to 392 mg/dl. Although the HDL cholesterol level significantly decreased due to the high-cholesterol diet, it recovered to the control level fed a regular diet in response to taurine. Bile acid production was stimulated and hepatic cholesterol was reduced by taurine supplementation. A quantitative analysis using aortic cross-sections showed that areas of oil-red O positive lipid accumulation significantly decreased by 74% after taurine supplementation. These results demonstrated the lipid-lowering and anti-atherosclerotic effects of taurine in a diet-induced hyperlipidemic LAP quail model. The prevention of atherosclerosis by taurine is mainly attributed to an improvement in the serum cholesterol and triglyceride levels, which may be related to changes in the hepatic cholesterol metabolism.

Novel role for CFTR in fluid absorption from the distal airspaces of the lung.

The active absorption of fluid from the airspaces of the lung is important for the resolution of clinical pulmonary edema. Although ENaC channels provide a major route for Na(+) absorption, the route of Cl(-) transport has been unclear. We applied a series of complementary approaches to define the role of Cl(-) transport in fluid clearance in the distal airspaces of the intact mouse lung, using wild-type and cystic fibrosis Delta F508 mice. Initial studies in wild-type mice showed marked inhibition of fluid clearance by Cl(-) channel inhibitors and Cl(-) ion substitution, providing evidence for a transcellular route for Cl(-) transport. In response to cAMP stimulation by isoproterenol, clearance was inhibited by the CFTR inhibitor glibenclamide in both wild-type mice and the normal human lung. Although isoproterenol markedly increased fluid absorption in wild-type mice, there was no effect in Delta F508 mice. Radioisotopic clearance studies done at 23 degrees C (to block active fluid absorption) showed approximately 20% clearance of (22)Na in 30 min both without and with isoproterenol. However, the clearance of (36)Cl was increased by 47% by isoproterenol in wild-type mice but was not changed in Delta F508 mice, providing independent evidence for involvement of CFTR in cAMP-stimulated Cl(-) transport. Further, CFTR played a major role in fluid clearance in a mouse model of acute volume-overload pulmonary edema. After infusion of saline (40% body weight), the lung wet-to-dry weight ratio increased by 28% in wild-type versus 64% in Delta F508 mice. These results provide direct evidence for a functionally important role for CFTR in the distal airspaces of the lung.

Double staining of ginsenosides by Western blotting using anti-ginsenoside Rb1 and Rg1 monoclonal antibodies.

Ginsenosides separated by silica gel TLC blotted to a polyvinylidene difluoride (PVDF) membrane was treated with a NaIO4 solution followed by bovine serum albumin (BSA), resulting in a ginsenoside-BSA conjugate on a PVDF membrane. The blotted bands were stained with anti-ginsenoside Rg1 and Rb1 monoclonal antibodies (MAbs). The newly established double staining with the Western blotting methods was applied for the determination of ginsenosides possessing protopanaxadiol or protopanaxatriol and the number of sugar depending on the stained color and their Rf values in the Panax plants.

Effects of bright light at lunchtime on sleep of patients in a geriatric hospital I.

The effects of lunchtime bright light exposure in patients of a geriatric hospital were investigated. Ten inpatients (six women and four men; mean age +/- SD: 81.2 +/- 8.8 years) with sleep disturbances were studied for 9 weeks. Nurses performed daily ratings for sleep-wakefulness disturbances. Approximately 8000 lx bright light exposure was performed for 3 weeks in the light therapy room. Before and after exposure, ocular function was evaluated. Clinical ratings of sleep-wakefulness improved in eight patients. The score of difficulty in falling asleep and drowsiness in the morning declined during the light exposure. The score of drowsiness in the afternoon decreased during the post-light exposure. Post-exposure ocular disturbances were not found.

Effects of bright light at lunchtime on sleep in patients in a geriatric hospital II.

Inpatients with sleep disturbances in a geriatric hospital received 1 h of exposure to approximately 8000 lx bright light per day for 3 weeks. Polysomnogram was recorded for four female patients. Two (aged 68 and 87 years) were non-demented patients with weak cataracts and the other two (aged 92 and 93 years) were demented patients with severe cataracts. Electroencephalogram results showed that light exposure decreased the proportion of Stage W, while increased the proportion of Stage 2, and these effects continued for at least 3 weeks after the cessation of light exposure. These results suggest that exposure to bright light is effective in improving the disturbed sleep of patients.

Applications of ELISA, western blotting and immunoaffinity concentration for survey of ginsenosides in crude drugs of Panax species and traditional Chinese herbal medicines.

A combination of ELISA, Western blotting and immunoaffinity concentration using an anti-ginsenoside Rb1 monoclonal antibody was applied for qualitative and quantitative surveys of ginsenoside Rb1 and related ginsenosides in roots and traditional Chinese herbal medicines. To improve the low correlation between ELISA and HPLC analysis, the crude extract of roots was immunoaffinity concentrated to make evident the effect of malonyl ginsenoside Rb1. Immunoaffinity column chromatography also concentrated an unknown ginsenoside which had the same cross-reaction with ginsenoside Rb1.

Effects of Momordica charantia powder on serum glucose levels and various lipid parameters in rats fed with cholesterol-free and cholesterol-enriched diets.

The effects of dietary bitter melon (Momordica charantia) freeze-dried powder on serum glucose level and lipid parameters of the serum and liver were studied in rats fed diets supplemented with and without cholesterol. Rats were fed the diets for 14 days containing bitter melon freeze-dried powder at the level of 0.5, 1 and 3% without an added dietary cholesterol (experiment I) and those containing bitter melon at the level of 1% with or without 0.5% cholesterol and 0.15% bile acid (experiment II). No adverse effect of dietary bitter melon powder on growth parameters and relative liver weight were noted. Dietary bitter melon resulted in a consistent decrease in serum glucose levels in rats fed cholesterol-free diets, but not in those fed cholesterol-enriched diets, although no dose-response was noted. Addition of cholesterol to the diets as compared to those without added cholesterol caused hypercholesterolemia and fatty liver. Bitter melon had little effect on serum lipid parameters, except for high density lipoprotein (HDL)-cholesterol; HDL-cholesterol levels tended to decrease by dietary cholesterol, while they were consistently elevated by dietary bitter melon both in the presence and absence of dietary cholesterol, indicating an antiatherogenic activity of bitter melon. In addition, bitter melon exhibited a marked reduction in the hepatic total cholesterol and triglyceride levels both in the presence and absence of dietary cholesterol; the reduction of triglyceride levels in the absence of dietary cholesterol was in a dose-dependent manner. These results suggest that bitter melon can be used as a health food.

Isolation of the pharmacologically active saponin ginsenoside Rb1 from ginseng by immunoaffinity column chromatography.

Immunoaffinity column chromatography using an anti-ginsenoside Rb1 monoclonal antibody has made possible a single-step separation of ginsenoside Rb1 from a crude extract of ginseng roots (Panax ginseng). The combination of immunoaffinity column chromatography and an enzyme-linked immunosorbent assay (ELISA) was also investigated.

Autonomic nervous function after evening bright light therapy: spectral analysis of heart rate variability.

In order to investigate the effects of 5000 lx evening bright light on autonomic nervous function, a spectral analysis was used to assess heart rate variability in consecutive 5-min epochs just after 60 min of bright light therapy was given to 12 young women (range: 20-21 years of age). The study revealed that a low frequency band (LF) increased in bright light conditions (BL) in comparison with controlled conditions (CL). High frequency band (HF), LF:HF ratio and the coefficient of variance (CV R-R) were not significantly different between the two conditions. These results indicate that 5000 lx evening bright light may affect sympathetic nervous system activity in healthy women.

Effect of short duration morning bright light in elderly men: sleep structure.

Sleep structure was measured in five healthy elderly men in their homes. The subjects were exposed to bright light (6000 lx) for 30 min in the morning or instructed to sit in front of a desktop lighting device without light. Relative to the control conditions, bright light exposure significantly decreased time in bed and the number of awakenings. Rapid eye movement sleep was significantly fragmented by stage 1 sleep in the control condition compared with the bright light condition. These findings indicate that a short duration of morning bright light changes sleep structure and is effective in maintaining sleep.

Effect of dietary sesamin on metabolic fate of an exogenous linolelaidic acid in perfused rat liver.

To estimate the relative significance of exogenous and endogenous fatty acid substrates in decreasing hepatic triacylglycerol secretion after sesamin feeding, livers from rats fed diets supplemented with and without sesamin (sesamin: episesamin, 1:1, w/w) were perfused in the presence and absence of an exogenous di-trans isomer of linoleic acid (linolelaidic acid, trans,trans-9,12-octadecadienoic acid). Both exogenous trans fatty acid and dietary sesamin, as compared with respective controls, resulted in a marked increase in hepatic ketogenesis; however, the beta-hydroxybutyrate to acetoacetate ratio was elevated by exogenous fatty acid and decreased by dietary sesamin. On the other hand, hepatic secretions of triacylglycerol, phospholipid and cholesterol were markedly lowered in rats fed sesamin, especially when exogenous fatty acid substrate was provided. The relative significance of the exogenous fatty acid was observed in the dietary sesamin-induced decrease in hepatic secretion of triacylglycerol. These results suggest that increased fatty acid oxidation by dietary sesamin, as reflected by enhanced ketone body production, leads to decreased partition of fatty acid substrates to the esterification pathways, and this in turn reduces the synthesis and secretion of triacylglycerol. The altered metabolism of exogenous fatty acids in the liver was therefore a major determinant for the synthesis and secretion of triacylglycerol.

Dietary conjugated linoleic acid reciprocally modifies ketogenesis and lipid secretion by the rat liver.

The effects of dietary conjugated linoleic acid (CLA) and linoleic acid (LA) on ketone body production and lipid secretion were compared in isolated perfused rat liver. After feeding the 1% CLA diet for 2 wk, the concentration of post-perfused liver cholesterol was significantly reduced by CLA feeding, whereas that of triacylglycerol remained unchanged. Livers from CLA-fed rats produced significantly more ketone bodies; and the ratio of beta-hydroxybutyrate to acetoacetate, an index of mitochondrial redox potential, tended to be consistently higher in the liver perfusate. Conversely, cumulative secretions of triacylglycerol and cholesterol were consistently lower in the livers of rats fed CLA, and the reduction in the latter was statistically significant. Thus dietary CLA appeared to exert its hypolipidemic effect at least in part through an enhanced beta-oxidation of fatty acids at the expense of esterification of fatty acid in the liver.

Effects of morning bright light in healthy elderly women: effects on wrist activity.

To investigate the effects of 8000 lux morning bright light in the elderly, home-based motor activity on sleep was monitored for 5 days in 10 healthy women (mean age: 59.7 years old, range: 50-69 years old). The activity level and movement index on night 4 were significantly lower in bright light conditions, compared with the controlled condition. The activity level during the day was not significantly different between the two conditions. These results indicate that 8000 lux morning bright light improves sleep quality in healthy elderly women.

Effects of morning bright light on sleep in healthy elderly women.

Subjective sleep feeling and polysomnography were measured in 10 elderly women to investigate the effects of 8000 lux morning bright light (BL) exposure. The profile of sleep feeling in the BL condition was better than in the control condition. The proportion of awakening time in the first one-third of night sleep decreased, and the amount of awakening time in the last one-third increased in BL condition. Daytime napping reduced in BL condition. These findings suggested the effectiveness of exposure to bright light on the improvement of sleep quality and daytime vigilance of healthy elderly women.

Effects of moderately bright light on subjective evaluations in healthy elderly women.

Eight healthy elderly women aged 56-72 years (mean age: 67.4 years) participated in this study. They were exposed to moderately bright light (1000 lux) for 1h in the morning every 6 days in their homes. Moderately bright light improved self evaluations for alertness, mood, motivation, happiness, refreshment, concentration and appetite after the second exposure to the light. Sleep maintenance, anxiety and integrated sleep feeling also improved after the fourth exposure to the light. The phase of rectal temperature rhythm did not change in a moderately bright light condition. These results suggest that bright light influences sleep quality and self evaluations without changing the biological rhythm phase.

Western blotting for ginseng saponins, ginsenosides using anti-ginsenoside Rb1 monoclonal antibody.

Ginsenosides separated by silica gel TLC were blotted to a polyvinylidene difluoride (PVDF) membrane which was treated with a NaIO4 solution followed by bovine serum albumine (BSA), resulting in a ginsenoside-BSA conjugate on a PVDF membrane. The blotted bands were stained with monoclonal antibody (MAb). The newly established Western blotting method was used for the determination of ginsenosides and their distribution in various Panax species.

Effects of short duration morning bright light in healthy elderly subjects. I: subjective feeling and ophthalmological examinations.

Seven aged subjects aged 61-78 years were exposed to 6000 lx bright light for 30 min during morning hours at their homes for 1 week. Visual analog scale was recorded before bedtime and after rising to assess subjective feelings. Ophthalmological examinations were made before and after light exposure, to exclude pre-existing ocular disorders and to detect ocular damage. Furthermore, ocular fatigue was self-evaluated immediately before and after exposure. Visual analog scale results indicated that alertness reduced significantly before bedtime. Ophthalmological abnormalities were not found after exposure. These findings suggest that short duration morning bright light exposure reduces night-time vigilance.

Effects of short duration morning bright light in healthy elderly. II: sleep and motor activity.

Subjective sleep feelings and motor activity were measured in seven healthy elderly subjects for 6 days. The subjects were exposed to bright light (6000 lux) for 30 min in the morning or instructed to sit in front of a desktop lighting device without light. The average level of motor activity during the night was significantly decreased in the bright light condition, compared with the controlled condition. However, daytime motor activity did not show significant differences between the two conditions. From these findings, even a short duration of morning bright light is effective in maintaining sleep without changing daytime activity.

Clinical application of pulsed Doppler tissue imaging for assessing abnormal left ventricular relaxation.

Conventional assessment of left ventricular (LV) relaxation by calculating the time constant of LV pressure decay during the isovolumic diastole requires an invasive approach. Conversely, noninvasive parameters obtained by measuring isovolumic relaxation time and transmitral flow velocity often give inaccurate information. Using LV pressure curve, pulsed Doppler echocardiography, and pulsed Doppler tissue imaging in 38 patients with heart disease and 12 control subjects, we calculated the time constant and recorded transmitral flow velocity and motion velocities at the endocardial portions of the ventricular septum and LV posterior wall. Compared with the controls, patients exhibited a prolonged time constant, a decreased peak early diastolic velocity of the LV posterior wall, and a prolonged time interval from the second heart sound to the peak of the early diastolic wave. The time constant correlated well with the isovolumic relaxation time and various parameters calculated from the transmitral flow velocity, except in patients with elevated LV end-diastolic pressure. In all subjects, the time constant correlated negatively with the peak early diastolic velocity of the posterior wall and positively with the time from the second heart sound to the peak of the early diastolic wave. Thus, early diastolic parameters derived from the motion velocity of the LV posterior wall by pulsed Doppler tissue imaging were closely related to the time constant. This technique may allow noninvasive evaluation of abnormal LV relaxation in patients with various heart diseases.

Molecular basis for the management of secondary hyperparathyroidism in chronic renal failure.

Recent clinical and experimental data suggest that the resistance of parathyroid cells to the physiological concentration of calcitriol plays an important role in the pathogenesis and the progression of secondary hyperparathyroidism in chronic renal failure. This resistance is due to the decreased density of the calcitriol receptor in parathyroid cells, which may result from impaired upregulation of calcitriol receptor. Since patients with larger parathyroid glands were more resistance to calcitriol pulse therapy than those with smaller glands and calcitriol receptor density inversely correlated with gland weight, the size of the parathyroid gland may serve as a marker for the degree of resistance to calcitriol. Furthermore, the possible role of phosphorus in the control of parathyroid function has been suggested recently. Thus, it is most important to prevent the progression of parathyroid hyperplasia in chronic renal failure by the early use of active vitamin D, calcitriol pulse therapy, and dietary phosphorus restriction.