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Introduction: Various emotions may arise in the context of extensive curriculum of paramedical education. Their association to biological aspects such as Vitamin D status is to be examined with regard to the prevalence of Vitamin D deficiency in the region. This research aims to evaluate the prevalence of anxiety symptoms and their relationship with Vitamin D status among Lebanese health-care students.Methods: A total of 157 university students aged 18-25 years old completed a questionnaire related to medical and psychiatric history, nutritional intake, lifestyle habits, and social difficulties. Anxiety symptoms were assessed by Hamilton Anxiety Rating Scale. Vitamin D serum levels were analyzed using ELISA technique.Results: Anxiety symptoms were present in 37.5% of students with 2.5% presenting severe anxiety. Anxiety symptoms were significantly associated to health problems (p = 0.0038), social difficulties (p = 0.001), and a family history of psychiatric disorders (p < 0.0001). Low Vitamin D levels were detected in 49.3% of participants; 77.5% having a Vitamin D insufficiency while the rest presenting a Vitamin D deficiency. Students with anxiety symptoms had significantly lower Vitamin D levels as compared to those having no anxiety manifestations (17.9 ng/mL ± 7.9 vs. 24.2 ng/mL ± 9.9, p = 0.0023). However, no significant correlation was registered between anxiety symptoms scores and Vitamin D levels.Conclusion: Anxiety symptoms were found to be relatively prevalent among health-care students and associated to low Vitamin D levels. Further studies are warranted to clarify the beneficial effect of Vitamin D supplementation in the prevention, management, and treatment of anxiety symptoms among health-care students.

Objective: Coenzyme Q10 (CoQ10) appears to be a promising agent in neurodegenerative disorders because they are associated with defects in the inner mitochondrial membrane and in oxidative phosphorylation. This report aims to highlight the role of CoQ10 in amyotrophic lateral sclerosis. Methods: A 75 year old medical scientist (1 st author TK) unbiased for treatment with CoQ10, volunteered for CoQ10 ad- ministration. He himself recorded his symptoms, mood, sensations, body weight, using limb Norris score, hand grip power for both hands. He received highly bioavailable CoQ10 in a dose of 500 mg twice daily initially followed by 200mg twice daily for treatment in 2005. (solubilized ubiquinol, Tishcon Corp. NY). His plasma CoQ10 level was ob- tained initially and after treatment with CoQ10. Results: He presented with weakness of left leg along with cramps in the left calf muscle with steppage gate in September 2000. He had wasting of muscles, fasciculations and exaggerated reflexes. He had rapid deterioration in hand grip power in the left hand and weakness in left lower limb followed by right limbs with inability in walking and routine activities. Treatment with ubiquinol in 2005, resulted in better hand grip power, mood and sensation within a month and in 2006, he reported that hand grip power and wasting of muscles are not progressing as rapidly as before administering CoQ10. Interpretations: Treatment with highly solubilized ubiquinol can provide benefit to patients with ALS. Further controlled trials would be necessary to confirm our findings.

A 6-month, twice-a-week exercise program emphasizing swimming was conducted for 11 men (57-73 years) and 24 women (51-68 years). The control group comprised 11 male (59-70 years) and 11 female (53-70) volunteers. The exercise program significantly improved the systolic and diastolic blood pressure (SBP/DBP) and lipid and glucose metabolism, with no change in the controls. Brachial-ankle pulse wave velocity (baPWV), as an index of systemic arterial stiffness, was measured during medical examinations before and after each exercise session using a volume-plethysmographic apparatus. SBP and DBP of the extremities were significantly decreased after exercise, but did not change in the controls. Average baPWV decreased significantly in the exercise group, from 1661±50 to 1581±40 cm per sec. No change was seen in the controls. The sway path of the center of balance was analyzed using a force plate. The length of postural sway, the length of postural sway per sec and the area of postural sway were measured with eyes open and eyes closed, and the rectangular area was calculated. The eyes open/eyes closed ratio (Romberg sign) was also calculated. All parameters of body sway were significantly lower after 6 months in the exercise group, with no change in the controls. The Romberg sign did not change for either group. In addition to promoting better health, as shown by the clinical data, this type of exercise program improves balance function, which could help prevent falls of the elderly.

We investigated the mechanism of the antihypertensive effect of less-sodium soy sauce containing gamma-aminobutyric acid (GABA) in spontaneously hypertensive rats (SHRs). When SHRs were given a diet with less-sodium soy sauce containing GABA (GABA-rich soy sauce group) for 6 weeks, the systolic blood pressure decreased as compared with that in rats fed diets with less-sodium soy sauce or a solution of salt. Renal sympathetic nerve activity (RSNA) and positive Na balance were reduced, and the urinary Na excretion tended to increase in the GABA-rich soy sauce group. Vascular hypertrophy of the thoracic aorta and the coronary and renal interlobular arteries tended to reduce in the GABA-rich soy sauce group. These results suggest that inhibition of Na retention by natriuresis, as a result of inhibition of RSNA by the GABA in the soy sauce contributed to the antihypertensive effect of GABA in the SHRs. Intake of less-sodium soy sauce containing GABA might help to reduce overall cardiovascular risk.

The distribution of an antihypertensive dipeptide, Val-Tyr (VY), in the tissues of spontaneously hypertensive rats (SHR) was investigated in this study. A single oral administration of VY (10 mg/kg) to 18-week-old SHR resulted in a prolonged reduction of systolic blood pressure (SBP) up to 9 h (SBP0h 198.0+/-3.6 mmHg; SBP9h 154.6+/-3.5 mmHg). As a result of VY determination, a roughly 10-fold higher increment of plasma VY level was observed at 1 h than that at 0 h, whereas thereafter the level declined rapidly. In tissues, VY was widely accumulated in the kidney, lung, heart, mesenteric artery and abdominal aorta with the area under the curve over 9 h of more than 40 pmol h/g tissue; of these a higher VY level was observed in the kidney and lung. In addition, a mean resident time (MRT) for each tissue (>5 h except for liver) revealed that VY preferably accumulated in the tissues rather than in the plasma (MRT 3.8 h). Significant reductions of tissue angiotensin I-converting enzyme activity and angiotensin II level were found in the abdominal aorta as well as in the kidney, suggesting that these organs could be a target site associated with the antihypertensive action of VY.

The aim of the present study was to determine the disease course of hypertensive male university students followed for 8 to 26 years (average, 17 years) after graduation. Subjects were classified into two groups. 1) A hypertensive group (H-group) consisting of 338 conclusively hypertensive male students followed from 1973 to 1990 at the Institute of Health Science, Kyushu University. Their ages ranged from 20 to 27 years, and all had high blood pressure (BP) of 140 mmHg or greater in systole (SBP) and/or 90 mmHg or greater in diastole (DBP) at a regular health check. This was confirmed by BP measurements for 3 days within 1 week. 2) A normotensive control group (N-group) consisting of 732 normotensive students (110-124 SBP/60-74mmHg DBP) for whom faculty, age, sex, height, weight, and examination period were matched to the H-group as closely as possible. In 1997, each subject was sent a questionnaire with items on height, weight, sitting BP, pulse rate, family history of hypertension, lifestyle habits (such as drinking and smoking), stress and personality type. Completing the questionnaire were 177 (52.4%) of the H-group and 206 (28.1%) of the N-group subjects. Hypertension continued in 44.6% of the H-group subjects, whereas 9.2% of the N-group subjects became hypertensive. The rate of hypertension at the end of the investigation was significantly higher in those subjects who had a family history of hypertension than in those who did not. Weight gain (+15.1%) was the highest in H-group subjects who were initially normotensive. These subjects showed a significantly higher incidence of smoking and drinking than the other subjects. These results confirmed lifestyle to be one of the most important factors in keeping BP normal throughout life and also suggested that fundamental health education should be introduced at an early age.

1. In the present study, the depressor action of the dipeptide Val-Tyr, with an in vivo antihypertensive effect, was investigated in transgenic mice carrying the human renin gene cross-mated with mice bearing the human angiotensinogen gene (Tsukuba Hypertensive Mouse; THM). 2. Single oral administration of Val-Tyr (0.1 mg/g) to 11-week-old THM resulted in a prolonged reduction of blood pressure for up to 9 h. The effect clearly demonstrated that the Val-Tyr absorbed acted on the enhanced human renin-angiotensin system (RAS). 3. After Val-Tyr administration, an approximate eightfold higher increment of plasma Val-Tyr was observed at 1 h (3406 +/- 211 fmol/mL plasma) compared with the level observed at 0 h; plasma concentrations of Val-Tyr returned to baseline levels at 6 h. 4. Transient changes in plasma concentrations of angiotensin (Ang) I and AngII only at 1 h were consistent with plasma Val-Tyr concentrations, suggesting that that the long-lasting reduction in blood pressure was achieved by the latent hypotensive mechanism of Val-Tyr and not by transient suppression of the circulatory RAS. 5. Ageing of the THM greatly affected the depressor action of Val-Tyr, with no significant reduction in blood pressure observed in 18- and 24-week-old THM.

1. The aim of the present study was to investigate the effects of a short (1 day) fast by testing biohumoral variables associated with the human circadian rhythm. 2. Fifteen clinically healthy male volunteers (32 +/- 8 years old) participated in the study. Subjects were fed a control diet for 7 days. The last day was a control day and the following 8th day was the fasting day. Each subject was asked to collect urine seven times over a 24 h period. Chemical and hormonal variables were measured in each fractionated urine specimen. The time- qualified urinary excretion rates were biometrically analysed using conventional and chronobiological methods. 3. During fasting, significant incremental changes were detected in the urinary excretion rates of potassium, aldosterone, 17-hydroxycorticosteroids and adrenaline and significant decremental changes were detected in the excretion rates of sodium, chloride, creatinine, urea nitrogen, uric acid, 17-ketosteroids, noradrenaline and dopamine. The circadian rhythmicity of the variables was well preserved and remained almost stable throughout the fasting phase. 4. Fasting affected the mean oscillatory levels and oscillatory amplitudes of variables, suggesting that nutrients may have played roles as tonic and phasic modulators on the mechanisms that physiologically regulate ircadian rhythmicity.

Estimation of salt intake by cumbersome 24-h urine collection is not suitable for individual patients because of substantial daily variation in intake. We developed the second morning urine (SMU) method for monitoring daily salt intake in healthy subjects by calculating the daily creatinine excretion and measuring the ratio of sodium to creatinine in the SMU specimen. To determine whether the SMU method was applicable to hypertensive patients, we tested it in hospitalized patients under an equilibrated sodium balance as a model population. This review focuses on application of the SMU method in hypertensive patients with mild target organ damage.

The aim of this study was to demonstrate that blood pressure (BP) has to be standardized according to its circadian variability, including the properties shown in its circadian rhythm. The BP time-qualified standards were derived from a sample of 644 clinically healthy normotensive Japanese subjects (320 males, 324 females; age range, 18-93 years), stratified by age-group and gender, who underwent noninvasive ambulatory monitoring according to a fixed protocol. The monitored data series shows that BP exhibits a within-day variability at any age of life in both males and females. Additionally, the monitored data series shows that BP exhibits a significant circadian rhythm at any age of life in both males and females. The age- and sex-related reference limits for the BP within-day variability constitute the time-qualified standards against which both the casual and monitored BP measurements can be compared in order to detect whether or not they are compatible with normotension. The reference limits for the BP circadian rhythm represent the rhythmometric standards against which the BP oscillatory curve can be compared in order to detect whether or not they are compatible with a physiological circadian rhythm.

This study was carried out to elucidate the prevalence of intestinal helminthic infections in rural communities in Nepal. Of 231 inhabitants randomly sampled in Kotyang and Judigaun, 140 (60.6%) were found to be infected with some soil-transmitted helminths. The highest prevalence was observed in hookworm infection (52.8%), followed by Trichuris trichiura (18.6%) and Ascaris lumbricoides (11.3%) infections. Some inhabitants harboured Vampirolepis nana and liver fluke. The female group aged 60 years old and more showed significantly higher T. trichiura infection rate than the male group with the same age (p

The plasma concentrations of angiotensin (Ang) I, Ang II, and their metabolites (Ang (3-8), (4-8), (5-8), and (3-4)) following in vitro ACE inhibitory activity were examined in young male normotensive (NT) (n = 7), and mild hypertensive (HT) volunteers (n = 6). There were no differences in supine plasma levels of Ang I, Ang II, and Ang (5-8) between the NT and HT groups: Ang I, 304 +/- 43 fmol/ml vs. 293 +/- 15 fmol/ml; Ang II, 32 +/- 6 fmol/ml vs. 43 +/- 10 fmol/ml; Ang (5-8), 176 +/- 22 fmol/ml vs. 133 +/- 32 fmol/ml. In addition, there were no significant differences between groups in any of these Ang levels when measured after standing for 60 min. However, the HT group showed significantly reduced supine and upright plasma Ang (3-8) and Ang (3-4) levels as compared to the NT group. In particular, the supine plasma level of Ang (3-4) (71 +/- 13 fmol/ml-plasma) in the HT group was significantly (1/3-fold) lower than that in the NT group (197 +/- 35 fmol/ml-plasma). An inverse correlation between the plasma level of Ang (3-4) and the upright systolic blood pressure (r = -0.627, p < 0.02, n = 13) was observed, indicating that the metabolism of Ang (3-4) might have been associated with the change in blood pressure.

It has recently been found that there were very few hypertensives in the inhabitants of one Nepalese village, even though their salt consumption, per capita, was as high as citizens in many western countries. To evaluate the genetic factors involved in this phenomenon, we studied whether they had a special genotype distribution of angiotensin-converting enzyme (ACE) gene I/D polymorphism, which was recently reported to be involved in salt sensitivity. One hundred and thirty-eight subjects were evaluated in Nepal. Only nine subjects (6.5%) in this population were hypertensives (over 140/90 mm Hg) while consuming 11 g salt/day, which confirmed the previous results. The distribution of genotypes and alleles of ACE gene I/D polymorphism was similar to that in the Japanese and Chinese, who had five-times more hypertensives while consuming almost as much salt as Nepalese, but significantly different from those in Caucasians. The present study reports, for the first time, the genotype distribution of ACE gene I/D polymorphism in Nepalese subjects. Furthermore, the results suggest ACE gene polymorphism may not be involved in the 'salt-resistance' in this population.

Serial measurements, taken around the clock in the laboratory and clinic, can be analyzed by computer-implemented curve-fitting to assess the approximate 24-hour (circadian) variation, among other rhythmic and chaotic components of the time structure (chronome) of any variable. This approach is particularly important to quantify blood pressure variability, which renders even the most accurate single measurement into a snapshot on a roller coaster. A seemingly acceptable blood pressure can be particularly misleading when accompanied by the recommendation of another check-up in 2 years, which is the official position of the World Health Organization. An overswinging of the blood pressure along the 24-hour scale may then be missed. This excessive circadian amplitude, called "circadian hyper-amplitude-tension" (CHAT), constitutes a new disease risk syndrome, warranting screening, diagnosis, and treatment. With or without the midline-estimating statistic of rhythm (MESOR) (i.e., the [chronome-adjusted] mean va...

In a double-blind, placebo-controlled study, thirty-three subjects were allocated to undergo either a 4-week treatment with oral Mg supplementation (Mg(OH)2; 411–548 mg Mg/d) or a placebo. The urinary excretion of Mg increased significantly in both the first 2 weeks and the following 2 weeks of Mg supplementation, while the urinary Na excretion also increased significantly over the experimental period. The systolic and diastolic blood pressure values decreased significantly in the Mg group, but not in the placebo group. The urinary aldosterone excretion and packed cell volume increased significantly during the last 2 weeks of the experimental period compared with the run-in period and first 2 weeks of supplementation. There was a statistically significant positive correlation between the values for urinary noradrenaline excretion and diastolic blood pressure at the end of the supplementation period (both expressed as a percentage of the run-in value). Statistically significant increases in lecithin-cholesterol acyltransferase (EC2.3.1.43; LCAT), HDL-cholesterol and apolipoprotein AI were also observed after Mg supplementation. A significant positive correlation was observed between the levels of LCAT and urinary Mg excretion for the experimental period (expressed as a percentage of the run-in value). The total cholesterol: HDL-cholesterol ratio decreased significantly during the last 2 weeks of Mg supplementation compared with the first 2 weeks and the run-in periods, but this did not occur in the placebo group. These results suggest that Mg supplementation may lower blood pressure through the suppression of the adrenergic activity and possible natriuresis, while also improving the serum lipids through the activation of LCAT in human subjects.

The effect of activating the renin-angiotensin system on the metabolism of angiotensins (ANGs) in normotensive human plasma was investigated. In normotensive supine human plasma, four peptides with in vitro angiotensin I-converting enzyme (ACE) inhibitory activity which correspond to the sequence of ANG (3-8), ANG (4-8), ANG (5-8), and ANG (3-4) existed at a concentration of > 39 fmol/ml of plasma. When activating the renin activity by keeping upright in posture for 60 min, ANG II and the four peptides significantly increased as compared with the levels in the supine posture, except for ANG I. In particular, Val-Tyr corresponding to ANG (3-4) in the upright posture was about 4-fold more than the value in the supine posture, and was predominantly present (447 fmol/ml of plasma) as well as ANG I. As a result of in vitro degradation tests on ANGs, ANG (3-4) was produced from ANG I, and not from ANG II, III or (3-8), during the 30-min incubation.

A wide range of definitions is used to distinguish subjects in whom blood pressure (BP) falls at night (dippers) from their counterparts (nondippers). In an attempt to standardize the definition of nondipping, we determined the nocturnal BP fall and night-day BP ratio by 24-hour ambulatory monitoring in 4765 normotensive and 2555 hypertensive subjects from 10 to 99 years old. In all subjects combined, the systolic/diastolic nocturnal fall and corresponding ratio averaged (±SD) −16.7±11.0/−13.6±8.1 mm Hg and 87.2±8.0%/83.1±9.6%, respectively. In normotensive subjects, the 95th percentiles were −0.3/−1.1 mm Hg for the nocturnal fall and 99.7%/98.3% for the night-day ratio. Both the fall and ratio showed a curvilinear correlation with age. The smallest fall and largest ratio were observed in older (≥70 years) subjects. A higher BP on conventional sphygmomanometry was associated with a larger systolic (partial r =.11) and diastolic ( r =.12) nocturnal BP fall. The diastolic ( r =.08) but not the systolic night-day ratio increased with higher conventional BP. The nocturnal BP fall was larger and the corresponding night-day ratio smaller in oscillometric (n=5884) than in auscultatory (n=1436) recordings, in males (n=3730) than in females (n=3590), and in Europe (n=4556) than in the other continents (n=2764). The distributions of the nocturnal BP fall and night-day ratio showed considerable overlap among normotensive and hypertensive subjects, but the overlap tended to be larger for the ratio than for the fall. Of all subjects, 3.2% had systolic and diastolic ratios of 100% or more. With adjustments applied for confounders, the probability of being a nondipper increased 2.8 times (95% confidence interval, 2.0-4.0) from 30 to 60 years and 5.7 times (4.4-7.4) from 60 to 80 years. The odds ratios were 1.0 (0.8-1.4) for males versus females, 1.6 (1.2-2.1) for subjects with definite hypertension versus normotensive subjects, 2.4 (1.2-4.7) for Asians (n=2213, 96% Japanese) versus inhabitants of the other continents, and 2.4 (1.5-3.8) for subjects examined with auscultatory versus oscillometric devices. In conclusion, the mathematical definition of nondipping, ie, having a night-day ratio of 100% or more for systolic and diastolic BPs, closely approximated the 95th percentiles of the night-day ratio in normotensive subjects. The ratio depends less on BP level than the nocturnal BP fall and is therefore to be preferred in the definition of dipping status. Notwithstanding the present findings, the reproducibility of nondipping and its prognostic significance need further clarification.

Objective To investigate the effects of chronic smoking on the 24 h blood pressure and heart rate pattern in normotensive subjects. Methods Twenty-five smokers and 25 age-, weight- and height-matched non-smokers, who were all clinically healthy young men, gave their informed consent to undergo non-invasive, automated, ambulatory blood pressure monitoring for 24 h. The smokers in this study consumed on average 25.4 cigarettes per day. The lifestyle of the two groups was comparable because they worked as clerks at the same company. The 24 h blood pressure and heart rate data were analysed according to chronobiological methods. Results Smokers were found to show a statistically significantly higher blood pressure versus non-smokers by day but not by night. Furthermore, smokers showed a slight increase in the mean level of circadian blood pressure rhythm versus non-smokers, accompanied by an amplification of one cyclic component of this periodicity. Conclusions The increase in diumal blood pressure in smokers might be regarded as the haemodynamic effect of chronic smoking in normotensive subjects. Such an effect seems to be substantiated pathophysiologically by an amplitude overmodulation of one of the harmonic components which confer the circadian blood pressure rhythmicity. Because the diumal increase in blood pressure persists for two-thirds of the day-night period, one can argue that this phenomenon in normotensive smokers might be a premonitory sign of future hypertension. Apart from this, one can hypothesize that the diumal increase in blood pressure might itself be a cause of target organ damage, given its consistent within-day duration and daily repetition.

To investigate the seasonal variations in ambulatory blood pressure patterns, 24-h blood pressure was measured every 15 minutes noninvasively in ten young normotensive women. Urine was collected every 4 hours. The examinations were repeated in spring, summer, autumn, and winter in a standardized living environment. The 24-h average systolic and diastolic blood pressures did not differ significantly among the seasons. Similarly, there were no significant differences in the average values of either daytime or nighttime blood pressure. In contrast, the average pulse rate during nighttime was significantly higher in winter than in summer (64±2beats/min vs. 59±2beats/min, p

When angiotensin fragments, Val-Tyr and Angiotensin III (ANG III), with potent ACE inhibitory activity were intravenously administered to spontaneously hypertensive rat (SHR), a significant reduction of diastolic blood pressure was observed. After incubation of ANG III with SHR plasma, four fragments with ACE inhibitory activity, Val-Tyr (ANG (3-4)) (IC50 = 26.0 microM), Ile-His-Pro-Phe (ANG (5-8)) (11.6 microM), Tyr-Ile-His-Pro-Phe (ANG (4-8)) (457.5 microM), and Val-Tyr-Ile-His-Pro-Phe (ANG (3-8)) (6.55 microM), were confirmed to generate in SHR plasma. Compared the metabolic behavior of ANG II in SHR plasma with that in normotensive Wistar plasma, the initial degradation rate (3.07 nmol/ml/min) in Wistar plasma was about 2-fold higher than that in the SHR one (1.75 nmol/ml/min).

Clinical, epidemiological and chronobiological studies on the relationship between blood pressure and mineral intake have been on-going for the past thirty years. They can be divided into five groups. 1) Clinical studies on salt sensitivity in patients with idiopathic hypertension. 2) Chronobiological studies of blood pressure (BP) fluctuation and urinary electrolyte excretion in relation to BP regulation. These include the Fukuoka-Minnesota collaborative chronoepidemiological study, studies on the circadian rhythns of urinary electrolyte excretion during total parenteral nutrition, and the reapportionment of salt intake in relation to circadian blood pressure patterns. 3) The estimation of the 24-h urinary sodium and potassium excretion from spot-urine specimens. 4) Comparative epidemiological studies on the genesis of hypertension in Nepal. 5) The effects of high-potassium, high-magnesium or high-fiber intake on blood pressure and the metabolism of lipids and carbo-hydrates in man. A larger proportion of te population are expected to suffer from either mild or borderline hypertension in the future. Non-pharmacological treatment of this condition by regulating the dietary intake of minerals such as sodium, potassium, magnesium and calcium, is now considered to be of increasing importance for the treatment of this condition.

An 18-year-old male high school student with school refusal and circadian rhythm disturbance is reported. At 17 years of age, he was unable to attend school because of a reversal of the daily rhythm and a moderate depressive feeling. Other circadian rhythms, including deep body temperature (DBT), and plasma melatonin, cortisol and beta-endorphin, also showed quite different or abnormal curves compared with those in normal controls. He was treated with methyl B12 and melatonin, which normalized the circadian rhythm, i.e. it became entrained to a 24-h period, and the DBT and hormonal rhythms became closer to normal patterns. These results suggest that desynchronization of the biorhythms, particularly the circadian rhythm, may be one of the important causes of school refusal in Japan, and melatonin and methyl B12 might be useful for treatment of the condition.

The change in plasma level of dipeptide, Val-Tyr (VY), with in vitro angiotensin I-converting enzyme inhibitory activity was investigated after a single oral administration of a VY-drink at doses of 0, 6 or 12 mg given to mild hypertensive subjects. During this protocol for up to 24 h after the intake, patient/subject blood pressure (BP) was measured for a 15 min period at designated times (0, 1, 2, 4, 8, 24 h) with the individual supine. Based on the VY determination, the maximal increment of plasma VY level was observed over the second hour postprandially (12 mg-dose; 2041+/-148 fmol/ml-plasma). In addition, the plasma VY level increased with the VY dosage. However, no marked BP change was observed with the increase of plasma VY level, suggesting that VY did not exert an acute hypotensive effect. The area under the curve at 12 mg-dose was estimated to be 8644+/-420 fmol x h/ml-plasma, comparable to that in normotensive subjects. This finding suggests that absorption of VY would not be influenced by a complaint of hypertension.

1. An assessment was made of the extent sodium (Na) and potassium (K) intake can be estimated from Na, K and creatinine (Cr) content of a second morning voiding urine (SMU) specimen collected within 4 h after the first voiding upon awakening but before breakfast in 159 clinically healthy, free-living individuals (20-79 years). The SMU and the rest of 24 h urine specimens for a 3-5 day period were collected. 2. The following equations for estimating 24 h urinary Na (24HUNaV) and K (24HUKV) excretions were developed, and the accuracy and the reliability of these equations were evaluated. Estimated value of 24HUNaV (mEq/day) = 16.3 square root of XNa; estimated value of 24HUKV (mEq/day) = 7.2 square root of XK, where XNa (or XK) = SMUNa (or SMUK)/SMUCr x predicted 24 h urinary Cr excretion. 3. Highly statistically significant correlations were detected between the values estimated and measured for both Na (r = 0.728, P0.001, n = 159) and K (r = 0.780, P0.001, n = 159). 4. These equations were applied to Group 1 subjects, who collected the urine for a single day, and to Group 2, for 3 days. The correlation coefficients between the values estimated and measured for Na and K were 0.531 and 0.443 in Group 1, and 0.821 and 0.590 in Group 2, respectively. No statistically significant differences were observed. 5. The SMU specimens provide a satisfactory alternative to both 24HUNaV and 24HUKV in adults for extensive epidemiological surveys but also for clinical application.

To investigate the nutritional condition in a hilly village (Kotyang) and a suburban village (Bhadrakali) in Nepal and to clarify the possible cause of the difference in total serum cholesterol level between the two groups of villagers habitually eating low fat diets, we carried out a nutrition survey using the 24-h recall method and blood sampling in 403 subjects (204 men and 199 women) in the hilly village and 466 (244 men and 222 women) in the suburban village. Total serum cholesterol was statistically significantly lower in the hilly villagers than in the suburban villagers for both sexes, but HDL-cholesterol was not. In both villages, 82% of the total energy was taken from carbohydrate, 7-8% from fat and 10% from protein. Energy, protein, fiber, potassium, magnesium, monounsaturated fatty acid, polyunsaturated fatty acid, and vitamin A in the hilly villagers were significantly higher than those in the suburban villagers. Total serum cholesterol was significantly associated with age and body fat percentage, suggesting that total serum cholesterol level was not directly associated with total fat intake in these Nepalese people.

A 67-year-old man affected by prostate cancer was incidentally found to have a nodular enlargement of the left adrenal gland without apparent changes in hormonal status. The adrenal mass was found to be scintigraphically active, the radiolabelled compound being concentrated in its context with a consensual suppression of the contralateral uptake. The patient underwent a resection of the adrenal tumor. Histologically and biochemically, the adrenal mass was found to be a non-functioning adenoma. The radioisotopic uptake along with the non-hormonal activity prompted us to call this tumor “Pre -Cushing's syndrome” of the adrenal cortex.

近年, 日本における食生活の洋風化, 運動量の不足並びにエネルギーの摂取過剰などによる小児期の肥満, 更に小児成人病またはその予備群の増加が憂慮されている。本報では, 中国遼寧省の収容施設 (1日3食) 及び通園施設 (昼・夕食の1日2食) における2～7歳児の食物摂取状況を調査し, 日本の現状と比較することにより, 近い将来中国が対面するであろうと考えられる小児成人病の予防に期することを目的とした。1) 身長, 体重などの体位は日本における標準値と差はなかった。肥満指数で肥満度をみると, 肥満傾向は収容施設5.3%, 通園施設4.6%で, やせの傾向は収容施設27.2%, 通園施設37.6%といずれも多かった。2) 収容施設のエネルギー摂取量は充足されていたが, たん白質, カルシウム, 鉄, ビタミンB1, B2, Cの摂取不足がみられた。通園施設でのエネルギー・給与量は1日の55.8%で, 不足分を朝食で補足することには無理もあり, エネルギーの摂取不足が憂慮された。3) 穀類エネルギー比は52～64%であった。米類に比べ小麦粉類の摂取が多く, 砂糖類の摂取量は日本の1.5倍であった。動物性たん白質比は38～41%と低かった。アミノ酸価は52と低く, 制限アミノ酸はリジンであった。4) 脂質エネルギー比は25%と望ましかったが, コレステロールの摂取量が多く, P/S比は低く, 脂質の摂取に問題が多かった。5) 血圧は日本の幼児に比して高い傾向がみられ, 肥満指数と正相関がみられた。

健康な若年女性9名を対象に基準食 (C食: NaCl 10g/日, K 2.5g/日), 高K食 (K食: 基準食+KCl 48meq (Kとして1.9g/日) の2種の食事を10日間摂取してもらい, 血圧ならびにその関連因子と脂質, 糖質代謝に及ぼすKの影響をおのおの卵胞期で検討した。1) Naの尿中排泄量は食間に差はなく, Kの尿中排泄量はK食でC食の約1.5倍と有意に大であった。2) 収縮期血圧はK食で有意に低値を示したが, 拡張期血圧に差は認められなかった。3) 血漿レニン活性はC食に比してK食で有意に低下した。血漿アルドステロン濃度はK食で有意に増加した。また尿中アルドステロン排泄量, カリクレイン排泄量もK食で有意に増加した。4) 血清KならびにMg濃度はC食に比してK食で高い傾向を示した。5) 血清総コレステロールならびに中性脂肪はK食で有意に低下した。HDL-コレステロールに変化はみられなかった。血清総コレステロール/HDL-コレステロール比はC食に比べK食で有意に低値を示した。6) 血清インスリン濃度はK食で有意に増加した。血清グルコースはC食に比しK食で低い傾向を示したが有意差はなかった。以上の結果からK負荷による血圧ならびに血清脂質の低下が示唆された。

Under standardized conditions, we determined circadian urinary excretion of sodium (Na) and free dopamine (DA), norepinephrine (NE) and epinephrine (E) in 20 normotensive, 20 borderline hypertensive and 10 mild hypertensive middle-aged men. The 24-hour excretions of water, Na, DA, NE and E were comparable between the normotensives and the hypertensives. In the total study population, these parameters showed significant time-related changes: high excretion during the daytime and low excretion in the night. The circadian variations of urinary DA, NE and E were similar among the 3 groups. The circadian curve of urinary DA was similar to those of Na and water excretion. In the total study population, 24-hour water and Na excretion correlated positively with urinary DA, but not with NE or E. These results suggest that endogenous DA may play a role in the circadian variation of water and sodium metabolism. The circadian excretion of urinary catecholamines may not be altered in middle-aged subjects with borderline or mild hypertension.

We report on an interesting case of longevity in an elderly Japanese woman whose blood pressure (BP) continued extremely high from her first recording at the age of 38 years to her first hospitalization at the age of 81. BP recordings taken by her physician indicated mostly severe or occasionally mild hypertension (HT): between 260/130 and 140/76 mmHg. No antihypertensive drugs were taken during the 25 year span between ages 56 and 80. After her physician died, when she was 80, she changed clinicians and was given several kinds of antihypertensive drugs. She began to feel faintness, dizziness, and severe fatigue. At the time of the first hospitalization, no remarkable cerebral or cardiac abnormalities were observed, despite her BP as high as 210/110 mmHg. BP as measured by nurses or the physician in charge were always above 160/80 mmHg. After discharge, she was asked to measure BP by herself at home. These readings were 140-150/70-80 mmHg on the average, indicating a rare case of long-term emotional blood pressure response. The patient died not of a cerebrocardiovascular accident, but of acute renal failure at 95 years of age. Even though her recorded BP was extremely high when measured by medical staff members and still far above the current conventional desired limit of 120 mmHg systolic (S) BP or the earlier limit of 140 mmHg SBP, it was actually acceptable for her retrospectively, insofar as she lived to age 95. Although antihypertensive drug therapy may be helpful in some cases, it may not be necessary in others. Intensive drug therapy may even be harmful for misdiagnosed emotionally HT patients particularly those misdiagnosed with refractory hypertension, when the response to health care professionals may be emotional.

We examined the relation between protein intake and blood pressure in a screened cohort in Okinawa, Japan. A total of 1,299 screened subjects, 885 men and 414 women, were examined at the Okinawa General Health Maintenance Association. Daily intake of sodium (Na) and potassium (K) was estimated from Na, K, and creatinine excretion by the method of Kawasaki et al., and daily protein intake was estimated by the method of Maroni et al. as the estimated daily urinary excretion of urea nitrogen. Mean (SD) daily protein intake was 71.8 (18.6) g in men and 54.0 (13.5) g in women, and the mean (SD) daily protein intake per unit kg body weight was 1.1 (0.2) g/kg in men and 1.0 (0.2) g/kg in women. In men, both systolic blood pressure (SBP) and diastolic blood pressure (DBP) were higher in those with lower protein intake (LP;1.0 g/kg/day) than in those with higher protein intake (HP;or = 1.0 g/kg/day) (p0 .05 for DBP). In women, both SBP and DBP were higher in those with LP than in those with HP, but these differences were not statistically significant. However, urinary excretion of both Na and K was lower in those with LP than in those with HP, respectively, both in men and women (p0.0001). In summary, estimated daily protein intake was about 1.1 g/kg in men and 1.0 g/kg in women. Despite the higher urinary excretion of Na, both SBP and DBP tended to be lower in those with higher daily protein intake, particularly in men.

Information regarding daily intake of sodium (Na) is useful for both normotensive and hypertensive subjects. We measured urinary excretion of sodium (U-Na) and urinary excretion of potassium (U-K) to estimate daily salt intake in a cohort of health screening subjects in Okinawa, Japan. Urine samples were obtained from 2,411 subjects (1,554 men and 857 women) who were examined on a half-day dry-doc at the Okinawa General Health Maintenance Association (OGHMA). Four hundred and one subjects were examined twice, once between September and November in 1997, and once between September and November in 1998. The mean U-Na was 182 mEq/day for men and 176 mEq/day for women. The mean U-K was 54 mEq/day for men and 50 mEq/day for women. U-Na was higher in young men, and U-K was lower in young women. In both men and women, smokers had a significantly lower Na excretion compared to nonsmokers. Subjects treated for hypertension had a significantly lower Na excretion (173 mEq/day) compared to subjects not treated for hypertension (192 mEq/day). Our findings suggest that Na excretion in screened subjects in Okinawa is lower than the national average. Sodium excretion, however, was higher in young men than in elderly subjects, and K excretion was lower in young women than in elderly subjects. Both trends are disadvantageous for controlling hypertension.

Pheochromocytoma is often associated with paroxysmal hypertension. We report a 49-year-old woman with pheochromocytoma whose blood pressure (BP) was elevated regularly only at night. Plasma norepinephrine (NE) and neuropeptide Y (NPY) concentrations increased in parallel with the elevation of BP. After resection of the adrenal tumor, these circadian changes disappeared. Plasma NE and NPY, especially the former, from the tumor were considered to be the cause of this unusual fluctuation in BP.

The present study was conducted to determine whether Valyl-Tyrosine (VY) has an antihypertensive effect on high-normal blood pressure and mild essential hypertension, as well as spontaneous hypertensive rats (SHR). A randomised double-blind placebo-controlled study was carried out on 29 volunteers. A 100-ml drink containing 3 mg of VY and a 100-ml placebo drink were prepared. The subjects were grouped as VY(16M/1F, 45.5 +/- 3.2 years, 146.4 +/- 2.3/90.5 +/- 1.8 mm Hg) and the placebo (P) (11 M/1F, 48.8 +/- 3.0 years, 145.5 +/- 2.4/92.3 +/- 1.8 mm Hg). At 3 weeks of the control (C) period, a VY- or P-drink was administered twice a day for 4 weeks in the experimental (E) period and during the 4-week recovery period, neither drink was given to either group. Blood pressure (BP) was measured every week in the morning in the sitting position. Blood specimens were taken on the last day of the C and E periods. In the VY-group, reduction in systolic (S) and diastolic (D) BP was 9.7 and 5.3 mm Hg (P < 0. 001) at 1 week, and 9.3 and 5.2 mm Hg (P < 0.001) at 4 weeks, following the start of the E period, respectively. Neither SBP nor DBP changed in the P-group. BP in the VY-group increased gradually by the end of the recovery period. Plasma angiotensin (Ang) I and VY concentrations significantly increased while Ang II and aldosterone significantly decreased after VY administration in the VY-group. VY appeared to have a significant antihypertensive effect on mild hypertensive subjects via Ang I-converting enzyme inhibition, as well as SHR, but no adverse effects could be detected at all.

A parallel controlled clinical trial was carried out to investigate the effect on blood pressure (BP) of replacing normal salt with mineral salt in seasonings. After a 2-wk run-in period, 21 subjects (10 men and 11 women; age, 66.0+/-7.6 yr) were given mineral salt in seasonings instead of normal salt [mineral salt (MS) group], while 20 subjects (10 men and 10 women; age, 65.9+/-7.4 yr) continued to receive normal salt in seasonings [regular salt (RS) group] for the next 5 wk in the experimental (E) period. In the MS group, systolic (S) and diastolic (D) BP decreased significantly from 134.7+/-17.2/77.2+/-9.7 at baseline (week 0) to 127.3+/-12.0/73.5+/-8.9 mmHg at the end of the E period (week 5), and the reductions in both SBP and DBP were larger in hypertensive subjects than in normotensive subjects in the MS group. The serum sodium and chloride concentrations decreased significantly, while the serum potassium and HDL-cholesterol concentrations increased significantly at week 5. The 24-h urinary sodium excretion decreased, and the 24-h potassium and magnesium excretions increased significantly from week 0 to week 5 in the MS group. In contrast, SBP, DBP, serum chemistry, and urinary electrolyte excretion did not change significantly in the RS group. These findings suggest that the excessive salt content and insufficient potassium and magnesium content of the present Japanese diet could be easily and safely corrected by replacing seasonings prepared with regular salt with those prepared with mineral salt.

The aim of this study was to investigate whether there is variation in blood pressure when we reapportion the percentage of total daily salt intake consumed at each of three regular meals. The study was conducted on seven clinically healthy normotensive female subjects who, in Stages LH and DH, consumed two-thirds of the normal daily salt intake (12 g/day) at lunchtime or at dinnertime, respectively. The total daily amounts of nutrients and dietary salt were similar in Stage-R (regulated salt intake), Stage-LH (a high-salt intake at lunchtime), and Stage-DH (a high-salt intake at dinnertime). The blood pressure response to the variation of sodium content in the meals was examined by means of noninvasive automated blood pressure monitoring (ABPM-630; readings every 15 or 30 min over 48h) and chronobiologic analysis. A significant shift of blood pressure circadian rhythm was observed in Stage-LH. Additionally, the 24-h mean level of blood pressure significantly increased when the prevailing salt intake was at lunch, and significantly decreased when the prevailing intake was at dinner. These opposite responses corroborate the view that the blood pressure susceptibility of human beings to salt intake varies during the day, showing its maximal expression at midday. Such a time-dependent sensitivity may be exploited for better nutritional prevention and treatment of arterial hypertension by reappor-tioning the salt intake so that two-thirds is consumed at dinner.

The direct assay of total renin (TRC) and active renin concentration (ARC) is a reality due to the availability of monoclonal antibodies against human renin. Because of this, a study has been performed in order to assess the circadian rhythmicity of TRC and ARC. The study was extended to plasma renin activity (PRA) and plasma aldosterone concentration (PAC) for a more complete assessment of the renin-angiotensin-aldosterone system (RAAS). Twelve clinically healthy subjects (6 males and 6 females, age from 20 to 25 years) volunteered for this study. Time-qualified data series were analysed by means of chronobiological procedures in order to validate the circadian rhythm and to correlate the sinusoidal profiles. The circadian rhythm was validated at a high significance for TRC, ARC, PRA and at a borderline significance for PAC. The periodic oscillations were significantly correlated, demonstrating that TRC, ARC, PRA and PAC cycles oscillate in synchronism during the 24-hour span.

Forty-two middle-age male subjects, aged from 47 to 54 years old, were divided into three groups; 14 normotensives (NT), 16 borderline hypertensives (BHT) and 12 hypertensives (HT). The environmental effects were neutralized as much as possible by keeping their activities synchronized and their plasma and urine variables simultaneously investigated using the same protocol as under normal physiologic conditions. The circadian rhythms of urinary excretions of Na, K, Cl, creatinine, aldosterone, adrenaline and noradrenaline were analyzed by a multivariate method (cosinor method). Both systolic and diastolic blood pressure were statistically significantly different among the three groups and body weight was greater in HT than in NT. Other plasma and urine variables examined, however, were not significantly different among the three groups. A statistically significant circadian rhythm was detected in the urine variables. The rhythm characteristics, such as the mesor, amplitude and acrophase, of the urine variables except for the acrophase of urinary Na excretion were not significantly different among the three groups; the circadian acrophase of urinary Na in HT and BHT appeared significantly earlier than in NT. The pathophysiological and clinical significance of the earlier appearance of the circadian acrophase of urinary Na in hypertensive subjects still remains a unique characteristic requiring further investigation.

The concentrations of luteinizing hormone, prolactin, estrone, estradiol, 17-hydroxyprogestrone, cortisol, aldosterone, dehydroepiandrosterone, thyrotropic hormone, triiodothyronine, thyroxin and insulin were determined in blood plasma obtained from women aged 15 to 59 years. Blood was sampled at intervals of 20 to 100 min throughout 24-hour spans in each of the four seasons and (in the case of cycling women) in four different stages of the menstrual cycle. With such sampling allowing for rhythmic and other fluctuations over a broad time scale it was possible to demonstrate statistically significant effects of age on hormones associated with the menstrual cycle (luteinizing hormone, prolactin, estrone, estradiol and 17-hydroxyprogesterone) and on dehydroepiandrosterone, but not on the remainder. The amplitude of circadian rhythms in several of the hormones also varied with age, thus affirming the value of sampling throughout this particular rhythm.

We report herein a method of solid-phase radioimmunoassay (RIA) for assessment of plasma cortisol concentration using 125I-labeled ligand [CORTCTK-125]. Plasma cortisol concentrations and its circadian rhythm in healthy young Japanese and American whie women were also evaluated using CORTCTK-125. Nineteen Japanese women, of an average age of 20.3 +/- 0.1 years, and 12 Caucasians of mixed ethnic origin (Minnesota), average 20.0 +/- 0.5 years, were studied using a similar protocol. The distribution of the menstrual stage of the two groups was similar. Blood was drawn from each subject into EDTA containers at 4-hour intervals starting at 0800 on one day and was continued for the ensuing 24 hours. The samples were immediately placed in a refrigerated centrifuge at 4 degrees C, and then stored at -20 degrees C until the assay. The samples from Minnesota were packed in dry ice and brought by air to Japan. Determinations of plasma cortisol concentration in samples from both groups were carried out at Kyushu University. Advantages of the solid-phase RIA method are as follows: (1) 0.05 ml of plasma or serum was sufficient for determination of plasma cortisol concentrations, (2) no other solvents or solutions for the extraction or purification were required, (3) the procedure was simple and readily facilitated, and (4) the concentration of cortisol in heparin-plasma was somewhat higher than that in serum or EDTA-plasma, but there was no statistical difference. Plasma cortisol concentrations in the samples from the Japanese (19.73 +/- 1.44 on the first and 18.94 +/- 1.32 microgram/dl on the second day) and that of the American group (17.48 +/- 2.38 and 19.37 +/- 2.16 microgram/dl, respectively) at 0800 was similar. The average value of 7 determinations at 4-hour intervals was 11.01 +/- 2.00 microgram/dl in the Japanese and 10.29 +/- 1.05 microgram/dl in the American group. A remarkable and similar circadian rhythm was observed in both groups with a peak at 0800 and with nadirs at 2000 in the Japanese (4.80 +/- 0.45 microgram/dl) and 2400 in the American group (5.18 +/- 0.83 microgram/dl). There were statistically significant differences between the values at the peak and the nadir. The related subjects were then classified into Group-F (9 subjects) and Group-T (9); the former included high body mass index [BMI: body weight(kg)/body height(m)2] of more than 24.0, and the latter included a relatively lower BMI of less than 21.5. The circadian rhythm of both groups revealed a similar pattern, whereas plasma cortisol concentration was always higher in Group-F than in Group-T, at all 7 determinations. There were no significant differences except for the value at 0400. Furthermore, the average values of plasma cortisol concentration and circadian rhythm were compared; the group with a larger body surface area (BSA) (Group-L) and the group with a smaller BSA (Group-S). No difference was found in the plasma cortisol concentration of Group-L and -S, and the circadian rhythm was similar in both groups...

Pathophysiology of malignant hypertension, of which underlying disease was essential hypertension (EHT) in 33 cases and chronic glomerulonephritis (CGN) in 26 cases, was studied with reference to the renin-angiotensin system. Plasma renin activity (PRA) was significantly higher in the EHT than in the CGN group, and angiotensin II antagonist [Sar1, Ile8]angiotensin II (AIIA) induced a significant lowering of blood pressure only in the former group. PRA was linearly correlated with both pretreatment mean blood pressure (MBP, r = 0.474, n = 29, p less than 0.01) and serum creatinine (r = 0.540, n = 29, p less than 0.01) in the EHT group but not in CGN patients, although there was an inverse correlation between PRA and serum sodium in both groups. Multiple regression analysis revealed that PRA was independently related to MBP, serum creatinine, and serum sodium in the EHT group, but not in the CGN group. These results suggest that the renin-angiotensin system plays a significant role in elevating blood pressure and deteriorating renal function in malignant hypertension derived from EHT, but it is less important in CGN related hypertension.

For the quantitative analysis of the effect of sodium balance on renin secretion, plasma renin activity (PRA) was measured in 9 healthy young males in the respective 3- or 4-day periods of sodium repletion, mild sodium restriction, moderate and severe sodium depletion. In the latter 2 periods, sodium balance was made negative by low salt diet and furosemide administration (120mg/day, p.o.) for 1 or 3 days. Blood samples for PRA determination were obtained at supine position (8:00 a.m.) and after 1-, 2-, and 4-hour's upright posture. PRA was also measured after furosemide stimulation (80mg, p.o.) plus 2-hour's upright posture in the period of sodium repletion.Change in the supine PRA was directly correlated with that in hematocrit (r=0.81) and inversely with that in body weight (r=-0.64). The PRA rose significantly from 1- to 2- and 4-hour's upright posture in the period of mild sodium restriction, whereas it reached the maximum level at 1-hour's upright posture and remained unchanged thereafter in either period of negative sodium balance. The upright PRA after furosemide stimulation in the period of sodium repletion was almost identical to 2- and 4-hour's upright PRA in the period of mild sodiom restriction, and less than 1-hour's upright PRA in either period of negative sodium balance.These data suggest that 1-hour's upright posture is enough to evaluate PRA when sodium balance is negative.

A circadian rhythm of plasma activity (PRA) was demonstrated for both Japanese and North American women, the latter mostly Caucasians of mixed ethnic origin. The results were based on blood samples withdrawn at 4-hour intervals during a 24-hour span (in March 1978) from 20 subjects from Fukuoka (average age 20.4 +/- 0.1 years) and 16 subjects from Minneapolis (average age 20.2 +/- 0.4 years). The rhythms in the two populations showed similarities in some characteristics and differences in others. The timing of high values, i.e., of acrophases, objectively assessed by curve-fitting (and of corresponding 95 per cent confidence limits) was at 07(36) (05(00), 10(16) and 06(32) (03(00), 10(00) for Japan and USA, respectively. As objective measures of the extent of predictable rhythmic change mean amplitudes, in nanograms per milliliter per hour (ng/ml/hour), were similar (0.31 and 0.32); a statistically significant difference (P less than 0.05) was found in mean amplitudes expressed as percentage of the rhythm-adjusted average. Mean rhythm-adjusted average values (mesors) were lower in women from Japan than in those from the United States: (1.64 +/- 0.14 and 2.39 +/- 0.23 ng/ml/hour, respectively; P less than 0.01). A statistically significant difference in dietary salt, indicated by differences between the Japanese and North American women in the urinary excretion of sodium and chloride (P less than 0.05), almost certainly contributed to these results.