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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.

Massless Dirac electrons in condensed matter have attracted considerable attention. Unlike conventional electrons, Dirac electrons are described in the form of two-component wave functions. In the surface state of topological insulators, these two components are associated with the spin degrees of freedom, hence governing the magnetic properties. Therefore, the observation of the two-component wave function provides a useful clue for exploring the novel spin phenomena. Here we show that the two-component nature is manifested in the Landau levels (LLs) whose degeneracy is lifted by a Coulomb potential. Using spectroscopic-imaging scanning tunneling microscopy, we visualize energy and spatial structures of LLs in a topological insulator Bi2Se3. The observed potential-induced LL splitting and internal structures of Landau orbits are distinct from those in a conventional electron system and are well reproduced by a two-component model Dirac Hamiltonian. Our model further predicts non-trivial energy-dependent spin-magnetization textures in a potential variation. This provides a way to manipulate spins in the topological surface state., Comment: Revised version to appear in Nature Physics. Supplementary information is available at http://www.riken.jp/epmrt/Hanaguri/SI/Bi2Se3_2comp/SI.html

SUMMARY 1. Few studies have been reported concerning the effect of ageing on renal functional and vascular responses to various stresses during ordinary life. In the present study, we examined the effect of age on changes in renal sodium handling and renal vascular resistance (RVR) in response to standing from a supine position in subjects with normal renal function. 2. We selected 43 healthy males in the second through to the seventh decade of life and gave them a constant dietary sodium intake before the study period. Renal function was estimated by standard clearance methods with the subject in a state of euvolaemia. 3. The mean daily urinary excretion of sodium was 236 ± 22 mEq. Standing from a supine position was associated with significant decreases (P < 0.0001) in creatinine clearance (from 125 ± 18 to 117 ± 19 mL/min per 1.73 m2), sodium excretion (from 178 ± 29 to 97 ± 23 μEq/min) and fractional excretion of sodium (from 1.02 ± 0.19 to 0.60 ± 0.13%). A significant increase (P < 0.0001) in the RVR index (from 0.11 ± 0.03 to 0.14 ± 0.04 units) was noted. Univariate analysis indicated that while the change in RVR associated with standing was significantly diminished (P < 0.05) in older subjects, orthostatic changes in other parameters associated with standing were minimally influenced by age. 4. In conclusion, although the renal vascular response is impaired in advanced age, the renal functional response to orthostasis is otherwise maintained in healthy elderly subjects under conditions of normal sodium intake and clinical euvolaemia.

Two-dimensional electron gas (2DEG) subjected to a spatially modulated magnetic field exhibits commensurability oscillation of magnetoresistance, analysis of which furnishes information on the modulation amplitude. Under a periodically modulated magnetic field with zero mean, the resistivity of the 2DEG gains an extra term expressed as Δρ=AT2+C. The temperature quadratic term is attributed to electron–electron umklapp scattering, while the constant term arises from combined effect of the lateral magnetic superlattice and random impurities. In the composite Fermion (CF) regime near the half-filling of lowest Landau levels, spatial variation of the electron density is equivalent to magnetic field variation. Use of a short period lateral superlattice has enabled us to observe the commensurability oscillation of the magnetoresistance of CFs near the filling factor ν=3/2. The positions of the resistance minima are consistent with those calculated by assuming magnetic modulation and fully spin-polarized CFs.

The vertical transport in multilayered quantum Hall systems has been studied under a tilted magnetic field. The out-of-plane resistance peaks at integer filling, and the peak value increases with increasing in-plane field component. The magnitude of the effect is almost the same in the low temperature regime and high temperature regime, and the effect can be accounted for by the suppression of the interlayer charge transfer by the in-plane field.

A 58-year-old woman was admitted to our hospital because of renal dysfunction that continued to progress even after withdrawal of cefdinir, the presumed cause of acute renal failure. Renal histologic findings included interstitial fibrosis accompanied by moderate lymphocytic infiltration, and tubular atrophy with reduced numbers of epithelial cells. Mesangial cells and glomerular basement membranes were nearly normal. Scintigraphy with 67gallium disclosed diffuse abnormal accumulation in both kidneys. A lymphocyte stimulation test with cefdinir was positive. The patient was diagnosed with acute tubulointerstitial nephritis caused by cefdinir. Serum creatinine concentrations continued to rise after withdrawal of the drug, but steroid therapy was effective in normalizing renal function.

A case of 46, XY pure gonadal dysgenesis with very tall stature was investigated. The 24-year-old, phenotypically female patient consulted our clinic because of linear growth persisting into adulthood. The patient was found to have no mutation or deletion of a sex-determining region of the Y chromosome, and also was found to have Graves' disease. Growth was arrested with height remaining at 187 cm after normalization of the thyroid function by treatment with an antithyroid agent, although follow-up to monitor growth was limited to 3 months. In some cases of gonadal dysgenesis, then, Graves' disease may contribute to an abnormally tall stature.

The vertical transport in weakly coupled multilayered two-dimensional electron systems has been studied in the integer quantum Hall regime. The current–voltage characteristics show prominent non-ohmicity in the vertical transport when each layer is in the quantum Hall state. The voltage dependence curves of the differential conductivity scaled by the mesa perimeter collapse onto a single curve at lower voltages, while those scaled by mesa area are on a single curve at higher voltages. This shows that the current flows through the surface of the sample at low-voltage region and through the bulk at high-voltage region. A crossover from the surface transport to the bulk transport occurs in a fairly narrow range of the bias voltage.

A rare, compound adrenal tumor consisting of ganglioneuroblastoma and pheochromocytoma was completely resected in an adult woman. Most of the tumor was occupied by the ganglioneuroblastoma component. This ganglioneuroblastoma was an intermixed tumor, which is known to have a favorable prognosis in children. Based on the lack of spread, the resectability of the tumor, and the histology of the ganglioneuroblastoma, no adjuvant therapy was employed. There was no evidence of recurrence at the 5-year follow-up. This suggests that adjuvant therapy may not be necessary in these compound tumors.

To determine the factors that affect seasonal variation in blood pressure (BP) in a fairly large number of patients with essential hypertension who stayed almost entirely indoors in a stable environmental temperature and who took a calcium channel blocker during the study. This prospective study of hypertensive patients was conducted during the summer and winter. BP was measured by ambulatory blood pressure monitoring; the indoor temperature was measured at the time of the BP measurement using an electrothermometer with the subject awake and indoors. Subjects comprised 38 men and 57 women. The subjects spent virtually the entire day indoors during both the summer (men, 22.1±1.6h; women, 23.0±0.9h) and winter (men, 23.0±0.9h; women, 22.9±0.9h). During the waking hours, the systolic/diastolic BPs were significantly higher during the winter than the summer. The differences were 8±9/4±5mmHg in men and 5±11/2±6mmHg in women; these values were not significantly different between men and women. No significant seasonal differences in BP during the sleeping hours were noted. There was a significant difference of approximately 6°C in the environmental temperature during waking hours, but there was no significant difference in urinary excretion of sodium or in exercise activity between the seasons. Only body height was significantly correlated with the winter increase in waking BP in both men and women, even after adjustment for potential confounding variables. Body height was a determinant of the increase in waking BP during the winter in hypertensive patients who lived almost entirely indoors. (Hypertens Res 2000; 23: 587-592)

The sympathoneural neurotransmitter norepinephrine (NE) is deaminated to 3,4-dihydroxymandelaldehyde (DHMAL) and subsequently converted to either 3,4-dihydroxymandelic acid (DHMA) or 3,4-dihydroxyphenylglycol (DHPG). In this study, we investigated the relative importance of aldose reductase versus aldehyde reductase in the formation of DHPG from DHMAL. The in vitro incubation of NE with aldose reductase in the presence of monoamine oxidase (MAO) resulted in the formation of DHPG, which was confirmed by mass spectrometry. Although aldehyde reductase also generated DHPG, its activity was much lower than that of aldose reductase. With northern blotting, the expression of both aldose reductase and aldehyde reductase was detected in rat superior cervical ganglia. However, with western blotting, only aldose reductase was immunologically detectable. Treatment of rats with aldose reductase inhibitors for 3 days increased the plasma level of DHMA. There was no correlation between the selectivity of inhibitors and effects on NE metabolite levels. A significant decrease in DHPG, however, was obtained only with an extremely high dose (9 mg/kg/day) of the nonselective inhibitor AL 1576. The present study confirmed that aldose reductase generates DHPG from NE in the presence of MAO. In rat sympathetic neurons, aldose reductase appears to be more important than aldehyde reductase for the formation of DHPG. However, when aldose reductase is inhibited, it appears that aldehyde reductase can compensate for the conversion of DHMAL to DHPG, indicating redundancy in the reduction pathway.

Vertical transport in GaAs/AlGaAs superlattices has been studied in the quantum Hall regime. Both the in-plane and out-of-plane resistances exhibit an Arrhenius-type temperature dependence with small values of activation energy. At very low temperatures, the out-of-plane conductance becomes almost temperature independent and its values scale with the sample perimeter, indicating that the current is carried by the chiral surface states. The vertical transport in this regime exhibits distinct non-Ohmicity, suggesting the onset of bulk transport at high bias voltages. Rather strong non-Ohmicity is also observed in the low bias voltage region where the chiral surface state is responsible for the vertical transport.

A 42-year-old man had biochemical and somatic abnormalities compatible with pseudohypoparathyroidism type I (PsHP) and also had high plasma renin activity (PRA). After 1, 25-dihydroxyvitamin D (calcitriol) supplementation the systolic/diastolic blood pressure, assessed by 24-hour non-invasive ambulatory blood pressure monitoring, was reduced from 145/96 mmHg to 128/85 mmHg with normalization of the serum calcium level and its related hormones, as well as decreased PRA. Calcitriol supplementation successfully reduced the blood pressure in this patient with PsHP and a high PRA, suggesting that calcium-related hormones and/or the renin-angiotensin system were involved in lowering the blood pressure.(Internal Medicine 38: 31-35, 1999)

We observe an adiabatic transport phenomena of electrons in valley-splitting quantum Hall edge channels for the first time using a high-mobility Si/SiGe two-dimensional electron system. We find that the scattering event between the valley-splitting edge channels is suppressed over a distance of ∼ 5 μ m , which is surprisingly longer than that expected from the valley-splitting energy gap in Si.

Vertical transport in GaAs/AlGaAs semiconductor superlattice has been studied as a function of magnetic field angle. A series of resistance peaks corresponding to the angular dependent magnetoresistance oscillation (ADMRO) effect were investigated. The present samples have higher carrier densities and wider well widths than previously studied. This allowed us to observe higher order ADMRO peaks. Another resistance peak is found at θ=90°(B‖layer). The origin of this peak structure is discussed in terms of occurrence of closed orbits in some part of a weakly corrugated cylindrical Fermi surface for this field orientation.

Neurotropin, a non-protein extract from the inflamed skin of rabbits inoculated with vaccinia virus, has been clinically used as an analgesic drug in Japan. Its analgesic effect has been demonstrated by reduced mechano-nociception in hyperalgesic rats exposed to SART-stress (a repeated cold stress) for 5 days. In order to clarify the mechanism of the analgesic effect of neurotropin at the spinal cord level, we examined the effects of several neurotransmitter receptor antagonists given by intrathecal (i.t.) injection on the antinociceptive effect of intraperitoneally (i.p.) injected neurotropin [100 and 200 Neurotropin Unit (NU)/kg]. The analgesic effect of neurotropin was significantly inhibited not only by methysergide (100 nmol Rat , i.t.), a non-selective antagonist against serotonin (5-HT), but also MDL 72222 (30 nmol Rat , i.t.), a selective 5-HT3 antagonist, but not influenced by ketanserin (100 nmol Rat , i.t.), a 5-HT2A antagonist. The antinociceptive effect of neurotropin (200 NU Kg , i.p.) was significantly inhibited also by yohimbine (30 nmol Rat , i.t.), a noradrenergic α2 antagonist. However, the analgesic effect of neurotropin (100 and 200 NU Kg , i.p.) was not influenced by naloxone (30 nmol Rat , i.t.), an opioid antagonist. These results suggest that the mechanism of the antinociceptive effect of neurotropin is via enhancement of endogenous descending pain inhibitory pathways of the serotonergic and noradrenergic systems, especially involving 5-HT3 and noradrenergic α2 receptors in spinal dorsal horn in which these neurons terminate. No influence of opioid receptors at the spinal cord level is indicated.

We have reproducibly fabricated suspended tungsten electrodes with a gap of less than 2nm on a suspended silicon nitride membrane with a slit. Our fabrication technique is based on the local deposition of tungsten by a focused ion beam. The length of the nanogap between the electrodes was controlled by detecting a tunneling current during the growth of the tungsten electrodes from both sides of the slit. The gap length can reach about 1nm, which corresponds to the size of a single molecule such as a fullerene.

After norepinephrine (NE) is deaminated by monoamine oxidase (MAO), the aldehyde formed is either metabolized to 3,4-dihydroxy-mandelic acid (DHMA) by aldehyde dehydrogenase or is converted to 3,4-dihydroxyphenylglycol (DHPG) by aldehyde or aldose reductase. The present study examined the effects of inhibition of aldehyde and aldose reductase on production of DHPG and DHMA in rats. Mean (+/- S.E.) baseline plasma concentrations of DHPG (4.73 +/- 0.21 pmol/ml) were 60-fold higher than those of DHMA (0.08 +/- 0.01 pmol/ml). Inhibition of aldose and aldehyde reductase reduced plasma DHPG concentrations to 1.88 +/- 0.14 pmol/ml and increased plasma DHMA to 4.43 +/- 0.29 pmol/ml; additional inhibition of MAO reduced plasma DHPG to 0.16 +/- 0.06 pmol/ml and DHMA to 0.19 +/- 0.02 pmol/ml. Inhibition of aldehyde and aldose reductase also increased brain tissue levels of DHMA from 8 +/- 2 to 384 +/- 47 pmol/g and decreased levels of DHPG from 70 +/- 9 to 44 +/- 5 pmol/g. The results show that DHMA is normally a minor metabolite of NE, but becomes a major metabolite after aldehyde/aldose reductase inhibition.

To evaluate the effects of prolonged intake of a high-sodium diet on glucose and lipid metabolism, we examined the relation of daily urinary sodium excretion to blood pressure, glucose metabolism, and lipid metabolism in 140 Japanese adults who lived in a region where the average daily consumption of sodium was high and stable during the past 15 yr; no subject had received any treatment for hypertension or metabolic disorders. Each subject was admitted to our health examination center for 2 d for measurement of blood pressure, sampling of blood, and glucose tolerance testing. A 24-h urine specimen was collected by each subject after discharge. Multiple regression analysis revealed that urinary sodium excretion was significantly independent of the mean blood pressure and was unrelated to the area under the serum glucose curve after glucose administration. The urinary sodium level was also unrelated to low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. The prevalence of hypertension in the group with a daily sodium excretion below 140 mEq (low sodium group) was 0%, while that in the group with a daily sodium excretion above 280 mEq (high sodium group) was 44%; this difference was significant (p < 0.01). No significant difference was observed in the prevalence of metabolic disorders between the two groups. Our results suggest that sodium intake has little influence on glucose and lipid metabolism but has a significant influence on blood pressure in normotensive and untreated hypertensive subjects who reside in an area with a relatively high sodium intake.

We study dynamic polarization and resistive detection of nuclear spins in a semiconductor quantum dot (QD) under the Kondo effect regime. We find that the differential conductance spectra of the QD exhibit hysteresis under the Kondo effect regime in magnetic fields. Relevance of nuclear spins to the hysteresis is confirmed by the detection of nuclear magnetic resonance signals by monitoring the differential conductance. We attribute the origin of the hysteresis to the dynamic nuclear spin polarization (DNP) induced in the QD. Using the DNP, we demonstrate nuclear spin relaxation rate measurements in the QD under the Kondo effect regime., Comment: 5 pages, 6 figures, accepted for publication in Phys. Rev. B

We investigated the correlations between the reduction in body weight (BW) induced by calorie restriction and reductions in blood pressure (BP) and improvement in metabolic disorders in overweight women with essential hypertension. After eating a standard diet (diet-I) for 2 weeks, women in the calorie-restricted group (n=25) received a low calorie diet for 2 weeks, and then standard diet-II for 1 week. Women in the calorie-nonrestricted group (n=13) ate standard diet-I for 5 weeks. The calorie-restricted group exhibited a significant reduction in BP in association with loss of BW; their levels of low-density lipoprotein cholesterol, and triglycerides levels, and their fasting levels of glucose and insulin were also reduced compared with the calorie-nonrestricted group. However, there were no significant differences in the level of high-density lipoprotein cholesterol, the areas under the 2-h glucose and insulin curves (AUCglu and AUCins), or the ratio of AUCglu to AUCins between groups. The change in BW was significantly correlated with a reduction in BP (r=0.62, p

We report a case of a thymic carcinoid associated with multiple endocrine neoplasia type 1( MEN-1). A 37-year-old man was referred to our hospital for further examination of an abnormal chest shadow. A chest computed tomography (CT) showed an anterior mediastinal mass measuring 6.5 cm in diameter. A pathological diagnosis of thymic carcinoid was made from a CT-guided needle biopsy specimen. Preoperative workup including endocrinological examination revealed a pituitary adenoma and hyperparathyroidism, and MEN-1 was clinically diagnosed. We performed total parathyroidectomy with autotransplantation and thymectomy with lymph node dissection through cervical collar incision and median sternotomy. The diagnosis of MEN-1 was confirmed by the genomic analysis postoperatively. Since 25% of thymic carcinoids are MEN-1 related and 95% of MEN-1 patients develop hyperparathyroidism, it should be kept in mind that this condition can be treated by thymectomy and concurrent parathyroidectomy.

The accuracy of the casual urine (CU) method for estimating daily salt intake was compared with the second morning urine (SMU) method and with 24-h urine collection (24 UC) method as the gold standard. Data were obtained from three previously reported studies, in which we evaluated the daily salt intake by the SMU method. Using SMU samples from 1315 outpatients, the estimated salt intake was lower with the CU method than the SMU method. In inpatients with a daily salt intake of 7, 8 or 18 g, the CU method was applied to SMU specimens. It underestimated salt intake compared with the 24-h collection method whereas the SMU method and 24 UC method gave similar results. In the present study, 24 UC was done and then urine was collected at 0800, 1100, 1400, 1700 and 1900 hours, with a daily salt intake of 6 g in 8 inpatients, 10 g in 11 inpatients or 15 g in 5 inpatients. In comparison with the 24 UC method, the CU method underestimated a high salt intake (15 g) when morning specimens were used and overestimated a low salt intake (6 g) when afternoon specimens were used. The correlation between the CU method and 24 UC method was weaker (R = 0.57) than that between the SMU method and 24 UC method (R = 0.85). In conclusion, the CU method is heavily influenced by the timing of urine collection and by the actual daily salt intake, so the SMU method provides a better estimate of individual salt intake.

We investigate Dirac fermions on the surface of the topological insulator ${\text{Bi}}_{2}{\text{Se}}_{3}$ using scanning tunneling spectroscopy. Landau levels (LLs) are observed in the tunneling spectra in a magnetic field. In contrast to LLs of conventional electrons, a field-independent LL appears at the Dirac point, which is a hallmark of Dirac fermions. A scaling analysis of LLs based on the Bohr-Sommerfeld quantization condition allowed us to determine the dispersion of the surface band. Near the Fermi energy, fine peaks mixed with LLs appear in the spectra, which may be responsible for the anomalous magnetofingerprint effect [J. G. Checkelsky et al., Phys. Rev. Lett. 103, 246601 (2009)].

We studied spatial distribution of dynamic nuclear polarization (DNP) in a Hall-bar device in a breakdown regime of the quantum Hall effect (QHE). We detected nuclear magnetic resonance (NMR) signals from the polarized nuclear spins by measuring the Hall voltage $V_{xy}$ using three pairs of voltage probes attached to the conducting channel of the Hall bar. We find that the amplitude of the NMR signal depends on the position of the Hall voltage probes and that the largest NMR signal is obtained from the pair of probes farthest from the electron-injecting electrode. Combined with results on pump-and-probe measurements, we conclude that the DNP induced by QHE breakdown develops along the electron-drift direction., Comment: 4 pages, 4 figures, accepted for publication in PRB

Angiotensin II does not increase renal prostaglandin E2 in response to pressure reduction. Whether angiotensin II (Ang II) stimulates renal secretion of prostaglandin E2 (PGE2) synthesized in response to pressure reduction was examined. PGE2 and Ang II in aortic and renal venous plasma were measured before and during renal arterial constriction in anesthetized dogs, with or without an intrarenal arterial infusion of an Ang II antagonist, losartan potassium (1 mg/min), or saralasin (3 µg/min). In other anesthetized dogs, two doses of Ang II (30 and then 300 ng/min) were infused into the renal artery, and plasma Ang II levels and renal PGE2 secretion were measured. When renal perfusion pressure was reduced to 75 and 45mm Hg by constriction, the renal secretion of PGE2 increased seven- and fourfold, respectively. Ang II levels in the renal venous plasma increased from 6.6 ± 1.8 to 21.7 ± 7.4 and then 48.1 ± 15.3 pg/ml (both P < 0.05) as the pressure decreased. Neither losartan nor saralasin suppressed the response of renal PGE2 secretion to the pressure reduction. The intrarenal infusion of Ang II (30 ng/min) elevated the Ang II level in the renal venous plasma from 9.8 ± 4.6 to 33.7 ± 4.2 pg/ml (P < 0.01), but did not increase PGE2 secretion. The higher dose (300 ng/min) of Ang II increased it, but the Ang II level in the renal venous plasma was 166 ± 63 pg/ml. These results suggest that the greater part of the increased renal synthesis of PGE2 in response to pressure reduction is not mediated by Ang II.

1. To examine the effect of chronic administration of angiotensin I-converting enzyme (ACE) inhibitor on circulating angiotensin II (AII) concentration, 20 mg of lisinopril was administered once daily for 7 consecutive days to eight healthy volunteers. 2. Plasma ACE activity was inhibited to less than approximately 30% of the pretreatment level during the repeated administration. 3. Mean arterial pressure (MAP) was slightly but significantly reduced during the administration period. Plasma AII concentration measured by an established method using high performance liquid chromatography combined with a radioimmunoassay, however, was maintained at approximately the pretreatment level when it was measured at 24 h intervals after each administration of lisinopril. 4. With the gradual recovery of ACE activity following discontinuation of administration, the plasma AII concentration correlated with AI concentration (r = 0.46), and also with the product of AI and ACE activity (AI x ACE; r = 0.80), corresponding to the formula obtained from the kinetics of ACE activity. No correlation was observed between MAP and AII levels throughout the study period. 5. We conclude that in normal subjects repeatedly administered with ACE inhibitor, the AII level in the circulation is still determined by an elevated level of AI and any remaining ACE activity, thus maintaining AII at pretreatment levels. We confirmed that it is not necessary to achieve a decrease in plasma AII concentration through the chronic administration of ACE inhibitor in order to effectively lower blood pressure.

Rats exposed to a cold environment (4 degrees C) for 30 min every 1 h during the day and at night show a gradual decrease in the nociceptive threshold for pressure stimulation. Such hyperalgesia, referred to as repeated cold stress (RCS)-induced hyperalgesia, is stable for at least 4 h and maintained for 3 days only by exposing to cold overnight; thus, no adaptation to RCS is apparent. Hyperalgesia gradually returns over 4 days after cold exposure ceases. To determine whether three neuropeptides, substance P (SP), calcitonin gene-related peptide (CGRP) and galanin (GAL), which are present in the superficial dorsal horn including primary afferent terminals, would be responsible for RCS-induced hyperalgesia, we examined the effects of intrathecal injections of their antibodies (used as inhibitors of neuropeptide-mediated synaptic transmission) on the nociceptive threshold of RCS rats, and compared this with the antibody effect on carrageenan-induced hyperalgesia. An intrathecal injection of anti-SP antibody significantly inhibited the hyperalgesia of RCS rats as well as carrageenan-induced hyperalgesia, and slightly increased the nociceptive threshold of non-RCS rats. Anti-CGRP antibody produced an improvement in the hyperalgesia of RCS rats as well as carrageenan-induced hyperalgesia without having an effect on the nociceptive threshold of non-RCS rats. Although anti-GAL antibody significantly inhibited carrageenan-induced hyperalgesia, it did not affect the nociceptive threshold of RCS and non-RCS rats. The present results suggest that enhancement of synaptic transmission mediated by SP and CGRP, but not GAL, in the spinal dorsal horn is, at least in part, involved in RCS-induced hyperalgesia.

1. The effects of dietary sodium on blood pressure and levels of sodium, other electrolytes and noradrenaline (NA) in the cerebrospinal fluid (CSF) and blood of 15 patients with essential hypertension were studied. The CSF and blood sampling was carried out after 7 days of a high salt intake (16-18 g/day) and after 7 days of a low salt intake (1-3 g/day). 2. Blood pressure and sodium concentrations in CSF and serum were significantly higher in the high salt period than the low salt period (CSF Na+ concentration: 147.7 +/- 0.4 mmol/L vs 145.3 +/- 0.5 mmol/L; P less than 0.001). Levels of CSF pressure and potassium or calcium concentrations were not different between the two periods. Plasma NA and plasma renin activity (PRA) were lower and CSF NA levels tended to be lower in the high salt period. 3. The levels and the changes in sodium and NA in CSF were not significantly different between the salt-sensitive (n = 8) and the non-salt-sensitive (n = 7) subjects, but the changes in plasma NA and PRA were smaller in the salt-sensitive subjects. 4. These results indicate that the sympathetic nervous system is less suppressed in salt-sensitive subjects during high salt intake. This may be due to altered neural responsiveness to sodium loading rather than being greater increases in sodium concentration in the central nervous system.

This study was performed to elucidate the effect of a hypocaloric diet on blood pressure and sodium balance in overweight women with essential hypertension. Hospitalized patients were fed a hypocaloric diet (900 kcal/day) for 3 weeks after being fed a standard diet (SD) for more than 2 weeks. During the study, the sodium and potassium intake was kept constant as was the level of exercise activity. After the mean arterial pressure (MAP) and body weight had stabilized during the last week on the SD, caloric restriction significantly reduced the body weight by 1.5kg in the first week and by 0.8-0.9 kg in subsequent weeks, and reduced the MAP by 5mmHg and by 1-3mmHg, respectively. Although caloric restriction reduced the excretion of urinary norepinephrine and C-peptide, and elevated the serum levels of ketone bodies that would induce natriuresis, the urinary sodium excretion remained unchanged, indicating that sodium balance was unchanged even by caloric restriction. These results suggest that caloric restriction lowers the blood pressure in a short time with no significant change in sodium balance. (Hypertens Res 1992; 15: 137-142)

INAGAMI, T., MIZUNO, K., KAWAMURA, M., OKAMURA, T., CLEMENS, D.L. and HIGASHIMORI, K. Localization of Components of the Renin-Angiotensin System within the Kidney and Sustained Release of Angiotensins from Isolated and Perfused Kidney. Tohoku J. Exp. Med., 1992, 166 (1), 17-26-We found colocalization of renin, angiotensin (Ang) I and Ang II in juxtaglomerular (JG) cells of the kidney. Coexistence of Ang II in renin granules was demonstrated by electron microscopic immunogold labeling of these components. Coexistence of both Ang I and Ang II in the high density renin storage granules were also demonstrated by gradient centrifugation of renal homogenate. These findings supported the synthesis of Ang I and Ang II in juxtaglomerular cells. Isolated and cultured JG cells showed the synthesis of Ang I, Ang II and renin. Ang I and Ang II were secreted from isolated and perfused rat kidneys at steady rates over 2hr. Their secretion rates were proportional to that of renin. The rate of Ang II secretion from the kidney was higher than that from the vascular bed. Ang II was also found in renal lymph. These findings indicate that a large amount of Ang II is generated in JG cells by the intracellular action of renin and may play a significant role in the regulation of renal function.

We study dynamic nuclear polarization (DNP) induced by breakdown of the fractional quantum Hall (FQH) effect. We find that voltage-current characteristics depend on current sweep rates at the quantum Hall states of Landau level filling factors $\nu$ = 1, 2/3, and 1/3. The sweep rate dependence is attributed to DNP occurring in the breakdown regime of FQH states. Results of a pump and probe experiment show that the polarities of the DNP induced in the breakdown regimes of the FQH states is opposite to that of the DNP induced in the breakdown regimes of odd-integer quantum Hall states., Comment: 4 pages, 4 figures

We show electrical coherent manipulation of quadrupole-split nuclear spin states in a GaAs/AlGaAs heterostructure on the basis of the breakdown of quantum Hall effect. The electric quadrupole splitting in nuclear spin energy levels is intentionally enhanced by applying an external stress to the heterostructure. Nuclear magnetic resonance spectra with clearly separated triple peaks are obtained, and Rabi oscillations are observed between the nuclear spin energy levels. The decay of the spin-echo signal is compared between the cases before and after the enhancement of quadrupole splitting., Comment: 4 pages, 4 figures

The effects of brain natriuretic peptide (BNP) on renin secretion were evaluated in normal and hypertonic saline-infused kidneys of anesthetized dogs. In the normal kidney (N = 5), intrarenal infusion of porcine BNP-(1-26) (pBNP) at a dose of 50 ng/kg per min attenuated the renin secretion rate significantly to 9 +/- 27% of control without exerting a significant effect on mean arterial pressure (MAP), renal blood flow (RBF) or glomerular filtration rate (GFR); urine flow (V) was significantly increased to 260 +/- 33% of control and urinary excretion of sodium (UNaV) to 480 +/- 140% of control. In the hypertonic saline infusion group (N = 6), intrarenal infusion of hypertonic saline (20% w/v) at 0.5, 0.8, and 1.0 mEq NaCl/min caused a decrease in GFR and natriuresis in a dose-dependent manner. The renin secretion rate was attenuated by hypertonic saline infusion (1 mEq NaCl/min) to 87 +/- 31% of control. In another group (N = 6), administration of pBNP at a dose of 50 ng/kg per min during hypertonic saline infusion (1 mEq NaCl/min) increased the renin secretion rate to 196 +/- 57%, increased RBF to 160 +/- 13%, increased GFR to 137 +/- 22%, increased V to 221 +/- 29%, and increased UNaV to 218 +/- 29% of the values measured during hypertonic saline infusion. Our results indicate that BNP inhibits renin secretion through sodium delivery to the macula densa and effectively inhibits the tubuloglomerular feedback response that is activated by intrarenal hypertonic saline infusion.

The effects of a calcium-entry blocker, nicardipine, on intrarenal hemodynamics were studied in essential hypertension. A 4-week study was performed in eight patients with essential hypertension who were given a regular sodium diet in the first and third weeks, and a sodium-restricted diet in the second and fourth weeks. Nicardipine, 60 mg/d, was administered in the third and fourth weeks. The urinary sodium excretion rate (U Na V) was plotted on the y-axis against the mean arterial pressure (MAP) on the x-axis before and after the administration of nicardipine. Assuming the difference between MAP and the x-intercept of this renal function curve represents the effective filtration pressure across the glomerular capillaries, the intrarenal hemodynamics such as afferent arteriolar resistance (R A ) and efferent arteriolar resistances (R E ), glomerular pressure (P G ), and gross filtration coefficient (K FG ) were calculated. Although the MAP on regular salt diet was lowered from 125 ± 3 to 109 ± 2 mm Hg by nicardipine, neither the renal blood flow rate (RBF) (670 ± 40 mLlmin) nor the glomerular filtration rate (GFR) (79 ± 2 mLlmin) was altered. The R A was estimated to be reduced from 9,300 ± 900 to 7,400 ± 700 dyne·s·cm −5 ( P E (4,900 ± 400 dyne·s·cm −5 ), P G (50 ± 1 mm Hg), or K FG (0.180 ± 0.041 [mL/s]/mm Hg). Essential hypertension has been chararacterized by a prominent increase in R A , resulting in maintenance of normal P G . This Ca-entry blocker worked to normalize intrarenal hemodynamics in essential hypertension by dilating afferent arterioles alone. The reason why neither the RBF nor the GFR was increased by a longterm administration of nicardipine seemed due mainly to a parallel reduction in MAP with the reduced R A .

近年, 透析患者の循環器疾患による死亡率は年々増加してきている. そこで, 透析患者の予後を決定する上で, 血圧がどの程度関与しているか検討した. 1977年から1987年までに当施設で血液透析に導入し, 転院し得た慢性腎不全患者195例 (男123例, 女72例, 平均年齢54±1歳) について導入期および, 維持期 (転院時) における血圧と1990年1月現在における生死との関連を検討した. 3年以上生存した生存群132例と3年未満に死亡した死亡群46例との比較では, 死亡群で平均年齢が高く (61±2歳vs 50±1歳), 糖尿病性腎症の割合が高く, 収縮期血圧は導入期 (178±4mmHg vs 167±2mmHg), 維持期 (165±4mmHg vs 147±2mmHg) とも高値であった. ただし, 拡張期血圧に関しては導入期, 維持期とも両群間に有意差を認めなかった. 非糖尿病性腎症例に限ると維持期収縮期血圧のみ死亡群で有意に高値であった. そこで, 維持期収縮期血圧に着目し160mmHg以上をHT群, 160mmHg未満をNT群とし, 累積生存率を比較検討した. 195例全例でも, 非糖尿病性腎症でも, 糖尿病性腎症例でもHT群に比しNT群で有意に生存率が高値を示した. 導入期から維持期に至る収縮期血圧の推移別に, 1. 導入期収縮期血圧が160mmHg以上であったが, 維持期には160mmHg未満に低下したHT-NT群, 2. 維持期にもなお160mmHg以上を示したHT-HT群, および3. 導入期, 維持期を通して160mmHg未満であったNT-NT群の3群に分類し累積生存率を比較した. HT-NT群はHT-HT群に比し有意に生存率が高くNT-NT群と有意差のないレベルに達していた. 以上より, 透析導入によって是正された後の維持期収縮期血圧が透析患者の予後を決定する重要な因子と考えられた.

Exposing mice to 24 and 4 degrees C in alternate 1 hr periods in the day time and maintaining 4 degrees C at night for several days decreases the tail clamp pressure required to evoke pain behavior. This model is referred to as SART (specific alternation rhythm of temperature) stress. An extract from inflamed skin of rabbits inoculated with vaccinia virus (neurotropin) clearly normalized the hyperalgesia in this SART stress model. To clarify the mechanism of the hyperalgesia in SART mice and the mode of the antinociceptive action of neurotropin in this model, the influence of systemically administered neurotransmitter related drugs was studied. 1) Neurotropin, 5-hydroxytryptophan and L-dihydroxyphenylalanine significantly normalized the decrease in nociceptive threshold, and muscimol tended to inhibit it in nociceptive threshold in SART stressed mice. 2) Haloperidol, phenoxybenzamine, reserpine, bicuculline, scopolamine, physostigmine and naloxone alone did not influence the nociceptive threshold in SART stressed mice. 3) The antinociceptive effect of neurotropin was significantly attenuated by p-chlorophenylalanine, haloperidol and phenoxybenzamine; and it was completely inhibited by reserpine. 4) Naloxone, bicuculline, scopolamine and physostigmine had no influence on the antinociceptive effect of neurotropin. These results suggest that hypofunction mainly of the monoaminergic systems contributes to hyperalgesia in SART stressed mice and that neurotropin produces the antinociceptive effect by restoring these neural functions.

Neurotropin, a nonprotein extract isolated from inflamed skin of rabbits inoculated with vaccinia virus, is widely used in Japan to treat chronic pain such as neuropathic pain. Although some studies have been conducted on the mechanism of the antiallodynic action of Neurotropin, this mechanism has yet to be adequately clarified.The left fifth lumbar nerve of rats was tightly ligated with silk sutures under pentobarbital anesthesia. Mechanical allodynia was confirmed by measuring the hindpaw withdrawal threshold in response to application of von Frey filaments. Behavioral tests were performed at 28 days after nerve ligation. Neurotropin was administered IV, intrathecally or intracerebroventricularly in L5 spinal nerve ligation (L5-SNL) rats. We examined the effects of noradrenergic, serotonergic and gamma-aminobutyric acid (GABA)ergic antagonists on the antiallodynic action of Neurotropin in L5-SNL rats. Yohimbine hydrochloride (yohimbine) was used as an alpha(2) adrenoceptor antagonist, ketanserin tartrate (ketanserin) as a 5-HT(2A) receptor antagonist, MDL72,222 as a 5-HT(3) receptor antagonist, (-)-bicuculline methobromide (bicuculline) as a GABA(A) receptor antagonist, and CGP35,348 as a GABA(B) receptor antagonist, and intrathecally injected.IV (50-100 NU/kg) doses of Neurotropin elicited an antiallodynic action in L5-SNL rats. Moreover, intracerebroventricular (400 mNU/rat), but not intrathecal, injection of Neurotropin inhibited allodynia. The antiallodynic action of Neurotropin (100 NU/kg, IV) was antagonized by intrathecal injections of yohimbine (10 nmol/rat), ketanserin (30 nmol/rat), MDL72,222(30 nmol/rat), bicuculline (0.6 nmol/rat) and CGP35348 (30 nmol/rat). On the other hand, the antiallodynic action of intrathecally injected m-CPBG (5-HT(3) receptor agonist) was reversed by intrathecal injection of bicuculline and CGP35348, suggesting interaction of 5-HT(3) receptors and spinal inhibitory (GABAergic) interneurons.These results suggest that the antiallodynic effect of Neurotropin is mediated via activation of descending pain inhibitory systems, such as the noradrenergic and serotonergic systems, which project from supraspinal sites to the spinal dorsal horn. In addition, activation of inhibitory GABAergic interneurons via 5-HT(3) receptors by serotonin released in the spinal dorsal horn may also be involved in the antiallodynic action of Neurotropin.

Objective Salt intake restriction is important to health maintenance in subjects tending toward excessive intake. For convenience salt intake is ordinarily estimated at health check up centers using a salt-preference questionnaire, but whether or not the questionnaire identifies excessive salt consumers is unclear. Methods Daily salt intake in 725 subjects including 452 men examined at our health-check center was estimated by a spot urine method developed by Kawasaki et al (Clin Exp Pharmacol Physiol 20:7-14, 1993). Results from the questionnaire were used to divide into salt preference and non-salt preference groups. Results Daily salt intake estimated by the spot urine method was 13.5±3.5 g in male subjects and 12.4±3.1 g in female subjects. Salt preference subjects included 42% men and 24% of women. As a daily salt intake of less than 10 g is recommended for the general population in Japan, subjects whose salt intake exceeded 10 g were considered excessive salt consumers. Among men, excessive salt consumers comprised 85% of the salt preference group and 84% of the non-salt preference group. Among women, 88% of the salt preference group and 76% of the non-salt preference group were excessive consumers. Conclusions A simple questionnaire for salt preference was not effective in identifying excessive salt consumers. Convenient, reliable methods for the estimation of salt intake, such as the spot urine method, are recommended in place of the questionaire.

We experimentally study the tunneling magnetoresistance (TMR) effect as a function of bias voltage $({V}_{\mathrm{SD}})$ in lateral $\mathrm{Ni}∕\mathrm{In}\mathrm{As}∕\mathrm{Ni}$ quantum-dot (QD) spin valves showing Coulomb blockade characteristics. With varying ${V}_{\mathrm{SD}}$, the TMR value oscillates and the oscillation period corresponds to conductance changes observed in the current-voltage $(I\text{\ensuremath{-}}{V}_{\mathrm{SD}})$ characteristics. We also find an inverse TMR effect near ${V}_{\mathrm{SD}}$ values where negative differential conductance is observed. A possible mechanism of the TMR oscillation is discussed in terms of spin accumulation on the QD and spin-dependent transport properties via excited states.

We investigated the possible role of renal prostaglandin (PG) E2 in natriuresis associated with supraventricular tachycardia (SVT). In five female patients with paroxysmal tachycardia, SVT was artificially induced and then stopped 60 min later. Before, during, and after SVT, plasma levels of arginine vasopressin and atrial natriuretic peptide (ANP) and the urinary excretion of sodium and PGE2 were measured. Polyuria was observed during SVT. However, natriuresis did not occur until immediately after the termination of SVT. During SVT, the plasma levels of arginine vasopressin tended to decrease. When SVT was terminated, the vasopressin levels increased significantly (p less than 0.01). Urinary excretion of PGE2 tended to decrease during SVT and then increased significantly (p less than 0.01) after SVT ended. Urinary excretion of sodium was correlated (r = 0.699, p less than 0.001) with the urinary excretion of PGE2. Plasma ANP increased during SVT, but there was no correlation with urinary sodium excretion. These results suggest that renal PGE2, the biosynthesis of which may be stimulated by a increase in plasma vasopressin, is an important factor contributing to the natriuresis observed after the end of SVT.

血液透析中に心電図上のST下降が認められたにもかかわらず, 冠動脈造影で有意狭窄病変 (70%狭窄以上) がなかった2症例を経験した. 症例1は28歳の女性で, 慢性腎炎による慢性腎不全で透析導入1年後に透析中の胸痛を主訴として入院した. 透析開始2時間後に胸痛が出現し, 心電図でST下降を示した. ニトログリセリンの舌下服用で胸痛が増悪した. 除水を中止し, 生理食塩水100mlを静注したところ, 胸痛が消失し, 心電図も正常化した. 冠動脈造影では有意狭窄が認められなかった. 症例2は49歳の男性で, 糖尿病性腎症のため血液透析を導入した. 透析開始2時間後に無症候性に心電図上ST下降が出現した. 透析中のST下降時に心筋シンチグラフィーを施行したところ, 左室前壁側に心筋虚血所見が検出されたため冠動脈造影を行った. しかし, 有意狭窄は認められなかった.症例1ではST下降時に胸痛を伴ったこと, 症例2ではST下降時の心筋シンチグラフィーで心筋虚血所見が認められたことから, これら2例の心電図ST下降は心筋虚血に起因すると考えられた. 冠動脈造影所見が正常であっても透析患者では貧血や左室肥大, また基礎疾患として高血圧, 糖尿病, 高脂血症, 腎不全に基づく心筋障害が存在するために透析中の血圧低下によって心筋虚血が生じることを示唆した.

人工腎治療患者の理想体重 (BWi) は, 血圧, 心胸比等から臨床的に決定されているが, 未だ, これを算出する方法は確立されていない. そこで, ureaおよびクレアチニンのkineticsを応用し, 総体液量 (TBF) と固形重量 (除脂肪体重-TBF) を算出し, 体液生理学的なBWiを決定した. 人工腎治療患者9名 (男7名, 女2名) を対象に血液濾過 (HF) を施行した. 後希釈法で約5時間, 20lの限外濾過, 体液置換を行い, HF前後の体重 (BW), 血清尿素窒素濃度, 濾液量, 濾液中の平均尿素窒素濃度, HF後と次回HF前の血清クレアチニン濃度とその間の尿中クレアチニン排泄量を測定した. TBFはurea kineticsを応用してHF前後のBW, 血清尿素窒素濃度, 濾液中の尿素窒素濃度から算出した. 固形重量 (S) はクレアチニン産生量 (GCr) と比例関係が成立することを利用して算出した. GCrは尿中クレアチニン排泄量, 体内クレアチニン蓄積量, 腎外性クレアチニン排泄量の総和から求めた. また, 理想状態におけるTBFと除脂肪体重 (LBM) との比は一定 (TBF/LBM=0.735) であることに基づき, 理想総体液量 (TBFi) の推定が可能である. 算出したTBFi, S, 脂肪重量は各々36.7±1.8l, 13.7±1.1kg, 3.7±2.3kgであった. これら3者の総和として求めたBWiは55.1±4.2kgで, 臨床上のdry weight (54.0±3.5kg) との間には有意な相関があり (r=0.9, p

The present study was designed to examine and compare the acute effects of lisinopril (20 mg) and enalapril (10 mg) after a single oral administration on the inhibition of the renin-angiotensin system (RAS) in eight normal subjects. Serum concentration of lisinopril and enalaprilat, an active metabolite of enalapril, reached the respective maximal levels at 6 and 4 hr after administration of the drugs. At 24 hr, the serum concentration of lisinopril was higher than that of enalapril; thus the rate of disappearance of lisinopril was retarded, in comparison to that of enalapril. The reduction of serum angiotensin I converting enzyme (ACE) activity was consistent with the pattern of increase of concentration of the drugs in the serum. However, with these two drugs, the concentration of plasma ANG II was decreased in a similar manner, and it returned to the pretreatment level within 24 hr. Thus, there was no significant difference in ANG II levels throughout the 24 hr-study between the lisinopril and enalapril treatment. The results indicate that a single administration of 20 mg lisinopril and 10 mg enalapril show similar potency for lowering the circulating ANG II level, although lisinopril exerts a more sustained inhibition of serum ACE activity. The measurement of ANG II provides useful informations for evaluating the efficacy of ACE inhibitors for the inhibition of circulatory RAS.

We demonstrate an electric-field control of tunneling magnetoresistance (TMR) effect in a semiconductor quantum-dot (QD) spin-valve device. By using ferromagnetic Ni nano-gap electrodes, we observe the Coulomb blockade oscillations at a small bias voltage. In the vicinity of the Coulomb blockade peak, the TMR effect is significantly modulated and even its sign is switched by changing the gate voltage, where the sign of the TMR value changes at the resonant condition., 3 pages, 3 figures

We study the edge-channel transport at quantum Hall (QH) transition regions for a high-mobility $\mathrm{Si}∕\mathrm{Si}\mathrm{Ge}$ QH conductor by measuring nonlocal resistance $({R}_{\mathrm{NL}})$. The ${R}_{\mathrm{NL}}$ as a function of magnetic field changes drastically after Landau-level crossings. The features of the ${R}_{\mathrm{NL}}$ depend on the spin configuration between the innermost edge channel and the bulk state: the ${R}_{\mathrm{NL}}$ appears only when the relevant edge-bulk states have opposite spin orientations. Also, an origin of the spin-dependent resistivity [Phys. Rev. Lett. 94, 176402 (2005)] at QH transition regions is discussed in terms of the spin-dependent inter-edge-bulk scattering.