Visualization of an axion insulating state at the transition between 2 chiral quantum anomalous Hall states.

Quantum-relativistic materials often host electronic phenomena with exotic spatial distributions. In particular, quantum anomalous Hall (QAH) insulators feature topological boundary currents whose chirality is determined by the magnetization orientation. However, understanding the microscopic nature of edge vs. bulk currents has remained a challenge due to the emergence of multidomain states at the phase transitions. Here we use microwave impedance microscopy (MIM) to directly image chiral edge currents and phase transitions in a magnetic topological insulator. Our images reveal a dramatic change in the edge state structure and an unexpected microwave response at the topological phase transition between the Chern number [Formula: see text] and [Formula: see text] states, consistent with the emergence of an insulating [Formula: see text] state. The magnetic transition width is independent of film thickness, but the transition pattern is distinct in differently initiated field sweeps. This behavior suggests that the [Formula: see text] state has 2 surface states with Hall conductivities of [Formula: see text] but with opposite signs.

Large Anomalous Hall Effect in Topological Insulators with Proximitized Ferromagnetic Insulators.

We report a proximity-driven large anomalous Hall effect in all-telluride heterostructures consisting of the ferromagnetic insulator Cr_{2}Ge_{2}Te_{6} and topological insulator (Bi,Sb)_{2}Te_{3}. Despite small magnetization in the (Bi,Sb)_{2}Te_{3} layer, the anomalous Hall conductivity reaches a large value of 0.2e^{2}/h in accord with a ferromagnetic response of the Cr_{2}Ge_{2}Te_{6}. The results show that the exchange coupling between the surface state of the topological insulator and the proximitized Cr_{2}Ge_{2}Te_{6} layer is effective and strong enough to open the sizable exchange gap in the surface state.

Current-Driven Instability of the Quantum Anomalous Hall Effect in Ferromagnetic Topological Insulators.

The instability of the quantum anomalous Hall (QAH) effect has been studied as a function of the electric current and temperature in ferromagnetic topological insulator thin films. We find that a characteristic current for the breakdown of the QAH effect is roughly proportional to the Hall-bar width, indicating that the Hall electric field is relevant to the breakdown. We also find that electron transport is dominated by variable range hopping (VRH) at low temperatures. Combining the current and temperature dependences of the conductivity in the VRH regime, the localization length of the QAH state is evaluated to be about 5 µm. The long localization length suggests a marginally insulating nature of the QAH state due to a large number of in-gap states.

Electronic Magnetization of a Quantum Point Contact Measured by Nuclear Magnetic Resonance.

We report an electronic magnetization measurement of a quantum point contact (QPC) based on nuclear magnetic resonance (NMR) spectroscopy. We find that NMR signals can be detected by measuring the QPC conductance under in-plane magnetic fields. This makes it possible to measure, from Knight shifts of the NMR spectra, the electronic magnetization of a QPC containing only a few electron spins. The magnetization changes smoothly with the QPC potential barrier height and peaks at the conductance plateau of 0.5×2e^{2}/h. The observed features are well captured by a model calculation assuming a smooth potential barrier, supporting a no bound state origin of the 0.7 structure.

Clinical application of the second morning urine method for estimating salt intake in patients with hypertension.

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.

[Thymic carcinoid associated with multiple endocrine neoplasia type 1].

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.

Current-induced switching of proximity-induced ferromagnetic surface states in a topological insulator.

Electrical manipulation of magnetization could be an essential function for energy-efficient spintronics technology. A magnetic topological insulator, possessing a magnetically gapped surface state with spin-polarized electrons, not only exhibits exotic topological phases relevant to the quantum anomalous Hall state but also enables the electrical control of its magnetic state at the surface. Here, we demonstrate efficient current-induced switching of the surface ferromagnetism in hetero-bilayers consisting of the topological insulator (Bi1-xSbx)2Te3 and the ferromagnetic insulator Cr2Ge2Te6, where the proximity-induced ferromagnetic surface states play two roles: efficient charge-to-spin current conversion and emergence of large anomalous Hall effect. The sign reversal of the surface ferromagnetic states with current injection is clearly observed, accompanying the nearly full magnetization reversal in the adjacent insulating Cr2Ge2Te6 layer of an optimal thickness range. The present results may facilitate an electrical control of dissipationless topological-current circuits.

Large non-reciprocal charge transport mediated by quantum anomalous Hall edge states.

The topological nature of the quantum anomalous Hall effect (QAHE) causes a dissipationless chiral edge current at the sample boundary1,2. Of fundamental interest is whether the chirality of the band structure manifests itself in charge transport properties. Here we report the observation of large non-reciprocal charge transport3 in a magnetic topological insulator, Cr-doped (Bi,Sb)2Te3. When the surface massive Dirac band is slightly carrier doped by a gate voltage, the edge state starts to dissipate and exhibits a current-direction-dependent resistance with a directional difference as large as 26%. The polarity of this diode effect depends on the magnetization direction as well as on the carrier type, electrons or holes. The correlation between the non-reciprocal resistance and the Hall resistance indicates that the non-reciprocity originates from the interplay between the chiral edge state and the Dirac surface state.

The antiallodynic effect of Neurotropin is mediated via activation of descending pain inhibitory systems in rats with spinal nerve ligation.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Neurotropin® inhibits calpain activity upregulated by specific alternation of rhythm in temperature in the mesencephalon of rats.

AIMS: Neurotropin® (NTP), an analgesic for chronic pain, has antihyperalgesic effects in specific alternation of rhythm in temperature (SART)-stressed rats. Previous studies have shown that SART stress induces hyperalgesia, as well as post-translational modification of proteins (including substrates for calpain, a calcium-dependent cysteine protease) in the mesencephalon of rats. To better understand the mechanism of action of NTP, we investigated whether SART stress activates calpain in the mesencephalon of rats and whether NTP inhibits this activation. MAIN METHODS: Wistar rats were exposed to SART stress for 5days. NTP (200NU/kg/day) was administered intraperitoneally every day from the onset of SART stress. The mechanical pain threshold was measured using the Randall-Selitto test on the 6th day. Thereafter, the rat mesencephalon was immediately collected and calpain activity was examined using western blot analysis with a calpain cleavage site-specific antibody. KEY FINDINGS: SART stress induced hyperalgesia and increased the calpain activity in the mesencephalon of rats. In contrast, NTP treatment attenuated the hyperalgesia and prevented the increase in calpain activity in the mesencephalon of SART-stressed rats. Interestingly, a negative correlation was identified between calpain activity and mechanical pain threshold in SART-stressed rats treated with or without NTP. Furthermore, NTP inhibited calpain activity on mammalian uncoordinated-18 in rat mesencephalon homogenate and Ac-LLY-AFC as substrates in an in vitro cell-free system. SIGNIFICANCE: Our data demonstrate that NTP treatment prevents SART stress-induced calpain activation in the mesencephalon of rats and suggests that NTP-mediated antihyperalgesia is associated with an inhibition of calpain activity in the mesencephalon.

Tailoring tricolor structure of magnetic topological insulator for robust axion insulator.

Exploration of novel electromagnetic phenomena is a subject of great interest in topological quantum materials. One of the unprecedented effects to be experimentally verified is the topological magnetoelectric (TME) effect originating from an unusual coupling of electric and magnetic fields in materials. A magnetic heterostructure of topological insulator (TI) hosts such exotic magnetoelectric coupling and can be expected to realize the TME effect as an axion insulator. We designed a magnetic TI with a tricolor structure where a nonmagnetic layer of (Bi, Sb)2Te3 is sandwiched by a soft ferromagnetic Cr-doped (Bi, Sb)2Te3 and a hard ferromagnetic V-doped (Bi, Sb)2Te3. Accompanied by the quantum anomalous Hall (QAH) effect, we observe zero Hall conductivity plateaus, which are a hallmark of the axion insulator state, in a wide range of magnetic fields between the coercive fields of Cr- and V-doped layers. The resistance of the axion insulator state reaches as high as 109 ohms, leading to a gigantic magnetoresistance ratio exceeding 10,000,000% upon the transition from the QAH state. The tricolor structure of the TI may not only be an ideal arena for the topologically distinct phenomena but can also provide magnetoresistive applications for advancing dissipation-less topological electronics.

Seasonal Variation in the Daily Urinary Sodium Excretion in Outpatients from the Morioka Region of Northern Japan.

Objective Although the daily urinary sodium excretion (UNaV) is considered to provide the most reliable estimate of the daily sodium intake, it may be affected by salt loss due to sweating in summer. However, the seasonal variation in the daily UNaV associated with a normal lifestyle is unknown. Methods This study was performed in 348 outpatients from the Morioka region during three seasons: summer (summer 1), winter, and the following summer (summer 2). The daily UNaV (g salt/day) was estimated by the second morning urine method three times during each season. Seasonal variation was defined as a significant trend across the three seasons together with a significant difference between winter and both summers. Results In women, the daily UNaV was higher in winter (11.8±3.0 g salt/day) than in summer 1 (11.2±2.9 g salt/day) or summer 2 (11.0±2.9 g salt/day). In contrast, there was no marked seasonal variation in men. An analysis stratified by age (4 quartiles) identified seasonal variation in the older 2 quartiles of women (aged ≥68 years). In these women, the mean seasonal difference in the daily UNaV was 0.9 g of salt/day for both winter vs. summer 1 and winter vs. summer 2, while it was 0.1-0.8 g of salt/day in the other groups. Conclusion Seasonal variation in the daily UNaV only occurred in older female patients and was relatively small. This is evidence for restricting salt intake throughout the year and should reassure patients who are anxious about salt loss due to sweating in summer.

Effectiveness of a spot urine method in evaluating daily salt intake in hypertensive patients taking oral antihypertensive drugs.

Kawasaki et al. developed a spot urine method (SUM) for evaluating daily salt intake using one pre-breakfast sample obtained after initial voiding upon arising. Their subjects were healthy persons who were not taking any regular medications. To determine whether SUM can be successfully used for patients taking antihypertensive drugs, we estimated daily salt intake in 73 hypertensive patients by SUM and by a food consumption method (FCM) when they were at home, and also by SUM in the hospital with a defined intake of 7 g of sodium chloride (NaCl). Forty-one patients took oral antihypertensive medications once daily, while 32 patients took none. Mean daily salt intakes by SUM during admission were 7-8 g of NaCl in both groups (95% confidence intervals: 5.0-10.6 g in the medication group; 5.2-11.1 g in the no-medication group), which corresponded well to the diet. In contrast, ambulatory daily salt intake by SUM varied widely (95% confidence intervals: 5.5-20.7 g in the medication group; 7.6-22.8 g in the no-medication group). However, the daily salt intakes determined by SUM and FCM correlated significantly with each other in the medication group (r=0.69, p<0.01) and the no-medication group (r=0.66, p<0.01). SUM is therefore a reliable method for evaluating daily salt intake in patients taking antihypertensive medication as well as unmedicated patients.

Excitatory effect of Neurotropin(®) on noradrenergic neurons in rat locus coeruleus.

AIMS: Although the clinical use of Neurotropin® as an analgesic for chronic pain has been firmly established, its analgesic mechanism is still unclear. In this study, we investigate the direct effects of Neurotropin using an electrophysiological method. MAIN METHODS: Blind patch-clamp recordings were made from rat locus coeruleus (LC) and periaqueductal gray (PAG) neurons in brainstem slices of normal rats. The effects of intracerebroventricular (icv) injection of Neurotropin on nociceptive transmission were recorded from spinal substantia gelatinosa (SG) neurons in fifth lumbar spinal nerve-ligated (L5-SNL) rats using an in vivo patch-clamp method. KEY FINDINGS: Neurotropin (0.2­1.0 NU/mL) dose-dependently increased the firing rate in noradrenergic LC neurons of normal rats. Under the voltage-clamp condition, Neurotropin induced an inward current in 90% of LC neurons thatwas not affected by tetrodotoxin or an injection of GDP-ß-S (G protein inhibitor) through recording pipettes. In contrast, Neurotropin had no effects on all PAG neurons tested. Using in vivo patch-clamp recordings, the icv injection of Neurotropin inhibited both frequency and amplitude of pinch-evoked excitatory postsynaptic currents of SG neurons in L5-SNL rats. These results suggest that Neurotropin directly excites the descending noradrenergic LC neurons and inhibits nociceptive transmission in the spinal dorsal horn. SIGNIFICANCE: This study is the first direct demonstration that Neurotropin activates the noradrenergic descending pain inhibitory systems, and this would reinforce the usefulness of Neurotropin in the treatment of human neuropathic pain.

Effects of intrathecal antibodies to substance P, calcitonin gene-related peptide and galanin on repeated cold stress-induced hyperalgesia: comparison with carrageenan-induced hyperalgesia.

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.

Aldose reductase: an aldehyde scavenging enzyme in the intraneuronal metabolism of norepinephrine in human sympathetic ganglia.

The neurotransmitter norepinephrine is metabolized by monoamine oxidase into an aldehyde intermediate that is further metabolized to the stable glycol derivative, 3,4-dihydroxyphenylglycol (DHPG). In this study, the possible role of aldose reductase in reducing this aldehyde intermediate in human sympathetic neurons has been examined. DHPG is formed when norepinephrine is incubated with aldose reductase in the presence of monoamine oxidase. DHPG metabolism is inhibited by the monoamine oxidase inhibitor, pargyline which prevents the deamination of norepinephrine, and by the aldose reductase inhibitor AL 1576, which inhibits DHPG formation without affecting the deamination of norepinephrine. Although similar formation of DHPG was observed with human liver aldehyde reductase, the production of DHPG was more effective with aldose reductase than aldehyde reductase. Two peaks of reductase activity corresponding to aldose reductase and aldehyde reductase were observed when sympathetic ganglia were chromatofocused. Molecular modeling studies indicate that the energy-minimized structure of 3,4-dihydroxymandelaldehyde bound to aldose reductase is similar to that of glyceraldehyde where the 2'-hydroxyl group forms hydrogen bonds with Trp111 and NADPH. These results suggest that aldose reductase may be important in metabolizing the potentially toxic aldehyde intermediate formed from norepinephrine in human sympathetic ganglia.

Water intake and 24-hour blood pressure monitoring in a patient with nephrogenic diabetes insipidus caused by a novel mutation of the vasopressin V2R gene.

A 47-year-old man presented with polydipsia, which had had since childhood, and recent onset of hypertension. Genetic analysis proved that he had nephrogenic diabetes insipidus caused by a novel mutation (deletion of 6 amino acids between G107 and C112) in the vasopressin V2 receptor gene. Results of 24-hour blood pressure monitoring disclosed a greater dipping pattern and greater blood pressure variability during waking hours than in male patients with only essential hypertension. This characteristic blood pressure profile may result from daily occurrence of free water depletion, as further observation indicated that water deprivation was associated with a reduction in blood pressure.

Effect of uni-adrenalectomy on blood pressure in a patient with excessive adrenal 18-hydroxy-11-deoxycorticosterone production bilaterally.

A 46-year-old woman was presented with mineralocorticoid excess syndrome and a large mass originating from the right adrenal gland. Clinical examination before right adrenalectomy revealed elevated serum concentrations of 18-hydroxy-11-deoxycorticosterone (18-OH-DOC) both systemically and in the adrenal veins bilaterally. Histopathological and immunohistochemical analyses of the surgical specimen demonstrated adrenal hyperplasia of outer fasciculata cells, and the presence of cystic mass. The adrenalectomy ameliorated her blood pressure (BP) from 156/96 mmHg to 148/87 mmHg with a concomitant increase of serum potassium concentration from 3.1 mEq/l to 3.5 mEq/l. These results suggest that uni-adrenalectomy is, at least in part, effective in ameliorating not only BP but also potassium concentration in a patient of adrenal hyperplasia with excessive bilateral 18-OH-DOC production.