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Ethyl pyruvate (EP), a simple aliphatic ester of pyruvic acid, has been shown to have antiinflammatory effects and to confer protective effects in various pathological conditions. Recently, a number of studies have reported EP inhibits high mobility group box 1 (HMGB1) secretion and suggest this might contribute to its antiinflammatory effect. Since EP is used in a calcium-containing balanced salt solution (Ringer solution), we wondered if EP directly chelates Ca(2+) and if it is related to the EP-mediated suppression of HMGB1 release. Calcium imaging assays revealed that EP significantly and dose-dependently suppressed high K(+)-induced transient [Ca(2+)]i surges in primary cortical neurons and, similarly, fluorometric assays showed that EP directly scavenges Ca(2+) as the peak of fluorescence emission intensities of Mag-Fura-2 (a low-affinity Ca(2+) indicator) was shifted in the presence of EP at concentrations of ≥7 mmol/L. Furthermore, EP markedly suppressed the A23187-induced intracellular Ca(2+) surge in BV2 cells and, under this condition, A23187-induced activations of Ca(2+)-mediated kinases (protein kinase Cα and calcium/calmodulin-dependent protein kinase IV), HMGB1 phosphorylation and subsequent secretion of HMGB1 also were suppressed. (A23187 is a calcium ionophore and BV2 cells are a microglia cell line.) Moreover, the above-mentioned EP-mediated effects were obtained independent of cell death or survival, which suggests that they are direct effects of EP. Together, these results indicate that EP directly chelates Ca(2+), and that it is, at least in part, responsible for the suppression of HMGB1 release by EP.

Active neutron personal dosimeters are now widely used to monitor the neutron personal dose equivalent. They are calibrated periodically in the standard neutron fields such as Cf, D2O-moderated Cf, and Am-Be sources. Type B uncertainty of calibration factors should be determined if they are not offered by the manufacturer. DMC 2000 GN and EPD-N2 dosimeters were chosen to evaluate Type B uncertainties. Dose dependence of calibration factors and minimum dose to the dose indication were also investigated with Cf source neutrons in the neutron irradiation room at Korea Research Institute of Standards and Science. The neutron dose was irradiated up to around 10 mSv for studying dose dependence. The calibration factor of EPD-N2 was stable above neutron dose around 2 mSv and that of DMC 2000 GN was stable above around 1 mSv. Type B uncertainties of DMC 2000 GN and EPD-N2 were evaluated to be 6 % and 12 % from the serial measurements. Type B uncertainty of EPD-N2 was also evaluated by fitting the normalized normal distribution of calibration factors with Gaussian function from 153 dosimeters. The result was in good agreement with the result from the serial measurement. Study of minimum dose to the dose indication showed that DMC 2000 GN is more sensitive than EPD-N2.

Glass composite dielectrics consisting of calcium aluminoborosilicate glass and nitride fillers such as aluminum nitride, boron nitride, and silicon nitride (AlN, BN, and Si3N4) were investigated. Densification and crystallization behavior depended on the type of filler, filler content, and firing temperature. AlN was most promising in generating desirable densification and dielectric properties (k of ~7.2 and tanδ of ~0.003) at 850°C with progressive crystallization of common anorthite phase. BN tended to show no significant densification and suppression of crystallization. Si3N4 resulted in abnormal behavior of densification, which can be highlighted with certain expansion at higher temperatures, as well as unexpected crystallization of CaSiO3 and CaAl2SiO6.

Recent studies have demonstrated that nitric oxide (NO) activates transient receptor potential vanilloid subtype 1 (TRPV1) via S-nitrosylation of the channel protein. NO also modulates various cellular functions via activation of the soluble guanylyl cyclase (sGC)/protein kinase G (PKG) pathway and the direct modification of proteins. Thus, in the present study, we investigated whether NO could indirectly modulate the activity of TRPV1 via a cGMP/PKG-dependent pathway in cultured rat dorsal root ganglion (DRG) neurons. NO donors, sodium nitroprusside (SNP) and S-nitro-N-acetylpenicillamine (SNAP), decreased capsaicin-evoked currents (I(cap)). NO scavengers, hemoglobin and 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (CPTIO), prevented the inhibitory effect of SNP on I(cap). Membrane-permeable cGMP analogs, 8-bromoguanosine 3', 5'-cyclic monophosphate (8bromo-cGMP) and 8-(4chlorophenylthio)-guanosine 3',5'-cyclic monophosphate (8-pCPT-cGMP), and the guanylyl cyclase stimulator YC-1 mimicked the effect of SNP on I(cap). The PKG inhibitor KT5823 prevented the inhibition of I(cap) by SNP. These results suggest that NO can downregulate the function of TRPV1 through activation of the cGMP/PKG pathway in peripheral sensory neurons.

Capsaicin, the pungent ingredient in hot pepper, activates nociceptors to produce pain and inflammation. However, prolonged exposures of capsaicin will cause desensitization to nociceptive stimuli. Hyperpolarization-activated cation currents (I(h)) contribute to the maintenance of the resting membrane potential and excitability of neurons. In the cultured dorsal root ganglion (DRG) neurons, we investigated mechanisms underlying capsaicin-mediated modulation of I(h) using patch clamp recordings. Capsaicin (1 µM) inhibited I(h) only in the capsaicin-sensitive neurons. The capsaicin-induced inhibition of I(h) was prevented by preexposing the TRPV1 antagonist, capsazepine (CPZ). Capsaicin-induced inhibition of I(h) was dose dependent (IC(50)= 0.68 µM) and partially abolished by intracellular BAPTA and cyclosporin A, specific calcineurin inhibitor. In summary, the inhibitory effects of capsaicin on I(h) are mediated by activation of TRPV1 and Ca(2+)-triggered cellular responses. Analgesic effects of capsaicin have been thought to be related to desensitization of nociceptive neurons due to depletion of pain-related substances. In addition, capsaicin-induced inhibition of I(h) is likely to be important in understanding the analgesic mechanism of capsaicin.

Fluoxetine과 tianeptine은 보편적으로 사용되는 항우울제 (AD)이며, haloperidol과 risperidone도 많이 사용되는 항정신성 (APD) 약물로 다양한 이온채널을 조절한다. TREK2 채널은 우울증과 정신분열증 같은 정신질환에 대한 병태생리학적으로 중요한 역할을 하는 TREK1 채널과 생리학적 성질이 매우 비슷하여, 정신성 및 우울증 약물의 TREK2 채널에 대한 효과가 TREK1과 유사하게 나타날 가능성이 있다. Excised inside-out 팻취 방법을 사용하여, 클론된 TREK2 채널이 발현된 CHO 세포에서 항정신성 약물과 항우울제의 효과를 조사했다. Fluoxetine (선택적 세로토닌 방출 억제제, SSRI)은 TREK2 채널을 농도 의존적으로 억제하였으나 ( $IC_{50}=13{\mu}M$ ), tianeptine (선택적 세로토닌 재흡수 증가제, SSRE)은 TREK2 채널 활성을 감소시키지 않고 증가시켰다. Haloperidol은 TREK2 채널을 농도 의존적으로 억제하였으나 ( $IC_{50}=44{\mu}M$ ), risperidone은 고농도 ( $100{\mu}M$ )에서도 TREK2 채널 활성을 완전히 억제 시키지 못했다. 본 연구는 tianeptine 보다 fluoxetine이 TREK2 채널을 더 잘 억제하고 risperidone 보다 haloperidol에 더 잘 억제됨을 보여 주었고, TREK2 채널에 대한 항정신성 약물과 항우울제의 차별적 작용이 약물 부작용의 어떤 기전에 기여 할 수 있음을 제시한다. 【Fluoxetine and tianeptine are commonly used as antidepressants (AD), and haloperidol and risperidone are widely used as antipsychotic drugs (APD), and it modulates various ion channels. TREK2 channel subfamily is very similar to physiological properties of TREK1 channel which can play important roles in the pathophysiology of mental disorders such as depression and schizophrenia, therefore, the pharmacological effect of psychiatric and depression drug on TREK2 channel may be similar to those of TREK1. Using the excised inside-out patch-clamp technique, we have examined the effects of APD and AD on cloned TREK2 channel expressed CHO cells. Fluoxetine (selective serotonin release inhibitor, SSRI) inhibited the TREK2 channel in a concentration-dependent manner ( $IC_{50}$ $13{\mu}M$ ), whereas selective serotonin reuptake enhancer (SSRE) tianeptine increased without reducing the TREK2 channel activity. Haloperidol also inhibited the TREK2 channel in a concentration-dependent manner ( $IC_{50}$ $44{\mu}M$ ), whereas even higher concentration ( $100{\mu}M$ ) of risperidone did not completely inhibit on the activity. This study showed that TREK2 channel was preferentially blocked by fluoxetine rather than tianeptine, and inhibited by haloperidol rather than risperidone, suggesting differential effect of TREK2 channels by APD and AD may contribute to some mechanism of adverse side effects.】

The involuntary dual control systems of the autonomic nervous system (ANS) in the bladder of awake spontaneously hypertensive rats (SHRs) were investigated through simultaneous registrations of intravesical and intraabdominal pressures to observe detrusor overactivity (DO) objectively as a core symptom of an overactive bladder. SHRs (n = 6) showed the features of overactive bladder syndrome during urodynamic study, especially DO during the filling phase. After injection of the nonselective sympathetic blocking agent labetalol, DO disappeared in 3 of 6 SHRs (50%). DO frequency decreased from 0.98 ± 0.22 min−1 to 0.28 ± 0.19 min−1 (p < 0.01), and DO pressure decreased from 3.82 ± 0.57 cm H2O to 1.90 ± 0.86 cm H2O (p < 0.05). This suggests that the DO originating from the overactive parasympathetic nervous system is attenuated by the nonselective blocking of the sympathetic nervous system. The detailed mechanism behind this result is still not known, but parasympathetic overactivity seems to require overactive sympathetic nervous system activity in a kind of balance between these two systems. These findings are consistent with recent clinical findings suggesting that patients with idiopathic overactive bladder may have ANS dysfunction, particularly a sympathetic dysfunction. The search for newer and better drugs than the current anticholinergic drugs as the mainstay for overactive bladder will be fueled by our research on these sympathetic mechanisms. Further studies of this principle are required.

Transient receptor potential vanilloid type 1 (TRPV1) receptor plays an important role as a molecular detector of noxious signals in primary sensory neurons. Activity of TRPV1 can be modulated by the change in the environment such as redox state and extracellular cations. In the present study, we investigated the effect of the mercury chloride (HgCl2) on the activity of TRPV1 in rat dorsal root ganglia (DRG) neurons using whole-cell patch clamp technique. Extracellular HgCl2 reversibly reduced the magnitudes of capsaicin-activated currents (I cap ) in DRG neurons in a dose-dependent manner. The blocking effect of HgCl2 was prevented by pretreatment with the reducing agent dithiothreitol (DTT). Inhibition of I cap by HgCl2 was abolished by point mutation of individual cysteine residues located on the extracellular surface of TRPV1. These results suggest that three extracellular cysteines of TRPV1, Cys616, Cys634 and Cys621, are responsible for the oxidative modulation of I cap by HgCl2.

Intrinsic excitability (IE) can be defined as an output of action potentials from a given input signal. Changes to the IE of a neuron are an important aspect of the cellular plasticity that underlies learning and memory process. In this study, long-term plastic change in IE of deep dorsal horn neurons (DHNs) was investigated. Associative spike pairing stimulation (PS) induced a long-lasting increase in IE. Buffering intracellular calcium with BAPTA (10mM) prevented the induction of a long-lasting increase in IE. PS failed to induce a long-lasting increase in IE in the presence of either D-APV (50 microM) or cadmium chloride (100 microM). Apamin (100 nM) partially blocked the induction of a long-lasting increase in IE. This intrinsic plasticity requires a rise in postsynaptic Ca(2+) and NMDA receptor activation during the induction period, and this process might be mediated by the down-regulation of small-conductance calcium-dependent potassium (SK) channels. In deep DHNs, PS induced excitatory postsynaptic potential (EPSP)-spike (E-S) potentiation, which increases the firing probability and the number of spikes, by consistent dorsal rootlet stimulation. Under bath application of bicuculline (10 microM) and strychnine (1 microM), PS induced E-S potentiation and long-lasting increases in IE. These results suggest that an increase in IE might underlie E-S potentiation, while a reduction in inhibitory transmission does not contribute to E-S potentiation and long-lasting increases in IE. We conclude that PS enhances the IE of deep DHNs, which may play an important role in spinal processing of nociceptive information.

Cerebellar Purkinje neurons have intracellular regulatory systems including Ca2+-binding proteins, intracellular Ca2+ stores, Ca2+-ATPase and Na+-Ca2+ exchanger (NCX) that keep intracellular Ca2+ concentration ([Ca2+]i) in physiological range. Among these, NCX interacts with AMPA receptors, activation of which induces cerebellar synaptic plasticity. And the activation of metabotropic glutamate receptor 1 (mGluR1) is also involved in the induction of cerebellar long-term depression. The interaction of NCX with mGluR1 is not known yet. Thus, in this study, the functional relationship between NCX and mGluR1 in modulating the [Ca2+]i in rat Purkinje neurons was investigated. The interaction between NCX and mGluR1 in Purkinje neurons was studied by measuring intracellular Ca2+ transients induced by an agonist of group I mGluRs, 3,5-dihydroxyphenylglycine (DHPG). The DHPG-induced Ca2+ transient was significantly reduced by treatments of NCX inhibitors, bepridil and KB-R7943. When cells were pretreated with antisense oligodeoxynucleotides of NCX, the DHPG-induced Ca2+ transient was also inhibited. These results suggest that NCX modulates the activity of mGluR1 in cerebellar Purkinje neurons. Therefore, NCX appears to play an important role in the physiological function of cerebellar Purkinje neurons such as synaptic plasticity.

Preparation of bioactive glasses was attempted utilizing waste bovine as raw resource. Bioactive and biodegradable batch compositions in the Na2O-CaO-SiO2 system were included with calcined bovine, whose phase was high-purity oxy-hydroxyapatite. Bovine inclusion as large as 40 mass% was shown to present highly bioactive glasses; bovine in the bioactive and biodegradable compositions presented glasses with controlled bioactivity and biodegradability, respectively. These indicate not only a plenty biological resource of bio-interactive materials, but also an alternative strategy for bioactive glasses with multi-functional applications.

Self-setting paste model in bioactive glass systems was investigated. Particulate glasses based on the systems CaO-SiO2-P2O5 and Na2O-CaO-SiO2 were combined with sodium phosphate solution to constitute paste models. Setting behavior of these pastes, i.e., workability and setting within 30 min were obtained by controlled composition-mass conditions. Specifically, it was found that the setting behavior could be controlled by glass compositions as well as mixing ratios of solids and solutions. These suggest new concept of bioactive cement for various biomedical applications.

Ceramic-polymer bi-structured nano-hybrid, in which the bioactive silicate surface is nano-hybridized with flexible polymeric bulk, was synthesized in the tetraethoxysilane (TEOS)-polydimethylsiloxane (PDMS) sol-gel system. Different solutions for surface and bulk, whose compositions of TEOS: PDMS were respectively fixed 100: 0 and varied from 50: 50 to 20: 80 with various molecular weight (Mw) of PDMS, were subjected to lamination and controlled polymerization and condensation process, producing a large transparent crack-free monolithic bulk. Characterizations at near-surface cross-section of the bi-structured hybrids revealed that typical bioactive silicate was combined with all types of bulk hybrids regardless of their PDMS contents and Mw without distinct interface, indicating possibility of a novel bioactive nano-composite with enhanced physical and biological functions.

Synthetic model of a large transparent crack-free monolithic ceramic-polymer hybrid, which was synthesized using triethoxysilane end-capped poly(tetramethylene oxide) (Si-PTMO) and tetraethoxysilane (TEOS), was examined in the CaO-SiO2-PTMO sol-gel system. Bulk precursor with nominal mass ratio of PTMO: TEOS = 80: 20 and surface precursor with nominal molar ratio of TEOS: Ca(NO3)2 = 1: 0.3 were subjected to hybridization through hydrolysis and condensation process, producing a bi-structured hybrid in which polymeric bulk was molecular hybridized with bioactive silicate surface. Spectroscopic and microscopic characterizations revealed that the surface of hybrid was typical bioactive silicate. In vitro study using a simulated body fluid (SBF) revealed that the hybrid formed an apatite on its surface within 6 hours in SBF, suggesting bioactive materials with high capability of tissue integration as well as polymeric physical properties.

TRPV1, a receptor for capsaicin, plays a key role in mediating thermal and inflammatory pain. Because the modulation of ion channels by the cellular redox state is a significant determinant of channel function, we investigated the effects of sulfhydryl modification on the activity of TRPV1. Thimerosal, which oxidizes sulfhydryls, blocked the capsaicin-activated inward current (I(cap)) in cultured sensory neurons, in a reversible and dose-dependent manner, which was prevented by the co-application of the reducing agent, dithiothreitol. Among the three cysteine residues of TRPV1 that are exposed to the extracellular space, the oxidation-induced effect of thimerosal on I(cap) was blocked only by a point mutation at Cys621. These results suggest that the modification of an extracellular thiol group can alter the activity of TRPV1. Consequently, we propose that such a modulation of the redox state might regulate the physiological activity of TRPV1.

The chemical solution-derived lead-free piezoelectric (Na0.5,K0.5)NbO3 (NKN) thin film was successfully prepared for an implantable cardio-mechanical electric sensor (CMES) in pacemakers. The NKN film on the tubular Pt for CMES showed a dense and uniform microstructure with a smooth surface. The maximum dielectric constant of the NKN film was 2000 at a low frequency of 10 Hz and the average hydrostatic piezoelectric dh value in an n-dodecan liquid solution was 19.1 pC/N at a pulse pressure of 0.025 MPa. These results prove that the lead-free NKN film is an attractive candidate for the implantable medical sensor applications.

Environmentally benign lead-free ferroelectric (K0.5,Na0.5)(Mn0.005,Nb0.995)O3 (KNMN) thin film capacitors with a small concentration of a BiFeO3 (BF) dopant were prepared by a cost effective chemical solution deposition method for high energy density storage device applications. 6 mol. % BF-doped KNMN thin films showed very slim hysteresis loops with high maximum and near-zero remanent polarization values due to a phase transition from the orthorhombic structure to the pseudo-cubic structure. Increasing the electric field up to 2 MV/cm, the total energy storage density (Jtotal), the effective recoverable energy density (Jeff), and the energy conversion efficiency (η) of lead-free KNMN-BF thin film capacitors were 31.0 J/cm3, 28.0 J/cm3, and 90.3%, respectively. In addition, these thin film capacitors exhibited a fast discharge time of a few μs and a high temperature stability up to 200 °C, proving their strong potential for high energy density storage and conversion applications.

Supplementary material, approximately 1.02 MB.

We have investigated the effect of capsaicin on Ca(2+) release from the intracellular calcium stores. Intracellular calcium concentration ([Ca(2+)](i)) was measured in rat dorsal root ganglion (DRG) neurons using microfluorimetry with fura-2 indicator. Brief application of capsaicin (1 microM) elevated [Ca(2+)](i) in Ca(2+)-free solution. Capsaicin-induced [Ca(2+)](i) transient in Ca(2+)-free solution was evoked in a dose-dependent manner. Resiniferatoxin, an analogue of capsaicin, also raised [Ca(2+)](i) in Ca(2+)-free solution. Capsazepine, an antagonist of capsaicin receptor, completely blocked the capsaicin-induced [Ca(2+)](i) transient. Caffeine completely abolished capsaicin-induced [Ca(2+)](i) transient. Dantrolene sodium and ruthenium red, antagonists of the ryanodine receptor, blocked the effect of capsaicin on [Ca(2+)](i). However, capsaicin-induced [Ca(2+)](i) transient was not affected by 2-APB, a membrane-permeable IP(3) receptor antagonist. Furthermore, depletion of IP(3)-sensitive Ca(2+) stores by bradykinin and phospholipase C inhibitors, neomycin, and U-73122, did not block capsaicin-induced [Ca(2+)](i) transient. In conclusion, capsaicin increases [Ca(2+)](i) through Ca(2+) release from ryanodine-sensitive Ca(2+) stores, but not from IP(3)-sensitive Ca(2+) stores in addition to Ca(2+) entry through capsaicin-activated nonselective cation channel in rat DRG neurons.

Capsaicin (CAP)-activated ion channel plays a key role in generating nociceptive neural signals in sensory neurons. Here we present evidence that intracellular ATP upregulates the activity of capsaicin receptor channel. In inside-out membrane patches isolated from sensory neurons, application of CAP activated a nonselective cation channel (icap). Further addition of ATP to the bath caused a significant increase inicap, with aK1/2of 3.3 mm. Nonhydrolyzable analogs of ATP, adenylimidodiphosphate and adenosine 5′-O-(3-thio)-triphosphate, also increasedicap. Neither Mg2+-free medium nor inhibitors of various kinases blocked the increase inicapinduced by ATP. The enhancing effect of ATP was also observed in inside-out patches of oocytes expressing vanilloid receptor 1, a cloned capsaicin receptor. Single point mutations (D178N, K735R) within the putative Walker type nucleotide-binding domains abolished the effect of ATP. These results show that ATP increasesicapin sensory neurons by direct interaction with the CAP channel without involvement of phosphorylation.

Capsaicin, a pungent ingredient of hot peppers, causes excitation of small sensory neurons, and thereby produces severe pain. A nonselective cation channel activated by capsaicin has been identified in sensory neurons and a cDNA encoding the channel has been cloned recently. However, an endogenous activator of the receptor has not yet been found. In this study, we show that several products of lipoxygenases directly activate the capsaicin-activated channel in isolated membrane patches of sensory neurons. Among them, 12- and 15-( S )-hydroperoxyeicosatetraenoic acids, 5- and 15-( S )-hydroxyeicosatetraenoic acids, and leukotriene B 4 possessed the highest potency. The eicosanoids also activated the cloned capsaicin receptor (VR1) expressed in HEK cells. Prostaglandins and unsaturated fatty acids failed to activate the channel. These results suggest a novel signaling mechanism underlying the pain sensory transduction.

In the present study, the presence of an endogenous capsaicin-like substance and the role of capsaicin receptors in nociception during inflammation were assessed using Fos immunohistochemistry and the paw-withdrawal test in rats. Intradermal injection of carrageenan in the hind-paw produced inflammation in the foot pad, increased the number of cells exhibiting Fos-like immunoreactivity in the dorsal horn of the spinal cord, and decreased the paw-withdrawal latency. Intradermal injection of capsazepine, a capsaicin-receptor antagonist, significantly reduced the number of cells exhibiting Fos-like immunoreactivity, significantly increased the paw-withdrawal latency, but did not decrease inflammation induced by carrageenan injection. Intradermal injection of capsaicin or formalin also increased Fos-positive neurons. Capsaicin- or formalin-induced Fos expression was reduced in both cases by pretreatment of capsazepine, but to a much lesser extent for formalin. The capsazepine inhibition of carrageenan inflammation-induced hyperalgesic responses strongly suggests that an endogenous capsaicin-like substance is released in inflamed tissues and produces nociceptive neural impulses by acting on capsaicin receptors present on sensory neurons. Furthermore, our results indicate that capsaicin receptors take part only in generating nociceptive signals in sensory neurons, but not in activating the inflammation-promoting cells.

The ubiquitin-proteasome system plays a central role in protein quality control through endoplasmic reticulum (ER)-associated degradation (ERAD) of unfolded and misfolded proteins. NF-E2-related factor 2 (Nrf2) is a transcription factor that controls the expression of an array of phase II detoxification and antioxidant genes. Nrf2 signaling has additionally been shown to upregulate the expression of the proteasome catalytic subunits in several cell types. Here, we investigated the role of Nrf2 in tunicamycin-induced ER stress using a murine insulinoma β-cell line, βTC-6. shRNA-mediated silencing of Nrf2 expression in βTC-6 cells significantly increased tunicamycin-induced cytotoxicity, elevated the expression of the pro-apoptotic ER stress marker Chop10, and inhibited tunicamycin-inducible expression of the proteasomal catalytic subunits Psmb5 and Psmb6. The effects of 3H-1,2-dithiole-3-thione (D3T), a small molecule Nrf2 activator, on ER stress were also examined in βTC-6 cells. D3T pretreatment reduced tunicamycin cytotoxicity and attenuated the tunicamycin-inducible Chop10 and protein kinase RNA-activated-like ER kinase (Perk). The protective effect of D3T was shown to be associated with increased ERAD. D3T increased the expression of Psmb5 and Psmb6 and elevated chymotrypsin-like peptidase activity; proteasome inhibitor treatment blocked D3T effects on tunicamycin cytotoxicity and ER stress marker changes. Similarly, silencing of Nrf2 abolished the protective effect of D3T against ER stress. These results indicate that the Nrf2 pathway contributes to the ER stress response in pancreatic β-cells by enhancing proteasome-mediated ERAD.

Solution-derived poly(vinylidene fluoride trifluoroethylene) (P(VDF-TrFE)) piezoelectric thin films on cellulose paper substrates were prepared as flexible power generators for wearable device applications. Optimization of appropriate annealing and cooling sequences of the co-polymer films resulted in the formation of dense and uniform microstructures exhibiting a well-developed β-phase. A maximum open-circuit voltage of 1.5 V was generated from the periodic bending and releasing of the paper power generator at approximately 1 Hz. To demonstrate the wearable applications, P(VDF-TrFE) piezoelectric film-based paper power generators were directly attached on the back of a human hand, and they generated a maximum output open-circuit voltage of 0.4 V at low bending frequencies of 0.25 Hz. Good open-circuit voltage performance at low frequencies makes P(VDF-TrFE) piezoelectric thin films on paper substrates a strong candidate for future self-powered wearable devices.

Previously, we have shown that nitric oxide (NO) directly activates the Maxi-K channels. In the present study, we have investigated whether NO has prolonged effects on the Maxi-K channels reconstituted in lipid bilayer. Application of S-nitroso-N-acetyl-D, L-penicillamine (SNAP), a NO donor, induced an immediate increase of open probability (Po) of Maxi-K channel in a dose-dependent manner. When SNAP was removed from the cytosolic solution, the Po did not simply returned to, but irreversibly decreased to a level lower than that of the control Po. At 0.2 mM, (Z)-[N-(3-Ammoniopropyl)-N-(n-propyl)amino] diazen-1-ium-1,2-diolate (PAPA-NO), another NO donor, produced a similar increase of Po and decrease of Po upon washout. The increasing effects of SNAP on Po were not blocked by either 50 U/ml superoxide dismutase (SOD) or 2 mM Nethylmaleimide (NEM) pre-treatments. However, NEM appears to be ineffective when applied after SNAP. These results suggest that NO can modulate Maxi-K channel via direct interaction and chemical modification, such as Snitrosylation in the brain.

The extracellular calcium sensing receptor (CaSR) belongs to the typeⅢ family of G-protein-coupled receptors, a family that comprises the metabotropic glutamate receptor and the putative vomeronasal organ receptors. The CaSR plays an important role for calcium homeostasis in parathyroid cells, kidney cells and other cells to directly ‘sense’ changes in the extracellular calcium ion concentration ([Ca 2+ ] o ). The mesangial cells are known to be involved in many pathologic sequences through the mediation of altered glomerular hemodynamics, cell proliferation, and matrix production. In this study, we examined the expression of the CaSR in the mouse mesangial cell lines (MMC, ATCC number CRL-1927). Reverse transcription- polymerase chain reaction (RT-PCR) was perform with CaSR-specific primers, and this was followed by nucleotide sequencing of the amplified product; this process identified the CaSR transcript in the MMCs. Moreover, CaSR protein was present in the MMCs as assessed by Western blot and immunocytochemical analysis using a polyclonal antibody specific for the CaSR. Functionally, [Ca 2+ ] o induced the increment of the intracellular calcium concentration ([Ca 2+ ] i ) in a dose-dependent manner. This [Ca 2+ ] i increment by [Ca 2+ ] o was attenuated by the pretreatment with a phospholipase C inhibitor (U73122) and also by a pretreatment with a CaSR antagonist (NPS 2390). The similar results were also obtained in IP3 accumulation by [Ca 2+ ] o . To investigate the physiological effect of the CaSR, the effect of the [Ca 2+ ] o on cell proliferation was studied. The increased [Ca 2+ ] o (up to 10 mM) produced a significant increase in the cell numbers. This mitogenic effect of [Ca 2+ ] o was inhibited by the co-treatment with a CaSR antagonist. From these results, the [Ca 2+ ] o -induced [Ca 2+ ]i elevation in the MMC is coupled with the extracellular calcium sensing receptor. Furthermore, [Ca 2+ ] o prouces a mitogenic effect in MMCs.

We investigated whether tetanic stimulation (TS) of peripheral afferent nerves induced long-term potentiation (LTP) in the spinal dorsal horn of rats. Extracellular recordings from a wide dynamic range of neurons in the lumbosacral enlargement were performed using urethane-anaesthetized rats. High frequency electrical TS of sciatic nerves has revealed three groups of neurons based on their responses: LTP-induced, no-change and long-term depression-induced neurons. The firing pattern of LTP-induced neurons showed a short interval between A- and C-responses in comparison to the no-change neurons, which displayed longer intervals between A- and C-responses. During TS, coincident depolarization increased the probability of LTP induction. It can be suggested that coincident depolarization or increase in excitability of the postsynaptic dorsal horn neurons during TS may be necessary for successful induction of LTP through the dorsal horn.

Although hypoxia is known to affect membrane excitability of various neurons by various mechanisms, the effects of hypoxia on substantia gelatinosa (SG) neurons have not yet been elucidated. In whole-cell or perforated patch-clamp recordings from SG neurons, we showed that acute hypoxia induces a reversible hyperpolarization of -6.1+/-1.3 mV of the resting membrane potential and an outwards current of 9.48+/-1.71 pA at a holding potential of -60 mV. The reversal potentials of the hypoxia-induced current depended on [K(+)](o). The hypoxia-induced hyperpolarization and outwards current were abolished completely by BaCl(2), but not by CsCl. Glibenclamide, a blocker of K(ATP) channels, blocked the hypoxia-induced hyperpolarization. Pretreatment with cromakalim, an opener of K(ATP) channels, occluded the hypoxia-induced hyperpolarization. Any alteration by hypoxia was not observed in the presence of an internal solution with a high [ATP] (10 mM). The above results suggest that hypoxia-induced hyperpolarization in SG neurons is mediated by activation of K(ATP) channels.

A solid-state half-cell structure with a Sn–Li2O composite (SLC) anode/LiPON/Li was prepared to improve upon the cycling stability at the second discharging cycle of the non-Li anode thin films for all-solid-state batteries. Based on the cycling behaviors of the all-solid half cell with SLC and pure Sn thin film electrodes at first and second discharging cycles, cycling stability at the initial charging–discharging cycle of the all-solid-state battery system was improved. The high retention value of SLC thin film electrodes with LiPON solid electrolyte might originate from (1) the structural stability of the SLC thin film, and (2) suppression of crack formation at the SLC surface owing to an increasing surface mechanical strength of the SLC thin film by the LiPON deposition on it. These results indicate that the SLC thin film has a high possibility as the stable solid anode material for use as an all-solid-state battery.

Magnetic and AC magnetically induced heating characteristics of Fe3O4 nanoparticles (IONs) with different mean diameters, d, systematically controlled from 4.2 to 22.5 nm were investigated to explore the physical relationship between magnetic phase and specific loss power (SLP) for hyperthermia agent applications. It was experimentally confirmed that the IONs had three magnetic phases and correspondingly different SLP characteristics depending on the particle sizes. Furthermore, it was demonstrated that pure superparamagnetic phase IONs (d

The objective of the present study was to establish the method of measurement of hydrogen peroxide and to estimate the anti-oxidative effect of genistein in the skin. UVB induced skin oxidation and anti-oxidative effect of genistein formulations were evaluated by determining levels of hydrogen peroxide. The mechanism involved in the determination of hydrogen peroxide is based on a color reaction between ferric ion (Fe(3+)) and xylenol orange, often called FOX assay and subsequent monitoring of absorbance values of the reactant at 540 nm. The reaction was to some extent pH-dependent and detection sensitivity was greatest at pH 1.75. Genistein liposomal gel demonstrated better anti-oxidative effect with regard to lowering hydrogen peroxide levels elevated by UVB irradiation compared to genistein-suspended gel. A linear relationship has been observed between anti-oxidative effect of genistein and drug deposition in the skin tissue. Genistein liposomal gel resulting in the localization of the drug in the deeper skin led to improved anti-oxidative effect compared to genistein gel. The suggested method for evaluation of oxidation of the skin can be used as a tool to screen effective anti-oxidative agents and their delivery systems acting on the skin.

Capsaicin (CAP) excites small sensory neurons, causing pain, neurogenic inflammation, and other visceral reflexes. These effects have been proposed to be the result of CAP activation of a nonselective cation current. It is generally assumed that CAP binds to an extracellular domain of the membrane receptor. However, the exact binding site is not known because of the lipophilic nature of CAP. To determine whether the binding domain is extracellular or intracellular, we tested the effect of a synthetic water-soluble CAP analog, DA-5018·HCl, on current activation. CAP activated the 45 pS (at −60 mV) nonselective cation channel from either side of the membrane. However, DA-5018·HCl, which had a greater potency and efficacy than CAP, activated the channels only from the cytosolic side of the patch membrane in a capsazepine, a CAP receptor antagonist, reversible manner. When applied extracellularly, DA-5018·HCl did not, but CAP did, activate whole-cell currents in sensory neurons, as well as in oocytes expressing vanilloid receptor 1, a recently cloned CAP receptor. Hydrogen ions, reported as a possible endogenous activator of cation current, failed to elicit any current when acidic medium (pH 5.0–6.0) was applied intracellularly, indicating that H+does not mediate the CAP effect. These results indicate that CAP and its analog bind to the cytosolic domain of the CAP receptor and suggest that an endogenous CAP-like substance other than H+may be present in the cell.