Cyclic lava effusion during the 2018 eruption of Kilauea Volcano.

Lava flows present a recurring threat to communities on active volcanoes, and volumetric eruption rate is one of the primary factors controlling flow behavior and hazard. The time scales and driving forces of eruption rate variability, however, remain poorly understood. In 2018, a highly destructive eruption occurred on the lower flank of Kilauea Volcano, Hawai'i, where the primary vent exhibited substantial cyclic eruption rates on both short (minutes) and long (tens of hours) time scales. We used multiparameter data to show that the short cycles were driven by shallow outgassing, whereas longer cycles were pressure-driven surges in magma supply triggered by summit caldera collapse events 40 kilometers upslope. The results provide a clear link between eruption rate fluctuations and their driving processes in the magmatic system.

Role of satellite cell-derived L-serine in the dorsal root ganglion in paclitaxel-induced painful peripheral neuropathy.

Paclitaxel is one of the most commonly used anti-neoplastic drugs for the treatment of solid tumors. Unfortunately, its use is often associated with dose-limiting painful peripheral neuropathy and subsequent neuropathic pain that is resistant to standard analgesics. However, there are few clinically available drugs or drug classes for the treatment of paclitaxel-induced neuropathy due to a lack of information regarding the mechanisms responsible for it. In this study, we examined the involvement of l-serine in paclitaxel-induced hyperalgesia/allodynia and decrease in sensory nerve conduction velocity (SNCV). We used a preclinical rat model of paclitaxel-induced painful peripheral neuropathy. Response to von Frey filaments, SNCV, 3-phosphoglycerate dehydrogenase (3PGDH) expression, and l-serine concentration were examined. Effects of l-serine administration were also investigated. Paclitaxel treatment induced mechanical allodynia/hyperalgesia and reduction of SNCV. Paclitaxel also decreased the l-serine concentration in the dorsal root ganglion (DRG) but not in the sciatic nerve or spinal cord. In addition, paclitaxel decreased expression of 3PGDH, a biosynthetic enzyme of l-serine, in the DRG. Immunohistochemistry showed that 3PGDH was localized in satellite cells but not in neurons in the DRG. Intraperitoneal administration of l-serine improved both paclitaxel-induced mechanical allodynia/hyperalgesia and the reduction of SNCV. These results suggest that satellite cell-derived l-serine in the DRG plays an important role in paclitaxel-induced painful peripheral neuropathy. These findings may lead to novel strategies for the treatment of paclitaxel-induced painful peripheral neuropathy.

Desflurane but not sevoflurane can increase lung resistance via tachykinin pathways.

BACKGROUND: Although there is evidence that the volatile anaesthetic desflurane directly relaxes preconstricted airway smooth muscle in vitro, the anaesthetic increases the lung resistance in vivo. The constrictive mechanisms of desflurane are, however, still unknown. This study was conducted to clarify the increasing mechanisms of desflurane on lung resistance by examining the vagal nerve reflexes in guinea pigs. METHODS: The effects of desflurane and sevoflurane on total lung resistance (R(L)) and dynamic lung compliance (C(Dyn)) were investigated in animals that were either untreated, pretreated with atropine or vagotomy, pretreated with the tachykinin receptor antagonists sendide or MEN-10376, or given chronic pretreatment with capsaicin. RESULTS: Desflurane biphasically and dose-dependently increased R(L) (by 180% and 230% at the first and second peaks, respectively, at 2 minimum alveolar concentration) concomitant with a decrease in C(Dyn). However, sevoflurane had little effect on either R(L) or C(Dyn). Although vagotomy partially inhibited the first peak of R(L) by 30%, neither atropine nor vagotomy had any effect on the other respiratory responses to desflurane. Antagonization of tachykinin receptors of airway smooth muscles completely diminished the increase in R(L) induced by desflurane. Desflurane also had little effect on respiratory parameters after the capsaicin pretreatment, in which tachykinin containing afferent C-fibres was desensitized. CONCLUSIONS: Desflurane but not sevoflurane increased R(L) concomitant with a decrease in C(Dyn) in guinea pigs. The increase in lung resistance by desflurane might be due to antidromic tachykinin release from afferent C-fibres but not acetylcholine release from parasympathetic efferent nerves.

Performance of four carbon dioxide absorbents in experimental and clinical settings.

To evaluate the performance of four kinds of carbon dioxide (CO(2)) absorbents (Medisorb GE Healthcare, Amsorb Plus Armstrong Medical, YabashiLime Yabashi Industries, and Sodasorb LF Grace Performance Chemicals), we measured their dust production, acceptability of colour indicator, and CO(2) absorption capacity in in vitro experimental settings and the concentration of compound A in an inspired anaesthetic circuit during in vivo clinical practice. In vitro, the order of the dust amount was Sodasorb LF > Medisorb > Amsorb Plus = YabashiLime both before and after shaking. The order of the color acceptability was similar: Sodasorb LF > Amsorb Plus = Medisorb > YabashiLime both initially and 16 h after CO(2) exhaustion. During exposure to 200 ml.min(-1) CO(2) in vitro, the period until 1 kg of fresh soda lime allowed inspired CO(2) to increase to 0.7 kPa (as a mark of utilisation of the absorbent) was longer with Medisorb (1978 min) than with the other absorbents (1270-1375 min). In vivo, compound A (1.0% inspired sevoflurane) was detected only when using Medisorb. While Medisorb has the best ability to absorb CO(2), it alone produces compound A.

SB366791, a TRPV1 antagonist, potentiates analgesic effects of systemic morphine in a murine model of bone cancer pain.

BACKGROUND: Bone cancer pain has a major impact on the quality of life of cancer patients but is difficult to treat. Therefore, development of a novel strategy for bone cancer pain is needed for improvement of the patient quality of life. In this study, we examined the analgesic effects of the combination of a transient receptor potential vanilloid subfamily 1 (TRPV1) antagonist and morphine on pain-related behaviours in a murine model of bone cancer pain. METHODS: C3H/HeJ mice underwent injection of osteolytic sarcoma cells into the intramedullary space of the femur. The analgesic effects of intraperitoneal morphine and the analgesic effect of a TRPV1 antagonist, SB366791 [N-(3-methoxyphenyl)-4-chlorocinnamide], on bone cancer pain-related behaviours were examined. The analgesic effects of the combination of SB366791 and morphine on bone cancer pain were also examined. RESULTS: Intraperitoneal morphine significantly reduced the number of spontaneous flinches and improved ambulation only at the highest dose of 10 mg kg(-1) whereas weight-bearing was not improved. Intraperitoneal SB366791 at doses of 0.3 and 1.0 mg kg(-1), but not at a dose of 0.1 mg kg(-1), reduced the number of spontaneous flinches, whereas neither weight-bearing nor ambulation was improved. Addition of a sub-analgesic dose of SB366791 (0.1 mg kg(-1)) to morphine significantly reduced the number of flinches and improved weight-bearing compared with the effects of morphine alone. CONCLUSIONS: Our findings showed that the combination of morphine and SB366791 has potent analgesic effects on bone cancer pain. The findings of this study may lead to novel strategies for the treatment of bone cancer pain.

Adenosine and adenosine uptake inhibitors potentiate the neuromuscular blocking action of rocuronium mediated by adenosine A(1) receptors in isolated rat diaphragms.

BACKGROUND: Adenosine, which pre-junctionally modulates neuromuscular transmission, and adenosine uptake inhibitors, which increase extracellular adenosine, have been used clinically. We investigated the effects of adenosine, dipyridamole and midazolam on the neuromuscular blocking action of rocuronium. METHODS: Isometric twitch tensions of rat nerve-hemidiaphragm preparations elicited by indirect (phrenic nerve) supra-maximal stimulation at 0.1 Hz were evaluated (n=6 in all data). RESULTS: Pre-treatments with adenosine (0.1 and 1 microM) and CCPA (1 microM, adenosine A(1) receptor agonist), but not that with CGS21680 (0.5 microM, A(2) receptor agonist), shifted the rocuronium concentration-twitch tension curves to the left and decreased the rocuronium concentration for 50% twitch depression (IC(50)) compared with the control (P<0.01). The leftward shift induced by 1 microM adenosine was inhibited by pre-treatments with theophylline (50 microM, non-selective adenosine receptor antagonist) and DPCPX (0.2 microM, A(1) receptor antagonist) but not by that with DPMA (5 microM, A(2) receptor antagonist). Pre-treatments with dipyridamole and midazolam, adenosine uptake inhibitors, shifted the curve to the left and decreased IC(50) at supra-therapeutic concentrations (10 and 2.5 microM, respectively) but not at clinical concentrations (2 and 0.5 microM, respectively), and the leftward shifts were inhibited by pre-treatment with DPCPX (0.2 microM). CONCLUSION: The results indicate that adenosine potentiates the neuromuscular blocking action of rocuronium mediated by adenosine A(1) receptors and that supra-therapeutic concentrations of dipyridamole and midazolam also potentiate the action of rocuronium by increasing endogenous adenosine concentration.

Contribution of transient receptor potential vanilloid subfamily 1 to endothelin-1-induced thermal hyperalgesia.

Endothelin-1 (ET-1) plays an important role in peripheral pain processing. However, the mechanisms of the nociceptive action of ET-1 have not been fully elucidated. In this study, we investigated the contribution of transient receptor potential vanilloid subfamily 1 (TRPV1) to ET-1-induced thermal hyperalgesia. Intraplantar ET-1-induced thermal hyperalgesia was examined by assessing the paw withdrawal latency to noxious heat stimuli. In electrophysiological study, whole-cell patch-clamp recordings were performed to investigate the interaction of ET-1 and TRPV1 using human embryonic kidney 293 (HEK293) cells expressing endothelin type A receptor (ET(A)) and TRPV1. Intraplantar ET-1 (3, 10 and 30 pmol) produced thermal hyperalgesia in a dose-dependent manner. Thermal hyperalgesia was attenuated by the inhibition of ET(A) and protein kinase C (PKC) but not that of ET(B). ET-1-induced thermal hyperalgesia was significantly attenuated in TRPV1-deficient mice compared with that in wild-type mice. In voltage-clamp experiments, 10 nM capsaicin evoked small inward currents in HEK293 cells expressing TRPV1 and ET(A). In the presence of ET-1, capsaicin produced much larger current responses (P<0.05). Mutation at PKC-specific TRPV1 phosphorylation sites (S800A/S502A) and PKC inhibitors inhibited the potentiating effect of ET-1. In addition, ET-1 decreased the temperature threshold for TRPV1 activation in a PKC-dependent manner (from 41.0+/-0.4 degrees C to 32.6+/-0.6 degrees C). In addition, Western blot analysis was also performed to confirm ET-1-induced phosphorylation of TRPV1. Incubation of ET-1 and intraplantar ET-1 evoked phosphorylation of TRPV1 in HEK293 cells expressing TRPV1 and ET(A) and the skin, respectively. These results suggest that the sensitization of TRPV1 activity through an ET(A)-PKC pathway contributes to ET-1-induced thermal hyperalgesia.

Down-regulation of mu opioid receptor expression within distinct subpopulations of dorsal root ganglion neurons in a murine model of bone cancer pain.

Although micro opioid receptor (MOR) agonists are used for treatment of most types of pain, a recent study has suggested that the sensitivity of bone cancer pain to systemic morphine was lower than that of inflammatory pain. However, the reasons for this have remained unclear. In this study, MOR expression and the analgesic effects of morphine in a bone cancer model were compared with those in an inflammatory pain model. A bone cancer pain model and an inflammatory pain model were made by implantation of sarcoma cells into the intramedullary space of the femur and hind-paw injection of complete Freund's adjuvant (CFA), respectively. In a behavioral study, sarcoma-implanted mice showed flinching behavior of magnitude comparable to that induced by CFA injection. The flinching behavior of sarcoma-implanted mice was less sensitive to intrathecal morphine than that of CFA-injected mice. Western blot analysis showed that MOR expression in the dorsal root ganglion (DRG) ipsilateral to sarcoma implantation was significantly reduced, while that in the DRG ipsilateral to CFA injection was increased. In sarcoma-implanted mice, the percentage of MOR-positive DRG neuronal profiles was lower than that in control mice (30.3% vs. 45.2%). In particular, MOR expression was reduced among calcitonin gene-related peptide- and transient receptor potential vanilloid subfamily 1-positive DRG neuronal profiles, which are considered to be involved in the generation of bone cancer pain (from 61.5% to 41.5% and from 72.1% to 48.4%, respectively). These results suggest that down-regulation of MOR in the distinct populations of DRG neurons contributes to the fact that higher doses of morphine are needed to produce analgesia in bone cancer as compared with those used in non-malignant inflammatory situations.

Inhibitory effects of the alpha-2 adrenergic agonists clonidine and dexmedetomidine on enhanced airway tone in ovalbumin-sensitized guinea pigs.

BACKGROUND AND OBJECTIVE: The alpha-2 adrenergic agonists clonidine and dexmedetomidine are used as an antihypertensive and a sedative, respectively. The aim of this study was to determine the effects of these agonists on ovalbumin-sensitized airway tone in guinea pigs. METHODS: The animals were divided into two groups: control and sensitized. The sensitized group received ovalbumin intraperitoneally and was boosted by exposure to aerosolized ovalbumin. The effects of the alpha-2 agonists were investigated by measuring (1) total lung resistance and (2) smooth muscle tension using a tracheal ring preparation. RESULTS: In the control group, acetylcholine significantly increased total lung resistance in a dose-dependent manner. In the sensitized animals, total lung resistance was significantly higher (by 95%) at 6 mug kg-1 acetylcholine than that in the control group. Both clonidine and dexmedetomidine had a slight but significant inhibitory effect on the response curve of lung resistance at higher concentrations of carbachol, a potent muscarinic receptor agonist. Similar to the data obtained in the control group, both clonidine and dexmedetomidine significantly decreased total lung resistance and the inhibitory effects of these alpha-2 agonists on lung resistance were significantly distinguishable. Similar direct inhibitory effects of the alpha-2 agonists on carbachol-induced muscle contraction were observed in both the control and sensitized groups, the inhibitory effects in the sensitized group being significantly greater. CONCLUSION: Both clonidine and dexmedetomidine can relax the airway even in the hyper-reactive state.

Propofol attenuates ischaemia-reperfusion injury in the rat heart in vivo.

BACKGROUND: We have previously demonstrated, in the isolated rat heart, that propofol attenuates hydrogen peroxide-induced damage and ischaemia-reperfusion injury, and that the beneficial effect of propofol is correlated with reduction of the lipid peroxidation. This study was designed to evaluate whether propofol has a cardioprotective effect against ischaemia-reperfusion injury in a rat model in vivo. METHODS: Adult rats were anaesthetized with pentobarbital 10 mg kg(-1) h(-1) alone (control group), pentobarbital 10 or 20 mg kg(-1) h(-1) + Intralipid as a vehicle (Pent-10, Pent-20 group), propofol 10 or 20 mg kg(-1) h(-1) (Prop-10, Prop-20 group) intravenously throughout the experiment. The left anterior descending coronary artery was occluded for 30 min followed by 120 min of reperfusion. Infarct size was determined at the end of reperfusion. The tissue concentration of malondialdehyde was measured at 30 min after reperfusion to evaluate lipid peroxidation. RESULTS: The infarct sizes (% of area at risk) were significantly smaller in the Prop-10 (54 +/- 11%; P < 0.01 vs. control) and Prop-20 (39 +/- 8%; P < 0.01 vs. control) groups than in the control (68 +/- 9%), Pent-10 (69 +/- 13%) and Pent-20 (68 +/- 14%) groups (n = 12). In the Pent-10 and Pent-20 groups, ischaemia-reperfusion produced significant increases in the values for tissue malondialdehyde (0.72 +/- 0.24 micromol mg protein-1; P < 0.05 and 0.63 +/- 0.33 micromol mg protein-1; P < 0.05 vs. 0.46 +/- 0.22 micromol mg protein-1 in non-ischaemic hearts, n = 8). However, the values of malondialdehyde in the Prop-10 and -20 groups were suppressed by 41% and 63%, respectively, compared with the Pent-10 group (P < 0.01). CONCLUSION: Our results suggest that propofol could be cardioprotective against ischaemia-reperfusion injury dose dependently in a rat model in vivo and that the beneficial action of propofol may be correlated with its antioxidant effect.

Analysis of the composition of 'original' and generic sevoflurane in routine use.

BACKGROUND: Original sevoflurane (Sevofrane) contains a small amount of water, which can inhibit the production of hydrofluoric acid. Hydrofluoric acid is highly pungent, and sevoflurane that contains a high concentration of hydrofluoric acid is not suitable for volatile induction of anaesthesia. Recently, generic sevoflurane (Sevoness) has become available in some countries. The generic product is produced by a different method and kept in a different kind of bottle. We questioned whether the original and generic sevoflurane differed in their composition and thus might differ in their resistance to degradation. METHODS: Sevoflurane from groups of three bottles of Sevofrane and three bottles of Sevoness was kept in the bottle at 24-37 degrees C for 2 weeks or in two kinds of vaporizer for 3 days, and the resulting contents measured by gas chromatography. RESULTS: Both products contained sevoflurane concentrations exceeding 99.998%. Fluoride ion concentration did not differ between the products (0.043 ppm). The original sevoflurane contained more (0.07% w/v) water than the generic anaesthetic (0.003% w/v). Original sevoflurane contained 5 ppm compound A, 10 ppm sevomethylether, and 5 ppm of unknown materials. Generic sevoflurane contained 32 ppm hexafluoroisopropanol and 12 ppm of unknown materials. While stored in a vaporizer for 3 days, the water content in the original sevoflurane decreased by two-thirds but the water in the generic sevoflurane increased by a factor of three-fold. CONCLUSIONS: Generic sevoflurane contains high-quality sevoflurane and only a small amount of fluoride ions, making it comparable with the original sevoflurane product.

Bone cancer increases transient receptor potential vanilloid subfamily 1 expression within distinct subpopulations of dorsal root ganglion neurons.

Bone cancer pain has a strong impact on the quality of life of patients but is difficult to treat. Therefore, the mechanisms of bone cancer pain require elucidation for the purpose of development of new therapeutics. A recent study showed that activation of transient receptor potential vanilloid subfamily 1 (TRPV1) was involved in bone cancer pain. In this study, we re-evaluated the analgesic effects of pharmacological blockade of TRPV1 using the potent TRPV1 antagonist 5-iodoresiniferatoxin (I-RTX) and examined whether bone cancer can change TRPV1 expression and distribution in the primary sensory neurons in a mouse model of bone cancer pain. Implantation of osteosarcoma into the femur induced ongoing and movement-evoked bone cancer-related pain behaviors. These behaviors were significantly reduced by i.p. administration of I-RTX, compared with vehicle. Western blot and reverse transcription-polymerase chain reaction (RT-PCR) analyses revealed that TRPV1 level was significantly increased in dorsal root ganglions (DRGs) ipsilateral to sarcoma implantation. Immunohistochemical analysis showed that implantation of osteosarcoma induced not only an increase in the percentage of TRPV1-positive neurons among DRG neurons (24.3+/-1.3% in sham mice and 31.2+/-1.3% in mice with osteosarcoma implantation, P<0.05) but also an overall shift in the distribution of area of profiles to the right. Colocalization study showed that the percentages of colocalization of TRPV1 with neurofilament 200 kD (NF200) and calcitonin gene-related peptide (CGRP) but not isolectin B4 (IB4) among DRG neurons in mice with osteosarcoma implantation were increased compared with those in sham mice (from 0.8+/-0.1% to 2.1+/-0.3% for TRPV1 and NF200 and from 21.1+/-1.3% to 26.5+/-0.2% for TRPV1 and CGRP). In conclusion, TRPV1 activation plays a critical role in the generation of bone cancer pain, and bone cancer increases TRPV1 expression within distinct subpopulation of DRG neurons. These findings may lead to novel strategies for the treatment of bone cancer pain.

Immunohistochemical analysis of acid-sensing ion channel 2 expression in rat dorsal root ganglion and effects of axotomy.

Several studies have suggested that acid-sensing ion channel 2 (ASIC2) plays a role in mechanoperception and acid sensing in the peripheral nervous system. We examined the expression and distribution of ASIC2 in the rat dorsal root ganglion, the co-localization of ASIC2 with tropomyosin-related kinase (trk) receptors, and the effects of axotomy on ASIC2 expression. ASIC2 immunoreactivity was observed in both neurons and satellite cells. ASIC2-positive neurons accounted for 16.5 +/- 2.4% of the total neurons in normal dorsal root ganglion. Most ASIC2-positive neurons were medium-to-large neurons and were labeled with neurofilament 200 kD (NF200). Within these neurons, ASIC2 was not evenly distributed throughout the cytoplasm, but rather was accumulated prominently in the cytoplasm adjacent to the axon hillock and axonal process. We next examined the co-localization of ASIC2 with trk receptors. trkA was expressed in few ASIC2-positive neurons, and trkB and trkC were observed in 85.2% and 53.4% of ASIC2-positive neurons, respectively, while only 6.9% of ASIC2-positive neurons were co-localized with trkC alone. Peripheral axotomy markedly reduced ASIC2 expression in the axotomized dorsal root ganglion neurons. On the other hand, intense ASIC2 staining was observed in satellite cells. These results show that ASIC2 is expressed in the distinct neurochemical population of sensory neurons as well as satellite cells, and that peripheral axotomy induced marked reductions in ASIC2 in neurons.

Effects of thiopental on bispectral index and heart rate variability.

BACKGROUND AND OBJECTIVE: Thiopental has been reported to reduce sympathetic tone, however, it is not clear whether change in heart rate variability is associated with depth of anaesthesia. The purpose of the present study was to evaluate changes in heart rate variability at different depths of hypnosis during induction of anaesthesia with thiopental. METHODS: We studied 17 ASA I patients scheduled for minor surgery. The depth of hypnosis was monitored by the BIS. Spectral analysis of heart rate variability using a maximum entropy method resulted in a characteristic power spectrum with two main regions, a high frequency and a low frequency. Haemodynamics, entropy, low frequency, high frequency and low frequency/high frequency were monitored in an awake state and after the induction of anaesthesia. RESULTS: Heart rate increased in a BIS-dependent manner, whereas blood pressure showed no significant changes during the study period. High frequency, entropy and low frequency decreased with a reduction in the BIS value. Low frequency/high frequency showed no significant change during the study period. CONCLUSIONS: Induction of anaesthesia with thiopental increased heart rate and decreased high frequency, entropy and low frequency in a BIS-dependent manner, indicating that thiopental reduces cardiac parasympathetic tone depending on the depth of hypnosis.

Performance of three systems for warming intravenous fluids at different flow rates.

This study compared the intravenous fluid warming capabilities of three systems at different flow rates. The devices studied were a water-bath warmer, a dry-heat plate warmer, and an intravenous fluid tube warmer Ambient temperature was controlled at 22 degrees to 24 degrees C. Normal saline (0.9% NaCl) at either room temperature (21 degrees to 23 degrees C) or at ice-cold temperature (3 degrees to 5 degrees C) was administered through each device at a range of flow rates (2 to 100 ml/min). To mimic clinical conditions, the temperature of the fluid was measured with thermocouples at the end of a one metre tube connected to the outflow of the warmer for the first two devices and at the end of the 1.2 m warming tubing for the intravenous fluid tube warmer The temperature of fluid delivered by the water bath warmer increased as the flow rate was increased up to 15 to 20 ml/min but decreased with greater flow rates. The temperature of the fluid delivered by the dry-heat plate warmer significantly increased as the flow rate was increased within the range tested (due to decreased cooling after leaving the device at higher flow rates). The temperature of fluid delivered by the intravenous fluid tube warmer did not depend on the flow rate up to 20 ml/min but significantly and fluid temperature-dependently decreased at higher flow rates (>30 ml/min). Under the conditions of our testing, the dry heat plate warmer delivered the highest temperature fluid at high flow rates.

Angular distributions of H-induced HD and D2 desorptions from the Si(100) surfaces.

We measured angular distributions of HD and D2 molecules desorbed via the reactions H+DSi(100)-->HD [abstraction (ABS)] and H+DSi(100)-->D2 [adsorption-induced-desorption (AID)], respectively. It was found that the angular distribution of HD molecules desorbed along ABS is broader than that of D2 molecules desorbed along AID, i.e., the former could be fit with cos(2.0+/-0.2) theta, while the latter with cos(5.0+/-0.5) theta. This difference of the angular distributions between the two reaction paths suggests that their dynamic mechanisms are different. The observed cos2 theta distribution for the ABS reaction was reproduced by the classical trajectory calculations over the London-Eyring-Polanyi-Sato potential-energy surfaces. The simulation suggests that the HD desorption along the ABS path takes place along the direction of Si-D bonds, but the apparent angular distribution is comprised of multiple components reflecting the different orientations of D-occupied Si dimers in the (2 x 1) and (1 x 2) double domain structures.

Desorption dynamics of deuterium molecules from the Si(100)-(3x1) dideuteride surface.

We measured polar angle (theta)-resolved time-of-flight spectra of D2 molecules desorbing from the Si(100)-(3x1) dideuteride surface. The desorbing D2 molecules exhibit a considerable translational heating with mean desorption kinetic energies of approximately 0.25 eV, which is mostly independent of the desorption angles for 0 degrees

Endothelin-1 enhances capsaicin-evoked intracellular Ca2+ response via activation of endothelin a receptor in a protein kinase Cepsilon-dependent manner in dorsal root ganglion neurons.

Increasing evidence indicates that endothelin-1 has a role for peripheral nociceptive signaling in animals and humans. However, the mechanisms of the nociceptive effects of endothelin-1 have not been fully understood. The current study investigated the effects of endothelin-1 on the capsaicin-evoked intracellular Ca2+ response of cultured adult mice dorsal root ganglion neurons. Dorsal root ganglia were harvested from adult male C57B6N mice and were cultured. With a digital image analysis system, we detected the [Ca2+]i image of cultured dorsal root ganglion cells after loading with Fura-2 acetoxymethyl. In addition, co-localization of protein kinase Cepsilon with transient receptor potential V1 and the translocation of protein kinase Cepsilon were investigated using immunohistochemical methods. Endothelin-1 (10 nM) enhanced an increase in [Ca2+]i by capsaicin (10 nM) from 87.6+/-11.6 nM to 414.8+/-62.3 nM (71 of 156 neurons). The inhibition of endothelin A receptor (BQ-123) significantly suppressed the enhancing effect of endothelin-1. In addition, a nonselective protein kinase C inhibitor (bisindolylmaleimide I) significantly suppressed the enhancing effect of endothelin-1. A myristoyl-tagged membrane-permeant-protein kinase Cepsilon V1-2 inhibitory peptide also significantly suppressed the enhancing effect of endothelin-1. In the immunocytochemical study, protein kinase Cepsilon immunoreactivity was found in most of transient receptor potential V1-positive neurons. After endothelin-1 application, protein kinase Cepsilon immunoreactivity was observed to be translocated from the cytosol to the cell membrane in transient receptor potential V1-positive neurons. Our results indicate that endothelin-1 enhances the response of dorsal root ganglion neurons to capsaicin in a protein kinase Cepsilon-dependent manner. Our findings may lead to a new strategy to treat pain associated with endothelin-1.