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Odontoblasts are involved in sensory generation as sensory receptor cells and in dentin formation. We previously reported that an increase in intracellular cAMP levels by cannabinoid 1 receptor activation induces Ca2+ influx via transient receptor potential vanilloid subfamily member 1 channels in odontoblasts, indicating that intracellular cAMP/Ca2+ signal coupling is involved in dentinal pain generation and reactionary dentin formation. Here, intracellular cAMP dynamics in cultured human odontoblasts were investigated to understand the detailed expression patterns of the intracellular cAMP signaling pathway activated by the Gs protein-coupled receptor and to clarify its role in cellular functions. The presence of plasma membrane Gαs as well as prostaglandin I2 (IP), 5-hydroxytryptamine 5-HT4 (5-HT4), dopamine D1 (D1), adenosine A2A (A2A), and vasoactive intestinal polypeptide (VIP) receptor immunoreactivity was observed in human odontoblasts. In the presence of extracellular Ca2+, the application of agonists for the IP (beraprost), 5-HT4 (BIMU8), D1 (SKF83959), A2A (PSB0777), and VIP (VIP) receptors increased intracellular cAMP levels. This increase in cAMP levels was inhibited by the application of the adenylyl cyclase (AC) inhibitor SQ22536 and each receptor antagonist, dose-dependently. These results suggested that odontoblasts express Gs protein-coupled IP, 5-HT4, D1, A2A, and VIP receptors. In addition, activation of these receptors increased intracellular cAMP levels by activating AC in odontoblasts. [ABSTRACT FROM AUTHOR]

An inflammatory response following dental pulp injury and/or infection often leads to neurogenic inflammation via the axon reflex. However, the detailed mechanism underlying the occurrence of the axon reflex in the dental pulp remains unclear. We sought to examine the intracellular cyclic adenosine monophosphate (cAMP) signaling pathway in odontoblasts via the activation of Gs protein-coupled receptors and intercellular trigeminal ganglion (TG) neuron–odontoblast communication following direct mechanical stimulation of TG neurons. Odontoblasts express heterotrimeric G-protein α-subunit Gαs and calcitonin receptor-like receptors. The application of an adenylyl cyclase (AC) activator and a calcitonin gene-related peptide (CGRP) receptor agonist increased the intracellular cAMP levels ([cAMP]i) in odontoblasts, which were significantly inhibited by the selective CGRP receptor antagonist and AC inhibitor. Mechanical stimulation of the small-sized CGRP-positive but neurofilament heavy chain-negative TG neurons increased [cAMP]i in odontoblasts localized near the stimulated neuron. This increase was inhibited by the CGRP receptor antagonist. In the mineralization assay, CGRP impaired the mineralization ability of the odontoblasts, which was reversed by treatment with a CGRP receptor antagonist and AC inhibitor. CGRP establishes an axon reflex in the dental pulp via intercellular communication between TG neurons and odontoblasts. Overall, CGRP and cAMP signaling negatively regulate dentinogenesis as defensive mechanisms. [ABSTRACT FROM AUTHOR]

Some RNA classes require folding into the proper higher-order structures to exert their functions. Hammerhead ribozyme (HHR) requires a folding conformation stabilized by tertiary interaction for full activity. A rationally engineered HHR was developed that was inactive, but could be activated by a synthetic RNA-binding ligand, naphthyridine carbamate tetramer with Z-stilbene linker ( Z-NCTS). Binding of Z-NCTS could induce the formation of an active folding structure and thereby restore ribozyme activity, where Z-NCTS acts as a molecular glue to bring two isolated RNA loops into contact with each other. Next, we designed a Z-NCTS-responsive genetic switch using the HHR sequence inserted into the 3′ untranslated region as a cis-acting element. We demonstrated that the rationally designed ribozyme switch enabled regulation of gene expression by Z-NCTS and was functional in mammalian cells. [ABSTRACT FROM AUTHOR]

Some RNA classes require folding into the proper higher-order structures to exert their functions. Hammerhead ribozyme (HHR) requires a folding conformation stabilized by tertiary interaction for full activity. A rationally engineered HHR was developed that was inactive, but could be activated by a synthetic RNA-binding ligand, naphthyridine carbamate tetramer with Z-stilbene linker ( Z-NCTS). Binding of Z-NCTS could induce the formation of an active folding structure and thereby restore ribozyme activity, where Z-NCTS acts as a molecular glue to bring two isolated RNA loops into contact with each other. Next, we designed a Z-NCTS-responsive genetic switch using the HHR sequence inserted into the 3′ untranslated region as a cis-acting element. We demonstrated that the rationally designed ribozyme switch enabled regulation of gene expression by Z-NCTS and was functional in mammalian cells. [ABSTRACT FROM AUTHOR]

Universities in the United Kingdom have experienced a transformation in the context of the government’s initiatives to widen participation and rapid socio-economic changes locally and globally. With more diverse students entering higher education, universities need to consider how they can create an inclusive environment. Indeed, in order to stress their openness and (international) excellence, many universities proclaim their ‘commitment’ to diversity and difference. However, as Sara Ahmed suggests, institutional speech acts, such as a claim to promote equality and diversity, do not go beyond pluralist understandings of diversity and are non-performative. Through the examination of policies and practices concerning issues of equality and diversity in English universities, this article, firstly, considers whether universities are successful in promoting equality amongst different (ethnic) groups. Then, through a case study of a university, it examines how students become raced, classed, gendered, or nationed subjects, while they struggle to form their own agency. [ABSTRACT FROM PUBLISHER]

We have been studying the blood compatibility of polymeric materials from the viewpoint of their water structure, and have proposed that freezable water interacting with polymer molecules plays an important role in determining that compatibility. As we found that water-soluble poly(acryloylmorpholine) interacted with water, resulting in the formation of 'bound water', we newly prepared water-non-soluble poly(acryloylmorpholine-r-butyl methacrylate) (denoted as ACMO co-polymer) with various composition ratios. In addition, the properties of a co-polymer based on N,N-diethylacrylamide (DEA co-polymer), where DEA has a similar chemical structure to ACMO, except that DEA has no ether oxygen, were compared with that of the ACMO co-polymer. Contact angle and DSC analysis revealed that an increase in the content of an N-substituted acrylamide unit in the co-polymers enhanced the hydrophilicity of the polymer and that the hydrophilicity of the ACMO co-polymer was stronger than that of the DEA co-polymer. As for the water structure, it was found that the ACMO co-polymer had a lot of bound water compared to the DEA co-polymer. The difference in these properties between the ACMO and DEA co-polymers was due to the ether oxygen of the morpholine group. At the same time, in vitro blood compatibility tests showed that the ACMO co-polymer exhibited a much better performance than the DEA co-polymer. The water structure and blood compatibility is discussed in detail. [ABSTRACT FROM AUTHOR]

The effects of thiopental on Ca2+ currents and intracellular Ca2+ transient in single atrial cells from guinea pigs were studied by means of a whole-cell voltage-clamp method and Ca2+-sensitive fluorescent dye. Thiopental inhibited L-type voltage-dependent Ca2+ currents in a concentration-dependent manner (IC50 = 2.8·10–5 mol/l). Moreover, the mode of Ca2+ current inhibition by thiopental showed no use dependency. Electrical stimulation-induced intracellular Ca2+ transient was significantly suppressed by 10–5 mol/l thiopental. However, the caffeine-sensitive Ca2+ releasing pathway from sarcoplasmic reticulum was not affected by thiopental. Our results indicate that thiopental inhibits L-type Ca2+ currents, but not release of Ca2+ from sarcoplasmic reticulum. These results suggest that the negative inotropic action of thiopental is mainly due to inhibition of L-type Ca2+ channels in guinea pig atrial myocytes. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: The stabilization of both the horizontal (H) and vertical (V) eye movements during voluntary fixation is believed to depend upon the visual feedback system in the upright position. However, ocular stability in the tilted position has been less well investigated. Therefore, in the present study, we examined the gaze stability of healthy human subjects in the three dimensions in the tilted position using a video image analysis system (VIAS).Methods: In 10 healthy human subjects, the eye movements were recorded after fixating the eye on a target in an upright position and also in the tilted position. The standard deviations of the eye movements in the three dimensions were calculated to evaluate the stability of the movements.Results: In the tilted position, there were no significant changes in the horizontal and vertical eye movements as compared those in the upright position. However, the standard deviation of the torsional (T) segment was significantly larger in the tilted position, compared to that in the upright position.Conclusion: From these results, we speculate that, a combination of otolith and somatosensory inputs play a major role in maintaining the stability of eye movements. [ABSTRACT FROM AUTHOR]

Intracellular Ca2+ signaling engendered by Ca2+ influx and mobilization in odontoblasts is critical for dentinogenesis induced by multiple stimuli at the dentin surface. Increased Ca2+ is exported by the Na+–Ca2+ exchanger (NCX) and plasma membrane Ca2+–ATPase (PMCA) to maintain Ca2+ homeostasis. We previously demonstrated a functional coupling between Ca2+ extrusion by NCX and its influx through transient receptor potential channels in odontoblasts. Although the presence of PMCA in odontoblasts has been previously described, steady-state levels of mRNA-encoding PMCA subtypes, pharmacological properties, and other cellular functions remain unclear. Thus, we investigated PMCA mRNA levels and their contribution to mineralization under physiological conditions. We also examined the role of PMCA in the Ca2+ extrusion pathway during hypotonic and alkaline stimulation-induced increases in intracellular free Ca2+ concentration ([Ca2+]i). We performed RT-PCR and mineralization assays in human odontoblasts. [Ca2+]i was measured using fura-2 fluorescence measurements in odontoblasts isolated from newborn Wistar rat incisor teeth and human odontoblasts. We detected mRNA encoding PMCA1–4 in human odontoblasts. The application of hypotonic or alkaline solutions transiently increased [Ca2+]i in odontoblasts in both rat and human odontoblasts. The Ca2+ extrusion efficiency during the hypotonic or alkaline solution-induced [Ca2+]i increase was decreased by PMCA inhibitors in both cell types. Alizarin red and von Kossa staining showed that PMCA inhibition suppressed mineralization. In addition, alkaline stimulation (not hypotonic stimulation) to human odontoblasts upregulated the mRNA levels of dentin matrix protein-1 (DMP-1) and dentin sialophosphoprotein (DSPP). The PMCA inhibitor did not affect DMP-1 or DSPP mRNA levels at pH 7.4–8.8 and under isotonic and hypotonic conditions, respectively. We also observed PMCA1 immunoreactivity using immunofluorescence analysis. These findings indicate that PMCA participates in maintaining [Ca2+]i homeostasis in odontoblasts by Ca2+ extrusion following [Ca2+]i elevation. In addition, PMCA participates in dentinogenesis by transporting Ca2+ to the mineralizing front (which is independent of non-collagenous dentin matrix protein secretion) under physiological and pathological conditions following mechanical stimulation by hydrodynamic force inside dentinal tubules, or direct alkaline stimulation by the application of high-pH dental materials. [ABSTRACT FROM AUTHOR]

Purinergic receptors play key signaling roles in neuropathic pain in the orofacial region, which is innervated by trigeminal ganglion (TG) neurons. The neuropathology of purinergic P2Y 12 receptors is well characterized in glia; however, their physiological role in TG neurons remains to be fully elucidated. The present study investigated the expression and function of P2Y 12 receptors in rat TG neurons. P2Y 12 receptor immunoreactivity was intense in the soma, dendrites, and axons, and colocalized with a pan-neuronal marker, neurofilament H, isolectin B4, and substance P. In the presence of extracellular Ca 2+ , 2-methylthio-ADP (an agonist of P2Y 1, 12, 13 receptors) transiently increased intracellular free Ca 2+ concentrations ([Ca 2+ ] i ), an effect that was abolished by P2Y 12 receptor antagonists. In the absence of extracellular Ca 2+ , ryanodine receptor/channel inhibitors diminished the 2-methylthio-ADP-induced increases in [Ca 2+ ] i . A sarcoplasmic reticulum Ca 2+ -ATPase (SERCA) inhibitor gradually increased [Ca 2+ ] i , and after a plateau, application of 2-MeS-ADP induced a rapid and transient, but additive increase in [Ca 2+ ] i . An adenylate cyclase inhibitor transiently increased [Ca 2+ ] i , while a phosphodiesterase inhibitor prevented the 2-methylthio-ADP-induced increase in [Ca 2+ ] i . Our study shows that P2Y 12 receptors are expressed in TG neurons, and act via a cAMP-dependent pathway to release intracellular Ca 2+ from ryanodine-sensitive Ca 2+ stores. [ABSTRACT FROM AUTHOR]

Various stimuli induce pain when applied to the surface of exposed dentin. However, the mechanisms underlying dentinal pain remain unclear. We investigated intercellular signal transduction between odontoblasts and trigeminal ganglion (TG) neurons following direct mechanical stimulation of odontoblasts. Mechanical stimulation of single odontoblasts increased the intracellular free calcium concentration ([Ca]) by activating the mechanosensitive-transient receptor potential (TRP) channels TRPV1, TRPV2, TRPV4, and TRPA1, but not TRPM8 channels. In cocultures of odontoblasts and TG neurons, increases in [Ca] were observed not only in mechanically stimulated odontoblasts, but also in neighboring odontoblasts and TG neurons. These increases in [Ca] were abolished in the absence of extracellular Ca and in the presence of mechanosensitive TRP channel antagonists. A pannexin-1 (ATP-permeable channel) inhibitor and ATP-degrading enzyme abolished the increases in [Ca] in neighboring odontoblasts and TG neurons, but not in the stimulated odontoblasts. G-protein-coupled P2Y nucleotide receptor antagonists also inhibited the increases in [Ca]. An ionotropic ATP (P2X) receptor antagonist inhibited the increase in [Ca] in neighboring TG neurons, but not in stimulated or neighboring odontoblasts. During mechanical stimulation of single odontoblasts, a connexin-43 blocker did not have any effects on the [Ca] responses observed in any of the cells. These results indicate that ATP, released from mechanically stimulated odontoblasts via pannexin-1 in response to TRP channel activation, transmits a signal to P2X receptors on TG neurons. We suggest that odontoblasts are sensory receptor cells and that ATP released from odontoblasts functions as a neurotransmitter in the sensory transduction sequence for dentinal pain. [ABSTRACT FROM AUTHOR]

The article focuses on the operating mechanism of artificial functional RNAs known as riboswitches with the designed ligand-RNA pair. It states that artificial riboswitches can provide designer gene regulation systems that are ideal for cellular programming, bioactive molecules detection, and controlled therapeutics gene expression. It notes that naphthyridine carbamate tetramer derivative (Z-NCTS) shows potentiality as an RNA-mismatch-binding ligand.

The article presents a study which aims to create a synthetic riboswitch through the use of the chemistry-based design of a ligand molecule and its target RNA sequence. It states that a ligand-aptamer pair is a vital element in the creation of riboswitch. Moreover, the study shows that the a ligand-aptamer pair could be attained by the rational design of a synthetic RNA-binding ligand without the use of selection methods.

Abstract: Unusual expansion of trinucleotide repeats has been identified as a common mechanism of hereditary neurodegenerative diseases. Although the actual mechanism of repeat expansion remains uncertain, trinucleotide repeat instability may be related to the increased stability of an alternative DNA hairpin structure formed in the repeat sequences. Here we report that a synthetic ligand naphthyridine carbamate dimer (NCD) selectively bound to and stabilized an intra-stranded hairpin structure in CGG repeat sequences. The NCD–CGG hairpin complex was a stable structure that efficiently interfered with DNA replication by Taq DNA polymerase. Considering the sequence preference of NCD, the use of NCD would be valuable to investigate the genetic instabilities of CGG/CCG repeat sequences in human genomes. [Copyright &y& Elsevier]

Abstract: Objective: Based on the hypothesis that the origin of nystagmus is from the posterior canal (PC), the nystagmus in the head hanging and sitting position should be mirror images. To clarify the anatomical origin of positioning nystagmus in BPPV patients, we analyzed the positioning nystagmus of benign paroxysmal positioning vertigo (BPPV) patients three-dimensionally. Methods: Twenty-six patients with BPPV participated in this study. The positioning nystagmus was recorded in complete darkness from the patient''s left eye by means of an infrared CCD camera. We performed three-dimensional analysis of nystagmus using video image analysis system (VIAS). Subsequently, the rotation axis of the 3D eye movements of the positioning nystagmus was calculated. Results: Among the 26 patients tested, 20 patients demonstrated the axes of nystagmus in good or relatively good alignment to the PC axis. However, in 11 of these 20 patients there was poor alignment of the axis of nystagmus in the sitting position to the PC axis. In addition, six patients showed axes of nystagmus with poor alignment to the PC in the head hanging position. Among them, two patients exhibited axes of nystagmus in good alignment with the anterior canal, in spite of diagnosis of these patients as PC BPPV by experienced examiner based on the positioning nystagmus test. Conclusion: These results demonstrated that only one-third of patients who were diagnosed as BPPV, could be diagnosed as true BPPV which originates from a PC pathology. Besides the possibility that the pathology may originate from the AC, it is still unclear which part of the inner ear may be the candidate site of origin of the pathology of BPPV in the other 15 patients. [Copyright &y& Elsevier]

Aims/Introduction: The preservation of pancreatic β‐cell mass is an essential factor in the onset and development of type 2 diabetes mellitus. Recently, sodium–glucose cotransporter 2 inhibitors have been launched as antihyperglycemic agents, and their organ‐protective effects are attracting attention. They are also reported to have favorable effects on the preservation of pancreatic β‐cell mass, but the appropriate timing for the administration of sodium–glucose cotransporter 2 inhibitors is obscure. Materials and Methods: In the present study, we administered a sodium–glucose cotransporter 2 inhibitor, dapagliflozin, to an animal model of type 2 diabetes mellitus, db/db mice, and investigated the adequate timing and duration for its administration. We also carried out microarray analysis using pancreatic islets from db/db mice. Results: We found that dapagliflozin preserved pancreatic β‐cell mass depending on the duration of administration and markedly improved blood glucose levels. If the duration was the same, the earlier administration of dapagliflozin was more effective in preserving pancreatic β‐cell mass, increasing serum insulin levels and improving blood glucose levels. From microarray analysis, we discovered that the expression of Agr2, Tff2 and Gkn3 was significantly upregulated after the early administration of dapagliflozin. This upregulated gene expression might provide a legacy effect for the preservation of pancreatic β‐cell mass. Conclusions: We expect that the early administration of dapagliflozin would provide a long‐lasting effect in preserving pancreatic β‐cell mass. [ABSTRACT FROM AUTHOR]

Recent studies demonstrated that insulin signaling plays important roles in the regulation of pancreatic β cell mass, the reduction of which is known to be involved in the development of diabetes. However, the mechanism underlying the alteration of insulin signaling in pancreatic β cells remains unclear. The involvement of epigenetic control in the onset of diabetes has also been reported. Thus, we analyzed the epigenetic control of insulin receptor substrate 2 (IRS2) expression in the MIN6 mouse insulinoma cell line. We found concomitant IRS2 up-regulation and enhanced insulin signaling in MIN6 cells, which resulted in an increase in cell proliferation. The H3K9 acetylation status of the Irs2 promoter was positively associated with IRS2 expression. Treatment of MIN6 cells with histone deacetylase inhibitors led to increased IRS2 expression, but this occurred in concert with low insulin signaling. We observed increased IRS2 lysine acetylation as a consequence of histone deacetylase inhibition, a modification that was coupled with a decrease in IRS2 tyrosine phosphorylation. These results suggest that insulin signaling in pancreatic β cells is regulated by histone deacetylases through two novel pathways affecting IRS2: the epigenetic control of IRS2 expression by H3K9 promoter acetylation, and the regulation of IRS2 activity through protein modification. The identification of the histone deacetylase isoform(s) involved in these mechanisms would be a valuable approach for the treatment of type 2 diabetes. [ABSTRACT FROM AUTHOR]

For the treatment of nasal and nostril stenosis caused by facial burn, it is necessary to perform rhinoplasty and nasal vestibuloplasty using various flaps, perform cicatrectomy of the nostrils with a rhinosurgical procedure, and prevent restenosis of the nostrils and nasal cavity for a certain period by methods such as placement of a nasal retainer or transnasal airway and gauze packing of the nasal cavity. With all methods, postoperative placement of a retainer or nasal treatment is necessary for the prevention of postoperative restenosis, and the patient's cooperation is essential. In a patient who did not cooperate in postoperative treatments due to autism and had recurrences of nasal and nostril stenosis after conventional surgical treatments, adequate patency of the nasal cavity and nostrils could be maintained with minimal postoperative treatment by placing a self-expandable metallic esophageal stent. [ABSTRACT FROM AUTHOR]

During the development of type 2 diabetes, endoplasmic reticulum (ER) stress leads to not only insulin resistance but also to pancreatic beta cell failure. Conversely, cell function under various stressed conditions can be restored by reducing ER stress by activating AMP-activated protein kinase (AMPK). However, the details of this mechanism are still obscure. Therefore, the current study aims to elucidate the role of AMPK activity during ER stress-associated pancreatic beta cell failure. MIN6 cells were loaded with 5-amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide (AICAR) and metformin to assess the relationship between AMPK activity and CCAAT enhancer binding protein β (C/EBPβ) expression levels. The effect of C/EBPβ phosphorylation on expression levels was also investigated. Vildagliptin and metformin were administered to pancreatic beta cell-specific C/EBPβ transgenic mice to investigate the relationship between C/EBPβ expression levels and AMPK activity in the pancreatic islets. When pancreatic beta cells are exposed to ER stress, the accumulation of the transcription factor C/EBPβ lowers the AMP/ATP ratio, thereby decreasing AMPK activity. In an opposite manner, incubation of MIN6 cells with AICAR or metformin activated AMPK, which suppressed C/EBPβ expression. In addition, administration of the dipeptidyl peptidase-4 inhibitor vildagliptin and metformin to pancreatic beta cell-specific C/EBPβ transgenic mice decreased C/EBPβ expression levels and enhanced pancreatic beta cell mass in proportion to the recovery of AMPK activity. Enhanced C/EBPβ expression and decreased AMPK activity act synergistically to induce ER stress-associated pancreatic beta cell failure. [ABSTRACT FROM AUTHOR]

The development of type 2 diabetes is accompanied by a progressive decline in β-cell mass and function. Vildagliptin, a dipeptidyl peptidase 4 inhibitor, is representative of a new class of antidiabetic agents that act through increasing the expression of glucagon-like peptide-1. The protective effect of this agent on β cells was studied in diabetic mice. Diabetic pancreatic β cell-specific C/EBPB transgenic (TG) mice exhibit decreased β-cell mass associated with increased apoptosis, decreased proliferation, and aggravated endoplasmic reticulum (ER) stress. Vildagliptin was orally administered to the TG mice for a period of 24 weeks, and the protective effects of this agent on β cells were examined, along with the potential molecular mechanism of protection. Vildagliptin ameliorated hyperglycemia in TG mice by increasing the serum concentration of insulin and decreasing the serum concentration of glucagon. This agent also markedly increased β-cell mass, improved aggravated ER stress, and restored attenuated insulin/IGF1 signaling. A decrease in pancreatic and duodenal homeobox 1 expression was also observed in β cells isolated from our mouse model, but this was also restored by vildagliptin treatment. The expression of C/EBPB protein, but not mRNA, was unexpectedly downregulated in vildagliptin-treated TG mice and in exenatide-treated MIN6 cells. Activation of the GLP1 pathway induced proteasome-dependent C/EBPB degradation in β cells as the proteasome inhibitor MG132 restored the downregulation of C/EBPB protein by exenatide. Vildagliptin elicits protective effects on pancreatic β cells, possibly through C/EBPB degradation, and has potential for preventing the progression of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Abstract: In order to record and analyze the rapid eye movement non-invasively in human subjects, a four times high-speed video camera (4TC) with a new computer software was developed and utilized. Nine healthy volunteers and four patients with vestibular dysfunction participated in this study. Caloric stimulation was applied to the healthy subjects and the eye movements were recorded using a standard camera (SC) and a 4TC. In four patients, the positional and/or positioning nystagmus was recorded using SC and 4TC. Analysis of the eye speed of the quick phase of nystagmus was performed manually from the print out of the chart. The quick phase of the caloric nystagmus was adequately analyzed from the data using 4TC. However, using SC the sampling rate was not sufficiently enough for this purpose, as prospected. The adaptability of the 4TC in clinical examination is exactly similar to that of SC, because of the size and weight of the camera. Although the time taken to analyze eye movements using 4TC is about four times longer than that using SC, this system is quite useful and adequate for analyzing the quick eye movements in vestibular nystagmus, in an out-patient clinic set up. [Copyright &y& Elsevier]

Abstract: Objectives:: Presently, the neurotological tests, using visual stimulation, such as optokinetic nystagmus test (OKN), eye-tracking test (ETT) is being widely used for the diagnosis of vertigo or disequilibrium. The problems of these tests are the large size of the visual stimulator and therefore a wide space requirement. Even if a small apparatus is developed, the apparatus itself would be very expensive. In this study, we developed a small visual stimulation test system comprising the virtual visor, which receives an image for visual stimulation from an on-line computer. Methods:: Using smooth pursuit and optokinetic stimulation onto a virtual visor we assessed the ENG recording in 20 normal subjects. Result:: We found the 30°/s OKN, horizontal eye tracking were adequately stimulated by this technique with reliable results. Conclusion:: This new method of smooth pursuit and optokinetic stimulating by a virtual visor is capable of producing reliable results and may be used in the clinical laboratory of vertigo. However, this stimulator also has some limitations, mainly because of the visual angle of the virtual visor stimulator. [Copyright &y& Elsevier]

The ionotropic P2X receptor, P2X7, is believed to regulate and/or generate nociceptive pain, and pain in several neuropathological diseases. Although there is a known relationship between P2X7 receptor activity and pain sensing, its detailed functional properties in trigeminal ganglion (TG) neurons remains unclear. We examined the electrophysiological and pharmacological characteristics of the P2X7 receptor and its functional coupling with other P2X receptors and pannexin-1 (PANX1) channels in primary cultured rat TG neurons, using whole-cell patch-clamp recordings. Application of ATP and Bz-ATP induced long-lasting biphasic inward currents that were more sensitive to extracellular Bz-ATP than ATP, indicating that the current was carried by P2X7 receptors. While the biphasic current densities of the first and second components were increased by Bz-ATP in a concentration dependent manner; current duration was only affected in the second component. These currents were significantly inhibited by P2X7 receptor antagonists, while only the second component was inhibited by P2X1, 3, and 4 receptor antagonists, PANX1 channel inhibitors, and extracellular ATPase. Taken together, our data suggests that autocrine or paracrine signaling via the P2X7-PANX1-P2X receptor/channel complex may play important roles in several pain sensing pathways via long-lasting neuronal activity driven by extracellular high-concentration ATP following tissue damage in the orofacial area. [ABSTRACT FROM AUTHOR]

• Swallowing timings were evaluated by two barometers in oral cavity and oropharynx. • Anterior and posterior intrinsic tongue EMGs were also recorded. • Timings of nasopharyngeal closure could be measured by the sensor in oral cavity. • Durations of oral and pharyngeal stages of swallowing were measured as 0.4 and 0.6 sec. • The tongue begins the activity for swallowing before nasopharyngeal closure. : The exact timings associated with swallowing are difficult to measure with the currently available methods. In this study, we aimed to elucidate the timings of action of the swallowing organs in the oral and pharyngeal stages of swallowing by recording the barometric pressure (BP) and tongue muscle activities. : Dry and water swallows were studied in 10 adults using electromyography and small barometers. BPs were recorded during swallowing in the oral cavity (BP-o) and pharynx (BP-p), associated with muscle activities of the anterior (TA) and posterior (TP) parts of the tongue and of the suprahyoid (SHy) muscle. To analyze the temporal pattern of each activity, times of onset, cessation, and peak were measured. : Two characteristic waveforms were obtained. BP-o peaked immediately after onset and decreased to atmospheric pressure following a short plateau. However, BP-p gradually increased, reached a peak, and returned to the atmospheric pressure immediately before the end of BP-o. Since pressure increments indicated that the sensor was compressed in a closed space, onset and cessation of BP-p could correspond to the duration of nasopharyngeal closure. The onset of BP-p and the peak time of BP-o occurred in close succession. Thus, nasopharyngeal closure could be evaluated from BP-o. The sensor and EMG measured durations of oral and pharyngeal stages as 0.4 and 0.6 sec, respectively. TA activation began earlier than the TP. TA and TP peaks appeared before the BP-o peak, suggesting that the tongue begins the activity for swallowing before nasopharyngeal closure. : This study revealed movements of swallowing organs in the two stages with high temporal resolution. BP-o detected the duration of nasopharyngeal closure. [ABSTRACT FROM AUTHOR]