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Postoperative health care-associated infections are associated with a greater deterioration in patients' general health status and social and economic burden, with at least 1 occurring in approximately 4% of acute care hospital patients. Antimicrobial prophylaxis prevents surgical site infections in various orthopedic procedures; however, its relationship with health care-associated infections remains unknown.To examine whether a shorter antimicrobial prophylaxis duration of less than 24 hours after surgery is not inferior to a longer duration in preventing health care-associated infections after clean orthopedic surgery.This open-label, multicenter, cluster randomized, noninferiority clinical trial was conducted in 5 tertiary referral hospitals in greater Tokyo metropolitan area, Japan, from May to December 2018. Adult patients undergoing clean orthopedic surgery were recruited until the planned number of participants was achieved (500 participants per group). Statistical analysis was conducted from July to December 2019.Antimicrobial prophylaxis was discontinued within 24 hours after surgery in group 24 and 24 to 48 hours after surgery in group 48. Group allocation was switched every 2 or 4 months according to the facility-based cluster rule. Study-group assignments were masked from participants.The primary outcome was the incidence of health care-associated infections requiring antibiotic therapies within 30 days after surgery. The noninferiority margin was 4%.Of the 1211 participants who underwent cluster allocation, 633 participants were in group 24 (median [IQR] age, 73 [61-80] years; 250 men [39.5%] and 383 women [60.5%]), 578 participants were in group 48 (median [IQR] age, 74 [62-81] years; 204 men [35.3%] and 374 women [64.7%]), and all were eligible for the intention-to-treat analyses. Health care-associated infections occurred in 29 patients (4.6%) in group 24 and 38 patients (6.6%) in group 48. Intention-to-treat analyses showed a risk difference of -1.99 percentage points (95% CI, -5.05 to 1.06 percentage points; P .001 for noninferiority) between groups, indicating noninferiority. Results of adjusted intention-to-treat, per-protocol, and per designated procedure population analyses supported this result, without a risk of antibiotic resistance and prolonged hospitalization.This cluster randomized trial found noninferiority of a shorter antimicrobial prophylaxis duration in preventing health care-associated infections without an increase in antibiotic resistance risk. These findings lend support to the global movement against antimicrobial resistance and provide additional information on adequate antimicrobial prophylaxis for clean orthopedic surgery.Identifier: UMIN000030929.

Purpose A new method inducing the physiologic rest position of the mandible using the lip contact position with the closed mouth have compared with those obtained using conventional methods of placing the mandible in the physiologic rest position. Methods The lip contact position with the closed mouth as a method was investigated whether the technique was useful for determining the occlusal vertical dimension. The relationship between the space between the maxillary and mandibular front teeth in the lip contact position with the closed mouth and the areas of the prolabia was also investigated. Results Median space between the maxillary and mandibular front teeth in the lip contact position with the closed mouth was 1.53 mm, a value intermediate between the value of 2.16 mm in the resting mandibular position obtained by the conventional technique and that of 1.33 mm in the swallowing position. The coefficient of variation of the space in the lip contact position with the closed mouth was significantly lower than those in the resting mandibular position and in the swallowing position. A significant positive correlation was recognized between the space in the lip contact position with the closed mouth and the area of the prolabium of the upper lip. Conclusions These results clarified that the lip contact position with the closed mouth obtained the excellent reproducibility comparing to the conventional methods. These findings suggested that the area of the prolabium of the upper lip might offer an effective index for individual determination of the correct free-way space.

The autonomic nervous system affects the gustatory responses in animals. Frog glossopharyngeal nerve (GPN) contains the parasympathetic nerve. We checked the effects of electrical stimulation (ES) of the parasympathetic nerves on the gustatory neural responses. The gustatory neural impulses of the GPNs were recorded using bipolar AgCl wires under normal blood circulation and integrated with a time constant of 1 s. Electrical stimuli were applied to the proximal side of the GPN with a pair of AgCl wires. The parasympathetic nerves of the GPN were strongly stimulated for 10 s with 6 V at 30 Hz before taste stimulation. The integrated neural responses to 0.5 M NaCl, 2.5 mM CaCl2, water, and 1 M sucrose were enhanced to 130-140% of the controls. On the other hand, the responses for 1 mM Q-HCl and 0.3 mM acetic acid were not changed by the preceding applied ES. After hexamethonium (a blocker of nicotinic ACh receptor) was intravenously injected, ES of the parasympathetic nerve did not modulate the responses for all six taste stimuli. The mechanism for enhancement of the gustatory neural responses is discussed.

PURPOSE The present study aimed to investigate the relationships between the crown form of the upper central incisor and their labial inclination, overbite, and overjet. MATERIALS AND METHODS Maxillary and mandibular casts of 169 healthy dentitions were subjected to 3D dental scanning, and analyzed using CAD software. The crown forms were divided into tapered, square, and ovoid based on the mesiodistal dimensions at 20% of the crown height to that at 40%. The degree of labial inclination of the upper central incisor was defined as the angle between the occlusal plane and the line connecting the incisal edge and tooth cervix. The incisal edges of the right upper and lower central incisor that in contact with lines parallel to the occlusal plane were used to determine the overbite and overjet. One-way ANOVA was performed to compare the labial inclination, overbite, and overjet among the crown forms. RESULTS The crown forms were classified into three types; crown forms with a 20%/40% dimension ratio of 1.00±0.01 were defined as square, >1.01 as tapered, and

The aim of this study was to investigate vacuum forming techniques for reduction of loss in mouthguard thickness effects of sheet grooving and thermal shrinkage of extruded sheets on molded mouthguard thickness. Mouthguards were fabricated with ethylene vinyl acetate (EVA) sheets (4.0 mm thick) using a vacuum forming machine. Sheet form was a convexing v-shaped groove toward the back, 10-40 mm from the anterior end. The sheets were placed in the forming machine with the sheet extrusion direction either vertical or parallel to the model's centerline of right and left. Molding was performed by crimping the sheet using suction when the most descending portion of the sheet sagged downwards from the clamp, 15 mm below the basal surface. Postmolding thickness was determined using a measuring device. Measurement points were the incisal portion (incisal edge and labial surface) and molar portion (cusp and buccal surface). Differences in molded mouthguard thickness with the sheet orientation of extruded EVA sheets were analyzed by student's t-test. The sheet in parallel axis orientation with the model's centerline yielded higher thickness than vertical orientation at the labial surface and the buccal surface. The present results suggested that addition of a groove to the sheet in conjunction with placement of the sheet with its axis of orientation parallel the centerline of the working model can effectively reduce thickness loss in the molded mouthguard with the equipment and materials used in this study.

Hyaluronan (HA) has been increasingly used as a dietary supplement to improve the skin. However, the effect of ingested HA may depend on its molecular weight (MW) because its physiological activities in the body vary with its MW. In this study, we examined the effects of ingested HA with varying MW on the skin. In this randomized, double blind, placebo controlled study, 61 subjects with dry skin received oral HA (120 mg/day), of MWs 800 k and 300 k or placebo, for 6 weeks. The skin moisture contents of the first two groups increased more than those of the placebo group during the ingestion period. In addition, group HA 300 k exhibited significant improvements in skin moisture content 2 weeks after ingestion ended compared with the placebo group. A questionnaire survey about subjective facial aging symptoms showed that the HA treated groups exhibited significantly improved the skin condition compared with the placebo treated group. Furthermore, dermatologists objectively evaluated the clinical symptoms of the facial and whole body skin, showing that no adverse events were related to daily ingestion of HA. This study shows that both of ingesting HAs (MWs 800 k and 300 k) improved the skin condition by increasing the moisture content.

A possibility of efferent innervation of gustatory and mechanosensitive afferent fiber endings was studied in frog fungiform papillae with a suction electrode. The amplitude of antidromic impulses in a papillary afferent fiber induced by antidromically stimulating an afferent fiber of glossopharyngeal nerve (GPN) with low voltage pulses was inhibited for 40 s after the parasympathetic efferent fibers of GPN were stimulated orthodromically with high voltage pulses at 30 Hz for 10 s. This implies that electrical positivity of the outer surface of papillary afferent membrane was reduced by the efferent fiber-induced excitatory postsynaptic potential. The inhibition of afferent responses in the papillae was blocked by substance P receptor blocker, L-703,606, indicating that substance P is probably released from the efferent fiber terminals. Slow negative synaptic potential, which corresponded to a slow depolarizing synaptic potential, was extracellularly induced in papillary afferent terminals for 45 s by stimulating the parasympathetic efferent fibers of GPN with high voltage pulses at 30 Hz for 10 s. This synaptic potential was also blocked by L-703,606. These data indicate that papillary afferent fiber endings are innervated by parasympathetic efferent fibers.

目的：本研究の目的は，リンガライズドオクルージョンを付与する場合に使用するブレードティースの起始部の形態が食品破砕時の義歯への荷重量に及ぼす影響を明らかにすることである．方法：実験はブレード先端からブレード基底面の起始部に線角と点角を明瞭に付与したブレードティース（BTC）とブレード先端からブレード基底面へ向かう陥凹した自然移行形態を付与したブレードティース（BTR）の2種類間で，性状の異なる代表的な4種の食品（ニンジン，ピーナッツ，カマボコ，タクアン）をシミュレーター上で測定して比較検討した．結果：各種食品破砕時に上下顎義歯に加わる最大垂直力は，いずれの食品においてもBTRが BTCよりも小さくなる傾向を示し，ニンジン，ピーナッツ，タクアンで有意差が認められ，軟性・弾力性食品であるカマボコでは有意差は認められなかった．各種食品破砕時に下顎義歯に加わる最大水平力には，頬側方向のニンジン，ピーナッツで有意差が認められたが，他の条件についてはBTRとBTC間に有意差は認められなかった．結論：リンガライズドオクルージョンをブレードティースで構成する場合に，ブレード起始部の形態は食品破砕時に義歯に加わる垂直力と水平力に影響を及ぼすことが明らかとなり，BTRが BTCより小さな力で食品の破砕が可能なことが明らかとなった．

Temperature sensitivity of frog taste cells was studied. The taste cell designated Type thermosensitive (TS) I cell was depolarized by warm stimulus at 30 degrees C and hyperpolarized by cold stimulus at 10 degrees C. The taste cell designated Type TS II cell was depolarized by the cold stimulus and hyperpolarized by the warm stimulus. Menthol solution at 20 degrees C, which selectively activates transient receptor potential (TRP) M8 channels sensitive to cold stimuli, depolarized Type TS II cells but not Types TS I cells. Thermal stimuli-induced receptor potentials were all blocked by a nonselective cation channel blocker flufenamic acid. The results indicate that Type TS I cells have warm sensor channels alone, Type TS II cells have cold sensor channels alone and both the channels are a nonselective cation channel. The candidate of cold sensor channel in Type TS II cells is a TRPM8 channel and that of warm sensor channel in Type TS I cells is likely to be a TRPM4-like channel from the published data. In a subset of taste cells, Types TS III and TS IV cells were found. The former was depolarized by both cold and warm stimuli, but the latter was hyperpolarized by both stimuli. Types TS III and TS IV cells might have both TRPM4-like and TRPM8 channels. It is supposed that depolarizations induced by both cold and warm stimuli were dominant in Type TS III cells and hyperpolarizations induced by both the thermal stimuli were dominant in Type TS IV cells.

A gap junction blocker, 18beta-glycyrrhetinic acid (beta-GA), increased the membrane resistance of Ia, Ib and II/III cells of frog taste disk by 50, 160, and 300 M Omega, respectively, by blocking the gap junction channels and hemichannels. The amplitudes of gustatory depolarizing potentials in the disk cells for 4 basic taste stimuli were reduced to 40-60% after intravenous injection of beta-GA at 1.0 mg/kg. beta-GA of 1.0 mg/kg did not affect the resting potentials and the reversal potentials for tastant-induced depolarizing potentials in any taste disk cells. The percentage of cells responding to each of 4 basic taste stimuli and varying numbers of 4 taste qualities did not differ between control and beta-GA-treated taste disk cells. This implies that gustatory depolarizing response profiles for 4 basic taste stimuli were very similar in control and beta-GA-treated taste disk cells. It is concluded that beta-GA at 1.0 mg/kg reduced the amplitude of gustatory depolarizing potentials in taste disk cells by strongly blocking depolarizing currents flowing through the gap junction channels and hemichannels, but probably weakly affected the gustatory transduction mechanisms for 4 taste stimuli., Cellular and molecular neurobiology, 29(4), pp.503-512; 2009

Electrical stimulation of parasympathetic nerve (PSN) efferent fibers in the glossopharyngeal nerve induced a slow depolarizing synaptic potential (DSP) in frog taste cells under hypoxia. The objective of this study is to examine the interaction between a gustatory depolarizing receptor potential (GDRP) and a slow DSP. The amplitude of slow DSP added to a tastant-induced GDRP of 10 mV was suppressed to 60% of control slow DSPs for NaCl and acetic acid stimulations, but to 20-30% for quinine-HCl (Q-HCl) and sucrose stimulations. On the other hand, when a GDRP was induced during a prolonged slow DSP, the amplitude of GDRPs induced by 1 M NaCl and 1 M sucrose was suppressed to 50% of controls, but that by 1 mM acetic acid and 10 mM Q-HCl unchanged. It is concluded that the interaction between GDRPs and efferent-induced slow DSPs in frog taste cells under hypoxia derives from the crosstalk between a gustatory receptor current across the receptive membrane and a slow depolarizing synaptic current across the proximal subsynaptic membrane of taste cells., Cellular and molecular neurobiology, 29(2), pp.243-252; 2009

We compared the electrical properties and gustatory response profiles of types Ia cell (mucus cell), Ib cell (wing cell), and II/III cell (receptor cell) in the taste disks of the frog fungiform papillae. The large depolarizing responses of all types of cell induced by 1 M NaCl were accompanied by a large decrease in the membrane resistance and had the same reversal potential of approximately +5 mV. The large depolarizing responses of all cell types for 1 mM acetic acid were accompanied by a small decrease in the membrane resistance. The small depolarizing responses of all cell types for 10 mM quinine--HCl (Q-HCl) were accompanied by an increase in the membrane resistance, but those for 1 M sucrose were accompanied by a decrease in the membrane resistance. The reversal potential of sucrose responses in all cell types were approximately +12 mV. Taken together, depolarizing responses of Ia, Ib, and II/III cells for each taste stimulus are likely to be generated by the same mechanisms. Gustatory depolarizing response profiles indicated that 1) each of Ia, Ib, and II/III cells responded 100% to 1 M NaCl and 1 mM acetic acid with depolarizing responses, 2) approximately 50% of each cell type responded to 10 mM Q-HCl with depolarizations, and 3) each approximately 40% of Ia and Ib cells and approximately 90% of II/III cells responded to 1 M sucrose with depolarizations. These results suggest that the receptor molecules for NaCl, acid, and Q-HCl stimuli are equivalently distributed on all cell types, but the receptor molecules for sugar stimuli are richer on II/III cells than on Ia and Ib cells. Type III cells having afferent synapses may play a main role in gustatory transduction and transmission., Chemical Senses, 33(4), pp.371-378; 2008

目的: MRIを用いて嚥下機能評価を行うには, 超高速のパルス印加により極短時間で撮像可能なシーケンスが必要であり, steady-state free precession sequences (SSFPシーケンス) が適した撮像方法であると考える, SSFPシーケンスではflip angleの条件により種々の嚥下機能に関連する組織のコントラストやノイズ発生様相が変化し, 嚥下の動的観察における画質に影響する.そこで本研究では, SSFPシーケンスを用いた超高速撮像において, flip angleの条件が, 静止状態における嚥下関連組織の信号強度および視覚評価に及ぼす影響を明らかにし, 嚥下機能評価に適用できる至適flip angleの検討を行った.方法: 顎口腔機能に異常を認めない有歯顎者7名 (平均年齢30.1歳) を被験者とし, 1.5Tesla超伝導MRI装置を用いてSSFPシーケンスにより撮像を行った.撮像条件は, 嚥下運動に対応できることが前提であるため, 繰り返し時間 (repetition time, TR) とエコー時間 (echo time, TE) をいずれも極めて短くした超高速撮像が不可欠であるが, 信号強度の測定精度を向上させる目的で, パルス印加を同条件にして頚部の静止状態を撮像した.本研究では, 撮像にあたり嚥下機能領域のコントラストの可変パラメータであるflip angleを10°から100°まで, 10°間隔の10条件と設定し, この各条件で得られた画像における嚥下関連組織 (軟口蓋, 舌筋, 喉頭蓋, 甲状軟骨, オトガイ舌骨筋, 下顎骨, 舌骨) の信号強度変化および視覚評価の検討を行った.結果: 嚥下関連組織の信号強度はflip angleにより有意に変化した.得られた画像においてコントラストを形成する各嚥下関連組織の信号強度の差が最も多く出現したのは, flip angle10°であり, 次いでflip angle20°, 30°の順に多く, flip angle 40°～100°ではほぼ同数で少なかった.嚥下関連組織の信号雑音比 (signa1-to-noise ratio, SNR) を総じて高い値に維持する条件は, flip angle20°, 30°, 40°であった.視覚評価ではflip angle30°および40°が嚥下関連組織の識別および, 画像の明瞭さの点で優れていた.結論: SSFPシーケンスによる超高速MRIを用いた嚥下関連組織の撮像条件は, 信号強度変化と視覚評価から検討した結果, flip angle 30°が至適撮像条件であり, 嚥下機能評価の動的観察における解剖学的形態描出の明瞭化においても有効であることが示唆された.

Strong electrical stimulation (ES) of the frog glossopharyngeal (GP) efferent nerve induced slow depolarizing potentials (DPs) in taste cells under hypoxia. This study aimed to elucidate whether the slow DPs were postsynaptically induced in taste cells. After a block of parasympathetic nerve (PSN) ganglia by tubocurarine, ES of GP nerve never induced slow DPs in the taste cells, so slow DPs were induced by PSN. When Ca(2+) in the blood plasma under hypoxia was decreased to approximately 0.5 mM, the slow DPs reduced in amplitude and lengthened in latency. Increasing the normal Ca(2+) to approximately 20 mM increased the amplitude of slow DPs and shortened the latency. Addition of Cd(2+) to the plasma greatly reduced the amplitude of slow DPs and lengthened the latency. These data suggest that the slow DPs depend on Ca(2+) and Cd(2+) concentration at the presynaptic PSN terminals of taste disk. Antagonists, [D-Arg(1), D-Trp(7,9), Leu(11)]-substance P and L-703 606, of neurotransmitter substance P neurokinin(1) receptor completely blocked the slow DPs. Intravenous application of substance P induced a DP of approximately 7 mV and a reduction of membrane resistance of approximately 48% in taste cells. A nonselective cation channel antagonist, flufenamic acid, completely blocked the slow DPs. These findings suggest that the slow DPs are postsynaptically initiated in frog taste cells under hypoxia by opening nonselective cation channels on the postsynaptic membrane after substance P is probably released from the presynaptic PSN axon terminals.

We investigated the relationship between the membrane potential of frog taste cells in the fungiform papillae and the tonic discharge of parasympathetic efferent fibers in the glossopharyngeal (GP) nerve. When the parasympathetic preganglionic fibers in the GP nerve were kept intact, the mean membrane potential of Ringer-adapted taste cells was -40 mV but decreased to -31 mV after transecting the preganglionic fibers in the GP nerve and crushing the postganglionic fibers in the papillary nerve. The same result occurred after blocking the nicotinic acetylcholine receptors on parasympathetic ganglion cells in the tongue and blocking the substance P neurokinin-1 (NK-1) receptors in the gustatory efferent synapses. This indicates that the parasympathetic nerve (PSN) hyperpolarizes the membrane potential of frog taste cells by -9 mV. Repetitive stimulation of a transected GP nerve revealed that a -9-mV hyperpolarization of taste cells maintained under the intact GP nerve derives from an approximately 10-Hz discharge of the PSN efferent fibers. The mean frequency of tonic discharges extracellularly recorded from PSN efferent fibers of the taste disks was 9.1 impulses/s. We conclude that the resting membrane potential of frog taste cells is continuously hyperpolarized by on average -9 mV by an approximately 10-Hz tonic discharge from the parasympathetic preganglionic neurons in the medulla oblongata.

We studied the anatomical properties of parasympathetic postganglionic neurons in the frog tongue and their modulatory effects on taste cell responses. Most of the parasympathetic ganglion cell bodies in the tongue were found in extremely small nerve bundles running near the fungiform papillae, which originate from the lingual branches of the glossopharyngeal (GP) nerve. The density of parasympathetic postganglionic neurons in the tongue was 8000-11,000/mm(3) of the extremely small nerve bundle. The mean major axis of parasympathetic ganglion cell bodies was 21 microm, and the mean length of parasympathetic postganglionic neurons was 1.45 mm. Electrical stimulation at 30 Hz of either the GP nerve or the papillary nerve produced slow hyperpolarizing potentials (HPs) in taste cells. After nicotinic acetyl choline receptors on the parasympathetic ganglion cells in the tongue had been blocked by intravenous (i.v.) injection of D-tubocurarine (1 mg/kg), stimulation of the GP nerve did not induce any slow HPs in taste cells but that of the papillary nerve did. A further i.v. injection of a substance P NK-1 antagonist, L-703,606, blocked the slow HPs induced by the papillary nerve stimulation. This suggests that the parasympathetic postganglionic efferent fibers innervate taste cells and are related to a generation of the slow HPs and that substance P is released from the parasympathetic postganglionic axon terminals. When the resting membrane potential of a taste cell was hyperpolarized by a prolonged slow HP, the gustatory receptor potentials for NaCl and sugar stimuli were enhanced in amplitude, but those for quinine-HCl and acetic acid stimuli remained unchanged. It is concluded that frog taste cell responses are modulated by activities of parasympathetic postganglionic efferent fibers innervating these cells.

Electrical stimulation of the frog glossopharyngeal (GP) nerve evoked slow hyperpolarizing potentials (HPs) in taste cells. This study aimed to clarify whether slow HPs were postsynaptically induced in taste cells. The slow HPs were recorded intracellularly with a microelectrode. When Ca2+ concentration in the blood plasma was decreased to approximately 0.5 mM, the amplitude of slow HPs reduced and their latency lengthened. When the Ca2+ concentration was increased to approximately 20 mM, the amplitude of slow HPs increased and their latency shortened. Addition of Cd2+ to the plasma greatly reduced the amplitude of slow HPs and lengthened their latency. These data suggest that the slow HPs are dependent on presynaptic activities in the GP nerve terminals in the taste disk. Of various antagonists injected intravenously for blocking receptors of neurotransmitter biogenic amines and peptides, only antagonists for substance P blocked the slow HPs at 2-4 mg/kg body wt. Application of substance P of 2 mg/kg to the plasma induced hyperpolarizing responses in taste cells, whose amplitude was the same as that of the slow HPs induced by GP nerve stimulation. Application of a nonselective cation channel antagonist, flufenamic acid, to the plasma blocked the slow HPs. These results suggest that the slow HPs are generated by closing the nonselective cation channels in the postsynaptic membrane of taste cells following possible release of substance P from the GP nerve terminals in the taste disk.

Intracellular recordings were made from the taste cells of atropinized bullfrogs while the glossopharyngeal (GP) nerve fibres were electrically stimulated. Two types of slow potential, slow hyperpolarizing potentials (HPs) and slow depolarizing potentials (DPs), were induced in the taste cells. The slow HPs appeared when the lingual capillary blood flow was kept above 0.7 mm/s, whereas the slow DPs appeared when the blood flow was slowed down below 0.7 mm/s. The membrane resistance of a taste cell increased during the generation of a slow HP, but decreased during the generation of a slow DP. The reversal potentials for the slow HPs and the slow DPs were recorded at the same membrane potential (-11 to approximately -13 mV). Activation of non-selective cation channels possibly induced the slow DP and inactivation of those channels possibly induced the slow HP in the taste cell membrane. Electrical stimulation of the GP nerve activated a population of C fibres in the nerve and possibly released neurotransmitters from the nerve terminals. Released neurotransmitters might cause modulation of the membrane conductance in taste cells that leads to generation of the slow potentials. The present data suggest that slow HPs and slow DPs evoked in the taste cells of atropinized frogs by GP nerve stimulation are induced by putative neurotransmitters in the taste disc.

The electrophysiological and pharmacological properties of the voltage-gated Ca2+ channels in MC3T3-E1 cells were analyzed using the perforated whole-cell patch-clamp technique. When the voltage was depolarized by step pulses from a holding potential of -104mV, the cells displayed transient inward currents (-4.25±0.25pA/pF, n=16) in 10mM Ba2+ solution. The activation threshold for the inward Ba2+current was about -60mV and the peak existed between -40 and -20mV. The steady state activation and inactivation properties of the inward Ba2+ current generated a window current in the range of -70 to -40 mV. Gd2+ (0.1mM) inhibited the inward Ba2+ currents by about 60%. Ni2+ (0.1mM, a blocker for T-type and R-type Ca2+ channels at this concentration), nifedipine (5μM, L-type Ca2+ channel blocker), ω-conotoxin GVIA (3μM, N-type Ca2+ channel blocker) and ω-agatoxin TK (200nM, a P/Q-type Ca2+ channel blocker) did not inhibit the currents. Bay K 8644 (0.5μM, a dihydropyridine agonist for L-type Ca2+ channel) also did not affect the Ba2+ currents. The results suggest that Ca2+ channels with novel properties are expressed in MC3T3-E1 cells.

Hyaluronan (HA) is present in many tissues of the body and is essential to maintain moistness in the skin tissues, which contain approximately half the body's HA mass. Due to its viscosity and moisturizing effect, HA is widely distributed as a medicine, cosmetic, food, and, recently marketed in Japan as a popular dietary supplement to promote skin moisture. In a randomized, double-blind, placebo-controlled clinical study it was found that ingested HA increased skin moisture and improved treatment outcomes for patients with dry skin. HA is also reported to be absorbed by the body distributed, in part, to the skin. Ingested HA contributes to the increased synthesis of HA and promotes cell proliferation in fibroblasts. These effects show that ingestion of HA moisturizes the skin and is expected to improve the quality of life for people who suffer from dry skin. This review examines the moisturizing effects of dry skin by ingested HA and summarizes the series of mechanisms from absorption to pharmacological action.

We identified a Cl^- channel, two K^+ channels and a cAMP-gated channel which were isolated from bullfrog fungiform papilla cell membranes and incorporated into phospholipid bilayers using the tip-dip method. The 156 pS channels were inhibited by 100μM 4, 4'-diisothiocyanostilbene-2, 2'-disulfonic acid (DIDS) and displayed the reversal potential identical to the equilibrium potential of Cl^-, it was identified as a Cl^- channel. Two types of K^+ channel had unitary conductances of 79 and 43 pS, which may correspond to those of Ca^-activated and cAMP-blockable K^+ channels observed in isolated intact frog taste cell membranes, respectively. These results suggest that the tip-dip method is useful for stable investigation of the properties of ion channels already identified in the taste cell. Furthermore, the 23 pS channels were newly found and were activated directly by internal cAMP as cyclic nucleotide-gated (CNG) nonselective cation channels established in olfactory receptor cells. Thus, our results suggest the possibility that besides Cl^- and K^+ channels, the cAMP-gated channels contribute to taste transduction., Zoological science 18(3) pp.299-307; 2001

本研究は人工ニューラルネットワークを用いて, ウサギの飲水時, ペレット咀嚼時, パン咀嚼時のそれぞれの下顎運動パタンの特徴を解析したものである。無麻酔, 無拘束下に導出されたウサギの摂食時咀嚼筋発火パタンをもとに, 3層パーセプトロン型の人工ニューラルネットワークをバックプロパゲーション学習法によって構築した。学習時には用いなかった咀嚼筋発火パタンに対するこのネットワークによる識別結果を調べ, 従来生理学的データ解析に用いられてきた, 発火タイミングや, 振幅を比較する解析方法と比較した。その結果, 咬筋活動からは従来の方法でも3種の下顎運動パタンを識別できたが, 人工ニューラルネットワークを用いると顎二腹筋活動からもそれぞれの下顎運動パタンを識別することが可能であった。それゆえ, 本手法が曖昧な情報を含む筋電図の解析に有用であることが明らかとなった。

When the glossopharyngeal nerve (GP) in the frog was strongly stimulated electrically, slow potentials were elicited from the tongue surface and taste cells in the fungiform papillae. Injection of atropine completely blocked these slow potentials. The present and previous data indicate that the slow potentials induced in the tongue surface and taste cells are due to a liquid junction potential between saliva secreted from the lingual glands due to parasympathetic fiber activity and an adapting solution on the tongue surface. Intracellularly recorded depolarizing receptor potentials in taste cells induced by 0.5 M NaCl and 3 mM acetic acid were enhanced by depolarizing slow potentials induced by GP nerve stimulation, but were depressed by the hyperpolarizing slow potentials. On average, the receptor potential of taste cells for 0.5 M NaCl was increased by 25% by the GP nerve-induced slow potential, but the receptor potential of taste cells for 3 mM acetic acid was decreased by 1% by the slow potential. These transformations of receptor potentials in frog taste cells were not due to a synaptic event initiated between taste cells and the efferent nerve fiber, but due to a non-synaptic event, a lingual junction potential generated in the dorsal lingual epithelium by GP nerve stimulation.

The transduction mechanism of the conductance activated by saccharin was analysed in isolated bullfrog taste cells under whole-cell voltage-clamp. Bath application of 30 mM saccharin induced an inward current of -34 +/- 12 pA (mean +/- SEM, n = 10) at a membrane potential of -50 mV in 10 (23%) of 44 rod cells. The concentration-response relationship for the saccharin-gated current was consistent with that of the gustatory neural response. The saccharin-induced current was accompanied with a conductance increase under internal low Cl- condition (E(Cl) = -56 mV), suggesting that saccharin activated a cation conductance. The reversal potential of the saccharin-induced current was -17 +/- 2 mV (n = 10). Intracellular dialysis of 0.5 mM guanosine 5'-O-(2-thiodiphosphate) (GDP-beta-S) completely blocked the saccharin-induced response, suggesting the involvement of a G protein in the transduction. The dialysis of heparin (1 mg/mL) also inhibited the response almost completely, but the dialysis of 1 mM 8-Br-cAMP did not affect the response significantly. Intracellular 50 microM inositol 1,4,5-trisphosphate (1,4,5 InsP(3)) also induced the inward current in five (38%) of 13 rod cells, but intracellular Pasteurella multocida toxin (5 microg/mL, G alpha q-coupled PLC activator) did not elicit any response in the cells. The results suggest that saccharin mainly activates a cation conductance in frog taste cells through the mediation of IP3 production.

目的: リンガライズド・オクルージョンの構成にあたり, 義歯の維持安定と咀嚼機能に影響を及ぼすと考えられる滑走間隙量の設定基準については, 未だに明らかにされていない. 今回の実験の目的は, リンガライズド・オクルージョンにおける滑走間隙量の違いが食品破砕時に義歯に加わる機能圧に及ぼす影響を明らかにすることである.方法: 実験にはシミュレーターを用い, 被験食品にニンジン, タクアン, カマボコ, ピーナッツを選択した. それぞれの滑走間隙量において, シミュレーター上で被験食品を破砕させたときに義歯に加わる垂直方向と水平方向 (頬側, 舌側, 近心, 遠心) の破砕力の最大値を測定し記録した.結果: 滑走間隙量が増大するとともに最大垂直力と舌側方向と遠心方向の最大水平力は, すべての被験食品において減少した. 頬側方向と近心方向の最大水平力はニンジン, タクアン, カマボコの破砕時に増加した.結論: 本論文の結果は, 食品破砕時における義歯への荷重量を減少させるためには, 滑走間隙量を1.0～1.5mmに設定する必要があることを示している. したがって, リンガライズド・オクルージョンにおける滑走間隙量を1.0～1.5mmに設定することは, 義歯の安定性を良好に保つことと, 顎堤の保全の両面で有効であると考える.

We have investigated the effect of 5-hydroxytryptamine (serotonin) (5-HT) on the membrane properties of bullfrog taste receptor cells (TRCs) using patch-clamp technique. External application of 5-HT reversibly suppressed the voltage-gated Na(+) current (I(Na)) in about half of the TRCs sampled. The magnitude of suppression of peak I(Na) was dependent on the holding potential of the cell. Forskolin and cyclic adenosine monophosphate (cAMP) mimicked the suppressive effect of 5-HT on I(Na), but an internal protein kinase A-inhibitor potentiated I(Na). These results suggest that 5-HT suppresses I(Na) of bullfrog TRCs via protein kinase A-dependent phosphorylation, resulting in suppression of the excitability of bullfrog TRCs.

When the glossopharyngeal (GP) nerve of the frog was stimulated electrically, electropositive slow potentials were recorded from the tongue surface and depolarizing slow potentials from taste cells in the fungiform papillae. The amplitude of the slow potentials was stimulus strength- and the frequency-dependent. Generation of the slow potentials was not related to antidromic activity of myelinated afferent fibers in the GP nerve, but to orthodromic activity of autonomic post-ganglionic C fibers in the GP nerve. Intravenous injection of atropine abolished the positive and depolarizing slow potentials evoked by GP nerve stimulation, suggesting that the slow potentials were induced by the activity of parasympathetic post-ganglionic fibers. The amplitude and polarity of the slow potentials depended on the concentration of adapting NaCl solutions applied to the tongue surface. These results suggest that the slow potentials recorded from the tongue surface and taste cells are due to the liquid junction potential generated between saliva secreted from the lingual glands by GP nerve stimulation and the adapting solution on the tongue surface.

無麻酔・無拘束下のウサギのリズミカルな咀嚼運動に対する嚥下の影響を調べた。咀嚼時と嚥下時に下顎運動軌跡と咬筋, 顎二腹筋, 甲状舌骨筋の筋電図を記録した。固形飼料の咀嚼運動中の嚥下の影響は5つのタイプに分類される。 (1) 嚥下が下顎運動の開口相に影響し休止期を示すもの (OPタイプ), (2) 閉口相に影響し休止期を示すもの (CLタイプ), (3) 閉口相と開口相の両方に影響し休止期を示すもの (CL/OPタイプ), (4) 閉口と開口の両相に対して影響しないもの (Non-influタイプ), (5) 不十分な閉口相を引き起こし, 長い休止期の後に開口相に移行させるもの (Pタイプ)。観察された嚥下の52%がOPタイプ, 26%がCLタイプ, 12%がCL/OPタイプで10%が他のタイプであった。CLタイプとCL/OPタイプでの閉口相の変調は, 固形飼料の咀嚼中歯根膜からの入力による咬筋活動の抑制に関与し, OPタイプとCL/OPタイプでの開口相の変調は, 咽頭性入力による顎二腹筋活動の抑制に関与すると結論できる。

The chorda tympani nerve responses to NaCl in a mouse strain, C57BL/6 are known to be much more sensitive than those in BALB/c. We compared the NaCl-induced responses obtained from taste cells of the fungiform papillae in these two strains of mice. Amiloride inhibited, in the same degree, the responses induced by a bath-application of normal extracellular solution (NES) containing 140 mM NaCl in either taste cells of C57BL/6 and BALB/c mice. In contrast, amiloride inhibited 62% of responses induced by an apically applied 0.5 M NaCl in the C57BL/6 strain, but only 33% of responses in the BALB/c strain. These results suggest that the difference in amiloride-sensitivity between taste cells in both strains mainly derives from the difference in density of functional amiloride sensitive Na+ channels at the apical receptive membrane but not at the basolateral membrane.

Burst patterns in the digastric, mylohyoid, and masseter muscles and the resultant jaw movement orbits during chewing and swallowing were investigated in the freely behaving rabbit. Activities in the posterior mylohyoid fibers consisted of two continuous bursts. Peaks in the first burst of the posterior fibers occurred in the middle part of opening and preceded the digastric burst. Peaks in the second burst occurred in the final part of opening and coincided with those in the working side of the digastric burst. After removal of the bilateral digastric muscles, the gape size during chewing was largely reduced in the final part of opening and in the early part of closing. The results suggest that (a) the digastric may have a role in opening the mandible widely beyond the rest position but may not have a major role in the control of the horizontal (mediolateral) jaw movement, (b) the posterior mylohyoid fibers may have a function as an elevator of the tongue in the early part of opening, and (c) the posterior mylohyoid fibers may have a function as a depressor of the jaw in the late part of opening. Electromyographic burst in the mylohyoid muscle began with marked activity in the mid-closing phase. The results support a role for the mylohyoid muscle as a leading muscle of swallowing. Swallowing events in the rabbit are easily distinguished from the activities of the mylohyoid muscle and the thyrohyoid muscle.

Streptococcus milleri group (S. milleri group)による化膿性感染症6症例を経験した。頭頸部の膿瘍3症例,腹膜炎術後感染2症例,食道癌術後感染1症例であった。6症例とも膿汁からS. milleri groupを検出した。4症例で混合感染を認め頭頸部感染では口腔内,腹腔内感染では消化管内に常在する微好気性あるいは嫌気性細菌であった。頸部膿瘍2症例は咽頭の感染症状から3,4日のうちに著しい頸部腫脹をきたし呼吸困難を主訴に来院し直ちに気道確保を必要とした。術後感染の3例は腹壁や皮下組織に膿瘍を形成し敗血症に至った。敗血症の症例では肺,肝,腎など多臓器障害を認めた。感染対策として嫌気性菌を含む広域スペクトラムの抗菌薬を使用し積極的にドレナージを行った。S. milleri groupによる感染では膿瘍形成,急速な腫脹と周囲への感染波及,嫌気性菌を含む他の細菌の混合感染に特徴があると思われた。

The purpose of this study was to achieve optimal contrast of imaging characteristics in 4 dimensional MR images of the temporomandibular joint (TMJ) for evaluating the TMJ structures during mandibular movement. Twelve TMJs from six subjects without any TMJ dysfunction were studied. MRI was performed using a 1.5 MR system with an eight-channel phased array coil. The images were acquired using a balanced steady-state free precession (b-SSFP) sequence. The optimal flip angle was determined for differentiation for the main anatomical structures of the TMJ; the posterior band of the articular disc, the retrodiscal tissues, the condylar head, and the lateral pterygoid muscle, by examining the signal intensity (SI-d) of TMJ structures on b-SSFP MR images obtained using various flip angles. Repeated measures two-way analysis of variance (ANOVA) was performed, followed by Bonferroni's multiple comparison analysis. The main anatomical structures of the TMJ had the highest SI-d at flip angles of 30 degrees and 40 degrees, and there were the most significant differences between the SI-d of the articular disc and all other structures at a flip angle of 40 degrees, followed by a flip angle of 30 degrees. These data suggest that a flip angle of approximately 30 degrees to 40 degrees is appropriate for obtaining the optimal contrast of imaging characteristics for 4 Dimensional MR images of the TMJ with b-SSFP sequence.

The amiloride-sensitive and -insensitive components of salt- and acid-induced responses in C57BL/6 and BALB/c mouse nondissociated taste cells were examined using the whole-cell clamp technique and localized taste stimulation method. Both amiloride-sensitive and -insensitive components were involved in a salt-induced depolarizing response. The taste cells of both mouse strains exhibited an amiloride-insensitive salt-induced response, which consisted of multiple components. In C57BL/6 mice, an amiloride-sensitive strain, more than 60% of salt-induced responses were amiloride-sensitive at the apical membrane, whereas in BALB/c mice, an amiloride-insensitive strain, less than 40% of responses were amiloride-sensitive. All the acid-induced responses in taste cells examined were insensitive to amiloride, and were markedly suppressed by the Cl channel blocker, 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB). These results suggest that multiple, different transduction mechanisms are involved in, and contribute to salty and sour transductions. In addition, we found that strain differences exist in salty transduction.

The effect of intracellular Ca2+ increase was analysed in isolated frog taste cells under the whole-cell patch clamp. External application of a Ca2+-ionophore, ionomycin (3 microM) induced the sustained inward current of -200+/-17 pA (mean +/- SE, n = 23) at -50 mV in taste cells. The ionomycin-induced response was observed in most of the cells exposed in the drug, but not when 10 mM BAPTA (1,2-bis (O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid) was included in the pipette (eight cells). Steady-state I-V relationships of ionomycin-induced currents were almost linear and reversed at -8+/-1 mV (n = 23). The simultaneous removal of Na+ and Ca2+ from the external solution eliminated the response completely (three cells). Intracellular dialysis with 1 mM Ca2+ or 50 microM inositol 1,4,5-trisphosphate (IP3) in K+-internal solution also induced an inward current in the taste cells. The Ca2+-induced and IP3-induced responses were observed in 82% and 36% of the cells dialysed with the drugs, respectively. The Ca2+-induced and IP3-induced currents were inhibited by external Cd2+ (1-2 mM). The reversal potentials of the inward currents were -15+/-3 mV (n = 9) in Ca2+ dialysis and -11+/-3 mV (n = 13) in IP3 dialysis. The half-maximal Ca2+ concentration in the pipette to induce the inward current was approximately 170 microM. The results suggest that IP3 can depolarize the taste cell with mediation by intracellular Ca2+.

Extracorporeal life support (ECLS) was used to treat three patients with near-fatal status asthmaticus who did not respond to aggressive medical therapies and mechanical ventilation under controlled permissive hypercapnia. ECLS was instituted in patient 1 because Paco 2 was excessively high and pH was excessively low, in patient 2 because hypoxemia and shock were not responsive to treatment, and in patient 3 because of sustained severe hypotension. ECLS supported adequate gas exchange until pulmonary function improved, diminishing the need for mechanical ventilation and preventing pulmonary complications. Pulmonary dysfunction improved markedly after only 21 to 86 hours of ECLS. Aggressive medical treatments were continued during ECLS. Our findings indicate that ECLS is a useful method for preventing death in patients with near-fatal status asthmaticus.

During nitric oxide (NO) inhalation therapy, toxicity may be produced by the reactive metabolite nitrogen dioxide (NO2). The purpose of the present study was to determine the NO2 concentration in a NO inhalation system used for respiratory failure in children at relatively low concentrations of NO (< 20 ppm). The production of NO2 in the NO inhalation system using the Servo Ventilator 900C connected to the test lung under each of 30 combinations of NO concentrations (0, 4, 8, 12, 16, and 19 ppm) and inspired oxygen (O2) concentrations (21, 40, 60, 80, and 100%). Pressure controlled ventilation was used with a respiratory rate of 20 breaths/min. NO and NO2 measurements were obtained on the inspiratory side of the Y-piece connected to the test lung. At a given NO level, increases in the concentration of inspired O2 resulted in increases in the concentration of NO2 produced, as did increases in the amount of NO at a given concentration of O2. The mean NO2 concentration at the inspiratory site of the Y-piece did not exceed 0.05 ppm (the limit of NO2 as an outdoor air pollutant in the United States) when the NO concentration did not exceed 8 ppm, regardless of the O2 concentration. NO inhalation therapy for children with severe respiratory failure using the Servo Ventilator 900C can be performed safely when the concentration of NO does not exceed 8 ppm.

Nitric oxide (NO) inhalation and high frequency oscillatory ventilation (HFOV) has been indicated in infants with severe respiratory failure. The purpose of the present study was to evaluate the safety of an NO inhalation system with HFOV in terms of nitrogen dioxide (NO2) production. The NO inhalation system consisted of a high frequency oscillatory ventilator, a neonatal circuit and a test lung. The NO concentration was changed from 0 to 19 p.p.m. At each level of NO, the oxygen (O2) concentration was changed from 21 to 100%. The NO and NO2 concentrations were measured with a chemiluminescence analyzer using a molybdenum converter. The NO2 concentration was increased when either the O2 or the NO concentration was increased. The interposition of the endotracheal tubes increased NO2 concentrations at 4 p.p.m. NO. The high stroke volume and high mean airway pressure produced a significant increase in NO2 production at 4 p.p.m. NO. The increase in NO2 production was prevented by placing a one-way valve at the joint of the NO gas line to the inspired limb. It was concluded that the NO inhalation system with HFOV can be safely used when a one-way valve is placed at the joint of the NO gas line to the inspired limb and when inhaled NO is at a relatively low concentration.

We present a case of pharyngeal foreign body in an infant. A 6-month-old girl whose oropharyngeal space was occupied by a cuttlefish hook, was sent to our intensive care unit. The double-banked, radial needles were stuck in the base of the tongue as well as the middle pharynx and were seen on a roentgenogram. Neither a laryngoscope nor even a small bronchofiberscope could be inserted into the oral space occupied by the foreign body. Prior to transoral removal of the foreign body, tracheostomy was performed. Intravenous anesthesia using ketamine and diazepam combined with the local anesthesia was chosen for the tracheostomy. A small dose of atropine was effective in reducing secretions and maintaining the patency of the upper airway. Induction of anesthesia was followed by isoflurane, nitrous oxide, and oxygen after tracheostomy, then surgery was performed successfully within 90 minutes. Tracheostomy is indicated for a patient in whom endotracheal intubation is difficult to perform. Upper airway management during tracheostomy is the main issue in such a case, especially in an infant with a large pharyngeal foreign body.

The percentage of non-tasters for phenylthiocarbamide in 915 Japanese students was 9.4%. The thresholds of the edge and back of the tongue to quinine hydrochloride were significantly smaller in the non-tasters than in the tasters. The thresholds of any tongue portions to NaCl, acetic acid or sucrose did not differ between the tasters and the non-tasters.