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Biomedical subjects

Takashi Mashimo

Publications and source records attributed to Takashi Mashimo.

At least 19 recordsLinked to original sources
PubMed2006

Two types of GABAergic miniature inhibitory postsynaptic currents in mouse substantia gelatinosa neurons.

The physiological and pharmacological properties of gamma-aminobutyric acid (GABA)ergic miniature inhibitory postsynaptic currents (mIPSCs) were investigated in substantia gelatinosa neurons of mouse spinal cord using whole-cell patch clamp recordings. Two cell populations were pharmacologically identified based on the effect of propofol (10 muM) on the mIPSC decay kinetics: those exhibiting propofol-sensitive mIPSCs, with a slow decay kinetic (mIPSC(SLOW)), and those exhibiting propofol-resistant mIPSCs, with a fast decay kinetic (mIPSC(FAST)) (decay time constants of 14.2+/-0.7 and 7.4+/-0.8 ms, respectively). The frequency and amplitude of both types of mIPSCs were not affected by propofol. Miniature IPSC(FAST) showed midazolam insensitivity, while midazolam prolonged the decay phase of mIPSC(SLOW) without modulation of the frequency and amplitude. Exogenous GABA-evoked responses in the neurons with mIPSC(SLOW) were potentiated by propofol, while those in neurons with mIPSC(FAST) were unaffected by propofol. Furthermore, non-stationary noise analysis of the two kinetically and pharmacologically distinct mIPSCs revealed different conductance of GABA(A) receptor channels underlying the synaptic events. Pharmacological responses to propofol and midazolam suggested that mIPSC(FAST) and mIPSC(SLOW) in substantia gelatinosa neurons can be mediated by GABA(A) receptors with different subunit compositions.

Animals↗
PubMed2006

GABAergic tonic inhibition of substantia gelatinosa neurons in mouse spinal cord.

We used whole-cell recording to identify, for the first time, GABAergic tonic current in subpopulations of substantia gelatinosa neurons in mouse spinal cord slices. Application of the gamma-aminobutyric acid type A receptor antagonist bicuculline revealed tonic currents in 49 of 73 substantia gelatinosa neurons. These tonic currents were dissected into three groups according to their diverse pharmacological properties. In the first group, furosemide failed to block the tonic current while midazolam and propofol potentiated it. In the second group, furosemide blocked the tonic current but midazolam and propofol failed to enhance the current. In the third group, furosemide blocked and 3alpha, 21-dihydroxy-5alpha-pregnan-20-one enhanced the tonic current. The presence of mRNAs for alpha4, alpha5, delta and epsilon subunits in the substantia gelatinosa (reverse-transcriptase polymerase chain reaction) suggest that gamma-aminobutyric acid type A receptors comprising alpha5betaxgamma2, alphaxbetaxepsilon and alpha4betaxdelta subunits are responsible for tonic currents.

Action Potentials↗
PubMed2006

Bolus administration of landiolol, a short-acting, selective beta1-blocker, to treat tachycardia during anesthesia: a dose-dependent study.

OBJECTIVES: The purpose of this study was to clarify the clinical efficacy of landiolol, a selective beta(1)-blocker, in patients developing tachycardia during anesthesia. DESIGN: A prospective, randomized, and placebo-controlled study. SETTING: A single university hospital. PARTICIPANTS: Patients undergoing resection of intracranial or maxillofacial tumors under general anesthesia. INTERVENTIONS: Intravenous bolus administration of landiolol. MEASUREMENTS AND MAIN RESULTS: Patients with heart rates exceeding 90 beats/min for more than 5 minutes received an intravenous bolus dose of landiolol. These patients who developed tachycardia were randomized into 4 groups receiving landiolol in the dose of 0, 0.1, 0.2, or 0.3 mg/kg. Heart rate and blood pressure were recorded before drug injection and 1, 3, 5, 7, 10, 15, 20, 25, and 30 minutes after the injection. Heart rate was significantly reduced with each dose of landiolol compared with the placebo group between 3 and 20 minutes after drug injection. The lowest heart rate was 93 +/- 4, 80 +/- 8, 79 +/- 8, and 77 +/- 6 beats/min (mean +/- standard deviation) in the landiolol 0, 0.1, 0.2, and 0.3 mg/kg groups, respectively. On the other hand, reduction of blood pressure was not as remarkable as that of heart rate. Landiolol, 0.1 and 0.2 mg/kg, did not significantly reduce systolic or diastolic blood pressure during the study period, although significant reduction of blood pressure was observed in the landiolol 0.3-mg/kg group between 5 and 10 minutes after drug injection. CONCLUSION: The results showed that bolus administration of landiolol was effective in the treatment of tachycardia during anesthesia in surgical patients. Landiolol was more efficacious in reducing heart rate than blood pressure.

Adrenergic beta-Antagonists↗
PubMed2006

Formation of signal transduction complexes during immobile phase of NGFR movements.

Nerve growth factor (NGF) is a secreted neurotrophin involved in the differentiation, growth, and maintenance of neurons. Here, we have used single-molecule imaging to characterize the behavior of Cy3-tagged NGF after binding to receptor complexes on the surfaces of PC12 cells. We show that NGF-receptor complexes have two distinct diffusive states, characterized as mobile and immobile phase. The transition between the two diffusive states occurred reversibly with duration times determined by a single rate limiting process. The abrupt transition to the immobile phase often occurred simultaneously with the clustering of NGF-receptor complexes. Immobilization depended on the phosphorylation of the TrkA NGF-receptor. Using dual-color imaging, it was demonstrated that the membrane recruitment of the intercellular signaling protein occurs with NGF-receptor complexes in the immobile phase indicating signal transduction occurs during this phase. Thus, NGF signaling is performed through a repetitive random process to induce transient formation of signaling complexes.

Animals↗
PubMed2006

Effect of Ono-EI-600 elastase inhibitor on high-tidal-volume-induced lung injury in rats.

We tested the effect of Ono-EI-600, an elastase inhibitor that suppresses cytokine release, on ventilator-induced lung injury in a rat model. After Wistar rats (aged 8-11 weeks) were anesthetized and tracheostomized, they were randomly assigned to four groups: high tidal volume (V(T)) group (H group: n = 10) receiving peak inspiratory pressure (PIP) 30 cmH(2)O for 240 min; high V(T) with drug group (HD group: n = 10) receiving the same ventilation settings as H group and also intravenous infusion 10 mg x kg(-1) x h(-1) of Ono-EI-600 during the protocol; the lower V(T) group (L group: n = 5) receiving PIP 10 cmH(2)O for 240 min; and control group (C group: n = 5) receiving the same ventilation as L group for 30 min. The cytokine levels (IL-6 and CINC-1) in the bronchoalveolar lavage fluid (BALF) of the H group were significantly higher than those of the C and L groups (P < 0.05). However, for the H and HD groups, no differences were found in arterial blood gas data, cytokine levels in BALF, and histological injury scores. Our experiment provided no evidence that elastase inhibitor Ono-EI-600 protects against lung injury induced by high V(T) ventilation.

Animals↗
PubMed2006

Effect of peak inspiratory flow on gas exchange, pulmonary mechanics, and lung histology in rabbits with injured lungs.

PURPOSE: The aim of this study was to evaluate, using a rabbit model, the little-known effect of different levels of peak inspiratory flow on acutely injured lungs. METHODS: Fourteen male rabbits (body weight, 2,711 +/- 146 g) were anesthetized and their lungs were injured by alveolar overstretch with mechanical ventilation until Pa(O(2)) was reduced below 300 mmHg. Injured animals were randomly assigned to: the P group-to receive pressure-regulated volume-control ventilation (PRVCV; n = 7); and the V group-to receive volume-control ventilation (VCV; n = 7). Other ventilator settings were: fraction of inspired oxygen (FI(O(2)), 1.0; tidal volume, 20 ml x kg(-1); positive end-expiratory pressure (PEEP) 5 cmH(2)O; and respiratory rate, 20 min(-1). The animals were thus ventilated for 4 h. Throughout the protocol, ventilatory parameters and blood gas were measured every 30 min. After the protocol, the lung wet-to-dry ratio and histological lung injury score were evaluated in the excised lungs. RESULTS: Throughout the protocol, peak inspiratory flow and mean inspiratory flow values in the P group were significantly higher than those in the V group (26.7 +/- 5.0 l x min(-1) vs 1.2 +/- 0.2 l x min(-1), and 4.3 +/- 0.3 l x min(-1) vs 1.1 +/- 0.1 l x min(-1); P < 0.05). The wet-to-dry ratio in the P group was also significantly higher than that in the V group (7.7 +/- 0.9 vs 6.3 +/- 0.5; P < 0.05). More animals in the P group than in the V group had end-of-protocol Pa(O(2))/FI(O(2)) ratios below 200 mmHg (43% vs 0%; P = 0.06). CONCLUSION: In rabbits with injured lungs, high peak inspiratory flow with high tidal volume (V(T)) reduces the Pa(O(2))/FI(O(2)) ratio and increases the lung wet-to-dry ratio.

Animals↗
PubMed2006

Effect of humidifying devices on the measurement of tidal volume by mechanical ventilators.

PURPOSE: We hypothesized that expiratory tidal volume was underestimated, because a heat-moisture exchanger traps the expired vapor. We, therefore, designed patient and bench studies to investigate the accuracy of tidal volume monitoring. METHODS: In a patient study, applying two humidifying systems (a heat-moisture exchanger and a heated humidifier) and two tidal volumes (12 and 6 ml x kg(-1)) with a Servo ventilator 300, we recorded the displayed expiratory tidal volume and thoracic volume displacement, measured by respiratory inductive plethysmography. Temperature, relative humidity, and absolute humidity were measured at the airway opening and at the end of the expiratory limb. Using a model lung, we also tested three different ventilators (Puritan-Bennett 7200ae, Evita 4, and Servo ventilator 300) to investigate whether the effects of the heat-moisture exchanger and the heated humidifier on monitored tidal volume varied according to the brand of ventilator. RESULTS: With the use of the heat-moisture exchanger, the displayed expiratory tidal volume was significantly smaller, by 12%-14%, than that with the heated humidifier, although thoracic volume displacement was identical in the two systems. The temperature and absolute humidity at the end of the expiratory limb were significantly lower with the heat-moisture exchanger than with the heated humidifier. In the model lung study, we investigated the effects of different brands of ventilator on the expiratory tidal volume. A similar degree (8%-14%) of underestimation of tidal volume was observed with the heat-moisture exchanger, regardless of ventilator brand. CONCLUSION: Monitored expiratory tidal volume was underestimated by approximately 10%, when using a heat-moisture exchanger.

Adolescent↗
PubMed2006

Regional blood flow in respiratory muscles during partial ventilatory assistance in rabbits.

We tested the hypothesis that even partial ventilatory assistance would reduce respiratory muscle blood flow to levels similar to those found during control mechanical ventilation (CMV). Three levels of pressure support ventilation (PSV) and 2 CMV settings were compared in 10 rabbits. PSV 0, 6, and 12 cm H2O, under continuous positive airway pressure mode, were applied, and then pressure control ventilation (PCV) values of 6 (36 breaths/min) and 12 cm H2O (18 per breaths/min) were applied to each CMV setting with a muscle relaxant. Using colored microspheres, we measured regional tissue blood flow in respiratory muscles, lower extremities, kidney, and liver. Regional tissue blood flow in the diaphragm during PSV6, PCV6, and PCV12 were less than those during PSV0. During PSV12, blood flow in the crural diaphragm was more than that during PCV12 and similar to that during PSV0. Whereas the transdiaphragmatic pressure of PSV6 was -0.8 +/- 1.6 cm H2O, that of PSV12 was -3.1 +/- 2.4 cm H2O. Inspiratory asynchrony, arising from an ineffective triggering effort, was observed in PSV12. The ventilatory settings did not affect blood flow of the lower extremities, liver, and kidney. In conclusion, ventilatory settings affected blood flow in the diaphragm. At certain PSV settings, blood flow in the diaphragm was minimal.

Animals↗
PubMed2006

Diabetes mellitus reduces the antiarrhythmic effect of ion channel blockers.

We designed the present study to examine whether diabetes mellitus affects the antiarrhythmic effect of flecainide, a sodium channel blocker, E-4031, a potassium channel blocker, and verapamil, a calcium channel blocker, in diabetic rats. The experiments were performed in intact and diabetic rats 2, 4, and 6 wk after administration of streptozotocin. Rats were anesthetized with halothane and monitored continuously for arterial blood pressure and premature ventricular contractions. The arrhythmogenic dose of epinephrine was defined as the smallest dose producing 3 or more premature ventricular contractions within a 15-s period. The arrhythmogenic doses of epinephrine in the presence of flecainide were 8.2 +/- 2.2 (mean +/- sd), 7.4 +/- 6.1, 5.5 +/- 2.8, and 2.0 +/- 0.5 microg/kg in intact and diabetic rats 2, 4, and 6 wk after streptozotocin administration, respectively. Similarly, the arrhythmogenic doses of epinephrine in the presence of E-4031 were 7.7 +/- 2.6, 2.3 +/- 0.7, 2.0 +/- 0.7, and 1.2 +/- 0.5 microg/kg, and those in the presence of verapamil were 8.2 +/- 2.1, 3.1 +/- 1.2, 2.3 +/- 0.9, and 1.5 +/- 0.5 microg/kg. Insulin partially recovered the antiarrhythmic effect of the blockers. We concluded that diabetes mellitus reduces the antiarrhythmic effects of flecainide, E-4031, and verapamil.

Animals↗
PubMed2006

[Adsorption of local anesthetic into disposable infusion balloon].

BACKGROUND: The aim of this study was to investigate the adsorption of local anesthetics lidocaine and ropivacaine, into disposable infusion balloons made from various kinds of plastics. METHODS: The concentration of local anesthetic that flows out of a balloon was measured. RESULTS: The concentration of both lidocaine and ropivacaine in clinical formula decreased only 4.5 percent regardless of infusion balloons. However, the concentration of lidocaine pH 7.4 decreased by 10 percent in the Syrinjector made from polypropylene and polyvinyl chloride, and that of 18-20 percent in other infusion balloons (Surefuser, Baxtor Infuser, DIB Catheter made from isoprene rubber and polyvinyl chloride, isoprene rubber and polyvinyl chloride, silicon and polyvinyl chloride, respectively). CONCLUSIONS: The adsorption of local anesthetic into infusion balloons has little effect in clinical situation. Whereas, in case of lidocaine pH 7.4, the adsorption depends on the specific type of plastics.

Adsorption↗
PubMed2005

Postoperative hyperbilirubinemia after implantation of left ventricular assist device is associated with poor postoperative liver perfusion.

Hyperbilirubinemia, a common complication associated with left ventricular assist device (LVAD) implantation, is evidence of liver dysfunction and is often a life-threatening problem after the implantation procedure. In this study we evaluated the relationship between hemodynamics after LVAD implantation and postoperative hyperbilirubinemia. Twenty-four patients who received LVADs at Osaka University Hospital between January 1994 and June 2002 were retrospectively reviewed. Patients were grouped according to the implanted LVAD: Group A (n = 4) Novacor, group B (n = 7) HeartMate 1000IP, group C (n = 13) Toyobo pneumatic pulsatile pump. Hemodynamic data and laboratory data, including total bilirubin on postoperative days (PODs) 1, 3, 7, and 14, were collected and statistically analyzed. In group C, the cardiac index (CI) on POD 1 was significantly lower (P < 0.01) than that for groups A and B. On PODs 3 and 7, total bilirubin levels in group C increased significantly over the preoperative value (P < 0.05) and were significantly higher than those in group A on POD 3 and higher than those in groups A and B on POD 7 (P < 0.05). Regression analysis of CI on POD 1 correlated significantly with total bilirubin on POD 7, as expressed by the formula y = 5.13/(x - 1.7)(0.719), where x is CI and y is total bilirubin (r(2) = 0.327, P < 0.05). Total bilirubin after LVAD implantation correlates with postoperative CI values. We suggest that it is essential to maintain the CI at the highest levels possible to avoid postoperative hyperbilirubinemia in LVAD patients.

Adult↗
PubMed2005

Activation of p38 MAPK in primary afferent neurons by noxious stimulation and its involvement in the development of thermal hyperalgesia.

Alterations in the intracellular signal transduction pathway in primary afferents may contribute to pain hypersensitivity. We demonstrated that very rapid phosphorylation of p38 mitogen-activated protein kinase occurred in dorsal root ganglion (DRG) neurons that were participating in the transmission of noxious signals. Capsaicin injection induced phosphorylated-p38 (p-p38) in small-to-medium diameter sensory neurons with a peak at 2 min after capsaicin injection. Furthermore, we examined the p-p38 labeling in the DRG after noxious thermal stimuli and found a stimulus intensity-dependent increase in labeled cell size and the number of activated neurons. Most of these p-p38-immunoreactive (IR) neurons were small- and medium-sized neurons, which coexpressed transient receptor potential ion channel TRPV1 and phosphorylated-extracellular signal-regulated protein kinase. Intrathecal administration of the p38 inhibitor, FR167653, reversed the thermal hyperalgesia produced by the capsaicin injection. Inhibition of p38 activation was confirmed by the decrease in the number of p-p38-IR neurons in the DRG following capsaicin injection. Taken together, these findings suggest that the activation of p38 pathways in primary afferents by noxious stimulation in vivo may be, at least in part, correlated with functional activity, and further, involved in the development of thermal hyperalgesia.

Animals↗
PubMed2005

Sorptive loss of volatile and gaseous anesthetics from in vitro drug application systems.

In in vitro pharmacological experiments, determination of effective concentration values for various anesthetics depends on understanding the exact concentration of the drugs dissolved in physiological solutions. Actual anesthetic concentration may differ from expectations because of drug adsorption, absorption or other loss, especially in tubing. We tested the hypothesis that delivered concentrations of anesthetics decrease when solutions pass through laboratory tubing and investigated such loss by measuring the entering and exiting dissolved concentrations of two volatile (sevoflurane and isoflurane) and two gaseous (nitrous oxide and xenon) anesthetics. We tested solutions passed through tubes (1 m x 2 mm ID x 4 mm OD) made of five different materials (glass, Teflon, polyethylene (PE), polyvinyl chloride (PVC), and silicon rubber). Exiting concentrations of anesthetics were significantly reduced when they were passed through PVC (>33%) and silicon (>43%) tubes. There were no decreases in anesthetic concentrations with glass, Teflon, or PE tubes. When sevoflurane solution flowed through PVC and silicon tubes, it took 20 and 30 min, respectively, after start of flow until the anesthetic loss became negligible. These results indicate that frequently used PVC and silicon tubes, whereas flexible and easy to handle, have serious drawbacks when used in inhaled anesthetic pharmacology experiments.

Adsorption↗
PubMed2005

The antiallodynic and antihyperalgesic effects of neurotropin in mice with spinal nerve ligation.

Although Neurotropin(R) (NTP) has been used clinically as an analgesic in Japan for many years, its effect on neuropathic pain in animal models has not been examined in detail. Its main effect has been indicated to be activation of the descending monoaminergic pain inhibitory systems. To study the effect of NTP on neuropathic pain, we subjected mice to spinal nerve ligation. NTP inhibited both tactile allodynia and mechanical and thermal hyperalgesia in a dose-dependent manner. When the effect of NTP was examined after depletion of monoamines in the spinal cord by intrathecal neurotoxins, the antiallodynic and antihyperalgesic effects were still observed after serotonergic denervation, but not after noradrenergic denervation. In addition, intracerebroventricular NTP increased withdrawal threshold and latency although intrathecal or local administration of NTP did not. These results suggest that the antiallodynic and antihyperalgesic effect of NTP on neuropathic pain induced by spinal nerve ligation is mediated principally through the action at supraspinal sites and through activation of spinal noradrenergic systems, possibly via the descending inhibitory pathway.

5,7-Dihydroxytryptamine↗
PubMed2005

Circulating mature adrenomedullin is related to blood volume in full-term pregnancy.

Plasma adrenomedullin concentration increases during pregnancy. We measured blood volume and mature adrenomedullin concentration in plasma and cerebrospinal fluid and examined whether mature adrenomedullin in plasma and cerebrospinal fluid was associated with increasing blood volume during pregnancy. We enrolled 47 women undergoing surgery with spinal anesthesia in this study. We first measured mature adrenomedullin concentration in plasma and cerebrospinal fluid of nonpregnant women undergoing orthopedic surgery, pregnant women between 15 and 18 wk of gestation undergoing gynecological surgery, and pregnant women at full-term undergoing cesarean delivery. The second study included 20 healthy and full-term parturients scheduled for cesarean delivery. We measured arterial blood pressure and blood volume by noninvasive pulse spectrophotometry using indocyanine green. Plasma-mature adrenomedullin concentration was 1.24 +/- 0.98, 2.79 +/- 1.23, 4.79 +/- 2.61 fmol/mL (mean +/- sd) in the nonpregnant, the early gestation, and the full-term groups, respectively. But in cerebrospinal fluid, mature adrenomedullin did not significantly increase. Furthermore, mature adrenomedullin in plasma, but not cerebrospinal fluid, had a significant correlation with blood volume per unit body weight (r2= 0.46; P = 0.0009). These findings demonstrate that plasma-mature adrenomedullin concentration increased and that increased plasma-mature adrenomedullin is associated with increased blood volume during pregnancy.

Adrenomedullin↗