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Biomedical subjects

T Mutoh

Publications and source records attributed to T Mutoh.

At least 55 records · Page 3Linked to original sources
PubMed1999

Comparison of sedative effects of medetomidine-midazolam, acepromazine-butorphanol and midazolam-butorphanol in dogs.

Sedative effects of medetomidine at 20 micrograms/kg and midazolam at 0.3 mg/kg (MM), acepromazine at 0.05 mg/kg and butorphanol at 0.2 mg/kg (AB), and midazolam at 0.1 mg/kg and butorphanol at 0.2 mg/kg (MB) were compared in dogs. All dogs given MM were laterally recumbent within 11 min of the administration of the drugs, and this combination also induced deep sedation accompanied by analgesia and muscle relaxation, and strongly depressed arousal reactions to external stimuli. However, undesirable effects such as bradycardia and decreased respiration were also observed in dogs given MM. Six of seven dogs given AB were laterally recumbent within 16 min of the administration of the drugs, and this combination induced relatively deep sedation but only a mild depression of arousal reactions to external stimuli. MB induced mild or moderate sedation with relatively large differences in effects among individuals. The recovery from sedation in each group was smooth and total recovery times were not significantly different.

Acepromazine↗
PubMed1999

Effects of permanent tracheostomy on respiratory reflexes to lung inflation and capsaicin in sevoflurane-anaesthetized dogs.

The aim of this study was to evaluate the effects of permanent tracheostomy on baseline breathing, reflex responses to lung hyperinflation (1.5 kPa) and right atrial capsaicin injection (5 micrograms/kg) before and at 3 and 5 weeks after tracheostomy in sevoflurane-anaesthetized spontaneously breathing dogs (n = 6). In all observation periods, apnoeic responses, represented by an increase in expiration time after lung inflation and right atrial capsaicin injection, were consistently observed to be a result of the Hering-Breuer inflation reflex and the pulmonary C-fibre chemoreflex. Investigation at 3 and 5 weeks after tracheostomy revealed no significant evidence of changing baseline breathing pattern or reflex responses to lung inflation and capsaicin in any ventilatory variable (inspiration time, expiration time, tidal volume, expired ventilation, and end-tidal PCO2) from levels recorded before surgery. These results indicate that permanent tracheostomy, at least up to 5 weeks, does not affect the baseline breathing pattern, the Hering-Breuer inflation reflex or the pulmonary C-fibre chemoreflex. Further, our investigation provides a useful canine model in respiratory physiology.

Anesthetics, Inhalation↗
PubMed1999

Comparison of cardiopulmonary effects of medetomidine-midazolam, acepromazine-butorphanol and midazolam-butorphanol in dogs.

Cardiopulmonary effects of intramuscular administration of medetomidine-midazolam at 20 micrograms/kg and 0.3 mg/kg, respectively (MM), acepromazine-butorphanol at 0.05 and 0.2 mg/kg, respectively (AB), and midazolam-butorphanol at 0.1 and 0.2 mg/kg, respectively (MB), were compared in dogs. MM produced relatively large cardiovascular changes such as bradycardia, hypertension, a decrease in cardiac output and vasoconstriction. AB produced moderate cardiovascular changes. Hypotension was observed within 5 min after administration and the mean arterial blood pressure decreased by 30% at 20 min after administration. MB produced decreases in arterial blood pressure and cardiac output, but these changes were small and, of the combinations evaluated in this study, MB had the mildest cardiovascular effects.

Acepromazine↗
PubMed1999

Chronic exposure to sidestream tobacco smoke augments lung C-fiber responsiveness in young guinea pigs.

Children chronically exposed to environmental tobacco smoke (ETS) have more coughs, wheezes, and airway obstruction, which may result in part from stimulation of lung C fibers. We examined the effect of chronic exposure to sidestream tobacco smoke (SS, a surrogate for ETS) on lung C-fiber responsiveness in guinea pigs, in which dynamic compliance (Cdyn), lung resistance, tracheal pressure, arterial blood pressure, and heart rate were also monitored. Guinea pigs were exposed to SS (1 mg/mm(3) total suspended particulates) or filtered air 5 days/wk from 1 to 6 wk of age. They were then anesthetized, and lung C fibers (n = 55), identified by a conduction velocity of <2.0 m/s, were tested for responsiveness to chemical and mechanical stimuli. SS exposure doubled C-fiber responsiveness to left atrial capsaicin (P = 0.02) and lung hyperinflation (P = 0.03) but had no effect on responsiveness to inhaled capsaicin or bradykinin or on baseline activity. The data indicate that chronically exposing young guinea pigs to SS enhances C-fiber sensitivity to certain stimuli and may help explain respiratory symptoms in children exposed to ETS.

Action Potentials↗
PubMed1999

Effects of volatile anesthetics on the activity of laryngeal 'drive' receptors in anesthetized dogs.

Effects of halothane, isoflurane and sevoflurane on laryngeal drive receptor activity were studied in the afferent activity of the superior laryngeal nerve in anesthetized spontaneously breathing dogs. Of 40 single units recorded, most of them (65%) responded to the volatile anesthetics applied to the isolated larynx at a concentration of 5%. The exposure to the anesthetics resulted in either an inspiratory increase (15%), both inspiratory and expiratory decrease (54%), or both inspiratory increase and expiratory decrease (31%) responses. The average discharge frequency of the receptors tended to be decreased on inhalation of the anesthetics, where significant decreases were observed in both respiratory phases for halothane and at expiration for isoflurane, but in neither respiratory phase for sevoflurane. These results support an advantage of sevoflurane over halothane and isoflurane for induction of anesthesia to minimize the influence of the activity of laryngeal drive receptors on the breathing pattern and airway stability.

Anesthetics, Inhalation↗
PubMed1999

The posterior nasal nerve plays an important role on cardiopulmonary reflexes to nasal application of capsaicin, distilled water and l-menthol in anesthetized dogs.

The sensory innervation of the cardiopulmonary reflexes to nasal application of capsaicin (CAPS), distilled water (DW) and l-menthol (LM) was studied in anesthetized dogs breathing through tracheostomy. A marked cardiopulmonary reflex was observed by CAPS and DW into the nasal cavity, while a prolongation of expiration was induced by LM. All these reflexes were significantly decreased by bilateral section of the posterior nasal nerve (PNN) and completely abolished by topical nasal anesthesia with lidocaine. Responses of the whole nerve activity of the PNN to these substances corresponded to the magnitude of the reflexes. These results indicate that PNN afferents play an important role on the reflex elicitation of the noxious, water and cold stimuli from the nasal cavity.

Administration, Intranasal↗
PubMed1999

Nasal sensory receptors responding to capsaicin, water and tactile stimuli in sevoflurane-anesthetized dogs.

Responses of nasal receptors to capsaicin and water were studied from afferent recordings of the posterior nasal nerve (PNN) in 12 anesthetized dogs. Out of 12 non-respiration-modulated nasal receptors, 7 responded only to capsaicin, 3 responded to both water and capsaicin, and 2 to neither of them. All the fibers showed a rapid adaptation to mechanical probing of the nasal mucosa. These results indicate that the presence of sensory receptors responding to capsaicin and water are involved in PNN afferents of the dog.

Anesthesia, Inhalation↗
PubMed1998

Influence of endogenous GM1 ganglioside on TrkB activity, in cultured neurons.

We verified the hypothesis that changes in the endogenous GM1 ganglioside density in the environment of TrkB, receptor of brain-derived neurotrophic factor, can affect receptor activity, and focused on rat cerebellar granule cells expressing both GM1 and TrkB. Changes of the amount of GM1 associated to immunoprecipitated TrkB and of receptor tyrosine phosphorylation were evaluated after treatment with phorbol-12-myristate-13-acetate (1 microM, 7 min), reported to affect the plasma membrane distribution of endogenous gangliosides in the same cells. After treatment, the amount of GM1 associated to receptor and TrkB phosphorylation decreased by about 40%. The amount of associated GM1 decreased by about 33% also after concomitant treatment with phorbol ester and brain-derived neurotrophic factor, but in this case the neurotrophin was unable to enhance receptor tyrosine phosphorylation. These results for the first time suggest that changes in the amount of endogenous GM1 in the environment of TrkB can modulate receptor activity, and offer new clues for a better understanding of physiological and pathological events of the nervous system.

Animals↗
PubMed1998

Differential signaling cascade of MAP kinase and S6 kinase depends on 3',5'-monophosphate concentration in schwann cells: correlation to cellular differentiation and proliferation.

Schwann cells produce myelin in the peripheral nervous system (PNS) and play an important role in the maintenance of the normal function of PNS. Our previous studies have shown that derivatives of adenosine 3',5'-monophosphate (cAMP) can regulate the cell-fate (i.e., proliferation and differentiation into cell surface galactocerebroside-positive cells) depending on its concentration in vitro. Higher concentration of cAMP can induce the expression of cell surface galactocerebroside, while proliferation can be induced by lower concentration of cAMP. However, the detailed molecular mechanism of how the same second messenger yields different phenotypes of Schwann cells depending on its concentration remains to be elucidated. Here we show that low concentration of 8-bromo cAMP, a cell-permeable derivative of cAMP, activates S6 kinase activity with a short-lived activation of mitogen-activated protein kinase (MAPK), whereas high dose of the reagent activates S6 kinase much less than that of low dose with a small and prolonged activation of MAPK in Schwann cells. These data clearly demonstrated that a rise in the intracellular cAMP uses the MAPK-S6 kinase pathway as an intracellular sinaling cascade and different magnitude and duration of the activation of this pathway might underlie the different cellular fate depending on the intensity of the stimulation.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1998

HMG-CoA reductase inhibitor-induced L6 myoblast cell death: involvement of the phosphatidylinositol 3-kinase pathway.

Our previous studies have shown that the HMG-CoA reductase inhibitor (HCRI) causes rhabdomyolysis and electrical myotonia in rabbits and also kills L6 myoblasts in culture. In the present study, we analyzed the intracellular signal transduction pathway of HCRI-induced cell death using L6 myoblasts as a model system. Here, we report that simvastatin, a lipophilic HCRI, efficiently inhibited isoprenylation of Ras proteins and therefore induced translocation of a significant part of Ras proteins from the membrane fraction into the cytosolic fraction within 10 min. With this translocation, PI 3-kinase activity of the Ras-bound form both in total and in the membrane fraction was also decreased profoundly. Furthermore, various PI 3-kinase inhibitors also caused cell death with morphological changes similar to those caused by simvastatin. These results might represent the molecular events of HCRI-induced cell death, and suggest the significance of PI 3-kinase activity of the Ras-bound form in the maintenance of cell viability.

Animals↗
PubMed1998

Glucosylceramide synthase inhibitor inhibits the action of nerve growth factor in PC12 cells.

Previous studies have shown that the ceramide analogue, D-threo-1-phenyl-2-decanoylamin-3-morpholino-propanol (D-PDMP), inhibits glucosylceramide synthase and thus leads to extensive depletion of glycosphingolipids derived from glucosyl ceramide. Our previous studies have shown that cholera toxin B subunit, which specifically binds to the cell surface ganglioside GM1, and GM1 itself can enhance the action of nerve growth factor (NGF) in responsive cells by enhancing the NGF-induced autophosphorylation of the high affinity NGF receptor, Trk. Using D-PDMP, we examined the effects of the inhibition of the biosynthesis of glycosphingolipids on intracellular NGF signaling pathway. D-PDMP was found to inhibit NGF-induced neurite outgrowth of PC12 cells. Moreover, D-PDMP clearly inhibited NGF-induced autophosphorylation of Trk and prevented the activation of phosphatidylinositol 3-kinase and mitogen-activated protein kinase, downstream targets of Trk-initiated intracellular protein kinase cascades. These effects of D-PDMP were abolished by the addition of GM1 but not by the addition of other ganglioside subspecies to the culture medium. Furthermore, the effect of D-PDMP seemed to be specific for the Trk receptor, because intracellular signaling pathway of epidermal growth factor was not affected by D-PDMP. Dimethylsphingosine and the cell-permeable analogue, C2-ceramide, did not show such a strong inhibitory effect on neurite outgrowth or on the autophosphorylation of Trk. The present results and our previous observations clearly demonstrate that Trk requires endogenous gangliosides, especially GM1, for its normal function in mediating the neurotrophic activity of NGF at least in PC12 cells.

Animals↗
PubMed1998

NGF prevention of neurotoxicity induced by cisplatin, vincristine and taxol depends on toxicity of each drug and NGF treatment schedule: in vitro study of adult rat sympathetic ganglion explants.

The simultaneous administration of nerve growth factor (NGF) has been found to prevent experimental neuropathies induced by anti-cancer drugs such as cisplatin, vincristine and taxol. However, it is clinically important to know whether NGF is beneficial once the neuropathy is already manifest. We established a bioassay system to examine the preventive effects of NGF in various treatment schedules. NGF significantly prevented the inhibition of neurite outgrowth by vincristine and taxol regardless of treatment schedules. The pre-treatment and co-treatment schedules were effective against cisplatin, but the post-treatment schedule was not. With regard to the neurite and nerve cell population densities, only the cisplatin group treated with NGF showed lower values than the control. These results indicate that NGF-treatment is effective for the toxic sympathetic nerve injury induced by vincristine and taxol regardless of the treatment schedule, but is not protective against cisplatin-induced nerve cell injury.

Analysis of Variance↗
PubMed1998

Effects of halothane, enflurane, isoflurane, and sevoflurane on slowly adapting pulmonary stretch receptor activity in anesthetized dogs.

The aim of this study was to evaluate the effects of halothane, enflurane, isoflurane, and sevoflurane on slowly adapting pulmonary stretch receptor (SAR) activity in dogs. Eight beagles were anesthetized with an intravenous injection of a mixture of urethane and alpha-chloralose as a basal anesthesia, then vagotomized, artificially ventilated, and chest opened. Single afferent activities from SARs were recorded from the peripheral nerve cut end of the left vagus. Changes in SAR activities with inhalation of halothane, enflurane, isoflurane, and sevoflurane at 1, 1.5, and 2 times the minimal alveolar anesthetic concentration (MAC) were measured, and differences in the discharges within and among four anesthetics were evaluated. As a result, two different types of SARs, low threshold SARs and high threshold SARs, were detected in this study. In all anesthetics, expiratory discharges of low threshold SARs decreased significantly in a dose-dependent manner, whereas inspiratory discharges did not change significantly at any anesthetic level. Discharges of high threshold SARs tended to decrease with increasing anesthetic level; however, no statistical significance was observed at any anesthetic level. Only one exception to these changes was observed at 1 MAC of halothane where no significant decrease in the expiratory discharge of low threshold SARs or significant increase in the discharge of high threshold SARs was induced against a control value. In conclusion, recent inhalation anesthetics, except for halothane at the light anesthetic level, tended to decrease SAR activities depending on the anesthetic level, suggesting attenuation of the Hering-Breuer inflation reflex.

Action Potentials↗
PubMed1998

Expression of low-affinity neurotrophin receptor p75NTR in the peripheral nervous system of human neuropathies.

Expression of low-affinity neurotrophin receptor (p75NTR) was immunohistochemically examined in the peripheral nerve trunks, dorsal root ganglia, sympathetic nerve ganglia and spinal cords in various human neurological diseases manifesting peripheral neuropathies. p75NTR was expressed in the nerves with axonal degeneration, and was also prominent in the nerves with newly regenerating axons. In contrast, axonal pathology tended to reduce the expression of p75NTR in the neuronal perikarya of the dorsal root ganglion and sympathetic nerve ganglion neurons. In the ventral and lateral horn cells, the p75NTR immunoreactivity was not detected in the normal and diseased nerves except for amyloid polyneuropathy. These p75NTR expressions in the diseased human peripheral nervous tissues would be regulated by an underlying pathology-related process, and could play a role in peripheral nerve repair.

Aged↗
PubMed1998

Responses of laryngeal capsaicin-sensitive receptors to volatile anesthetics in anesthetized dogs.

The responses of laryngeal capsaicin (CAPS)-sensitive receptors to halothane, enflurane, isoflurane and sevoflurane were evaluated in anesthetized spontaneously breathing dogs from the afferent activity of the internal branch of the superior laryngeal nerve. The CAPS-sensitive receptors were clearly distinguished from irritant receptors by their responsiveness to CAPS and their lack of responsiveness to water. All the CAPS-sensitive receptors were significantly stimulated by all volatile anesthetics in a concentration-related manner, and the activation by halothane, enflurane, and isoflurane was significantly greater than by sevoflurane. In contrast, responses of irritant receptors to the volatile anesthetics were divided into three types (stimulation, inhibition or non-response), and did not differ among anesthetics. In conclusion, the present study demonstrated that the CAPS-sensitive receptors were consistently stimulated by halogenated volatile anesthetics and especially by halothane, enflurane, and isoflurane, and that these responses were dissimilar to the variable responses of irritant receptors.

Afferent Pathways↗
PubMed1998

Effects of volatile anesthetics on vagal C-fiber activities and their reflexes in anesthetized dogs.

Effects of halothane, enflurane, isoflurane, and sevoflurane on vagal capsaicin (CAPS)-sensitive C-fibers were elucidated in anesthetized dogs. The CAPS-sensitive C-fibers were significantly stimulated by all volatile anesthetics with a significantly greater response to halothane than with sevoflurane. A significant increase in respiratory frequency (fR) and a significant decrease in tidal volume (VT) were observed with halothane and isoflurane, and a significant increase in fR was observed with sevoflurane. In contrast, a significant decrease in fR was induced by enflurane. The tachypnea induced by halothane, isoflurane, and sevoflurane was significantly reduced or no longer observed after perineural CAPS-treatment or bilateral vagotomy, whereas the slowing of respiration observed with enflurane was not affected by either of these treatments. These results suggest that vagal C-fibers play an important role in the reflex tachypnea that occurs with halothane, isoflurane, and sevoflurane.

Anesthesia↗