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T Mashimo

Publications and source records attributed to T Mashimo.

At least 73 records · Page 4Linked to original sources
PubMed1998

Gamma subunit dependent modulation by nitric oxide (NO) in recombinant GABAA receptor.

The effect of nitric oxide (NO) on GABA induced Cl- current of recombinant GABAA receptors was studied. Either alpha 1 beta 2 gamma 2s or alpha 1 beta 2 subunit mRNAs synthesized from cDNA of mouse brain were injected into Xenopus oocytes and functional GABAA receptors were expressed. GABA-induced Cl- current was measured with the two electrode voltage clamp technique. The NO donor NOC-18 reduced the GABA-induced Cl- current in the alpha 1 beta 2 gamma 2s subunit receptor in a dose-dependent manner. In alpha 1,beta 2 subunit receptor, NOC-18 had no effects on GABA-induced currents at low concentrations but showed potentiation at high concentration. These effects were antagonized by the NO extinguisher, carboxy-PTIO. The cGMP analogue 8-Br-cGMP failed to induce NO-like effects. NO directly acts at the GABAA receptor and the gamma 2s subunit is involved in its action.

Animals↗
PubMed1998

Construction of a rat genetic map by using randomly amplified microsatellite polymorphism (RAMP) markers.

Many rat strains have been employed in the genetic study of quantitative traits such as blood pressure. In such genetic studies, it is essential to prepare rat genetic maps fine enough to identify the genes regulating quantitative traits. However, it is not an easy task to isolate a sufficient number of genetic markers polymorphic between a particular pair of rat strains. In this study, we applied the randomly amplified microsatellite polymorphism (RAMP) method, a simple method to identify co-dominant markers (Wu et al. Nucleic Acids Res 22, 3257, 1994), to isolate markers polymorphic between the stroke-prone spontaneously hypertensive rat and the Wistar-Kyoto rat, a genetically hypertensive strain and its normotensive control strain, which share a common genetic background. We successfully identified 111 RAMP markers distributed throughout the rat genome after screening 3046 sets of primers. We also showed that we could isolate ordinary simple-sequence-length-polymorphism markers by cloning RAMP markers. The RAMP method is a simple and efficient way to identify co-dominant genetic markers on mammalian genomes.

Animals↗
PubMed1998

Nitric oxide-induced cytotoxicity attenuation by thiopentone sodium but not pentobarbitone sodium in primary brain cultures.

1. We describe the effects of barbiturates on the neurotoxicity induced by nitric oxide (NO) on foetal rat cultured cortical and hippocampal neurones. Cessation of cerebral blood flow leads to an initiation of a neurotoxic cascade including NO and peroxynitrite. Barbiturates are often used to protect neurones against cerebrovascular disorders clinically. However, its neuroprotective mechanism remains unclear. 2. In the present experiment, we established a new in vitro model of brain injury mediated by NO with an NO-donor, 1-hydroxy-2-oxo-3-(3-aminopropyl)-3-isopropyl-1-triazene (NOC-5) on grid tissue culture wells. We also investigated the mechanisms of protection of CNS neurones from NO-induced neurotoxicity by thiopentone sodium, which contains a sulphydryl group (SH-) in the medium, and pentobarbitone sodium, which does not contain SH-. 3. Primary cultures of cortical and hippocampal neurones (prepared from 16-day gestational rat foetuses) were used after 13-14 days in culture. The cells were exposed to NOC-5 at the various concentrations for 24 h in the culture to evaluate a dose-dependent effect of NOC-5. 4. To evaluate the role of the barbiturates, neurones were exposed to 4, 40 and 400 microM of thiopentone sodium or pentobarbitone sodium with or without 30 microM NOC-5. In addition, superoxide dismutase (SOD) at 1000 u ml(-1) and 30 microM NOC-5 were co-administered for 24 h to evaluate the role of SOD. 5. Exposure to NOC-5 induced neural cell death in a dose-dependent manner in both cortical and hippocampal cultured neurones. Approximately 90% of the cultured neurones were killed by 100 microM NOC-5. 6. This NOC-5-induced neurotoxicity was significantly attenuated by high concentrations of thiopentone sodium (40 and 400 microM) as well as SOD, but not by pentobarbitone sodium. The survival rates of the cortical neurones and hippocampal neurones that were exposed to 30 microM NOC-5 were 11.2+/-4.2% and 37.2+/-3.0%, respectively, and in the presence of 400 microM thiopentone sodium, the survival rate increased to 65.3+/-3.5% in the cortical neurones and 74.6+/-2.2% in the hippocampal neurones. 7. These findings demonstrate that thiopentone sodium, which acts as a free radical scavenger, protects the CNS neurones against NO-mediated cytotoxicity in vitro. In conclusion, thiopentone sodium is one of the best of the currently available pharmacological agents for protection of neurones against intraoperative cerebral ischaemia.

Animals↗
PubMed1998

Arterial oxygenation and shunt fraction during one-lung ventilation: a comparison of isoflurane and sevoflurane.

UNLABELLED: The aim of this study was to evaluate the effect of isoflurane and sevoflurane on oxygenation and shunt fraction during one-lung ventilation (OLV). Twenty patients undergoing lobectomy for lung cancer and scheduled for long-term OLV were enrolled in this study. Patients were allocated to treatment with either isoflurane or sevoflurane. Arterial oxygenation, shunt fraction, and hemodynamics were evaluated at the end of two-lung ventilation; 20 min after the initiation of OLV; 20 min after the application of 4-cm positive end-expiratory pressure (PEEP) to the dependent lung; 20 min after 8-cm PEEP; and 20 min after the conversion from OLV to two-lung ventilation. There was no significant difference between isoflurane and sevoflurane with regard to oxygenation, shunt fraction, or hemodynamics during OLV. PaO2 values after the application of 4-cm PEEP increased from 131.1 +/- 11.8 mm Hg to 190.6 +/- 22.9 mm Hg in the isoflurane group (P < 0.05) and from 127.2 +/- 14.3 mm Hg to 192.4 +/- 26.9 mm Hg in the sevoflurane group (P < 0.05). The selection of either isoflurane or sevoflurane for OLV was made without regard to arterial oxygenation and shunt fraction. PEEP application to the dependent lung is useful for improving oxygenation during OLV, but 8-cm PEEP had no added effect compared with 4-cm PEEP. IMPLICATIONS: We compared the effects of isoflurane and sevoflurane on oxygenation, hemodynamics, and shunt fraction during one-lung ventilation in 20 patients undergoing scheduled lobectomy for lung cancer. There was no significant difference between isoflurane and sevoflurane with regard to oxygenation, shunt fraction, and hemodynamics during one-lung ventilation. The application of 4-cm positive end-expiratory pressure increased the partial pressure of arterial oxygen during one-lung ventilation.

Aged↗
PubMed1998

Effect of barbiturate on central pain: difference between intravenous administration and oral administration.

OBJECTIVE: To examine whether the oral administration of barbiturates is of clinical use in a patient with central pain. SETTING: Pain Clinic, Osaka University Medical Hospital, Osaka, Japan. PATIENT: A patient with central pain after loss of his left upper extremity. INTERVENTIONS: A 50-mg dose of intravenous amobarbital, which produced a plasma concentration of 2.5-4.0 microg/ml, was effective in reducing the central pain. Subsequently, doses of 300-400 mg/day were administered orally; these succeeded in achieving similar plasma concentration levels. RESULTS AND CONCLUSIONS: Oral administration of barbiturate did not alleviate central pain, even when the plasma concentration was the same as the effective level in intravenous use. Pharmacokinetic and pharmacodynamic factors more complex than simple plasma concentrations may be involved in producing the difference in the effects.

Administration, Oral↗
PubMed1998

Measurement of blood volume using indocyanine green measured with pulse-spectrophotometry: its reproducibility and reliability.

OBJECTIVE: To systematically investigate the reproducibility and reliability of a newly developed, less invasive approach of estimating blood volume (BV), using indocyanine green (ICG) measured with pulse-spectrophotometry. DESIGN: Prospective, clinical study. SETTING: Surgical unit at a university hospital. PATIENTS: Twenty-two patients undergoing general anesthesia for elective surgery and seven healthy volunteers. INTERVENTIONS: Catheters were inserted into the forearm veins of healthy volunteers for the administration of ICG and blood sampling for the measurement of hemoglobin concentration. MEASUREMENTS AND MAIN RESULTS: The distribution volumes of ICG in seven healthy volunteers were estimated repetitively following three or four consecutive intravenous administrations at 30-min intervals. A low intrasubject coefficient of variation of 3.94 +/- 2.03 (SEM) % and a reasonable intersubject coefficient of variation of 13.3 +/- 5.52% (in mL/kg) for the BV measurements were obtained. In addition, ICG was administered to 22 patients, first under general anesthesia by a bolus, and then by a bolus with a constant-rate infusion. The ICG blood concentration was noninvasively measured with pulse-spectrophotometry. The blood concentration time courses following both bolus and constant-rate infusion were well fitted by the one-compartment model, indicating that the distribution equilibrium of ICG is instantaneous. The distribution volumes estimated following bolus injection correlate closely with the distribution volume estimated based on constant-rate infusion administration (r2 = .90). CONCLUSIONS: The BV estimation with a bolus injection of ICG and pulse-spectrophotometry is reliable, as reflected by the reproducible BVs estimated in the same subject. The integrated pulse-spectrophotometry monitoring system offers a less invasive and useful tool for bedside estimation of BV.

Adolescent↗
PubMed1998

[Total intravenous anesthesia with propofol is advantageous than thiopental-sevoflurane anesthesia in the recovery phase].

A randomized, prospective and multi-institutional study was performed to investigate whether different anesthetic methods affected differently the quality of recovery from anesthesia. Two hundred and eleven patients were allocated to one of two groups; total intravenous anesthesia (TIVA) with propofol and fentanyl (group P, n = 107) and general anesthesia with thiopental, sevoflurane and nitrous oxide (group TS, n = 104). The rapidity of emergence from anesthesia and postoperative incidence of nausea, vomiting, and headache were compared between the two groups. The group P showed significantly shorter emergence times for verbal command responses (7.4 +/- 5.6 min), extubation (10.0 +/- 6.0 min) and orientation (13.1 +/- 7.8 min) than the group TS (9.1 +/- 5.0 min, 11.7 +/- 6.2 min, 16.4 +/- 7.9 min, respectively). The postoperative incidence of vomiting was not significantly different between the two groups (3.7% in the group P and 9.6% in the group TS), but the postoperative incidences of nausea and headache were significantly lower in the group P compared with the group TS (10.3%, 17.8%, respectively in the group P and 34.6%, 29.8%, respectively in the group TS). We conclude that TIVA with propofol is advantageous than thiopental-sevoflurane anesthesia in the recovery phase.

Adult↗
PubMed1997

Intrathecal administration of a new nitric oxide donor, NOC-18, produces acute thermal hyperalgesia in the rat.

A nitric oxide releasing compound, NOC-18, was injected intrathecally in order to determine the role of NO in spinal nociceptive mechanisms in rats. The nociceptive threshold was evaluated by the radiant heat tail-flick test. The effects of intrathecal injection of N-nitro-L-arginine methyl ester (L-NAME), an NO synthase inhibitor; methylene blue (MB), a soluble guanylate cyclase inhibitor and hemoglobin (Hb), an NO scavenger, on the nociceptive threshold were measured in the presence and absence of 0.1, 1 and 10 microg of NOC-18. The results were compared with a control group of rats which were injected with the same volume of normal saline. NOC-18 caused a dose-dependent curtailment of the tail-flick latency during the period from 15 to 150 min. L-NAME, MB and Hb all produced prolongation of the tail-flick latency during the same time period. The hyperalgesia induced by this concentration range of NOC-18 was completely blocked by Hb, but was not affected by either L-NAME or MB. These findings indicate that NO plays a direct role in thermal hyperalgesia in the spinal cord, and that an another pathway in addition to the NO-cGMP pathway may be involved.

Animals↗
PubMed1997

Augmentation of obese (ob) gene expression and leptin secretion in obese spontaneously hypertensive rats (obese SHR or Koletsky rats).

To explore the pathophysiologic roles of the obese (ob) gene product, leptin, in the development of obesity and hypertension, we examined ob gene expression and leptin secretion in obese spontaneously hypertensive rats (obese SHR or Koletsky rats) at the stage of established obesity and hypertension. Expression of the ob gene was augmented in the epididymal, mesenteric, subcutaneous, and retroperitoneal white adipose tissue (WAT) from 20-week-old male obese SHR compared to their lean littermates (lean SHR). Using a radioimmunoassay for rat leptin, we also measured plasma leptin levels in 20-week-old lean and obese SHR. Plasma leptin levels in obese SHR (292.5 +/- 37.1 ng/ml) were more than 100-fold higher than those in lean SHR (2.8 +/- 1.0 ng/ml). The present study demonstrates that ob gene expression and leptin secretion are markedly augmented in obese SHR.

Animals↗
PubMed1997

Effects of vasodilators guanethidine, nicardipine, nitroglycerin, and prostaglandin E1 on primary afferent nociceptors in humans.

Although vasodilator agents have been used to alleviate the pain of complex regional pain syndromes, the precise mechanism of pain relief is not well known. In this study the effects of various kinds of vasodilators on primary afferent nociceptors were investigated by measuring the thermal pain threshold. Evaluated in the study were the effects of guanethidine (2 mg/mL), nicardipine (0.2 mg/mL). Nitroglycerin (0.3 mg/mL), and prostaglandin E1 (1 microgram/mL) on the cutaneous pain threshold and blood flow at 7-day intervals in six healthy volunteers. Each aliquot of 0.5 mL of the test vasodilator or lidocaine (10 mg/mL) and saline (control) were intradermally injected at three sites each on both forearms. The pricking-pain threshold and skin tissue blood flow were determined using a radiant heat-stimulating system and a laser-Doppler tissue-blood flowmeter, respectively. The pain threshold increased with lidocaine, guanethidine, and nicardipine; remained unchanged with Nitroglycerin; but decreased with prostaglandin E1. In contrast, the skin tissue blood flow increased by four to nine times with all vasodilators. These results indicate that the effect of vasodilators on primary afferent nociceptors is not related to the vasodilating effect and may not involve a common mechanism of action for pain relief in complex regional pain syndromes.

Adult↗
PubMed1997

Carcinogenesis in accessory sex organs of rats induced by 3,2'-dimethyl-4-aminobiphenyl: response to androgen deprivation.

It is generally accepted that early human prostate cancers reveal higher androgen dependency than do advanced ones. In the present study, we examined whether the animal model of prostate cancer has already lost androgen dependency at the early stages of carcinogenesis. At experimental week 46, androgen deprivation was induced in rats and the incidences of atypical hyperplasia and cancer were examined in the ventral, dorsolateral prostate, coagulating glands, and seminal vesicles. Androgen deprivation significantly lowered the incidence of atypical hyperplasia in all four organs. As for the incidence of cancer, no significant differences were observed in the coagulating glands and seminal vesicles. Regarding atypical hyperplasia, androgen deprivation significantly decreased the proliferative cell nuclear antigen labeling index in the coagulating gland and seminal vesicles. The presence of cancer was also decreased in the coagulating gland but not in the seminal vesicles. With control group specimens, more intense staining of androgen receptor was observed in atypical hyperplasias than in cancers. Compared with the atypical hyperplasias, the cancers revealed low androgen dependency at the early stages of carcinogenesis. The cancers in the seminal vesicles also revealed higher androgen independency than did those in the coagulating gland.

Aminobiphenyl Compounds↗
PubMed1997

Sequence and functional analysis of the 5'-flanking region of the mouse growth inhibitory factor gene.

1. The growth inhibitory factor (GIF) is a 68-amino acid protein which is capable of inhibiting the growth of neuronal cells in vitro. 2. We have cloned and sequenced the 5'-flanking region of the mouse GIF gene, which spans from the transcriptional initiation site to the -1854 nucleotide. 3. This region contains sequences homologous to hgcs, SPE, and the JCV silencer domain that functions in a glial cell specific manner. This region also contains two metal responding elements and putative binding sites for AP-1, AP-2, Sp-1, SP-2, NF-1, and CREB. 4. An analysis of the reporter plasmids containing the various regions of the 5'-flanking sequence revealed that the region indeed functioned in a tissue-specific manner in glial cells and that the region between -328 and 175 is responsible for suppression, while the region between -175 and -49 is involved in the activation of gene expression.

3T3 Cells↗
PubMed1997

Interactions between neuronal histamine and halothane anesthesia in rats.

Using an in vivo microdialysis method, we measured the release of histamine in the anterior hypothalamic area (AHy) of rats under several concentrations of halothane anesthesia (1, 0.5, and 0.2%). The release of histamine increased to 341 and 325% at halothane concentrations of 0.5 and 0.2%, compared with the basal level at anesthesia induced by 1% halothane. alpha-Fluoromethylhistidine (100 mg/kg i.v.), a specific and irreversible inhibitor of histidine decarboxylase, reduced the histamine release to <35% of the basal value at 1% halothane anesthesia in the AHy, and also decreased the anesthetic requirement for halothane, evaluated as the minimum alveolar concentration (MAC), by 26%. Furthermore, pyrilamine (20 mg/kg i.v.), a brain-penetrating H1 antagonist, and zolantidine (20 mg/kg i.v.), a brain-penetrating H2 antagonist, reduced the MAC for halothane by 28.5 and 16%, respectively. Although thioperamide (5 mg/kg i.v.), an antagonist of presynaptic H3 autoreceptor, induced an approximate twofold increase in the level of histamine release in conscious freely moving rats, the same dose of thioperamide had little effect on the release of histamine under 1% halothane anesthesia in the AHy. Furthermore, thioperamide did not change the anesthetic requirement (MAC) for halothane. The present findings indicate that halothane anesthesia inhibits the release of neuronal histamine and that histaminergic neuron activities change the anesthetic requirement (MAC) for halothane through H1 as well as H2 receptors.

Anesthetics, Inhalation↗
PubMed1997

Laser Doppler skin blood flow and sympathetic nervous responses to surgical incision during halothane and isoflurane anesthesia.

The aim of the present study was to evaluate whether a sudden decrease in skin blood flow measured using a laser Doppler velocimeter reflects sympathetic nervous response to surgical skin incision during halothane (n = 17) and isoflurane (n = 16) anesthesia in 33 ASA physical status I or II patients scheduled for laparotomy. Plasma norepinephrine concentrations in the responding patients who showed a sudden decrease in the skin blood flow after surgical incision increased significantly and continued to increase 1-10 min after skin incision under halothane and isoflurane anesthesia. Although plasma norepinephrine concentrations in the nonresponders did not increase after surgical incision with halothane, the concentrations increased significantly at 1 min, but not at 3 and 10 min, after skin incision with isoflurane. The results indicate that the sudden decrease in laser Doppler flow reflects the sympathetic response to surgical incision. However, these also suggest that the factors that control the skin blood flow may not be simply sympathetic but may reflect other modulators as well. Plasma epinephrine concentration increased during skin incision, but the concentrations did not differ between the patients with and without a sudden decrease in skin blood flow. Increases in systolic blood pressure and rate-pressure product on skin incision were also significantly more in patients with skin blood flow response compared with those without the response. The magnitude of changes in plasma norepinephrine concentration and hemodynamic variables with skin incision was greater with isoflurane than with halothane at the same minimum alveolar anesthetic concentration level.

Adult↗
PubMed1997

The effects of epidural fentanyl on hemodynamic responses during emergence from isoflurane anesthesia and tracheal extubation: a comparison with intravenous fentanyl.

To investigate the effects of epidural fentanyl infusion on hemodynamic responses to recovery of consciousness and tracheal extubation, we studied 50 unpremedicated patients scheduled for abdominal hysterectomy. All patients underwent epidural catheterization and blind infusion of placebo and study drug. Patients were assigned randomly to three groups: Group I received epidural and intravenous (i.v.) bolus injections and infusion of saline at the rate of 0.2 mL x kg(-1) x h(-1); Group II received an i.v. injection of fentanyl 2 microg/kg for 30 s followed by 25 ng x kg(-1) x min(-1), and Group III received epidural injection and infusion using the same administration regimen as Group II. Anesthesia was induced with and maintained by isoflurane alone in an air-oxygen mixture. The study drug was administered at the start of retroperitoneal suturing. Hemodynamic variables, including systolic and diastolic arterial pressures (SAP and DAP, respectively) and heart rate (HR), were recorded every minute between the start of administration of the study and 5 min after tracheal extubation. During emergence from anesthesia and tracheal extubation, the increases in SAP, DAP, and HR in Groups II and III were significantly diminished (P < 0.05) compared with those in Group I. Arterial pressures, but not HR, were attenuated more significantly in Group III than in Group II during and after tracheal extubation, although the plasma fentanyl concentration was significantly lower (P < 0.01) in Group III (0.64 +/- 0.03 ng/ mL, [mean +/- SD]) than in Group II (1.15 +/- 0.09 ng/mL). The incidence of coughing during and after extubation was also lower with Group III. Suppression of respiratory rate prior to tracheal extubation was similar in the two groups receiving fentanyl. These findings suggest that the significant reduction in arterial pressures responses to tracheal extubation due to epidural fentanyl infusion may arise from more suppression of cough reflex than i.v. fentanyl infusion, which could be provided by the spinal action of epidural fentanyl as well as the supraspinal action.

Adjuvants, Anesthesia↗
PubMed1997

A comparative study of the antinociceptive action of xenon and nitrous oxide in rats.

UNLABELLED: We attempted to clarify the mechanism of antinociceptive action induced by xenon and nitrous oxide. Eighty percent of nitrous oxide or 80% xenon was applied to rats inside enclosed clear plastic glass cylinders with their tails protruding for assessment of the tail-flick response to radiant heat. With repeated testing, there was a rapid reduction to nitrous oxide antinociception within 90 min, which was interpreted as development of tolerance, but not to xenon antinociception. Nitrous oxide antinociception was blocked by the intraperitoneal administration of 0.1 or 1.0 mg/kg yohimbine, but not by 1.0 or 5.0 mg/kg L659-066 or by 5.0 or 10 mg/kg naloxone. Xenon antinociception was not affected by any of these drugs. Yohimbine and L659-066 are characterized as alpha 2-adrenoceptor antagonists. Although yohimbine penetrates the blood-brain barrier after systemic administration, L659-066 does not penetrate it and act peripherally. Therefore, the results indicate that alpha 2-adrenoceptors, but not opioid receptors, may play a key role in antinociception induced by nitrous oxide in the central nervous system. Furthermore, the mechanism of xenon antinociception differs from that of nitrous oxide because it does not involve either alpha 2 or opioid receptors. IMPLICATIONS: The precise mechanism of antinociceptive action of nitrous oxide and xenon remains unknown. It is still controversial whether an opioid system plays a role in antinociception induced by nitrous oxide. The results of the study showed that antagonism of central alpha 2-adrenoceptors, but not opioid receptors, reverses the antinociception induced by nitrous oxide but not by xenon, which indicates that alpha 2-adrenoceptors may play a key role in nitrous oxide antinociception.

Analgesics, Non-Narcotic↗
PubMed1997

The effect of imidazoline receptors and alpha2-adrenoceptors on the anesthetic requirement (MAC) for halothane in rats.

BACKGROUND: Recent evidences have documented that several pharmacologic actions of alpha2-adrenoceptor agonists are mediated via activation of not only alpha2-adrenoceptors, but also by imidazoline receptors, which are nonadrenergic receptors in the central nervous system. However, the effect of imidazoline receptors on the anesthesia is not well known, and it is important to clarify the effects of both receptors on anesthesia. METHODS: Seventy-two rats were anesthetized with halothane, and the anesthetic requirement for halothane was evaluated as minimum alveolar concentration (MAC). The MAC for halothane was determined in the presence of dexmedetomidine (0, 10, 20, and 30 microg/kg, intraperitoneally [IP]), a selective alpha2-adrenoceptor agonist with weak affinity for imidazoline receptors. Then, the authors evaluated the inhibitory effect of rauwolscine (20 mg/kg, IP), an alpha2-adrenoceptor antagonist with little affinity for imidazoline receptors, on the MAC-reducing action of dexmedetomidine (30 microg/kg). Further, the effect of rilmenidine (20, 50, 100, 1000 microg/kg, IP), a selective imidazoline receptor agonist, on the MAC for halothane was also investigated. RESULTS: Dexmedetomidine decreased the MAC for halothane dose-dependently, and this MAC-reducing action of dexmedetomidine was completely blocked by rauwolscine. Rilmenidine alone did not change the MAC for halothane. CONCLUSIONS: The present data indicate that the anesthetic sparing action of dexmedetomidine is most likely mediated through alpha2- adrenoceptors, and the stimulation of imidazoline receptors exerts little effect on the anesthetic requirement for halothane.

Adrenergic alpha-Agonists↗