Biomedical subjects

A Shigematsu

Publications and source records attributed to A Shigematsu.

At least 91 records · Page 5Linked to original sources

PubMed1995

[A fundamental study on accumulation of [125I]IBZM in the rat striatum and on effect of non-labeled ligand].

Iodo-125-labeled iodobenzamide ([125I]IBZM) is used as a specific binding radioligand to dopamine D2 receptors with high affinity and selectivity. The radioligand was homogenously distributed in the whole brain initially after administration, and rapidly washed out from the dopamine receptor-poor area followed by persistent retention in the striatum. Regression curve generated from striatum/cortex PSL ratio indicated the constant washout rate from striatum and cortex respectively. In the pretreated rat by cold benzamide (2 mg/kg), the accumulation of the radioligand was significantly suppressed in the striatum (48.8%). Iodine-125-labeled iodo-benzamide has the promise for investigation of dopamine D2 receptors in the living brain.

Animals↗

PubMed1994

Isoflurane inhibits nicotinic acetylcholine receptor-mediated 22Na+ influx and muscarinic receptor-evoked cyclic GMP production in cultured bovine adrenal medullary cells.

The effects of isoflurane on 22Na+ influx, 45Ca2+ influx, catecholamine secretion and cyclic GMP production induced by three kinds of secretagogue (nicotinic agonists, veratridine and a high concentration of K+) have been investigated using cultured bovine adrenal medullary cells. (1) Isoflurane (1-6%) inhibited catecholamine secretion stimulated by carbachol, nicotine and dimethyl-4-phenylpiperazinium in a concentration-dependent manner. Isoflurane suppressed carbachol-evoked 22Na+ influx and 45Ca2+ influx at concentrations similar to those which suppressed catecholamine secretion. The inhibition of catecholamine secretion by isoflurane was not overcome by increasing the concentration of carbachol. (2) The inhibitory effects of isoflurane on veratridine-induced 22Na+ influx, 45Ca2+ influx and catecholamine secretion became evident when the concentration of isoflurane was raised to 4-6%, i.e. 2-3 fold higher than the concentrations (1-2%) employed clinically. (3) High K(+)-evoked 45Ca2+ influx and catecholamine secretion were not affected by isoflurane (1-6%). (4) Isoflurane (1-6%) attenuated the production of cyclic GMP caused by muscarine, but not that caused by atrial natriuretic peptide or by sodium nitroprusside. These results suggest that isoflurane, at clinical anesthetic concentrations, inhibits nicotinic acetylcholine receptor-mediated cell responses as well as muscarinic receptor-mediated cyclic GMP production in adrenal medullary cells.

Adrenal Medulla↗

PubMed1994

Ketamine suppresses endotoxin-induced tumor necrosis factor alpha production in mice.

BACKGROUND: The cytokines play important roles in the pathophysiologic alterations associated with sepsis, but there are no reports about the effect of anesthetics on their production. Therefore, the authors examined the effect of ketamine on lipopolysaccharide (LPS)-induced and calcium ionophore A23187-induced tumor necrosis factor alpha (TNF-alpha) production in thioglycolate (TGC)-elicited peritoneal macrophages (MPs) in ddY mice. METHODS: Ketamine was added to TGC-elicited MPs at various times after the stimulation with LPS or A23187. After the MPs were stimulated by LPS or A23187 and incubated, TNF-alpha activities in the supernatant of MPs were determined by an L929 cytotoxic assay. In vivo, the ddY mice were injected intraperitoneally with TGC. Four days later, they were injected subcutaneously with ketamine and then injected intravenously with LPS. Two hours after the LPS challenge, TNF-alpha activities of the sera were determined. RESULTS: Ketamine suppressed both LPS-induced and A23187-induced TNF-alpha production in a dose-dependent manner. The simultaneous addition of ketamine to LPS-stimulated and A23187-stimulated MPs resulted in a 50% inhibition of TNF-alpha production at 20 micrograms/ml and 12.5 micrograms/ml, respectively. Ketamine also caused a significant suppression of TNF-alpha production even when added to the MPs 2 h after the LPS challenge. There was a significant decrease in A23187-induced TNF-alpha production in TGC-elicited MPs in a calcium-depleted medium when compared with that in a calcium-containing medium. Conversely, LPS-induced TNF-alpha production did not cause such a result. In addition, ketamine could suppress LPS-induced TNF-alpha production in TGC-pretreated mice in vivo. CONCLUSIONS: Ketamine suppresses LPS-induced TNF-alpha production in both TGC-elicited MPs and TGC-pretreated mice.

Animals↗

PubMed1994

Effect of peripheral benzodiazepine receptor ligands on lipopolysaccharide-induced tumor necrosis factor activity in thioglycolate-treated mice.

To investigate the effect of peripheral and central benzodiazepine receptor ligands on lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF) activity in mouse macrophages, three types of ligands, 4'-chlorodiazepam (pure peripheral), midazolam (mixed), and clonazepam (pure central), were compared. Midazolam and 4'-chlorodiazepam significantly suppressed LPS (1-microgram/ml)-induced TNF activity in thioglycolate-elicited mouse macrophages. In every concentration examined (0.001 to 100 microM), 4'-chlorodiazepam was the most effective agent, clonazepam was the least effective agent, and midazolam had an effect intermediate between those of the other two ligands. The peripheral benzodiazepine receptor ligands had a dose-dependent suppressive effect, and the 50% inhibitory concentrations were 0.01 microM for 4'-chlorodiazepam and 5 microM for midazolam. Concomitant use of PK 11195 (10 microM), an antagonist of the peripheral benzodiazepine receptor, reversed this suppressive effect with 4'-chlorodiazepam (10 microM) or midazolam (10 microM). PK 11195 showed this antagonistic effect in a dose-dependent manner. Intravenous 4'-chlorodiazepam (5 mg/kg of body weight) significantly suppressed LPS (100-micrograms)-induced TNF activity of sera (2 h postchallenge with LPS) from thioglycolate-treated mice. The present findings suggest that the peripheral benzodiazepine receptor plays an important role in modulating LPS-induced TNF activity in mouse macrophages.

Animals↗

PubMed1994

Comparison of the effects of ioversol and other contrast media on the blood-brain barrier.

Little information is available concerning the neurotoxicity of ioversol injected in animals. The effects of ioversol and other contrast media as well as vehicle control on the blood-brain barrier (BBB) were examined by injection into the left carotid artery of Mongolian gerbils 1 min prior to the i.v. injection of [8-14C]dopamine. The animals were sacrificed 1 min after the i.v. injection to prepare the frontal brain sections following the stereotaxic atlas. No uptake of the labeled substance was observed when the vehicle control and ioversol were used, suggesting that exposure to ioversol does not damage the BBB. Both meglumine sodium amidotrizoate and iohexol caused damage to the BBB, as shown in the cerebral cortex, brain stem, and hippocampus sections in the left semisphere. Iopaidol induced a much less but significant effect. Our results suggest that ioversol is an useful contrast medium.

Animals↗

PubMed1994

Autoradioluminography, a novel quantitative method of TLC-autoradiography.

In pharmacokinetic studies, ordinary methods of identifying or quantitatively measuring metabolites have been complicated and become difficult to handle. Here, a novel TLC-autoradioluminography (TLC-ARLG) is reported. This technique is especially suited for quantitatively measuring a minute amount, below-1 ng, of many radioactive metabolites in plasma, tissues or organs, thus eliminating cumbersome extraction procedures. The method has an extremely wide dynamic range and could offer a powerful analytical technique for studying a radioactive compound and its metabolites in a biological specimen. Autoradioluminography is a new quantitative technology developed by combining autoradiography with radioluminography. Radioluminography is a kind of radiography in which a specially designed radio-sensor plate, called an "Imaging plate (IP)," developed by Fuji Photo Film Co., Ltd., is used. The radio-sensor is made of fine crystals of BaF:Eu2+, and the technology is based on photo-luminescence phenomena.

Animals↗

PubMed1994

Ketamine suppresses tumor necrosis factor-alpha activity and mortality in carrageenan-sensitized endotoxin shock model.

We have reported that an intravenous anesthetic, ketamine, has a potent suppressive effect on lipopolysaccharide (LPS)-induced TNF-alpha production in vitro [Takenaka et al., Anesthesiology 80:402-408, 1994]. The purpose of the present study was to investigate the overall effects of ketamine on hemodynamics, serum TNF-alpha level, arterial blood gases (ABGs), blood glucose level, liver function, and lethality in carrageenan (CAR)-sensitized endotoxemic models. All animals were pretreated intraperitoneally with CAR (150 mg/kg) 16 hr before LPS stimulation. The control rats were injected LPS with 0.5 mg/kg intravenously (i.v.). The ketamine-treated rats were injected with 100 mg/kg of ketamine intramuscularly 30 min before LPS (0.5 mg/kg) i.v. injection, followed by an i.v. infusion at 0, 5, or 10 mg/kg/hr. Serum TNF-alpha, ABGs, blood glucose, and hematological studies were determined at 0, 2, and 6 hr after the LPS challenge. Serum hepatocellular enzyme levels were measured at 6 hr after the injection. In CAR-sensitized rats, serum TNF-alpha activity remarkably increased in accordance with the mild decrease of mean arterial pressure (MAP) at 2 hr after LPS stimulation. In addition, severe metabolic acidosis, hypoglycemia as well as severe hepatic injury were induced at 6 hr after the LPS challenge. By contrast, ketamine treatment significantly attenuated the decrease in MAP and LPS-induced TNF-alpha activity. Ketamine also significantly improved arterial oxygen tension (PaO2), metabolic acidosis and hypoglycemia, and attenuated endotoxin-induced hepatic injury in a dose-dependent fashion. In addition, ketamine treatment significantly improved LPS-induced lethality in CAR-sensitized mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗

PubMed1994

[Response to a questionnaire on DNR-order from 307 trustee members of Japanese Medical Societies].

A questionnaire on the use of DNR-order was conducted on 427 trustee members of Japan Society of Reanimatology, Intensive Care Medicine and Anesthesiology with responses from 307 or 71.9%. The results of the questionnaire are as follows: DNR-order is unnecessary, 2.9%. Necessary depending on the situation, 96.7%. Here dying in dignity was the main reason for necessity of DNR-order and ethical, legal and technical problems were the reasons cited for objection. Patients' will is indispensable for DNR-order, 11.4%. Patients' will is not indispensable, 84.9%. Quality and quantity of treatment after the decision of DNR-order should not be limited or withdrawn, 21.2%. Should be withdrawn except for respirator, 60.6%. The percentage of those who had carried out a DNR-order was 69.1% (most of them more than once), but half of them did not describe the order on the chart. A guideline for a DNR-order by scientific societies and/or governmental policy for a DNR-order should be made and publicized not only for the benefit of the patients and their families but also for physicians themselves.

Adult↗

PubMed1993

Intra-operative blood pressure control by prostaglandin E1 in patients with hypertension and ischemic heart disease--a multi-center study.

The purpose of this multi-center study was to evaluate the efficacy and safety of prostaglandin E1 (PGE1) administration in achieving deliberate hypotension and in treating intraoperative hypertension for patients with a history of hypertension and ischemic heart disease. PGE1 (0.08 microg.kg(-1).min(-1)) decreased systolic blood pressure from 125 +/- 29 to 106 +/- 22 mmHg (mean +/- SD) in the deliberate hypotension group (n = 158) and from 155 +/- 34 to 125 +/- 32 mmHg in the antihypertension group (n = 55). The heart rate significantly increased from 80 +/- 15 to 85 +/- 18 beats.min(-1) in the deliberate hypotension group, but was not significantly altered in the antihypertension group. The time required to obtain the desired level of blood pressure was approximately 20 min in the deliberate hypotension group. When the infusion was stopped, blood pressure returned approximately to the preinfusion level within about 20 min. No rebound hypertension was observed. PGE1 significantly increased the urine flow in patients who had a low urine flow before PGE1 infusion. Thirteen out of 213 patients (5.6%) had side effects such as excessive hypotension (1%), phlebitis (3%), and unexpected tachycardia (1%), which were alleviated gradually after discontinuation of PGE1 infusion. No dysarrhythmia and further ST segment changes in the electrocardiograms were observed. These findings suggest that PGE1 can be safely used to control arterial blood pressure during surgery in patients having preoperative hypertension and ischemic heart disease.

Journal Article↗

PubMed1993

Dextran sulphate enhancement of lipopolysaccharide-induced tumour necrosis factor-alpha production by murine peritoneal macrophages: correlation with macrophage blockade.

Proteose peptone-induced murine peritoneal macrophages (M phi) were preincubated with 100-800 micrograms/ml of dextran sulphate (DS) 500 (M(r) 500,000) or DS1000 (M(r) 1,000,000). After 2-24 h of the preincubation, the M phi were stimulated with 1 microgram/ml of lipopolysaccharide (LPS) in vitro for 18 h in DS-free culture medium. The culture supernatants were then collected for TNF assay. The LPS-induced TNF activity of M phi supernatant preincubated with DS500 or DS1000 for 6 h was enhanced by up to about ten-fold compared with those preincubated without DS. This enhancing effect was not observed when M phi were preincubated with 100-800 micrograms/ml of low molecular weight DS5 (M(r) 5,000) or neutral dextran (Dex) 500 (M(r) 500,000). The enhancement of LPS-induced TNF-alpha production from M phi was observed after 2 or 4 h of incubation with DS1000 or DS500, respectively. The phagocytic activity of M phi was determined in vitro by the ingestion index and phagocytic capacity using Saccharomyces cerevisiae. Treatment with DS500 or DS1000 significantly suppressed the phagocytic activity from 2 h after the incubation, but this suppression was not observed in M phi incubated with DS5 or Dex500. Our experiments indicate that DS500 and DS1000 act directly on M phi and enhance LPS-induced TNF-alpha production from M phi, and that the enhancement is closely related to the suppression of M phi phagocytic function.

Animals↗

PubMed1993

An antagonist of platelet-activating factor suppresses endotoxin-induced tumor necrosis factor and mortality in mice pretreated with carrageenan.

We found that carrageenan (CAR), that is, sulfated polygalactose, can enhance both lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF) production and the rate of lethality in mice (M. Ogata, S. Yoshida, M. Kamochi, A. Shigematsu, and Y. Mizuguchi, Infect. Immun. 59:679-683, 1991). It has been reported that platelet-activating factor (PAF) antagonists reduce the rate of mortality from endotoxin shock. However, there are few reports regarding the effect of PAF antagonists on TNF production. The aim of the present study is to examine the effect of TCV-309, a new PAF antagonist, on LPS-induced TNF production and mortality in mice pretreated with CAR. ddY mice (6 to 7 weeks old) were injected intraperitoneally with CAR (5 mg per mouse) and were then divided into two groups: mice treated with a PAF antagonist (TCV-309; Takeda Pharmaceutical Co.) and control mice. The mice treated with PAF antagonist received indicated doses of TCV-309 subcutaneously (s.c.) at 30 min before LPS injection, while the control mice received 1 ml of saline s.c. at the same time. All mice were stimulated by intravenous injection of LPS (50 micrograms per mouse) at 24 h after pretreatment with CAR. At intervals after injection of LPS, serum samples were obtained for a TNF assay in which cytotoxicity to L929 cells was measured. TCV-309 both significantly suppressed LPS-induced TNF production and reduced mortality in a dose-dependent manner. When TCV-309 was administered at 30 min before injection of LPS, the effect of TCV-309 on the suppression of TNF activity was at its peak. Treatment with TCV-309 (990 micrograms per mouse) s.c. significantly improved the survival rate after challenge with LPS compared with the survival rate of control mice. Although the 50% lethal dose of LPS was 15 micrograms per mouse for control mice, it increased to 102 micrograms per mouse for mice that were treated s.c. with TCV-309 (990 micrograms per mouse). Even in vitro, TCV-309 also inhibited LPS-induced TNF production in thioglycolate-elicited macrophages. It was concluded that PAF plays an important role in endotoxin-induced TNF production and mortality.

Animals↗

PubMed1993

The effects of glucose on plasma amino acids and pyruvate during upper abdominal surgery.

To assess the potential benefits of perioperative glucose administration, the plasma concentrations of insulin, free fatty acids, ketone bodies, amino acids, lactate, and pyruvate were measured in 20 patients undergoing partial gastrectomy. Ten patients received intravenous glucose at 10 g/h during the operation, and the other 10 patients, as control, received no glucose. Plasma glucose, insulin activity, pyruvate and alanine concentrations in the glucose-receiving group increased significantly during the operation in comparison with the control group. In contrast, in the glucose-receiving group the plasma ketone bodies and branched-chain amino acids, especially leucine and isoleucine, decreased significantly during surgery. These results suggest that administration of glucose stimulated insulin secretion and resulted in accumulation of the substrates such as pyruvate and alanine which were utilized readily in the body. Glucose administration is useful in suppressing catabolism during upper abdominal surgery.

Amino Acids↗

PubMed1992

Distribution of hypobaric tetracaine within cerebrospinal fluid in a spinal canal model.

We studied the distribution of hypobaric tetracaine within cerebrospinal fluid (CSF) using a spinal canal model to examine the spread of a hypobaric anesthetic solution during spinal anesthesia. In our study, 0.2% tetracaine colored with methylene blue was observed to migrate upwards rapidly and spread horizontally in the upper portion of the model placed horizontally and filled with CSF which was collected from several neurosurgical patients. The boundary between the hypobaric solution and CSF could be clearly identified. These results suggest that the hypobaric tetracaine will distribute in the upper portion of the spinal canal during spinal anesthesia. It can be used to produce unilateral spinal blockade in the lateral decubitus position despite a small difference in specific gravity between the hypobaric anesthetic and CSF. In addition, the fact that the hypobaric solution showed a rapid horizontal spread suggests that correct positioning both during and following administration of the anesthetic is important to control the level of anesthesia.

Journal Article↗

PubMed1992

Blood pressure, heart rate and catecholamine response during fiberoptic nasotracheal intubation under general anesthesia.

Arterial blood pressure (ABP) and heart rate were recorded at one-minute intervals during several stages of intubation in the fiberscope group and the laryngoscope group, to determine if fiberoptic nasotracheal intubation would result in fewer hemodynamic and catecholamine responses than when intubation was performed with a Macintosh laryngoscope. Blood samples were also taken to measure plasma catecholamine concentration immediately after intubation with the fiberscope. The mean ABP in the laryngoscope group was slightly greater than that of the fiberscope group for 4 min after intubation. Heart rates at 2 min and 4 min after intubation in the laryngoscope group were significantly greater than those for the fiberscope group. Even immediately after intubation, the mean plasma levels of epinephrine and norepinephrine were unchanged in the fiberscope group. Arterial oxygen saturation (Sp(O)(2)) was maintained within normal range during both of intubation procedures, although the time required for intubation was longer than in the laryngoscope group. Other cardiovascular complications were more common in the laryngoscope group than in the fiberscope group. These results suggest that fiberoptic intubation results in less severe stress than does laryngoscopic intubation. Fiberoptic intubation should therefore be used not only in patients with difficult airway, hypertension, ischemic heart disease, or cerebrovascular atherosclerosis, but also it is recommended for all patients for whom nasotracheal intubation is indicated.

Journal Article↗

PubMed1992

Priming effect of dextran sulphates on lipopolysaccharide-induced tumour necrosis factor production in mice.

Dextran sulphate (DS) 500 (M.W. 500,000) is commonly used as a reticuloendothelial (RE) blocker. We found that lipopolysaccharide (LPS)-induced tumour necrosis factor (TNF) production in sera was enhanced when mice were pretreated with DS500. When mice were pretreated with DS1000 (M.W. 1,000,000), TNF activity in sera was also significantly enhanced by the LPS injection in comparison with the saline-treated group, but not by the pretreatment with the low molecular weight of DS5 (M.W. 5,000), neutral dextran (Dex) 500, or positively-charged diethylaminoethyl dextran (DEAE-Dex) 500. The enhancement of LPS-induced TNF production occurred from 2 h after DS500 pretreatment. Pretreatment with DS500 or DS1000 significantly suppressed the carbon clearance from the blood in mice from 2 h after DS injection, but this suppression was not detected by the pretreatment with DS5, Dex500, or DEAE-Dex500. We suggest that negative-charge and high molecular weight are essential for dextran derivatives to enhance LPS-induced TNF production, and that the enhancing effect of DS is closely related to the suppression of the RE function.

Animals↗

PubMed1992

Protective effects of a leukotriene inhibitor and a leukotriene antagonist on endotoxin-induced mortality in carrageenan-pretreated mice.

The leukotrienes and tumor necrosis factor (TNF) play an important role in the pathophysiology of septic shock, in which hypotension, leukopenia, thrombocytopenia, and hemoconcentration are observed. This study was performed to examine the effects of a 5-lipoxygenase inhibitor (AA-861), a selective leukotriene receptor antagonist (ONO-1078), and a cyclooxygenase inhibitor (indomethacin) on endotoxin-induced mortality and TNF production in mice. Mice were injected intraperitoneally with carrageenan (5 mg per mouse), which we previously reported as an effective priming agent for lipopolysaccharide (LPS)-induced TNF production and mortality (M. Ogata, S. Yoshida, M. Kamochi, A. Shigematsu, and Y. Mizuguchi, Infect. Immun. 59:679-683, 1991). The indicated doses of AA-861, ONO-1078, indomethacin, or controls were administrated subcutaneously 30 min before LPS (50 micrograms per mouse) provocation. The mortality of mice was significantly decreased by pretreatment with AA-861 (P less than 0.001) or ONO-1078 (P less than 0.01) but not by pretreatment with indomethacin. The 50% lethal dose of LPS in the mice treated with dimethyl sulfoxide or ethanol was 32 or 33 micrograms, respectively, and it increased to 83 micrograms with AA-861 or 59 micrograms with ONO-1078, respectively. Neither AA-861 nor ONO-1078 suppressed LPS-induced TNF production in sera. Treatment with AA-861 significantly decreased the leukopenia and thrombocytopenia, and ONO-1078 significantly decreased the hemoconcentration and thrombocytopenia. The role of endogenous TNF was also examined in the carrageenan-pretreated mice. Treatment with 2 x 10(5) U of rabbit anti TNF-alpha antibody intravenously 2 h before LPS challenge significantly suppressed the LPS-induced TNF activity and decreased the mortality. Therefore, both leukotrienes and TNF play important roles in endotoxin-induced shock and mortality.

Animals↗

PubMed1992

The changes of gasoline compounds in blood in a case of gasoline intoxication.

A 44 year-old man, found in his gasoline vapor filled car, died of multiple organ failure on d 9. Blood samples from d 2-7 were analyzed by gas chromatography/mass spectrometry. The estimated half-lives of gasoline, toluene, ethylbenzene, m,p-xylene, and o-xylene were 16.9, 21.4, 27.5, 32.8, and 25.8 h respectively. The estimated initial gasoline concentration in blood was 247 micrograms/ml.

Acidosis↗

PubMed1992

[Resection of tracheal carcinoma using partial cardiopulmonary bypass--report of a case].

A 43-year-old male was admitted to our hospital with chief complaints of stridor and dyspnea. Bronchoscopy revealed a tumor obstructing almost the whole lumen of the trachea. As it was impossible to insert an endotracheal tube into the distal site of the stenosis in the mediastinum, we used partial cardiopulmonary bypass to maintain gas exchange. The axillary artery and the femoral artery and vein were cannulated for the bypass using local anesthesia. During 105 minutes of bypass, the PaO2 value was good but the PaCO2 value increased up to 70 mmHg. After the trachea was opened, the anesthetic gas was administered across the operative field through the endotracheal tube and the cardiopulmonary bypass was discontinued. Tracheolaryngectomy and permanent tracheostomy with relocation to the right and caudal side of the brachiocephalic artery was performed successfully. The post operative course was very smooth. The patient has been well for 6 months since the surgery. Partial cardiopulmonary bypass proved to be useful for maintaining gas exchange during reconstructive surgery of the trachea. We treated a case of tracheal carcinoma by resection while using partial cardiopulmonary bypass. We believe this is the ninth such case reported Japanese literature.

Adult↗