Biomedical subjects

Tetsuo Satoh

Publications and source records attributed to Tetsuo Satoh.

18 recordsLinked to original sources

PubMed2003

Purification, molecular cloning, and functional expression of inducible liver acylcarnitine hydrolase in C57BL/6 mouse, belonging to the carboxylesterase multigene family.

To identify the peroxisome proliferator-inducible acylcarnitine hydrolase in C57BL/6 mice, acylcarnitine hydrolase was purified to homogeneity using column chromatography. The purified enzyme, named ACH M1, had a subunit molecular weight of 60kDa. ACH M1 could hydrolyze classical carboxylesterase (CES) substrates as well as palmitoyl-dl-carnitine and these activities were inhibited by anti-rat CES antibodies. The peptide fragments of ACH M1 were identical to those of the deduced amino acid sequence of mouse CES2 isozyme. These findings suggested that ACH M1 was a member of the CES2 family. The mouse CES2 cDNA, designated mCES2, was cloned from mouse liver. The recombinant mCES2 expressing in Sf9 cells showed high level of catalytic activity toward acylcarnitines. Furthermore, the biological characteristics of the expressed protein were identical with those of ACH M1 in many cases, suggesting that mCES2 encodes mouse liver ACH M1.

Amino Acid Sequence↗

PubMed2003

Toxicological aspects of Kampo medicines in clinical use.

Among 210 medicinal prescriptions used in present-day Japan, the clinical uses and the acute, chronic and mutagenic toxicity study of 16 Kampo (Japanese herbal) medicines are summarized. These Kampo medicines are classified into two categories; eight prescriptions containing Bupleurum root (Bupleurum falcatum L.) such as Sho-saiko-to and Saiko-keishi-to, and eight prescriptions not containing Bupleurum root such as Juzen-taiho-to and Ninjin-yoei-to. Studies of some potential interaction between herbal medicine and western drugs are also described.

Animals↗

PubMed2003

Use of human liver S9 in the Ames test: assay of three procarcinogens using human S9 derived from multiple donors.

The purpose of the present study was to examine the inter-individual variation in the mutagenicity of chemicals using a variety of human S9 fractions. For this purpose, three procarcinogens, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), benzo[a]pyrene (BP), and dimethylnitrosamine (DMN), were selected for the Ames test and their mutagenicity was examined using human liver S9 fractions prepared from 18 different donors and one pooled liver S9 fraction prepared from 15 different donors. In addition, rat S9 fraction prepared from male rats pretreated with phenobarbital and 5,6-benzoflavone (PB/BF) was used as reference in order to examine the mutagenic differences between human and rat (PB/BF) S9 fractions. The data demonstrate a large inter-individual diversity in the mutagenic response to procarcinogens. The mutagenicity of IQ and BP in the presence of a human liver S9 fraction (lot HLS-014) was equal to that observed in the presence of rat (PB/BF) S9 fraction. The mutagenicity of IQ and BP in the presence of a pooled human liver S9 fraction was lower (90 and 95%, respectively) than that observed in the presence of rat (PB/BF) S9. On the contrary, the mutagenicity of DMN in the presence of either a selected human liver S9 fraction (lot HLS-014) or pooled fraction was 8-fold higher than that found in the presence of rat (PB/BF) S9 fraction. Human liver S9 fraction (lot HLS-014) had one of the highest cytochrome P450 enzyme activities among the 18 different donors and higher than the pooled human liver S9 fraction. These results suggest that the use of both selected human liver S9 fractions with high metabolic activity (e.g., lot HLS-014 as used in this study) and a pooled S9 fraction with moderate metabolic activity could be used as a means to evaluate the inter-individual variability in mutagenic response to chemicals and to confirm positive responses from studies completed with rodent S9.

Adult↗

PubMed2003

Tissue distribution of mRNA expression of human cytochrome P450 isoforms assessed by high-sensitivity real-time reverse transcription PCR.

Pairs of forward and reverse primers and TaqMan probes specific to each human cytochrome P450 isoform were prepared. Analysis of the mRNA level of each CYP isoform in total RNA from pooled specimens of various human organs was performed by real-time reverse transcription PCR using an ABI PRISM 7700 sequence detector system. The expression of CYP3A4 mRNA was similar to that of CYP3A7 mRNA in the fetal liver, and CYP3A4 mRNA levels in the fetal liver were about 0.1 times lower than in the adult liver. CYP2E1 showed the highest level of mRNA expression in the liver. The mRNA expression of 30 CYP isoforms (CYP1A1, 1A2, 1B1, 2A6, 2A7, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 2J2, 3A4, 3A5, 3A7, 4A11, 4F2, 4F3, 5A1, 7B1, 8A1, 8B1, 17, 26A1, 27, 27B1, 39A1, 46, and 51) in the liver was successfully detected by this method. CYP2F1, 4B1, 4F8, 11s (11A, 11B1, and 11B2), 19, and 24 mRNA levels were the highest in the lung, lung, prostate, adrenal gland, placenta, and kidney, respectively; however, the mRNA expression of these eight CYP isoforms in the liver was not detected by this method. The mRNA levels of the CYP isoforms determined in various human tissues were in good agreement with previously reported data. The method described here has the advantages of high specificity and excellent quantification over a wide range of mRNA concentrations, making it suitable for the evaluation of a large number of samples in the assessment of the expression profile of drug-metabolizing enzymes.

Cytochrome P-450 Enzyme System↗

PubMed2003

[Sudden increase in bispectral index during propofol anesthesia in three patients].

We report 3 patients who developed a sudden unpredicted increase in bispectral index (BIS) value during propofol and fentanyl anesthesia. The patients were induced with propofol 2-mg.kg-1 and fentanyl 2-micrograms.kg-1 and muscle relaxation was obtained by vecuronium 0.12-mg.kg-1. During induction of anesthesia, BIS value went down to below 50 in all three cases, and anesthesia was maintained by continuous infusion of propofol at a rate of 5 mg.kg-1.hr-1 and intermittent administration of fentanyl. Forty to sixty min after starting the operation, BIS value increased suddenly (up to 80) and the body movement of the patients was observed. The serum concentration of propofol was approximately 2.5 micrograms.ml-1. All patients were successfully treated with increasing the infusion rate of propofol and additional administration of fentanyl. No clear recall or explicit memory during operation was observed after anesthesia, but, anesthesiologists might have to pay more attention to unpredictable changes of anesthetic depth during propofol anesthesia using target controlled infusion.

Adult↗

PubMed2003

[Determination of cotinine in human urine by gas chromatograph-mass spectrometry].

A gas chromatograph-mass spectrometric assay has been developed for the quantitation of cotinine, the major metabolite of nicotine, in human urine. Extraction or condensing procedure was not required and the method reduced time involved in sample preparation. The analytes were separated on the fused-silica capillary column. The operating conditions were: injector, 250 degrees C; detector, 280 degrees C; column, 50-250 degrees C. The total gas flow-rate of helium (carrier) was 50 ml.min-1 and the pressure of column inlet was 100-200 kPa. The retention time was 18.1 min and the limit of quantitation was 5 ng.ml-1. This method provides an easy and simple assay for the detection of cotinine in clinical settings.

Adolescent↗

PubMed2002

Complementary DNA cloning and characterization of cytochrome P450 2D29 from Japanese monkey liver.

A cDNA was cloned from Japanese monkey liver mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR) using oligonucleotide primers based on the marmoset cytochrome P450 2D19 (CYP2D19) nucleotide sequence. The full-length cDNA encoded a 497 amino acid protein (designated CYP2D29) that is 96, 91, and 88% homologous to human CYP2D6, cynomolgus monkey CYP2D17, and marmoset monkey CYP2D19, respectively. Yeast cells (Saccharomyces cerevisiae AH-22 strain) transfected with pGYR1 vectors containing the CYP2D29 cDNA were cultured, and microsomal fractions were obtained. Reduced carbon monoxide-difference spectra and western blot analysis using polyclonal antibodies raised against rat CYP2D2 demonstrated that in yeast cell microsomal fractions, the level of CYP2D29 holoenzyme was similar to that of CYP2D6 holoenzyme. However, western blot analysis indicated that the level of CYP2D29 in Japanese monkey liver microsomes might be much higher than that of CYP2D6 in human liver microsomes. Japanese monkey liver microsomes exhibited much higher activities than did human liver microsomes, expressed as nmol/min/mg protein, for debrisoquine (DB) 4-hydroxylation and bufuralol (BF) 1"-hydroxylation (typical reactions catalyzed by CYP2D6), whereas recombinant CYP2D29 activity, expressed as nmol/min/nmol CYP, was similar to that of CYP2D6 for DB and BF hydroxylation. In kinetic analyses, the K(m) value of CYP2D29 for DB 4-hydroxylation was much lower than that of Japanese monkey liver microsomes, whereas the K(m) value of CYP2D6 for DB 4-hydroxylation was similar to that of human liver microsomes. In contrast, K(m) values for BF 1"-hydroxylation were similar for Japanese monkey and human liver microsomes and yeast cell microsomal fractions expressing recombinant CYP2D29 or CYP2D6. These results suggest that the properties of Japanese monkey CYP2D29 are similar to those of human CYP2D6, but their populations and/or some other factors in liver microsomes may cause the difference in microsomal DB 4-hydroxylase activities between Japanese monkeys and humans.

Amino Acid Sequence↗

PubMed2002

Halothane enhances acetylcholine release by decreasing dopaminergic activity in rat striatal slices.

The present study investigated the effect of halothane on acetylcholine (ACh) and dopamine (DA) release from the rat striatum. Halothane decreased DA release in a concentration-dependent manner, while increased ACh release. In our previous investigation, a volatile anesthetic, halothane, inhibited DA release from the rat striatal slices in a concentration-dependent manner. Although the release of ACh from cholinergic interneurons is tonically modulated by DA in the striatum, the effect of halothane on the relationship between the release of ACh and DA has not been discussed. Using double-labeled techniques, we investigated the effect of halothane on ACh and DA release simultaneously. The slices were incubated with [14C]-choline and [3H]-DA and superfused with modified Krebs solution containing 1 microM of hemicholinium-3. We applied electrical field stimulation (2 Hz, 240 shocks), and the amount of the release of radioactivity evoked by stimulation was calculated by subtraction of the basal radioactive outflow from the total outflow at the beginning of the respective stimulation periods. The effects of drugs on the release were expressed as the ratio of stimulation-evoked fractional releases (FR), measured in the presence and absence (FRS2/FRS1) of the drug. Halothane decreased DA release in a concentration-dependent manner (FRS2/FRS1=0.767+/-0.021, 0.715+/-0.026, 0.671+/-0.014 and 0.639+/-0.033 at the concentration of 0, 0.5, 2 and 4%, respectively), while ACh release showed a biphasic change in the presence of different concentrations of halothane. The release of ACh was significantly increased at the concentration of 2%, but not at 0.5 or 4%. Halothane failed to increase the release of ACh in striatal slices after lesion by 6-OH-dopamine. The application of amphetamine reduced the release of ACh and abolished the effect of halothane. These results indicate that the effect of halothane on ACh release is indirect: it increases the release by attenuating the inhibitory effect of DA released from the nigro-striatal pathway. The nonsynaptic interaction between DA and ACh release is involved in the effect of halothane on ACh release.

Acetylcholine↗

PubMed2002

Oral clonidine premedication reduces the awakening concentration of propofol.

UNLABELLED: To investigate the effects of oral clonidine premedication on emergence from propofol/fentanyl anesthesia, we studied 72 healthy male patients who were undergoing elective orthopedic surgery: the Control group, the 2.5 microg/kg Clonidine group, and the 5.0 microg/kg Clonidine group (n = 24 each). Nothing was administered to the Control group. Clonidine (2.5 or 5.0 microg/kg) was orally administered 90 min before the induction of anesthesia in the Clonidine groups. Patients were anesthetized with computer-assisted continuous infusion of propofol and fentanyl, with the three groups receiving the same concentrations of propofol (3 microg/mL) and fentanyl (1 ng/mL) starting 20 to 30 min before the end of surgery. Propofol infusion was then abruptly discontinued at the end of surgery in all patients. After propofol was discontinued, the response to verbal commands was evaluated every 30 s, and arterial blood samples for propofol and clonidine concentrations were taken when the patients opened their eyes. The time required to respond to a verbal command was 14.9 plus/minus 8.3 min for the 5.0 microg/kg Clonidine group, and this was significantly longer than the Control (8.2 plus/minus 5.0 min) and the 2.5 microg/kg Clonidine (9.0 plus/minus 3.7 min) groups (P < 0.01). Serum propofol concentration at awakening in the 5.0 microg/kg Clonidine group was 1.0 plus/minus 0.4 microg/mL, which was significantly smaller than the Control (1.6 plus/minus 0.4 microg/mL) and the 2.5 microg/kg Clonidine (1.4 plus/minus 0.3 microg/mL) groups (P < 0.01). The blood clonidine concentration was associated with a decrease in the awakening propofol concentration. In conclusion, 5 microg/kg oral clonidine premedication decreases the awakening propofol concentration and delays arousal from propofol/fentanyl anesthesia. IMPLICATIONS: Preanesthetic medication with 5 microg/kg oral clonidine, but not 2.5 microg/kg clonidine, is associated with prolonged recovery from propofol/fentanyl anesthesia.

Administration, Oral↗

PubMed2002

The interaction between propofol and clonidine for loss of consciousness.

UNLABELLED: Clonidine premedication reduces the intraoperative requirement for opioids and volatile anesthetics. Clonidine also reduces the induction dose of IV anesthetics. There is no information, however, regarding the effect of oral clonidine premedication on the propofol blood concentrations required for loss of consciousness, and the interaction between propofol and clonidine. We randomly administered target effect-site concentrations of propofol ranging from 0.5 to 5. 0 microg/mL by using computer-assisted target-controlled infusion to 3 groups of healthy male patients: Control (n = 35), 2.5 microg/kg Clonidine (n = 36), and 5.0 microg/kg Clonidine (n = 36) groups. Nothing was administered to the Control group. Clonidine (2.5 or 5.0 microg/kg) was administered orally 90 min before the induction of anesthesia in the Clonidine groups. After equilibration between the blood and effect-site for 15 min, a verbal command to open their eyes was given two times to the patients. Arterial blood samples for analysis of the serum propofol and clonidine concentrations were taken immediately before verbal commands were given. Measured serum propofol concentrations in equilibrium with the effect-site at which 50% of the patients did not respond to verbal commands (EC50 for loss of consciousness) were determined by logistic regression. The EC50 +/- SE values in the Control, 2.5 microg/kg Clonidine, and 5.0 microg/kg Clonidine groups were 2.67 +/- 0.18, 1.31 +/- 0.12, and 0.91 +/- 0.13 microg/mL, respectively. The EC50 in the 2.5 and 5.0 microg/kg clonidine groups was significantly smaller than that in the Control group (P < 0.001). The use of a response surface modeling analysis indicated that there was an additive interaction between measured arterial propofol and clonidine concentrations in relation to loss of consciousness. These results indicate that propofol and clonidine act additively for loss of consciousness. IMPLICATIONS: Oral clonidine 2.5 and 5.0 microg/kg premedication decreases the propofol concentration required for loss of consciousness.

Administration, Oral↗

PubMed2002

Current progress on esterases: from molecular structure to function.

This article reports on a symposium sponsored by the American Society for Pharmacology and Experimental Therapeutics and held at the April 2001 Experimental Biology meeting. Current developments in molecular-based studies into the structure and function of cholinesterases, carboxylesterases, and paraoxonases are described. This article covers mechanisms of regulation of gene expression of the various esterases by developmental factors and xenobiotics, as well as the interplay between physiological and chemical regulation of enzyme activity.

Animals↗

PubMed2002

Stereoselective metabolism of bufuralol racemate and enantiomers in human liver microsomes.

A new HPLC method was developed using a chiral column to efficiently separate four 1"-hydroxybufuralol (1"-OH-BF) diastereomers that are major metabolites of bufuralol (BF). Employing this method, we examined diastereomer selectivity in the formation of 1"-OH-BF from BF racemate or enantiomers in four individual samples of human liver microsomes. Three different human liver microsomes showed a selectivity of 1"R-OH < 1"S-OH for BF enantiomers, which was similar to that of recombinant CYP2D6 expressed in insect cell microsomes, whereas one human liver microsomal fraction yielded a selectivity of 1"R-OH > 1"S-OH for BF enantiomers, which was similar to those of recombinant CYP2C19 expressed in insect cell microsomes. Recombinant CYP1A2 and CYP3A4 showed a selectivity similar to that of CYP2D6, but their BF 1"-hydroxylase activities were much lower than those of CYP2D6. In inhibition studies, quinidine, a known CYP2D6 inhibitor, markedly inhibited BF 1"-hydroxylation in the fractions of human liver microsomes that showed the CYP2D6-type selectivity. Furthermore, omeprazole, a known CYP2C19 inhibitor, efficiently suppressed the formation of 1"-OH-BF diastereomers from BF in the microsomal fraction that showed the CYP2C19-type selectivity. From these results, we concluded that the diastereomer selectivity in the formation of 1"-OH-BF from BF differs between CYP2D6 and CYP2C19, both of which can be determinant enzymes in the diastereoselective 1"-hydroxylation of BF in human liver microsomes.

Adult↗

PubMed2002

[The effect of normobaric oxygen inhalation and halothane anesthesia on the level of interstitial striatal dopamine of rats using in vivo microdialysis study].

We investigated the effect of normobaric oxygen inhalation on the level of interstitial dopamine and its metabolites in in vivo brain striatum of awake, free moving rats using microdialysis techniques. Rats were implanted a microdialysis probe to the right striatum of the brain and administered pure oxygen for 1 hour, and dialysates from the probe were examined every 20 minutes by HPLC. Normobaric oxygen inhalation reduced the amount of dopamine derived from the dialysate and increased that of metabolites. Halothane anesthesia with oxygen showed a slight effect on the changes induced by oxygen inhalation, whereas halothane significantly increased the level of dopamine metabolites. Pretreatment with glutathione failed to prevent increase of dopamine metabolites. We hypothesized that oxygen inhalation and halothane anesthesia might increase the level of dopamine metabolites in different mechanisms, and the changes induced by oxygen inhalation might not be the result of simple oxidative stress in rat striatum.

Administration, Inhalation↗

PubMed2002

[Repeated coronary artery spasm under general anesthesia].

A 52-year-old man without history of angina pectoris underwent emergent abdominal surgery for acute abdomen. General anesthesia was maintained with isoflurane, nitrous oxide and fentanyl. The depth of anesthesia during surgery was considered adequate for the stimuli, but the patient developed ECG abnormality repeatedly finally followed by short run. After anesthesia, we re-examined the recorded ECG and coronary spasm was strongly suspected. Fatal arrhythmia might be avoidable if the prior abnormality in ECG is properly assessed.

Abdomen, Acute↗

PubMed2002

[A simple method for determination of flurbiprofen in human plasma by gas chromatography-mass spectrometry].

A method for gas chromatograph-mass spectrometric assay has been developed for the quantitation of flurbiprofen in human plasma. Extraction or condensing procedure was not required and the method reduced time involved in sample preparation. The analytes were separated on the fused-silica capillary column. The operating conditions were: injector, 250 degrees C; detector, 300 degrees C; and column, 50-280 degrees C. The total gas flow-rate of helium (carrier) was 50 ml.min-1 and the pressure of column inlet was 100-200 kPa. The retention time was 18.1 min and the limit of quantitation was 0.5 microgram.ml-1. This method provides an easy and simple method for the detection of flurbiprofen.

Flurbiprofen↗

PubMed2002

[Intubation in a patient with lingual tonsil hypertrophy using an intubating laryngeal mask airway in combination with fiberoptic intubation].

A 66-yr-old man was scheduled for colon resection under general anesthesia. There were no findings suggesting difficulty of airway management. After induction of anesthesia, manual ventilation via a facemask was suboptimal, but increased fresh gas flow improved it. At direct laryngoscopy after achieving muscular relaxation, the arytenoids and epiglottis could not be seen even by an expert anesthesiologist. Intubating laryngeal mask airway (ILMA) was inserted to patient's larynx and ventilation could be continued. Tracheal intubation through ILMA was impossible because of hard resistance for inserting the endotracheal tube. Fiberoptic bronchoscopy revealed that the hypertrophied lingual tonsil obstructed the aperture of ILMA. Several attempts were made for intubation using fiberoptic tracheal intubation technique through ILMA and finally the patient's trachea was intubated without any bleeding or swelling of laryngeal tissues. The effectiveness of ILMA for the patient with lingual tonsil hypertrophy is still unknown, but the insertion of ILMA might be considered for safe airway management in combination with a fiberscope.

Aged↗

PubMed2002

[The changes of bispectral index induced by administration of midazolam during propofol anesthesia].

The effect of the additional administration of midazolam or flumazenil on bispectral index (BIS) during propofol anesthesia was investigated in 22 scheduled surgical patients. Midazolam 10 or 30 micrograms.kg-1, or flumazenil 6 or 12 micrograms.kg-1 was injected to the patients to evaluate their effect on BIS after achieving steady state of hypnosis more than 1 hr of propofol anesthesia with 5 mg.kg-1.hr-1. The only midazolam 30 micrograms.kg-1 significantly reduced BIS value from 47.8 +/- 8.6 to 36.8 +/- 6.5. The synergistic interaction between midazolam and propofol assessed by BIS might be less clear than that assessed by hypnotic dose of propofol using psychopharmacological investigation.

Adjuvants, Anesthesia↗

PubMed2002

[The effectiveness of perioperative intravenous flurbiprofen in minor ear, neck and nose surgery].

To evaluate the effect of perioperative intravenous administration of flurbiprofen, a nonsteroidal anti-inflammatory drug, on the postoperative pain after minor ear, neck and nose surgery, eighty patients were randomly allocated into three groups. Control group of 40 patients, received a placebo. The second group (n = 20) received 1 mg.kg-1 flurbiprofen i.v. at the end of surgery, and the third group (n = 20) received the same dose of flurbiprofen before the start of surgery. The ratio of the patients and the time for requirement of analgesics after the operation and the serum concentration of flurbiprofen were assessed. The ratio of the patients who required analgesics was higher in control group (0.45, 0.35 and 0.10 in each group). The time without analgesics was longer in pre-treatment group. The serum concentration of flurbiprofen decreased in pre-treatment group at the end of surgery, but the effectiveness of flurbiprofen on postoperative pain might be more apparent in pre-treatment group. Administration of flurbiprofen before the start of surgery is more effective for peri-operative analgesia in minor ear, neck and nose surgery.

Adult↗