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T Kumazawa

Publications and source records attributed to T Kumazawa.

At least 55 records · Page 3Linked to original sources
PubMed2000

Synthesis of tricyclic compounds as steroid 5alpha-reductase inhibitors.

A series of 4-phenoxybutyric acid derivatives attached to a tricyclic skeleton were prepared and evaluated as 5alpha-reductase inhibitors. Structure activity relationships for these compounds in terms of rat epididymis (type 2) 5alpha-reductase inhibitory activities reveal that 1) the substitution pattern at the 11-position of dibenz[b,e]oxepin influenced potency, 2) higher lipophilicity of the tricyclic skeleton improved potency, whereas the existence of a basic nitrogen atom in this skeleton was detrimental to potency, and 3) isobutyl substitution at the 8 positon of the azepine skeleton was tolerated. Among the tricyclic compounds studied, 4-[3-[5-benzyl-8-(2-methyl)propyl-10,11-dihydrodibenz[b,f]azepine- 2-carboxamido]phenoxy]butyric acid (26) was the most potent inhibitor of rat type 2 5alpha-reductase at 0.1 microM.

5-alpha Reductase Inhibitors↗
PubMed2000

Effects of prestimulus respiratory levels on inhibitory respiratory response by nociceptive muscular afferents.

We have previously shown that the inhibitory respiratory response, which we call post-stimulus suppression, is induced by nociceptive muscular afferents. This phenomenon is thought to be caused by a negative feedback induced by excessive afferent inputs. In the present study, we investigated whether augmented levels of prestimulus respiration would influence the magnitude of poststimulus suppression by recording the phrenic nerve discharges in chloralose-urethane anesthetized, vagotomized, paralyzed and artificially ventilated cats. The respiratory level was augmented by means of either hypercapnia, hypoxia or naloxone administration, all of which markedly facilitated the peak amplitude (PK) of integrated phrenic discharges, neural tidal volume. When the electrical stimulation of thin-fiber muscular afferents was performed at these augmented PK levels, the magnitude of poststimulus suppression in the PK was markedly attenuated without consistently altering the facilitatory response during the stimulation period. It seems that the facilitatory component of the augmented level of resting respiration may reduce the inhibitory component of poststimulus suppression. The results indicate that prestimulus respiratory activity is an important factor in determining the magnitude of poststimulus suppression.

Animals↗
PubMed2000

Morphine inhibits resting respiration, but it attenuates reflexive respiratory suppression in anesthetized cat through kappa-receptor.

Noxious stimulation of thin-fiber muscular afferents induces a reflexive respiratory suppression that we call "poststimulus respiratory suppression." In anesthetized, vagotomized, paralyzed, and artificially ventilated cats, morphine depressed the level of resting respiration (inhibitory effect on resting respiration) and attenuated the magnitude of the poststimulus respiratory suppression (excitatory effect on the reflexively modified respiration). These two kinds of morphine effects were antagonized by naloxone, suggesting the participation of opioid receptors. To clarify the opioid receptor subtypes responsible for these effects of morphine, three type-selective opioid antagonists-naltrindole (delta antagonist), gamma-funaltrexamine (mu antagonist), and Mr2266 (kappa antagonist)-were tested. The morphine-induced depression in the resting respiration was antagonized by pretreatment with the kappa antagonist, not with the mu or delta antagonist. Furthermore, the morphine-induced attenuation in the magnitude of the poststimulus suppression was also blocked by the kappa antagonist, but not by the mu or delta antagonist. In conclusion, (1) morphine inhibits resting respiration, but it attenuates the magnitude of the poststimulus respiratory suppression; (2) both these morphine effects are mediated by kappa opioid receptors. The possibility that the kappa(3) receptor, one of the kappa receptors subtypes, mediates the two kinds of morphine effects has been discussed.

Analgesics, Opioid↗
PubMed2000

[Use of modified infrared aural canal thermometers during cardiac surgery].

Two kinds of modified infrared aural canal thermometers (Mimippi, Superthermo) are currently available in Japan. We therefore evaluated their accuracy and precision for clinical use. For the purpose of this investigation, we considered accuracy to be the mean difference between the test thermometers and the reference thermocouple. Precision was examined from the standard deviation of the difference between the test and reference values. We evaluated ten patients for cardiopulmonary bypass surgery under mild hypothermia (approximately 32 degrees C). Aural canal temperatures were measured in a random order with each infrared thermometer, and compared with readings from a thermocouple positioned at the contralateral tympanic membrane. Compared with the thermocouple, the Mimippi had regression slope 0.87 and correlation coefficient 0.79. In contrast, slope of the Superthermo regression was 0.74. The correlation coefficient for the Superthermo was 0.71. The accuracy (offset, or bias) was 0.91 degree C with the Mimippi. In contrast, it was 1.32 degrees C with the Superthermo. The precision (standard deviation) of the Mimippi was 0.65. In contrast, it was 0.73 degree C with the Superthermo. We conclude that both thermometers were moderately accurate and precise for perioperative use.

Body Temperature↗
PubMed2000

[Effect of pre-mixed lidocaine with propofol on propofol injection pain in elderly patients].

The purpose of this study was to compare the younger and older patients in the incidence and the severity of the pain during injection of propofol. Thirty-four, elderly patients (60-80-yr-old) and 52 patients (20-40-yr-old) scheduled to undergo elective surgery were studied. We conducted a prospective, randomized and double-blinded trial. All patients were randomly allocated to one of two groups according to the agents added to 1% propofol 20 ml; Group S, normal saline 2 ml, and Group L, 2% lidocaine 2 ml. The pain on injection was rated as none, mild, moderate, or severe. Seventy percent of patients in the S group of elderly patients experienced pain, while 22% of patients experienced pain in the L group in elderly patients. The incidence of pain on injection in the S group of older patients was comparable with S group of younger patients. The severity of pain in elderly patients was significantly decreased after premixing with lidocaine. There were no significant differences between older and younger patients in the severity of propofol injection pain in both S group and L group. In conclusion, elderly patients suffered the pain on injection of propofol with the same incidence as the younger patients did. Lidocaine premixed with propofol significantly reduces the incidence and the severity of pain associated with propofol in elderly patients.

Adult↗
PubMed1999

Analysis of methanol or formic acid in body fluids by headspace solid-phase microextraction and capillary gas chromatography.

Methanol and its metabolite formic acid have been found extractable from human whole blood and urine by headspace solid-phase microextraction (SPME) with a Carboxen/polydimethylsiloxane fiber. The headspace SPME for formic acid was carried out after derivatization to methyl formate under acidic conditions. The determinations of both compounds were made by using acetonitrile as internal standard (IS) and capillary gas chromatography (GC) with flame ionization detection. The headspace SPME-GC gave sharp peaks for methanol, methyl formate and I.S.; and low background noises for whole blood and urine samples. Extraction efficiencies were 0.25-1.05% of methanol and 0.38-0.84% formic acid for whole blood and urine. The calibration curves for methanol and formic acid showed excellent linearity in the range of 1.56 to 800 and 1.56 to 500 microg/0.5 ml of whole blood or urine, respectively. The detection limits were 0.1-0.5 microg/0.5 ml for methanol and 0.6 microg/0.5 ml for formic acid for both body fluids. The within-day relative standard deviations in terms of extraction efficiency for both compounds in whole blood and urine samples were not greater than 9.8%. By using the established SPME method, methanol and formic acid were successfully separated and determined in rat blood after oral administration of methanol.

Acetonitriles↗
PubMed1999

Identification and quantification of cardiac glycosides in blood and urine samples by HPLC/MS/MS.

Cardiac glycosides (CG) are of forensic importance because of their toxicity and the fact that very limited methods are available for identification of CG in biological samples. In this study, we have developed an identification and quantification method for digoxin, digitoxin, deslanoside, digoxigenin, and digitoxigenin by high-performance liquid chromatography tandem mass spectrometry (HPLC/MS/MS). CG formed abundant [M + NH4]+ ions and much less abundant [M + H]+ ions as observed with electrospray ionization (ESI) source and ammonium formate buffer. Under mild conditions for collision-induced dissociation (CID), each [M + NH4]+ ion fragmented to produce a dominant daughter ion, which was essential to the sensitive method of selected reaction monitoring (SRM) quantification of CG achieved in this study. SRM was compared with selected ion monitoring (SIM) regarding the effects of sample matrixes on the methodology. SRM produced lower detection limits with biological samples than SIM, while both methods produced equal detection limits with CG standards. On the basis of the HPLC/MS/MS results for CG, we have proposed some generalized points for conducting sensitive SRM measurements, in view of the property of analytes as well as instrumental conditions such as the type of HPLC/MS interface and CID parameters. Analytes of which the molecular ion can produce one abundant daughter ion with high yield under CID conditions may be sensitively measured by SRM. ESI is the most soft ionization source developed so far and can afford formation of the fragile molecular ions that are necessary for sensitive SRM detection. Mild CID conditions such as low collision energy and low pressure of collision gas favor production of an abundant daughter ion that is essential to sensitive SRM detection. This knowledge may provide some guidelines for conducting sensitive SRM measurements of very low concentrations of drugs or toxicants in biological samples.

Animals↗
PubMed1999

Use of an ion-pairing reagent for high-performance liquid chromatography-atmospheric pressure chemical ionization mass spectrometry determination of anionic anticoagulant rodenticides in body fluids.

The on-line combination of high-performance liquid chromatography with mass spectrometry (HPLC-MS) has become a powerful tool for trace analysis thanks to the developments in interface techniques. However, non-volatile salts such as ion-pairing reagents are considered to be incompatible with HPLC-MS systems; they cause drops in analyte signals because of contamination of mass analyzers and also because of blocking of the capillary transferring ions from atmospheric pressure to the vacuum manifold. In this work, a new type of ion-pairing reagent, di-n-butylammonium acetate (DBA), was evaluated for use in HPLC-MS. DBA did not cause these problems to HPLC-MS systems; a possible explanation might be that DBA decomposed to volatile compounds under APCI conditions. In addition, DBA was very useful for obtaining sharp peaks, which resulted in high sensitivity. With this ion-pairing reagent, we developed a procedure for the measurement of five (including internal standard) anticoagulant rodenticides in whole blood and urine samples by SIM detection of [M-H]- ions. Calibration range, recoveries and precision of the method were examined; detection limits as low as 1-5 ng/ml blood sample or 0.5-2.5 ng/ml urine sample were achieved.

Animals↗
PubMed1999

Ultra-sensitive method for determination of ethanol in whole blood by headspace capillary gas chromatography with cryogenic oven trapping.

We have established an ultra-sensitive method for determination of ethanol in whole blood by headspace capillary gas chromatography (GC) with cryogenic oven trapping. After heating a blood sample containing ethanol and isobutyl alcohol (internal standard, IS) in a 7.0-ml vial at 55 degrees C for 15 min, 5 ml of the headspace vapor was drawn into a glass syringe and injected into a GC port. All vapor was introduced into an Rtx-BAC2 wide-bore capillary column in the splitless mode at -60 degrees C oven temperature to trap entire analytes, and then the oven temperature was programmed up to 240 degrees C for GC measurements with flame ionization detection. The present method gave sharp peaks of ethanol and IS, and low background noise for whole blood samples. The mean partition into the gaseous phase for ethanol and IS was 3.06+/-0.733 and 8.33+/-2.19%, respectively. The calibration curves showed linearity in the range 0.02-5.0 microg/ml whole blood. The detection limit was estimated to be 0.01 microg/ml. The coefficients of intra-day and inter-day variation for spiked ethanol were 8.72 and 9.47%, respectively. Because of the extremely high sensitivity, we could measure low levels of endogenous ethanol in whole blood of subjects without drinking. The concentration of endogenous ethanol measured for 10 subjects under uncontrolled conditions varied from 0 to 0.377 microg/ml (mean, 0.180 microg/ml). Data on the diurnal changes of endogenous ethanol in whole blood of five subjects under strict food control are also presented; they are in accordance with the idea that endogenous blood ethanol is of enteric bacterial origin.

Calibration↗
PubMed1999

High performance liquid chromatography/electrospray tandem mass spectrometry for phenothiazines with heavy side chains in whole blood.

Eleven phenothiazine derivatives with heavy side chains contained in human whole blood have been analyzed by high-performance liquid chromatography (HPLC)/electrospray (ES) tandem mass spectrometry (MS). All compounds gave the base peaks due to [M + 1](+) by HPLC/ES single MS. The product ions formed from each quasi-molecular ion by HPLC/ES tandem MS showed the base peaks due to side chains liberated. The mass chromatography of HPLC/ES tandem MS showed much higher sensitivity than that of HPLC/ES single MS for phenothiazines spiked to whole blood. Therefore, regression equations, detection limits, recovery rates and reproducibility were studied for thiethylperazine, clospirazine and flupentixol spiked to human whole blood by means of mass chromatography of HPLC/ES tandem MS. The three compounds showed good linearity in the range of 2-40 ng/mL with a detection limit of about 0.5 ng/mL. Recoveries of the three compounds spiked to whole blood (2 and 8 ng added to 1 mL whole blood) were 43.4-72.5 %; the coefficients of intraday and interday variations were 3.7-9.3 and 12.6-17.9 %, respectively. Thiethylperazine, clospirazine and flupentixol in whole blood could actually be determined with sufficient sensitivity 3 and 6 h after oral administration of 5-10 mg of each compound in a volunteer.

Administration, Oral↗
PubMed1999

Hydroxyl radical formation during inhalation anesthesia in the reperfused working rat heart.

PURPOSE: To determine whether isoflurane, sevoflurane and halothane influenced hydroxyl radical production in the ischemic rat heart. METHODS: Twenty-four male Wistar rats were divided into four groups; control (C), isoflurane 1.4% (I), sevoflurane 2.5% (S) and halothane 1% (H). The hearts were perfused with modified Krebs-Henseleit bicarbonate buffer by a working heart model for 10 min. Then, whole heart ischemia was induced by severely restricting coronary perfusion for 15 min. Reperfusion of the hearts after this ischemic period lasted for 20 min. The coronary effluent was collected before and during ischemia and at 1, 5, 10, 20 min after reperfusion. At the end of reperfusion, hearts were removed and prepared for measurement. Hydroxyl radicals were identified by their reaction with salicylic acid to yield dihydroxybenzoic acids (DHBAs). RESULTS: Before and after ischemia, there were no differences in coronary flow and heart rate among the four groups, but cardiac output and LV dP/dt maximum in the anesthetic groups were lower than in the control group. Hydroxyl radical products in the heart were significantly lower in the I group than the other groups (e.g. C vs I, 278.1 +/- 24.3 vs 219.3 +/- 14.4 microM x g(-1), P < 0.05). The concentrations of DHBAs in the coronary effluent at some points in the I and H groups were less than in the C and S groups. CONCLUSION: These results indicate that isoflurane and halothane (to a lesser extent), reduce hydroxyl radical production in the ischemic heart, but sevoflurane does not.

Anesthetics, Inhalation↗
PubMed1999

Effects of melatonin and superoxide dismutase on free radical formation in the postischemic reperfused heart.

PURPOSE: Melatonin has been reported to protect against oxygen free radicals. We investigated whether melatonin or superoxide dismutase (SOD) would decrease hydroxyl radical concentration in the postischemic reperfused heart. METHODS: An isolated rat heart-lung preparation was used. Eighty-one male Wistar rats were allocated into control (no drug), S1 (SOD 400 U.ml(-1)), S2 (SOD 2000 U.ml(-1)), M1 (melatonin 0.1 microg.ml(-1)), M2 (melatonin 1.0 microg.ml(-1)), M3 (melatonin 10 microg.ml(-1)), SM (SOD 400 U.ml(-1) and melatonin 1.0 microg.ml(-1)) groups. The heart was perfused initially at the cardiac output of 30 ml.min(-1) and the mean arterial pressure of 70 mmHg. Drugs were administered into the reservoir 7 min after the start of perfusion. Ten minutes after the start of perfusion, the heart was rendered globally ischemic for 10 min by reducing the preload and afterload to zero and then reperfused for 10 min. At the end of reperfusion, the heart was freeze-dried for 6 days. The perfusate blood was collected just before and after ischemia and at the end of reperfusion. The formation of hydroxyl radicals in perfusate blood and heart was measured with high-performance liquid chromatography using salicylic acid. Hydroxyl radicals react with salicylic acid, yielding 2,3-, 2,4-, 2,5-, and 3,4-dihydroxybenzoic acid (DHBA). RESULTS: Before and after ischemia, there were no significant differences among the groups in cardiac output, systolic pressure, heart rate, and right atrial pressure. The concentrations of DHBAs in the perfusate blood and heart after ischemia and reperfusion in all groups were significantly higher than those before ischemia. DHBAs in the heart of all drug-administered groups were significantly lower than those in the control group. In the perfusate blood, DHBAs in the S2 group were significantly lower than those in the control group. CONCLUSIONS: SOD and melatonin decrease hydroxyl radical concentration in the postischemic reperfused heart.

Journal Article↗
PubMed1999

Schizophrenia, monoamine oxidase activity, and cigarette smoking.

Reduced monoamine oxidase activity has been proposed as a marker for vulnerability to schizophrenia. Reduced monamine oxidase activity has also been shown to occur in cigarette smokers. This study compared monamine oxidase activity level in a matched group of patients with schizophrenia who smoked with a group who did not. Lower levels of monoamine oxidase activity were found in the smokers and this is the likely explanation for the low levels hypothesized as a marker for schizophrenia.

Adult↗
PubMed1999

Large-scale preparation of high-molecular weight DNA from buccal mucosa.

Four non-invasive methods of sampling DNA from buccal mucosa, simple rinses, scrubbing with cotton balls, scrubbing with toothbrushes and rinses after scrubbing with toothbrushes, were investigated. Scrubbing with toothbrushes yielded 5.79 +/- 5.56 microg of DNA rich in high-molecules, while less than one eighth the amount was recovered by scrubbing with cotton balls. Rinses after scrubbing with toothbrushes gave 50.0 +/- 46.0 microg of DNA and simple rinses 34.4 +/- 35.7 microg, although the DNA was considerably degraded. DNA specimens obtained from buccal cells were shown to be more or less in the process of degradation including apoptosis. For minisatellite analysis, only DNA prepared by scrubbing with toothbrushes could be used, while all specimens could be applied to PCR analyses. Since scrubbing with toothbrushes is painless and harmless, we recommend this method. Subsequent rinsing will yield a large amount of DNA suitable for many PCR analyses.

Journal Article↗
PubMed1999

Improved extraction of thinner components from human body fluids by headspace solid-phase microextraction with a Carboxen/polydimethylsiloxane-coated fiber.

An improved method for extraction of thinner components in human whole blood and urine samples by headspace solid-phase microextraction (SPME) with a Carboxen/polydimethylsiloxane-coated fiber is presented. The body fluid samples, containing ethyl acetate, benzene, 1-butanol, toluene, butyl acetate, isoamyl acetate and ethylbenzene as internal standard (IS), were heated at 70 degrees C in a silicone-rubber septum-capped vial in the presence of distilled water plus NaCl; a Carboxen/polydimethylsiloxane-coated SPME fiber was then exposed to the headspace of the vial to allow adsorption of the compounds before capillary gas chromatography (GC) with flame-ionization detection. For whole blood, extraction efficiencies of 1-butanol, ethyl acetate and isoamyl acetate were 8.72-31.1%, and those of IS, butyl acetate, toluene and benzene were 42.9-74.1%. For urine, those of all compounds were 10.7-75.4%. The regression equations for six thinner components extracted from whole blood and urine were linear in the range of 3-500 ng/0.5 ml for ethyl acetate and 1-butanol, and 0.5-500 ng/0.5 ml for benzene, toluene, butyl acetate and isoamyl acetate. The detection limits for each of the components were 0.25-1.5 ng/0.5 ml for both samples. The coefficients of within-day and day-to-day variation for all components were satisfactory and not greater than 11 and 13%, respectively. The data obtained from actual determination of ethyl acetate, benzene and toluene in rat whole blood and urine after inhalation of the compounds were also presented.

Journal Article↗
PubMed1999

Extraction of chloroform and methylene chloride in human whole blood and urine by headspace solid phase microextraction (SPME).

Chloroform and methylene chloride were extracted from human whole blood and urine by headspace solid phase microextraction (SPME) using a Carboxen/polydimethylsiloxane (Carboxen/PDMS) fibre before capillary gas chromatography (GC)/flame ionization detection (FID). Whole blood or urine was placed in a vial and mixed with distilled water. The vial was heated at 30 degrees C, and the solvents were extracted from the headspace by SPME. The extraction efficiencies of chloroform and methylene chloride from whole blood were 40.3% and 35.8%, respectively; those for urine were 57.0% and 43.6%, respectively. The calibration curves for chloroform were linear in the range of 1-8 micrograms/ml for blood and urine samples, and those for methylene chloride in the range of 0.5-8 micrograms/ml. The detection limits for both compounds were 0.3 microgram/ml for whole blood and 0.2 microgram/ml for urine. The headspace SPME with Carboxen/PDMS fibre coupled with GC/FID seems useful for analyses of chloroform and methylene chloride in forensic toxicology and environmental chemistry.

Blood Chemical Analysis↗