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Biomedical subjects

T Kumazawa

Publications and source records attributed to T Kumazawa.

At least 37 records · Page 2Linked to original sources

Effects of propofol on ischemia and reperfusion in the isolated rat heart compared with thiamylal.

The aim of the present study was to investigate whether clinical doses of propofol and thiamylal affect oxygen free radical production and intracellular calcium concentration ([Ca2+]i) in the post-ischemic reperfused heart. Forty-eight rat hearts were perfused with a Langendorff system and loaded with Fura-2 / AM as a [Ca2+]i marker. The hearts were divided into 6 groups as follows (each group: n = 8); Group S (saline), Group TL (thiamylal 100 microM), Group TH (thiamylal 300 microM), Group I (Intralipid), Group PL (propofol 3 microM), and Group PH (propofol 10 microM). All hearts were initially perfused for 5 min as control aerobic perfusion. Afterwards, no-flow ischemia was induced for 15 min, followed by reperfusion for 20 min. The formation of hydroxyl radicals in the coronary effluent was measured with high performance liquid chromatography using salicylic acid. At the beginning of the ischemia and reperfusion periods, increases in systolic and diastolic [Ca2+]i were observed in all groups except Group TH. The high dose of thiamylal significantly suppressed this initial increase in cytosolic [Ca2+]i (Group S 1.30+/-0.15; Group TL 0.99+/-0.17; Group TH 0.70+/-0.09, at 1 min after reperfusion; systolic [Ca2+]i : p < 0.05). Total DHBAs in the coronary effluent of all groups increased significantly 1 min after reperfusion, however, there were no significant differences among the groups. Clinical doses of propofol had no significant effect on myocardial function and [Ca2+]i before and after ischemia, whereas thiamylal suppressed the increase in [Ca2+]i during ischemia and reperfusion. However, free radical formation during reperfusion was unaffected by thiamylal and propofol.

Analysis of Variance↗

[Anesthetic management for mitral valve replacement in a patient with idiopathic hypereosinophilic syndrome].

We have experienced anesthetic management for mitral valve replacement in a 48-year-old female with idiopathic hypereosinophilic syndrome. Preoperative examination showed mild biventricular dysfunction. Anesthesia was induced and maintained with meticulous administration of fentanyl and midazolam in 66% oxygen. Administration of dopamine, dobutamine and prostaglandin E1 contributed to reducing afterload and maintaining cardiac output. The operative and postoperative courses were uneventful. Hypereosinophilic syndrome is one of the identified causes of restrictive cardiomyopathy. Anesthesia for patients with hypereosinophilic syndrome must be carried out carefully, because heart or respiratory failure is the most dangerous complication. In patients with hypereosinophilic syndrome requiring general anesthesia, perioperative steroid cover is advisable. This may reduce or prevent serious lung complications.

Anesthesia, General↗

[The influence of N-nitro-L-arginine methyl ester (L-NAME) on hydroxyl free radical formation in the post-ischemic reperfused heart of anesthetized rats].

N-nitro-L-arginine methyl ester (L-NAME) has been reported to have protective action against hydroxyl free radicals. We have investigated whether L-NAME influences free radical formation in the post-ischemic reperfused heart of anesthetized rats. An isolated rat heart-lung preparation was used. Forty male Wistar rats were allocated into D (D-NAME 100 microMol.l-1), L (L-NAME 100 microMol.l-1), LH (L-NAME 100 microMol.l-1 and 1MAC halothane), LI (L-NAME 100 microMol.l-1 and 1MAC isoflurane), and LS (L-NAME 100 microMol.l-1 and 1MAC sevoflurane) groups. The heart was perfused initially at the cardiac output of 30 ml.min-1 and the atrial pressure of 70 mmHg. Drugs were administered into the reservor 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 4 days. The perfusate blood was collected just before and after ischemia and at the end of reperfusion. The formation of hydroxyl radicals in the perfusate blood and heart was measured with high-performance liquid chromatography using salicylic acid. Hydroxyl radicals react with salicylic acid, yielding dihydroxybenzoic acid (DHBA). Before and after ischemia, there were no significant differences among the groups in cardiac output, systolic pressure, heart rate, and right atrial pressure. DHBAs in the heart of L, LH, LI, and LS groups were significantly lower than those of D group. However, there were no differences in the DHBA levels among 4 groups. The concentrations of DHBA in the perfusate blood after ischemia and reperfusion were significantly higher than those before ischemia in all groups. DHBAs in the perfusate blood after ischemia and reperfusion of L, LH, LI, and LS groups were significantly lower than those of D group. However, there were no differences in the DHBA levels among 4 groups administered L-NAME. This study indicates that L-NAME reduces hydroxyl free radical formation in the post-ischemic reperfused heart in anesthetized rats and volatile anesthetics do not influence the depressant effect of hydroxyl free radical formation by L-NAME.

Anesthetics, Inhalation↗

[Anesthetic management of a child with congenital sensory neuropathy with anhydrosis].

Congenital sensory neuropathy with anhydrosis is a rare disorder characterized by insensitivity to pain with normal tactile perception, self-mutilation, anhydrosis, recurrent unexplained fever, mental retardation and variable autonomic abnormality. We managed a 14-year-old boy with this syndrome who underwent repair of right femur fracture. Anesthesia was induced with propofol and ketamine. Adequate depth of anesthesia was carefully controlled by processed electroencephalogram, and core body temperature was maintained at 37.0 degrees C during the surgery. The patient was well sedated, and nausea and vomiting were not noted postoperatively. Use of droperidol and propofol may be beneficial for anesthetic management of this syndrome, because droperidol exerts residual hypnotic effect postoperatively, and both drugs have antiemetic property.

Adolescent↗

Synthesis of C-pentopyranosylphloroacetophenone derivatives and their anomerization.

A 3-C-beta-D-xylopyranosylphloroacetophenone derivative was synthesized via reaction of 2,3,4-tri-O-benzyl-alpha-D-xylopyranosyl fluoride and 2,4-di-O-benzylphloroacetophenone in the presence of boron trifluoride diethyl etherate. Alternatively, the reaction of 2,3,4-tri-O-benzyl-beta-L-arabinopyranosyl fluoride with 2,4-di-O-benzylphloroacetophenone afforded both the 3-C-alpha-L- and the 3-C-beta-L-arabinopyranosylphloroacetophenone derivatives under identical reaction conditions. The C-beta-L-arabinoside, the thermodynanic product, was produced via anomerization of the C-alpha-L-arabinoside, the kinetic product during the reaction. The composition of this product mixture is apparently dictated by both 1,3-diaxial and 2,4-diaxial interactions.

Acetophenones↗

An effective synthesis of isoorientin: the regioselective synthesis of a 6-C-glucosylflavone.

Isoorientin, a 6-C-beta-D-glucopyranosyl-3',4',5,7-tetrahydroxyflavone, was synthesized in a 15% overall yield, in ten steps, starting from the commercially available phloroacetophenone. The C-glucosyl phloroacetophenone derivative, a synthetic intermediate that contains a free hydroxyl group that is para to the glucosyl moiety, was obtained by hydrogenolysis by taking advantage of differences in the hydrogenolysis rates between a benzyl protecting group and a 2-methylbenzyl protecting group. Aldol condensation of the C-glucosyl phloroacetophenone derivative with 3,4-bis-benzyloxybenzaldehyde afforded the corresponding chalcone as a precursor of the 6-C-glucosyl flavone. Construction of the flavone system by application of I2-DMSO, followed by deprotection, yielded isoorientin.

Flavonoids↗

The conversion of 3-C-beta-D-galactopyranosyl phloroacetophenone to a spiroketal derivative.

Treatment of 3-C-beta-D-galactopyranosylphloroacetophenone in hot water with a catalytic amount of p-toluenesulfonic acid afforded a spiroketal compound as the main product. The chirality of the spiro carbon of the product was R, which is the opposite of the spiroketal obtained by the conversion of 3-C-beta-D-glucopyranosyl phloroacetophenone under identical conditions. The structure was determined by 1H-1H COSY, 1H-13C COSY, NOESY and HMBC spectroscopy.

Acetophenones↗

Separation methods for amino group-possessing pesticides in biological samples.

The separation methods for pesticides include liquid-liquid extraction, solid-phase extraction and solid-phase microextraction, gas chromatography (GC), GC-mass spectrometry (MS), GC-MS-MS, high-performance liquid chromatography (LC), LC-MS and LC-MS-MS. This review deals with each technique commonly used for extraction, chromatographic separation and detection of amino group possessing pesticides, such as diazines, triazines, carbamates, dinitroanilines and chloroacetanilides in biological samples. The methods presented for analysis of the pesticides in complicated biological matrices seem to be easily applicable to surface or groundwater in environmental chemistry.

Chromatography, Gas↗

Analyses of butyrophenones and their analogues in whole blood by high-performance liquid chromatography-electrospray tandem mass spectrometry.

Five butyrophenones and two analogues 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 at m/z 165 for four compounds. The mass chromatography of HPLC-ES-tandem MS showed much higher sensitivity than that of HPLC-ES-single MS for all drugs spiked to whole blood. Therefore, regression equations, detection limits, recovery rates and precision were studied for haloperidol, bromperidol and fluoropipamide 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 0.2-0.8 ng/ml with a detection limit of about 0.1 ng/ml. Recoveries of the three compounds spiked to whole blood (0.2 and 0.8 ng added to 1 ml whole blood) were 23.6-81.2%; the coefficients of intra- and inter-day variations were 8.4-10.4 and 14.5-17.5%, respectively. The three compounds in whole blood could be actually determined 3 and 6 h after oral administration of 1 mg each of haloperidol and bromperidol, and 10 mg of floropipamide in a volunteer.

Butyrophenones↗

Ultrasensitive determination of phencyclidine in body fluids by surface ionization organic mass spectrometry.

Gas chromatography (GC)/surface ionization organic mass spectrometry (SIOMS) has been found to give much higher sensitivity for measurements of phencyclidine (PCP) than the conventional GC/electron impact (EI)-mass spectrometry (MS). Thus, we have established a detailed procedure for measurements of PCP in body fluids by both mass chromatography and selected-ion monitoring (SIM) of SIOMS using pethidine as an internal standard (IS). Good linearity was found in the range of 0.25-10 ng/mL of whole blood or urine, when measured by mass chromatography, and in the range of 0.025-1.0 ng/mL of whole blood by SIM. The recoveries of PCP and IS spiked to whole blood were 106 +/- 17% at 1 ng/mL and 113 +/- 11% at 5 ng/mL; that of IS was 97.8 +/- 10.4% at 5 ng/mL. The detection limits (signal-to-noise ratio = 3) were estimated to be 0.05 ng/mL of whole blood or urine by mass chromatography and 0.01 ng/mL of whole blood by SIM. The coefficients of intraday and interday variations were not greater than 10.3%. We could detect PCP from rat whole blood 2 h after subcutaneous injection of PCP (1 mg/kg) by mass chromatography. The mean PCP concentration in rat blood was 47.7 +/- 6.2 ng/mL (mean +/- SD, n = 4).

Animals↗

Determination of pentazocine in human whole blood and urine by gas chromatography/surface ionization organic mass spectrometry.

Pentazocine has been found to be measurable with much higher sensitivity by gas chromatography (GC)/surface ionization (SI) organic mass spectrometry (OMS) than by the conventional GC/electron ionization (EI) mass spectrometry. The compound was extracted from human whole blood and urine with Sep-Pak C(18) cartridges before analysis by GC/SIOMS; recoveries were > 96.6% for both samples. The calibration curves were linear in the range 6.25-100 ng ml(-1) and the detection limits were 500 pg ml(-1) of a sample by selected ion monitoring (SIM) with GC/SIOMS. The intra- and inter-day relative standard deviations for the determination of pentazocine in whole blood and urine were not greater than 9.6%. The sensitivity for pentazocine obtained by SI-SIM was about 60 times higher than that obtained by EI-SIM. To validate the present GC/SIOMS method for pentazocine, whole blood and urine samples collected from two volunteers 1-6 h after intramuscular injection of 15 mg of pentazocine were analyzed. The concentrations were 13.5-59.3 ng ml(-1) for whole blood and 0.39-4.00 microg ml(-1) for urine.

Analgesics, Opioid↗

Determination of phenothiazines in human body fluids by solid-phase microextraction and liquid chromatography/tandem mass spectrometry.

Eleven phenothiazine derivatives with heavy side-chains were found to be extractable from human whole blood and urine samples by solid-phase microextraction (SPME) with a polyacrylate-coated fiber. The fiber was then injected into the desorption chamber of an SPME-liquid chromatography (LC) interface for LC/tandem mass spectrometry (MS/MS) with positive ion electrospray (ES) ionization. All compounds formed base peaks due to [M + 1](+) ions by LC/ES-MS/MS. By use of LC/ES-MS/MS, the product ions produced from each [M + 1](+) ion showed base peaks due to side-chain liberation. Selected reaction monitoring (SRM) and selected ion monitoring (SIM) were compared for the detection of the 11 phenothiazine derivatives from human whole blood and urine. SRM showed much higher sensitivity than SIM for both types of sample. Therefore, a detailed procedure for the detection of drugs by SRM with SPME-LC/MS/MS was established and carefully validated. The extraction efficiencies of the 11 phenothiazine derivatives spiked into whole blood and urine were 0. 0002-0.12 and 2.6-39.8%, respectively. The regression equations for the 11 phenothiazine derivatives showed excellent linearity with detection limits of 0.2-200 ng ml(-1) for whole blood and 4-22 pg ml(-1) for urine. The intra- and inter-day precisions for whole blood and urine samples were not greater than 15.1%. The data obtained after oral administration of perazine or flupentixol to a male subject are presented.

Adult↗

Possible contribution of protein kinase C in the effects of histamine on the visceral nociceptor activities in vitro.

To clarify the possible contribution of protein kinase C activation in histamine-induced excitation and sensitization of the heat response of testicular polymodal receptors, the effects of staurosporine, a protein kinase C inhibitor, and phorbol 12,13-dibutyrate, a protein kinase C activating phorbol ester, were studied in visceral polymodal receptors. Single polymodal receptor activities were recorded in vitro from testis-spermatic nerve preparations obtained from deeply anesthetized dogs (pentobarbital sodium, 30 mg/kg, i.v.). Histamine (10 microM)-induced excitation and facilitation of the heat response of polymodal receptors were both suppressed by staurosporine (1 microM), suggesting that activation of protein kinase C is involved in both these effects of histamine. Application of phorbol 12,13-dibutyrate (0.1 microM) mixed with histamine increased the histamine-induced excitation, whereas a 5 min application of phorbol 12,13-dibutyrate before histamine suppressed it. These results suggest that phorbol 12,13-dibutyrate-activated protein kinase C has inactivation as well as activation effects on the intracellular cascade connected to histamine receptors, and that the former has a slower time course.

Animals↗

A curious autopsy case of accidental carbon monoxide poisoning in a motor vehicle.

A 26-year-old man was found dead in his car. All doors and windows were locked inside. The ignition key was in the "on" position; but the engine was not running and the fuel tank was empty. His post-mortem lividity was cherry-pink, and marked congestion was observed in the lungs and brain macroscopically. Massive intracardiac blood containing a small amount of cruor was found in the heart. In histological examination of the heart, partial disarrangement or necrosis was found in the myocardium. The liver cells showed derangement and degenerative changes, with focal lymphocyte infiltration in the portal regions, although they were not severe. The chemical tests showed that the blood concentration of carboxyhemoglobin was 46.6%. Stimulants were also detected from his blood and urine; the concentrations of methamphetamine and amphetamine were 3.25 and 0.84 microg/ml, respectively, for his cardiac blood. Therefore, it seemed reasonable to judge that the cause of his death was carbon monoxide poisoning; the cardiomyopathy and the presence of stimulants in blood might facilitate his death. Upon careful investigation of his car, it was disclosed that exhaust gas, leaked from small holes of the exhaust pipe due to rust-through, invaded the interior through four holes on the floor of the car during parking with the engine being on for the purpose of air-conditioning of the interior. It is very common to commit suicide by introducing exhaust gas into an interior of a closed motor car, but the present accidental case of carbon monoxide poisoning in a car seems rare and worthwhile reporting.

Journal Article↗

Reproductive toxicity of 1-bromopropane, a newly introduced alternative to ozone layer depleting solvents, in male rats.

1-Bromopropane has been newly introduced as an alternative to ozone-depleting solvents. We aimed to clarify its dose-dependent reproductive toxicity in male rats. Thirty-six Wistar male rats were randomly divided into 4 groups of 9. The groups were exposed to 200, 400, or 800 ppm 1-bromopropane or only fresh air, 8 h per day for 12 weeks. Epididymal sperm indices were evaluated after a 12-week exposure. The testes, epididymides, seminal vesicle, prostate, and other organs were weighed and examined histopathologically. Spermatogenic cells, in stage VII seminiferous tubules, and retained spermatids, at the basal region of stages IX-XI seminiferous epithelium, were counted. Plasma testosterone levels were measured by radioimmunoassay. The testicular weight did not significantly change, but the weight of epididymides, seminal vesicle, and prostate dose-dependently decreased. The weight of seminal vesicle decreased significantly at the lowest concentration of 200-ppm and over. 1-Bromopropane induced a dose-dependent decrease in the epididymal sperm count and in motility, as well as an increase in tailless sperm and sperm with an immature head shape. The spermatogonia, preleptotene spermatocytes, pachytene spermatocytes, and round spermatids did not decrease significantly at stage VII. Retained, elongated spermatids near the basement membrane at the postspermiation stages IX-XI increased dose-dependently. Plasma testosterone levels significantly decreased at the 800-ppm dosage. 1-Bromopropane caused failure of spermiation. Its reproductive toxicity is different from that of 2-bromopropane, which specifically impairs spermatogonia. Thus, this solvent may have serious reproductive toxic effects in men, and should be used very cautiously in the workplace.

Administration, Inhalation↗

1-Bromopropane, an alternative to ozone layer depleting solvents, is dose-dependently neurotoxic to rats in long-term inhalation exposure.

1-Bromopropane has been newly introduced as an alternative to ozone layer-depleting solvents. We aimed to clarify the dose-dependent effects of 1-bromopropane on the nervous system. Forty-four Wistar male rats were randomly divided into 4 groups of 11 each. The groups were exposed to 200, 400, or 800 ppm of 1-bromopropane or only fresh air 8 h per day for 12 weeks. Grip strength of forelimbs and hind limbs, maximum motor nerve conduction velocity (MCV), and distal latency (DL) of the tail nerve were measured in 9 rats of each group every 4 weeks. The other 2 rats of each group were perfused at the end of the experiment for morphological examinations. The rats of the 800-ppm group showed poor kicking and were not able to stand still on the slope. After a 12-week exposure, forelimb grip strength decreased significantly at 800 ppm and hind limb grip strength decreased significantly at both 400 and 800 ppm or after a 12-week exposure. MCV and DL of the tail nerve deteriorated significantly at 800 ppm. Ovoid or bubble-like debris of myelin sheaths was prominent in the unraveled muscular branch of the posterior tibial nerve in the 800-ppm group. Swelling of preterminal axons in the gracile nucleus increased in a dose-dependent manner. Plasma creatine phosphokinase (CPK) decreased dose-dependently with significant changes at 400 and 800 ppm. 1-Bromopropane induced weakness in the muscle strength of rat limbs and deterioration of MCV and DL in a dose-dependent manner, with morphological changes in peripheral nerve and preterminal axon in the gracile nucleus. 1-Bromopropane may be seriously neurotoxic to humans and should thus be used carefully in the workplace.

Administration, Inhalation↗

Comparison of infrared thermometer with thermocouple for monitoring skin temperature.

OBJECTIVE: To test the hypothesis that the infrared thermometer (Genius) is comparably useful with thermocouples that are routinely used for skin temperature monitoring. DESIGN: Prospective, controlled, not blinded study. SETTING: Operating room of a university hospital. SUBJECTS: Ten healthy male volunteers. INTERVENTIONS: Volunteers were minimally clothed and were initially warmed by a forced air warmer until they became vasodilated at the finger and the foot for approximately 30 mins. Subsequently, they were kept in the room with no blanket. MEASUREMENTS AND MAIN RESULTS: Skin temperatures were measured continuously with the Mon-a-Therm thermocouple and were also measured with the Genius thermometer just before and after the warming and subsequently every 10 mins for 70 mins. Forearm and finger-tip skin temperatures and skin-surface temperature gradients (from arm to finger and from calf to toe) measured by the Genius thermometer were compared with those measured by the Mon-a-Therm thermocouple using linear regression and Bland and Altman statistics. Forearm temperature and finger-tip temperature ranged from approximately 31 degrees to approximately 36.5 degrees C (87.8-97.7 degrees F) and approximately 22.5 degrees to approximately 36 degrees C (72.5-96.8 degrees F), respectively. Gradients (from arm to finger and from calf to toe) ranged from approximately -3 degrees to approximately 10 degrees C (26.6-50.0 degrees F) and approximately -3 degrees to approximately 11 degrees C (26.6-51.8 degrees F), respectively. Correlations between the temperatures measured by the Genius thermometer and those by the Mon-a-Therm thermocouple were similar and reliable. The correlation coefficients were as follows: 0.78 at forearm, 0.97 at finger-tip, and 0.97 at skin-surface temperature gradients. CONCLUSIONS: The infrared thermometer with a special probe is useful to measure the change of skin-surface temperatures and to evaluate the severity of shock in patients.

Adult↗