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Biomedical subjects

T Kumazawa

Publications and source records attributed to T Kumazawa.

At least 109 records · Page 6Linked to original sources
PubMed1997

The minimum alveolar concentration of sevoflurane in rats.

There are only limited data on sevoflurane minimum alveolar concentration (MAC) in rats. This study was designed to determine the minimum alveolar concentration value for sevoflurane in younger and older rats. Minimum alveolar concentration determination was performed in spontaneously breathing animals, 9-week-old rats (younger, n = 8) and more than 13-month-old rats (older, n = 8). Rats were instrumented with a silastic catheter in the abdominal aorta via the femoral artery to allow for arterial blood gas sampling. Subsequently, minimum alveolar concentration for sevoflurane was determined in 40 younger and 38 older rats. Minimum alveolar concentration for sevoflurane in younger rats was significantly higher than in the older rats (2.68 +/- 0.19 vs. 2.29 +/- 0.19, P < 0.001). Subgroup analysis indicated that minimum alveolar concentration for sevoflurane was not affected by the presence of an arterial catheter in the abdominal aorta (younger, 2.75 +/- 0.08 vs. 2.67 +/- 0.21; older, 2.23 +/- 0.19 vs. 2.30 +/- 0.18). Minimum alveolar concentration is profoundly affected by the age of the animal, but not by limited instrumentation.

Aging↗
PubMed1997

Mechanism of the negative inotropic effect of midazolam and diazepam in cultured foetal mouse cardiac myocytes.

We have investigated the effects of midazolam and diazepam on intracellular calcium (Ca2+) handling in foetal mouse ventricular myocytes using the Ca(2+)-sensitive fluorescent indicator, indo-1. We also investigated separately whether flumazenil or the L-type Ca2+ channel agonist, Bay K8644, antagonized these myocardial depressive effects. Midazolam and diazepam decreased the Ca2+ transient and beating rate in a concentration-dependent manner, and these decreases were prevented by Bay K8644. Flumazenil did not antagonize the myocardial depressive effects. In myocytes whose sarcoplasmic reticulum was inhibited by ryanodine, midazolam and diazepam had the same potent cardiodepressive effects. Midazolam and diazepam are direct cardiac depressants, which decrease the Ca2+ transient and beating rate, and the L-type Ca2+ channel is important in the negative inotropism and chronotropism caused by these drugs.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1997

I.m. midazolam as premedication produces a concentration-dependent decrease in core temperature in male volunteers.

We tested the hypothesis that premedication with i.m. midazolam decreases core temperature dose-dependently. We studied six male volunteers, in random order, on 3 days: (1) no midazolam administration (control day), (2) midazolam 0.025 mg kg-1 i.m., (3) midazolam 0.075 mg kg-1 i.m. On the first day, subjects were maintained alert during a 30-min control period. On the second and third days, midazolam 0.025 or 0.075 mg kg-1 was administered i.m. Core temperatures were measured at the right tympanic membrane. Four adhesive skin surface probes were fixed on the chest, upper right arm, lateral calf and thigh. Finger tip perfusion was evaluated using forearm minus fingertip and calf minus toe, skin surface temperature gradients. Thirty minutes after midazolam i.m., the level of sedation in the volunteers was assessed. Peripheral venous blood was obtained immediately after the assessment of the level of sedation. Tympanic membrane temperatures after administration of midazolam 0.075 mg kg-1 i.m. were significantly lower than those on the control and midazolam 0.025 mg kg-1 i.m. days at 20 and 30 min. The decreases in tympanic membrane temperatures at 30 min after midazolam i.m. became larger as the volunteers were more deeply sedated. i.m. midazolam produced a concentration-dependent decrease in tympanic membrane temperature at 30 min after midazolam 0.025 and 0.075 mg kg-1 i.m. We conclude that midazolam impaired tonic thermoregulatory vasoconstriction, allowing core-to-peripheral heat redistribution in a dose-dependent manner after i.m. administration.

Adult↗
PubMed1997

Simple analysis of diphenylmethane antihistaminics and their analogues in bodily fluids by headspace solid-phase microextraction-capillary gas chromatography.

Thirteen antihistaminic drugs and their analogues are tested for their extraction by headspace solid-phase microextraction from human whole blood and urine. Their determination is made by using capillary gas chromatography with flame ionization detection. Relatively high recoveries are obtained for terodiline, diphenhydramine, diphenylpyraline, and orphenadrine in urine; but the recoveries in blood extracts are 4-51 times lower than those in urine extracts for all drugs. Benactyzine and piperilate are not suited for the extraction method. The calibration curves are drawn for four drugs spiked to whole blood and for eleven drugs spiked to urine; excellent linearity is confirmed for the drugs. The detection limits for the drugs are 76-473 ng/mL in blood and 13-186 ng/mL in urine. Diphenhydramine is determined for whole blood obtained from a male subject who had received oral administration of 30 mg diphenhydramine-HCl 150 min before the sampling; the concentrations of the drug are 0.12 and 1.22 micrograms/mL for blood and urine, respectively.

Adult↗
PubMed1997

Detection of tricyclic antidepressants in whole blood by headspace solid-phase microextraction and capillary gas chromatography.

A simple method for the extraction of four tricyclic antidepressants from whole blood by headspace solid-phase microextraction (SPME) is presented. The whole blood samples contain four drugs (amitriptyline, chlorimipramine, imipramine, and trimipramine) and are heated at 100 degrees C in a septum-capped vial in the presence of distilled water and NaOH solution; a polydimethylsiloxane-coated SPME fiber is exposed to the headspace of the vial to allow adsorption of the drugs before capillary gas chromatography (GC) with flame-ionization detection. The headspace SPME-GC produces intense peaks for each drug with very little background noise. Recoveries of the four drugs by the present method are 5.3-12.9%. The calibration curves for the drugs show linearity in the range of 31-1000 ng/0.5 mL. The detection limits of each drug are 16-25 ng/0.5 mL. Imipramine is detectable from rat blood 5 h after oral administration of imipramine (500 mg/kg body weight); the concentration is 1.44 +/- 0.209 micrograms/mL.

Amitriptyline↗
PubMed1997

Nonfatal suicidal intoxication by clozapine.

CASE REPORT: A rare case of clozapine intoxication of a 23-year-old woman, who intended suicide by its overdose, but recovered under medical treatments, is presented. METHOD: Gas chromatography/mass spectrometry and gas chromatography with nitrogen phosphorus detection were employed for its identification and quantitation, respectively. RESULTS: Clozapine serum concentration reached 3.62 micrograms/mL 3 h after ingestion. The urine concentration 32 h after ingestion was 4.28 micrograms/mL.

Adult↗
PubMed1997

[Effects of steroids on hepatic ATP and L/P ratio in rats subjected to acute hemorrhage].

Both steroids and hemorrhage may affect the hepatic energy metabolism. The effects of steroids (5 mg.kg-1 of methylpredonisolone, 50 mg.kg-1 of methylpredonisolone, 25 mg.kg-1 of hydrocortisone and 250 mg.kg-1 of hydrocortisone) on hepatic ATP level and L/P ratio were evaluated in rats under acute hemorrhage. There were no significant differences in the hepatic ATP levels and L/P ratio among 5 groups. However, the base excess in 3 steroid groups (50 mg.kg-1 of methylpredonisolone, 25 mg.kg-1 of hydrocortisone and 250 mg.kg-1 of hydrocortisone) was significantly higher than that in the control group. This result suggests that steroids may improve the metabolic acidosis during acute hemorrhage.

Acidosis, Lactic↗
PubMed1996

Indole derivatives as a new class of steroid 5 alpha-reductase inhibitors.

A series of indole derivatives with varied substituents on the alpha, beta-unsaturated double bond were synthesized and evaluated for their ability to inhibit rat prostatic 5 alpha-reductase. Compounds possessing an ethyl substituent at the beta-position of the double bond showed potent inhibitory activity. Among them, (Z)-4-{2-[[3-[1-(4,4'-difluorobenzhydryl)indol-5-yl]-2-pentenoy l]- amino]phenoxy}butyric acid (16, KF20405) showed the maximum potency with an IC50 value of 0.48 +/- 0.086 nM, which was 20-fold higher potency than 1 (MK-906). Compound 16 effectively inhibited DHT production 4 h after a 3 mg/kg oral administration. Several potent indole derivatives, 1 and 2 ((+/-)-ONO-3805), were tested versus rat and human isozymes. Nonsteroidal inhibitors such as indole derivatives and 2 were 2-3 orders of magnitude less potent for human type 2 isozyme than steroidal inhibitor 1 and expressed a significant species deference for these isozymes.

5-alpha Reductase Inhibitors↗
PubMed1996

Sympathetically induced paradoxical increases of the cutaneous blood flow in chronically inflamed rats.

In adjuvant arthritic (AA) rats, an abnormal responsiveness of nociceptors (C-fibre polymodal receptors) to sympathetic activities, i.e., alpha 2-adrenoceptor mediated activation of C-fibre polymodal receptors (CPRs), has been observed. The present investigations were undertaken to determine if a similar plastic change would occur in the cutaneous vascular system in the rat chronic inflammation model. The vascular responses were measured by a laser-Doppler flowmeter in the hindpaw skin of the AA rats after electrical stimulation of lumbar sympathetic trunk (sympathetic stimulation). In control non-arthritic rats, the sympathetic stimulation caused decrease in blood flow of the skin (SkBF) in all animals tested (n = 7). On the other hand, the sympathetic stimulation in the AA rats caused both increase (n = 15) as well as decrease (n = 11) in SkBF. In contrast to the abnormal responsiveness of CPRs, the intra-arterial injection of noradrenaline caused the expected decrease in SkBF in all animals tested, and in no instances increases in SkBF were observed. To determine whether activation of nitric oxide (NO), which is known to be a potent endogenous vasodilatation substance, was involved in the vasodilating effect to sympathetic stimulation, an inhibitor of NO synthase, NG-monomethyl-L-arginine (L-NMMA), was applied systemically. L-NMMA significantly increased baseline blood pressure in the control and the AA rats, but it did not significantly alter the SkBF in the control or the AA rats after the sympathetic stimulation, suggesting that NO is not a mediator in the vasoactive responses. The results of the current studies showed for the first time that electrical stimulation of the lumbar sympathetic trunk causes vasodilatation in the skin of the AA rats. This abnormal responsiveness of regional SkBF after sympathetic stimulation was not mediated by adrenergic or NO system.

Animals↗
PubMed1996

Segmental distribution of afferent neurons innervating the canine testis.

To clarify the afferent innervation of the canine scrotal contents, retrograde labeling of neurons in the dorsal root ganglia (DRG) has been carried out using two methods: (1) horseradish peroxidase (HRP) injection into the surface of the testis and epididymis; and (2) exposure of the superior spermatic nerve to a fluorescent dye (Fast blue; FB). Injections of HRP resulted in labeling of DRG cells located predominantly from T10 to L4 (87%) and, to a lesser extent, at S1-S3 (13%). Transection of the vas deferens previous to testicular injections eliminated labeling in the S1-S3 DRG, but not at thoracolumbar levels. These findings indicated that primary afferent fibers of the testis and epididymis project mainly to the DRG at higher than L4 through the superior spermatic nerve, but an additional population of the fibers also projects the sacral level through the inferior spermatic nerve. Exposure of the superior spermatic nerve to FB resulted in a similar distribution of labeled cells as compared with testicular injections of HRP after vasectomy. Labeled cells (8.1%) were also observed in the contralateral T13-L3 DRG. In both FB and HRP groups, the major part of the labeled cells was located in L1 and L2. The sizes of HRP- and FB-labeled cells were smaller than those of unlabeled cells in the L1 and L2 DRG. The cumulative frequency distribution histogram for the diameter of HRP- and FB-labeled cells could be fitted by a normal distribution.

Amidines↗
PubMed1996

Excitation and sensitization of the heat response induced by a phorbol ester in canine visceral polymodal receptors studied in vitro.

To clarify the possible involvement of protein kinase (PK) C activation in the excitation and sensitization of polymodal receptors (PMRs), the effects of phorbol 12,13-dibutyrate (PDBu) on PMRs were studied in canine testis-spermatic nerve preparations in vitro. Application of PDBu (10(-7), 10(-6), AND 10(-5) M) for 5 min evoked a significant increase in the ongoing activity of the PMRs within 15 min. PDBu (10(-8) to 10(-5) M) significantly augmented the subsequent heat responses of the PMRs. Staurosporine (10(-6) M), a PK inhibitor, attenuated the effect of PDBu on heat responses. These data suggest that activation of PKC contributes to the activities of PMRs.

Alkaloids↗
PubMed1996

Simple and sensitive detection of phencyclidine in body fluids by gas chromatography with surface ionization detection.

Phencyclidine (PCP) can be detected in body fluids with very high sensitivity by gas chromatography (GC) with surface ionization detection (SID) using pethidine as internal standard. PCP was extracted with Sep-Pak C18 cartridges from whole blood and urine samples, which gave clean extracts. The calibration curve for spiked whole blood was linear in the range 1.25-20 ng/ml. The detection limit of PCP was approximately 15 pg on-column (0.75 ng/ml sample), which was much lower than by GC-nitrogen phosphorus detection. The recovery of PCP and pethidine from spiked whole blood or urine samples was above 85%. This method seems very useful for the determination of PCP in forensic and clinical toxicology.

Body Fluids↗
PubMed1996

A comparison of four infrared tympanic thermometers with tympanic membrane temperatures measured by thermocouples.

PURPOSE: To compare measurements made with four infrared tympanic thermometers (Genius, Thermopit, Quickthermo, and Thermoscan) with those recorded from thermocouples positioned in the contralateral ear. METHODS: Four tympanic thermometers were evaluated in 50 healthy volunteers (12 female and 38 male). Temperatures were measured, in random order, at the right tympanic membrane four times and the highest temperature was considered to be the true value measured by each thermometer. The control temperature was measured at the left tympanic membrane using Mon-a-Therm thermocouples. RESULTS: The tympanic membrane temperature measured by Genius correlated best with the Mon-a-therm measurement (TM) (r = 0.74). The tympanic membrane temperatures measured by Thermopit, Quickthermo, and Thermoscan correlated moderately with TM (r = 0.56, 0.63, and 0.58, respectively). Mean differences between TM and each temperature (TG, TTP, TQ, and TTS) were -0.3, 0.73, 0.42, and -0.3 degrees C, respectively. Likewise standard deviations were 0.33, 0.37, 0.35, and 0.35. CONCLUSION: We conclude that all but the Thermopit (TTP) are similarly useful for the management of patients during anaesthesia.

Adult↗
PubMed1996

Coexistence of calcitonin gene-related peptide- and substance P-like immunoreactivity in retrogradely labeled superior spermatic neurons in the dog.

The coexistence of calcitonin gene-related peptide (CGRP) and substance P (SP) was determined in primary afferent neurons of the superior spermatic nerve of the dog. Testicular afferent neurons were visualized by retrograde labeling with the fluorescent dye fast blue. CGRP-like immunoreactivity (LI) was found in about 80% of testicular L1 and L2 dorsal root ganglion cells, and 81% of CGRP-positive neurons also contained SP. Conversely, SP-LI was found in 66% of testicular afferents, and 96% of SP-positive neurons simultaneously contained CGRP. Both CGRP- and SP-LI were observed in the whole size range of the testicular afferent neurons. No significant difference in the diameter was detected between CGRP- and SP-positive testicular afferent neurons. In contrast, the diameter of SP-positive cells was significantly smaller than that of CGRP-positive cells in the whole population of dorsal root ganglion (DRG) neurons. Compared to skin and muscle afferents, a larger population of the testicular afferents contain these peptides. This is considered to be one of the characteristic features of visceral afferents. Coexistence of CGRP and SP in testicular afferent neurons suggest a close functional relationship between these two neuropeptides in the sensory nervous system.

Amidines↗
PubMed1996

Opposite effects of increased intracellular cyclic AMP on the heat and bradykinin responses of canine visceral polymodal receptors in vitro.

To clarify the validity of the long standing hypothesis that effects of E series prostaglandin (PG)S are mediated by cyclic AMP (cAMP), we studied the effects of increases in intracellular cAMP on the heat and bradykinin responses of testicular polymodal receptors. Polymodal receptor activities were recorded in vitro from testis-spermatic nerve preparations excised from dogs anesthetized with pentobarbital (30 mg/kg, i.v.). Increases in intracellular cAMP induced by either forskolin (5 or 10 microM), an adenylyl cyclase activator, or a mixture of dibutyryl cAMP (20-100 microM), a membrane permeable cAMP analog, and 3-isobutyl-1-methyl xanthine (20-100 microM), an inhibitor of the cAMP degrading enzyme, significantly augmented the response to heat (42-48 degrees C). In contrast, these substances failed to facilitate the response to bradykinin (0.1 or 1 microM) and instead suppressed it. Dideoxyforskolin (10 microM), an inactive analog of forskolin, had no effects on both the heat and bradykinin responses. These results demonstrate that an increase in intracellular cAMP induces opposite effects on the heat and bradykinin responses. Possible involvement of intracellular cAMP in the facilitatory effects of PGE2 on both responses was discussed in connection with the PGE receptor subtypes involved in the sensitization of the bradykinin and heat responses.

Animals↗
PubMed1996

A case of coronary artery spasm during spinal anesthesia.

We present a rare case of coronary artery spasm during spinal anesthesia in a patient who had neither complications nor prior history of coronary artery disease. Some factors are involved in the occurrence of perioperative coronary artery spasm. Many cases of coronary artery spasm during general anesthesia, or general plus epidural anesthesia, have been reported. Although spinal anesthesia by itself has not been reported to be a cause of coronary artery spasm, it is likely, in the current case, that the combination of the activated parasympathetic nerve system by the retraction of the peritoneum and spinal anesthesia might have caused the coronary artery spasm. Anesthesiologists need to be aware that coronary artery spasm may occur during spinal anesthesia, especially when the peritoneum is retracted.

Adult↗