PubMed Health⌕ Search

Biomedical subjects

M Morio

Publications and source records attributed to M Morio.

At least 19 recordsLinked to original sources
PubMed1996

Assessment of cerebral fat embolism by magnetic resonance imaging in the acute stage.

The authors assessed the characteristic appearance of magnetic resonance imaging (MRI) of cerebral fat embolism in three patients. The MRI features in the acute stage were characterized by widespread, spotty lesions in the white matter, which appeared hyperintense on T2-weighted images and iso- or hypointense on T1-weighted images. The relation between clinical features and MRI findings are discussed.

Acute Disease↗
PubMed1994

[Clinical evaluation of controlled hypotensive anesthesia with MR7S1].

Efficacy, safety and the optimal dose of MR7S1, an injectable preparation of sodium nitroprusside, were studied in 37 patients (ASA class I and II) under nitrous oxide-oxygen-enflurane anesthesia. MR7S1 was administered by intravenous infusion. The dose of MR7S1 was increased gradually starting from 0.25 micrograms.kg-1.min-1 to the dose which could achieve the target value of systolic blood pressure (80-100 mmHg). Thereafter this dose level was maintained. During the period in which the dose was increased, the blood pressure was reduced in proportion to the rate of administration. With the rate of administration of 1.0 to 3.0 micrograms.kg-1.min-1, a significant decrease in systolic blood pressure (SBP) was observed compared with the pretreatment level of SBP. During the maintenance period, the SBP was maintained around 80 to 100 mmHg at a rate of administration of 0.25 to 3.5 micrograms.kg-1.min-1. Two out of 37 patients showed a slight decrease in PaO2, but these values returned to normal without any treatment. These findings suggest that MR7S1 is a useful agent to control blood pressure for the hypotensive anesthesia.

Adult↗
PubMed1992

Changes in lipid peroxidation levels and lipid composition in the lungs, livers, kidneys and brains of mice treated with paraquat.

We examined lipid peroxide levels and the lipid composition of homogenates prepared from the lungs, livers, kidneys and brains of 48 male ICR mice treated with 30 mg kg-1 paraquat (1,1'-dimethyl-4,4'-bipyridylium dichloride). The mice were divided into eight groups, in which they were killed 0, 1.5, 3, 6, 12, 24, 48 and 120 h after the administration of paraquat. A significant increase in the lipid peroxide level was identified only in the liver. Change in lipid composition was identified in all the examined organs. However, the change was not a characteristic one in which there is a selective decrease of polyunsaturated fatty acids which become degraded in a lipid peroxidation reaction. It is possible that the mechanism of paraquat toxicity may differ in different organs.

Animals↗
PubMed1992

Reaction of sevoflurane and its degradation products with soda lime. Toxicity of the byproducts.

Sevoflurane previously has been reported to undergo extensive degradation in the presence of soda lime. To more completely characterize the extent and significnce of this reaction, we studied degradation of sevoflurane with and without soda lime, as well as the toxicity and mutagenicity of the degradation products. Two degradation products detected were CF2 = C(CF3)OCH2F (compound A) and CH3OCF2CH(CF3)OCH2F (compound B). During circulation of 1%, 2%, and 3% sevoflurance in a closed anesthesia circuit for 8 h, peak concentrations of compound A were 13.3 +/- 0.27, 30.2 +/- 0.10, and 42.1 +/- 1.07 ppm at 2 h, respectively. The concentrations of compound B did not exceed 2 ppm. The temperature of the soda lime was 43.3 +/- 2.8 degrees C at 1 h and increased gradually to 47.9 +/- 1.5 degrees C after 8 h. In closed flasks with soda lime, the magnitude of the decrease in sevoflurance concentrations (3%) and of the increase in compound A concentrations was temperature dependent. The peak concentrations of compound A at 23 degrees C, 37 degrees C, and 54 degrees C were 32.8 +/- 6.8 at 2 h, 46.6 +/- 1.0 at 0.5 h, and 78.5 +/- 2.3 ppm at 0.5 h, respectively. The LC50 (50% lethal concentration) of compound A in Wistar rats was 1,090 ppm in males and 1,050 ppm in females exposed for 1 h. The LC50 was 420 ppm in males and 400 ppm in females exposed for 3 h. The chronic toxicity of compound A in Wistar rats was studied by exposing rats 24 times, for 3 h each, to initial concentrations of 30, 60, or 120 ppm in a ventilated chamber. At all concentrations, there were no apparent effects other than a loss of body weight in females (120 ppm) on the final day (P < 0.01). Compound A did not induce mutation on the reverse (Ames) test at less than 2,500 micrograms/dish (culture medium 2.7 ml) with activation by S-9 mixture, and below 1,250 micrograms/dish (culture medium 2.7 ml) without activation, in four strains of S. typhimurium and in 1 strain of E. coli. Exposure of fibroblasts to 7,500 ppm of compound A for 1 h, compound A did not induce structural change. In a study of acute toxicity of compound B, there was no toxicity in Wistar rats after 3 h of exposure at 2,400 ppm. The reverse (Ames) test for compound B was negative at 625-1,250 micrograms/dish.(ABSTRACT TRUNCATED AT 400 WORDS)

Absorption↗
PubMed1991

Effect of calcium channel blocking agents on the reductive metabolism of halothane.

The effect of calcium channel blocking agents on the reductive metabolism of halothane in liver microsomes of guinea pigs was investigated. The reaction mixture for the measurement of the end products consisted of microsomal suspension, 5 mM NADPH, calcium channel blocking agents (verapamil, diltiazem, nicardipine and nifedipine) and halothane in 0.1 M phosphate buffer (pH 7.4). The reductive metabolism of halothane was inhibited competitively by verapamil, diltiazem and nicardipine. The binding spectra for the interaction of these three drugs with cytochrome P-450 in microsomes were investigated. Verapamil caused the reverse type I difference spectrum and diltiazem caused the type I difference spectrum. However, the change caused by nicardipine was not observed by the presence of its specific spectra. NADPH-cytochrome P-450 reductase activity in microsomes did not change by the addition of these three drugs. These results suggest that these three calcium channel blocking agents inhibit the production of radical intermediates during the reductive metabolism of halothane.

Animals↗
PubMed1991

Dose-related sevoflurane metabolism to inorganic fluoride in rabbits.

Serum concentrations and urinary excretion of inorganic fluoride (fluoride ion), a metabolite of sevoflurane, were measured by an ion-chromatographic analyzer after inhalation of three different concentrations of sevoflurane in adult, male Japanese white rabbits weighing 2.6-3.6 kg. Sevoflurane was administered at concentrations of 0% (control), 1%, 2% and 3% (Groups I, II, III and IV, respectively) through a sevoflurane vaporizer for 2 hr under controlled ventilation. Blood and urine samples were collected during and after termination of sevoflurane inhalation at scheduled time intervals for 24 hr. The total volume of urine, the urinary pH and the osmolality of serum and urine were not significantly different among any of the groups. Osmolality of the serum and urine was within normal range in all groups of animals. The mean serum peak values of fluoride ion were 0.7 +/- 0.5, 22.8 +/- 8.7, 31.8 +/- 11.0 and 41.5 +/- 13.2 microM (mean +/- SD) in groups I, II, III and IV, respectively. Peak values were recorded within 15 min after the termination of inhalation. The cumulative amounts of fluoride ion excreted in urine in 24 hr were calculated to be 5.0 +/- 1.6, 26.1 +/- 6.7, 41.4 +/- 11.3 and 64.3 +/- 18.0 mumol (mean +/- SD) in groups I, II, III and IV, respectively. Regression analysis revealed significant correlations between the formation and excretion of fluoride ion, and the dose of sevoflurane (r = 0.85, p less than 0.05 and r = 0.89, p less than 0.05, respectively). The authors conclude that the formation and excretion of fluoride ion after sevoflurane anesthesia is dependent on the dose of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1991

Aerobic dehalogenation of halothane showing different substrate dependency from anaerobic dehalogenation in liver microsomes of guinea pig.

The formation of trifluoroacetic acid (TFAA) from halothane under aerobic conditions and that of chlorotrifluoroethane (CTE) and chlorodifluoroethylene (CDE) from halothane under anaerobic conditions were studied using guinea pig liver microsomes. The formation of TFAA was inhibited by specific inhibitors of cytochrome P450 (P450), such as carbon monoxide and metyrapone and was dependent upon P450 contents. The maximum activity of the TFAA formation was obtained at pH 6.0. On the other hand, the maximum activity to form CTE and CDE was obtained at pH 7.4. The formation of TFAA reached a plateau at a halothane concentration above 0.17 mM, but the rate of formation of CDE and CTE was dependent upon a halothane concentration up to 1.5 mM. The values of apparent Michaelis-Menten constant (Km) and maximum velocity (Vmax) for TFAA formation were 0.067 mM and 0.349 nmol/nmol P450/min respectively, those for CDE formation were 0.983 mM and 0.326 nmol/nmol P450/min respectively, and those for CTE formation were 1.71 mM and 0.752 nmol/nmol P450/min respectively. These results showed clearly that the formation of TFAA, CDE and CTE was catalyzed by the P450 system in guinea pig liver microsomes. Under optimal conditions, saturation was observed in the formation of TFAA from halothane at a halothane concentration above 0.17 mM but the formation of CDE and CTE was not saturated at this concentration, and the value of apparent Km for TFAA formation was lower than those for CDE and CTE formation.

Aerobiosis↗
PubMed1991

Effects of several volatile anesthetics on the Ca(2+)-related functions of skinned skeletal muscle fibers from the guinea pig.

The effects of various volatile anesthetics on intramuscular Ca(2+)-related functions were studied with the skinned fiber technique in guinea pig skeletal muscles. All the volatile anesthetics tested significantly enhanced Ca(2+)-induced Ca2+ release (CICR) from the sarcoplasmic reticulum (SR) at clinical concentrations with negligible effects both on Ca2+ sensitivity of the contractile system and on Ca2+ uptake by the SR. A comparison was made of the enhancing effect of several volatile anesthetics on CICR at clinical concentrations. Halothane was the most potent, followed by methoxyflurane, isoflurane, enflurane, sevoflurane and diethyl ether. If CICR plays an important role in triggering MH, this order of volatile anesthetics on their enhancing effect on CICR, also corresponds to their potency in triggering MH.

Anesthetics↗
PubMed1990

Biotransformation and toxicity of inhalational anaesthetics.

In summary, anaesthetics and drugs used perioperatively are all xenobiotics and can be metabolized mainly by microsomal enzyme systems, which have a high activity in the liver. These enzyme systems are induced by repeated pre-administration of drugs, such as barbiturates and others which are used during the preoperative period. However, according to some reports, aerobic and anaerobic metabolism is inhibited by the simultaneous administration of drugs, such as isoflurane and halothane, halothane and enflurane, and cimetidine and halothane. Hypoxia is also an important factor in hepatic disorders and it is well known that anaerobic metabolism of halothane is increased by hypoxia and its intermediate production produces a free radical. Theoretically, this free radical is involved in hepatic disorders. In practice, in order to prevent hepatic dysfunction before, during and after anaesthesia, hypoxia and repeated pre-administration of enzyme-inducing drugs should be avoided. However, the choice and combination of drugs which inhibit drug metabolism and prevent hepato and/or nephro toxicity should be examined by further investigation.

Anesthesia, Inhalation↗
PubMed1990

Structural changes of Kupffer cells in rat liver following experimental thermal injury.

Changes in plasma haemoglobin levels and morphology of Kupffer cells were studied in rats following lethal thermal injury. Severe haemolysis was observed immediately after thermal injury. The plasma haemoglobin levels rapidly increased to a maximum level 15 min after injury and then rapidly decreased with time. However, the values were still higher 5 h after injury than those found before injury. Soon after burning the Kupffer cells phagocytized not only circulating cell debris including erythrocyte membranes and degenerate leucocytes but also large amounts of haemoglobin. The degradation of phagocytized haemoglobin was relatively slow compared to that of other cell debris. This phagocytized haemoglobin is considered to inhibit the generation of bactericidal-free radicals and to depress Kupffer cell function. The number of Kupffer cells was markedly decreased 5 h after thermal injury, and probably relates to the persistent depletion of the reticuloendothelial system function which follows lethal thermal injury. In contrast to the decreased number of Kupffer cells, a small number of monocytic cells appeared in the sinusoidal spaces and adhered to the endothelial cells. These monocytic cells may transform into Kupffer cells.

Animals↗
PubMed1990

Mesenteric lymphatic vasomotion following hemorrhage and retransfusion in the rat.

The effect of hemorrhage and retransfusion on the rhythmic contraction of mesenteric lymphatic vessels was studied in 24 rats, anesthetized with pentobarbital. The rats were divided into four groups according to the amount of blood withdrawn: 0.5ml/100g body weight (BW), 1ml/100g, 2ml/100g, and 2.5ml/100g. Immediately following hemorrhage at the rate of 0.5ml/100g/min, lymphatic contraction frequencies were decreased to 67 +/- 12.5, 45 +/- 24.7, 43 +/- 33.1, and 31 +/- 17.8% of the prehemorrhage values in each of the above four groups, respectively (p less than 0.01). Twenty minutes after hemorrhage, lymphatic contraction frequencies were decreased to 70 +/- 17.2, 46 +/- 36.8, and 34 +/- 41.3% in the 0.5ml/100g, 2ml/100g, and 2.5ml/100g, respectively (p less than 0.05). Immediately following hemorrhage, the lymphatic contracted diameters were also reduced to 77 +/- 9.7 and 61 +/- 9.0% of the prehemorrhage values in the 1ml/100g and 2.5ml/100g groups, respectively (p less than 0.01). Twenty minutes after hemorrhage, all withdrawn blood was reinfused. Lymphatic contraction frequency and contracted diameter recovered after retransfusion in each group but 20 minutes after retransfusion, the lymphatic contraction frequency in the 2ml/100g group was still decreased to 42 +/- 30.3% (p less than 0.01). Lymphatic contraction frequency not only decreased proportionately with hypotension during hemorrhage but after retransfusion contraction frequency correlated directly with the mean arterial pressure 20 min after hemorrhage. These data suggest that mean arterial pressure and by inference capillary blood flow and tissue oxygenation are major factors regulating lymphatic vasomotion.

Animals↗
PubMed1990

A comparative study on reductive dehalogenation of halothane in liver, kidney and lung of the rabbit.

The contents of cytochrome P-450 (P-450) and cytochrome b5, and the activity of NADPH-cytochrome c reductase and the reductive metabolites of halothane, 2-chloro-1, 1-difluoroethylene (CDE) and 2-chloro-1, 1, 1-trifluoroethane (CTE) were measured in microsomes from the liver, kidney and lung of phenobarbital (PB) pretreated and untreated Japanese white strain rabbits. Microsomal P-450 levels in the liver, kidney (renal cortex) and lung of the rabbits were 1.91 +/- 0.35, 0.19 +/- 0.04 and 0.42 +/- 0.11 nmol/mg protein (mean +/- SD), respectively. In vivo phenobarbital pretreatment (PB-pretreatment) increased the content of P-450 to 2.95 +/- 0.40 nmol/mg protein (154%) in the liver and to 0.40 +/- 0.11 nmol/mg protein (211%) in the kidney, but had little effect in the lung. The activity of CDE formation was 0.72 +/- 0.10, 0.08 +/- 0.04 and 0.03 +/- 0.01 nmol/mg protein/min in the liver, kidney and lung, respectively. PB-pretreatment enhanced the activity of CDE formation to 1.59 +/- 0.49 nmol/mg protein (221%) in the liver, and to 0.29 +/- 0.16 nmol/mg protein/min (363%) in the kidney, but showed little enhancement in the lung. The activity of CTE formation was 1.30 +/- 0.19, 0.12 +/- 0.04 and 0.09 +/- 0.02 nmol/mg protein/min, in the liver, kidney and lung, respectively. PB-pretreatment enhanced the activity of CTE formation to 1.80 +/- 0.44 nmol/mg protein/min (138%) in the liver, but caused only slight enhancement in the kidney and lung. PB-pretreatment markedly enhanced the activity of CDE formation in the kidney. The authors conclude that cytotoxicity by reductive dehalogenation of halothane is possible not only in the liver but also in the kidney with PB-pretreatment.

Animals↗
PubMed1990

Effects of in vivo pretreatment with various barbiturates on anaerobic halothane metabolism in rat liver microsomes.

The effects of in vivo pretreatment with phenobarbital (PB), thiopental (TP), thiamylal (TA), pentobarbital (PT), and secobarbital (SB) on hepatic microsomal enzymes, and the effects on anaerobic halothane dehalogenation, aminopyrine N-demethylation, and aniline hydroxylation in the microsomes were studied in male Wistar rats. Three hundred twenty mumol/kg (0.1 ml) of PB, TP, TA, PT, SB, or 0.1ml of 0.9% saline were administered daily, intramuscularly, for periods of one day up to ten days. Daily administration of PB, TP, TA, or PT induced cytochrome P-450, NADPH-cytochrome P-450 reductase and/or cytochrome b5. However, administration of SB did not induce these enzymes. The potency of these enzyme inductions ranged in descending order as follows: PB, TP, TA, and PT. After five days of daily administration of PB, TP, or TA, the production of the anaerobic halothane metabolite, CDFE, increased to 187%, 134%, and 130% of the control, respectively. The production of another halothane metabolite, CTFE, likewise increased to 197%, 168%, and 163%. However, pretreatment with PT or SB had no effect on anaerobic halothane dehalogenation. Aminopyrine N-demethylation also increased after five days of daily administration of PB, TP, and TA. However, aniline hydroxylation decreased after five days of daily administration of TA. Other barbiturates had no effect on aniline hydroxylation. In this study we showed that whereas PT and SB did not enhance anaerobic halothane dehalogenation, PB, TP and TA did. We conclude that not only PB, and also TP and TA, may be enhancing factors in halothane hepatotoxicity. We recommend that, if barbiturates are necessary, SB and PT be used in the preadministration of halothane anesthesia.

Anaerobiosis↗
PubMed1990

Paraquat inhibits the lipid peroxidation caused by carbon tetrachloride in guinea pig liver microsome.

Pentane, which is an index of lipid peroxidation, was formed in a mixture of microsomes, carbon tetrachloride (CCl4) and NADPH. Trichloromethyl radical adduct of the N-tert-butyl-alpha-phenylnitrone-trichroromethyl (BPN) was also formed in the mixture with BPN. The formation of pentane and the radical adduct were reduced in the presence of paraquat. Furthermore a spectrophotometric study showed that substrate-induced difference spectra in the Soret region (Type I) caused by CCl4 and microsomes were changed after adding paraquat. We conclude that paraquat inhibits the lipid peroxidation mediated by the radical intermediate of CCl4 by inhibiting the mixed function oxidase system.

Animals↗
PubMed1990

The association of halothane-induced lipid peroxidation with the anaerobic metabolism of halothane: an in vitro study in guinea pig liver microsomes.

The formation of pentane and anaerobic metabolites of halothane (2-chloro-1,1,1-trifluoroethane and 2-chloro-1,1-difluoroethylene) in a mixture of guinea pig liver microsomes and halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) in the presence of NADPH was studied by gas chromatography. Under anaerobic conditions, pentane was formed without halothane and was inhibited by oxygen tension. This anaerobic pentane formation was potentiated 2.5 times by addition of halothane. Halothane-induced pentane formation increased dose-dependently with a halothane concentration of up to 2.1 mmol/liter and then decreased in the presence of increasing concentrations of halothane. Inhibition by a higher substrate was also observed in the formation of anaerobic metabolites of halothane. Antioxidant agents, vitamin E and glutathione, reduced the pentane formation, but did not reduce the anaerobic metabolites of halothane. Metyrapone, an inhibitor of cytochrome P-450, reduced both the pentane and anaerobic metabolites of halothane. These results show halothane-induced lipid peroxidation in association with the anaerobic metabolism of halothane in guinea pig liver microsomes.

Anaerobiosis↗
PubMed1989

Halothane-induced hepatic microsomal lipid peroxidation in guinea pigs and rats.

Halothane-induced hepatic microsomal lipid peroxidation in guinea pigs and rats was examined with respect to the mixed function oxidase system, anaerobic dehalogenation activity of halothane, and the antioxidant system. The levels of cytochrome P-450 and NADPH-cytochrome P-450 reductase were significantly higher in guinea pigs than in rats. There was no difference between the two animals in anaerobic dehalogenation activity of halothane per cytochrome P-450 in microsomes. Microsomal alpha-tocopherol was significantly lower in guinea pigs than in rats, and was increased by multiple exposure to halothane in guinea pigs but remained lower than in rats. Microsomal alpha-tocopherol was decreased in rats by multiple exposure. The concentration of reduced glutathione and ascorbic acid was decreased significantly by multiple exposure to halothane in guinea pigs but not in rats. These results suggest that the higher level of halothane-induced hepatic microsomal lipid peroxidation in guinea pigs is due to the large production of radical metabolites resulting from the large amounts of cytochrome P-450, the high activity of NADPH-cytochrome P-450 reductase, and the low concentration of microsomal alpha-tocopherol.

Animals↗
PubMed1989

The effects of vasoactive drugs on halothane inhibition of contractions of rat mesenteric lymphatics.

The effects of halothane on alpha-adrenergic receptors, beta-adrenergic receptors, and the process of Ca++ dependent contractions on rat mesenteric lymphatics were examined. Halothane depressed the contraction rate of mesenteric lymphatics but did not effect the increase in lymphatic contraction rate caused by noradrenaline (an alpha-agonist). The depressant effect of halothane on the contraction rate was also not antagonized by propranolol (a beta-blocker), but was partly reversed by CaCl2. These findings suggest that the depressant effect of halothane on the lymphatic contraction rate derives not from blocking lymphatic alpha-receptors or stimulating lymphatic beta-receptors but rather by halothane inhibition on the process of Ca++ dependent lymphatic contractions.

Animals↗