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Biomedical subjects

H Yoshimura

Publications and source records attributed to H Yoshimura.

At least 415 records · Page 23Linked to original sources
PubMed1988

Identification of cannabielsoin, a new metabolite of cannabidiol formed by guinea-pig hepatic microsomal enzymes, and its pharmacological activity in mice.

Metabolism of cannabidiol (CBD), one of the major components of marihuana, was studied in the guinea pig both in vitro and in vivo. Analyses of metabolites by gas chromatography and gas chromatography-mass spectrometry proved that cannabielsoin (CBE) was formed from CBD as a novel metabolite, and that the amount was about one-sixth of 7-hydroxy-CBD, which was the most abundant metabolite under in vitro conditions in the presence of microsomal monooxygenase (cytochrome P-450). CBE was also found in the liver of the guinea pig that was given CBD (100 mg/kg) intraperitoneally 1 h before sacrifice. The effects of CBE on pentobarbital-induced sleep and body temperature were assessed in the mouse; CBE possessed little activity in either case.

Animals↗
PubMed1988

Comparison of the effects of benzodiazepine and nonbenzodiazepine anxiolytics on mouse-killing behavior in rats.

The present study investigated the effects of nonbenzodiazepine anxiolytics on mouse-killing behavior in rats, compared with the effects of benzodiazepine anxiolytics. Mouse-killing behavior was induced by bilateral olfactory bulbectomy. The following drugs were administered intraperitoneally: chlordiazepoxide, diazepam, ethyl loflazepate, fludiazepam, zopiclone, suriclone, and CL 218,872. Among these drugs, suriclone (ED50 = 1.3 mg/kg) and fludiazepam (ED50 = 5.9 mg/kg) showed potent suppressive effects. Diazepam, ethyl loflazepate, and CL 218,872 showed only weak actions on mouse-killing behavior.

Aggression↗
PubMed1988

Peroxidase activity and thyroglobulin iodination activity of thyroid peroxidase in non-functioning thyroid tumours.

Both lesion (L) and adjacent normal (N) thyroid tissue from 48 patients with non-functioning adenomas and adenomatous goitres were assayed for peroxidase activity by the 'mini' assay method employing guaiacol or iodide as the second substrate. A considerable proportion of thyroids (46% of adenomas and 22% of adenomatous goitres) demonstrated no iodide oxidation activity in L although they had guaiacol oxidation activity, and these were grouped as subgroups A. The rest of these non-functioning tumours, termed subgroups B, had both guaiacol and iodide oxidation activity which was higher (3.0-4.6 times in guaiacol assay and 7.3-14.1 times in iodide assay) in L than in N. These data indicate that the non-functioning in subgroups A may be due to a lack of iodide oxidation activity and that some other defects such as an iodide transport defect may be involved in subgroups B. Furthermore, a precise and rapid assay method for thyroglobulin iodination activity of thyroid peroxidase was developed, with modifications of previous methods. On the basis of this method, we found that there is a good correlation (r = 0.94) between iodide oxidation assay and thyroglobulin iodination assay, leading to the conclusion that thyroglobulin iodination assay can be replaced by iodide oxidation assay.

Adenoma↗
PubMed1988

Participation of cytochrome P-450 isozymes in N-demethylation, N-hydroxylation and aromatic hydroxylation of methamphetamine.

1. Five isozymes of cytochrome P-450 were purified from liver microsomes of phenobarbital-pretreated (P-450-SD-I and -II), 3-methylcholanthrene-pretreated (P-450-SD-III) and untreated rats (P-450-SD-IV and -V) to determine their catalytic activities in metabolic reactions of methamphetamine. 2. All the isozymes except P-450-SD-III showed considerably high N-hydroxylating activity of methamphetamine. The cytochromes P-450 initiate N-demethylation of this drug by two metabolic pathways, C-hydroxylation and N-hydroxylation. 3. Both N-demethylation and N-hydroxylation of methamphetamine were efficiently catalysed by the phenobarbital-inducible forms P-450-SD-I and -II and constitutive forms P-450-SD-IV and -V. 4. The constitutive forms P-450-SD-IV and -V revealed high catalytic activities of p-hydroxylation of methamphetamine, but phenobarbital- and 3-methylcholanthrene-inducible isozymes showed only low activities. 5. The present results indicate that the different extents of the metabolic intermediate complex formation with cytochrome P-450 (455 nm complex) in the microsomes from phenobarbital-, 3-methylcholanthrene-pretreated, and untreated rats is not attributable to the activities of the respective isozymes of cytochrome P-450 to form the precursor of the complex, N-hydroxymethamphetamine.

Animals↗
PubMed1988

Enhanced faecal excretion of 2,3,4,7,8-pentachlorodibenzofuran in rats by a long-term treatment with activated charcoal beads.

1. The effect of activated charcoal beads on the faecal excretion of 2,3,4,7,8-pentachlorodibenzofuran (PenCDF), a causal agent of yusho, which accumulates in the body, was studied for 12 weeks in rats. 2. Diets supplemented with 1% and 5% activated charcoal beads stimulated faecal excretion of PenCDF about 2- and 4-fold, respectively. The concentration of PenCDF in liver, the major storage site, was decreased significantly and dose-dependently by the treatment. 3. The charcoal bead treatment decreased the extent of fatty liver, thymic atrophy, and induction of hepatic benzo[a]pyrene hydroxylase.

Animals↗
PubMed1988

Metabolic fate of fenetylline in rat and man.

1. Metabolic fate of 7-[2-(alpha-methylphenylethylamino)ethyl]theophylline hydrochloride (fenetylline) was investigated in male Sprague-Dawley rats and three male volunteers. 2. Six metabolites were identified in the rat urine as amphetamine(AP), p-hydroxy-AP, acetylaminoethyl-theophylline(TP), aminoethyl-TP, hydroxyethyl-TP and carboxymethyl-TP by comparison of their spectral properties and h.p.l.c. and g.l.c. characteristics with those of authentic samples. All these metabolites was also detected in the urine of humans receiving fenetylline. 3. Quantification of these metabolites using h.p.l.c. and g.l.c. showed that carboxymethyl-TP, p-hydroxy-AP and acetylaminoethyl-TP were the major metabolites in 0-24 h rat urine at 13.7%, 11.2% and 9.3% of dose, respectively. In men, carboxymethyl-TP(39-43% dose) and AP(23-33% dose) were the major metabolites in 0-48 h urine. 4. These results suggest that fenetylline metabolism proceeds via oxidative cleavage at two different sites to produce aminoethyl-TP and AP, respectively. The pathway producing AP predominates, in both man and rat, but is more predominant in the former.

Adult↗
PubMed1988

Optical anisotropy decay studies of the dynamic structure of myosin filaments.

We applied flash-induced absorption and phosphorescence anisotropy decay methods to the study of rotational motions of myosin heads in solution), myofibrils and muscle fibers); myosin heads were selectively labeled with a triplet probe EMI (5-eosinylmaleimide). EMI-labeled subfragment 1 (S1) showed a single exponential decay of anisotropy over two decades; the analysis indicated that if S1 is modeled as a prolate ellipsoid of revolution, the major axis was 16-17 nm and the minor axis 4.7-4.5 nm. The decay curve of myosin filaments could be simulated by double-exponentials-plus-constant approximation. The data could be analyzed by a double-cone model), in which we assumed that a head part (S1), wobbles in the first cone and a rod portion next to the head also wobbles in the second cone. The semiangle of each cone was estimated to be 35 and 48 degrees, respectively. We found that myosin heads in myofibrils under relaxing conditions extensively rotated as in myosin filaments in solution. When the spacing between thick and thin filaments was artificially reduced by the increase of osmotic pressure with the addition of polyvinylpyrrolidone (PVP), restriction of the angular range of the rotational motion was observed. Under rigor conditions no motion was observed in a 10 microsecond time scale, indicating that the heads were immobilized by binding to thin filaments. Preliminary results on the rotational motions of myosin heads in muscle fibers are also reported.

Animals↗
PubMed1987

Self-catalyzed inactivation of cytochrome P-450 during microsomal metabolism of cannabidiol.

When cannabidiol (CBD) was incubated with hepatic microsomes of mice in the presence of an NADPH-generating system, a significant decrease of cytochrome P-450 content was observed by measuring its carbon monoxide difference spectra. The decrease of cytochrome P-450 by CBD required NADPH and molecular oxygen. The effect was partially inhibited by SKF 525-A but not by various scavengers of active oxygen species, superoxide anion, hydroxyl radical and singlet oxygen. The incubation of CBD with hepatic microsomes did not affect total heme but decreased significantly free sulfhydryl contents in the microsomes. The derivatives of CBD modified in the resorcinol moiety, CBD-monomethyl- and dimethylethers, almost lost the effect on cytochrome P-450, whereas those modified in the terpene moiety, 8,9-dihydro- and 1,2,8,9-tetrahydro-CBDs exhibited some potency to inactivate cytochrome P-450. The inactivation of cytochrome P-450 by CBD and related compounds led to the inhibition of hepatic microsomal p-nitroanisole O-demethylase and aniline hydroxylase activities. These results suggest that the resorcinol moiety of CBD plays some role in the inactivation of cytochrome P-450 by the cannabinoid.

Animals↗
PubMed1987

Change in hypothermia and catalepsy induced by cannabinoids or morphine in mice tolerant to these substances.

delta 8-Tetrahydrocannabinol (THC)- and 8 beta, 9 beta-epoxyhexahydrocannabinol (EHHC)-tolerant mice were tolerant to the hypothermia produced by morphine while 8 alpha, 9 alpha-EHHC-tolerant mice were not. Morphine-tolerant mice acquired partial tolerance to the hypothermic effect of 8 alpha,9 alpha-EHHC, but not to the effect of delta 8-THC and 8 beta,9 beta-EHHC. Cataleptogenic effects of all cannabinoids were enhanced in morphine-tolerant mice as compared to non-tolerant animals. It seems that morphine-tolerant mice exhibited hypersensitivity to the cataleptogenic effect of the cannabinoids without potentiation of the hypothermia. These results suggest that the morphine-tolerant mouse may acquire 'latent' cross-tolerance to the hypothermic effect of the cannabinoids.

Animals↗
PubMed1987

Enhanced binding of morphine and nalorphine to opioid delta receptor by glucuronate and sulfate conjugations at the 6-position.

Effect of the modification of morphine and nalorphine by glucuronate and sulfate conjugations at the 3- and 6-positions on the binding to opioid receptors was examined in a particulate fraction of rat brain. Competing potencies of both drugs against [3H]morphine and [3H]leucine enkephalin bindings were extremely decreased by either glucuronate or sulfate conjugation at the 3-position. On the other hand, the potencies of morphine and nalorphine against [3H]leucine enkephalin binding were considerably enhanced by the conjugations at the 6-position, whereas the potencies against [3H]morphine binding were decreased. These altered interactions of the conjugates at the 6-position with the two ligands were attributed to their enhanced binding to delta-receptor and reduced binding to mu-receptor by Hill plot and modified Scatchard analysis. Resulted comparable and simultaneous interactions with mu- and delta- receptors were assumed to be a cause of the enhanced mu-receptor-directed analgesia of morphine and elevated same receptor-directed antagonistic effect of nalorphine, which have been found previously in our laboratory.

Animals↗
PubMed1987

Rotational motions of myosin heads in myofibril studied by phosphorescence anisotropy decay measurements.

We studied the rotational Brownian motions of myosin heads, of which the sulfhydryl group was selectively labeled with the triplet probe 5-eosinylmaleimide, in myofibril by using flash-induced phosphorescence anisotropy decay measurements. The anisotropy decay curve under relaxing conditions consisted of a fast (submicrosecond) and a slow (a few microseconds) component and a small constant part as in the synthetic myosin filaments in solution. The decay curves could be analyzed by assuming that a head part, i.e. subfragment 1 (S1), wobbles in the first cone and a part connecting S1 and the tail of a myosin molecule of which the length is shorter than subfragment 2 (S2) wobbles in the second cone (a double-cone model); the semiangles of the former and the latter cones were about 30 degrees and 50 degrees, respectively. The rotational freedom of myosin heads was only slightly restricted by the limited space of the filament lattice in myofibrils. Under rigor conditions, no motion of myosin heads was observed in the 10-microseconds time scale.

Animals↗
PubMed1987

Psychotropic effects of adrenergic beta-blockers on agonistic behavior between resident and intruder mice.

The present study was conducted to investigate the effect of adrenergic beta-blockers on agonistic behavior in male mice, using quantitative ethological methods. Agonistic behavior was evoked using a resident-intruder paradigm. The following drugs were administered orally at four dose levels (vehicle, 5, 10 and 20 mg/kg) to either resident or intruder mice: dl-propranolol, practolol, d-propranolol, and l-propranolol. When the resident was treated with either dl-propranolol or l-propranolol, aggressive episodes (offensive sideways posture, attack bite, tail rattle) were suppressed significantly in a dose-dependent manner, whereas practolol and d-propranolol were ineffective. All treatments except the high dose of l-propranolol failed to affect the resident's solitary behavior (locomotion). When the intruder was treated with beta-blockers, agonistic behavior was not altered. Since practolol does not cross the blood-brain barrier, the differential suppression of agonistic behavior is due to the central action of beta-blockers. d-Propranolol does cross the blood-brain barrier but is devoid of beta-receptor blocking property; hence l-propranolol suppression of agonistic behavior implies inactivation of brain adrenergic beta-receptors. The findings seem to indicate that beta-blockers such as dl-propranolol and l-propranolol have a psychotropic action.

Adrenergic beta-Antagonists↗
PubMed1987

Embryolethal and teratogenic effects of bromofenofos in rats.

Bromofenofos, an organophosphorus anthelmintic, was administered by gavage to rats as a single dose (50 mg/kg) on one of days 6 through 14 of pregnancy. The dams were killed on day 21, and the fetuses were removed, weighed and examined by routine teratological methods. A significant increase in fetal resorptions occurred after administration on days 9 through 13, with a maximum on day 10. Approximately 72% of the implants were resorbed after administration on day 10. Fetal body weights were significantly decreased when dams were treated on day 8 or later. The greatest decrease in fetal body weights was observed on day 10, when the fetuses weighed less than the controls by about 44% on the average. The incidence of fetuses with gross, skeletal and internal malformations was significantly increased on days 8 through 10, on days 8 through 11 and on days 8 and 9, respectively. Although various types of malformations were observed, most of them occurred on day 8, when no significant increase in fetal resorptions did occur. Cleft lip, short tail, brachygnathia, anal atresia, absence of genital tubercle, fused pelvic legs and perineal testicles were seen on day 8 as gross malformations. Skeletal malformations mainly affected the vertebrae and ribs. Major internal malformations on day 8 were hydronephrosis, hydroureter, anophthalmia, cleft palate, agenesis of the bladder and renal agenesis. Anophthalmia and/or microphthalmia were observed on days 8 through 10, with the highest incidence on day 9.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗