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Biomedical subjects

N Yamada

Publications and source records attributed to N Yamada.

At least 793 records · Page 44Linked to original sources
PubMed1986

Induction of rat liver microsomal drug-metabolizing enzymes by a new sleep inducer 450191-S and plasma levels of 450191-S-metabolites.

Liver microsomal 7-alkoxycoumarin O-dealkylase activities in rats were stimulated by the administration of large doses of 5-[(2-aminoacetamide)methyl]-1-[4-chloro-2-(o-chlorobenzoyl)phenyl ]-N, N-dimethyl-1 H-s-triazole-3-carboxamide hydrochloride dihydrate (450191-S), a new sleep inducer which is a 1H-1,2,4-triazolyl benzophenone derivative. To obtain the correlation between the stimulation or induction of hepatic enzymes and the plasma level of the metabolites of 450191-S, various amounts of 450191-S were administered orally to rats and the metabolites in plasma were determined by high performance liquid chromatography. Plasma concentration-time profiles for metabolites in rats showed the appearance of metabolites in plasma followed by their rapid disappearance from blood when the animals received non-inducing amounts of 450191-S. On the other hand, the profiles of metabolites in rats administered higher amounts of the drug showed very high plasma concentrations of metabolites, especially 8-chloro-6-(2-chlorophenyl)-N-methyl-4H-1,2,4-triazolo [1,5-a] [1,4]benzodiazepine-2-carboxamide (M-2) and 8-chloro-6-(2- chlorophenyl)-N-hydroxymethyl-4H-1,2,4-triazolo [1,5-a] [1,4]benzodiazepine-2-carboxamide (M-A), which were maintained for a long time with slow elimination. These results led to the conclusion that the induction of hepatic drug-metabolizing enzymes is closely correlated with the high plasma concentrations of metabolites and their prolonged existence in plasma.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1986

[Inhibitory effect on the release of mediators from rat peritoneal exudate cells and the antagonistic effect against mediators of MY-5116 and other anti-allergic agents].

The effects of a new anti-allergic agent, MY-5116: isoamyl 5,6-dihydro-7,8-dimethyl-4,5-dioxo-4H-pyrano [3,2-c] quinoline-2-carboxylate, and its main metabolite, MY-1250: 5,6-dihydro-7,8-dimethyl-4,5-dioxo-4H-pyrano [3,2-c] quinoline-2-carboxylic acid, on 48 hr homologous PCA (PCA) in rats and the release of histamine and SRS from rat peritoneal exudate cells (PEC) induced by IgE antibody in comparison with other anti-allergic agents were investigated. Also, the effects of MY-5116 and MY-1250 on antagonistic action against histamine and LTD4 were studied. MY-5116, tranilast and ketotifen inhibited PCA at oral doses of more than 3 mg/kg, 300 mg/kg and 0.3 mg/kg, respectively. MY-1250, DSCG and tranilast inhibited significantly the release of histamine from PEC induced by the antigen-antibody reaction in a dose-dependent manner, and the values of IC50 were 4.9 X 10(-8), 4.8 X 10(-6) and 4.6 X 10(-6) g/ml, respectively. Ketotifen inhibited significantly the release of histamine at a concentration of 10(-5) g/ml, but it accelerated significantly the release of histamine from PEC at a concentration of 10(-4) g/ml. MY-1250 and tranilast suppressed the release of SRS from PEC induced by the antigen-antibody reaction. The values of IC50 of MY-1250 and tranilast were 1.5 X 10(-6) and 2.1 X 10(-6) g/ml, respectively. MY-1250 suppressed slightly the release of SRS from PEC induced by A23187. MY-5116 showed no effect on the increase of vascular permeability induced by histamine, bradykinin and serotonin in rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

[Effects of MY-5116 on experimental animal models of type I-type IV allergic reactions and the formation of IgE antibody].

The effects of a new anti-allergic agent, MY-5116: isoamyl 5,6-dihydro-7,8-dimethyl-4,5-dioxo-4H-pyrano [3,2-c] quinoline-2-carboxylate, on experimental animal models of type I approximately type IV allergic reactions and the formation of IgE antibody were investigated. MY-5116 administered intraperitoneally at doses of 30 and 100 mg/kg suppressed significantly the homologous PCA in guinea pigs. MY-5116 administered intraperitoneally at the dose of 100 mg/kg also suppressed significantly the heterologous PCA in guinea pigs. MY-1250, the main active metabolite of MY-5116, showed no suppression on the Schultz-Dale reaction in guinea pigs, and MY-5116 showed no inhibition on the active systemic anaphylaxis in mice (type I). MY-5116 showed no inhibition on the reversed cutaneous anaphylaxis in rats (type II), the Forssman reaction in guinea pigs (type II), the Arthus reaction in mice (type III) and the delayed type hypersensitivity in mice (type IV). MY-5116 showed no suppression on the formation of IgE antibody in C3H/He and BALB/c mice and rats. From these results, it is concluded that MY-5116 selectively suppresses the experimental models of type I allergic reaction.

Anaphylaxis↗
PubMed1986

Cytochrome P-450-dependent monooxygenase activities in prenatal and postnatal human livers: comparison of human liver 7-alkoxycoumarin O-dealkylases with rat liver enzymes.

Human liver samples from 17 embryos, 5 fetuses, 5 infants and 4 adults were used to investigate human liver cytochrome P-450-dependent 7-alkoxycoumarin O-dealkylase activities, and their drug-metabolizing activities were compared to those of rat livers. The O-dealkylase activities in human embryos and fetuses were very low, although detectable, similar to those in fetal rats. Both male and female rats showed a postnatal increase of hepatic O-dealkylase activities with a maximum at about 30-40 days after birth and then a decline in the activities which was marked in female rats. Adult female rats showed a marked decrease in the hepatic enzyme activity observed in the O-depropylation reaction rather than the O-demethylation and O-deethylation reactions. During the developmental period of human infants, the O-demethylase activity, but not O-depropylase activity, increased gradually. Enzymes in adult human livers metabolize the O-methyl derivative of 7-hydroxycoumarin in preference to the O-ethyl and O-propyl derivatives. The metabolic activities of human adult enzymes for 7-alkoxycoumarin resembled those in adult female rats and were quite different from those in male rats. The study demonstrated that caution must be exercised in extrapolating pharmacological results from animal to man in the field of drug metabolism.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1986

Adult adrenoleucodystrophy with hypercortisolemia.

A 39-year-old male showed rapid progression of cerebral white matter involvement after 8 years' duration of adrenomyeloneuropathy. Increased ratio of C:26 to C:22 in the fatty acid composition of sphyngomyelin in the blood and needle-like cytoplasmic inclusions in the biopsied peripheral nerve were indicative of adrenoleucodystrophy or adrenoleucomyeloneuropathy. Plasma ACTH levels were extremely elevated, but most of ACTH immunoactivity was eluted at the molecular weight of 55000. Plasma cortisol levels were initially within normal range and were elevated in the final stage. Possible mechanism of elevated ACTH in this disorder was briefly discussed.

Adrenocorticotropic Hormone↗
PubMed1986

Measurement of apolipoprotein B radioactivity in whole blood plasma by precipitation with isopropanol.

A method to measure apolipoprotein B radioactivity in whole blood plasma is described that is suitable for routine use in kinetic experiments in vivo. Radiolabeled apolipoprotein B is precipitated from plasma diluted 15- to 30-fold in the presence of carrier low density lipoproteins by 50% isopropanol. The amount of radioiodine in apoB is estimated from the difference between total radioiodine concentration in whole plasma and the fraction soluble in 50% isopropanol. Addition of up to 100 microliters of plasma to radioiodinated lipoproteins did not alter the percent of radioiodine precipitated in 1500 microliters of 50% isopropanol. The percent of radioiodine precipitated by isopropanol 3 min after intravenous injection of homologous radioiodinated very low density lipoproteins, intermediate density lipoproteins, and low density lipoproteins into rabbits was almost identical to that in the injected lipoproteins (y = 1.009 X +/- 0.462; r = 0.997).

1-Propanol↗
PubMed1986

[Local cerebral blood flow and glucose metabolism in experimental meningeal carcinomatosis].

Patients with meningeal carcinomatosis often evolve signs of impairment in higher mental function. Yet, common findings of histological observation are only a sheet of tumor cells on the cortical surface, and no intracerebral mass are noted. To elucidate mechanism of mental disturbances in meningeal carcinomatosis, local cerebral blood flow and glucose metabolism were evaluated in a model of experimental meningeal carcinomatosis. Viable cells (1 X 10(4) of Walker 256 tumor were inoculated into cisterna magna of Wistar rats. Animals were used for autoradiographic study at 1 to 12 days after tumor inoculation. Local cerebral glucose utilization (LCGU) and local cerebral blood flow (LCBF) were measured with quantitative autoradiographic technique using 14C-iodoantipyrine and 14C-deoxyglucose as a tracer, respectively. In the early stage of tumor growth (1 to 3 days after tumor inoculation), reduction of LCGU was averaged to be 31% in the cerebral cortex and 28% in the deep structures, whereas reduction of LCBF was 28% in cerebral cortex and 19% in deep structures on average. In the late stage of tumor growth (4 to 12 days after tumor inoculation), average reduction of LCGU was 57% in the cerebral cortex and 47% in the deep structures. On the other hand, reduction of LCBF was averaged to be 42% in the cerebral cortex and 38% in the deep structures in the late stage of the disease. Reduction of LCGU and LCBF was especially evident in the sensory cortices such as parietal cortex, visual cortex and auditory cortex, and in the auditory centers of the brain stem such as medial geniculate body and inferior colliculus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Direct radioimmunoassay of cortisol in saliva and its application to the dexamethasone suppression test in affective disorders.

In order to perform the dexamethasone suppression test (DST) with saliva as an alternative to serum, we assayed directly the cortisol concentrations in 25 microliters saliva samples, using a commercial radioimmunoassay kit for serum cortisol with minor modifications. Cortisol in saliva showed a diurnal rhythm parallel to that of cortisol in serum samples collected simultaneously. Saliva cortisol levels increased significantly after ACTH injection, but with a 60 min delay in reaching their peak compared to peak serum cortisol levels. The increase in saliva cortisol was five-fold, while that in serum was two-fold. Saliva cortisol levels continued to increase in some subjects while serum total cortisol levels already had begun to decline. In those subjects, the correlation of saliva with serum cortisol was greater when a quadratic curve was fitted than when calculated for a linear correlation. Considerable variation was observed for within-subject correlations, ranging from + 0.48 to + 0.999. The DST with saliva sample collection was performed on 43 inpatients with affective disorders. Sensitivity, specificity and diagnostic confidence of the DST for major depressive episode with melancholia were 33%, 91%, and 78%, respectively, at the criterion value of 0.3 microgram/100 ml for saliva cortisol, which are similar to those most often reported for the DST with serum cortisol determination. These results indicate that saliva cortisol levels do not always parallel serum cortisol levels and thus are not an unequivocal substitute. The findings for the DST in psychiatric patients, however, support the practical clinical usefulness of saliva cortisol measurements.

Adrenocorticotropic Hormone↗
PubMed1985

Dog coronary artery adenosine receptor: structure of the N6-alkyl subregion.

The moderately potent and stereoselective coronary vasoactivity of N6-[1-phenyl-2(R)-propyl]adenosine (1) is the basis for the present study that maps the N6 region of the coronary artery adenosine receptor by means of the structure-coronary vasoactivity relationships of 81 analogues of 1 in the open-thorax dog. Stereoselectivity is a general property of N6-substituted adenosines that have a chiral center adjacent to N6. The activity ratio of 1 to its S diastereomer is 10, the result of the positive interaction with the receptor of the propyl C-3 group of the R diastereomer in combination with the steric hindrance exerted by this group of the S diastereomer. Replacing the benzyl moiety of 1 by an ethyl, phenyl, phenethyl, or naphthyl group lowers potency of the R diastereomer and, accordingly, the R/S ratio. Propyl C-1 of 1 interacts with a receptor region large enough to accommodate three methylene residues and the propyl C-3 residue with a separate region large enough to accommodate two. The receptor subregion that interacts with the propyl C-1 of 1 is more tolerant of bulk and of polar substituents than the subregion that interacts with propyl C-3. Evidence bearing on the possible contribution of N6 to activity, e.g. through hydrogen bonding, is ambiguous. These results support a provisional model of the N6-alkyl subregion.

Adenosine↗