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Biomedical subjects

E Tanaka

Publications and source records attributed to E Tanaka.

At least 595 records · Page 33Linked to original sources

Trimethadione as a model drug for the evaluation of hepatic drug-metabolizing capacity in normal and alpha-naphthylisothiocyanate-intoxicated rats.

The relationship between the plasma concentration ratio of 5,5-dimethyl-2,4-oxazolidinedione (DMO) to trimethadione (TMO) and cytochrome P-450-dependent drug-metabolizing enzyme activities in rats pretreated with different dose levels of alpha-naphthylisothiocyanate (ANIT) was investigated. Pretreatment of rats with different dose levels of ANIT resulted in a prolongation of TMO half-life, an increase of the area under the curve (AUC), a decrease of clearance (CL) and a decrease of the apparent volume of distribution (Vd). At any dose of ANIT used, there was a good correlation between the ratio of DMO to TMO in plasma and activities of hepatic cytochrome P-450-dependent drug-metabolizing enzymes, such as cytochrome P-450 and cytochrome b5 contents and aminopyrine N-demethylase, TMO N-demethylase and aniline hydroxylase. These results, together with the previous findings, indicate that determination of the plasma levels of TMO and DMO might be a useful index of drug-metabolizing capacity of the liver.

1-Naphthylisothiocyanate↗

Studies on the trimethadione metabolism as a tool for the assessment of drug-metabolizing capacity using plasma and urine of rats pretreated with phenobarbital and 3-methylcholanthrene.

To determine whether concentrations of trimethadione (TMO) and its metabolite 5,5-dimethyl-2,4-oxazolidinedione (DMO) in plasma as well as in urine of rats are useful indicator of drug-metabolizing capacity or not, the following experiments were carried out. Plasma TMO and DMO concentrations were measured in phenobarbital (PB) or 3-methylcholanthrene (3-MC)-pretreated rats following the administration of TMO. In PB-pretreated rats, there was a good correlation between elimination rate constant (Kel and plasma DMO/TMO ratio; r = 0.991 at 1 h, r = 0.967 at 2 h). However, there was no good correlation in 3-MC-pretreated rats (r = 0.780 at 1 h, r = 0.720 at 2 h). TMO and DMO excretion in PB and 3-MC pretreated rats following the administration of TMO were not significantly different in 24-h urine. These experiments, together with the previous findings, indicate that concentrations of TMO and DMO in plasma, but not in urine, in PB-pretreated rats may be a useful indicator of drug-metabolizing capacity.

Animals↗

Histochemical study of the efferent nervous system in the guinea pig inner ear.

The efferent nervous system of the guinea pig inner ear is histochemically investigated. Remarkable activity of alkaline phosphatase and acetylcholinesterase is demonstrated by Burstone's (1958) azo dye method and Koelle's (1949) method as modified by Gomori (1952) respectively. The distribution pattern of both enzymes in the efferent nervous system is entirely similar. The intraganglionic spiral bundles, fascicles of the osseous spiral lamina and efferent plexus of the organ of Corti reacted intensely for both enzymes. Afferent nerve fibers give no histochemical reaction for both alkaline phosphatase and acetylcholinesterase. However, spiral and vestibular ganglion cells are rich in both enzymes, though they belong to the afferent nervous system. The significance of both enzymes in the nervous system of the guinea pig inner ear is briefly discussed.

Acetylcholinesterase↗

Pharmacokinetic studies of trimethadione and its metabolite in rats with chemical-induced liver injury.

A rapid and sensitive gas-liquid chromatographic procedure was developed for the measurements of trimethadione (TMO) and its metabolite, 5, 5-dimethyl-2, 4-oxazolidine-dione (DMO) in plasma. TMO and DMO were extracted from plasma by a micro-extraction method and chromatographed on a 10% Carbowax 6000 column using paramethadione as an internal standard. Recoveries of TMO and DMO ranged from 96 to 104% using a 0.1 ml of plasma. The method is capable of measuring at least 5 microgram of TMO and DMO per milliliter. After an oral administration of TMO at a dose of 100 mg/kg, mean plasma levels of TMO and DMO in 6 rats reached a peak of 98 microgram/ml at 0.6 h and 163 microgram/ml at 8 h and declined with a half-life of 2.2 h and 39.4 h, respectively. After the intravenous administration of TMO at a dose of 100 microgram/kg, half-lives of TMO and DMO were 2.5 h and 39.1 h, respectively. Pretreatment of rats with carbon tetrachloride, d-galactosamine amd alpha-naphthyl isothiocyanate, prolonged T 1/2 and Tmax of TMO, reduced the Km value and increased the AUC. These results suggest that plasma levels of TMO and DMO might be useful as an index of drug metabolizing capacity in animal and man.

1-Naphthylisothiocyanate↗

Saliva levels of trimethadione and its metabolite as an index of drug metabolizing activity in rats.

1. It was investigated in normal and liver-injured rats administered with trimethadione (TMO) as to whether concentrations of TMO in plasma are able to be predicted from the corresponding saliva levels. 2. The saliva/plasma (S/P)ratio of TMO was about 1, while its metabolite 5,5-dimethyl-2,4-oxazolidinedione (DMO) showed a S/P ratio of 0.65. 3. In normal rats, there was a high correlation between saliva and plasma concentration of TMO and DMO. (TMO: r=0.966, DMO: r=0.950). 4. In liver-injured pretreated rats with carbon tetrachloride, alpha-naphthyl isothiocyanate or D-galactosamine, there was a high correlation between the saliva DMO/TMO ratio and the plasma DMO/TMO ratio after oral administration of TMO (r=0.983 at 1 h, r=0.952 at 2 h). 5. The saliva DMO/TMO ratio, as well as the plasma DMO/TMO ratio, may be utilized as an index of drug-metabolizing activity of the liver.

Animals↗

Determination of plasma trimethadione and its metabolite carbon tetrachloride-intoxicated rat liver: a useful tool for estimation of hepatic drug metabolizing capacity.

1. The relationship between the plasma concentration ratio of 5,5-dimethyl-2,4-oxazolidinedione (DMO) to trimethadione (TMO) and cytochrome P-450 dependent drug-metabolizing enzyme activities after administration of TMO to rats pretreated with different dose levels of carbon tetrachloride (CCl4) was investigated. 2. Pretreatment of rats with different dose levels of CCl4 resulted in a prolongation of TMO half-life, and increase of the area under the curve (AUC), and a decrease of clearance, but the apparent volume of distribution (Vd) was not significantly decreased. 3. Depending on the extent of liver-injury by CCl4, there was a good correlation between the ratio of DMO to TMO in plasma and hepatic cytochrome P-450 dependent drug -metabolizing enzyme activities such as cytochrome P-450 content (r=0.796 at 1 h, r=0849 at 2 h), aminopyrine N-demethylase activity (r=0.877 t 1 h, r=0905 at 2 h), TMO N-demethylase activity (r=0.876 at 1 h,r=0.928 at 2 h) and aniline hydroxylase activity (r=0.900 at 1 h, r=0.936 at 2 h). 4. These results, together with the previous findings, indicate determination of the plasma levels of TMO and DMO might be a useful tool as an index of drug metabolizing capacity of rat livers.

Animals↗

Guillain-Barré syndrome presenting with signs of ophthalmoplegia.

Two cases of Guillain-Barré syndrome (GBS) presenting with signs of ophthalmoplegia were reported. One showed unilateral internal ophthalmoplegia without external ophthalmoplegia, and the other displayed partial external ophthalmoplegia with sluggish pupillary response to light. It is important to keep in mind the possibility of GBS with acute onset of internal and/or external ophthalmoplegias.

Child↗

New Anger scintillation cameras with improved count rate capability.

This paper proposes scintillation cameras which can handle input pulse rates beyond 1 Mcps with negligible as spatial resolution and energy resolution at low pulse rates. The cameras are based on the "variable sampling-time technique", in which phototube current pulses are first shortened in width and then selectively integrated by gated integrators followed by sample-and-hold circuits. The period of integration before sampling is not fixed but shortened by the arrival of the following pulse to keep a high pulse-pair time resolution. An approximate expression for the count rate characteristics has been derived, and its validity was confirmed by Monte Carlo simulation. The results indicates that the maximum observed count rate will reach 420-520 kcps with an energy window fraction of 0.5 for typical design parameters.

Scintillation Counting↗