Search PubMed⌕ Search

Biomedical subjects

Y Kasuya

Publications and source records attributed to Y Kasuya.

At least 343 records · Page 19Linked to original sources
PubMed1981

Lack of parallelism between the positive inotropic effects of various cardiac stimulants and their activities to produce the slow channels in the depolarized myocardium.

Positive inotropic actions in the normal guinea pig cardiac muscle and the activities required to produce electrical and mechanical responses in the depolarized muscle were examined using epinephrine, dopamine, metanephrine, aminophylline, histamine, serotonin, tyramine, tetraethylammonium (TEA), tetramethylammonium (TMA), and X-537A, a calcium ionophore. In the normal cardiac muscle, histamine produced the greatest positive inotropic action, followed by epinephrine, dopamine and TEA. In the cardiac muscle made inexcitable by the elevated potassium (30 mM), all of the agents tested produced electrical and mechanical responses. Aminophylline was the most potent in the activity to produce the mechanical response in the depolarized muscle; the potencies of histamine, dopamine, X-537A, epinephrine and TEA were much the same. From these results, it was concluded that the positive inotropic effects of the cardiac stimulants are not produced solely through the mechanisms related to the slow channels, but that other mechanisms must be involved in the normal condition where the fast sodium channels are functioning.

Aminophylline↗
PubMed1981

Studies on nitrosamine formation by the interaction between drugs and nitrite. I. Measurement of the amount of nitrosamine formed in rat and guinea pig stomachs.

The amounts of nitrosamine formed by the interaction of several drugs and nitrite in rat and guinea pig stomachs were estimated. The nitrosamine formation from aminopyrine and nitrite was much more in guinea pig stomachs than in rat stomachs. It seemed that this result was due to the difference in gastric contents of these animals. As the nitrosamine formation was also indicated in the interaction of a clinically prescribed dose of aminopyrine and very low doses of nitrite in rat and guinea pig stomachs, there is a possibility that the nitrosation of aminopyrine takes place in human stomachs, too. Minocycline also interacted with nitrite and formed N-nitrosodimethylamine. However, the amount of nitrosamine formed was less in minocycline than in aminopyrine. Oxytetracycline was not found to form nitrosamine in the stomachs of these animals. The effects of several compounds on the nitrosamine formation by the interaction of aminopyrine and nitrite were also investigated. Ascorbic acid, sodium erythorbate, propyl gallate and butylated hydroxyanisole reduced the nitrosamine formation but the effect of alpha tocopherol, sorbic acid and butylated hydroxytoluene was not observed in the stomach.

Aminopyrine↗
PubMed1981

Studies on nitrosamine formation by the interaction between drugs and nitrite. II. Hepatotoxicity by the simultaneous administration of several drugs and nitrite.

The alterations of biochemical parameters, namely, glutamic oxaloacetic transaminase and glutamic pyruvic transaminase in serum, hepatic microsomal drug oxidation systems, glucose-6-phosphate dehydrogenase and lysozomal enzymes in hepatic soluble fraction were investigated for the purpose of semiquantitatively estimating the hepatotoxicity caused by the interaction of several drugs and sodium nitrite in rats. The simultaneous administration of aminopyrine and sodium nitrite induced the alterations of these parameters. However, these alterations were not induced by the administration of antipyrine and sodium nitrite. Therefore the alterations were thought to be mainly due to N-nitrosodimethylamine formed. The administration of 0.4 mmole/kg of aminopyrine and 1.0 mmole/kg of sodium nitrite was thought to induce the alterations to almost the same extent as induced by 0.15 mmole/kg of N-nitrosodimethylamine. The simultaneous administrations of sodium nitrite and several other drugs with tertiary amino groups, namely oxytetracycline, diphenhydramine, oleandomycin, erythromycin and minocycline induced small alterations of these parameters. However, these alterations were not thought to relate to the hepatic injury induced by N-nitrosodimethylamine. Therefore the amount of N-nitrosodimethylamine formed from these drugs in rats was thought to be rather small. We also investigated the effect of several antioxidants on the alterations of biochemical parameters induced by aminopyrine and sodium nitrite. Ascorbic acid, sodium erythorbate and propyl gallate inhibited these alterations. On the other hand, sorbic acid did not.

Aminopyrine↗
PubMed1981

Manifestation of latent alpha-excitatory response in the canine tracheal smooth muscle preparation--relation to basal tone.

Alpha-adrenergic contractile response of the tracheal smooth muscle preparation isolated from young adult dogs was investigated. When the basal tone of the preparation was elevated by spasmogens, methacholine, K+, etc., in the presence of 1 microM propranolol, norepinephrine and phenylephrine caused contraction of the preparation. Isoproterenol did not. The contraction was specifically antagonized by phentolamine. The height of contraction caused by alpha-stimulants depended on the height of basal tone. The relationship of them was essentially the same whether methacholine on K+ was used as spasmogen, and if the Ca ion concentration in Krebs' solution was reduced to 0.1 mM. It was concluded that the tracheal smooth muscle of young adult dogs which is usually insensitive to alpha-stimulants responds to them when the basal tone is elevated by spasmogens, and it was suggested that an elevated intracellular free-Ca ion level contributed to this phenomenon.

Animals↗
PubMed1981

Vasodilating effect of flunarizine in anesthetized dogs.

The effect of flunarizine on the peripheral vascular beds of anesthetized dogs was investigated and compared with those of cinnarizine and papaverine. Flunarizine, cinnarizine and papaverine generally caused hypotension, tachycardia and vasodilation, although bradycardia preceded by tachycardia was observed after the high doses of flunarizine and cinnarizine. There was no significant difference between the changes in vertebral, hindquarter and mesenteric vascular resistances induced by flunarizine and cinnarizine, while the duration of the vasodilating effect of flunarizine was longer than that of cinnarizine especially in the vertebral vascular bed. Furthermore, the duration of the effect of flunarizine on the vertebral vascular bed was significantly longer than that on the mesenteric vascular bed.

Animals↗
PubMed1981

The role of morphological and functional changes in adrenergic nerves for the development of colchicine-induced supersensitivity in the rat vas deferens.

Local application of colchicine to the hypogastric plexus produced degenerative changes in about 40% of adrenergic nerve endings and a decrease in the neuromuscular transmission in the rat vas deferens. Unlike after denervation, both decreases in the number of normal nerve terminals and neuromuscular transmission induced by colchicine were incomplete and reversible. Although the time course of these changes was apparently related to that of the development of supersensitivity after colchicine treatment, the degeneration of adrenergic nerves does not seem to be an essential factor for the manifestation of colchicine-induced supersensitivity which is quantitatively and qualitatively identical to that induced by denervation. It is suggested that some neurotrophic factor(s) may contribute to the control of responsiveness of the smooth muscle and that the denervation-like supersensitivity is induced by colchicine through an interference of axonal transport in adrenergic nerves.

Animals↗
PubMed1980

Replacement of K+ with Rb+ or Cs+, and its effects on the mechanical responses to norepinephrine and methacholine in the rat vas deferens.

The rat vas deferens was stored overnight in cold, K+-free Krebs solution to deplete intracellular K+ then incubated in K+-, Rb+-, or Cs+-containing Krebs solution at 37 degrees C to load these ions inside the cells. After 4 h, the contents of K+ or Rb+ reached the level of K+ in the fresh vas deferens; the content of Cs+ was less than half that of the fresh vas deferens. Dose-response curves to norepinephrine and methacholine were determined under these conditions, and the curves in Rb+ or Cs+ solution were compared with those in K+ solution. The cold storage per se had little effect on the dose-response curves in K+ solution except that it slightly decreased the maximal response to norepinephrine. The dose-response curves in Rb+ solution were to the left of those in K+ solution. The maximal response to methacholine was greatly increased. On the other hand, the dose-response curves in Cs+ solution were to the right of those in K+ solution. The maximal responses were greatly decreased with both drugs. The results suggest that Rb+ but not Cs+ can fully substitute for K+ in the rat vas deferens response to norepinephrine and methacholine.

Animals↗
PubMed1980

Use of stable isotopes in the study of pharmacokinetics of drugs by mass fragmentography II: Detailed examination of pharmacokinetics of a single oral dose of phenytoin in humans.

To study the pharmacokinetics of phenytoin in detail, a mass fragmentographic method was applied for the precise, sensitive, and specific analysis of phenytoin, 5-(4-hydroxyphenyl)-5-phenylhydantoin, and 5-(4-hydroxyphenyl)-5-phenylhydantoin glucuronide in plasma and urine after administration of a single oral dose of phenytoin to two healthy volunteers. Salivary phenytoin concentrations also were measured. Phenytoin and 5-(4-hydroxyphenyl)-5-phenylhydantoin were analyzed after the addition of deuterium-labeled internal standards and conversion to volatile methyl derivatives for mass fragmentographic analysis. The lower limit of detection was approximately 10 ng/ml. The simultaneous pharmacokinetic analysis of the plasma levels and urinary excretion data of phenytoin and its major metabolite, 5-(4-hydroxyphenyl)-5-phenylhydantoin, yielded detailed information about the pharmacokinetics of phenytoin.

Administration, Oral↗
PubMed1980

Changes in sensitivity to histamine of guinea pig cardiac muscles during postnatal development.

Histamine stimulates the heart by interacting with cardiac histamine receptors. We investigated the postnatal changes in histamine sensitivity with spontaneously beating right atria and electrically driven left atria and right ventricular papillary muscles from 0-, 5-, and 10-day-old and adult guinea pigs. The positive chronotropic response to histamine in right atria was antagonized by cimetidine but not by chlorpheniramine at any age. Chlorpheniramine did not antagonize the positive inotropic effect of histamine and 2-(2-pyridyl)ethylamine in the immature left atria but it blocked the positive inotropic effect in the adult; cimetidine had no effect. The positive inotropic effect of histamine in right ventricular muscles was not affected by chlorpheniramine in immature right ventricular muscles but was antagonized in the adult. These results suggest that, in immature left atria and right ventricular muscles, there is no H1-receptor system mediating the positive inotropic effect of histamine and that, as age advances, this system begins to mediate the positive inotropic effect. In immature left atria, non-H1 and non-H2 receptors exist and mediate the positive inotropic effect of histamine.

Animals↗
PubMed1980

Differentiation between endogenous and exogenous testosterone in human plasma and urine after oral administration of deuterium-labeled testosterone by mass fragmentography.

A mass fragmentographic method employing stable isotopically labeled testosterone was employed to simultaneously determine the concentrations of endogenous and exogenous testosterone in the urine and plasma of two healthy male volunteers. After oral administration of 20 mg testosterone-19,19,19-d3, a slight but significant amount of the deuterated testosterone appeared in the plasma and was rapidly cleared. The results show that the exogenous testosterone did not influence the plasma levels or urinary excretion of endogenous testosterone.

Administration, Oral↗
PubMed1980

Absorption, metabolism, and excretion of oral testosterone in humans by mass fragmentography.

A mass fragmentographic method employing stable isotopically labeled testosterone was employed to follow the time course of urinary excretion of the two main testosterone metabolites, androsterone glucuronide and etiocholanolone glucuronide, in humans after the oral administration of 20 mg testosterone-19.19.19-d3. The results indicate that the extensive metabolism of testosterone in the liver could be the reason that the orally administered testosterone appeared in the circulation only in small amounts, even though testosterone was completely absorbed from the gastrointestinal tract.

Administration, Oral↗
PubMed1980

Negative chronotropic effect of dibutyryl cyclic AMP on the cultured chick embryonic heart cells and the prolongation of the action potential duration.

It was shown that there were clear differences between the effects of norepinephrine and dibutyryl cyclic AMP on the cultured chick embryonic heart cells. Norepinephrine and dibutyryl cyclic AMP was applied to the cultured chick embryonic heart cells, and the changes in the beating rate and the action potential configuration were examined. Norepinephrine increased the beating rate, but dibutyryl cyclic AMP produced the significant negative chronotropic effect. Norepinephrine increased the slope of the diastolic depolarization with little affecting the duration of the action potential. In contrast, dibutyryl cyclic AMP significantly prolonged the action potential duration without changing the slope of the diastolic depolarization. Thus, it was shown that dibutyryl cyclic AMP did not always produce the positive chronotropism, and it was suggested that the negative chronotropism on the cultured chick embryonic heart cells was related to the prolongation of the action potential duration.

Action Potentials↗
PubMed1980

Cardiotonic effect of phthalazinol (EG-626) in the isolated guinea pig by myocardium: mechanical and electrophysiological study.

EG-626, 7-ethoxycarbonyl-6, 8-dimethyl-4-hydroxymethyl-1 (2H)-phthalazinone, was found to be a considerably potent cardiotonic agent. It produced both the positive chronotropic and inotropic actions in the guinea pig heart muscle. Positive inotropic action of isoproterenol was potentiated by EG-626 at the concentration which did not produce a substantial positive inotropic action by itself. Cardiac action potential was not modified by EG-626 at concentrations sufficient to produce positive inotropic actions. EG-626 has a strong activity to produce slow responses in the depolarized myocardium, indicating that it can increase the density of the slow channels. The possibility was shown that the increase in the density of the slow channel may play an important role in the positive inotropic action of EG-626. The increase in the intracellular cyclic AMP due to the phosphodiesterase inhibition is tentatively most likely to be the cause of the EG-626 induced in the density of the slow channels.

Adrenergic alpha-Agonists↗
PubMed1980

Effects of nonspecific smooth muscle relaxants on glycogen phosphorylase activity in depolarized taenia caecum of guinea pig.

Effects of papaverine, Aspaminol (an antispasmodic drug), D-600, 2, 4-dinitrophenol and Ca ions on glycogen phosphorylase activity in the KCl-depolarized taenia caecum of guinea pig were tested. External Ca ions dose-dependently activated phosphorylase, indicating that Ca ions, which entered the smooth muscle cells, played an important role in the regulation of phosphorylase activity. Aspaminol, D-600 and removal of Ca ions from bath fluid inhibited phosphorylase activity. Since these treatments relaxed the taenia caecum, the decrease of phosphorylase activity after the treatments may be mainly due to the decrease of energy consumption. Papaverine and 2, 4-dinitrophenol induced an activation of phosphorylase which might be for replenishment of energy stores decreased by them.

Animals↗
PubMed1980

Electrophysiological effects of a new antiarrhythmic agent, lorcainide, on the isolated cardiac muscle fiber as compared with disopyramide.

Electrophysiological effects of a new antiarrhythmic agent, lorcainide, were studied in the isolated guinea pig ventricular myocardium and were compared with those of disopyramide; some of the experiments were also made by using the canine ventricular myocardium. Both lorcainide and disopyramide selectively depressed the maximum rate of rise of the action potential with little effect on the resting and overshooting potential. The action potential duration tended to be shortened slightly, and the prolongation of the refractory period produced by these agents was only slight. Both agents did not produce the substantial modification of the slow response produced by isoproterenol in the depolarized muscle at the concentrations enough to depress the maximum rate of rise of the action potential. Both agents also produced the marked depression of the rate of the action potential of the canine ventricular muscle, and the conduction velocity measured in the canine false tendon was markedly decreased by both agents. It was concluded that both lorcainide and disopyramide are typical Class I agents according to the classification proposed by Vaughan Williams and that lorcainide is about 10 times (at least 3 times) more potent than disopyramide in this respect.

Action Potentials↗