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Biomedical subjects

Y Ishida

Publications and source records attributed to Y Ishida.

At least 595 records · Page 33Linked to original sources

Pharmacokinetics of TZU-0460, a new H2-receptor antagonist, in patients with impaired renal function.

We have studied pharmacokinetics of a new H2-receptor antagonist, TZU-0460, in patients with varying degrees of renal impairment. The apparent volume of distribution at steady-state was 1.70 l/kg, and the plasma protein binding of TZU-0460 or its active metabolite, desacetyl TZU-0460 was less than 10% in normal subjects. These variables were not altered with renal impairment. Sixty percent of TZU-0460 given orally was excreted via the kidney, mainly by tubular secretion. The half-time of elimination was 3.94 h in normal subjects, and was prolonged to 12.13 h in severe renal failure (creatinine clearance below 30 ml/min/1.48 m2). Dosage adjustment of TZU-0460 is necessary in renal failure.

Adult↗

Electrocardiograms recorded from the body surface of the carp, Cyprinus carpio.

The electrocardiograms (ECGs) in five kinds of bipolar leads were recorded from the body surface of the carp under water. Each component constituting the ECG wave could be detected by the present method. The potentials of the ECGs recorded by the present method were relatively small, the values being 2-64 microV. The electrical axis in most carp was directed toward the right lateral side.

Animals↗

Effects of cadmium ions, D-600 and chlorpromazine on the skinned smooth muscle of guinea-pig taenia coli.

The effects of Cd2+ on the skinned taenia coli were compared with that of Ca2+ channel blocker, D-600 and calmodulin inhibitor, chlorpromazine. The Cd2+ (0.001-0.5 mM) inhibited the contraction of skinned fibres in a dose-dependent manner. In contrast, the contraction of skinned fibres was not inhibited by pretreatment with 1 X 10(-6) M D-600. However, chlorpromazine (10(-4) M) inhibited the contraction of skinned taenia coli. The inhibition of contraction by Cd2+ in skinned taenia coli was completely reversed by washing with solution containing EDTA, following a treatment with 0.5 mM Cd2+ for 15 min. The skinned fibres had rapidly taken up a far greater amount of Cd2+ than intact muscle of taenia coli. EDTA increased Cd2+ efflux in skinned fibres and only 5% of the original tissue content retained. Thus, EDTA, which was ineffective on intact taenia coli, can be considered to act on Cd2+ of intracellular compartment after disruption of the cell membrane with saponin. In conclusion, there is the possibility that Cd2+ inhibits the contractile system, such as contractile proteins and calmodulin, which results in tension inhibitory effect.

Animals↗

Potent alpha-adrenoceptor blocking action of SGB-1534, a new quinazoline antihypertensive agent in vitro experiments.

SGB-1534 inhibited the contractile response to norepinephrine (NE), methoxamine (MO) and electrical transmural stimulation in the rabbit aorta, basilar and cat coronary arteries and only in the rabbit aorta its inhibitor action was a competitive manner. In the rabbit aorta, the potency (pA2) of SGB was greater than that of prazosin, whereas in the other preparations, the effect of SGB was comparable to that of prazosin. In the rabbit aorta, both SGB and prazosin abolished the contraction induced by transmural stimulation. In the guinea-pig vas deferens, SGB failed to affect the inhibitory effect of clonidine on the response to electrical field stimulation. SGB had no inhibitory effects on the contractile response to potassium, 5-hydroxytryptamine, PGF2 alpha and an excess Ca2+ and the relaxing response to isoproterenol in the vascular tissues. In the electrically driven left atria of guinea-pigs, SGB had no effect on the electromechanical parameters and the isoproterenol induced inotropic effect. On the specific binding of [3H]prazosin in the rabbit aorta, the inhibitory effect of SGB was greater than that of prazosin and phentolamine.

Adrenergic alpha-Antagonists↗

Ketanserin potentiates the prejunctional inhibitory effect of 5-hydroxytryptamine on rat vas deferens.

5-Hydroxytryptamine (5-HT) slightly inhibited the twitch contractions of rat vas deferens caused by single pulse field stimulation at 0.1 Hz. The inhibitory effect of 5-HT was much less in the epididymal portion than in the prostatic portion of the vas deferens. Ketanserin potentiated the prejunctional inhibitory effect of 5-HT and attenuated its stimulatory effect. This potentiation was observable only in the epididymal portion, of the vas deferens. Cyproheptadine and mianserin, but not methysergide, had essentially similar potentiating effects to those of ketanserin. These results suggest that the 5-HT receptor that mediates prejunctional inhibition is not of the 5-HT2 type, and that ketanserin acts by suppressing the 5-HT-induced stimulatory effect, which is possibly mediated by a postjunctional 5-HT2 receptor, thus unmasking the inhibitory effect of 5-HT.

Animals↗

Left ventricular filling dynamics: influence of left ventricular relaxation and left atrial pressure.

Peak rapid filling rate (PRFR) is often used clinically as an index of left ventricular relaxation, i.e., of early diastolic function. This study tests the hypothesis that early filling rate is a function of the atrioventricular pressure difference and hence is influenced by the left atrial pressure as well as by the rate of left ventricular relaxation. As indexes, we chose the left atrial pressure at the atrioventricular pressure crossover (PCO), and the time constant (T) of an assumed exponential decline in left ventricular pressure. We accurately determined the magnitude and timing of filling parameters in conscious dogs by direct measurement of phasic mitral flow (electromagnetically) and high-fidelity chamber pressures. To obtain a diverse hemodynamic data base, loading conditions were changed by infusions of volume and angiotensin II. The latter was administered to produce a change in left ventricular pressure of less than 35% (A-1) or a change in peak left ventricular pressure of greater than 35% (A-2). PRFR increased with volume loading, was unchanged with A-1, and was decreased with A-2; T and PCO increased in all three groups (p less than .005 for all changes). PRFR correlated strongly with the diastolic atrioventricular pressure difference at the time of PRFR (r = .899, p less than .001) and weakly with both T (r = .369, p less than .01) and PCO (r = .601, p less than .001). The correlation improved significantly when T and PCO were both included in the multivariate regression (r = .797, p less than .0001). PRFR is thus determined by both the left atrial pressure and the left ventricular relaxation rate and should be used with caution as an index of left ventricular diastolic function.

Angiotensin II↗

The long term effects of percutaneous transluminal angioplasty for treating patients with renovascular hypertension: case studies.

Percutaneous transluminal angioplasty was performed on 10 patients with unilateral renovascular hypertension (7 with atheromatous and 3 with fibromuscular stenoses) who were then followed for an average of 42 months (range, 24 to 67 months). Dilation of the stenosis was initially successful in all patients except one who had severe atheromatous stenosis. Among patients with atheromatous disease, normotension was attained for 40, 25 and 24 months in 3 patients given no antihypertensive medication and for 67 and 55 months in 2 patients given only nicardipine. The remaining one patient had a recurrent stenosis 3 months after angioplasty. All patients with fibromuscular dysplasia have been normotensive without any hypotensive medication for more than 4 years. Plasma renin activity declined within one week after angioplasty and remained unchanged thereafter in all patients except the one case suffering from a recurrent stenosis. Renal blood flow and glomerular filtration rate remained increased after angioplasty. These results suggest that hypertension can be controlled and renal dysfunction in patients with renal artery stenosis caused by atheroma or fibromuscular dysplasia improved for long periods by percutaneous transluminal angioplasty. The antihypertensive effect obtained by this procedure was more valuable for the patients with fibromuscular dysplasia than in those with atheromatous disease.

Adolescent↗

[Radionuclide ventriculographic assessment of cardiac function based on the analysis of cardiac reserve during dynamic exercise].

To evaluate the contribution of myocardial contractility and preload to increase cardiac output during supine bicycle exercise, quantitative radionuclide ventriculography was performed at rest (R) and during peak exercise (Ex) in 43 patients with coronary artery disease (CAD) and 13 normal subjects. Myocardial contractility was estimated from the ratio of peak systolic pressure to end-systolic volume index (P/V index). During Ex in normal subjects, P/V index invariably increased and its percent change from R to Ex averaged 98 +/- 46 percent. Stroke index (SI) in normal subjects increased from 48 +/- 9 to 57 +/- 7 ml/m2 during Ex (p less than 0.001) without an increase in end-diastolic volume index (EDVI) (76 +/- 11 vs 78 +/- 11 ml/m2, NS). Ten of 43 patients with CAD, whose percent increase in P/V index was more than 40 percent, showed a significant increase in SI during Ex (44 +/- 5 vs 51 +/- 12 ml/m2, p +/- 0.05) without an increase in EDVI (86 +/- 14 vs 87 +/- 15 ml/m2, NS). In 16 of 43 patients with CAD whose percent increase in P/V index was less than 40 percent, SI increased from 44 +/- 10 to 51 +/- 15 ml/m2 (p less than 0.01) during Ex with an increase in EDVI (102 +/- 24 vs 117 +/- 29 ml/m2, p less than 0.001). In the remaining 17 patients with CAD whose P/V index decreased during Ex, SI did not increase during Ex (48 +/- 14 vs 44 +/- 12 ml/m2, NS) despite an increase in EDVI (80 +/- 19 vs 94 +/- 18 ml/m2, p less than 0.01). These results indicate that the Frank-Starling mechanism operates under limited augmentation in myocardial contractility, and that its compensatory function may have limitations under the severely depressed reserve of myocardial contractility.

Aged↗

Photosynthetic phagotrophy of Chrysophyceae: evolutionary aspects.

Phagotrophy must have arisen fundamentally in all eukaryotes. Chrysophyceae, which exhibit both phagocytosis and photosynthesis, are an interesting subject for evolutionary study. On the basis of a handful of articles, we boldly assumed that Ochromonas and Uroglena are in an intermediate stage of evolution towards animal cells and will evolve a divergent dichotomy in future.

Biological Evolution↗

Possible mechanism of action of diazepam as an adenosine potentiator.

Diazepam (10(-5)-3 X 10(-4) M) selectively enhanced the negative inotropic responses of guinea-pig atria and the relaxation of guinea-pig taenia coli caused by adenosine and ATP. In the atria, the effect of 2-chloroadenosine, a stable analog of adenosine, was not affected by diazepam. Segments of guinea-pig atria or taenia coli took up 3H-activity during incubation with [3H]adenosine but did not take up 32P-activity from [32P]ATP. Diazepam at concentrations sufficient to enhance the in vitro responses reduced by half the uptake of 3H-activity into the preparations. Adenosine (10(-6) M) and ATP (10(-6) M) were degraded to inactive inosine during incubation with atrial segments and their degradation was inhibited by diazepam. In contrast, in rat atria, diazepam did not enhance the negative inotropic effects of adenosine and ATP, and did not prevent the uptake of adenosine. These results suggest that in guinea-pig atria and taenia coli, diazepam like dipyridamole, acts as an adenosine potentiator by preventing the uptake and degradation of adenosine.

2-Chloroadenosine↗

Enzyme activities of cultured erythroblasts.

The enzyme activities of cultured early erythroid progenitor cells (burst-forming unit erythroid, BFU-E) were measured and were compared with the activities of mature erythrocytes. The enzyme activity of acetylcholinesterase was not detectable in the erythroblasts. The ratios of phosphofructokinase and glutathione peroxidase were low due to low enzyme activities in both the erythroblasts and erythrocytes. The ratios of triose phosphate isomerase, phosphoglycerate kinase, and adenylate kinase were low due to high enzyme activities in both the erythroblasts and erythrocytes. The ratios of hexokinase, glucose phosphate isomerase, monophosphoglyceromutase, pyruvate kinase, and adenosine deaminase were high due to high enzyme activities in the erythroblasts. The isozyme of erythroblast hexokinase was of the prototype isozyme I, while pyruvate kinase was predominantly of the prototype M2, with two hybrid isozymes to the anodal side by electrophoresis. These facts suggest that there is a greatly different metabolic pattern during the maturation of the erythroid cells.

Cells, Cultured↗