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Biomedical subjects

S Kinoshita

Publications and source records attributed to S Kinoshita.

At least 19 recordsLinked to original sources

Cardiovascular actions of OPC-18790: a novel positive inotropic agent with little chronotropic action.

OPC-18790 [(+/-)-6-[3-(3,4-dimethoxybenzylamino)-2-hydroxypropoxy]- 2(1H)-quinolinone], a novel positive inotropic agent, was investigated in several in vitro and in vivo experiments to elucidate its cardiovascular effects and its mechanism of action. In isolated blood-perfused dog heart preparations, OPC-18790 increased contractile force at 10 to 1,000 nmol i.a.; increased coronary arterial blood flow at 30 to 1,000 nmol; and decreased sinus rate slightly at 1,000 nmol. Atrio-ventricular nodal conduction was slightly facilitated with OPC-18790 (10 to 1,000 nmol), whereas ventricular automaticity tended to decrease. OPC-18790 (10(-6) to 10(-4) M) increased contractile force in isolated ventricular muscles of dogs, cats, rabbits and guinea pigs but not rats. OPC-18790 increased left ventricular contractile force dose-dependently in anesthetized open-chest dogs and in conscious dogs with slight or no changes in heart rate and blood pressure. The positive inotropic effect of OPC-18790 was not affected by beta-blockade. OPC-18790 (10(-5) to 10(-4) M) prolonged the duration of action potential in guinea pig papillary muscles. Na+, K(+)-ATPase was not inhibited, but peak-III phosphodiesterase (low Km cyclic AMP specific fraction, inhibited by cyclic GMP) was inhibited by OPC-18790 (IC50 = 0.41 x 10(-6) M) in dog myocardium. However, such an inhibitory action of phosphodiesterase can hardly be reconciled with the lack of a positive chronotropic effect shown by OPC-18790. Thus, these results suggest that OPC-18790 may have an additional mechanism. The cardiovascular effects revealed by this study suggest that OPC-18790 may exert a beneficial effect in the treatment of congestive heart failure.

Animals

Differentiation between parasystole and reentry in concealed bigeminy.

There are two different theories to explain the mechanism of concealed bigeminy: one is '2:1 concealed reentry'; the other is 'irregular parasystole.' Two exemplary cases of the even-number variant of concealed bigeminy are presented. In case 1, the mechanism can be explained by an irregular parasystole due to a modulated parasystole; however, findings during temporary sinus arrest caused by vagal stimulation indicate that this case is not governed by a parasystole, but by a 2:1 concealed reentry. In case 2, the mechanism can be explained by a 2:1 concealed reentry without parasystole; however, findings during temporary sinus arrest indicate that this case is governed by an irregular parasystole due to a type-I second-degree entrance block. Thus, in cases of concealed bigeminy without pure ectopic cycles, it does not seem easy to explain the mechanism of concealed bigeminy on the theory of a modulated parasystole.

Adult

Nematocidal activity of long alkyl chain amides, amines, and their derivatives on dog roundworm larvae.

The nematocidal activity of amides and amines having a long alkyl chain against the second-stage larva of dog roundworm, Toxocara canis, was examined. Long chain acyl amides with smaller substituents on the nitrogen showed stronger activity and the activity of cyclic amine amides was stronger than that of acyclic ones. In a series of homologous amides, the activity was dependent on the alkyl chain length: it reached a maximum at an optimal chain length and decreased in both shorter and longer homologues. The relationship between the activity and hydrophobicity of the homologues was analysed by the use of the bilinear model. The hydrophobicity of a compound, which gives a maximal activity, was similar for all neutral amides, but amides which have an additional amine group in the molecule had different values. Tertiary amines and their salts having a long alkyl chain also showed nematocidal activities comparable to those of the corresponding amides. The salts killed the larva at concentrations lower than their critical micell concentration, suggesting that they behave as a single molecule for the nematocidal action.

Amides

Recombinant human epidermal growth factor and corneal neovascularization.

With a view toward possible future clinical application, we investigated whether recombinant human epidermal growth factor (hEGF) could induce corneal neovascularization. Ethylene-vinyl-acetate copolymer slow-release pellets containing either 250 ng, 500 ng or 1 microgram of hEGF or 250 ng of bovine serum albumin (BSA) were implanted into rabbit corneal stroma, and the corneas were examined by slitlamp biomicroscope for 3 weeks. The results indicated that less than 1 microgram of hEGF per pellet did not induce neovascularization in the cornea. However, when pellets containing 250 ng of basic fibroblast growth factor (bFGF) were implanted, corneal neovascularization toward these pellets occurred within 10 days. The same phenomenon occurred toward the 250 ng hEGF pellets embedded in the ipsilateral or contralateral cornea of the same animal, but was significantly less severe. When a pellet containing 250 ng bFGF was intramuscularly implanted in the animal's back, similar neovascularization was observed toward the pellets containing hEGF implanted in the same animal's cornea, but not toward implanted pellets containing BSA. These results suggest that less than 1 microgram of hEGF cannot initiate corneal angiogenesis, but can promote new vessel formation if the limbal vasculature is activated by a sprouting signal from a certain substance as trace amounts of bFGF.

Animals

A cause of paired ventricular extrasystoles.

Eight patients with ventricular extrasystoles are reported in whom coupling intervals of the extrasystoles to the proceding sinus beats were variable and in whom paired ventricular extrasystoles were occasionally seen. In all patients, paired ventricular extrasystoles were initiated only by comparatively late coupled ventricular extrasystoles. However, the interval between the first and the second of these paired extrasystoles was always much shorter than the coupling interval of this first extrasystole to the preceding sinus beat, so that the latter extrasystole often interrupted the T wave of the first one, indicating the R-on-T phenomenon. In two patients there was a gap between the ranges of coupling intervals for single extrasystoles and for the first ones of paired extrasystoles. These observations suggest the presence of longitudinal dissociation in the reentrant pathway as one of the causes of paired ventricular extrasystoles.

Adult

Abrasive properties of commonly used dentifrices.

This study was conducted to examine the effect of various dentifrices on the abrasion of acrylic resin and extracted human tooth. The influence of the difference in the hardness of the filament of the toothbrush on the abrasion was also studied, using three kinds of toothbrushes. The specimens (acrylic resin and extracted human tooth) were brushed 3,000 times by the back- and -forth stroke movement using a toothbrushing machine for two hours. The surface irregularities of the specimen were analyzed by the surface analyzer and observed by the scanning electron microscopy before and after the brushing procedure. Moreover, the weight loss of the test specimens of the acrylic resin materials was determined, weighing them by a microbalance before and after brushing. The abrasiveness of the dentifrices showed a wide range, but the abrasiveness of the toothbrush itself was not observed. All dentifrices except one which did not contain the abrasive materials had abrasive effects on both the acrylic resin and human tooth. There was a high correlation (r = 0.96) between the weight loss and the surface irregularities in the case of acrylic resin.

Acrylic Resins