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Biomedical subjects

M Asano

Publications and source records attributed to M Asano.

At least 505 records · Page 28Linked to original sources
PubMed1983

Alterations in pharmacological receptor activities of rabbit arteries by sulfhydryl reagents.

The addition of 1 X 10(-3) M or 1 X 10(-2) M 2-mercaptoethanol (2-MEt), a sulfhydryl reagent, produced a leftward displacement (potentiation) of the dose-response curves of mesenteric arterial strips for histamine, norepinephrine, serotonin, angiotensin II, prostaglandin F2 alpha and KCl. N-ethylmaleimide abolished the 2-MEt-induced potentiation of the arterial responses. Dithiothreitol (DTT) and cysteine also potentiated the contraction by these agonists in mesenteric arterial strips, suggesting that the sulfhydryl group plays a role in the arterial responses to various contractile agonists. In contrast to the mesenteric arterial strips, 2-MEt abolished the contraction by angiotensin II without greatly affecting contraction by norepinephrine in the thoracic aorta, femoral, renal and carotid arterial strips. These data suggest that there are regional differences in the responsiveness of rabbit arteries to sulfhydryl reagents. In mesenteric arterial strips treated with 1 X 10(-6) M histamine, 6 X 10(-8) M norepinephrine or 1 X 10(-9) M angiotensin II after exposure to Ca2+-free Krebs' bicarbonate solutions containing 0.1 mM EGTA, the addition of 2.5 mM CaCl2 caused a contraction (agonist-induced Ca2+-contraction). Sulfhydryl reagents potentiated each agonist-induced Ca2+-contraction in this artery. Moreover, in thoracic aortic strips, sulfhydryl reagents enhanced only histamine-induced Ca2+-contraction and attenuated norepinephrine- and angiotensin II-induced Ca2+-contractions. It is concluded that the reduction of a disulfide bond of the arterial strips to a sulfhydryl group affects the pharmacological receptor activities of the strips and that the changes in the receptor activities may be related to the changes in the transmembrane influx of calcium.

Animals↗
PubMed1983

Affinities for alpha- and beta-adrenoceptor subtypes of YM-09538, a new combined alpha- and beta-adrenoceptor antagonist, by radioligand binding assay.

The binding properties of YM-09538 and some known adrenoceptor agonists and antagonists to alpha- and beta-adrenoceptors were studied by radioligand binding assays using [3H]-prazosin, [3H]-clonidine and (-)-[3H]-dihydroalprenolol ([3H]-DHA). The relative order of potencies of YM-09538 and 5 alpha-adrenergic agents for inhibition of [3H]-prazosin binding to rat brain membranes was as follows: prazosin greater than YM-09538 = phentolamine greater than labetalol greater than yohimbine greater than clonidine. In contrast, the order of potencies of these agents for [3H]-clonidine sites was as follows: clonidine greater than phentolamine greater than yohimbine greater than prazosin greater than YM-09538 greater than labetalol. The rank order of potencies of YM-09538 and 4 beta-adrenergic agents in inhibiting the binding of [3H]-DHA to guinea-pig heart membranes was the same as that to guinea-pig lung membranes: pindolol greater than propranolol greater than labetalol greater than YM-09538 greater than atenolol. Based on Ki values, YM-09538 displayed a 1,380-fold alpha 1-selectivity at alpha-adrenoceptors and no selectivity at beta-adrenoceptors. The biochemical potencies of YM-09538 observed in the present study correlated well with its pharmacological potencies obtained from previously reported literature.

Adrenergic alpha-Antagonists↗
PubMed1982

Adrenoceptor blocking hemodynamic and coronary effects of YM-09538, a new combined alpha- and beta-adrenoceptor blocking drug, in anesthetized dogs.

In anesthetized dogs. YM-09538, a new sulfonamide-substituted phenylethylamine, competitively antagonised the phenylephrine-induced vasopressor response with a DR10 of 0.50 mg/kg i.v. and the isoproterenol-induced positive chronotropic response with a DR10 of 0.66 mg/kg i.v., indicating that YM-09538 blocks both alpha 1- and beta 1-adrenoceptors and almost to the same extent. YM-09538 was 4 times more potent than phentolamine in blocking alpha 1-adrenoceptors and 3 times less potent than propranolol in blocking beta 1-adrenoceptors. YM-09538 non-selectively blocked cardiac beta 1- and vascular beta 2-receptors and was devoid of intrinsic beta-sympathomimetic and local anesthetic activities. In anesthetized closed-chest dogs, YM-09538 resembled propranolol in reducing heart rate, cardiac output, max. dLVP/dt and left ventricular cardiac work but differed from propranolol in decreasing total peripheral resistance, in increasing femoral blood flow, in causing larger falls in arterial blood pressure and in decreasing pulmonary arterial pressure. In anesthetized open-chest dogs, YM-09538 reduced heart rate, myocardial contractile force and arterial blood pressure. In non-ischemic myocardium, transmural flow and coronary vascular resistance were respectively strongly increased and decreased and the endo/epi flow ratio was slightly but not significantly reduced. In ischemic myocardium, YM-09538 also increased transmural flow and since endocardial and epicardial flows were augmented to the same extent, the endo/epi flow ratio remained unchanged. All these hemodynamic and coronary effects of YM-09538 can be accounted for the drug's combined alpha- and beta-adrenoceptors blocking properties.

Adrenergic alpha-Antagonists↗
PubMed1982

Changes in hepatic energy charge, blood ketone body ratio, and indocyanine green clearance in relation to DNA synthesis after hepatectomy.

The changes in the energy charge (ATP + 0.5 ADP)/(ATP + ADP + AMP) levels of the remnant liver were studied in relation to changes in the incorporation rate of methyl-3H-thymidine into DNA, the blood ratio of acetoacetate/beta-hydroxybutyrate and indocyanine green (ICG) clearance in 70% hepatectomized rabbits. The energy charge levels of the remnant liver decreased rapidly to 0.767 from 0.856 of normal, despite a marked enhancement of mitochondrial phosphorylative activity, concomitant with the fall in blood ketone body ratio, before a maximal increase of DNA synthesis after hepatectomy. Blood ketone body ratio was correlated with hepatic energy charge (r = 0.696, p less than 0.01). After a maximal increase of DNA synthesis, hepatic energy charge levels and the blood ketone body ratios increased gradually to normal levels, concomitant with a rise in ICG clearance. Energy charge levels of the remnant liver can be evaluated by the blood ketone body ratio.

Animals↗
PubMed1982

In vivo release of testosterone from protein--vinyl polymer composites.

Hydrophilic vinyl polymer-protein composites containing testosterone were made by means of thermal denaturation of albumin after radiation-induced polymerization of 2-hydroxyethylmethacrylate (HEMA) at--78 degrees C. The albumin-HEMA mixed polymer can be considerably digested with trypsin. The degree of digestion was smaller than that expected from calculation. It was deduced that the digestion of the albumin component was retarded in the presence of HEMA. The same tendency was observed in in vivo experiments. At the same time, in vivo release of testosterone was depressed in albumin-HEMA mixed polymer composite in accordance with the weight decrease of polymer composite resulting from digestion. The effect of testosterone on the weight of ventral prostate was investigated using composites in castrated Wistar rats. The effect was larger in the controlled slow release from implanted composites rather than that of dosage by injection. The microscopic observation showed that the inflammation and foreign body reaction in rat tissue were retarded in albumin-HEMA mixture polymer composite compared with 100% albumin composite.

Animals↗
PubMed1982

Clinical experience of postoperative hepatic failure treatment with pig or baboon liver cross-hemodialysis with an interposed membrane.

The present study emphasizes the principle of using liver support to restore the blood ketone body ratio (acetoacetate/beta-hydroxybutyrate), which reflects the redox potential of liver mitochondria and correlates with hepatic energy charge (ATP + 0.5ADP/ATP + ADP + AMP). Eleven surgical patients with grade IV hepatic coma were treated by an ex vivo pig or baboon liver cross-hemodialysis with an interposed Cuprophan membrane when their blood ketone body ratios had decreased to below 0.4 compared with the normal of above 0.7. Three patients were treated by cross-hemodialysis using a standard Cuprophan membrane dialyzer without increase of blood ketone body ratio and without marked beneficial effect. However, five of eight patients who had blood ketone body ratios of above 0.25 became fully alert after treatment by cross-hemodialysis using the larger pore size and greater surface area Cuprophan membrane, concurrent with a rise in the decreased blood ketone body ratio, and three of them were later discharged. By contrast, in the three patients with blood ketone body ratios below 0.25, there was no restoration of consciousness and no improvement in their blood ketone body ratios by this liver support. It is suggested that, as long as the blood ketone body ratio remained over 0.25, this metabolic liver support is effective in restoring grade IV hepatic coma.

Aged↗
PubMed1982

The effects of heterologous liver cross-hemodialysis on adenylate energy charge of the remnant liver after major hepatic resection.

The effect of liver support on the adenylate energy charge (ATP + 0.5ADP)/(ATP + ADP + AMP) of the remnant liver after major hepatic resection was studied in rabbits. The present study emphasized the principle of restoring the decreased energy charge level of the remnant liver after major hepatic resection by use of an ex vivo heterologous liver cross-hemodialysis with an interposed Cuprophan membrane. The energy charge level provides the cell with a very sensitive intracellular control mechanism. Regulatory enzymes from biosynthetic sequences exhibit very little activity at low levels of energy charge, and their activities increase sharply at high-energy charge levels. The energy charge level of the remnant liver maximally decreased from the control level of 0.860 to 0.767 at 24 hours after 70% hepatectomy. The energy charge level increased from 0.767 to 0.857 after two hours of cross-hemodialysis with an interposed Cuprophan membrane between the 24-hour, 70% hepatectomized rabbit and an ex vivo pig liver with high energy charge. The above results suggest that this ex vivo pig cross-hemodialysis may be effective for biosynthesis in the regenerative processes of the remnant liver.

Adenosine Monophosphate↗
PubMed1982

Alteration of norepinephrine release from [3h]-norepinephrine preloaded basilar artery by naphthalenesulfonamides.

The effects of W-7, W-5, No. 233, and chlorpromazine on sympathetic nerve transmitter efflux were compared in superfused canine basilar arterial preparations preloaded with [3H]-norepinephrine. In vitro experiments suggest that these agents are selective calmodulin antagonists. The electrical transmural stimulation-induced efflux of tritium was reduced by W-7 and W-5, although they were unexpectedly equipotent since W-5 is a chloride-deficient derivative of W-7 and has a lower affinity for calmodulin than does W-7. The median inhibitory concentration (IC50) of W-7 for stimulation-induced efflux was 3.4 X 10(-6) M. The addition of No. 233 at relatively high concentrations (3 X 10(-5) M and 5 X 10(-5) M) caused a reduction in stimulation-induced efflux. Chlorpromazine produced a dual effect on the efflux: enhancement at low concentrations (below 1 X 10(-6) M) and reduction at high concentrations. The IC50 values of No. 233 and chlorpromazine were 3.5 X 10(-5) M and 2.5 X 10(-5) M, respectively. The additions of these four agents also caused a significant elevation in the spontaneous basal efflux of tritium from the preparations. The concentrations of the agents that elevated the spontaneous efflux to the level of half the stimulation-induced efflux were closely fitted to the IC50 values for stimulation-induced efflux. This finding indicates that the elevation in spontaneous efflux is directly proportional to the reduction in electrical stimulation-induced efflux. From these findings, it is concluded that naphthalenesulfonamides including W-7 have a direct effect on sympathetic nerve terminals which is independent of the effect on calmodulin.

Animals↗
PubMed1982

Vasodilator and hypotensive effects of the optical isomers of nicardipine (YC-93), a new Ca2+-antagonist.

Vasodilator and hypotensive effects of (+) and (-) nicardipine were investigated in anesthetized dogs. When administered intravenously, (+) nicardipine was 3 times as potent as the (-) isomer in increasing vertebral blood flow and in lowering mean blood pressure. When injected into the vertebral artery, (+) nicardipine was also 3 times as potent as the (-) isomer in increasing vertebral blood flow. Upon both routes of administration, the duration of the action after (+) nicardipine was longer than that after the (-) isomer. However, there were no differences of plasma nicardipine levels after intravenous injection of both isomers to conscious beagle dogs. The LD50 values of (+) nicardipine in mice and rats upon intravenous injection were only 1.5-2 times smaller than those of the (-) isomer. These results indicate that there exists a stereoselectivity of vasodilator and hypotensive actions among the nicardipine isomers.

Animals↗
PubMed1982

Assay of alpha-cysteine proteinase inhibitor in serum or plasma.

A new proteinase inhibitor has recently been found in human serum or plasma which specifically inhibits cysteine proteinases such as ficin, papain, bromelain and cathepsin B. However, serum contains alpha 2-macroglobulin which also inhibits these cysteine proteinases and, consequently, interferes with the assay of the new alpha-cysteine proteinase inhibitor. Therefore, assay of the inhibitor in serum has not been established previously. In the present method, the alpha 2-macroglobulin is inactivated by preincubating the serum in methylamine solution at 55 degrees C, while the alpha-cysteine proteinase inhibitor retains its activity. The inhibitory power against cysteine proteinases is found to be due mainly to this protein in human serum. This inhibitor is also found in mammals such as cows, pigs and rats. Vitamin E deficient rats show a very high inhibitor level. Therefore, the present method will enable us to investigate the relation between diseases and the activity of the alpha-cysteine proteinase inhibitor. Also, this method is simple and inexpensive. The necessary amount of serum is only 10 microliter.

Animals↗
PubMed1982

Antihypertensive and adrenoceptor blocking properties of new sulfonamide-substituted phenylethylamines.

Studies on the structure-activity relationship using 9 new 3-sulfamoylphenylethylamines revealed that YM-09538, YM-09649 and YM-09686 were competitive antagonists at both beta- and post-synaptic alpha-receptors. The following order of adrenoceptor blocking activities was obtained : propranolol greater than labetalol greater than YM-09538 greater than YM-09649 greater than YM-09686 for beta-receptors and prazosin greater than YM-09686 greater than YM-09649 greater than YM-09538 greater than phentolamine greater than labetalol for postsynaptic alpha-receptors. In contrast to phentolamine, three YM-compounds showed low affinities for presynaptic alpha-receptors similar to prazosin and labetalol. These antagonists except propranolol effectively lowered blood pressure in conscious SHR and their relative effectiveness parallels the postsynaptic alpha-blocking activity. At hypotensive doses, phentolamine markedly and prazosin, YM-09686 and YM-09649 moderately increased heart rate, whereas YM-09538 and labetalol failed to increase the rate. These results indicate that the postsynaptic alpha-blocking activity of YM-compounds contributes to their hypotensive activities and that both beta-blocking and low presynaptic alpha-blocking activities contribute to attenuation of the tachycardia.

Animals↗
PubMed1982

Primary liver carcinoma and liver cirrhosis in atomic bomb survivors, Hiroshima and Nagasaki, 1961-75, with special reference to hepatitis B surface antigen.

During 1961-75, 128 cases of primary liver carcinoma (PLC) in the Radiation Effects Research Foundation life-span study extended sample and 301 cases of liver cirrhosis in the pathology study sample were observed. The presence of hepatitis B surface antigen (HBsAg) was assessed in all of the cases with the use of orcein and aldehyde fuchsin stains and was confirmed by the immunofluorescence technique. The incidence of PLC was two times higher in Nagasaki than in Hiroshima, which was statistically significant, but little difference was noted in the prevalence of cirrhosis in the two cities. Findings that might possibly explain the higher PLC incidence in Nagasaki were 1) the 2.3 times higher presence in Nagasaki than in Hiroshima of HBsAg in the livers of subjects without liver disease and 2) the two times higher prevalence in Nagasaki than in Hiroshima of cirrhosis with PLC. We believe that the higher incidence of PLC in Nagasaki is attributable to hepatitis B virus infection, although other factors (e.g., immunologic competence affected by radiation) cannot be excluded. In both cities, a suggestive relationship of radiation dose to cirrhosis prevalence, but not to PCL prevalence, was noted. To clarify possible radiation effects on cirrhosis prevalence, further follow-up of the populations of these two cities is necessary.

Adult↗