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Biomedical subjects

K Shuto

Publications and source records attributed to K Shuto.

At least 91 records · Page 5Linked to original sources
PubMed1984

Evidence that KF4939, a new anti-platelet agent, inhibits phospholipase activation in rabbit platelets: different aspects from cyclic AMP increasing agents and calmodulin antagonist.

KF4939 [2, 2'-dithiobis (N-2- hydroxypropylbenzamide )] inhibited malondialdehyde (MDA) production induced by thrombin and A23187. The per cent inhibitions obtained in the medium with and without external calcium were about the same. Thromboxane A2 (TXA2) production induced by thrombin and collagen was also inhibited by KF4939 . This agent, however, did not block the conversion of exogenous arachidonate to MDA and TXA2. In contrast to KF4939 , prostaglandin E1 and 3- isobuthyl -l-methyl xanthine caused an inhibition of thrombin but not of A23187 induced production of MDA. Although chlorpromazine caused an inhibition in both thrombin- and A23187-stimulated platelets, the per cent inhibitions obtained in the medium with external calcium were lower than that in the medium without calcium. In addition, no synergisms between KF4939 and PGE1 or theophylline were observed in platelet aggregation induced by ADP. These results indicate that KF4939 inhibits the stimulus-activated arachidonic acid mobilization from membrane phospholipids, possibly through other mechanisms than elevation of cyclic AMP and calmodulin antagonism.

Animals↗
PubMed1984

Radical scavenging action of flunarizine in rat brain in vitro.

In view of recent investigations suggesting that generation of free radicals with subsequent peroxidative disintegration of cellular membranes may be involved in ischemic brain damage, free radical scavenging or antioxidant activity of flunarizine, a calcium-entry blocker with brain protective effects, was investigated in vitro. The experimental systems used were 1) prevention of autoxidation in rat brain homogenate, 2) prevention of lipid peroxidation and swelling induced by Fe2+ and ascorbic acid in rat brain mitochondria, and 3) radical scavenging action against diphenyl-p-picrylhydrazyl, a stable free radical. Although flunarizine was shown to be active in any system, the most pronounced activity of this compound was elicited in the mitochondria, where it was three times greater than that of alpha-tocopherol, a typical intracellular antioxidant. This suggests that the free radical scavenging or antioxidant activity of flunarizine may play a role in its brain protective action.

Animals↗
PubMed1984

[A case report of minimal cancer of the thyroid gland with lymph node metastasis].

The patient, a 54-year old woman died after open heart surgery. A minimal thyroid carcinoma with lymph node metastasis was incidentally found at autopsy. The tumor was in the left lower pole, it was 0.9 mm in diameter. Histologically, it was follicular carcinoma. Metastasis was found in three lymph nodes around the tumor. A review of the literature suggests this to be the smallest follicular carcinoma reported to data.

Adenocarcinoma↗
PubMed1983

Anti-inflammatory effect of proteinase inhibitors on carrageenin-induced inflammation in rats.

Proteinase inhibitors were evaluated for their anti-inflammatory actions on carrageenin-induced inflammation in rats. The development of granulation tissue and the exudate were markedly suppressed by a single injection of L-1-tosylamide-2-phenylethyl chloromethyl ketone (TPCK) into the carrageenin-air-pouch immediately after carrageenin injection, whereas a single injection of TPCK at 12 or 24 hr after carrageenin injection was less effective or slightly effective respectively. These results suggest that proteinase inhibitors exert their anti-inflammatory actions by interfering with the initial inflammatory reactions after carrageenin injection. When the wet weight of granulation tissue and the weight of exudate were measured on day 4 after the simultaneous injection of carrageenin and inhibitors, a single injection of serine- and thiol-proteinase inhibitors including TPCK, leupeptin, antipain, chymostatin and cystamine suppressed the development of granulation tissue, though EDTA and o-phenanthroline, metallo-proteinase inhibitors, were also effective at a high dose. Exudate was reduced by treatment with TPCK in a dose-dependent manner, while EDTA and o-phenanthroline were effective only at a high dose. On the other hand, the migration of polymorphonuclear leukocytes into the carrageenin-air-pouch (the inflammatory lesion) was markedly suppressed by TPCK and leupeptin, while a high dose of cystamine and o-phenanthroline was slightly effective, and antipain, chymostatin, pepstatin, elastatinal, EDTA, trans-1-aminomethylcyclohexane 4-carboxylic acid and aprotinin were without effect.

Animals↗
PubMed1983

Inhibition of platelet aggregation by a new agent, 2,2'-dithiobis-(N-2-hydroxypropyl benzamide) (KF4939).

KF4939, 2,2'-dithiobis-(N-2-hydroxypropylbenzamide), is a potent inhibitor of platelet aggregation in vitro in rabbit and human PRP. This agent inhibited both cyclooxygenase product-dependent (collagen and arachidonate) and independent (ADP and thrombin)-platelet aggregations. This action carried over to ex vivo situation following intraduodenal dosing as demonstrated in rabbits. KF4939 inhibited experimentally induced thrombocytopenias in rats and pulmonary thrombosis in mice following oral doses in a range of 25-300mg/kg. These results indicate that KF4939 is a new orally active inhibitor of platelet aggregation possessing a different mode of action from cyclooxygenase inhibition.

Adenosine Diphosphate↗
PubMed1983

Exacerbation of acetic acid ulcer induced by non-steroidal anti-inflammatory drugs in rats.

The influences of non-steroidal anti-inflammatory drugs (NSAID) on acetic acid ulcer were examined in rats. NSAID used in this study were aspirin (ASP, 200 mg/kg), indomethacin (IND, 2 mg/kg) and phenylbutazone (PHE, 100 mg/kg). These NSAID were administered consecutively for 5 days once a day at the early stage of the ulcer. Eleven days after the ulceration, suppression of the healing was observed in rats treated with all of the NSAID. In the rats treated with either ASP or IND, a delay of healing was observed not only 11 days after ulceration, but also 16 days after ulceration. The ulcer index in rats treated with either ASP or IND 16 days after ulceration was greater than that at 11 days after ulceration. Further studies were performed regarding the progressive change of mucosal hexosamine content, gastric secretion and gastric emptying during the healing process of the ulcer. It was found that the increase of hexosamine plays an important role in the healing of the ulcer and that a durable fall in hexosamine content was related to the remarkable exacerbation of ulcer induced by either ASP or IND. Hypersecretion, back diffusion of hydrogen ion or a delay of gastric emptying cannot be regarded as a cause of the exacerbation of the ulcer.

Acetates↗
PubMed1983

Hypotensive action of a new benzimidazolinone derivative, threo-1-(2-hydroxy-2-(3,4,5-trimethoxyphenyl)-1-methylethyl)-4-(1,3-dihydro-2H-benzimidazol-2-one-1-yl)piperidine (KF-4942): prazosin-like mode of action.

Among a series of benzimidazolinone derivatives, KF-4942 was examined on its mode of hypotensive action. It was found that KF-4942 was a potent hypotensive agent, and that the hypotension was produced mostly by alpha-adrenergic blockade. Alpha-adrenergic blocking action of KF-4942 was suggested to be selective to the postsynaptic receptor. Thus, KF-4942 was concluded to be an agent with properties similar to prazosin.

Adrenergic alpha-Antagonists↗
PubMed1983

[Pharmacological studies on oxatomide: (6) Effect on the peripheral organs].

The effects of oxatomide, an anti-allergic drug, on the cardiovascular, digestive and autonomic nervous systems were investigated, and the following results were obtained: Intravenous administration of oxatomide, at doses of 1 mg/kg or more, lowered arterial blood pressure, decreased heart rate, increased femoral blood flow, and depressed the gastrointestinal and uterine movement in anesthetized dogs, rabbits and rats. In in vitro experiments, oxatomide inhibited spontaneous movements of isolated rabbit ileum, isolated guinea pig atrium and isolated rat uterus at considerably high concentrations of 10(-6)M or more. The antagonistic activity of oxatomide for histamine in isolated guinea pig ileum and trachea was observed at concentrations of 3 X 10(-8)M or more. Oral administration of oxatomide, however, had no significant influence on the cardiovascular, digestive and autonomic nervous systems and urogenital organs, at doses up to 100 mg/kg. The antigenicity of oxatomide was studied with immunological procedures such as active anaphylactic shock, passive cutaneous anaphylaxis and passive hemagglutination test in guinea pigs, rats and mice. In these tests, neither anaphylactic shock nor allergic reaction was observed. From these results, it is suggested that oxatomide shows little effect on peripheral organs at a dose which elicits the anti-allergic actions and may have no antigenicity to experimental animals.

Animals↗
PubMed1983

[Pharmacological studies on oxatomide. (5). Effect on the central and peripheral nervous systems].

The effect of oxatomide, an antiallergic drug, on the central and peripheral nervous systems were investigated, and the following results were obtained: Oxatomide at oral doses of 30-100 mg/kg produced little or no effect on the spontaneous and cooperative movements in mice, hexobarbital-induced hypnosis in mice, body temperature in rats, and did not induce muscle relaxation, the analgesic effect, anticonvulsive effects and anti-physostigmine effect. Oxatomide at doses of 300 mg/kg or more produced sedation followed by an increase in the responses to stimuli in mice and rats. These behavioral changes diminished within 7-8 hours. Oxatomide (2 mg/kg, i.v.) changed the EEG to a slightly drowsy pattern in unanesthetized, unrestrained rabbits. Neither the EEG arousal responses evoked by auditory stimulation or electrical stimulation to the mesencephalic reticular formation, nor the limic afterdischarges induced by electrical stimulation to the hippocampus or amygdala were affected by oxatomide at any of the doses employed. Oxatomide had no effect on the spinal reflex in cats, conditioned behavior in rats or local anesthesia in guinea pigs. These results suggest that oxatomide shows little effect on the central and peripheral nervous systems at a dose sufficient to elicit the antiallergic actions.

Analgesics↗
PubMed1983

Pharmacology of 4-(2-hydroxy-3-[(1-methyl-3-phenylpropyl)-amino]propoxy)benzeneacetamide (KF-4317).

4-(2-Hydroxy-3-[(1-methyl-3-phenylpropyl)amino] propoxy)benzeneacetamide (KF-4317) differs from conventional adrenoceptor antagonists in producing a competitive blockade at both alpha- and beta 1-adrenoceptors. In blocking beta 1-adrenoceptors, KF-4317 is as active as labetalol in both in vitro and in vivo experiments, and 22 times less potent (in vitro) and 2 times less potent (in vivo) than propranolol. In blocking beta 2-adrenoceptors, KF-4317 is 776 times less potent (in vitro) and 83 times less potent (in vivo) than propranolol. The ratio of beta 1-blocking activity to beta 2-blocking activity is 33 to 145 for practolol, 37 for KF-4317, 1 for propranolol and 0.16 to 1 for labetalol, respectively. In blocking alpha-adrenoceptors, KF-4317 is 55 times less potent than phentolamine and 6 times less potent than labetalol in in vitro experiments, but as active as labetalol in in vivo experiments. These results show that KF-4317 possesses a novel type of adrenoceptor antagonistic property.

Adrenergic alpha-Antagonists↗
PubMed1983

[Pharmacological studies on oxatomide (KW-4354). (7) Antagonistic effects on chemical mediators].

The effects of oxatomide, an anti-allergic drug, on the actions of chemical mediators were investigated in guinea pigs, rats and cats; and the following results were obtained: Studies on the guinea pig ileum revealed oxatomide to be a potent antagonist of histamine with a dual type of action, being competitive at low doses and noncompetitive at higher doses. Oxatomide at concentrations of 0.1 microM or higher inhibited the contractile responses evoked by crude SRS-A from sensitized guinea pig lung. Oxatomide (0.1 to 10 microM) did not inhibit the chronotropic effect of histamine in guinea pig atrium. In anaesthetized guinea pigs, serotonin-induced bronchoconstriction was antagonized by oxatomide (0.1 to 1 mg/kg, i.v.) as effectively as histamine-induced bronchoconstriction. However, oxatomide (up to 1 mg/kg, i.v.) did not inhibit acetylcholine-induced or arachidonic acid-induced bronchoconstriction. Oxatomide given orally in the range of 5 to 30 mg/kg markedly inhibited the increased vascular permeability by histamine, serotonin, and bradykinin in rats. Oxatomide at doses of 0.03 mg/kg (i.v.) or higher also prevented the contraction of the nictitating membrane induced by serotonin in cats. Oxatomide (0.3 microM and 1 microM) inhibited competitively the calcium-induced contracture of fully-depolarized taenia coli of guinea pigs. From these results, oxatomide appears to have potent antagonistic activities on the actions of various chemical mediators. These properties of oxatomide may contribute to its anti-allergic activity.

Acetylcholine↗
PubMed1983

[Muscle-relaxant effects of intravenously administered micronomicin].

Pharmacological effects, mainly on its muscle-relaxant of micronomicin (MCR) were studied. Intravenous infusion of MCR at a dose of 20 mg/kg/hour did not influence on both respiration rate and cardiovascular functions in anesthetized rabbits. When MCR was injected to anesthetized rabbit at an intravenous dose of 100 mg/kg, a respiratory arrest followed by a cardiac arrest was observed. This effect was antagonized by either treatment with CaCl2 or artificial respiration. In slant test, MCR at a dose of 100 mg/kg (i.v.) in mice induced muscle relaxation. This effect was weakened by slowing the injection speed of the drug. Intravenous injection of MCR potentiated the lethality induced by either d-tubocurarine or succinylcholine. Intravenous injection of MCR influenced on neither pentobarbital sodium-, ethyl ether-, nor halothane-induced anesthesia in mice. From these results, intravenous infusion of MCR at a dose of 20 mg/kg/hour that is considered as 5 approximately 10 times of clinical dose (120 approximately 240 mg/day) did not influence on both respiration and cardiovascular functions.

Aminoglycosides↗
PubMed1982

Protective effect of flunarizine against cerebral hypoxia-anoxia in mice and rats.

The protective effect of flunarizine against cerebral hypoxia-anoxia was investigated with various experimental models in mice and rats. The effect of flunarizine was compared with those of cinnarizine, verapamil and pentobarbital. The oral treatment of animals with flunarizine resulted in a consistent and long-lasting-protection against cerebral hypoxia-anoxia in all the models examined: Cytotoxic anoxia by KCN injection, hypercapnic anoxia induced by stopping artificial respiration, hypobaric hypoxia and normobaric hypoxia. The minimal effective dose of flunarizine was 1 to 20 mg/kg. The activity of flunarizine was 4 to 30 times as potent as that of cinnarizine and pentobarbital. Verapamil showed little or no protective effect. The mode of action of flunarizine was different from that of pentobarbital, which showed protection at anaesthetizing doses. These results indicate that flunarizine possesses a universal protective effect against cerebral hypoxia-anoxia, through the mechanism involved remains to be clarified. Hence, it is suggested that flunarizine might exert a beneficial effect on oxygen insufficiency of the brain resulting from cerebral ischemia.

Animals↗
PubMed1982

Effect of proteinase inhibitors having anti-inflammatory activity on gelatinase, elastase and cathepsin G isolated from rat polymorphonuclear leukocytes.

Gelatinase, elastase and cathepsin G isolated from the granule extract of rat polymorphonuclear leukocytes (PMNs) had similar properties to the enzymes of human PMNs already reported. Effect of proteinase inhibitors on these neutral proteinases isolated from rat PMNs was studied. Epsilon-Amino-n-caproic acid n-hexyl ester, a proteinase inhibitor having anti-inflammatory activity, inhibited cathepsin G, whereas elastase was activated by the inhibitor. On the other hand, leupeptin, L-1-tosylamide-2-phenylethyl chloromethyl ketone and N-alpha-p-tosyl-L-lysine chloromethyl ketone, which had been reported as anti-inflammatory inhibitors, had no inhibitory effect on these neutral proteinases. These results suggest that proteinase inhibitors reported as anti-inflammatory agents exert their anti-inflammatory actions not by direct inhibition of the neutral proteinases released from PMNs, but by other effects such as suppression of the infiltration of PMNs into inflammatory locus.

Animals↗
PubMed1982

Lipid-lowering effects of N-[4-methylbenzylthiocarbonyl]-L-phenylalanine (KF1492), a new phenylalanine derivative.

Lipid-lowering effects of KF1492, N-[4-methylbenzylthiocarbonyl]-L-phenylalanine, were evaluated in comparison with clofibrate. This compound lowered serum cholesterol (s-CL) and triglyceride(s-TG) in cholesterol-fed, Triton-injected and glycerol-fed rats as well as in normal rats. The dose of KF1492 required to show these effects was almost equal to that of clofibrate. In addition, KF1492 produced significant reductions of s-CL and s-TG in thiouracil-fed rats and decreasing phase of Triton-induced hyperlipemia of rats. In these models, clofibrate produced no significant reductions. Clofibrate produced a marked increase of liver size and shortened the pentobarbital-induced sleeping time in rats. On the contrary, the increase of liver size by KF1492 was less marked than clofibrate, and KF1492 caused no change in the sleeping time. Thus, it is apparent that KF1492 is a new lipid-lowering compound with less hepatic effect than clofibrate and that the lipid-lowering profile of KF1492 differs from that of clofibrate in some points.

Animals↗
PubMed1982

Effects of ecarazine, prazosin, phentolamine and hexamethonium on the vasopressor reflexes induced by bilateral carotid artery occlusion and head-up tilting in cats.

In order to examine clinical potential for ecarazine, prazosin, phentolamine and hexamethonium to cause orthostatic hypotension in man, the effects of these drugs on the vasopressor reflexes induced by bilateral carotid artery occlusion (BCO) or head-up tilting (Tilt) have been investigated in gallamine-immobilized cats. Ecarazine at doses of 0.1 to 10 mg/kg i.v. decreased blood pressure in a dose-dependent way whereas at 0.1 to 1 mg/kg it did not affect the pressor response to BCO or Tilt and at 10 mg/kg it suppressed only the response to BCO slightly. On the other hand, prazosin, phentolamine and hexamethonium, at hypotensive doses, not only decreased blood pressure but also inhibited pressor responses to both BCO and Tilt. Because ecarazine lacks in producing orthostatic hypotension, it seems likely that the clinical propensity of drugs to cause such side effect is correlated with the inhibition of Tilt response rather than with that to BCO. The results of comparison of the inhibition by these drugs of Tilt response indicate that ecarazine is the most favorable drug among these four drugs and that phentolamine has the highest incidence of orthostatic hypotension. With respect to the effects of prazosin, phentolamine and hexamethonium, statistically significant correlation between the inhibition of the response to BCO and that to the compensatory reflex to Tilt has been observed. Hence it is suggested that the agents which decrease blood pressure by affecting peripheral sympathetic mechanisms might depress each efferent sympathetic pathway to the same degree.

Animals↗