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Biomedical subjects

K Shuto

Publications and source records attributed to K Shuto.

At least 55 records · Page 3Linked to original sources
PubMed1993

Effect of vinconate against regional age-related changes in the gerbil brain.

We investigated age-related changes in the binding sites of muscarinic acetylcholine, forskolin, adenosine 3',5'-cyclic monophosphate (cAMP), and of a voltage-dependent L-type calcium channel blocker in the gerbil brain using receptor autoradiography. [3H]Quinuclidinyl benzilate (QNB), [3H]forskolin, [3H]cAMP, and [3H]PN200-110 were used to label muscarinic receptors, adenylate cyclase, cAMP-dependent protein kinase, and L-type calcium channels, respectively. In middle-aged animals (16-month-old gerbils), [3H]QNB, [3H]PN200-110, [3H]forskolin, and [3H]cAMP binding sites were elevated in the hippocampal region compared with that of young gerbils (4 weeks old). Further, a significant elevation in [3H]forskolin binding was seen in the nucleus accumbens. In contrast, [3H]QNB, [3H]PN200-110, and [3H]forskolin binding sites were reduced in the cerebellum, neocortex and thalamus, and hypothalamus in middle-aged animals, respectively. [3H]cAMP binding was not altered in other regions except for an elevation in the hippocampus. Thus, the age-related alterations in receptor binding may proceed by different mechanisms in various brain regions. Chronic vinconate treatment partly modulated the age-related alterations in [3H]QNB, [3H]forskolin, and [3H]cAMP binding in the hippocampus, but not that of [3H]PN200-110. Vinconate also regulated the age-related changes in [3H]forskolin binding in the nucleus accumbens. These results indicate that the age-related alterations in the binding sites of muscarinic acetylcholine, forskolin, cAMP, and L-type calcium channel blocker occur in particular in the hippocampus. Further, they suggest that a novel vinca alkaloid derivative, vinconate, can partly modulate age-related changes in these binding sites.

Acetylcholine↗
PubMed1993

Effect of OM-853, a cerebral metabolic ameliorator, on ambulatory activity and passive and active avoidance responses in mice and Mongolian gerbils.

Behavioral effects of OM-853 were investigated in both mice and Mongolian gerbils. In mice, OM-853 alone produced no marked change in the ambulatory activity, although it tended to lower it at 100 mg/kg, and this drug (5-100 mg/kg, p.o.) reduced the ambulation-increasing effect of scopolamine (0.5 mg/kg, s.c.) in a dose-dependent manner. Moreover, OM-853 (50 and 100 mg/kg, p.o.) prolonged the latency times shortened by scopolamine under the passive avoidance. On the other hand, in the discrete avoidance situation, OM-853 facilitated the acquisition of shuttle avoidance at 10 and 25 mg/kg, p.o. and lever-press avoidance at 25 and 50 mg/kg, p.o. in the pre-training administration schedule, and the former at 25-100 mg/kg, p.o. and the latter at 10 and 25 mg/kg, p.o. in the post-training administration schedule. In gerbils, OM-853 (50 mg/kg, i.p.) ameliorated the learning deficit of the lever-press avoidance response induced by forebrain ischemia. The present results suggest that OM-853 has beneficial actions on some types of learning and memory in normal, scopolamine-treated and ischemic animals. The possible mechanisms involved are discussed.

Animals↗
PubMed1993

Effects of OM-853, a novel indolonaphthyridine derivative, on behavioral responses in the forced swim test in rats.

Effects of OM-853 on behavioral responses in the forced swim test were studied. OM-853 significantly reduced the duration of immobility without any change in the exploratory activity. Imipramine also reduced the duration of immobility, but idebenone did not. On the other hand, vinpocetine enhanced the duration with a suppressive effect on ambulation. The anti-immobility effect of OM-853 was reversed by pretreatment with haloperidol. These results demonstrate that the effect of OM-853 on the swim test is different from that of idebenone and vinpocetine. Furthermore, the present results suggest that OM-853 may exert its anti-immobility activity through facilitated transmission of the dopaminergic and/or adrenergic systems.

Animals↗
PubMed1993

[A case of subpulmonary membranous stenosis associated with atrial septal defect].

The patient was a 5 years old male who had had the cyanosis and congestive heart failure from his neonatal period. Dopamine, digitalis and diuretics disappeared his symptoms and he had been followed up as the out-patient. Preoperative cardiac catheterization revealed atrial septal defect and moderately pulmonary stenosis with two-staged systolic pressure gradient in a right ventricular cavity. Right ventriculogram showed subpulmonary crescent-shaped, linear filling defect. Ventricular septal defect was not detected. He was underwent open heart surgery and subpulmonary membranous stenosis was found out. Pressure gradient across the right ventricular outflow tract was diminished by the resection of the membranous structure. Atrial septal defect without lower margin was closed directly. Postoperative course was uneventful. Right ventricular apical systolic pressure was decreased to the degree of 27 mmHg postoperatively.

Child, Preschool↗
PubMed1992

Autoradiographic mapping of neurotransmitter system receptors in mammalian brain.

Regional localization of neurotransmitter system receptors was visualized in the gerbil grain and in the rat brain using receptor autoradiography. [3H]Quinuclidinyl benzilate (QNB), [3H]cyclohexyladenosine (CHA), [3H]muscimol, [3H]MK-801, [3H]SCH 23390, [3H]PN200-110, [3H]spiperone, and [3H]naloxone were label muscarinic receptors, adenosine A1 receptors, GABAA receptors, N-methyl-D-aspartate (NMDA) receptors, dopamine D1 receptors, L-type calcium channels, spirodecanone receptors, and opioid receptors, respectively. Regional localization of [3H]QNB, [3H]muscimol, [3H]MK-801, [3H]SCH 23390, and [3H]PN200-110 binding sites in the gerbil brain was relatively similar to that in the rat brain. In contrast, the autoradiographic distribution of [3H]spiperone and [3H]naloxone binding sites in the gerbil was quite different from that in the rat. This phenomenon was found especially in the hippocampus and the cerebellum. The results suggest that the gerbil differs from the rat with respect to spirodecanone and opioid binding sites in the hippocampus and the cerebellum. This finding may help to further elucidate the species differences and relationships for brain function and behavioral pharmacology.

Animals↗
PubMed1992

[Use of the newly designed long-handled forceps for respiratory surgery].

We report on use of the newly designed long-handled forceps for respiratory surgery. The forceps have a curved-end in the same plane as its handles. This contributes to the easier clamping of vessels running horizontally in the deep fields. It is very useful not only in thoracic surgery, such as respiratory and esophageal surgery, but also in pelvic surgery.

Equipment Design↗
PubMed1991

[Effect of recombinant human erythropoietin on autologous blood pre-donation in open heart surgery].

We have used recombinant human erythropoietin (EPO) with an autologous blood predonation in open heart surgery looking forward to preventing patient's blood level of hemoglobin and quick recovery in post-operative period. In our results, patient's value of hemoglobin (Hb) and hematocrit (Ht) decreased due to autologous blood predonation. In group A (autologous blood predonation with EPO administration), however, predonated blood volume were larger than in group B (without EPO administration), decreased value of Hb and Ht were smaller than in group B. The counts of reticulocyte were higher in group A at the operative day. Among six cases phlebotomized with EPO administration, five cases required no homologous blood transfusion for their hospital course. Postoperative recovery of patient's Ht value were earlier in preoperative blood donation group. In particular, patients who administered EPO intravenously have showed fair recovery from anemia. EPO is very effective drug to prevent patients from the developing anemia as a complication of autologous blood predonation. We conclude that autologous blood predonation with EPO administration is beneficial method to reduce homologous blood requirement in open heart surgery.

Adolescent↗
PubMed1990

[Studies on acetylspiramycin. II. Biological activities of spiramycin components].

Acetylspiramycin (ASPM) was fractionated using high performance liquid chromatography (HPLC). The peak fractions were named F1 to F7 successively in order of increasing retention times (Rt), i.e., increasing hydrophobicity, and studied for 1) antibacterial activities (MIC), 2) antibacterial potency against Bacillus subtilis ATCC 6633, 3) therapeutic effect on mice infected with Streptococcus pneumoniae III, Staphylococcus aureus Smith, 4) acute toxicity by i.p. administration to mice (LD50) and 5) cytotoxicities to fibroblasts derived from Chinese-hamster lung (CHL), cow pulmonary artery endothelial cells (CPAE) and rat hepatic cells. The results obtained are summarized below. 1. Components F1 and 4'-acetylspiramycin F2 had significantly different biological activities from those of other components: F1 showed the lowest antibacterial potency of 492 micrograms (potency)/mg, F2 showed the highest antibacterial potency of 2,040 micrograms (potency)/mg and correspondingly the lowest LD50 value of 692 mg/kg (the highest toxicity). The therapeutic effect of F2 on infections in mice was found to be the second smallest and was superior only to that of F1. The LD50 value of F1 was 1,200 mg/kg and similar to that of ASPM. 2. Antibacterial potencies of F3, F4, F5 and F6 were 1,165, 1,266, 1,374 and 1,530 micrograms (potency)/mg, respectively; fraction with the higher antibacterial activities corresponded to the longer retention times, i.e., the greater hydrophobicities. The most hydrophobic component, F7, 3-propionyl-3",4"-diacetylspiramycin, however, showed a low antibacterial potency of 1,085 micrograms (potency)/mg, next to the lowest one, F1, a fact which was in contradiction to with the sequential relation between hydrophobicities and potencies from F3 to F6.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

[A case of two-chambered right ventricle complicating severe cyanosis due to tricuspid regurgitation and patent foramen ovale].

A 63-year-old female of two-chambered right ventricle (TCRV) associated with tricuspid regurgitation (TR), patent foramen ovale (PFO) and small ventricular septal defect (VSD) underwent corrective surgery successfully. She suffered severe heart failure and cyanosis with 47.7% of right-to-left shunt through PFO. The VSD was so small that no significant shunt was shown in catheterization data. Operative findings suggested that TR was caused by elongation of the chorda as a consequence of long-term pressure load of right ventricular inflow chamber. Among reported cases of TCRV, the present case is the oldest one who underwent corrective surgery successfully.

Female↗
PubMed1989

Augmentation of the gastric mucosal defense mechanism induced by KW-5805, a novel antiulcer agent.

KW-5805 (a new antiulcer agent), given p. o. at 30 mg/kg to rats, significantly increased the amount of gastric adherent mucus and mucosal glycoproteins. Gastric mucosal glucosamine synthetase activity was significantly enhanced by KW-5805 (30 mg/kg, p. o.). KW-5805 (10, 30 mg/kg, p. o.) significantly suppressed the decrease of gastric mucosal blood volume and oxygen sufficiency induced by hemorrhagic shock. The agent also significantly inhibited the extravasation of Evans blue into the gastric mucosa after ischemia-reinfusion. In conclusion, KW-5805 increased biosynthesis, storage and secretion of gastric mucus and improved the gastric mucosal hemodynamics.

Animals↗
PubMed1988

Synthesis and antiulcer activity of 5,11-dihydro[1]benzoxepino[3,4-b]pyridines.

A series of substituted 5,11-dihydro[1]benzoxepino[3,4-b]pyridines was synthesized and evaluated for antiulcer activity in water immersion/restrained stress ulcer assay in rats. Structure-activity relationships are described. Most of the tested compounds exhibited low affinity to the muscarinic acetylcholine receptor. The molecular features for the best activities are the 2-(diethylamino)ethylenediamine group at the 5-position of the oxepin ring and an oxepin skeleton rather than a thiepin or a pyran skeleton. Methyl and chlorine substitution on the benzene ring reduced the activity. Compound 11, 5-[[2-(diethylamino)ethyl]amino]-5,11-dihydro[1]benzoxepino [3,4-b]pyridine trihydrochloride was selected for further evaluation. Synthesis and antiulcer activity of optically active 11 is described. There were no statistically significant differences between (+)-, (-)-, and (+/-)-11. Compound 11 showed weak antisecretory activity in pylorus-ligated rats. It is now under clinical evaluation as KW 5805.

Animals↗
PubMed1988

Effects of flunarizine on induced nystagmus and cochlear blood flow.

The effects of flunarizine on induced nystagmus and cochlear blood flow were compared with those of cinnarizine and diphenidol. Flunarizine significantly inhibited caloric (cool water)-induced nystagmus frequency and duration of nystagmus in rabbits at 5 mg/kg i.v., whereas cinnarizine and diphenidol only slightly decreased the frequency of nystagmus at 5 mg/kg, i.v. As for optokinetic stimuli-induced nystagmus in rabbits, flunarizine significantly decreased the amplitude of nystagmus at 2.5 mg/kg i.v., and cinnarizine and diphenidol inhibited nystagmus at 5 mg/kg, i.v. Flunarizine had no effect on nystagmus induced by electrical stimulation of the lateral geniculate body in rabbits at doses up to 5 mg/kg, i.v. Flunarizine increased the cochlear blood flow in anesthetized guinea pigs dose-dependently (0.312-1.25 mg/kg i.v.) On the other hand, cinnarizine (0.625-2.5 mg/kg i.v.) and diphenidol (0.625-2.5 mg/kg i.v.) increased cochlear blood flow, but the duration of action of both cinnarizine and diphenidol was shorter than that of flunarizine at the same dose. As stated above, flunarizine inhibited nystagmus experimentally induced by caloric or optokinetic stimuli. Increased cochlear blood flow suggested that the enhancement of vestibular blood flow might play an important role in the treatment of vestibular dysfunctions with this drug.

Animals↗
PubMed1988

Antihypertensive effects of the new calcium antagonist benidipine hydrochloride in rats.

Using spontaneously hypertensive rats (SHR), DOCA-NaCl hypertensive rats (DHR) and normotensive rats (NTR), the antihypertensive action of (+/-)-(R*)-2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dic arb oxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) was comparatively evaluated with those of nicardipine and hydralazine. Administration of KW-3049 at 0.5, 1 and 3 mg/kg (p.o.) showed dose-dependent antihypertensive action. This action appeared gradually and it lasted longer than those of nicardipine and hydralazine. The administration of KW-3049 at 0.5 mg/kg (p.o.) did not show any effect on the blood pressure of NTR, but a long-lasting blood pressure lowering action was observed by the administration at 1 and 3 mg/kg (p.o.). This antihypertensive action specific to the hypertensive animals was similar to that of nicardipine, however, it was different from that of hydralazine, with which the blood pressure in SHR, DHR and NTR was lowered in similar degrees. Also, administration of KW-3049 caused tachycardia concomitant with the fall of blood pressure, however, it was mild as compared with those of nicardipine and hydralazine. When KW-3049 at doses of 3 and 10 mg/kg (p.o.) once a day was continuously administered to SHR for 31 days and changes of the antihypertensive action were observed, no tolerance developed and rebound hypertension following the discontinuation of medication did not occur. When the effect on the urinary volume and electrolyte excretion was evaluated in rats loaded with physiological saline solution, a natriuretic effect was observed by the administration of KW-3049 at 0.5, 1 and 3 mg/kg (p.o.).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Effects of benidipine hydrochloride on atrioventricular conduction time and postural reflex in gallamine-immobilized cats.

Using gallamine-immobilized cats, the effect of (+/-)-(R*)-2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dic arb oxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) was compared with those of other drugs in terms of the propensity for atrioventricular conduction disturbances and orthostatic hypotension. The administration of KW-3049 at doses of 1 to 300 micrograms/kg i.v. dose-dependently lowered the blood pressure and also reduced the heart rate. In terms of the maximum blood pressure lowering activity, KW-3049 was similar in degree to nifedipine and approximately 30 times as potent as diltiazem, verapamil and phenoxybenzamine. KW-3049 as well as nifedipine, at doses with which the mean blood pressure can be reduced by 50 mmHg, hardly affected the PR-interval of ECG, whereas diltiazem and verapamil at their hypotensive doses markedly prolonged the PR interval. These four calcium antagonists at their high doses elicited 2nd or 3rd degree atrioventricular blocks in some cases. On the other hand, phenoxybenzamine did not affect the atrioventricular conduction at its hypotensive doses. Inhibitory action on the pressor responses to head-up tilting in cats was observed neither in KW-3049, nifedipine, verapamil nor diltiazem. On the contrary, phenoxybenzamine strongly inhibited the orthostatic pressor reflexes. From these results, it was suggested that in terms of the prolongation action of atrioventricular conduction KW-3049 is less potent than diltiazem and verapamil but similar in degree to nifedipine, and that KW-3049 is not likely to cause orthostatic hypotension.

Animals↗
PubMed1988

Antianginal effects of the new calcium antagonist benidipine hydrochloride in anesthetized rats and spontaneously hypertensive rats. Electrocardiographic study.

Antianginal effects of (+/-)-(R*)-2,6-dimethyl-4-(m-nitrophenyl)- 1,4-dihydropyridine-3,5-dicarboxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) in various experimental angina-pectoris models (anesthetized rats, spontaneously hypertensive rats (SHR] were compared with those of nifedipine, propranolol and hydralazine. Furthermore, the effects of these drugs on the pressure-rate product were evaluated. 1. Vasopressin test (SHR): The administration of KW-3049 at 10 micrograms/kg (i.v.) developed an inhibitory effect comparable to that of nifedipine at 200 micrograms/kg (i.v.) against the ischemic ECG changes caused by the intravenous administration of vasopressin at 1 U/kg. The effects of KW-3049 at 3 and 10 mg/kg (p.o.) lasted for 8 h or more. 2. Coronary occlusion test (rat): The rise of T-wave of epicardial ECG following ligation of coronary artery was inhibited by the administration of KW-3049 at doses of 30 and 100 micrograms/kg i.v. Nifedipine at dose of 200 micrograms/kg i.v. was slightly effective. 3. Isoproterenol (isoprenaline) test (rat): The fall of ST in ECG by the continuous infusion of isoprenaline (10 micrograms/kg/min) was almost completely prevented by propranolol (500 micrograms/kg i.v.). Also, KW-3049 (200 micrograms/kg i.v.) and nifedipine (200 micrograms/kg i.v.) significantly inhibited the decline of ST, in which the former was more effective than the latter. 4. Anoxia test (SHR): The fall of ST and rise of T-wave of ECG, induced by stopping artificial respiration of gallamine-immobilized SHR, were suppressed by the administration of KW-3049 at doses of 10 and 30 micrograms/kg i.v.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗
PubMed1988

Vasodilating effects of the new calcium antagonist benidipine hydrochloride in anesthetized dogs and cats.

Vasodilating effects of a new 1,4-dihydropyridine derivative, (+/-)-(R*)-2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3, 5-dicarboxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) were investigated in anesthetized dogs and cats. Intravenous administrations of KW-3049 at doses of 0.3 to 10 micrograms/kg exhibited a greater vasodilation in vertebral and coronary arteries than in common carotid and femoral arteries. The maximal effects of KW-3049 were equal to or more potent than those of nifedipine and nicardipine. Vertebral and coronary vasodilation following intravenous administration of 10 micrograms/kg of KW-3049 continued for 240 min or more, whereas those following nifedipine or nicardipine (10 micrograms/kg i.v.) disappeared within 30 min. A gradual and long-lasting increase of the vertebral and coronary blood flows following the intraduodenal administration of KW-3049 (0.1 mg/kg) was observed as compared with those of nifedipine (0.3 mg/kg i.d.) and nicardipine (0.3 mg/kg i.d.). When KW-3049 at a dose of 0.1 micrograms/kg was intraarterially administered to vertebral or coronary arteries, the blood flow increased without affecting systemic blood pressure and its effects lasted longer than those of nifedipine and nicardipine (0.1 micrograms/kg i.a.). In particular, the duration time in increase of coronary blood flow by KW-3049 was extremely longer, i.e. 11-fold and 6-fold those by nifedipine and nicardipine, respectively. Coronary vasodilating effect of KW-3049 was influenced neither by propranolol, atropine, diphenhydramine nor by aminophylline. Moreover, KW-3049 did not affect the vasodilator effect of adenosine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Beneficial effects of the new calcium antagonist benidipine hydrochloride on myocardial dysfunction following coronary occlusion and reperfusion in anesthetized dogs.

The protective effect of (+/-)-(R*)-2,6-dimethyl-4-(m-nitrophenyl)-1, 4-dihydropyridine-3,5-dicarboxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) on ischemic myocardium was examined comparing with that of nifedipine in anesthetized dogs subjected to a brief (10 min) coronary artery occlusion and reperfusion (2h). Occlusion of left anterior descending coronary artery elicited elevation of ST-segment and T-wave of epicardial ECG in the ischemic area. Regional myocardial contractile force in this area was depressed throughout the reperfusion period as well as during coronary occlusion period. LV max dp/dt, stroke volume and cardiac output tended to be reduced. In the dogs pretreated with 10 micrograms/kg of KW-3049 (i.v.) and 50 micrograms/kg of nifedipine (i.v.), both of which lowered the blood pressure to the same extent, elevation of ST-segment and T-wave was inhibited, and the prevention of irreversible depression of regional myocardial contraction observed at reperfusion periods was slightly more prominent in KW-3049 administration group. Stroke volume and cardiac output in both KW-3049 and nifedipine administration groups were maintained at higher levels than those in control group throughout coronary occlusion and the following reperfusion periods. LV max dp/dt of KW-3049 administration group was kept higher than that of the control group, while the value of the nifedipine administration group changed as that of the control group. These results demonstrate that KW-3049 as well as nifedipine exert protective effects on ischemic myocardium induced by coronary occlusion and reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗