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T Ishimori

Publications and source records attributed to T Ishimori.

At least 37 records · Page 2Linked to original sources
PubMed1998

Studies on agents with vasodilator and beta-blocking activities. V. Synthesis and pharmacological activity of the optical isomers of TZC-5665.

Synthesis of the four optical isomers of TZC-5665 (1), a candidate for the treatment of congestive heart failure, was achieved by the reaction of chiral diaminopyridazinone (2) with chiral glycidyl ether. (3). The hypotensive and beta-blocking activities of 1 and its optical isomers were examined when given intravenously into anesthetized rats. Furthermore these compounds were evaluated for inhibitory activity on cAMP phosphodiesterase III. Among the four optical isomers, Ra,Sb-one (1c) possessed the essential activities of TZC-5665 (1).

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1998

High-resolution MR cholangiopancreatography.

1. High-resolution MRCP is a noninvasive imaging modality for depicting the pancreatobiliary tree. The imaging quality of high-resolution MRCP is satisfactory. MRCP can demonstrate dilation, stenosis, and intraductal filling defects of both the biliary tract and the pancreatic duct, which meets the clinical demand for pancreatobiliary imaging. 2. MRCP was successful in almost all the patients. However, the causes of MRCP failure were patient motion, irregular respiratory rhythm, severe pneumobilia, and massive ascitic fluid. 3. When only MIP reconstructed images were used for interpretation, small intraductal filling defects such as a gallstone can be missed. In combination with coronal source images, the ability to detect intraductal stones can be increased. 4. Ferrite ammonium citrate (FAC) is useful in suppressing the background signal intensity of gastrointestinal contents so that the ducts can be clearly visualized. The other technique for decreasing the background signal intensity is target MIP postprocessing, which works well for better visualization of the ducts. 5. The degree of ductal narrowing tends to be overestimated with MRCP because of MIP reconstruction artifact and lower spatial resolution of MRCP than ERCP. 6. MRCP has a diagnostic pitfall of a pseudostenosis of extrahepatic ducts, which may lead to a false-positive diagnosis of ductal narrowing. This pitfall may be caused not only by MIP postprocessing artifacts but by gas, surgical metal, and vascular compression of right hepatic artery. There is another diagnostic pitfall that it is difficult to differentiate intraductal mucin from pancreatic fluid in dilate pancreatic ducts, although ERCP identifies mucin as intraductal filling defects.

Biliary Tract↗
PubMed1998

[Clinical usefulness of fat suppression technique for MR cholangiopancreatography (MRCP)].

In order to obtain high quality of MRCP image, it is important to reduce the background signal intensity and increase the contrast of the pancreatobiliary ducts relative to surrounding fat tissue. The combination of long effective-TE and fat suppression technique including the short-TI inversion recovery and chemical-selective fat suppression enables to suppress the background signal intensity enough to obtain high quality MR cholangiopancreatogram. However, susceptibility artifacts from the metal, gastroduodenal gas, and vascular pulsation can be augmented by using the chemical-selective fat suppression technique, which may result in signal loss of the pancreatobiliary ducts. This potential diagnostic pitfalls can be avoided by interpreting the coronal source images obtained with long effective-TE and without fat suppression technique.

Adipose Tissue↗
PubMed1997

[MR dynamic subtraction angiography (MRDSA)].

We have developed magnetic resonance dynamic subtraction angiography (MRDSA), which depicts the long segments of arteries from the upper abdomen to the lower leg by using a small dose of Gd-DTPA. The lower half of the body was divided into three imaging regions, abdomen, thigh and lower leg, in the order of scanning. The contrast-enhanced three-dimensional breath-hold fast field echo technique with half Fourier acquisition was performed in 3 normal volunteers and 12 patients with vascular diseases (4: abdominal aortic aneurysm, 8: atherosclerotic occlusive disease). The images were reconstructed into composite images by using maximum-intensity-projection postprocessing after the subtraction of precontrast images. A bolus intravenous injection of a small dose of Gd-DTPA (0.02-0.05 mmol/kg) was given, followed by the five sets of scans. The acquisition time of each set was 8 to 16 seconds, and the total dose used in MRDSA was 0.1 to 0.15 mmol/kg. The image quality of MRDSA was satisfactory in 3 normal volunteers and 12 patients with vascular diseases. MRDSA demonstrated aortic aneurysm and atherosclerotic obstruction as clearly as conventional angiography. MRDSA can replace conventional angiography.

Angiography, Digital Subtraction↗
PubMed1996

Studies on agents with vasodilator and beta-blocking activities. IV.

A series of novel pyridazinone derivatives (II) having a phenoxypropanolamine moiety was synthesized. Their hypotensive and beta-blocking activities were evaluated after intravenous administration of the compounds to anesthetized rats. Among them, the 5-chloro-2-cyanophenoxy derivative (29) showed the promising dual activities and was selected for further studies.

Adrenergic beta-Antagonists↗
PubMed1995

Studies on agents with vasodilator and beta-blocking activities. III. Synthesis and activity of optical isomers of TZC-1370.

Optical isomers of TZC-1370 (1) were prepared from (R)- and (S)-1-(2-chlorophenoxy)-2,3-epoxypropane. When given intravenously to anesthetized rats, the (S)-isomer was about 40 times more potent in terms of beta-blocking activity than the (R)-isomer, while their hypotensive activities were equipotent with that of the racemic compound, TZC-1370.

Adrenergic beta-Antagonists↗
PubMed1995

Studies on agents with vasodilator and beta-blocking activities. II.

A series of phenoxypropanolamines having a hydrazinopyridazinyl moiety was synthesized. Their hypotensive and beta-blocking activities were evaluated after intravenous administration of the compounds to anesthetized rats. Some of them exhibited both activities. In particular, compound 20k is a candidate for clinical use due to its hypotensive activity, equal to that of hydralazine, and its beta-blocking activity, 2.7-fold more potent than that of propranolol.

Adrenergic beta-Antagonists↗
PubMed1994

Studies on agents with vasodilator and beta-blocking activities. I.

A series of hydrazinopyridazine derivatives combined with a beta-blocking side chain were synthesized. When they were given intravenously to anesthetized rats, some of them exhibited both hypotensive and beta-blocking activities. Their structure-activity relationships for hypotensive and beta-blocking activities are discussed. Compound 11c had the best profile and was selected for further study.

Adrenergic beta-Antagonists↗
PubMed1994

Cardiac effects of the novel pyridazinone derivative 6-[4-[2-[3-(5-chloro-2-cyanophenoxy)-2-hydroxypropylamino]- 2- methylpropylamino]phenyl]-4,5-dihydro-5-methyl-3(2H) pyridazinone monoethyl maleate and its metabolite in isolated heart preparations of guinea pigs and dogs.

The cardiovascular effects of 6-[4-[2-[3-(5-chloro-2-cyanophenoxy)-2- hydroxypropylamino]-2-methylpropylamino]phenyl]-4,5-dihydro- 5-methyl-3(2H) pyridazinone monoethyl maleate (salt) (TZC-5665, CAS 114856-47-2) and its main metabolite in human, M-2, were investigated in isolated atrial and ventricular muscles of guinea pigs and dogs, in guinea pig atrial and right ventricular papillary muscles. TZC-5665 showed negative chronotropic and inotropic effects, whereas M-2 showed a potent positive inotropic effect with a slight positive chronotropic effect. The positive inotropic effect of M-2 was not modified by phentolamine, propranolol and cimetidine, but completely depressed by carbachol. In blood-perfused dog heart preparations, M-2 increased the contractile force and coronary blood flow of paced papillary muscles and sinus rate. Although TZC-5665 scarcely affected the contractile force and sinus rate, it increased coronary blood flow. TZC-5665 scarcely affected atrio-ventricular (AV) conduction time, whereas M-2 slightly shortened AV conduction time. The rate of ventricular automaticity was slightly increased by M-2, but suppressed by TZC-5665 at higher doses. TZC-5665 showed a non-selective beta-adrenoceptor blocking activity comparable to that of propranolol in guinea-pig atrial and tracheal preparations. In enzyme preparations, TZC-5665 and M-2 were more potent and selective inhibitors of phosphodiesterase (PDE) III than milrinone. Combination of beta-adrenoceptor blocking effect of TZC-5665 and positive inotropic effect of M-2 could be useful in the treatment of congestive heart failure by mutual prevention of undesirable effects.

Adrenergic beta-Antagonists↗
PubMed1991

Prospective community evaluation of the signal-averaged electrocardiogram in predicting malignant ventricular arrhythmias: beneficial outcome with electrophysiology guided therapy.

The role of the signal-averaged ECG was prospectively assessed in 517 patients in whom there was a suspicion for malignant ventricular arrhythmias. Patients were divided into Group I with a normal surface QRS width less than 120 ms (426 patients) and Group II with a prolonged QRS duration greater than or equal to 120 ms (91 patients). Late potentials were present in 42 (10%) Group I patients and in 24 (26%) Group II patients. Programmed ventricular stimulation was performed for standard indications in 55 patients without late potentials and in 42 patients with late potentials, combining both groups. The sudden death or recurrent sustained ventricular tachycardia rate in follow-up was evaluated based on the presence or absence of late potentials and whether programmed ventricular stimulation was performed. In the patients without late potentials, these rates were 4 patients (1.0%) in the no EP group and 3 patients (5.5%) in the EP group (p less than .05), respectively (overall 1.6%). In the patients with late potentials, these rates were 7 patients (29%) in the no EP group and 7 patients (17%) in the EP group (p = .19), respectively (overall 21%). In addition, appropriate automatic defibrillator shocks were present in 1 patient without late potentials and in 8 patients with late potentials which were not included in the recurrent sudden death or sustained ventricular tachycardia statistics. The signal-averaged ECG accurately defines patients at a higher risk for malignant ventricular arrhythmias regardless of unfiltered QRS duration.(ABSTRACT TRUNCATED AT 250 WORDS)

Electric Countershock↗
PubMed1988

Different responses to beta-adrenoceptor blocking drugs of the blood pressure and heart rate in the urethane-anesthetized dog and rat.

I.v. propranolol (Prop) produced sustained pressor responses in rats but not in dogs under urethane anesthesia. In the dogs there was a progressive reduction in systolic blood pressure (SBP) in accordance with a significant heart rate (HR) reduction. Even at the i.v. dose (5 mg/kg) where vasoconstrictor response to i.v. norepinephrine (NE) is changed to the vasodilator one in rats, phenoxybenzamine could not completely suppress the NE-induced vasoconstriction in dogs. In pithed dogs, unlike pithed rats, i.v. Prop augmented neither sympathetic nerve stimulation- nor i.v. epinephrine (Epi)-induced pressor responses. Urethane anesthesia brought much higher concentrations in plasma Epi and NE in the dog than in the rat. In comparison with their respective values under the conscious state, SBP and HR of the dog were higher and those of the rat were lower under urethane anesthesia. As in urethane-anesthetized dogs, i.v. Prop elicited remarkable HR reduction accompanied by progressive hypotension in coronary-ligated rats with high sympathetic activity. Thus the reason for the absence of pressor response to beta-receptor blockage in the dog may be due to less functional significance of beta 2-adrenoceptor-mediated vasodilation in determining the peripheral vascular tone; and also, the possibility that there may be the involvement of an inverse influence of urethane on the cardiovascular regulatory system in terms of enhancing sympathetic nervous activity in the dog and a decreasing one in the rat can not be ruled out.

Adrenergic beta-Antagonists↗
PubMed1985

Membrane proteins in Rh+, Rh- and Rh: -29, 38 (- - -/- - -, rh) red cells compared by using SDS-polyacrylamide gel electrophoresis.

Since Rh: -29, 38 (- - -/- - -, rh) phenotype of the Rh blood groups (--- in text) revealed unusual red cells, such as stomatocytes and microspherocytes and the relatively shortened half life of 17 days, red cell membrane proteins from Rh + (D), Rh - (d) and --- were compared by using SDS-polyacrylamide gel electrophoresis (SDS-PAGE). No differences were observed among the patterns of the reduced and non-reduced membrane proteins from Rh+, Rh- and --- red cells. Two-dimensional gel electrophoresis of --- red cell membrane proteins also revealed a pattern similar to Rh+ and Rh- red cell membrane proteins. It is suggested that the lack of all Rh antigens causes no visible alteration of red cell membrane proteins detected by the method of Fairbanks G., Steck T.L. and Wallach D.F.H. (1971) Biochemistry, N.Y. 10, 2606-2617.

Electrophoresis, Polyacrylamide Gel↗
PubMed1984

Role of beta 2-adrenoceptor blockade and circulating adrenaline level for the pressor responses to beta-adrenoceptor blocking drugs in rats.

The present experiments were designed to elucidate what mechanism(s) would be responsible for beta-adrenoceptor blocking drugs (beta-blockers)-induced pressor responses in rats. In urethane-anaesthetized rats, 6 beta-blockers at i.v. doses ranging from 0.3 to 300 micrograms/kg evoked the pressor response in a dose-dependent manner. The relative potency in causing the pressor action was correlated not to their beta 1-blocking activities (r = 0.374, P greater than 0.05) but to their beta 2-blocking ones (r = 0.856, P less than 0.05). In pithed or adrenalectomized rats with low levels of plasma catecholamines, however, propranolol failed to exert its sustained pressor action. Propranolol (300 micrograms/kg i.v.) distinctly potentiated the pressor responses not to noradrenaline but to adrenaline and to electrical stimulation of the sympathetic outflow (E.S.) in pithed rats. On the contrary, there was not any potentiation of pressor response to E.S. in pithed, adrenalectomized rats treated with propranolol (300 micrograms/kg i.v.). In rats treated with phenoxybenzamine (5 mg/kg i.v.), adrenaline was shown to have much more potent vasodilating action resulting from beta 2-stimulation than noradrenaline, the dose difference for causing the diastolic blood pressure decrease by a 25 mm Hg being almost 80 times. In pithed rats, infusion of adrenaline at the rate of 0.02 micrograms/min caused a significant increase in plasma adrenaline level from 0.02 +/- 0.01 to 0.45 +/- 0.048 ng/ml, being close to basal level obtained in urethane-anaesthetized rats. Under this situation, propranolol (1-100 micrograms/kg i.v.) showed a distinct pressor response in a dose-dependent fashion as observed in adrenal intact rats anaesthetized with urethane.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗
PubMed1983

Variability in coronary hemodynamics in response to ergonovine in patients with normal coronary arteries and atypical chest pain.

Because an increase in coronary vascular resistance in response to ergonovine maleate has been suggested as a possible diagnostic aid for variant angina, changes were evaluated in coronary hemodynamics and serial myocardial thallium-201 perfusion scans in 15 patients without angina and with normal coronary arteries in response to ergonovine (0.05, 0.10 and 0.20 mg intravenously). For the group, heart rate-blood pressure product increased significantly (p less than 0.001) without any change in coronary sinus flow, coronary vascular resistance, myocardial oxygen extraction, arterial-coronary sinus oxygen difference and lactate extraction. In 7 of 15 patients, however, coronary vascular resistance increased (mean 39%, range 11 to 75%, probability [p] less than 0.001), and coronary sinus flow decreased (14%, p less than 0.001), despite an increase in heart rate-blood pressure product (36%, p less than 0.02). No electrocardiographic, metabolic or thallium-201 scan abnormalities occurred. Therefore, significant increases in coronary vascular resistance in response to ergonovine may occur in patients with normal coronary arteries and atypical chest pain.

Adolescent↗
PubMed1983

Drug-induced inhibition of guinea pig platelet aggregation unrelated to their beta-adrenolytic actions.

Inhibitory actions on adenosine diphosphate (ADP)-induced platelet aggregation of atenolol, dl- and d-D-32, IPS-339, pindolol and propranolol were investigated in guinea pigs for the purpose of obtaining a clue about a possible mechanism for the disaggregatory phenomenon of beta-adrenoceptor blocking agents. The effects of verapamil and procaine on guinea pig platelet aggregation were also examined. All of these agents including verapamil and procaine showed a dose-dependent inhibitory effect on platelet aggregation, and their relative potencies determined on the basis of the molar concentrations producing a 50% inhibition of ADP-induced aggregation were in descending order: IPS-339 greater than propranolol greater than verapamil greater than dl-D-32 not equal to d-D-32 greater than pindolol greater than procaine greater than atenolol. This order of relative potencies of the inhibitory actions of these test compounds on platelet aggregation was well correlated to those of local anaesthetic action in guinea pigs (r = 0.932, P less than 0.01) and lipophilicity (r = -0.899, P less than 0.01), while it did not agree with the orders of potency of beta-adrenoceptor blocking action, intrinsic sympathomimetic action and vasodilator action. From these results, it may be reasonable to propose that inhibitory actions of beta-adrenoceptor blocking agents and local anaesthetics on platelet aggregation are caused through the same mechanism or through a very similar one.

Adrenergic beta-Antagonists↗
PubMed1982

[Antihypertensive action of adrenergic beta-receptor blockers and its effect on the entire sympathetic outflow in spontaneously hypertensive rats].

Three kinds of beta-adrenoceptor blocking agents were orally administered to spontaneously hypertensive rats (SH rats) from 5 to 13 weeks of age, and their effects on the development of hypertension and on peripheral sympathetic nervous system were investigated. In SH rats treated with the vehicle (2% Tween 80) for 8 weeks, systolic blood pressure increased from 132 +/- 1.3 to 179 +/- 2.7 mmHg (n = 10). Treatment with propranolol (2 X 50 mg/kg/day p.o., n = 8), pindolol (2 X 15 mg/kg/day p.o., n = 8) and D-32 (2 X 15 or 2 X 50 mg/kg/day p.o., n = 9) for 8 weeks slightly but definitely depressed the aforesaid development of hypertension, and their average reduction in systolic blood pressure was approximately 15 mmHg. In the pressor response to electrical stimulation of pre-ganglionic sympathetic nerves, there was not any difference between SH rats treated with vehicle and beta-adrenoceptor blocking agents (propranolol and D-32). P.o. administration of guanethidine or phentolamine, however, caused a slight hypotension and produced a significant reduction in the pressor response to electrical stimulation. SH rats treated with propranolol showed a leftward shift of the pressor response curve not to norepinephrine but to angiotensin II as compared with that obtained from vehicle treated SH rats. This phenomenon is probably due to the decreased renin release by the prolonged-treatment with drug. On the basis of these results, we could not obtain any clear evidence that the antihypertensive action exerted by beta-adrenoceptor blocking agents resulted from some interference with the function of the peripheral sympathetic nervous system.

Adrenergic beta-Antagonists↗