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Biomedical subjects

Y Shiokawa

Publications and source records attributed to Y Shiokawa.

At least 73 records · Page 4Linked to original sources
PubMed1996

Agents for the treatment of overactive detrusor. IX. Synthesis and pharmacological properties of metabolites of N-tert-Butyl-4,4-diphenyl-2-cyclopentenylamine (FK584) in human urine.

We synthesized the racemates of the five presumed metabolites (1b-f) of (S)-(--)-N-tert-butyl-4,4-diphenyl-2-cyclopentenylamine hydrochloride (FK584, S(--)-1a), a novel agent for the treatment of overactive detrusor syndrome, in order to confirm the structures of the metabolites and also to evaluate their inhibitory activity against detrusor contraction. (+/-)-N-tert-Butyl-4-(4-hydroxyphenyl)- and 4-(4-hydroxyphenyl)- and 4-phenyl-2-cyclopentenylamines (1b--e) were synthesized via 5-(4-methoxyphenyl)- and 5-(4-benzyloxy-3-methoxyphenyl)-5-phenyl-2-cyclopenten-1-one (9g, h), respectively. Compounds 1b-f prepared in this study were identical with the metabolites in human urine in gas chromatography-mass spectrometry and analytical HPLC. The inhibitory activity of compounds 1b-f against detrusor contraction in vitro induced by electrical field stimulation in guinea-pigs was less potent than that of FK584.

Amines↗
PubMed1996

Agents for the treatment of overactive detrusor. V. Synthesis and inhibitory activity on detrusor contraction of N-tert-butyl-4,4-diphenyl-2-cyclopentenylamine.

N-tert-Butyl-4,4-diphenyl-2-cyclopentenylamine ((+/-)-3) was designed to restrict the conformation of terodiline 1 and was synthesized in a 6-step approach starting with diphenylacetaldehyde (10) or in a 4-step approach starting with 2,2-diphenyl-4-pentenoic acid (17). Using di-p-toluoyltartaric acid as a resolving agent, the synthetic (+/-)-3 was resolved into its optically pure forms, (-)- and (+)-3. The (-)-enantiomer (-)-3.HCl (FK584) showed about ten times more potent inhibitory activity on urinary bladder rhythmic contraction in rats (ED30 = 0.18 mg/kg, i.v.) than terodiline (ED30 = 1.9 mg/kg, i.v.), while the (+)-enantiomer (+)-3.HCl showed no inhibitory activity at 1.0 mg/kg i.v. Compound (-)-3.HCl (FK584) has pharmacological properties similar to those of terodiline, as evaluated by in vitro assay and is currently in clinical development for the treatment of overactive detrusor.

Amines↗
PubMed1996

Successful management of junctional tachycardia by hypothermia after a Fontan operation.

We report herein the findings of a 2-year-old boy in whom junctional tachycardia developed 2 days after he underwent a modified Fontan operation and thereafter was successfully treated by hypothermia without paralyzing and artificially ventilating the patient. Chlorpromazine was useful in achieving moderate hypothermia by surface cooling without producing any unfavorable effects associated with topical cooling.

Child, Preschool↗
PubMed1996

General pharmacology of the new non-xanthine adenosine A1 receptor antagonist (+)-(R)-[(E)-3-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)acryloyl]-2- piperidine ethanol.

FK 453 ((+)-(R)-[(E)-3-(2-phenylpyrazolo[1,5-a]pyridin-3-yl) acryloyl]-2-piperidine ethanol, CAS 121524-18-3) is a potent non-xanthine adenosine A1 receptor antagonist with diuretic and renal vasodilatory activity. The general pharmacology of FK 453 was investigated in mice, rats, guinea-pigs and dogs. In in vivo tests, FK 453 had little effect on the central nervous system (general behaviour, spontaneous motor activity, potentiation of barbiturate anesthesia, anticonvulsant activity, analgesic activity and body temperature), hematological system (bleeding time, coagulation time and recalcification time) and intestinal charcoal transit. FK 453 also did not show any cardiovascular (blood pressure, heart rate and femoral blood flow) or respiratory effects. In in vitro tests, although FK 453 had little effect on noradrenaline-induced contraction in rat vas deferens and histamine-induced contraction in guinea-pig trachea, FK 453 inhibited the acetylcholine-, histamine- and barium-induced contraction in isolated guinea-pig ileum and serotonin-induced contraction in isolated rat stomach. FK 453 also exerted significant inhibitory activity on collagen- and U 46619-induced platelet aggregation. However these effects of FK 453 on isolated tissue and platelet were observed only at high concentrations. These results suggest that FK 453 possesses a selective pharmacological profile, and one promising therapeutic site for this drug is in the kidney.

Analgesics↗
PubMed1995

A novel non-xanthine adenosine A1 receptor antagonist.

FK453, (+)-(R)-[(E)-3-(2-phenylpyrazolo[1,5-alpha]pyridin-3-yl) acryloyl]-2-piperidine ethanol, was examined for adenosine receptor antagonistic activity using isolated guinea-pig atria and aorta and for affinity for adenosine receptors in the rat cerebral cortex and striatum in comparison with FR113452 (S enantiomer of FK453), PD116948 (1,3-dipropyl-8-cyclopentylxanthine), theophylline (1,3-dimethylxanthine) and CGS15943 ([1,2,4]triazolo[1,5-c]quinazolone). FK453 showed potent inhibition of the negative inotropic activity elicited by 10 microM adenosine with an IC50 of 560 pM in guinea-pig atria. However, FK453 was less potent in inhibiting the relaxation induced by 3.2 microM adenosine and had an IC50 of 1.18 microM in guinea-pig aorta. The IC50 values for FR113452, PD116948, theophylline and CGS15943 were 1.18 microM, 1.31 nM, 20.2 microM and 74.2 nM in atria and > 100 microM, 656 nM, 239 microM, 127 nM in aorta respectively. In the binding study, FK453 antagonized [3H]N6-cyclohexyladenosine binding to the rat cortical adenosine A1 receptor with an IC50 of 17.2 nM. The IC50 values for FR113452, PD116948, theophylline and CGS15943 were 10.1 microM, 4.7 nM, 67.7 microM and 241 nM respectively. FK453 inhibited [3H]5'-N-ethylcarboxamideadenosine binding to rat striatum adenosine A2 receptor with an IC50 of 11.3 microM. FK453 had no adenosine A1 receptor agonistic activity, since it had no negative inotropic activity up to 100 microM in isolated guinea-pig atria. These results demonstrate that FK453 is a novel non-xanthine adenosine receptor antagonist and is potent and selective for the adenosine A1 receptor subtype.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1995

Parasellar Aspergillus granuloma extending from the sphenoid sinus: report of two cases.

BACKGROUND: Sphenoid sinus aspergillosis is a rare disease known to show an aggressive course with high mortality. Early diagnosis, though difficult, is required to prevent lethal fungal meningoencephalitis. CASE REPORT: We describe two cases of parasellar Aspergillus granuloma extending from the sphenoid sinus clinically indistinguishable from intracranial neoplasms. In the first patient, the fungus colony was visualized by computed tomography (CT) and magnetic resonance imaging (MRI) as a calcified concretion and total removal was curative. In the second patient, partial removal and subsequent antifungal therapy had minimal effect. CONCLUSIONS: The prognosis of the patients with this disease depends on prompt surgical treatment before intradural invasion occurs, and CT and MRI are useful diagnostic maneuvers for detecting calcified Aspergillus colonies.

Aged↗
PubMed1995

Delayed parent artery narrowing occurring months after aneurysm surgery: a complication after aneurysm surgery--technical case report.

The authors report two patients with a rare complication of parent artery narrowing that occurred 3 and 6 months after aneurysm surgery. In both cases, the stenosed arteries had been wrapped around their entire circumferences with neurosurgical sponge (cotton linter) and coated with plastic adhesive (cyanoacrylate compounds) and the aneurysmal neck had been clipped. This reinforcement procedure was considered to have caused the unusual delayed arterial narrowing. The importance of avoiding circumferential parent artery wrapping with plastic-adhesive coating is emphasized.

Aged↗
PubMed1995

Agents for the treatment of overactive detrusor. VIII. Synthesis and pharmacological properties of 4,4-diphenyl-2-cycloalkenylamines including FK584 and 3,3- or 4,4-diphenylcycloalkylamines.

This article describes the synthesis of 4,4-diphenyl-2-cycloalkenylamines (3, 5a) including FK584 (S(-)-3a) and 3,3- or 4,4-diphenylcycloalkylamines (2, 4, 5b) and their inhibitory activities against detrusor contraction. The order of inhibitory activity (i.v.) of the N-tert-butylamine derivatives against urinary bladder rhythmic contraction in rats was as follows: S(-)-4,4-diphenyl-2-cyclopentenylamine (FK584, S(-)-3a) > 4,4-diphenylcyclohexylamine (5b) = R(-)-3,3-diphenylcyclopentylamine (R(-)-4) > or = 3,3-diphenylcyclobutylamine (2) > or = terodiline hydrochloride (HCl) (1) = RS(+/-)-4,4-diphenyl-2-cyclohexenylamine (5a) > R(+)-4,4-diphenyl-2-cyclopentenylamine (R(+)-3a) > or = S(+)-3,3-diphenylcyclopentylamine (S(+)-4). Although the inhibitory activity of FK584 and compounds R(-)-4 and 5b against detrusor contraction in vitro induced with KCl in guinea-pigs was less potent than that of terodiline HCl, their inhibitory activities against detrusor contractions in vitro induced by electrical field stimulation and carbachol were more potent than those of terodiline HCl.

Amines↗
PubMed1995

[Postoperative pulmonary stenosis after arterial switch operation, comparison in three methods of pulmonary reconstruction: modified Pacifico, autologous pericardial patch, and equine pericardial patch].

To prevent postoperative pulmonary stenosis in arterial switch operation for transposition of the great arteries, pulmonary reconstruction without patch augmentation (modified Pacifico method: Pa-group) and reconstruction using W-shaped fresh autologous pericardium (AW-group) were introduced instead of the former method using equine pericardium (XW-group). Postoperative pulmonary stenosis (RV-PA pressure gradient greater than 30 mmHg) was not seen among the 17 cases in the Pa-group (0%), and was seen in 2/14 (14.3%) in the AW-group and in 4/14 (29%) in the XW-group. Progressive increase in pressure gradient was seen in the XW-group in the midterm cardiac catheterization (p < 0.01), but such tendency was not observed in the Pa-group and the AW-group. Sectional area at the pulmonary valve ring, at the anastomotic site in the main pulmonary artery, and at the pulmonary branches just distal to the bifurcation, standardized by the body surface area, increased in the Pa-group and the AW-group, but were unchanged or slightly decreased in the XW-group in the midterm cardiac angiography. We believe that postoperative pulmonary stenosis can be best avoided if modified Pacifico method is used. The cases in which postoperative pulmonary stenosis or coronary artery compression is anticipated such as those with side-by-side aortopulmonary relationship or after pulmonary artery banding, should be operated upon using fresh autologous pericardial patch.

Humans↗
PubMed1995

[Surgical results of valvuloplasty for common atrioventricular valve regurgitation in single ventricle].

From 1988 through 1994, 18 patients who had common atrioventricular valve regurgitation associated with single ventricle underwent valvuloplasty. All patients had isomerism heart (right isomerism: 16, left isomerism: 2). The preoperative degree of regurgitation was 3.3 +/- 0.4 (Sellers). Valvuloplasty was performed by two different procedures. Semi-circular annuloplasty was used in nine patients. Dividing the common atrioventricular valve orifice into two parts (bivalvation) with or without annuloplasty was used in nine. The concomitant procedures varied: three patients underwent systemic pulmonary shunt, two underwent repair of total anomalous pulmonary venous drainage, one underwent pulmonary arterial banding, five underwent bidirectional Glenn, shunt, and four underwent Fontan operation. One early death and three late deaths have occurred. The early postoperative degree of regurgitation was reduced to 1.3 +/- 1.0. In nine patients, however, the degree of regurgitation increased late postoperatively. Seven patients were reoperated on because of regurgitation: three patients had valve replacement and four had reannuloplasty. Increased incidence of deterioration of regurgitation in late period was seen in patients under 2 years old and those receiving a concomitant Blalock shunt. Lower event-free rate after 2 years was seen in patients with double inlet right or indeterminate ventricle and those underwent the annuloplasty alone. We conclude that the dividing common atrioventricular valve orifice into two parts with annuloplasty could effectively reduce the regurgitation in most patients with isomerism heart, and the concomitant ventricular unloading operation seems to offer promise for improving long-term results.

Adolescent↗
PubMed1995

[Valve replacement in an infant with congenital mitral stenosis--report of a case which showed hemodynamics similar to that of hypoplastic left heart syndrome in neonatal period].

In the neonatal period, the patient showed severely hypoplastic left ventricle, severe mitral stenosis, patent foramen ovale and patent ductus arteriosus with right-to-left shunting, which resulted in the hemodynamics similar to that of hypoplastic left heart syndrome. However, progressive left ventricular growth was recognized after spontaneous closure of the foramen ovale, and the cardiac catheterization at the age of 6 months revealed almost normal left ventricular volume and systolic forward flow from the left ventricle to the descending aorta. The operation was performed at the age of 7 months under cardiopulmonary bypass with moderate hypothermia and cardiac arrest. The mitral leaflets were thickened and dysplastic, two short papillary muscles were hypertrophic and very closely related, and the chordae were extremely short and fused each other making the interchordal space obstructed. Because the mitral annular diameter (13 mm) was too small for conventional valve replacement, the prosthetic valve (CarboMedics #16) was sewn to the left atrial wall 5 to 10 mm above the mitral annulus. The ductus arteriosus was ligated. The postoperative cardiac catheterization showed residual pulmonary hypertension, but pulmonary vascular response to oxygen-inhalation was recognized. We consider that there were two important hemodynamic factors which led to successful biventricular repair in this case. First, early spontaneous closure of the foramen ovale accerelated the left ventricular growth and prevented right ventricular failure resulting from increased pulmonary blood flow. Second, considerable part of the systemic output was supplied through a large ductus arteriosus, and thus over-systemic pulmonary hypertension was avoided.

Cardiopulmonary Bypass↗
PubMed1995

[Medical care of AIDS patients by hospitals in Tokyo].

An anonymous questionnaire survey was performed in 1991 in all 749 hospitals in Tokyo, by the Tokyo Metropolitan Government's Acquired Immunodeficiency Syndrome (AIDS) and Human Immunodeficiency Virus (HIV) Infection Research Team, to collect information relating to hospital services for persons with AIDS or HIV infection. The response rate was 61%. The following results were obtained: 1) Sixty-five hospitals (14%) had seen persons with AIDS or HIV infection. Hospitals with a greater number of beds had more experience in seeing persons with AIDS or HIV infection. Thirty-four hospitals (7%) provided outpatient services for patients with AIDS or HIV infection, and 30 hospitals (7%) had the facilities for inpatients. Three hundred forty-seven hospitals (78%) were capable of HIV antibody tests. Ninety-one hospitals (20%) had organized training courses for hospital workers to prevent HIV infection. Two hundred eight hospitals (46%) expressed preference that persons with AIDS or HIV infection be treated at public (non-private) hospitals. 2) The results of multivariate logistic regression analysis indicated that a hospital's acceptance of persons with AIDS or HIV infection for diagnosis or treatment was significantly related to past experience in seeing persons with AIDS or HIV infection, availability of an examination room that protects privacy of patients, presence of a department of internal medicine, and awareness of the availability of special AIDS counselor dispatch services by the Tokyo metropolitan government.

Acquired Immunodeficiency Syndrome↗
PubMed1994

The temporo-polar approach to basilar artery aneurysms with or without zygomatic arch translocation.

Since the publication of the temporo-polar approach to basilar artery aneurysms by Sano (1980 and 1987), various modifications of the approach were reported. The approach provides a better view and a wider operating field than the subtemporal or pterional ones. Usually the approach does not need temporary remove of the zygomatic arch. If however, a basilar tip aneurysm is located very high above the posterior clinoid, temporary removal of the zygomatic arch is necessary which is sutured back to its original position at the end of the operation.

Basilar Artery↗
PubMed1994

Cerebrovascular sensory innervation involved in the development of cerebral vasospasm following a subarachnoid hemorrhage.

Cerebral vasospasm following subarachnoid hemorrhage was induced in the squirrel monkey in order to evaluate the involvement of cerebrovascular sensory nerves in the development of the vasospasm. A unilateral surgical section of the trigeminal nerve at post- but not at pre-Gasserian level caused constriction of the major ipsilateral cerebral arteries. A pre- or postganglionic trigeminal lesion induced an increased glucose uptake globally without influencing the cerebral blood flow. Following a subarachnoid hemorrhage, the decrease in cerebral blood flow was similar of that seen in control animals, while post-ganglionically lesioned animals had an additional increase in glucose uptake. Intrathecal injection of gamma-globulin against substance P prevented the occurrence of vasospasm and the decrease in cerebral blood flow, while calcitonin gene-related peptide (CGRP) anti-gamma-globulin injection significantly reduced the resting vessel diameter and did not influence spasm development. It is concluded that a nervous reflex mechanism could underlie cerebral vasospasm. The cerebrovascular sensory nerves have both a peripheral and a central function. A peripheral or axon reflex mechanism exerts a tonic effect on the cerebral arteries. Central neurotransmission seems to be involved in the regulation of cerebral metabolism and possibly in the coordination of cerebral blood flow and glucose metabolism. CGRP could be the transmitter involved in a peripheral axon reflex and substance P might be the neurotransmitter conveying information to the brainstem vascular centers.

Animals↗