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Biomedical subjects

K Tokoro

Publications and source records attributed to K Tokoro.

At least 19 recordsLinked to original sources
PubMed1995

General pharmacology of the new antimuscarinic compound vamicamide.

The general pharmacology of the new antimuscarinic compound vamicamide (FK176, (+/-)-(2R*, 4R*)-4-dimethylamino-2-phenyl-2- (2-pyridyl)valeramide, CAS 132373-81-0) was investigated using mice, rats, guinea pigs and dogs, and was in part compared with that of oxybutynin hydrochloride (oxybutynin, CAS 1508-65-2), a similar type of compound. 1. Vamicamide induced mydriasis after oral administration (p.o.) of 10 mg/kg or more, and suppressed defecation after 32 mg/kg or more in the general activity and behavior test with rats. 2. Vamicamide increased spontaneous locomotor activity in mice at 32 mg/kg or more (p.o.) and suppressed tonic convulsions in the electroconvulsive shock test with mice at 100 mg/kg. The compound at 10-100 mg/kg (p.o) did not show significant effects on hexobarbital-induced anesthesia, pentetrazole-induced convulsions and pain response by Haffner's method in mice, body temperature in rats or spontaneous electroencephalogram (EEG) in rabbits. On the other hand, oxybutynin increased high voltage slow waves of spontaneous EEG in rabbits at 32 mg/kg or more (p.o.) and prolonged hexobarbital-induced anesthesia time in mice at 100 mg/kg. 3. Vamicamide in concentrations of 0.001-1% (1 x 10(-4)-1 x 10(-1) g/ml) did not show local anesthetic effect on the corneal reflex test with guinea pigs. The compound in concentrations of 1 x 10(-5) and 1 x 10(-4) g/ml also had no effects on contractions of the isolated rat diaphragm caused by electrical stimulation of the phrenic nerve. 4. Vamicamide on the highest concentration of 1 x 10(-4) g/ml augmented contractions of isolated rat vas deferens induced by noradrenaline, resting tonus of the isolated guinea pig trachea, and contractile force of spontaneous movement of the isolated rat nonpregnant uterus. The compound at 1 x 10(-4) g/ml had no significant effects on KCl-induced contraction of the isolated rat thoracic aorta. 5. Vamicamide elevated systemic blood pressure and increased heart rate but had no effects on respiratory movement of the chest in conscious dogs at an oral dose of 10 mg/kg or more. The compound in intraduodenal (i.d.) doses of 3.2-32 mg/kg had no effect on femoral blood flow in anesthetized dogs. Vamicamide augmented contractile force and reduced beating rate in isolated guinea pig atria at a concentration of 1 x 10(-5) g/ml or more. Oxybutynin increased heart rate at 3.2 mg/kg or more (p.o.), and elevated blood pressure at 10 mg/kg or more in conscious dogs. 6. Vamicamide slightly inhibited small intestinal transit in rats at 3.2 mg/kg or more (p.o.). On the other hand, oxybutynin inhibited the transit in rats at 0.32 mg/kg or more. 7. Vamicamide had no effects on urine volume, urinary excretion of Na+, K+, Cl- and uric acid in rats at an oral dose of 100 mg/kg or less, or on renal function in anesthetized dogs at an i.d. dose of 32 mg/kg or less. 8. Vamicamide showed no effects on bleeding time in mice at 100 mg/kg p.o., rabbit platelet aggregation induced by adenosine diphosphate or collagen at 1 x 10(-4) g/ml, blood coagulation systems in rats at 100 mg/kg p.o., or hemolysis on rabbit blood at a concentration of 1% or less. Thus, vamicamide in the doses used inhibited gastrointestinal motility, and caused mydriasis as effects possibly due to its anticholinergic action. The compound had no effects on the central nervous system, cardiovascular system, renal functions, or blood system.

Animals↗
PubMed1994

Importance of anti-siphon devices in the treatment of pediatric hydrocephalus.

The effects of an anti-siphon device (ASD) on shunt flow and intracranial pressure (ICP) in 16 children with hypertensive hydrocephalus were examined using quantitative radionuclide shuntography (99mTc) with the children in supine and sitting positions. The average age of these patients was 9.5 years. Results were compared with those recorded in 36 patients with adult normal-pressure hydrocephalus (NPH). The closing pressure levels of shunt valve used were low in 8 cases, medium in 7 and high in 1. Half the children (8) had shunt systems with, and the other 8 without, ASD. In the children who had the shunt system without ASD, sitting shunt flow was significantly greater than supine shunt flow, which indicated overdrainage. Conversely, in children who had the shunt system with ASD, supine shunt flow was greater than sitting shunt flow. Because ASD prevented overdrainage, ICP was higher with the shunt system with ASD than with the shunt system without ASD. Without ASD, sitting shunt flow of children was lower than that of adult patients with NPH because of the lower hydrostatic pressure, which correlated with their height. Conversely, in the presence of a shunt system with ASD, sitting shunt flow of children was greater than that of adults, because of the higher ICP and lower hydrostatic pressure. The effect of ASD was smaller in children than in adults, because positive pressure over the ASD was greater (hypertension vs normal pressure) and negative pressure under the ASD was less (short vs tall) in children than in adults. Thus, in children the ASD was effective in preventing overdrainage.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Pharmacological profile of FK480, a novel cholecystokinin type-A receptor antagonist: comparison to loxiglumide.

The pharmacological profile of FK480[(S)-(+)-N-<1-(2)-fluorophenyl)-3,4,6,7-tetra hydro-4-oxo-pyrrolo(3,2,1-jk) (1,4)benzodiaze-pine-3-yl>-1H-indole-2- carboxamide], a novel cholecystokinin type-A (CCK-A) receptor antagonist, was compared with that of the CCK-A receptor antagonist, loxiglumide. Both FK480 and loxiglumide inhibited 125I-labeled CCK-8 (125I-CCK-8) binding to rat pancreatic and guinea-pig gallbladder membranes with IC50 values of 0.40 +/- 0.04 and 0.06 +/- 0.02 nM for FK480 and 330 +/- 66 and 66 +/- 10 nM for loxiglumide, respectively. These two agents also inhibited 125I-CCK-8 binding to guinea-pig brain (cerebral cortex) receptors with respective IC50 values of 72 +/- 11 nM and > 10 microM, indicating less affinity to central receptors. Intravenous administration of FK480 (ED50 = 18 micrograms/kg) was 2800 times more potent than that of loxiglumide (ED50 = 50 mg/kg) in inhibiting CCK-8-induced pancreatic amylase secretion in rats. Furthermore, FK480 had ED50 values of 10 and 8.4 micrograms/kg, respectively, in antagonizing CCK-8-induced inhibition of charcoal meal gastric emptying in mice when administered orally 1 or 5 hr before the CCK-8. Loxiglumide (ED50 = 23.5 mg/kg, when administered orally 1 hr before the CCK-8) also antagonized it, but its activity was 2400 times less than that of FK480. We conclude that FK480 is a potent, orally effective CCK-A receptor antagonist with long duration of action.

Amylases↗
PubMed1993

Pineal ganglioglioma in a patient with familial basal ganglia calcification and elevated serum alpha-fetoprotein: case report.

Pineal ganglioglioma was diagnosed in a 36-year-old man with familial basal ganglia calcification and elevated serum alpha-fetoprotein. The patient was treated surgically with a good result. Only four other cases of this tumor have been reported. His 38-year-old brother also showed basal ganglia calcification and elevated serum chorionic gonadotropin as well as alpha-fetoprotein. Familial basal ganglia calcification with elevated serum alpha-fetoprotein in a nonhepatic benign condition is rare. The pathogenesis of these conditions is discussed.

Adult↗
PubMed1993

Pharmacological characterization of FK1052, a dihydropyridoindole derivative, as a new serotonin 3 and 4 dual receptor antagonist.

(+)-8,9-Dihydro-10-dihydro-10-methyl-7-[(5-methyl-4-imidazolyl) methyl]pyrido-[1,2-a]indol-6(7H)-one hydrochloride (FK1052) is a newly designed and synthesized 5-hydroxytryptamine (5-HT)3 receptor antagonist with 5-HT4 receptor antagonistic activity. This compound, as well as ondansetron and granisetron, dose-dependently inhibited the von Bezold-Jarish reflex, a 5-HT3 receptor-mediated response, after intravenous (i.v.) and intraduodenal (i.d.) dosing to rats. The ID50 values showed FK1052 (0.28 microgram/kg, i.v., 5.23 micrograms/kg, i.d.) to be more potent than ondansetron (5.23 micrograms/kg, i.v., 170 micrograms/kg, i.d.) and granisetron (0.70 micrograms/kg, i.v., 66 micrograms/kg, i.d.). Furthermore, bioavailabilities of the test drugs by ID50 ratio (i.d./i.v.) showed that FK1052(17) was better absorbed than ondansetron(33) and granisetron(94) and possessed a similar duration of action to that of ondansetron and granisetron. We also examined the effects on 2-methyl-5-HT-, 5-HT- and 5-methoxytryptamine-induced contractions of guinea pig isolated ileum. FK1052, ondansetron and granisetron concentration-dependently inhibited 2-methyl-5-HT, a 5-HT3 agonist-induced contraction. The pA2 values for the 5-HT3 receptor indicated that FK1052 (8.36) was 40 times and three times more potent than ondansetron (6.79) and granisetron (7.86), respectively. FK1052, unlike ondansetron and granisetron, inhibited the 5-HT4-mediated component of concentration-response curve to 5-HT. Furthermore, FK1052 suppressed 5-methoxytryptamine, a 5-HT4 agonist-induced contraction in a concentration-dependent but insurmountable manner.(ABSTRACT TRUNCATED AT 250 WORDS)

5-Methoxytryptamine↗
PubMed1992

Biotransformation of isoeugenol and eugenol by cultured cells of Eucalyptus perriniana.

Three new biotransformation products, eugenyl beta-rutinoside, and isoeugenyl beta-gentiobioside and beta-rutinoside, together with eugenyl beta-glucoside and beta-gentiobioside, and isoeugenyl beta-glucoside, were isolated from jar fermentor culture of Eucalyptus perriniana following administration of eugenol and isoeugenol, respectively. This is the first report of rhamnosylation in a biotransformation catalysed by cultured cells of E. perriniana.

Acetylation↗
PubMed1991

Optimum position for an anti-siphon device in a cerebrospinal fluid shunt system.

The effects on shunt flow from the position of an antisiphon device (ASD) and from changes in posture in hydrocephalic patients were examined. Fifty patients with hydrocephalus (including 36 with normal pressure hydrocephalus) were investigated, using quantitative radionuclide shuntography (99mtechnetium-pertechnetate) in the supine, sitting, and standing positions. The types of shunt valve used were as follows: Mishler dual chamber low pressure without ASD (16 cases), with ASD 40 cm below the level of the foramen of Monro (three cases), and with ASD 10 cm below the level of the foramen of Monro (12 cases); low pressure with integral ASD (14 cases); and medium pressure with integral ASD (five cases). In patients with a low pressure valve without ASD, shunt flow was least in the supine position (0.0011 ml/min) but increased significantly in the sitting position (0.4381 ml/min, P less than 0.001) because of the siphon effect. Conversely, in patients with a low pressure valve with integral ASD, shunt flow was maximal in the supine position (0.1056 ml/min) and decreased significantly in the sitting position (0.0017 ml/min, P less than 0.001), indicating overfunction of the ASD. Intracranial pressure (ICP) in the supine position increased significantly compared with patients with a low pressure valve without ASD (93.6 and 20.7 mm H2O, respectively, P less than 0.01). Intermediate values for shunt flow in the supine and sitting positions (0.0279 and 0.0896 ml/min, respectively) and for ICP (55.8 mm H2O) were obtained with patients with a low pressure valve with the ASD 10 cm below the level of the foramen of Monro (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Subarachnoid dissemination of pineal germinoma 9 years after radiation therapy without local relapse--case report.

A 22-year-old female developed intracranial and spinal subarachnoid metastases 9 years after radiation therapy for a pineal germinoma. Computed tomographic scans showed no evidence of local recurrence. Cerebrospinal axis irradiation achieved total remission. Delayed subarachnoid dissemination may be caused by germinoma cells remaining dormant in the subarachnoid space, outside the radiation field.

Brain Neoplasms↗
PubMed1991

[Traumatic carotid-cavernous fistula presenting subarachnoid hemorrhage 5 years after head injury; case report].

A case of traumatic carotid-cavernous fistula (CCF) which presented subarachnoid hemorrhage long after the injury is reported. A 24-year-old male was admitted to the National Yokohama Hospital with complaints of severe headache and nausea. CT scan and cerebral angiography showed subarachnoid hemorrhage due to ruptured CCF. His right visual acuity has disappeared after a traffic accident 5 years before, and he had hit his forehead again 3 years previously. He experienced severe headache twice for 2 weeks after his admission. He was transferred to Kanagawa Rehabilitation Center to be treated with intravascular surgery. Plain CT showed high density areas in the basal cisterns. CT after contrast infusion disclosed a small enlarged high density area in the right cavernous sinus, and showed an enhanced mass lesion in contact with the right ventrolateral side of the midpons. The right internal carotid angiogram showed high flow CCF, fed only by the internal carotid artery. It drained mainly into the basilar plexus, partially into the basal vein of Rosenthal and the inferior petrosal sinus. The CCF was found at the C4 portion of the right internal carotid artery. CT and the angiogram revealed a part of the CCF developing into a varix in the ventral side of the prepontine cistern. It ruptured and the patient developed subarachnoid hemorrhage 5 years after the head injury. The CCF was intravascularly embolized by a detachable balloon. Early treatment for CCF is necessary to prevent the occurrence of subarachnoid hemorrhage if a part of the CCF develops into a varix.

Adult↗
PubMed1990

Multicentric intracranial fibrous xanthoma--case report.

Intracranial fibrous xanthoma is extremely rare; only 11 cases have been reported so far. The authors report a case of multicentric intracranial fibrous xanthoma. Precontrast computed tomographic (CT) scans revealed a left frontal subdural mass, which had previously been diagnosed as a chronic subdural hematoma at another hospital. However, operation disclosed no hematoma but a granulomatous tumor. The biopsied specimen was histologically diagnosed as fibrous xanthoma. Postoperative postcontrast CT scans showed intense homogeneous enhancement at the clival and the left frontal regions, both of which appeared as iso- to low-intensity areas on T1-weighted magnetic resonance (MR) images and as low-intensity areas on T2-weighted MR images. She gradually recovered by conservative treatment but suddenly died of cerebral infarction. Autopsy revealed fibrous xanthomas in the left frontal and the clival regions. This is the first report of the use of MR imaging for intracranial fibrous xanthoma, and its features differ from those of common intracranial parenchymal tumors, MR imaging can be helpful in the diagnosis of this tumor.

Aged↗
PubMed1989

Cordectomy for syringobulbo-myelia with sleep apnea secondary to a spinal extramedullary tumor: case report.

The case of a 40-year-old man with syringobulbo-myelia secondary to an unresectable spinal extramedullary tumor is described. Fifteen years previously, the patient had undergone a laminectomy of T8 through T12 for a "benign" spinal cord tumor at another hospital and had become paraplegic; the tumor (neurinoma) had been neglected for 12 years. Magnetic resonance imaging demonstrated a large thoracolumbar spinal tumor with syringobulbo-myelia. Polysomnography showed central-, peripheral-, and mixed-type sleep apneas. After the failure of an attempted syringoperitoneal shunt, cordectomy at the level of T6 was performed with a good result. The mechanisms of the formation of syringomyelia and sleep apnea secondary to a caudal spinal extramedullary tumor are discussed.

Adult↗
PubMed1989

Late infection after cranioplasty--review of 14 cases.

The incidence of late infection after cranioplasty was studied in 130 patients with 133 cranioplasties. The materials used were prefabricated resin in 62 cases, autogenic bone in 38, intraoperatively fashioned resin in 25, and vitallium in eight. Six infections were documented, for an infection rate of 4.5%. In addition to these six cases, we studied eight patients with infections who had undergone cranioplasty elsewhere but had the infected plates removed in our hospitals. Among the 14 cases of infection, the intervals between cranioplasty and plate removal were 3 to 43 months (average, 10.5 months). The eight patients referred from other hospitals had a significantly shorter average interval between external decompression and cranioplasty than did patients who did not develop infection (2.6 versus 6.7 months; p less than 0.005). Systemic signs were mild despite obvious local signs of infection. Of the 11 first infections, nine (82%) were associated with discharge of pus from a fistula; in these cases a galeal suture had become infected apparently through scratching by the patients. In contrast, in the three patients who had had a previous infection, the second infection manifested as subgaleal and epidural empyema or meningitis without a fistula or pus discharge. Nine infections (69%) were due to Staphylococcus. All but two patients required removal of the infected plates. One recovered with conservative therapy and one died of meningitis, giving a mortality rate of 0.8%. No matter how mild the systemic signs, late infection warrants surgical debridement and plate removal. The risk factors for late infection of cranioplasty are discussed.

Adolescent↗
PubMed1988

Acute spontaneous subdural hematoma of arterial origin.

Acute spontaneous subdural hematoma of arterial origin is very rare. We have encountered two such cases and verified the arterial origin of the bleeding at operation. Both patients had no history of head trauma and developed progressive neurological deficits, becoming comatose. The source of bleeding was identified as a cortical artery located on the temporal lobe near the Sylvian region. This type of lesion is reviewed in the literature and the etiology is discussed.

Acute Disease↗
PubMed1988

Infantile chronic subdural hematoma with local protrusion of the skull in a case of osteogenesis imperfecta.

Osteogenesis imperfecta with infantile chronic subdural hematoma is extremely rare and has not been previously described in the literature. Our patient was a baby girl suffering from osteogenesis imperfecta tarda (Type I) who had an acute subdural hematoma at birth and who developed a progressive chronic subdural hematoma with local protrusion of the overlying skull. She was treated surgically with a good result. This rare complication is due to weakness of an insufficiently calcified skull, which is peculiar to this disorder of bone and connective tissue development.

Chronic Disease↗
PubMed1987

Subdural empyema occurring 20 years after trauma: case report.

The authors report a case of subdural empyema that occurred 20 years after a severe closed head injury and was treated surgically with good results. Traumatic subdural empyema of this late onset is rare. The literature is reviewed, and the mechanism of a delayed presentation is discussed.

Brain Injuries↗