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Biomedical subjects

A Ogata

Publications and source records attributed to A Ogata.

At least 163 records · Page 9Linked to original sources

Effects of pretreatment with SKF-525A or sodium phenobarbital on thiabendazole-induced teratogenicity in ICR mice.

To study the effects of SKF-525A, an inhibitor of cytochrome P-450, and of sodium phenobarbital (PB), a drug-metabolizing enzyme inducer, on the teratogenicity of thiabendazole (TBZ), pregnant mice were given ip either a single dose of 40 mg SKF-525A/kg 1 hr before oral dosing with 250 or 500 mg TBZ/kg or a dose of 75 mg PB/kg/day on three consecutive days before oral administration of a dose of 500 or 1000 mg TBZ/kg. In either case the TBZ dose was given on day 9 of gestation. All foetuses were removed from the uterus on day 18 of gestation, and were examined for external and skeletal anomalies. The spectrum of malformations in the groups of mice pretreated with SKF-525A or PB was similar to that in mice treated only with TBZ. In the group pretreated with SKF-525A, however, the incidence of resorbed foetuses was higher than in the group treated with TBZ alone and there was a tendency towards an increase in the number of foetuses with skeletal fusion and reduction deformity of the limbs, an anomaly characteristically induced by TBZ. On the other hand, in mice pretreated with PB, the incidence of resorbed foetuses tended to be lower, the numbers and body weights of live foetuses were higher and the incidence of external and skeletal malformations was lower than in the groups treated with TBZ only. No reduction deformity of the limbs was observed in the groups pretreated with PB. These results suggest that with TBZ the ultimate teratogen may be the parent compound rather than its metabolites.

Abnormalities, Drug-Induced↗

A survey of 37 cases with basal ganglia calcification (BGC): CT-scan findings of BGC and its relationship to underlying diseases and epilepsy.

Thirty-seven cases that showed bilateral basal ganglia calcification (BGC) were found in 5987 patients. These cases (0.6%) were studied in relation to their CT findings, underlying diseases and epilepsy. CT findings of BGC were divided into "localized" type (33 cases) and "diffuse" type (4 cases). The number of patients with the "localized" type clearly seemed to increase with age. The M:F ratio of the "localized" type was 1:2. The "localized" type was seen in both idiopathic BGC and familial BGC. The "diffuse" type was seen in hypoparathyroidism only. The specific relationship of these two types of BGC to underlying diseases, however, does not fully agree with results so far reported. We experienced a case with familial BGC during this study that appears to be only the 15th so far reported. Partial epilepsy occurred in 75% of epilepsy with BGC, but there seemed to be no direct relationship between BGC and epileptogenicity.

Basal Ganglia Diseases↗

[Glioblastoma multiforme with extracranial metastases without previous surgery: demonstration of extracranial metastases by peroxidase antiperoxidase staining and clinicopathological study].

Spontaneous extracranial metastases of glioblastoma multiforme in the absence of previous surgery have been rarely reported (Table 1). We presented an autopsy case of glioblastoma multiforme which spontaneously metastasized to the lungs, bronchial lymph nodes, liver, kidney, heart and spleen. A 68-year-old man was admitted to the Department of Neurosurgery at our hospital with chief complaints of right sided weakness in July 1984. He was well until November 1983, when he noticed weakness of right lower extremity followed one month later by the weakness in the right arm. He was treated at another hospital under the diagnosis of cerebral infarction, but his right sided weakness gradually progressed. In June 1984, a diagnosis of brain tumor was made by the neurological findings and CT scan, and he was transferred to our hospital for further evaluation and treatment. Neurological examination revealed disorientation, bilateral papilledema, right hemiparesis, right hyperreflexia and right hemisensory disturbance. CT scan revealed abnormal low density area in the left fronto-parietal lobe (Fig. 1) with irregular enhanced lesions on contrast CT scan (Fig. 2). Chest x-ray showed abnormal shadow in the right middle and lower lobe (Fig. 3) and a diagnosis of pulmonary infarction was suspected. The clinical states of this patient took downhill course and he expired on July 13, 1984 by the complication of disseminated intravascular coagulation syndrome. The brain weight was 1400 gr. Dura mater and falx cerebri were tightly adherent to the left parietal lobe (Fig. 4). Primary brain tumor was found in the left fronto-parietal region. The tumor was poorly defined with necrosis and hemorrhage (Fig. 5).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Irreversible in vivo binding of thiabendazole to macromolecules in pregnant mice and its relation to teratogenicity.

The binding of [14C]thiabendazole ([14C]TBZ) to macromolecules in the liver, foetus and other tissues was investigated in Jcl:ICR mice on day 13 of gestation. TBZ suspended in olive oil was given orally in a dose of 1 g/kg body weight (5 microCi/mouse) and the mice (in groups of three) were killed 0.5, 1, 3, 6, 24 and 96 hr later. The bound radioactivity in the liver and foetus was at a maximum between 3 and 24 hr after treatment. The rate of decrease of the bound radioactivity was slower than that of total radioactivity. Bound radioactivity was also present in other tissues (including kidney, lung, heart, placenta and spleen). The level of bound radioactivity was measured in the liver and foetuses after oral administration of teratogenic doses of 200-1600 mg/kg. Disproportionate increases in bound radioactivity were observed in both tissues after administration of the highest dose.

Abnormalities, Drug-Induced↗

Prevention from naturally acquired viral respiratory infection by interferon nasal spray.

Human leukocyte interferon (IFN-alpha), 50,000 IU per day, was sprayed into the nasal cavity of 73 volunteers twice a day from January 9 till March 4, 1984. The rise in complement fixation antibody titers against influenza A virus was not significantly different between the interferon group and the placebo group. However, the number of subjects without elevated antibody titers and without symptoms in the interferon group was significantly higher than that in the placebo group (p less than 0.05). Prophylactic nasal spray of IFN-alpha seems to protect against upper respiratory viral infection.

Administration, Intranasal↗

The maternal-foetal distribution of thiabendazole administered in two different vehicles to pregnant mice.

We have compared the effects of two vehicles on the maternal-foetal distribution of 14C-thiabendazole ([14C]TBZ) given orally to Jcl: ICR mice on day 9 or 16 of gestation. TBZ, either suspended in olive oil (TBZ-O) or in a 0.5% aqueous solution of gum arabic (TBZ-G), was given orally on day 9 of gestation at a dose of 1 g/kg body weight (1 microCi/mouse). The mice were killed 0.5, 1, 3, 6, 12, 24 or 72 hr later. In mice treated with TBZ-O maximum levels of radioactivity in plasma and conceptuses were observed at 0.5 hr, whereas in those treated with TBZ-G maximum 14C levels were observed at 6 hr. The uptake of radioactivity from TBZ-O into the plasma and conceptuses was significantly higher than that from TBZ-G. Only trace levels of radioactivity were detected at 72 hr in both treatment groups. The placental transfer of [14C]TBZ was examined in mice treated with doses of 1 g/kg body weight (1 microCi/mouse) given as TBZ-O or TBZ-G on day 16 of gestation. The radioactivity in foetuses, placentas and maternal plasma was higher in mice treated with TBZ-O than those given TBZ-G. The placental transfer of [14C]TBZ was also examined by whole-body autoradiography in mice treated on day 16 of gestation.

Animals↗

Teratogenicity of thiabendazole in ICR mice.

Thiabendazole (TBZ) was tested for teratogenicity using Jcl:ICR mice. TBZ suspended in olive oil was given orally to pregnant mice at different stages of organogenesis. All foetuses were removed from the uterus on day 18 of gestation, and were examined for external and skeletal anomalies. In mice given 700, 1300 or 2400 mg TBZ/kg body weight/day on days 7-15 of gestation, dose-dependent external and skeletal anomalies, especially cleft palate and fusion of vertebrae, were observed. In mice given a single dose of TBZ (2400 mg/kg) on any one of days 6-13, an increased number of malformations was observed. Various types of malformation occurred, especially in the mice treated on day 9. Reduction deformity of limbs was found in mice given TBZ on days 9-12, a change that has not previously been observed to occur spontaneously in normal ICR mice in our laboratory. In order to determine a dose-response relationship, groups of mice were given one of 17 doses of TBZ (30-2400 mg/kg) on day 9 of gestation. The number of litters having foetuses with reduction deformity of limbs and of those having foetuses with skeletal fusion increased in proportion to the dose of TBZ. The regression lines of Y (probit response) on X (log dose) for reduction deformity of limbs and for skeletal fusion were Y = 2.47X - 3.65 and Y = 1.54X + 0.48, respectively. The effective doses (ED1) for the two malformations were 362.0 and 26.4 mg/kg, respectively.

Animals↗

Sustained release of theophylline from hydroxypropylcellulose tablets.

Compressed tablets were prepared from theophylline and hydroxypropylcellulose. Effects of the viscosity grades of the polymer, the mixing ratios of two polymers with different viscosity grades, and the polymer contents in the tablets on release patterns of theophylline were examined in vitro. Release rate was decreased with increasing viscosity designation and polymer contents in the tablets. In salivary level profiles of theophylline following oral administration of sustained-release tablets to five human volunteers, a low but sustained level was noted indicating sustained release of the drug from the tablets in vivo.

Administration, Oral↗

Human erythrocyte prolidase and prolidase deficiency.

Biochemical studies on human prolidase (EC 3.4.13.9) and prolidase deficiency are described. The urine sample from a 32-year-old female with prolidase deficiency was examined. Diagnosis was based on clinical features and defects of prolidase in her erythrocytes. She excreted massive amounts of iminopeptides, where three major peptides were identified; aspartyl-proline, glutamyl-proline and glycyl-proline. The prolidase was purified approximately 10,000-fold from the normal human erythrocytes through an eight step procedure. The purified enzyme consisted of two identical subunits of which the molecular weight was calculated to be 55,000. The relative cleavage rates of the enzyme for glycyl-L-proline, L-alanyl-L-proline, L-leucyl-L-proline, L-prolyl-L-proline, and glycyl-hydroxy-L-proline were 100%, 53%, 27%, 31% and 2%, respectively. The relative substrate specificity of the enzyme offers a reasonable explantation for the presence of a higher level of urinary imidodipeptides in a patient with prolidase deficiency. An attempt at erythrocyte transfusion was performed, aimed at enzyme replacement therapy. After the transfusion (erythrocytes from 800 ml of whole blood), the prolidase activity of the peripheral erythrocyte was elevated to approximately 35% of the normal values and gradually decreased (half-life, 41 days). During this period urinary peptide-bound proline was monitored, but no significant change was observed.

Adult↗