Search PubMed⌕ Search

Biomedical subjects

T Hata

Publications and source records attributed to T Hata.

At least 541 records · Page 30Linked to original sources

Effects of midecamycin acetate (miocamycin), a new macrolide antibiotic, on reproductive performances in rats and rabbits.

Miocamycin (MOM) is a derivative of midecamycin, a macrolide antibiotic isolated from a culture broth of Streptomyces mycarofaciens. The objective of this study was to determine the effect of MOM on reproductive performance in rats and rabbits. MOM, non-crystalline solid, was suspended in 0.1% CMC solution immediately before use. In this study, reproductive performance was studied according to the following designs: Fertility test (Segment I) in Wistar rats Teratogenicity test (Segment II) in Wistar rats Peri- and post-natal tests (Segment III) in Wistar rats Behavioral test in rat newborns in Segments II and III Teratogenicity test (Segment II) in New Zealand white rabbits In conclusion, MOM, non-crystalline solid, might have no teratogenesis and little influence on dams and their fetuses and offsprings.

Abnormalities, Drug-Induced↗

[The abnormal ECG and the appearance of methacholine-induced arrhythmias in SART mice and effects of beta-blockers, oxprenolol, propranolol, and carteolol].

Protective effects of beta-blockers (oxprenolol, propranolol and carteolol) on the abnormal ECG of the sympathicotonia type were studied in male ddY SART stressed mice. Oxprenolol and carteolol were observed to have mild effects on the abnormal ECG as compared with propranolol. Experimental arrhythmias were induced by drugs in SART mice, and their frequencies of appearance were examined. The types of arrhythmias used as indices were sinus arrhythmia, supraventricular and ventricular extrasystole, the 1st and 2nd degrees of atrio-ventricular (A-V) block, sino-atrial (S-A) block and sinus standstill. The frequency of appearance of arrhythmia of any type induced by adrenaline was lower in SART mice than in normal mice. The frequency of appearance of methacholine (MCh)-induced arrhythmia of any type was significantly higher in SART mice than in normal mice. Protective effects of the 3 beta-blockers on the worsening of MCh-arrhythmias in SART mice were studied. With a single dose of 5 or 10 mg/kg, the drugs were effective on supraventricular extrasystole and S-A block. Continuous administrations of oxprenolol and carteolol inhibited the occurrence of supraventricular extrasystole, A-V block and S-A block, but not the occurrence of ventricular extrasystole. Continuous administrations of propranolol were effective on any type of arrhythmias except for sinus arrhythmia. These results further support our viewpoint that the SART mouse is of the sympathicotonia type with respect to the heart, and they suggest that oxprenolol and carteolol may be effective clinically on arrhythmias caused by autonomic imbalance.

Animals↗

[Toxicological studies on a new cephamycin, MT-141. VIII. Its fertility test in rats].

A fertility study of MT-141 was performed in SD rats with the intramuscular (i.m.) injections at the dose levels of 400, 800 and 1,600 mg/kg/day. The male rats were injected with MT-141 for 63 days before mating and during the mating period, while the female rats were injected with MT-141 from the 14th day before mating up to the day 7 of gestation. All pregnant rats were sacrificed on day 20 of gestation followed by external, visceral and skeletal observations of their fetuses. The results are summarized as follows. The suppression of body weight gain was observed in males given above 800 mg/kg/day i.m. and in females of all treated groups during early period of gestation. However, no significant differences were found between treated groups and the control with regard to copulation rate and conception rate. Though no defects were observed for visceral and skeletal specimens in the fetuses of treated groups, MT-141 produced a delayed ossification of forelimbs in the fetuses at the doses above 800 mg/kg/day and of sternebrae at the dose of 1,600 mg/kg/day. It is concluded from the above-mentioned results that the maximal "no 'effective" dose of MT-141 on the fertility is above 1,600 mg/kg/day i.m. in parental rats and less than 800 mg/kg/day i.m. for the fetuses.

Animals↗

[Toxicological studies on a new cephamycin, MT-141 IX. Its teratogenicity test in rats and rabbits].

A teratogenicity study of MT-141 was performed in SD rats and Japanese white rabbits. The pregnant rats were administered intramuscularly (i.m.) with MT-141 at the dose levels of 200, 400, 800 and 1,600 mg/kg/day from the day 7 up to the day 17 of gestation. The pregnant rabbits were administered intravenously (i.v.) with the drug at the dose levels of 10, 20 and 40 mg/kg/day from the day 6 up to the day 18 of gestation. The results are summarized as follows. Rats: Though the administrations with MT-141 at all dose levels did not change body weight gain and water intake of treated dams, a slight suppression in the food consumption was produced by MT-141 at the dose of 1,600 mg/kg/day. The examinations on cesarean section revealed no effect of MT-141 on teratological parameters such as external malformation and frequency of visceral and skeletal anomalies in the fetuses. MT-141 at all dose levels exerted no toxic effect on developmental, functional and behavioral parameters in F1 rats and on mating, fertility and pregnancy of F1 rats. Furthermore, there was no effect of MT-141 on the findings in cesarean section of F1 rats. The fetuses from F1 rats had no malformation of external appearance, viscera and skeleton. Rabbits: MT-141 had no significant effect on body weight gain and food consumption of dams at the all dose levels, but caused a slight suppression in the water intake at the doses more than 20 mg/kg/day. One rabbit aborted in each group given 20 or 40 mg/kg/day. One rabbit died in the group given 20 mg/kg/day. Examinations on cesarean section showed that MT-141 at the dose of 40 mg/kg/day produced a decrease in body weights of females and an increase in dead or resorbed fetuses followed by a decrease in live fetuses. MT-141 is no effect malformation of external appearance, viscera and skeleton in the fetuses of all treated groups. The above-mentioned results suggest that MT-141 has no teratogenic effect on pregnant rats and rabbits. It is concluded from these results that the maximal "no effective" dose of MT-141 on fetal toxicity is above 1,600 mg/kg/day i.m. for pregnant rats and 10 mg/kg/day i.v. for pregnant rabbits.

Abnormalities, Drug-Induced↗

[Toxicological studies on a new cephamycin, MT-141. X. Its perinatal and postnatal test in rats].

A perinatal and postnatal study of MT-141 was performed in SD rats. The dams were administered intramuscularly (i.m.) with MT-141 at the dose levels of 400, 800 and 1,600 mg/kg/day from the day 17 of gestation until the day 21 post delivery. The results are summarized as follows. No significant adverse effects of MT-141 were observed on the body weight gain, food consumption and water intake in dams of all groups treated with the drug during the perinatal and postnatal period. MT-141 did not change parameters of reproductive study in birth, development, physiological function and behavior of F1 rat. This compound had no effect on the fertility in F1 rats and also did not caused significant defects in the external appearance, viscera and skeleton of fetuses from dams (F1). It is concluded from these results that the maximal "no effective" dose of MT-141 is above 1,600 mg/kg/day i.m. for dams and the offsprings.

Animals↗

[The clinical significance of an oscillating flap in the acute stage of dissecting aneurysm: report of three cases].

The important two-dimensional echocardiographic finding of dissecting aneurysm in the acute stage is characterized by the presence of an oscillating intimal flap which is thought to be of highly diagnostic value. This report describes about three cases with dissecting aneurysm in which an oscillating flap was transiently observed. In Case 1 (62-year-old female), an oscillating flap observed in the aortic arch seven hours after the onset was not detected three days later. A flap in Case 2 (65-year-old male) which had been present in the descending aorta three hours after the onset of illness disappeared two days later. In Case 3 (55-year-old male), only an intimal flap without fine oscillation was demonstrated in the abdominal aorta by echocardiography performed three days after the onset of illness. In the acute phase of dissection, the echocardiographic detection of an oscillating flap seems to depend on the time of the study after the attack.

Aged↗

Increase of serotonin receptors in rat uterus induced by estradiol.

[3H]Spiroperidol was used to label uterine membrane-binding sites that have the characteristics expected of serotonergic receptors. The characteristics of specific [3H]spiroperidol binding to the uterine membrane of 17 beta-estradiol-3-benzoate-treated ovariectomized rats were studied. The specific [3H]spiroperidol binding was rapid and reversible, and the half-maximal saturation, taken as the apparent dissociation constant (KD) for [3H]spiroperidol, was 5.16 +/- 0.24 (n = 12) nM [3H]spiroperidol. Scatchard plots of saturation curves of the specific [3H]spiroperidol binding were convex and the Hill coefficient was 2.06 +/- 0.11 (n = 12). Cinanserin, mianserin, metergoline (which are serotonergic antagonists), and serotonin (5-HT) inhibited the [3H]spiroperidol binding with apparent Ki values of 21.2, 14.1, 14.1, and 176.5 microM, respectively. Concentrations of 1 mM sulpiride (a dopaminergic antagonist) and dopamine reduced [3H]spiroperidol binding only 26 and 23%, respectively. 1 mM GTP reduced the potency of 5-HT (10(-6) - 10(-3) M) to displace bound [3H]spiroperidol. The uterine membranes were treated with various enzymes and protein-modifying reagents, and binding studies on the treated uterine membranes showed that protein(s), phospholipids, and N-acetyl-neuraminic acid in uterine membranes were important as specific binding sites of [3H]spiroperidol. Measurement of the specific binding of [3H]spiroperidol to uterine membranes from untreated and estradiol-treated ovariectomized rats showed that estradiol significantly increased the number of specific binding sites of [3H]spiroperidol, but did not change the apparent affinity of specific [3H]spiroperidol binding. Estradiol also did not change the dissociation constant or the number of binding sites for [3H]3-quinuclidinyl benzilate, which binds to muscarinic acetylcholine receptors. These findings suggest that [3H]spiroperidol mainly binds to 5-HT receptors in the uterine membrane of estradiol-treated ovariectomized rats. The finding that administration of estradiol significantly increased the number of [3H]spiroperidol-binding sites is consistent with the specific increase in the contractile response to 5-HT observed in isolated uterus from ovariectomized rats treated with estradiol.

Animals↗

Precise day of ovulation determined by real-time ultrasound evidence of graafian follicular development.

Real-time ultrasonic scanning was performed in 21 infertile Japanese women during 37 menstrual cycles. The maximum diameter prior to ovulation was 23.3 +/- 2.9 mm in spontaneous ovulation cycles, 29.6 +/- 5.2 mm in case of clomiphene therapies, and 26.7 +/- 3.9 mm in HMG-HCG therapies, respectively. Size of the graafian follicles was maximum at almost the same time as the LH peak in the plasma and urine, respectively. The LH peak in the urine was determined by the hemagglutination inhibition assay, the results of which were obtainable within 2 h. Four patients became pregnant (19.0%). There was no statistical correlation between the diameter of the largest follicle and the plasma estradiols (r = 0.28, 0.2 less than P less than 0.3) or between the diameter of the largest follicle and the peak luteinising hormone level (r = 0.27, 0.3 less than P less than 0.4). Therefore, the combination of the real-time ultrasound and a hemagglutination inhibition assay for LH in urine can be clinically applied to detect the precise day of the ovulation.

Female↗

Prognostic value of cerebral blood flow autoregulation in the long-term prognosis of ischemic cerebrovascular disease.

The correlation between long-term prognosis, cerebral blood flow (CBF) and CBF autoregulation was studied in 34 patients with cerebral infarction (mean age, 64 years). CBF was measured by the nitrous oxide method 1-6 months (mean 87 days) after disease onset. CBF autoregulation was evaluated quantitatively from the Dysautoregulation Index (DI) (delta CBF/delta effective MABP). Reductions in effective MABP were induced with a tilt table. No significant correlation was noted among CBF, DI and activities of daily living at the time of measurement. The patients' physical condition was reevaluated by questionnaire 2 years or more (mean 32 months) later. Better functional state at follow-up was related to higher CBF and lower DI values although the differences were not significant. The relationships among CBF, DI and changes in physical condition during the period were evaluated. The mean CBF values in patients with a better prognosis exceeded those of poor prognosis patients. The CBF values in the group who became independent significantly exceeded those in the group that deteriorated (P less than 0.05). The CBF values in the latter showed small but significant decreases during head-up tilting (P less than 0.05). The DI in this group was significantly higher than in the groups with a less severe outcome (P less than 0.01, P less than 0.05, respectively). In conclusion, determinations of CBF autoregulation, together with flow values, in the chronic state may have some value in predicting the long-term prognosis in cerebral infarction.

Adult↗

Levels of plasma 6-keto-PGF1 alpha in normotensive and essential hypertensive males with and without a family history of hypertension.

Prostacyclin may act physiologically as an antihypertensive hormone. It remains uncertain, however, whether prostacyclin may be involved in the etiology of primary hypertension. As an index of prostacyclin production, we measured the levels of venous plasma 6-keto-PGF1 alpha by specific radioimmunoassay after silicic acid column chromatographic purification in 31 normotensive and 36 hypertensive males. The subjects were grouped according to the presence or absence of a family history of hypertension, and matched for age and blood pressure. Levels of 6-keto-PGF1 alpha in normotensive males with a family history of hypertension (12.0 +/- 1.7 pg/ml; mean +/- SEM; n = 18) were lower than in normotensive males without a family history of hypertension (17.7 +/- 2.0 pg/ml; n = 13) (p less than 0.01). Levels of plasma 6-keto-PGF1 alpha in hypertensive males with a family history of hypertension (10.2 +/- 1.2 pg/ml; n = 15) were lower than in hypertensive males without a family history of hypertension (20.5 +/- 1.5 pg/ml; n = 21) (p less than 0.005). The levels of plasma 6-keto-PGF1 alpha in males with a family history of hypertension may be decreased genetically. The decrease in production of prostacyclin in males with a family history of hypertension may be a factor in the etiology of hypertension.

6-Ketoprostaglandin F1 alpha↗

Effect of aging on 6-keto-PGF1 alpha levels in normotensive and essential hypertensive males.

Prostacyclin (PGI2) is produced in the vessel wall and acts as a vasodilator hormone. Measurement of plasma 6-keto-PGF1 alpha is considered to be an index of PGI2 production. In the present study the effects of aging on the plasma 6-keto-PGF1 alpha levels were studied in 64 normotensive and 48 essential hypertensive males. The subjects were divided into 3 groups, i.e., young (24-39 years), middle-aged (40-55 years) and elderly (over 56 years) groups. Plasma 6-keto-PGF1 alpha was measured by specific radioimmunoassay after silicic acid column chromatographic purification. The 6-keto-PGF1 alpha levels were lower in elderly normotensive males (10.3 +/- 1.4 pg/ml, mean +/- SE, n = 12) than in normotensive young males (15.3 +/- 2.3, n = 30, p less than 0.05). The plasma 6-keto-PGF1 alpha levels in hypertensive elderly males (10.6 +/- 1.3 pg/ml, n = 10) is lower than in hypertensive young males (19.8 +/- 2.2, n = 17, p less than 0.01). These results indicate that the plasma 6-keto-PGF1 alpha levels decreased with age in both normotensive and hypertensive groups. Thus, PGI2 production may decrease with age.

6-Ketoprostaglandin F1 alpha↗

Studies on the site of action of neurotropin in experiments on denervation-supersensitivity of the duodenum and vas deferens of rats and mice.

In order to clarify to a greater extent its action on peripheral nerves, various experiments were conducted using denervated animals to determine the effects of the nervous sedative, Neurotropin (NSP, containing many types of polysaccharides), on the site considered to be the periphery of autonomic nerves and the central nervous system. The increase in response to ACh due to bilateral cardiac vagotomy was significantly inhibited by a daily administration of NSP, but the increase in the response to noradrenaline (NA) due to celiac sympathectomy was hardly affected by this administration. The supersensitivity to the muscarinic action of ACh or methacholine of a denervated rat vas deferens, owing to ablation of the serous membrane, was significantly inhibited by the daily administrations of NSP. However, supersensitivity to NA was hardly affected. NSP never had any effect on the increase in the NA response of the duodenum and vas deferens isolated from mice given 6-hydroxydopamine, an adrenergic degenerator. Thus, an inhibitory action of NSP on denervation-supersensitivity is conceivably exerted on the parasympathetic nerves, rather than on the sympathetic nerves, and on a muscarinic receptor site, instead of a nicotinic site.

Acetylcholine↗