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Biomedical subjects

T Asami

Publications and source records attributed to T Asami.

125 records · Page 7Linked to original sources

[Effects of repeated administration of bromocriptine on ambulatory activity in mice, and changes in methamphetamine sensitivity in bromocriptine-experienced mice].

Effects of repeated administration of bromocriptine, a long-acting dopamine agonist, as well as interaction between bromocriptine and methamphetamine were investigated by mean of ambulatory activity in mice. The ambulatory activity of each mouse was measured by a tilting-type activity cage for 6 and 3 hr after administration of bromocriptine and methamphetamine, respectively. The repeated 5 times administration of bromocriptine and of methamphetamine was at intervals of 7 days and of 3-4 days, respectively. Bromocriptine tended to suppress the activity at low doses (1 and 2mg/kg, ip), but increased the activity at high doses (8 and 16 mg/kg, ip), showing biphasic effects depending on the doses administered. Both the ambulation-suppressing and -increasing effects of bromocriptine were enhanced when the drug was repeatedly administered. The mice that experienced the repeated administration of low doses and high doses of bromocriptine exhibited a decrease and an increase, respectively, in the sensitivity to the ambulation-increasing effect of methamphetamine (2 mg/kg, sc). Repeated administration of methamphetamine (2 mg/kg, sc) elicited an increase in sensitivity not only to methamphetamine itself, showing reverse tolerance, but also to high doses of bromocriptine, showing cross reverse tolerance. However, the reverse tolerance to methamphetamine, once produced, was not affected by the repeated administration of low doses of bromocriptine.

Animals↗

[Rapid establishment of nicotine intravenous self-administration behavior in rats].

The reinforcing effect of nicotine was investigated using the intravenous self-administration method in rats. After forced iv injection of nicotine (3, 10 and 30 micrograms/kg/inj) at 1-hr intervals for 3 days in 3 dose-level groups, self-administration sessions under the continuous reinforcement schedule were carried out for 15 days. Rats initiated self-administration of nicotine rapidly in 10 and 30 micrograms/kg/inj groups. Daily self-administration responses by nicotine (30 micrograms/kg/inj) were 3-10 times the control levels. Total self-administration responses for 15 days increased in a dose dependent manner. When the fixed ratio was increased from 1 to 4 and 8 after the 15 days self-administration session in the nicotine (10 and 30 micrograms/kg/inj) groups, lever press responses increased only about 2 times, and self-administration responses decreased in the both groups. These findings suggest that nicotine becomes a reinforcer rapidly, but the magnitude of reinforcing effect is relatively week after the acquisition of nicotine for a short period.

Animals↗

[Effects of single and repeated oral administration of MK-421 and captopril on blood pressures in normotensive and experimental hypertensive rats].

In the single dose study, the aortic blood pressure in conscious normotensive rats, 2-kidney, 1-clip renal hypertensive rats (2K-RHR), 1-kidney, 1-clip renal hypertensive rats (1K-RHR) or DOCA hypertensive rats was measured for 24 hr after the oral administration of angiotensin converting enzyme (ACE) inhibitors such as MK-421 or captopril. MK-421 at 3 mg/kg and captopril at 10 mg/kg markedly lowered the blood pressure of 2K-RHR. MK-421 at 10 mg/kg and captopril at 30 mg/kg only modestly lowered the blood pressure of 1K-RHR. In contrast, both ACE inhibitors failed to reduce blood pressure in DOCA and normotensive rats. In the repeated dose study, the systolic blood pressures in normotensive rats, 2K-RHR or spontaneously hypertensive rats (SHR) were measured twice a week for 3 weeks treatment of either MK-421 at 3 mg/kg or captopril at 10 mg/kg. Both ACE inhibitors produced significant antihypertensive effects in these model rats, and the effects were sustained throughout the treatment period. The antihypertensive effects in 2K-RHR were greater than those in SHR and normotensive rats. These results indicate that MK-421 and captopril cause the most significant antihypertensive effect in 2K-RHR in which the renin-angiotensin system played a dominant role in blood pressure regulation. The antihypertensive effect of MK-421 was approximately 3 times as potent as that of captopril in these hypertensive models.

Animals↗

[Correlation between the inhibition of renin-angiotensin system and antihypertensive effect of MK-421 and captopril in 2-kidney, 1-clip renal hypertensive rats after single and repeated oral administration of MK-421 or captopril].

The angiotensin converting enzyme (ACE) activity in tissues and plasma renin activity (PRA) were measured in 2-kidney, 1-clip renal hypertensive rats (2K-RHR) and normotensive rats after a single and 3-weeks oral administrations of ACE inhibitors such as MK-421 and captopril. In the single dose study, MK-421 (1 and 3 mg/kg) and captopril (3 and 10 mg/kg) inhibited the ACE activities in kidney, aorta and plasma in a dose-dependent fashion. The inhibition of ACE activity in kidney or aorta was observed for a longer time than that in plasma. PRA took a time course reversal to that of plasma ACE activity. In the 3-weeks repeated dose study, the ACE activity in kidney and aorta was strongly inhibited after the administration of each ACE inhibitor, while there was no significant change in lung ACE activity at any time point examined. The plasma ACE activity markedly elevated after the administration of each agent. PRA significantly increased after the administration of either agent, while the plasma angiotensin II level was significantly inhibited. These results indicate that the inhibition of the ACE activity in blood vessel or kidney correlate well with the antihypertensive activity in 2K-RHR after a single and repeated administration of both ACE inhibitors, but not well with the inhibition of plasma ACE activity.

Angiotensin-Converting Enzyme Inhibitors↗

Elevated serum and urine sialic acid levels in renal diseases of childhood.

Serum and urine sialic acid levels were measured in various renal diseases of childhood. Serum sialic acid levels were found to be elevated in patients with idiopathic nephrotic syndrome (INS) at onsets and relapses, acute poststreptococcal glomerulonephritis (PSGN) and chronic glomerulonephritis (CGN) found by chance proteinuria and/or hematuria. A large amount of bound sialic acids were excreted in the urine in INS at onsets and relapses, although the serum sialic acid levels were increased. Sephadex G-200 column chromatography revealed three separate peaks with sialoglycoproteins in a patient with INS at onset, but only two peaks in a normal control subject. These results suggest that some sialoglycoproteins are involved in the development of INS, PSGN and CGN.

Acetylglucosaminidase↗

[Fundamental and clinical studies on cefoperazone in pediatrics, with special reference to renal toxicity].

Fundamental, clinical studies on cefoperazone (CPZ), a new synthetic antibiotic of cephalosporins was conducted to obtain results as follows. This preparation, 11.4-50 mg/kg was administered to 11 cases of children by intravenous drip infusion for 30 minutes, and serum levels were studied. The highest serum level at the completion of infusion was 40.0-138.0 mcg/ml. A dose response was observed. The half-life in serum averaged 1.55 hours except 2.4 hours observed with 1 case of liver dysfunction. When the urinary excretion during 30 minutes drip infusion was examined, the urinary recovery rate at 0-6 hours in 2 cases of children averaged 17.2% and was low at 5.3% in 1 case of membranoproliferative glomerulonephritis. In terms of the clinical effect on bacterial infections in pediatric field, CPZ proved effective in all of the 21 cases in which it was used alone. And it showed an excellent antibacterial activity against all the bacteria isolated from cases used as the subjects. When side effects were studied, diarrhea and slight impairment of the liver were observed, but all were transient. As a result of a study on the renal toxicity of CPZ, CPZ was deemed as being a drug which hardly causes disturbance of renal tubules judging from the aspect of the beta-D-N-acetylglucosaminidase activity in urine and variations in the urine beta 2-microglobulin levels.

Adolescent↗

Pericentric inversion of chromosome No. 8.

Chromosome studies of an infant with multiple malformations were made by means of the trypsin-Giemsa banding as well as conventional Giemsa staining methods. The propositus showed 46, XY +3, -C, and it was indicated that the abnormal metacentric chromosome was induced by the pericentric inversion of chromosome No. 8, in which chromosomal breakage had occurred most likely at the bands 8p23 and 8q23. The probable formula of the inversion is 46, XY, inv (8) (p23q23). Karyotypic analyses of the parents revealed no abnormalities, and the inversion therefore occurred spontaneously. Clinical features of the porpositus are postulated to be caused by a loss of very small portions of the chromosomal material with the occurrence of the pericentric inversion.

Abnormalities, Multiple↗

Standard RUS skeletal maturation of Tokyo children.

A total of 704 girls and 753 boys, all healthy, from 3 to 18 years of age, from Tokyo and its suburbs, were radiographed on the left hand and wrist in 1986. Their RUS (TW2) skeletal maturity was estimated, the 50th-centile skeletal maturity scores were obtained, and the smoothed RUS maturity curves were determined applying the cubic spline function to the 50th-centile scores. On this maturity curve the score at each 0.1 year of chronological age was obtained and allocated as a given RUS skeletal age. This set of scores and ages we termed the TW2-J RUS, i.e. the Japanese TW2 RUS maturity standard. Comparing this RUS standard with the British standard, the Belgian, the southern Chinese, and the northern Indian, it became clear that Japanese children's RUS skeletal maturity progresses rapidly during puberty (after ages 9 in girls and 11 in boys), and that the maximum score difference between neighbouring age groups was observed at ages 12.5 in girls and 14.5 in boys on the spline-smoothed curve. Japanese children attain the adult stage 1 or 2 years earlier than other groups of children (at ages 15 in girls and 16 in boys).

Adolescent↗

Cross-dependence on ethanol and pentobarbital in rats reinforced on diazepam.

Cross-dependence on ethanol and pentobarbital was studied in rats reinforced on diazepam, using an intravenous self-administration method. Five rats were allowed to self-administer diazepam 2.0 mg/kg per injection intravenously by pressing a lever on a continuous reinforcement schedule over a 20 day period. The total daily dose of diazepam delivered reached 50 mg/kg/day. Thereafter, ethanol (50 or 100 mg/kg per injection) and then pentobarbital (6 mg/kg per injection) were substituted for diazepam for 3 and 2 days, respectively. During these substitution periods, responding for self-administration, food intake and body weight were recorded. When ethanol was substituted, self-administration responding increased and then decreased. Food intake and body weight also decreased during this period. These changes during the ethanol substitution session resembled those observed during withdrawal sessions. In contrast, when pentobarbital was substituted, no significant changes in self-administration responses, food intake or body weight were seen. These findings suggest that diazepam produces cross-dependence on pentobarbital, but not on ethanol at the doses used in this experiment.

Animals↗