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Biomedical subjects

A Takagi

Publications and source records attributed to A Takagi.

At least 343 records · Page 19Linked to original sources

[A simplified direct radioimmunoassay for urinary aldosterone (author's transl)].

A simplified direct radioimmunoassay for urinary acid labile aldosterone was developed. One ml of urine was hydrolysed with 2 ml of 0.2N HCL at 30 degrees C for 16hrs. One tenth ml of hydrolysed urine diluted 10 times with charcoal treated aldosterone-free calf serum was used for the radioimmunoassay. The radioimmunoasssay was done with a specific antibody, 125I-aldosterone, as the labeled antigen and polyethylene glycol for bound-free separation. There were excellent correlations between the present methods and other methods, i.e., i) a method using dichloromethane extraction before the assay as well as pre-extraction before hydrolysis and ii) a commercial kit using 3H-aldosterone. The intra-assay coefficient of variation was 5.8%, and the inter-assay coefficient of variation was 9.5%. The normal value of urinary aldosterone was excretion was 3.7 plus or minus 2.5 micrograms/day by the present method, and values of patients with primary aldosteronism were between 24 to 43 micrograms/day.

Aldosterone↗

Chronopharmacological study of neuroleptics. II. Circadian susceptibility rhythm to chlorpromazine.

In order to study differences in the effect of the neuroleptics due to time of administration, rats were administered chlorpromazine (CPZ) in a variety of combinations of dose and time and the sedation period was measured. There was daily fluctuation in the sedative effect and the pattern of fluctuation differed according to dosage. A similar study under the condition of reversed light and dark gave a reversed curve of the daily fluctuation, showing that the rhythm of light and dark controls the fluctuation externally. In an attempt to elucidate the mechanism of these phenomena, CPZ was administered at two different times, between which there was a significant difference in the sedation period, and time-course changes in plasma and brain concentration of the drug and its metabolites were measured. No difference was found. These results are interpreted as indicating that the phenomena could arise at the level of amine-receptor activity in the brain. In addidtion, daily fluctuation due to time of administration was noted in lethality.

Animals↗

Single-skinned human muscle fibers: activation by calcium and strontium.

Single-skinned fibers were prepared from human skeletal muscle. Tension generation was measured in solutions containing different amounts of free calcium or strontium ion. Fibers were classified into two types, on the basis of distinct differences in their regulation by strontium. One group developed maximal tension in 3 x 10-5 M free strontium, whereas the other developed minimal or no tension in the same concentration of strontium. It seemed most probable that the former represented type 1 (slow twitch) fiber and the latter type 2 (fast twitch) fiber because of similar patterns observed in guinea pig soleus and extensor digitorum longus muscle fibers.

Calcium↗

[Studies on circadian susceptibility rhythm to haloperidol (author's transl)].

Rats were given haloperidol in a variety of doses and time combinations and the sedation period were then measured. A clear-cut daily fluctuation in the sedative effect was observed, and the pattern of fluctuation differed depending on the dosage. In an attempt to elucidate the mechanism of this phenomenon, haloperidol was administered at two different times between which there was a significant difference in the sedation period. No difference was found. Thus it is presumed that daily fluctuation in the sedative effect of haloperidol may be ascribed not to the daily fluctuation in the levels of absorption, excretion, metabolism, or distribution of this drug, but rather to the daily fluctuation at the level of catecholamine receptors in the brain. There was a daily fluctuation in the antiapomorphine effect of haloperidol in a variety of doses and time combinations, and the pattern of fluctuation almost equaled that of the sedative effects of haloperidol. The daily fluctuation of the sedative effect is probably due to effects of circadian rhythm in brain dopamine receptors.

Animals↗

Animal model of depression. III. Mechanism of action of tetrabenazine.

A study was undertaken to gain an understanding of the biochemical mechanism whereby tetrabenazine (TBZ) produces a sedative effect on the locomotor activity of rats. Rats injected with L-5-hydroxytryptophan (L-5-HTP, 30 mg/kg), the immediate precursor of 5-hydroxytryptamine (5-HT), showed the characteristic bison appearance, pitosis, and catalepsy normally observed after injecting TBZ (30 mg/kg). The treatment of rats with low doses of L-5-HTP (9 mg/kg) plus TBZ (2 mg/kg) significantly decreased locomotor activity, whereas low doses of either one of these drugs given alone had no significant effect on locomotor activity. The level of 5-hydroxyindoleacetic acid (5-HIAA) was elevated in the brain of rats sacrificed 3 hr after treatment with low doses of either L-5-HTP or TBZ alone. Treatment of rats with p-chlorophenylalanine to inhibit the synthesis of 5-HT had an inhibitory effect on the duration of sedation following an injection of TBZ (30 mg/kg). The results of the biochemical and pharmacological studies as reflected by changes in locomotor activity were interpreted to indicate that the sedative action of TBZ was due to an excess of functional 5-HT.

5-Hydroxytryptophan↗

Circadian susceptibility rhythm to neuroleptics: tetrabenazine.

In order to clarify the influences of situational factors on the effects of psychotropic drugs, the sedative effects of tetrabenazine after injection at various times of the day were studied. When 50 mg/kg body weight of tetrabenazine was injected into rats at eight different times of the day (07:30-19:30 dark, 19:30-07:30 light), a circadian rhythm of sedative effect was observed with a peak sedative time of 1490 min at 10:30 and a nadir of 736 min at 07:30. With 10 mg/kg body weight of tetrabenazine a similar circadian rhythm of sedative effect was observed. This rhythm did not appear to be due to differences of metabolism of tetrabenazine in the tissues, but rather to be closely related to daily fluctuation of serotonin synthesis and release in the brain.

Animals↗

[A simplified radioimmunoassay for serum aldosterone--non-extraction method with 125I-labeled aldosterone (author's transl)].

A simplified direct radioimmunoassay system for serum aldosterone measurement was developed by using radio iodine-labeled aldosterone and highly specific antiserum to aldosterone. 8-anilino-1-naphthalene sulfonic acid(ANS) was used to prevent the binding of aldosterone to serum proteins. Polyethylene glycol was used to separate the antibody-bound aldosterone from the free aldosterone as the precipitant. The minimum measurable concentration of aldosterone is 30pg/ml of serum by short incubation method (at 25 degrees C for 3hr incubation) and 15pg/ml of serum by long incubation method (at 4 degrees C for 20 hr incubation) respectively. Present radioimmunoassay eliminates extraction of the aldosterone from serum and chromatographic separation procedures, and requires only 0.1ml of serum sample for assay. The intra-assay precision was C. V. 6.9% (average of 4 samples) and the inter-assay precision was C. V. 10.7% (average of 4 samples). There is an excellent correlation between the extraction method and this direct method in serum aldosterone value obtained (correlation coefficient, 0.96). The normal value was 36.8+/-25.9pg/ml (recumbent) and 113.6+/-6.15pg/ml (upright).

Aldosterone↗

A non-chromatographic non-extraction radioimmunoassay for serum aldosterone.

A direct radioimmunoassay for serum aldosterone was developed using a highly specific sntibody and 8-anilino-1-naphthalene sulfonic acid as a blocking agent to inhibit the binding of aldosterone to serum proteins. 125I-labeled aldosterone was used as the labeled antigen and polyethylene glycol was used to separate antibody-bound and free aldosterone. The minimum detectable concentration was 1.5 pg/tube. There were excellent correlations between the present method and other methods, i.e., 1) a method using tritiated aldosterone, 2) a method using dichloromethane extraction before assay, and 3) a commercial kit method. The intra-assay coefficient of variation was 6.9%, and the inter-assay coefficient of variation was 10.7%. The values found in normal human serum were comparable with those reported using other methods. The present radioimmunoassay eliminates both extraction of aldosterone from serum and chromatographic separation and requires only 0.1 ml of serum for assay.

Aldosterone↗