On-line extraction, evaporation, and injection for liquid chromatographic determination of serum corticosteroids.
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Biomedical subjects
Publications and source records attributed to K Minagawa.
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The kinetics of desensitization in normal calcium buffer was studied in leukocytes resuspended at a maximum concentration of 50,000 basophils/ml (total available histamine, greater than 5 x 10(-7) M). The time constant of desensitization, k, ranged between 0.01 and 0.02 under subthreshold preincubation conditions (50% inactivation; t 1/2 = 60-120 min). Fractional addition of antigen reduced preincubation histamine release. The degree of IgE bridging required for virtually complete desensitization was complete within the first seconds of incubation of cells with anti-IgE. Hence the slow development of subthreshold and suboptimal desensitization in the presence of calcium must be related to events which occur after IgE cross-linking.
Desensitization in human basophils was induced by suboptimal levels of antihuman IgE or antigen under normal calcium buffer conditions. Low doses of anti-IgE triggered only 0-12% histamine release during a 3-hour preincubation, yet initiated up to 100% desensitization upon rechallenge. After 24-27 h preincubation with allergen a, the cells did not regain releasability when rechallenged with either allergen a, allergen b or anti-IgE. Low dose, IgE-mediated desensitization in human basophils may lead to an irreversible and nonspecific inhibition of degranulation.
Cord basophil preparations from 53 term neonates were studied for various factors affecting immediate hypersensitivity reactions including: basophil IgE receptor density and histamine releasability following incubation with calcium ionophore A23187, zymosan-activated serum (C5a), and anti-IgE. Basophil histamine content (geometric mean, 0.4 pg/basophil, with content in 14/28 cord blood samples below 0.2 pg/cell) is considerably below that of atopic and nonatopic individuals (geometric mean, 2.3 pg/basophil). Histamine release is normal with both A23187 (range 33% to 88%) and C5a (range 11% to 58%). Normal release with anti-IgE was shown in five of nine cord blood samples (range 13% of 52%), but four of five cell preparations required IgE preincubation. Indirect evidence indicates that basophils from newborns contain less than 30,000 total IgE receptors/cell. IgE-mediated histamine release in basophils from newborns is minimized by suboptimal IgE binding. Optimal IgE binding is not favored in basophils from neonates because of low serum IgE and low IgE receptor density. Serum IgE and IgE receptors increase to a variable degree as the child grows older and may determine the clinical onset of allergic disease.
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Of 196 children with febrile convulsions, 6.9 were placed on phenobarbital, 4-5 mg/kg/day b.i.d., and 32 on primidone, 15-20 mg/kg/day b.i.d. The remaining 95 children were given sodium valproate; the dosage was 20-25 mg/kg/day b.i.d. in 38 of them, 20-25 mg/kg/day t.i.d. in 24 of them, and 30 mg/kg/day b.i.d. in 33 patients. Recurrence rate of febrile convulsions during one year were not statistically different among these five groups. However, the dosage regimen of valproate of 20-25 mg/kg/day b.i.d. was relatively inferior to the other regimens of valproate in the prophylactic effect. This may be explained by the facts that when the same daily dosage of sodium valproate was given, the daily fluctuation of plasma levels was greater with the b.i.d.-regimen than with the t.i.d.-regimen, and that when the dosage interval was the same, the minimum plasma level of the day was lower with the smaller daily dosage regimen than with the larger one.
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Phenobarbital pharmacokinetics after a single intramuscular dose of approximately 10 mg/kg of phenobarbital sodium or acid were studied in twelve infants with febrile convulsions. The mean peak time after phenobarbital sodium (0.92 hr) was significantly (p less than 0.01) shorter than that after phenobarbital acid (5.83 hr), whereas the mean peak levels (16.2 vs 13.8 microgram/ml) did not reach statistical difference (p less than 0.2) between both dosage forms. The values of the absorption rate constant and the area under the curves calculated from 0- to up to 6-hr periods were significantly higher (P less than 0.001 to 9.005) after the sodium form. There were no significant differences in such parameters as t1/2, Vd/F, and C1/F between the two preparations. The overall mean values of these variables were: t1/2, 64.0 hr, Vd/F, 0.667 1/kg, and C1/F, 0.136 m1/min/kg. Some delay in rising phenobarbital concentration in cerebrospinal fluid (CSF) as compared with that in plasma after phenobarbital sodium was observed, though the absolute values of phenobarbital concentrations in CSF were similar from both dosage forms around the time when peak plasma levels were attained.
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Michaelis-Menten pharmacokinetics were evaluated for diphenylhydantoin given to 104 patients 0.5 to 16 years of age with seizures. A method for individualizing the dosage regimen of DPH for each patient was evaluated retrospectively. The Vmax was inversely related to age (r = 0.552, P less than 0.001) but there was no such relationship for Km. The individual pharmacokinetics were characteristic of that person and could be used to adjust dosage so that toxicity would be avoided. We present a nomogram for adjusting the dosage of DPH in the pediatric age groups.
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Carbaryl and dieldrin were accumulated mostly in the liver, and paraquat was accumulated in the kidney of normal diet (casein 24.5%) rats at 1 hr after the oral administration. At 5 hr after the administration, the concentration of carbaryl in liver or fat, and that of paraquat in kidney were markedly decreased. However, dieldrin in liver, kidney, lung, fat or others was signficantly increased at the same period. The absorption of paraquat from gastrointestinal tract was the least among the chemicals used. Biliary excretion of carbaryl was the highest and that of paraquat was the least by 5 hr after intravenous administration. The excretion ratio was about 100: 10: 1 for carbaryl, dieldrin and paraquat in normal diet rats. Biliary excretion of these chemicals was higher in high protein diet (casein 45%) rats and retention of the chemicals in tissue was higher in low protein diet (casein 5%) rats.