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I Tamai

Publications and source records attributed to I Tamai.

131 records · Page 8Linked to original sources

Evidence for the existence of a common transport system of beta-lactam antibiotics in isolated rat hepatocytes.

The inhibition effect of several beta-lactam antibiotics on the uptake of [14C]benzylpenicillin (PCG) into isolated rat hepatocytes was studied. Monobasic beta-lactam antibiotics such as apalcillin, cloxacillin, nafcillin, piperacillin, cefmetazole, cefoperazone, cefpiramide and cephalothin significantly inhibited the uptake of PCG, while amphoteric beta-lactam antibiotics such as amoxicillin, ciclacillin, cephradine, cephalexin and cephaloridine had a slight inhibitory effect on the uptake of PCG. Five monobasic compounds of these antibiotics used (apalcillin, nafcillin, piperacillin, cefmetazole and cefoperazone) which have a tendency to be excreted into bile to a large extent, inhibited the initial uptake rate of PCG in a fully competitive fashion according to the Lineweaver-Burk plots and the corresponding modified Inui-Christensen plots. Thus, it was concluded that almost all beta-lactam antibiotics have a common carrier system responsible for their uptake into isolated rat hepatocytes, but it is still uncertain whether or not amphoteric beta-lactam antibiotics have another specific transport system.

Animals↗

Kinetic analysis and characterization of the bacterial regrowth after treatment of Escherichia coli with beta-lactam antibiotics.

The generation curves of Escherichia coli B/r and E. coli NIHJ JC-2 in the presence of several beta-lactam antibiotics were studied from the kinetic point of view. Apparent first-order regrowth of resistant organisms was observed approximately 6 h after addition of these antibiotics. The time courses of apparent viable counts could be interpreted in terms of the sum of the viable counts of sensitive and resistant organisms. To clarify the nature of the regrowth, experiments involving a second addition of antibiotic, single colonization by subculture, and synchronous cell culture were carried out. Several possible explanations for the results are discussed, including beta-lactamase production, selection in terms of membrane permeability, and mutation to acquire drug resistance. A selection process or a modification of membrane permeability caused by contact with the drug seems to be the most probable reason for the regrowth of the organisms.

Ampicillin↗

Prostaglandin F2 alpha concentrations in the cerebrospinal fluid of children with febrile convulsions, epilepsy and meningitis.

Cerebrospinal fluid prostaglandin F2 alpha (CSF PGF2 alpha) levels were measured by radioimmunoassay in children as follows: Febrile convulsions (31 cases), epilepsies (32 cases), meningitides (31 cases) and non-neurological diseases (20 cases), totaling 114 cases. A 4.5-fold increase in CSF PGF2 alpha levels was seen in simple febrile convulsion, and a 2.5-fold increase in those with complex febrile convulsion as compared to those with non-neurological diseases. On the other hand, no increase in CSF PGF2 alpha levels was seen in children with epilepsy. When the body temperature was normal, the mean CSF PGF2 alpha levels showed no relation with age. When the body temperature was between 37.5 degrees C and 40 degrees C, the CSF PGF2 alpha levels in infants were higher than those in older children. The CSF PGF2 alpha levels in children with meningitis were high. The mean CSF PGF2 alpha levels in bacterial meningitis were not statistically (p greater than 0.05) different from those in viral meningitis. The CSF PGF2 alpha levels in meningitis were high on admission and gradually decreased with therapy. The results of our studies indicate that PGF2 alpha of the central nervous system markedly increased in infants and children with febrile convulsions or meningitis but not in those with epilepsy.

Adolescent↗

Transient brain shrinkage in infantile spasms after ACTH treatment. Report of two cases.

This is the report of two cases of infantile spasms, manifesting transient brain shrinkage in computerized tomography (CT) after ACTH treatment. ACTH was given for 8 weeks to a 8-months-old Japanese girl with infantile spasms. First CT performed at 2 weeks after the final ACTH injection, displayed moderate brain shrinkage. Second CT at 4 months showed marked diminution of the shrinkage. ACTH was also given for 8 weeks to a 14 months old Japanese boy with infantile spasms. First CT, just before ACTH treatment, showed mild cortical atrophy, the second at 7 days after the final ACTH injection revealed marked brain shrinkage and moderate ventricular dilatation, and the third at 2 months, disclosed mild improvement of the shrinkage. ACTH or corticoateroid has widespread effects on the developing nervous system. In animal experiments, ACTH or steroids interfere with brain growth of young rats. CT findings of transient brain shrinkage in a child with infantile spasms might suggest that intensive treatment with ACTH or steroids in infancy interferes with brain growth as seen in the results of animal experiments.

Adrenocorticotropic Hormone↗

Physiologically based pharmacokinetics of a new penem, SUN5555, for evaluation of in vivo efficacy.

SUN5555, (5R,6S)-6-[(R)-1-hydroxyethyl]-7-oxo-3-[(R)-2- tetrahydrofuryl]-4-thia-1-azabicyclo-[3.2.0]-hept-2-ene-carboxylic acid, is a newly developed and orally effective penem with a broad antibacterial spectrum. SUN5555 was degraded in rat tissue homogenates and serum, and its degradations in the kidney and lung homogenates were significantly inhibited by cilastatin, an inhibitor of dehydropeptidase I. The pulmonary extraction was evaluated to be 0.033 by comparing the AUCs resulting from iv and intra-arterial administration of 10 mg/kg. From the arterial-to-venous concentration differences under steady state conditions in rats, extraction ratios of SUN5555 across the kidney, hind leg, gut, and liver were determined to be 0.333, 0.104, 0.071 and 0.053, respectively, whereas no appreciable extraction across the brain was observed. Therefore, organ clearances of SUN5555 are limited by the product of plasma unbound fraction and organ intrinsic clearances in various tissues. Using a physiologically based pharmacokinetic model, unbound concentrations of SUN5555 in the tissue interstitial fluids, which are the measure of in vivo antibacterial efficacy, were estimated to be almost identical with, or higher than, those in plasma in rats. Similarly, serum concentration-time profiles of SUN5555 after iv administration in other animal species were predicted and found to be in good agreement with the observed data in dogs. A preliminary prediction of the pharmacokinetics of SUN5555 in a human subject was also attempted by animal scale-up technique.

Animals↗