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Biomedical subjects

M Nishida

Publications and source records attributed to M Nishida.

At least 541 records · Page 30Linked to original sources
PubMed1980

Pharmacokinetics of ceftizoxime in animals after parenteral dosing.

The pharmacokinetic profile of ceftizoxime was studied in mice, rats, dogs, and monkeys given the drug in a single parenteral dose. The serum data after an intravenous injection were analyzed by the two-compartment open model. Cefotiam, cefmetazole, cefotaxime, and cefamandole were used as reference drugs. High concentrations of ceftizoxime were attained in the sera of all test animals and in the tissues of rats after parenteral dosing. The serum concentrations of ceftizoxime were higher than those of the other antibiotics in large animals (dogs and monkeys), but were lower in small animals (mice and rats). About 80% of ceftizoxime was excreted unchanged in the 24-h urine of all species tested. The biliary excretion of ceftizoxime was low: 3.7% in rats and 0.59% in dogs. However, therapeutically significant concentrations of ceftizoxime were found in the bile of dogs. Ceftizoxime was stable in biological fluids such as serum, urine, and tissue homogenates, but cefotaxime was unstable in rat tissue homogenates. Binding of ceftizoxime to serum protein in all species was the lowest of all the antibiotics: 31% for humans, 17% for dogs, and 32% for rats.

Animals↗
PubMed1980

New in vitro kinetic model for evaluating bactericidal efficacy of antibiotics.

A new in vitro model was devised for evaluating the bactericidal activity of antibiotics under dynamic conditions. This model accurately reproduced the observed serum levels of antibiotics after intravenous dosing. The apparatus consists of two vessels which correspond to the central and peripheral compartments of a two-compartment open model. The volume of medium in each vessel and flow rates of media were determined from the pharmacokinetic parameters calculated from the observed serum levels selected for simulation. The bactericidal activity of cefazolin against strains of Escherichia coli and Klebsiella pneumoniae showing different minimal inhibitory concentrations was investigated with the apparatus simulating serum levels after intravenous injection, and the bactericidal activity was evaluated with respect to the relationship between the minimal inhibitory concentration and the serum levels.

Anti-Bacterial Agents↗
PubMed1980

Inhibitory effect of Pseudomonas aeruginosa on phagocytosis and killing of rabbit polymorphonuclear leukocytes.

Polymorphonuclear leukocyte (PMN)-resistant strains of Pseudomonas aeruginosa had the ability to interfere with phagocytosis of Escherichia coli, whereas PMN-sensitive strains of P. aeruginosa did not. When mice were infected with an ordinarily nonpathogenic strain of E. coli, addition of a PMN-resistant strain of P. aeruginosa gave a mortality considerably higher than that obtained with P. aeruginosa alone, whereas addition of a PMN-sensitive strain of P. aeruginosa gave a mortality not different from that observed with P. aeruginosa alone. This increased mortality in mixed infection with E. coli and PMN-resistant P. aeruginosa was obtained by facilitation of tissue invasion by both bacteria from the inoculum site.

Animals↗
PubMed1980

Antibiotic resistance of indole-positive Klebsiella pneumoniae.

Resistance patterns to antibiotics differed markedly between indole-positive and indole-negative Klebsiella pneumoniae strains. Multiple-drug-resistant strains were almost exclusively indole-negative. Ampicillin and kanamycin resistances in the indolepositive strains tested were not transmissible, whereas many of those resistances in the indole-negative strains were transmissible, together with other drug resistances to an Escherichia coli recipient. The substrate profile of the beta-lactamase from the indole-positive strains was fairly different from that of the beta-lactamase mediated by the ampicillin resistance plasmid.

Ampicillin↗
PubMed1980

Effects of organic and inorganic mercurials on thyroidal functions.

Acute effects of methylmercuric chloride and mercuric chloride on thyroidal functions were examined. The organic mercurial concentration of 4 x 10(-5) M inhibited by 50% of Na+K+ATPase in the membraneous preparation from the hog thyroid, and 6 x 10(-7) M of the inorganic mercurial showed the same extent of the inhibition. The Mg2+ ATPase activity in the preparation was neither affected by CH3HgCl up to a concentration of 2 x 10(-3) M, nor by HgCl2 up to 1 x 10(-4) M. After an intraperitoneal injection to mice of 5 micrograms of mercurial per gram body weight daily for 2 consecutive days, the 4-hour and the 24-hour uptakes of 131I by the thyroids were partially reduced by both organic and inorganic mercurials. A significant reduction in percentages of labeled iodothyronines was demonstrated to suggest that mercurial may cause a coupling defect in the synthesis of iodothyronines. Incubation of hog thyroglobulin with 8 x 10(-3) M of methylmercuric chloride caused no observable aberration in slab disc electrophoreogram, but the protein was apparently denatured by the same concentration of mercuric chloride suggesting that thyroglobulin may carry a large binding capacity against either mercurial, but the inorganic mercurial can be more potent denaturant of the protein. The in vitro lysosomal hydrolysis of the mercurial-pretreated rat thyroglobulin which was labeled with 125I in vivo and fortified with the carrier hog thyroglobulin was not affected, but the direct addition of either mercurial in the medium resulted in a significant inhibition of the proteolytic action. Iodotyrosine deiodinase in the thyroid was inhibited by both mercurials in in vitro and in vivo systems. A partial reduction in the serum bound 131I-iodide in both mercurial treated groups was observed at 4 hours and 24 hours after the radioiodide administration. The blood thyroxine levels estimated by radioimmunoassay were quite reduced in the inorganic mercurial treated group and also moderately reduced in the methylmercurial treated group, indicating that the hormone secretion was affected by mercurials.

Adenosine Triphosphatases↗
PubMed1980

Influence of thymosin and the supernatant of cultured mouse thymus reticuloepithelial cell on mouse immune responses.

Effects of the humoral factor extracted from the calf thymus (thymosin: Goldstein et al.) and the supernatant of cultured mouse thymus reticuloepithelial cell (TRC) on immunological functions of the mouse lymphocytes were studied, and the following conclusions were drawn: Thymosin treatment did not alter the capacity to form anti-SRBC antibody in adult mice which were lethally irradiated and reconsituted with bone marrow cells. When the spleen cells from JCL-ICR mice thymectomized within 24 hr after birth were cultured with thymosin or supernatant of cultured ICR-TRC, the Thy 1 positive cells were increased. A significant increase in the mitogenic (PHA, Con A) reactivity of BALB/C spleen cells was observed when these cells were preincubated in medium containing thymosin for 24 hr. The NZB spleen cells, however, exhibited spleen cells showed a slightly potentiated response only to Con A. Similarly, thymosin enhanced the MLC reaction of the spleen cells from BALB/C mice with preincubation for 2 hr, but not enhanced that from NZB mice.

Animals↗
PubMed1980

A novel method for evaluating the outer membrane permeability to beta-lactamase-stable beta-lactam antibiotics.

A novel method is described which allows estimation of the outer membrane permeability to beta-lactamase-stable beta-lactams by determining antibiotic concentrations in the periplasm. The method is based on measurement of the inhibiting activity of beta-lactamase-stable beta-lactams on the hydrolysis of a substrate by periplasmic beta-lactamase. Application of the method to carbenicillin revealed that the high level of resistance to carbenicillin of an Escherichia coli strain acquiring the plasmid encoding ampicillin resistance resulted from the poor ability of carbenicillin to penetrate the outer membrane of E. coli.

Anti-Bacterial Agents↗
PubMed1980

Enterobacter cloacae outer membrane permeability to ceftizoxime (FK 749) and five other new cephalosporin derivatives.

The ability of ceftizoxime to penetrate the outer membrane was compared with those of five other new cephalosporins: cefotiam, cefuroxime, cefotaxime, cefmetazole and cefoxitin, using a clinical isolate of Enterobacter cloacae as a test strain. Estimation of permeability was performed by a method utilizing the inhibitory activities of the cephalosporins against beta-lactamase located in the periplasm. Of the cephalosporins tested, both ceftizoxime and cefmetazole gave remarkably high concentrations in the periplasm, several times higher than those of cefotaxime and cefoxitin and ten or more times higher than those of cefuroxime and cefotiam. The approximate permeability coefficient of ceftizoxime was also several times higher than those of cefotiam and cefmetazole and over ten times higher than those of cefoxitin, cefuroxime and cefotaxime.

Cefmetazole↗
PubMed1980

In vitro and in vivo antibacterial activities of FR-31564, a new phosphonic acid antibiotic.

FR-31564, a new phosphonic acid antibiotic, was active against most Gram-negative bacteria except Serratia marcescens and glucose-nonfermenting Gram-negative rods excluding Pseudomonas aeruginosa. The antibacterial activity in vitro of FR-31564 was stronger than that of fosfomycin especially against Escherichia coli, Klebsiella pneumoniae, Enterobacter species and P. aeruginosa. FR-31564 also was active against Gram-negative bacteria resistant to beta-lactam antibiotics and against gentamicin-resistant strains of P. aeruginosa. The antibacterial activity in vitro of FR-31564, like that of fosfomycin, was enhanced when 10% rabbit blood was added to the nutrient agar. The therapeutic efficacy of FR-31564 in experimental infections in mice was superior to that of fosfomycin in infections due to most Gram-negative bacteria used, and was similar to that of gentamicin in infections due to Citrobacter freundii, Proteus rettgeri and Proteus inconstans B. The protective effect of FR-31564, particularly in the P. aeruginosa infection, was superior to that of other control drugs including gentamicin.

Animals↗
PubMed1980

FR-31564, a new phosphonic acid antibiotic: bacterial resistance and membrane permeability.

Mutants which acquired resistance to FR-31564 were also resistant to fosfomycin and vice versa. Some exceptions to cross-resistance were found among clinical isolates of certain species. FR-31564 was found to be incorporated into bacterial cells more efficiently than fosfomycin although the extent of incorporation varied among species. In particular, the uptake rate of FR-31564 by a strain of Pseudomonas aeruginosa was ten times that of fosfomycin. The uptake rate of FR-31564 by both FR-31564- and fosfomycin-resistant mutants was less than one-tenth of that by the parent strain. FR-31564 was scarcely inactivated in the culture broths of FR-31564-resistant strains. All of the FR-31564-resistant mutants of P. aeruginosa came under the classification of strains lacking an L-alpha-glycerophosphate transport system.

Anti-Bacterial Agents↗
PubMed1980

[Competitive in vitro binding of bilirubin and ceftizoxime to human serum albumin (author's transl)].

The competitive effect of ceftizoxime, a new cephalosporin, on in vitro binding of bilirubin to human serum albumin was investigated and compared with that of other beta-lactam antibiotics. At the normal range of the albumin (3.48 g/dl) and bilirubin (0.936 mg/dl) concentrations in the serum of healthy infants, free bilirubin concentration was not increased by adding ceftizoxime and the other beta-lactam antibiotic concentrations tested (up to 640 micrograms/ml). The same results were obtained even under the same condition except that the bilirubin concentration was increased to 10 mg/dl. Under the condition that the albumin concentration decreased to one fifth of the normal concentration, bilirubin was competitively displaced to some extent by adding dicloxacillin (MDIPC), cefazolin (CEZ) and cefmetazole (CMZ) but not by adding ceftizoxime at the concentration of 640 micrograms/ml.

Bilirubin↗
PubMed1980

[Mechanism of renal excretion of ceftizoxime in rabbits and dogs (author's transl)].

The mechanism of renal excretion of ceftizoxime was investigated by renal clearance test and stop flow analysis in rabbits and dogs. The serum half life of ceftizoxime after dosing of probenecid and ceftizoxime in combination was about twice longer in rabbits than and almost the same in dogs as that after dosing of ceftizoxime alone. Renal clearance test and stop flow analysis were performed with the following results: (1) Renal clearance of ceftizoxime was about 3.2 times higher in rabbits than and almost the same in dogs as creatinine clearance. (2) Ceftizoxime was scarcely excreted and reabsorbed in the proximal and distal areas of dogs. (3) Ceftizoxime was excreted in the proximal area and not reabsorbed in the distal area of rabbit. These findings indicate that 60% of the urinary excretion of ceftizoxime was obtained through proximal tubule and remaining amount by glomerular filtration in rabbits, and most of the urinary excretion was obtained by glomerular filtration in dogs.

Animals↗
PubMed1980

Laboratory evaluation of ceftizoxime, a new parenteral cephalosporin.

(6,7R)-7-[(Z)-2-(2-Amino-4-thiazoyl)-2-methoxyiminoacetamido]-8-oxo-5-thia-1 -azabicyclo[4,2,0]oct-2-ene-2-carboxylate (ceftizoxime), a new parenteral cephalosporin, in more potently active in vitro and in vivo against various gram-negative bacilli including the opportunistic pathogens such as Enterobacter, Citrobacter species and Serratia marcescens than cephalosporins and cephamycins recently developed. Ceftizoxime is extremely stable to various types of beta-lactamases, and has a high ability to penetrate the outer membrane of gram-negative organisms.

Animals↗