Biomedical subjects
Publications and source records attributed to M Nishida.
A 22/22 Robertsonian translocation has been identified in a woman with recurrent abortions by a Giemsa banding technique. Cytogenetic studies of the embryonic tissue derived from one of her spontaneous abortions have demonstrated that the aborted fetus had a 46,XX,-22,+t(22q22q) karyotype.
Ceftezole, a new cephalosporin derivative, was compared with cefazolin, cephaloridine, and cephalothin. Data obtained indicate that it is a broad-spectrum antibiotic, with almost identical antimicrobial activity against pathogenic organisms isolated from patients. The therapeutic effect of ceftezole on experimental infections in mice was similar to that of cefazolin and was superior to that of cephalothin. The binding of ceftezole to serum proteins was somewhat less than that of cefazolin. The concentrations of ceftezole in the sera of test animals and human volunteers were determined after intramuscular injection of 20 mg/kg and after a single dose of 500 mg, respectively. The concentration of ceftezole in the serum of volunteers peaked at 24.9 mug/ml 15 min after injection and remained effective (about 2.6 mug/ml) at 4 h. The half-life in serum under the same conditions was 56 min, i.e., about one-half that of cefazolin. The 24-h urinary recovery rate was 87.5%. Most of the administered ceftezole was excreted unchanged mainly through the urinary tract. The biliary excretion rate in SD strain rats after intramuscular injection of 20 mg/kg was about 4.4%. As compared with commercially available cephalosporins, ceftezole was second only to cefazolin in biliary excretion rate. Various tissue levels of ceftezole in animals were higher than cephalothin but, with the exception of renal levels in the early stage after administration, were lower than cefazolin.
The biliary excretion of cefazolin was compared with that of cephalothin and cephaloridine in rats and man. In rats, the biliary levels were dose-related with cefazolin and cephalothin but not with cephaloridine. Biliary levels were higher than serum levels after injection of 10--80 mg/kg of cefazolin and cephalothin, whereas serum levels of cephaloridine after injection were higher than biliary levels. The highest biliary levels of cefazolin were obtained by intravenous injection, followed by intramuscular injection and drip infusion. In man, a crossover study was made to compare biliary levels of cefazolin with those of cephaloridine and cephalothin. After a single 1-gram intravenous injection, the peak levels of cefazolin ranged from 0.85 to 21 mug/ml and those of cephaloridine varied from 0.55 to 3.9 mug/ml. After a 3-gram intravenous injection, the peak biliary levels of cefazolin ranged from 35.5 to 270 mug/ml and those of cephalothin from 0.3 to 64 mug/ml. The chemotherapeutic biliary levels of cefazolin able to inhibit susceptible organisms were obtained by 3-gram intravenous injections.
The effect of antibiotics on phagocytosis and killing of Pseudomonas aeruginosa by rabbit polymorphonuclear leukocytes was studied. Carbenicillin and sulbenicillin, when added to an incubation medium at a concentration as low as 1/16 MIC, increased phagocytosis and killing of P. aeruginosa by PMN. Meanwhile, gentamicin and 3',4'-dideoxykanamycin B gave no influence on the PMN activity, and polymyxin B and colistin enhanced the activity only at MIC. The PMN activity was not facilitated even when the cells of P. aeruginosa had been pretreated with antibiotics. The bactericidal activity of PMN decreased after sonification, but was restored following addition of carbenicillin.
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Nalidixate inhibited the post-uv survival of E. coli B. TAU-bar and Ts-7, but not Bs-1 or B/r when included in the plating medium. Removal of the drug sensitivity by photoreactivation was consistent with pyrimidine dimers as the target for the effect. Nalidixate did not inhibit liquid-holding recovery from uv when included in the holding medium, but survival was inhibited if the drug was in the subsequent plating medium. In fact, there was an actual increase in the number of nonsurvivors due to the drug following a period of holding.
FR10612, like cephalexin, is a broad-spectrum oral cephalosporin derivative. The antimicrobial activity of FR10612 against clinical isolates was similar to cephalexin; however, at a low inoculum size its activity was greater than cephalexin against Klebsiella pneumonia and Proteus mirabilis strains. Like cephalexin, the in vitro bactericidal activity of FR10612 was more influenced by the duration of contact with the test organism than by drug concentration. The bactericidal activity of FR10612 against E. coli 317 was greater than that of cephalexin in an in vitro model system which simulated the serum levels of FR10612 and cephalexin achieved in healthy volunteers after a single oral dose. The protein binding of FR10612 to human and animal serum was extremely low. FR10612 was resistant to beta-lactamases from gram-negative bacilli. It showed resistance similar to cephalexin, but was more resistant to beta-lactamases than were cephaloridine, cephalothin and cefazolin. The protective effect of FR10612 in mice infected with various pathogens was greater than cephalexin. The serum levels of FR10612 in rats were higher and more prolonged than those of cephalexin. Tissue levels of FR10612 in rats also persisted for a long time period reflecting the serum levels. In healthy volunteers, rabbits and monkeys the serum levels of FR10612 were initially lower than those of cephalexin but persisted for a longer time period. The total 24-hour urinary excretion of FR10612 in healthy volunteers after oral administration was almost the same as that of cephalexin, but the excretion rate of FR10612 was slower, and the urinary levels were more persistent than those of cephalexin.
Though pyrrolnitrin is surpassed by clotrimazole in in vitro antitrichophyton activity against Trichophyton sp., the therapeutic effect of pyrrolnitrin against experimental trichophytosis in guinea pigs was more potent than that of clotrimazole. The detection of antifungal activity from topically treated guinea pigs suggests that pyrrolnitrin obtains higher concentrations than clotrimazole in dermal tissue.
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Nadilidixic acid at 5 x 10(-6) M produced a substantial increase in thermal susceptibility of Ts-7, suggesting either that the thermal and nalidixic acid targets are identical or closely interdependent.
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