摘要:

Metabolism of 5-fluorocytosine-6-14C (5-FC) was studied in mice, rats, rabbits and dogs after oral and subcutaneous, single and repeated administration. In the urines of all species, intact 5-FC accounted for more than 90% of the total radioactivity at any time of the various treatment schedules. The average proportion of the urinary metabolites was around 5% in dogs, 3% in rabbits, 2.5% in rats and 2% in mice of the total radioactivity. At repeated dosage, there was an increase of metabolites in mice but a decrease in rats treated subcutaneously. Neither increase nor decrease was observed in rabbits (treated orally) and dogs. Two metabolites were identified, α-fluoro-β-ureido-propionic acid (FUPA) and α-fluoro-β-alanine, the latter occurring mainly after oral treatment. These compounds represent probably that part of 5-FC which was deaminated to 5-fluorouracil (5-FU) or directly to 5-fluorodihydroura

ISSN:0009-3157    

DOI:10.1159/000221923

出版商:S. Karger AG    

年代:1976

数据来源: Karger

摘要:

The pharmacological and microbiological properties of cyclacillin were discussed and its usefulness in the management of a variety of infections was reviewed. The antibacterial spectrum and clinical utility of this agent generally parallels that of ampicillin, but there are minor differences in specificity with regard to individual microorganisms. The in vitro activity of cyclacillin against gram-negative pathogens varies greatly, the results fluctuating in accordance with the composition of the assay medium or method. The drug has demonstrated excellent therapeutic-effectiveness against experimental infections produced by both gram-positive and gram-negative pathogens, thus making questionable a prediction of therapeutic effectiveness from in vitro susceptibility tests alone. Cyclacillin is more resistant to β-lactamase hydrolysis than ampicillin, is much better absorbed when given by mouth and, as a result, the levels reached in the blood and in the urine are considerably higher than those obtained with the same dose of ampicillin. Cyclacillin produces fewer and milder side-effects than ampicillin.

ISSN:0009-3157    

DOI:10.1159/000221924

出版商:S. Karger AG    

年代:1976

数据来源: Karger

摘要:

The penicillins ciclacillin and dicloxacillin demonstrate marked similarities in biological activity but, as far as can be determined, differ substantially in respect to the degree of protein binding, which is relatively low for ciclacillin and relatively high for dicloxacillin. In mice infected with Staphylococcus aureus Smith, ciclacillin is considerably more active than dicloxacillin, although both drugs are similarly effective in vitro and similarly absorbed and eliminated in vivo. The high degree of protein binding exhibited by dicloxacillin could therefore very probably explain its relatively low chemotherapeutic activity. Moreover, the in vitro and in vivo findings of the study are inconsistent with the tenets of the τ/2 thesis

ISSN:0009-3157    

DOI:10.1159/000221925

出版商:S. Karger AG    

年代:1976

数据来源: Karger

摘要:

Antibacterial susceptibility testing of urine specimens by the dip-slide method was compared to the standardized disc diffusion method. A boarder line of 12 mm inhibition zone on the slide could be used to select strains resistant to sulphisadimidine, ampicillin, nitrofurantoin or nalidixic acid. In the case of the sulphon-amide, the results were greatly influenced by composition of the medium. Susceptibility testing with the dip-slide method seems to be a usefull test to differentiate strains likely to respond to therapy from resistant strains.

ISSN:0009-3157    

DOI:10.1159/000221926

出版商:S. Karger AG    

年代:1976

数据来源: Karger

摘要:

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 carbenicil

ISSN:0009-3157    

DOI:10.1159/000221927

出版商:S. Karger AG    

年代:1976

数据来源: Karger

摘要:

The antibacterial and antimycotic activity of econazole base, an imidazole derivative, was examined in vitro and in experimental infections of mice. Comparative minimal inhibitory concentration (MIC) determinations indicate econazole as well as miconazole to be of moderate activity against gram-positive bacteria (MICs: 0.78–25 μg/ml) and yeasts (MICs: 1.56–25 μg/ml). Against filamentous fungi, econazole exhibits better in vitro activity than miconazole and – with the exception of Rhizopus oryzae and Absidia corymbifera – MICs are markedly lower than against yeasts. No effect of nutrient media and no effect of the inoculum were observed with the four drugs. A strong influence of bovine serum on MIC values, however, suggested a strong protein binding. In experimental candidiasis of mice, no therapeutic effect with econazole base administered orally or intraperitoneally could be observed (ED50 200mg/kg). In experimental aspergillosis of mice, a slight effect, as demonstrated by the ‘minimum life-prolonging dose’ of 100 mg/kg, was found. The in vitro and in vivo results are discussed in the light of the available pharmacokinetic and toxicological data. It is concluded that more studies, especially on the pharmacology of econazole and about the clinical efficacy, are needed to come to a d

ISSN:0009-3157    

DOI:10.1159/000221928

出版商:S. Karger AG    

年代:1976

数据来源: Karger

摘要:

The effects of 5-trifluoromethyluracil (F3Thy), 5-trifluorome-thyl-2′-deoxyuridine (F3dThd), F3dThd-5′-P, and F3dThd-5′-methylphosphonate on the growth of HeLa cells, Novikoff hepatoma cells, L5178Y mouse leukemia cells, and on the replication of vaccinia virus in HeLa. cells have been determined. F3Thy and F3dThd-5′-methylphosphonate were approximately 500-fold and 100-fold less effective, respectively, than F3dThd or F3dThd-5′-P in their inhibition of these cells. F3dThd and F3dThd-5′-P are potent inhibitors of vaccinia viral replication of HeLa cells. The nucleoside and nucleotide were 1,000-fold more inhibitory than the free base. F3dThd was most inhibitory when added between 1 and 2 h post-infection; however, it was also somewhat inhibitory when added at

ISSN:0009-3157    

DOI:10.1159/000221929

出版商:S. Karger AG    

年代:1976

数据来源: Karger

摘要:

Amide penicillin Wy-12,556 and DBED penicillin were studied for their antibacterial effect in CD-1 mice repeatedly infected with Streptococcus pyogenes C203 and/or Staphylococcus aureus Smith. Animals infected with S. aureus Smith failed to show a difference between the therapeutic activity of DBED penicillin and Wy-12,556. Wy-12,556 was significantly more effective than DBED penicillin in protecting the animals challenged repeatedly with S. pyogenes C203. Wy-12,556 provoked a positive transient chemotactic response in uninfected mice. 24 h after intraperitoneal challenge the exudate showed a high neutrophilic count.

ISSN:0009-3157    

DOI:10.1159/000221930

出版商:S. Karger AG    

年代:1976

数据来源: Karger

摘要:

Rifampicin (RMP) and two riminophenazine compounds (B663 and B1912) suppressed the growth of Mycobacterium marinumin vitro and in a mouse footpad infection. At appropriate concentrations and dietary dosage, all three drugs showed bactericidal activity in vitro and in vivo. On the basis of minimum inhibitory concentration, RMP was considerably more active than the other two substances in vitro. However, the rate of bactericidal effect was similar for all three drugs. In vivo, the minimum bactericidal dietary dosages of RMP, B663 and B1912 were 0.03, 0.03 and ≤0.01 %, respectively. Results suggest that these drugs may be of value for the treatment of clinical M. marinum infection

ISSN:0009-3157    

DOI:10.1159/000221931

出版商:S. Karger AG    

年代:1976

数据来源: Karger

摘要:

Chick embryo fibroblasts cultivated in vitro and treated with cis-dichlorodiamino platinum (II) have been analysed by cytological and cytochemical methods. Morphological alterations (in the nucleoli, in the chromatin and in the cytoplasm), inhibition of DNA and RNA syntheses and of cell multiplication have been noted. Under some conditions, cells are blocked just before entering into mitosis (G2 block) and can become polyploid. A high degree of cell degeneration has also been observed.

ISSN:0009-3157    

DOI:10.1159/000221932

出版商:S. Karger AG    

年代:1976

数据来源: Karger