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Biomedical subjects

W A Zygmunt

Publications and source records attributed to W A Zygmunt.

At least 19 recordsLinked to original sources

Tissue culture cytotoxicity assay for cyclophosphamide metabolites in rat body fluids.

An in vitro cytotoxicity assay for cyclophosphamide metabolites in rat body fluids is described. Of the two tissue culture tumor cell lines employed, the Walker-256 rat carcinosarcoma was more sensitive to metabolite levels than the L-1210 mouse lymphocytic leukemia. The Walker-256 system detected cyclophosphamide metabolite levels two orders of magnitude lower than the commonly used 4-(p-nitrobenzyl)pyridine analytical procedure.

Animals↗

Antigenic response to topically applied proteins.

Six different proteins varying widely in molecular weight, ribonuclease, lysostaphin, ovalbumin, penicillinase, collagenase, and Varidase were tested for their ability to induce circulating antibody formation in rabbits after repeated topical application of the proteins in a water-soluble gel vehicle. After a 12-week exposure period, significant hemagglutinin titers were noted in rabbits treated with ovalbumin, lysostaphin, or ribonuclease; markedly elevated, passive cutaneous anaphylaxis-reacting sera were obtained only from collagenase- or lysostaphin-treated animals. Precipitin antibodies as evidenced by gel diffusion were also found in sera from collagenas- and lysostaphin-treated animals. Topical application of penicillinase was only marginally effective and Varidase was totally ineffective in elicting a positive circulating antibody response. In all cases, topical application of proteins for periods in excess of 3 weeks was required for induction of circulating antibody formation.

Administration, Topical↗

Haloprogin: a topical antifungal agent.

Haloprogin was shown to be a highly effective agent for the treatment of experimentally induced topical mycotic infections in guinea pigs. Its in vitro spectrum of activity also includes yeasts, yeastlike fungi (Candida species), and certain gram-positive bacteria. The in vitro and in vivo antifungal activity of haloprogin against dermatophytes was equal to that observed with tolnaftate. The striking differences between the two agents were the marked antimonilial and selective antibacterial activities shown by haloprogin, contrasted with the negligible activities found with tolnaftate. Addition of serum decreased the in vitro antifungal activity of haloprogin to a greater extent than that of tolnaftate; however, diminished antifungal activity was not observed when haloprogin was applied topically to experimental dermatophytic infections. Based on its broad spectrum of antimicrobial activity, haloprogin may prove to be a superior topical agent in the treatment of dermatophytic and monilial infections in man.

Animals↗

Some active derivatives of penicillin.

The antibacterial activities of a number of amide derivatives of penicillin against both penicillin-sensitive and penicillin-resistant cultures were determined. Several of them were found to possess significant inhibitory activity against certain gram-positive bacteria. The amides, although resistant to the destructive action of beta-lactamase, did not protect G in competitive experiments. One derivative, the O-benzylhydroxamide of penicillin G, was active against six or eight penicillin-resistant strains of Staphylococcus aureus (minimal inhibitory concentration, 0.2 mug/ml or less), but was found to have only a minimal in vivo activity against mouse Streptococcus infections.

Amides↗

Susceptibility of coagulase-negative staphylococci to lysostaphin and other antibiotics.

In general, coagulase-negative staphylococci were found to be relatively less susceptible to the lytic action of lysostaphin than coagulase-positive staphylococci. To achieve, arbitrarily, a lysis greater than 75%, it was necessary to use an increased concentration of enzyme or a longer incubation period than that usually required with coagulase-positive strains. For the most part, the cultures studied were sensitive to oxacillin, cloxacillin, dicloxacillin, nafcillin, ancillin, cephalothin, cephaloridine, fusidic acid, lincomycin, novobiocin, and neomycin [median minimal inhibitory concentrations (MIC) of 1.56 mug/ml or less]. Some degree of resistance (median MIC values of 12.5 mug/ml or greater) to benzylpenicillin, ampicillin, methicillin, tetracycline, chloretetracycline, erythromycin, ristocetin, and lysostaphin was found. Ten methicillin-resistant, coagulase-negative staphylococal strains were found to be cross-resistant to all nine of the penicillins tested, but much less resistant to the two cephalosporin analogues. In several instances, some of these strains seemed to be more sensitive to benzylpenicillin and to certain of the semisynthetic penicillins than to methicillin. Of the 18 antibiotics tested with the viable plate count method, the methicillin-resistant strains were found to be the most sensitive to lincomycin and novobiocin.

Amino Acids↗

Comparative inhibition of methicillin-resistant strains of Staphylococcus aureus by lysostaphin and other antibiotics.

Sixteen methicillin-resistant strains of Staphylococcus aureus obtained from Europe were found to be sensitive to the lytic activity of lysotaphin. With only minor exceptions, the strains were found to be sensitive to novobiocin, erythromycin, fusidic acid, and lincomycin, and slightly less sensitive to vancomycin and chloramphenicol. All strains were resistant to tetracycline, penicillinase-sensitive penicillins (benzylpenicillin, ampicillin, and propicillin), penicillinase-resistant penicillins (methicillin, nafcillin, ancillin, oxacillin, cloxacillin, and dicloxacillin), and two cephalosporin antibiotics (cephalothin and cephaloridine).

Anti-Bacterial Agents↗

Lysostaphin in experimental renal infections.

By use of a renal staphylococcal infection model in mice, single intravenous doses of lysostaphin ranging from 1.56 to 50 mg/kg were effective in: (i) controlling the staphylococcal population of kidneys, (ii) reducing the mortality rate, and (iii) clearing high numbers of kidneys of infection. Semisynthetic penicillins and other antistaphylococcal antibiotics given in the same manner did not have significant activity. Only by the administration of a long-acting, depot form of penicillin (Bicillin) could results comparable to those seen with lysostaphin be obtained. The results of this study suggest that lysostaphin may be useful in staphylococcal septicemias in preventing the establishment of new foci of infection.

Animals↗

Steroid interference with antifungal activity of polyene antibiotics.

Wide differences exist among the polyene antibiotics, nystatin, rimocidin, filipin, pimaricin, and amphotericin B, with reference to steroid interference with their antifungal activities against Candida albicans. Of the numerous steroids tested, ergosterol was the only one which effectively antagonized the antifungal activity of all five polyene antibiotics. The antifungal activities of nystatin and amphotericin B were the least subject to vitiation by the addition of steroids other than ergosterol, and those of filipin, rimocidin, and pimaricin were the most sensitive to interference. Attempts to delineate the structural requirements of steroids possessing polyene-neutralizing activity in growing cultures of C. albicans are discussed. The ultraviolet absorbance of certain antibiotic steroid combinations was also studied.

Journal Article↗

Intracellular Loss of Potassium in Candida albicans After Exposure to Polyene Antifungal Antibiotics.

Eleven antifungal antibiotics, representing three broad macrolide classes, were studied in Candida albicans for their effect on growth and on the fate of intracellular K. Marked differences were observed among these antibiotics between their growth-inhibitory activities and their adverse effects on the integrity of the cellular membrane as evidenced by loss of K. Antibiotics most active in inhibiting growth of C. albicans were amphotericin B, trichomycin, candidin, candicidin (all heptaenes), and nystatin (a tetraene). In addition to those antibiotics, filipin and fungichromin also caused rapid leakage of K from yeast cells. Interestingly, fungichromin was the least active of the 11 antibiotics in inhibiting growth. Concentrations of rimocidin 10 times as great as those required for growth inhibition caused only a slight loss in intracellular K after 60 min.

Journal Article↗