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Biomedical subjects

I Haller

Publications and source records attributed to I Haller.

At least 19 recordsLinked to original sources
PubMed1987

Evaluation of ciprofloxacin alone and in combination with other antibiotics in a murine model of thigh muscle infection.

The therapeutic efficacies of ciprofloxacin and some comparative drugs were evaluated in a model of thigh muscle infection in neutropenic mice. Ciprofloxacin was found to be highly effective against all gram-negative and gram-positive bacteria tested. Combinations of ciprofloxacin and either gentamicin or beta-lactam antibiotics exhibited additive or slightly synergistic effects against the Enterobacteriaceae and gram-positive isolates. Azlocillin was found to increase significantly the efficacy of ciprofloxacin against Pseudomonas aeruginosa. Antagonistic interactions with vancomycin, which impaired the bactericidal activity of ciprofloxacin against Streptococcus faecalis, were observed only in vitro but not in vivo, whereas erythromycin also slightly reduced the therapeutic efficacy of ciprofloxacin in vivo.

Animals↗
PubMed1986

Comprehensive evaluation of ciprofloxacin in combination with beta-lactam antibiotics against Enterobacteriaceae and Pseudomonas aeruginosa.

1-cyclopropyl-6-fluoro-1, 4-dihydro-4-oxo-7-piperazine-1-ylquinoline-3-carboxylic acid (ciprofloxacin, Bay o-9867, Bay q-3939) was evaluated by checkerboard assay in combination with ampicillin, ticarcillin, mezlocillin, azlocillin, piperacillin, cefamandole, cefoxitin, cefotaxime, and ceftazidime. A total of 220 clinical isolates of enterobacteriaceae and Pseudomonas aeruginosa (11 species, 20 strains each) were examined. Predominantly additive combination effects were seen with all antibiotic combinations tested. Synergy was obtained with only a few test strains while antagonistic drug interactions were not observed at all. Time-kill experiments which were performed to assess the bactericidal activities, confirmed these findings. The antibiotic combinations were also evaluated in vivo using a model of experimental thigh muscle infection in neutropenic mice. In-difference or additive therapeutic effects resulted when the beta-lactam compounds and ciprofloxacin were given in combination at doses which were also effective alone. Subinhibitory doses of azlocillin and mezlocillin, on the other hand, appeared to increase the efficacy of ciprofloxacin. The influence of various application schedules was examined by time-kill experiments and in mice. Sequential administration of the drugs at intervals of 2 h did not alter the combination effects regardless of the sequence of administration.

Animals↗
PubMed1986

Distribution of [14C]-ciprofloxacin in experimentally induced intramuscular abscesses of rats.

Wistar rats were infected by injection of 0.05 ml of a dense oily suspension of Staphylococcus aureus into the posterior thigh muscles of the hind leg. Three days later, solid abscesses had formed which were characterized by a peripheral accumulation of polymorphocytes and incipient central necrosis. At this time, 10 mg/kg of [14C]-ciprofloxacin (1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-piperazin-1-ylquino line-3-carboxylic acid, Bay o 9867; designated tradename: Ciprobay) were administered intravenously. The animals were sacrificed at various time intervals after treatment and the distribution of radioactivity was examined by whole-body autoradiography. Five min after administration of ciprofloxacin, the radioactivity was found to be differentially distributed among all organs and tissues, but no radioactivity was detectable in the abscess. Beginning from 1 h post appl., increasing relative amounts of radioactivity were seen inside the abscesses. The relative enrichment as compared to the surrounding muscle tissue was most pronounced after 5 h, indicating that the radioactivity was eliminated more rapidly from the muscle than from the abscess. Some radioactivity was still present in the abscess 8 h after treatment of the animals. The comparison of autoradiograms and corresponding histological sections revealed a distinct affinity of [14C]-ciprofloxacin and/or its potential radioactive metabolites to the areas of inflammatory cellular infiltrates.

Abscess↗
PubMed1985

Mode of action of clotrimazole: implications for therapy.

Ergosterol is an essential constituent of the fungal cytoplasmic membrane. Clotrimazole and other azoles interfere with the ergosterol biosynthesis in a concentration-dependent fashion. Although low concentrations exhibit only a partially inhibitory effect, high concentrations may completely block ergosterol synthesis. Reduction of fungal growth and inhibition of growth and fungicidal action during prolonged incubation are the corresponding effects at the cellular level that are a consequence of ergosterol depletion. The inoculum effect, the influence of the incubation period, and the influence of nutrient media, three factors that often complicate susceptibility testing in vitro, can also be explained by the mode of action of azole compounds. Another interesting characteristic of azole antifungals was revealed by the observation that hyphae and pseudomycelia of Candida albicans are much more susceptible to azoles than are yeast cells. Even 1% of the minimum inhibitory concentration of clotrimazole may totally inhibit mycelial growth in vitro. This may be of clinical importance, since germination was reported to enhance adherence of C. albicans to buccal and vaginal epithelial cells.

Azoles↗
PubMed1985

A model to show the role of extracellular beta-lactamases in mediating staphylococcal resistance.

Considerable amounts of extracellular beta-lactamase are liberated from penicillin-resistant staphylococci into the surrounding medium. The accumulation of exoenzyme in conventional in-vitro test systems may result in rapid inactivation of hydrolysable antibiotics, while in vivo the concentration of extracellular beta-lactamase varies depending on the site of infection. Using a new open test model designed to eliminate the effect of exoenzyme, it could be shown that resistance of beta-lactamase-producing staphylococci to mezlocillin as seen in the broth dilution test was mediated predominantly by the extracellular beta-lactamase fraction. Animal experiments suggested that mezlocillin may exhibit a therapeutic effect against beta-lactamase-producing staphylococci under certain conditions in vivo which prevent build-up of exoenzyme.

Animals↗
PubMed1985

Penetration of antibiotics through cell culture monolayers.

Commercial tissue culture chambers were modified in such a way that they contained two portions of medium separated by a horizontal membrane. When grown on this membrane, Vero (monkey kidney) cells formed continuous cell monolayers. By comparing the penetration of antibiotics through monolayer-covered and cell-free membranes, the retention brought about by the cell layer could be measured. Only minor differences were seen between oxacillin, mezlocillin and ciprofloxacin. Penetration of polymyxin B through the cell layer proved to be reduced by about 40% in comparison to oxacillin.

Animals↗
PubMed1985

Comprehensive evaluation of ciprofloxacin-aminoglycoside combinations against Enterobacteriaceae and Pseudomonas aeruginosa strains.

The in vitro activities of antibiotic combinations containing ciprofloxacin and either gentamicin, sisomicin, netilmicin, amikacin, or tobramycin were evaluated by checkerboard assay (agar dilution method). A total of 220 strains of Enterobacteriaceae and Pseudomonas aeruginosa (11 species, 20 strains each) were tested. Synergistic or antagonistic effects were observed in less than 1% of the tests performed; they appeared to represent method-dependent fluctuations rather than true antibiotic interactions. No significant differences among the five aminoglycosides tested were seen. Time-kill experiments performed with three representative strains of Escherichia coli and Serratia marcescens showed additive combination effects with respect to the kill rates and inhibition of bacterial regrowth. Exposure of Serratia strains to either ciprofloxacin or gentamicin before the addition of the second drug had little influence on the combination effects observed. No antagonistic drug interactions were seen in vivo when combination therapy with ciprofloxacin and gentamicin was evaluated in a model of E. coli thigh muscle infection in neutropenic mice. Comparable therapeutic effects were obtained, regardless of whether the two compounds were administered simultaneously or sequentially at 1- or 2-h intervals.

Aminoglycosides↗
PubMed1979

Modern aspects of testing azole antifungals.

Difficulties in the in vitro testing of azole antimycotics are described. The value of minimal inhibitory concentration results are discussed and contrasted to those obtained with polyene antimycotics.

Antifungal Agents↗
PubMed1979

[Experimental aspergillosis in mice].

The experimentally induced aspergillosis of mice is discussed as a useful parameter for the screening of new antimycotics. There are important differences between this test model and aspergillus infections in humans. Mice must be infected intravenously with more than 10(6) spores of Aspergillus fumigatus to provoke multiple abscess formation in the kidneys which induces an acute, lethal course of infection. Intratracheal administration of 2 x 10(6) spores did not evoke any symptoms. The therapeutic efficacy of several antimycotics was examined; amphotericin B, 5-fluorocytosine and BAY h 4364--as the only imidazole-derivative--proved to be effective.

Amphotericin B↗
PubMed1978

Kidney homogenate, a test medium to determine the inhibitory effect of antimycotics on yeasts.

The test procedure described in this paper aims at assessing the effectiveness of antimycotics against yeasts. The inhibitory effect on Candida albicans growth is determined in the presence of kidney homogenate, an in vitro test medium offering fungal growth conditions similar to physiological conditions. The inoculum consists of kidney material from Candida-infected mice. By dilution with kidney material from uninfected mice the initial number of viable particles is standardised. Specimens withdrawn from this inoculum are mixed with different concentrations of the test substance and incubated for 24 hours. The inhibition of fungal growth is assessed on the basis of the number of colony-forming units in comparison with controls to which no test substance was added. The growth phase of C. albicans during incubation in vitro resembles that observed in the kidney in vivo, i.e. besides yeast cells, the fungus produces a great number of pseudomycelia and mycelia. The results of the tests conducted with the top-ranking antimycotics give good evidence of their therapeutic efficacy. The testing of further active substances revealed advantages of the new test model over existing test methods.

Animals↗
PubMed1978

[Determination of antimicrobial activity of a combination of acidamfenicol, clotrimazole and dexamethasone in vitro (author's transl)].

The in vitro antimicrobial activity of the antieczematic Bay f 4797 was studied. This combination drug contains the three active components acidamfenicol, clotrimazole and dexamethasone (prospective trade name: Baycuten). Various bacterial and fungal species of importance in dermatology served as test organisms. All the bacterial strains examined were found to be moderately susceptible to acidamfenicol; clotrimazole showed good inhibitory values agaisnt all the fungal species and the gram-positive bacterial strains. Additionally it was checked whether a synergistic or antagonistic interaction occurs with respect to the antimicrobial activity. An interference which could lead to impairment of the therapeutic activity was not observed.

Bacteria↗
PubMed1977

[The effect of therapeutic doses of gamma radiation on candida albicans cells in vitro (author's transl)].

The problem of side effects of radiotherapy in genital carcinomas on a concomitant vaginal yeast infection was investigated by subjecting candida albicans cells in vitro to the effects of gamma radiation. Agar plates with a defined number of candida albicans cells were irradiated with the conventional gynaecological sources of radium applicators and tele-cobalt. The experimental incubation of the agar plates showed that the number and growth of the yeast colonies were either completely inhibited or stunted by the effect of the radiation. There were also mutations in the cell morphology, animal pathogenecity and sensitivity to antimycotic drugs. The clinical implications of these results are discussed.

Animals↗
PubMed1976

Structural changes in bilayer membranes by multivalent ions.

Formation of microlenses, a reduction in thickness, and a change in mechanical properties have been observed when Ca2+ or other multivalent ions are added to bathing solutions of Mueller-Rudin membranes of acidic phospholipids. The observations are interpreted as an extrusion of residual solvent from the hydrocarbon core of the bilayer due to changes in packing imposed by the reduction of electrostatic repulsion of the head groups.

Calcium↗
PubMed1975

Apparent high degree of asymmetry of protein arrangement in the Escherichia coli outer cell envelope membrane.

Ghosts from Escherichia coli have been oxidized with CuSO4-o-phenanthroline or ferricyanide-ferrocene. Upon oxidation they became resistant to boiling dodecyl sulfate. The resulting rod-shaped "oxidation containers" apparently held together by disulfide bridges, are practically pure protein. They are soluble in dodecyl sulfate when reduced and they contain a set of about 30 different polypeptide chains. The four major ghost membrane proteins are not represented among the "oxidation proteins." Comparison of data obtained from digestion of ghosts with trypsin or particle-bound trypsin showed that most of the "oxidation proteins" appear to be located at the outer surface of the ghost membrane which is derived from the outer cell envelope membrane. One of the major ghost membrane proteins, II, is partially digested by trypsin, and it is shown that its trypsin sensitive part is also exposed only at the outer surface of the ghost membrane. Native cells could be oxidized only with low yields of "oxidation containers." However, cell envelopes prepared without detergents or chelating agents, as well as cells depleted of phospholipid or treated with sucrose-Triton X-100, are completely accessible to oxidation. In each case, the same set of proteins as that present in "oxidation containers" from ghosts was found to be covalently linked. Treatment of cells with trypsin caused the loss of about five "oxidation proteins" and a complete loss of oxidizability of the ghosts derived from these cells. It therefore appears that arrangement and localization of the "oxidation proteins" are not greatly different in cells and in ghosts, i.e., that these proteins are also situated asymmetrically at the outer cell envelope membrane.

Amino Acids↗