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Biomedical subjects

R F Cosgrove

Publications and source records attributed to R F Cosgrove.

15 recordsLinked to original sources

In-vivo studies of amphotericin B liposomes derived from proliposomes: effect of formulation on toxicity and tissue disposition of the drug in mice.

The repeat dose toxicity of various liposomal formulations containing amphotericin B has been determined in mice. In general, small liposomes (e.g. 100-150 nm) were found to be more toxic than their large counterparts (e.g. about 2000 nm). However, the repeat dose toxicity of small liposomes could be diminished substantially by the inclusion of sterol (i.e. ergosterol) into the liposomal membranes. Tissue accumulation studies of amphotericin B after repeat dosing may be a useful adjunct to formulation development.

Amphotericin B

Assessment of oral candidiasis in patients with respiratory disease and efficacy of a new nystatin formulation.

Fifty consecutive patients with respiratory diseases who developed oropharyngeal candidiasis were assessed clinically and microbiologically before and after seven days' treatment with nystatin suspension or pastilles (a new formulation). In 45 patients in whom microbiology yielded positive results there was frequent associated use of oral corticosteroids, antibiotics, sedatives, and inhaled corticosteroid, while in a few patients atropine analogues may have predisposed to infection. Dentures were worn by 32 of the infected patients. Concomitant treatment of dentures in chronically infected patients appeared to improve the therapeutic response. Pastilles and suspension were equally efficacious both clinically and microbiologically. The potential for enhanced drug delivery to the oropharynx suggests that nystatin pastilles may be useful in patients in whom poor compliance seems likely.

Administration, Oral

Effect of butylated hydroxyanisole on the antifungal activity of amphotericin B.

Monitoring the growth curves of Candida albicans has shown that in the presence of sub-MIC levels of amphotericin B the lag phase is extended. If butylated hydroxyanisole (BHA) is added prior to, or with the amphotericin B the lag phase is extended further. However, if BHA is added after the antibiotic, the growth curve is identical to that produced in the presence of amphotericin B alone. The effect of BHA was found to follow the kinetics of a zero order reaction, and adsorption data for amphotericin B to yeast cells shows that BHA may occupy sites in the cell wall of the organism normally occupied by amphotericin B. It is suggested that if the polyene binding capacity in the cell wall is satisfied by the BHA, then the effective concentration of amphotericin B available to exert its lethal effect on the sterol in the cell membrane is increased.

Amphotericin B

On the uptake of nystatin by saccharomyces cerevisiae. 5 The release of amino acids.

The release of amino acids from Saccharomyces cerevisiae under the action of nystatin has been studied. The kinetic results do not show any dependence upon molecular size but do support earlier results suggesting that interactions depend upon slow diffusion processes through the cell wall. The effects of temperature, sterol concentration and the presence of calcium ion have also been investigated.

Alanine

A study of fluctuations in Escherichia coli sensitivity patterns from pigs fed a halquinol supplemented diet.

Escherichia coli isolated from pigs fed on a medicated diet containing 120 p.p.m. halquinol did not develop any resistance to this addition over a 6-week period. Sensitivity patterns of the E. coli isolates to eight antimicrobial substances, although fluctuating slightly during the test period (but no more than a control group), did not significantly alter. However, the patterns did change significantly when for 17 days after the completion of the halquinol trial the pigs were fed a normal commercial ration medicated with a commonly used feed additive containing chlortetracycline hydrochloride, procaine penicillin and sulphadimidine.

Animals

The application of cryobiology to the microbiological assay of nystatin.

Improvements in the reproducibility of nystatin agar diffusion assays have been achieved by the use of liquid nitrogen stored inocula and deep frozen standard stock solutions. The overall percentage variability of the assay has been reduced from over 5% with daily prepared standards and inocula to around 1% with a frozen inocula and to 0.6% with a combination of frozen inocula and standards. The implications of these improvements in the standardization of nystatin assays, and microbiological assays generally are discussed.

Biological Assay

A comparative study of the microbiological assays currently available for nystatin raw material.

The classical agar diffusion and turbidimetric methods of assay for nystatin are compared with the more recently documented assays for this antibiotic which depend upon physicochemical measurement of the response of micro-organisms. Liquid nitrogen stored inocula were used throughout. It is concluded that the newer methods of assay are as reproducible and reliable as the agar diffusion and turbidimetric methods and that they are generally more sensitive. The choice between the assay methods compared can thus be based on speed, cost and sample through-put.

Biological Assay

Long-term storage of microorganisms used in antimicrobial effectiveness tests.

Liquid nitrogen storage of organisms designated in the U.S. Pharmacopeia (XIX) for the assessment of antimicrobial effectiveness is described. By use of simple apparatus and procedures, 85-95% viabilities of pre-frozen cells are attained immediately upon freezing. Viability levels have remained constant over a 3-year period and the use of such inocula has considerably improved the reliability of the test. The superiority of liquid nitrogen storage for microbial test inocular over other types of storage is discussed.

Bacteria

In vitro activity of chlorhydroxyquinoline against mycoplasma species.

The in vitro activities of 5-chloro-8-hydroxyquinoline (CHQ) against single strains of 12 different species of mycoplasma and the impacts of repeated exposure of these strains to CHQ on their susceptibility to this agent have been studied. On initial exposure, the minimal inhibitory concentrations for these strains ranged from 0.24 to 1.92 micrograms of CHQ per ml of test medium; activities remained unchanged during 10 serial transfers in CHQ-containing medium.

Chloroquinolinols

In vitro studies of amphotericin B in combination with the imidazole antifungal compounds clotrimazole and miconazole.

The clinically important polyene antibiotic amphotericin B, in combination with two antifungal imidazole compounds, clotrimazole and miconazole, was studied in vitro. With use of results of cytoplasmic leakage, metabolic heat output, and minimal inhibitory concentration studies, a definite antagonistic response was demonstrated. It is suggested that, if combined antifungal drug therapy is clinically indicated, the drug combination be tested against the isolate by the simple technique of measuring cytoplasmic leakage or by the more elaborate method of flow microcalorimetry.

Adsorption

Bioassay method for polyene antibiotics based on the measurement of rubidium efflux from rubidium-loaded yeast cells.

A bioassay method for the polyene antibiotics nystatin and amphotericin B is proposed based on the measurement of the efflux of rubidium ions from a rubidium-loaded yeast culture challenged with the antibiotics. For this purpose a major proportion of the intracellular K(+) ions in a Saccharomyces cerevisiae culture has been substituted by Rb(+) ions. The rubidium leakage is measured by atomic absorption spectrophotometry, and a straight-line, dose-response correlation has been obtained for both antibiotics.

Amphotericin B