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J F Ryley

Publications and source records attributed to J F Ryley.

At least 19 recordsLinked to original sources
PubMed1996

Cure of short- and long-term experimental Chagas' disease using D0870.

Chagas' disease, a protozoan infection by the kinetoplastid Trypanosoma cruzi, constitutes a major public health problem in Latin America. With the use of mouse models of both short- and long-term forms of the disease, the efficacy of D0870, a bis-triazole derivative, was tested. D0870 was able to prevent death and induced parasitological cure in 70 to 90 percent of animals, in both the short- and long-term disease. In contrast, currently used drugs such as nifurtimox or ketoconazole prolonged survival but did not induce significant curing effects. D0870 may be useful in the treatment of human long-term Chagas' disease, a condition that is currently incurable.

Animals↗
PubMed1990

Pathogenicity of 5-fluorocytosine resistant strains of Candida albicans.

Mutants of Candida albicans blocked in pyrimidine transport and salvage metabolism were produced by a two step mutagenic procedure and selected by their resistance to 5-fluorocytosine (flucytosine). The growth rates and growth yields of these mutants did not differ significantly from the parental strain of C. albicans. Examination of their pathogenicity to mice demonstrated that a defect in the uridine transport function decreased the pathogenicity of C. albicans.

Animals↗
PubMed1990

Candida albicans--do mycelia matter?

Growth of Candida albicans in the mycelial phase is neither necessary for initiation of infection in the kidney of the mouse, following intravenous inoculation, nor for the establishment of chronic renal colonization. However, mycelial formation would appear to be important in the establishment of pelvic lesions with their associated pathological changes. Two mycelia-less mutants, CA-2 and MM2002, in the early stages of infection tended to develop in the glomeruli of the mouse kidney cortex while the wild-type parent strains spread throughout the cortex and medulla, with only occasional involvement of glomeruli. The mutants appeared to stimulate a milder inflammatory response than the parent strains. In chronic infections with wild-type strains, tangled masses of mycelia filled the renal pelvis, but pyelonephritis and hydronephrosis did not depend on a persistent cortical infestation. Yeasts of the mutant strains persisted in the body of the kidney and stimulated a continuing neutrophil response. Systemic infections with wild-type strains were eliminated by treatment with low doses of an azole antifungal drug, ICI 195,739, or with amphotericin B, whereas systemic infections with the mutant strains were much reduced, but not eliminated, by relatively high doses of either of the two drugs. Unlike azole drugs, amphotericin B does not show differential activity against the two morphological forms of C. albicans. Because kidney infections with the mutant strains are relatively resistant to amphotericin B as well as the azole tested, we conclude that the impressive activity of azoles in vivo may not be explained entirely by their inhibition of mycelial growth.

Amphotericin B↗
PubMed1988

A multi-infection model for antifungal screening in vivo.

A new in-vivo antifungal screen is described in which each mouse is given a vaginal infection with Candida albicans, a dermal infection with Trichophyton quinckeanum, a systemic infection with Can. albicans and a lung infection with Cryptococcus neoformans. Mice are dosed orally once daily on days 0-3 and infections evaluated on day 6 by visually scoring the dermal lesions and by culturing vaginal samples and kidney and lung homogenates. Mice carrying the multiple infections show no signs of distress at this time. Validation studies with eight antifungal agents show there is no interference between the four infections, and illustrate the different patterns of activity which result from differences in innate sensitivity and pharmacological behaviour of drugs in the host. This screen provides the maximum amount of information for a minimal investment of compound and effort, and naturally uses fewer animals than multiple tests using single infections.

Animals↗
PubMed1988

Activity of ICI 195,739--a novel, orally active bistriazole--in rodent models of fungal and protozoal infections.

ICI 195,739 shows superior potency to other azoles in eliminating vaginal candidosis or dermatophyte infections in animal models of infection by both oral dosing and topical application; effective doses are in the range of 0.5-5.0 mg/kg/day or 0.01-0.30% in a topical formulation. ICI 195,739 is likewise effective in models of systemic fungal infection; 1, 10, 25 mg/kg/day will protect animals given a lethal inoculum of C. albicans, C. neoformans, or A. fumigatus, respectively, as long as dosing is continued, showing activity in this respect superior to that of other azoles tested. ICI 195,739 will suppress infections in mice with T. cruzi and prevent mortality with five daily doses of 1 mg/kg; cure rather than suppression of patent infections has been achieved with 35 daily doses of 10 mg/kg.

Animals↗
PubMed1986

Quantification of vaginal Candida albicans infections in rodents.

Estradiol-treated mice and estradiol-treated ovariectomized rats support vaginal infections with Candida albicans for several months; low-grade uterine infections occur in around half the animals. A comparison has been made and the relative advantages discussed of quantifying these infections by sampling with a wire loop and plating on BiGGY agar, sampling by vaginal washing, or removal and homogenization of the vagina followed by dilution and plate counting.

Animals↗
PubMed1985

A comparison of phospholipase activity, cellular adherence and pathogenicity of yeasts.

Phospholipase A and lysophospholipase activities were measured in the culture fluid and in the blastospores of Candida albicans. When phospholipase activity was measured in six yeasts (four strains of C. albicans and a single strain each of Candida parapsilosis and Saccharomyces cerevisiae) a correlation was found between this activity and two potential parameters of pathogenicity. The C. albicans isolates which adhered most strongly to buccal epithelial cells and were most pathogenic in mice had the highest phospholipase activities. Non-pathogenic yeasts, including C. albicans isolates which did not adhere and did not kill mice, had lower phospholipase activities.

Candida↗
PubMed1984

Azole resistance in Candida albicans.

Two isolates of Candida albicans from chronic mucocutaneous candidosis patients who initially responded to ketoconazole treatment but who later relapsed, have shown an abnormal response to ketoconazole in four out of five systems in vitro and in three animal models of vaginal or systemic infection. They have also shown abnormal resistance to inhibition of ergosterol biosynthesis in whole cells, but not in cell-free systems, and to inhibition of amino acid uptake. We conclude that the behaviour of the isolates is consistent with the development of drug resistance to ketoconazole. In all systems the two isolates have shown cross-resistance to the triazole antifungal ICI 153,066. In addition they fail to take up radiolabelled ICI 153,066--in contrast to normal isolates--indicating that resistance is due to changes in the properties of the cell membrane rather than internal enzymology.

Amino Acids↗
PubMed1978

The use of vitamin K deficient diets in the screening and evaluation of anticoccidial drugs.

Vitamin K (as menaphthone sodium bisulphite) added to a deficient diet reduced mortality due to Eimeria tenella or E. necatrix, had a slight effect on haematocrit, but had no obvious effect on weight gain or faecal blood; 0.1 ppm gave a maximal response. The effect of vitamin K on mortality was not absolute; the magnitude of the effect depended on the size of the challenge dose of oocysts. Likewise, the response of an infection to anticoccidial drugs, particularly monensin, depended on the severity of challenge. The effect of adding vitamin K in the presence of drug was to effectively reduce the coccidial challenge; no other interaction of vitamin K and drug has been found. No effects with vitamin K deficiency or supplementation were seen in cases of infections with E. acervulina, E. brunetti or E. maxima. The use of a deficient diet for experimental work is therefore quite justified--particularly as it results in a 4-fold saving of oocysts for inoculation purposes in the case of the haemorrhagic species.

Animals↗