Comparison of the kidney fungal burden in experimental disseminated candidiasis by species of the Candida parapsilosis complex treated with fluconazole, amphotericin B and caspofungin in a temporarily neutropenic murine model.

BACKGROUND: The efficacy of fluconazole (FLU), amphotericin B (AMB) and caspofungin (CAS) was tested against three Candida orthopsilosis, three C. metapsilosis and two C. parapsilosis sensu stricto isolates in neutropenic mice. METHODS: Mice were immunosuppressed by 200 mg/kg cyclophosphamide. Five-day intraperitoneal treatment was started 24 h after infection. Kidney burden was analyzed using the Kruskal-Wallis test. RESULTS: FLU 10 and 20 mg/kg as well as AMB 1 mg/kg significantly decreased the fungal burden (p < 0.05) for all eight isolates of the three species. CAS 2 and 5 mg/kg were efficacious against all C. orthopsilosis and C. metapsilosis isolates (p < 0.05), but only 5 mg/kg CAS was effective against C. parapsilosis isolates (p < 0.05). CONCLUSIONS: The efficacy of FLU and AMB against the three species was comparable. Though the activity of CAS was higher against C. orthopsilosis and C. metapsilosis, the current treatment guidelines for C. parapsilosis sensu stricto seem to be applicable to other 'psilosis' species.

[Methionine metabolism. 2. Biochemical and histological studies in rats]. / Untersuchung des Methionin-Stoffwechsels. 2. Biochemische und histologische Untersuchungen an Ratten

Male rats weighing 100 g were used in a 19-day trial. The rats received diets containing varying proportions of methionine. Their absolute liver weight was lower, due to the high methionine levels, than that of the animals fed optimum rations, whereas the relative liver weight was found to be lower only in the pair-fed group. No essential differences were observed between the levels of dry matter, protein, and fat. Glycogen levels were found to be lowered only in cases when high methionine doses were administered. Pathologically low levels of glycogen were found in animals of the pair-fed group. High methionine consumption reduced the percentages of 12 glucogenetic amino acids in the liver. This, in turn, suggests an increased rate of glucose formation from amino acids, a process which was not observed in animals of the pair-fed group. High methionine doses produced a condition of hyperglycaemia, while in the pair-fed group hypoglycaemia was observed. The highest rate of secretion of thyroid hormones was found in animals receiving the optimum ration; a lower rate of secretion was observed in the animals consuming less or more methionine. In animals receiving high methionine levels the rate of hormone secretion decreased in a stepwise manner with increasing methionine supplementation. Only the highest methionine doses (5,3%) were found to have a negative effect on the maximum rate of iodine incorporation into the thyroid gland. These findings were also substantiated by histological investigations because a true pathological picture was only found in histological sections of thyroid tissue from animals fed the highest methionine doses (5,3%) The thyroid tissue of these animals consisted predominantly of small glandular alveoli whose colloid was slightly coloured. The epithelial cells of these alveoli were degenerated; some cases of liver cell disintegration and, more rarely, cellular necrosis were noted.