Effects of gastrointestinal candidiasis, antibiotics, dietary arabinitol, and cortisone acetate on levels of the Candida metabolite D-arabinitol in rat serum and urine.

We studied the effects of gastrointestinal (GI) colonization by Candida albicans, dietary arabinitol, intragastric antibiotics, and cortisone on levels of the Candida metabolite D-arabinitol in rat serum and urine. Rats given conventional laboratory chow, intragastric gentamicin and chloramphenicol, and 6.0 x 10(8) live C. albicans B311 blastoconidia by gavage had minimal invasive GI disease and no more DL-arabinitol in the urine than controls given killed C. albicans. However, colonized and uncolonized rats given intragastric antibiotics had transiently higher urine arabinitol levels than the corresponding controls given saline. Rats given conventional laboratory chow (which contained 50 micrograms of arabinitol per g) had higher serum and urine arabinitol levels than rats given no dietary arabinitol, but the differences were less than expected. Moreover, intragastric antibiotics did not cause increased arabinitol excretion in rats given no dietary arabinitol. Rats given intragastric antibiotics and live C. albicans but no dietary arabinitol had no more arabinitol in their serum or urine than controls given antibiotics and killed C. albicans or saline and live or killed C. albicans. Lastly, cortisone acetate (10 mg/kg of body weight per day intramuscularly for 10 days) did not cause increased serum or urine arabinitol levels. We conclude that neither GI colonization by C. albicans nor cortisone should interfere with the usefulness of arabinitol as a marker for invasive candidiasis; antibiotics appear to increase arabinitol excretion by suppressing GI bacteria capable of consuming dietary arabinitol.

Levels of the Candida metabolite D-arabinitol in sera of steroid-treated and untreated patients with sarcoidosis.

We measured the Candida metabolite D-arabinitol and its enantiomer L-arabinitol in 42 serum samples from 33 patients with sarcoidosis and compared the results with those from 27 healthy adults and 4 patients with candidiasis. The D- and L-arabinitol concentrations and the D- and L-arabinitol/creatinine ratios did not differ significantly in the sarcoidosis patients and the controls; the D-arabinitol concentrations and the D-arabinitol/creatinine ratios were much higher in the patients with candidiasis. Among the patients with sarcoidosis, the D- and L-arabinitol levels in the steroid recipients did not differ significantly from those in patients not receiving steroids. Higher D-arabinitol/creatinine ratios were associated with roentgenographic evidence of pulmonary fibrosis and low forced vital capacities, but not with disease activity as determined by the proportion of lymphocytes to total nucleated cells in bronchoalveolar lavage fluid or the CD4/CD8 ratio in bronchoalveolar lymphocytes. We conclude that neither sarcoidosis nor corticosteroid treatment is associated with high levels of D-arabinitol in serum.

Increased amounts of the Aspergillus metabolite D-mannitol in tissue and serum of rats with experimental aspergillosis.

Several Aspergillus species produce large amounts of the hexitol D-mannitol in vitro, but it is not known whether these species also produce D-mannitol in vivo. Serum samples and homogenized tissues were analyzed from rats pretreated with cortisone and cyclophosphamide and then given 2 x 10(6) preincubated conidia of Aspergillus fumigatus intravenously. The resulting infection was lethal by 48 h and was characterized by much more severe disease in the liver than in the kidneys, spleen, or lungs. A compound present in increased amounts in the livers and sera of the infected rats was shown to be D-mannitol by gas chromatography (GC) and GC/mass spectrometry and enzymatically. Quantitative analysis by GC showed that the infected rats had more D-mannitol in their livers (but not in their lungs or kidneys) after 12 h (P less than .01 at 12, 24, and 36 h) and higher serum D-mannitol concentrations and serum D-mannitol/creatinine ratios after 36 h (P less than .05) than did uninfected controls. These results indicate that A. fumigatus can produce and release sufficient D-mannitol in the tissues of infected animals to raise serum D-mannitol levels. Thus, D-mannitol is a potential diagnostic marker for aspergillosis.

Enantioselective measurement of fungal D-arabinitol in the sera of normal adults and patients with candidiasis.

A new method was used to measure D-arabinitol enantioselectively in the sera of 27 healthy adults and four patients with candidiasis. Arabinitol was measured by gas chromatography in serum that was treated with and without the Klebsiella pneumoniae enzyme D-arabinitol dehydrogenase, lactic dehydrogenase, NAD, and sodium pyruvate. Since enzyme treatment removed 98% of 0 to 20 micrograms of D-arabinitol per ml and none of 0 to 20 micrograms of L-arabinitol per ml from spiked sera, D-arabinitol could be determined from the difference in the treated and untreated samples. The concentrations of D- and L-arabinitol in serum from normal subjects were 0.22 +/- 0.052 and 0.16 +/- 0.055 micrograms/ml, respectively, and their D-arabinitol/creatinine and L-arabinitol/creatinine ratios were 0.024 +/- 0.0089 and 0.017 +/- 0.0053 (all means +/- standard deviations). The infected patients all had markedly elevated serum D-arabinitol levels, but their L-arabinitol levels were either normal or proportionately much lower. The excess arabinitol in the sera of individuals with candidiasis is D-arabinitol, and use of enantioselective analytical methods should result in improved ability to diagnose and estimate the severity of candidiasis.

Induced parasexual processes in Claviceps sp. strain SD58.

A homokaryotic, clavine alkaloid-producing strain of ergot, Claviceps sp. strain SD 58, was used in an attempt to demonstrate parasexuality. Genetically marked auxotrophic strains were produced by mutation with N-methyl-N'-nitro-N-nitrosoguanidine. Protoplast fusion of pairs of unlike doubly auxotrophic strains and isolation of stable prototrophic fusion products were carried out. By growth of the fusion products on complete medium, selective pressure for prototrophy was removed and auxotrophic segregants were allowed to form. Analysis of these and recovery of segregants with nonleaky, non-parent-type combinations of auxotrophic characteristics has provided strong evidence that a parasexual cycle can function in Claviceps sp. strain SD 58. Preliminary work suggests that the genetics of ergot might be studied by mitotic analysis and that protoplast fusion and selection procedures might be useful for the enhancement of favorable characteristics in Claviceps strains.