Candidiasis In Rats Research Articles

Development of a Gold Immunochromatographic Assay Method Using Candida Biofilm Antigen as a Bioreceptor for Candidiasis in Rats

AbstractThe gold immunochromatography assay (GICA), a new immunochromatography technique, uses a nitrocellulose membrane as a carrier and a colloidal gold-labeled antigen or antibody as a tracer (bioreceptor). This technology has many advantages over other immunoassays, including its simplicity, rapidity, cheapness, and the lack of a requirement for special training or expensive equipment, and it can be used to detect either antigens or antibodies. Therefore, we chose to develop this method for the diagnosis of candidiasis in Indonesia. The objective of the present study was to develop a diagnostic test for Candida albicans in rats using the GICA method. GICA bioreceptors were developed from biofilm antigens isolated from biofim Candida albicans grown on the surface of nitrocellulose membranes. The formation of biofilms was confirmed using scanning electron microscopy. Antigen levels as bioreceptors were optimized by using the immuno dot method. The samples to be analyzed were antibody serum, in the form of blood serum samples from heart mice that have been induced to become candidiasis. To this end, we optimized the antigen and antibody volumes necessary to make this diagnosis. The results show that the optimum concentration of antigen to be used in the test is 2.5 μg/μL and the optimum volume of antibody is 10 μL. The control rats produced a single red stripe on the control line and the candidiasis rat samples produced a double red stripe, with the bottom line being the control line and the upper line the test line. The test chip was successfully used for the diagnosis of candidiasis in rats and given the name “Candiday Kit.”. We anticipate that this test will be suitable for the diagnosis of candidiasis in humans

Evaluation of antifungal activity of blended cinnamon oil and usnic acid nanoemulsion using candidiasis and dermatophytosis models

Abstract Fungal infections are one of the most important health issues facing by people since a long time. The objective of the present study was to evaluate antifungal activity of a prepared blended cinnamon oil and usnic acid nanoemulsion (CUN) using candidiasis and dermatophytosis models both in vitro and in vivo. In vitro activity was performed using cup plate method; minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs) were determined using brain heart infusion (BHI). In vivo antifungal activity was determined on cutaneous candidiasis in rats and on dermatophytosis guinea pig model. In vitro study of CUN exhibited maximum antifungal activity after 48 h. The maximum zone of inhibition was 1.19 cm for CUN (10 mg/mL), which was near to the fluconazole (1 mg/mL) i.e. 1.82 cm. The MIC of CUN for C. albicans and T. mentagrophytes were 60 and 55 μg/mL, respectively, which was more than cinnamon oil and usnic acid solution (CUS). In vivo study of CUN in cutaneous candidiasis model showed significant antifungal activity. The log colony forming unit per infected site of CUN was 1.36 in comparison to untreated control group (3.91). However, the clinical efficacy profile of CUN on dermatophytosis guinea pig model was more than the standard drug (41.3%) and CUS (35.6%). Its mycological efficacy was 81.4%, which was greater than standard drug (79.6%) and CUS (74.5%). Thus, the present study substantiated that CUN can be used as a feasible formulation for topical application against fungal infections.

Induction of Severe Chronic Hyperplastic Candidiasis in Rat by Opportunistic Infection of C. albicans through Combination of Diabetes and Intermittent Prednisolone Administration

Chronic hyperplastic candidiasis progresses from squamous cell hyperplasia to squamous cell carcinoma (SCC); however, the oncogenic mechanism remains unclear. In the present study, we attempted to induce opportunistic Candida albicans infection and establish chronic hyperplastic candidiasis in rats by combining diabetic condition and prednisolone administration, followed by analysis of the inflammatory cells involved in the disease progression. Female Wistar Bunn/Kobori (WBN/Kob) rats were divided into 3 groups: alloxan-induced diabetic rats (A group) along with diabetic (AP group) and nondiabetic (P group) rats intermittently treated with prednisolone. Animals were euthanized at 42 weeks of age. Squamous cell hyperplasia following C. albicans infection in the forestomach was observed in almost all AP and A group rats. The lesions in the AP group were significantly more severe than those in the A group. In addition, SCC was detected in 1 AP group animal. Cluster of differentiation (CD)4-positive T cell and CD68-positive macrophage infiltration in the AP group was significantly stronger than that in the A group. These findings suggest that the combination of diabetes and intermittent prednisolone administration could induce chronic hyperplastic candidiasis without direct C. albicans inoculation and that CD4-positive T cells and CD68-positive macrophages may be highly involved in the pathogenesis of these hyperplastic lesions.

Potentiating Antifungal Activity of Fluconazole or Nystatin with Methanol Bark Extract of Harungana madagascariensis Stem Bark

The therapeutic failures and the increasingly high costs of treating resistant bacterial infections calls for alternative means of care. The present study was initiated to evaluate the antifungal properties of the Harungana madagascariensis methanol barks extract and potent interactions with some usual drugs. The extract was prepared by maceration of the dry stem bark powder in methanol. Phytochemical analysis was carried out by colorimetric assays. Antifungal activity as well as interactions between extract, Nystatin or Fluconazole was evaluated by broth microdilution method. The therapeutic efficacies of H. madagascariensis extract and Fluconazole – extract mixture as compared to Fluconazole extract was studied in experimental models of oral and vulvovaginal candidiasis in rats by oral route. Results showed that methanol extract of H. madagascariensis stem barks had antifungal activity ranging from 128 to 1024 µg/ml. This extract also had a fungicidal activity on all of the tested yeasts. Moreover, the extract presented in vitro synergetic and additive interactions with Nystatin and Fluconazole. In both oral and vaginal infection model, all the treatment significantly reduced (P less than 0.05) the number of colony formant unit (UFC) of C. albicans compared with untreated control. Moreover, significant decrease in the percentage of animals showing positive cultures was observed in rats treated with Fluconazole-extract mixture. In both therapeutic efficacy studies, the histological findings confirmed the microbiological results. The results of this study constitute a base for the usage of H. madagascariensis stem barks in association with Fluconazole to overcome yeast infection.

Efficacy of an oral and tropically stable lipid-based formulation of Amphotericin B (iCo-010) in an experimental mouse model of systemic candidiasis

ObjectiveAn oral lipid based formulation that exhibits tropical stability (iCo-010) was developed to enhance the absorption of orally administered amphotericin B (AmB). iCo-010 has previously shown high efficacy in an acute model of systemic candidiasis in rats, directing the focus of this study to be its efficacy in a chronic model of systemic candidiasis in mice.MethodsMice were infected with 0.6 to 1×108 CFUs of Candida albicans ATCC 18804 strain by tail vein injection and were left for three days to develop the infection after which time treatment was initiated. The infected animals were assigned to the following treatment groups: no treatment (control) or iCo-010 at 5, 10 and 20 mg/kg administered by oral gavage once daily (QD) for 5 consecutive days. The animals were sacrificed 7 days after the last dose and the concentration of AmB and the fungal burden were assessed within the liver, kidneys, heart, lungs, spleen and brain.ResultsAlthough the infection was relatively low (~ 60–100 CFUs/ 1 ml tissue homogenate) in the liver, lungs and heart, the infection level was very high (70 000 CFUs / 1 ml tissue homogenate) in the kidney tissues for the control group. The highest concentrations of AmB were recovered in the kidneys and the spleen. The fungal burden in the tissues was lowered by 69-96% in the treatment groups when compared to the control group.ConclusionOral iCo-010 is an effective treatment of systemic candidiasis in the mouse model.

Antimicrobial photodynamic therapy in rat experimental candidiasis: evaluation of pathogenicity factors of Candida albicans

This study evaluated the effects of photodynamic therapy on pathogenicity of Candida albicans. Fifty-six rats were submitted to development of candidiasis on the tongue dorsum by C. albicans inoculations. After 5 days, different treatments were administered: laser and photosynthesizer methylene blue (L+P+); laser only (L+P-); photosensitizer only (L-P+); and physiologic solution only (L-P-). Samples of the oral cavity were collected for a count of colony-forming units per mL. Colonies were isolated for evaluation of proteinase and phospholipase activities. The rats were killed for microscopic analysis of the tongue dorsum. The data were analyzed by analysis of variance, Kruskal-Wallis, and Bonferroni tests. The number of C. albicans recovered from the oral cavity of the rats was similar between the groups (P = .106). The L+P+ group showed fewer microscopic lesions of candidiasis than the L-P- group (P = .001). The L+P+ group presented lower proteinase activity compared with the other groups, with significant difference between the groups L+P+ and L-P+ (P = .018). Photodynamic therapy reduced the microscopic lesions of experimental candidiasis in rats and inhibited the proteinase activity of C. albicans.

Candida parapsilosis-specific Monoclonal Antibodies and Their Use for Detection of Candida Antigens in Experimental Systemic Candidiasis

Candida parapsilosis has emerged as one of the most common causes of bloodstream infection worldwide. The diagnosis of invasive candidiasis etiological agents to the species level remains a laboratory and clinical challenge. Thus, specific monoclonal antibodies to detect systemic candidiasis and to identify Candida virulence factors and associated pathogenesis through immunohistochemistry would be very useful. Inbred Balb/c mice were immunized with C. parapsilosis antigens, and blood was checked for the presence of reactive antibodies using ELISA. Fusion was performed using the harvested spleen cells and NS1 myeloma cells, and the clones were screened for the presence of antibody producing hybrid cells by dot-blot. The 1B11 clone secreted IgG2a monoclonal antibody that was reactive with the C. parapsilosis antigen at MW of 59 kDa and cross-reacted with C. tropicalis but not with other fungal and bacterial antigens tested. Another 3D1 clone secreted IgG1 monoclonal antibody that was reactive with C. parapsilosis antigen at MW of 30 kDa. The 3D1 monoclonal antibody was found to be species specific. Experimental systemic candidiasis in rats was induced through intravenous injection of C. parapsilosis, and all the vital organs were collected for immunohistochemistry study. These monoclonal antibodies were reactive against surface epitopes on the yeast cells, pseudohyphae, and immune complexes in tissue sections. Sandwich ELISAs using these antibodies were developed and were able to detect circulating antigens in experimental candidiasis in rats at 0.2 μg/μL. These monoclonal antibodies may have potential as primary capture antibodies for the development of rapid diagnostic test for human systemic fungal infection.

Effects of Psychological Stress and Fluoxetine on Development of Oral Candidiasis in Rats

Psychological stress has been found to suppress cell-mediated immune responses that are important for limiting the proliferation of Candida albicans. Fluoxetine has been observed to reduce negative consequences of stress on the immune system in experimental and clinical models, but there are no data on its effects on oral candidiasis. We designed experiments to evaluate the effects of fluoxetine on the development of oral candidiasis in Sprague-Dawley rats exposed to a chronic auditory stressor. Animals were submitted to surgical hyposalivation in order to facilitate the establishment and persistence of C. albicans infection. Stress application and treatment with drugs (placebo or fluoxetine) were initiated 7 days before C. albicans inoculation and lasted until the end of the experiments, on day 15 postinoculation. Establishment of C. albicans infection was evaluated on days 2 and 15 after inoculation. Tissue injury was determined by the quantification of the number and type (normal or abnormal) of papillae on the dorsal tongue per microscopic field. A semiquantitative scale was devised to assess the degree of colonization of the epithelium by fungal hyphae. Our results showed that stress exacerbates C. albicans infection in the tongues of rats. Significant increases in Candida counts, the percentage of the tongue's surface covered with clinical lesions, the percentage of abnormal papillae, and the colonization of the epithelium by hyphae were found in stressed rats compared to the nonstressed ones. Treatment with fluoxetine significantly reversed these adverse effects of stress. Besides the psychopharmacological properties of fluoxetine against stress, it has consequences for Candida infection.

Photodynamic therapy for the treatment of buccal candidiasis in rats

The study objective was to evaluate the effects of photodynamic therapy on buccal candidiasis in rats. After experimental candidiasis had been induced on the tongue dorsum, 72 rats were distributed into four groups according to treatment: treated with laser and methylene blue photosensitizer (L+P+); treated only with laser (L+P-); treated only with photosensitizer (L--P+); not treated with laser or photosensitizer (L-P-). The rats were killed immediately, 1 day, or 5 days after treatment, for microscopic analysis of the tongue dorsum. Observation verified that the photodynamic therapy group (L+P+) exhibited fewer epithelial alterations and a lower chronic inflammatory response than the L-P- group. The group L+P- presented more intense epithelial alterations and chronic inflammatory response than the remaining groups. The L-P+ group showed tissue lesions similar to those of the L-P- group. In conclusion, rats treated with photodynamic therapy developed more discrete candidiasis lesions than did the remaining groups.

Effects of psychological stress and alprazolam on development of oral candidiasis in rats.

Psychological stress has been found to suppress cell-mediated immune responses that are important in limiting the proliferation of Candida albicans. Since anxiolytic drugs can restore cellular immunity in rodents exposed to stress conditions, we designed experiments conducted to evaluate the effects of alprazolam (1 mg/kg of body weight/day), a central benzodiazepine anxiolytic agonist, on the development of oral candidiasis in Sprague-Dawley rats exposed to a chronic auditory stressor. Animals were submitted to surgical hyposalivation in order to facilitate the establishment and persistence of C. albicans infection. Application of stress and treatment with drugs (placebo or alprazolam) were initiated 7 days before C. albicans inoculation and lasted until the end of the experiments (day 15 postinoculation). Establishment of C. albicans infection was evaluated by swabbing the inoculated oral cavity with a sterile cotton applicator on days 2 and 15 after inoculation, followed by plating on YEPD (yeast extract-peptone-dextrose) agar. Tissue injury was determined by the quantification of the number and type (normal or abnormal) of papillae on the dorsal tongue per microscopic field. A semiquantitative scale was devised to assess the degree of colonization of the epithelium by fungal hyphae. Our results show that stress exacerbates C. albicans infection of the tongues of rats. Significant increases in Candida counts, the percentage of the tongue's surface covered with clinical lesions, the percentage of abnormal papillae, and the colonization of the epithelium by fungal hyphae were found in stressed rats compared to those found in the unstressed rats. Treatment with alprazolam significantly reversed these adverse effects of stress, showing that, besides the psychopharmacological properties of this anxiolytic drug against stress, it has consequences for Candida infection.

Efficacy of ER-30346, a novel oral triazole antifungal agent, in experimental models of aspergillosis, candidiasis, and cryptococcosis.

ER-30346 is a novel oral triazole with a broad spectrum of potent activity against a wide range of fungi. In the present study, we investigated the therapeutic effects of oral ER-30346 on experimental local infections caused by Aspergillus fumigatus, Candida albicans, and Cryptococcus neoformans and compared them with those of itraconazole and fluconazole. In experimental murine models of pulmonary aspergillosis, candidiasis, and cryptococcosis, ER-30346 reduced the numbers of CFU in the lungs significantly compared with the numbers of CFU in the lungs of the controls (P < 0.05). ER-30346 was as effective as or more effective than itraconazole against pulmonary aspergillosis. Against pulmonary candidiasis and cryptococcosis, ER-30346 was more effective than itraconazole and was as effective as fluconazole. ER-30346 was also effective against pulmonary candidiasis caused by fluconazole-resistant C. albicans. In mice with intracranial cryptococcosis, ER-30346 reduced the numbers of CFU in the brains significantly compared with the numbers of CFU in the brains of the controls (P < 0.05) and was more effective than itraconazole and as effective as fluconazole. In an experimental model of oral candidiasis in rats, ER-30346 reduced the numbers of CFU in oral swabs significantly compared with the numbers of CFU in oral swabs from the controls (P < 0.05) and was more effective than itraconazole and as effective as fluconazole. Thus, ER-30346 shows efficacy in murine aspergillosis, candidiasis, and cryptococcosis models. Further studies are needed to determine the potential of ER-30346 for use in the treatment of these infections.

The in vitro activity of terconazole against yeasts: Its topical long-acting therapeutic efficacy in experimental vaginal candidiasis in rats

The activity of the broad-spectrum triazole antifungal terconazole was evaluated in vitro by the serial decimal dilution technique in broth media. The best correlation between in vitro and in vivo activity was found in brain-heart infusion broth and Eagle's minimum essential medium. All strains of Candida albicans, C. tropicalis, C. krusei, C. parapsilosis, C. guilliermondii, C. glabrata, and Trichosporon beigelii tested were susceptible. Terconazole blocked the morphogenetic transformation from the yeast into the filamentous form at concentrations of 0.008 to 0.05 microgram/ml. In experimental candidiasis in castrated rats with estrogen-induced permanent pseudoestrus, topical treatment with terconazole was superior to miconazole, clotrimazole, econazole, butoconazole, tioconazole, sulconazole, bifonazole, valconazole, fenticonazole, nystatin, and amphotericin B in the various schedules used. A 3-day once-daily intravaginal application of terconazole 0.8% was usually sufficient to provide a functional therapeutic period of 7 days because of prolonged high biologically active antifungal levels in the vagina. No side effects were observed at any concentration of terconazole.

In vivo efficacy of SM-8668 (Sch 39304), a new oral triazole antifungal agent

SM-8668 (Sch 39304) is a new oral antifungal agent which we evaluated in comparison with fluconazole in various fungal infection models. The prophylactic effect of SM-8668 was excellent against systemic candidiasis, aspergillosis, and cryptococcosis in mice. The 50% effective dose for SM-8668 was assessed at 10 days after infection and was 0.18, 3.7, and 5.9 mg/kg (body weight), respectively, for the above-mentioned fungal diseases. Fluconazole was about four times less effective than SM-8668 against systemic candidiasis and was only slightly effective at doses of 80 and 25 mg/kg against systemic aspergilosis and cryptococcosis, respectively. SM-8668 was also about four to eight times more active than fluconazole against vaginal candidiasis in rats and against dermatophytic infection in guinea pigs. In addition, topical SM-8668 was as effective as topical miconazole or tioconazole against skin mycosis in guinea pigs. After oral administration, SM-8668 showed a maximum concentration in serum similar to that of fluconazole in both mice and rats, but the elimination half-life and area under the serum concentration-time curve for SM-8668 were twice those for fluconazole.

In vitro susceptibilities of yeasts to a new antifungal triazole, SCH 39304: effects of test conditions and relation to in vivo efficacy

We used six candidal strains (two Candida albicans and one each of four other species) to study the effects of test conditions on the activity of SCH 39304 compared with that of fluconazole in broth macro- and microdilution assays. Increasing the inoculum from 10(2) to 10(5) yeasts per ml raised the MICs for all isolates up to greater than 512-fold. In contrast, results with a 50% turbidimetric endpoint (50% inhibitory concentration; IC1/2) varied no more than twofold. Similar effects were seen with fluconazole, and both drugs were found to have an associated delay in onset of action. Acidity was found to increase both MICs and IC1/2s. Other effects were observed among four synthetic media, but a consistent pattern was not identified. Incubation temperatures of 37, 35, and 30 degrees C yielded equivalent results. Broth microdilution IC1/2s against most of 40 isolates of C. albicans were 0.31 microgram/ml +/- fourfold for SCH 39304 and 0.16 microgram/ml +/- twofold for fluconazole. Treatment of experimental candidiasis in rats with SCH 39304 and fluconazole resulted in 50% effective doses of 0.33 and 0.49 mg/kg per day, respectively. In contrast, another C. albicans isolate, previously identified as resistant to other azoles, had IC1/2s of 20 micrograms of SCH 39304 per ml and, in vivo, a 50% effective dose of 2.25 mg/kg per day. We conclude that the in vivo efficacy of SCH 39304 correlates with MIC results when broth macrodilution testing is performed with a small inoculum and with IC1/2 results which are independent of inoculum size.

Activity of terbinafine in experimental fungal infections of laboratory animals.

The allylamine derivative terbinafine is the first antifungal agent with primary fungicidal properties against dermatophytes which acts systemically after oral application as well as locally after topical application. Comparative oral studies carried out with griseofulvin and ketoconazole in model infections such as guinea pig trichophytosis and microsporosis revealed terbinafine to be superior to the reference compounds both clinically and mycologically. An excellent antimycotic activity of terbinafine was also demonstrable after topical treatment of guinea pig dermatophytoses caused by Trichophyton mentagrophytes or Microsporum canis. Results of comparative chemotherapeutic studies carried out with econazole and tolnaftate demonstrated superior efficacy of terbinafine in the treatment of both trichophytosis and microsporosis. Skin infections of guinea pigs caused by Candida albicans and vaginal candidiasis in rats proved to be responsive to a topical application of terbinafine also. However, the reference compounds, clotrimazole and miconazole, exhibited activity superior to that of terbinafine in both models.

Hormonal factors in vaginal candidiasis in rats.

The hormonal status of rats affected vaginal infection with Candida albicans. Four hours after infection viable counts were higher and germ tubes were longer in those animals in estrous than in other animals. However, the infection was not maintained with the change in epithelial cell type which occurred as part of the estrous cycle. Estrogen dosing following ovariectomy predisposed toward infection, while progesterone dosing did not. In rats injected with progesterone, germ tube clumping was seen, leukocytes were present, and elimination occurred before hyphal growth was evident. In rats injected with estrogen, however, infection was maintained, with hyphal growth extending throughout the cornified epithelial layer. Vaginal washings from rats dosed with estrogen promoted elongation of germ tubes in vitro to a greater extent than washings from other rats. Preincubation of blastospores in progesterone and subsequent infection of rats in pseudoestrous promoted clumping of germ tubes in the vagina. Strains of C. albicans varied in their virulence, which correlated with their ability to produce germ tubes in vitro. Loss of virulence occurred on subculture of a clinical isolate.

Ornithyl amphotericin methyl ester treatment of experimental candidiasis in rats.

After intravenous Candida albicans infection, rats received orinthyl amphotericin methyl ester, amphotericin B, or diluent intravenously. At doses of 0.1 and 0.5 mg/kg, the drugs were equally effective in preventing deaths. However, at doses of 2.0 mg/kg, mortality after treatment with amphotericin B was greater than that after placebo, whereas orinthyl amphotericin methyl ester was fully protective.

Critical role of germ tube formation in the pathogenesis of candidal vaginitis.

A variant strain of Candida albicans incapable of hyphal production at 37 degrees C was used to study the role of germ tube formation in the pathogenesis of experimental vaginal candidiasis in rats. No difference was observed in the in vitro adherence at 25 degrees C of blastoconidia of the variant strain to vaginal epithelial cells when compared with the parent wild-type, germ tube-producing strain and multiple clinical isolates of C. albicans. However, after exposure to conditions favoring germ tube production, the adherence of the variant strain to epithelial cells was significantly less than that of germinated strains (P less than 0.01). In vivo animal studies revealed that the variant strain was less likely to result in vaginal colonization and infection than the wild-type strain and the other clinical isolates. Furthermore, infection, when established, was milder, often transient, and with significantly lower titers of cultured vaginal microorganisms obtained by lavage. Electron microscopic studies confirmed the failure of the variant strain to produce hyphae in vivo. The capacity of C. albicans to produce hyphae appears to be an important but nonessential virulence factor in the pathogenesis of candidal vaginitis.

The antifungal activity of ketoconazole

The antifungal properties of ketoconazole were investigated both in vitro and in vivo. The antifungal potency of ketoconazole in vitro was studied in Sabouraud's broth for 715 fungal strains belonging to 85 species and several strains were tested in other media, including Eagle's minimal essential medium. Ketoconazole is highly active in vitro and possesses broadspectrum activity. Its in vitro activity is largely dependent on the medium used. Ketoconazole's activity is increased in medium enriched with serum and in Eagle's minimal essential medium. Ketoconazole is very potent in the topical treatment of skin dermatophytosis, skin candidiasis, and in vaginal candidiasis of laboratory animals. Ketoconazole is superior to griseofulvin in the oral treatment of skin dermatophytosis. Furthermore, ketoconazole is orally highly active in skin candidiasis in guinea pigs, in vaginal candidiasis in rats, and in gastrointestinal candidiasis in various animal animal species. In systemic candidiasis and in disseminated dermatophytosis in guinea pigs cure with oral ketoconazole is achieved. No side effects are observed.

Increased Arabinitol Levels in Experimental Candidiasis in Rats: Arabinitol Appearance Rates, Arabinitol/Creatinine Ratios, and Severity of Infection

Renal colony counts, total arabinitol appearance, and the arabinitol/creatinine ratios in the serum and urine of rats with lethal candidiasis were measured. Total arabinitol appearance and the arabinitol/creatinine ratios increased significantly after infection. The serum arabinitol/creatinine ratio was high (2 SD above the mean value in normal animals) in five of six infected rats at 24 hr, in eight of eight at 48 hr, and in none of the control animals. The urinary arabinitol/creatinine ratio was high in 14 of 19 infected rats by 24 hr, in 11 of 11 by 48 hr, and in none of the control animals. Total arabinitol appearance and the arabinitol/creatinine ratios were highly correlated with renal colony counts. Arabinitol production in vitro was sufficient to account for the increased arabinitol appearance observed in vivo in 12 of 14 rats. Thus it is concluded that the excess arabinitol that appeared in vivo was produced by the infecting fungus and that arabinitol is a quantitative marker substance for candidiasis.