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Candida-specific interferon-gamma deficiency and toll-like receptor polymorphisms in patients with chronic mucocutaneous candidiasis.

Chronic mucocutaneous candidiasis (CMC) is a group of disorders, characterised by persistent mucocutaneous infections with Candida species. The underlying defect of CMC has not been elucidated, but a defective cytokine response may be involved. Therefore, we investigated whether an imbalance between IFNgamma and IL-10 may play a role in this disorder. We assessed the cytokine production in whole-blood cultures from CMC patients using Candida albicans, lipopolysaccharide and phytohaemagglutinin as stimuli. As the Toll-like receptors are important pattern recognition receptors for Candida species, we also investigated Toll-like receptor polymorphisms in these patients. Patients with CMC had a significantly decreased IFNgamma production when whole blood was stimulated with C. albicans (232 +/- 120 vs 2279 +/- 609 pg/ml, p<0.02). When stimulated with phytohaemagglutinin, the differences were not significant (3549 +/- 1320 vs 7631 +/- 1790 pg/ml). The Candida-stimulated production of IL-10 tended to be higher in CMC patients, whereas TNF and IL-1beta production were similar in patients and controls. Stimulation with LPS showed no differences in cytokine production between patients and controls. Two out of seven patients had the TLR4 Asp299Gly polymorphism and none had the TLR2 Arg677Trp polymorphism. These data support the hypothesis that deficient IFNgamma production is involved in the pathogenesis of CMC, whereas a role for genetic polymorphisms of Toll-like receptor 2 and 4 is not obvious in these patients.

Adolescent↗

[The characteristics of the ultrastructural changes in yeast-like fungi of the genus Candida exposed to therapeutic-range ultrasound and nystatin].

The electron microscopic study of the ultrastructure of yeast-like fungi of the genus Candida under the action of nystatin and sonication, as well as the action of these two factors used in combination, was carried out. In this study the degree of preservation of the structure of fungal cells was evaluated and the percentage of cells with different ultrastructural changes was determined. Observations made 3 and 24 hours after sonication and treatment with nystatin, used in combination, showed that ultrastructural changes in fungal cells were more pronounced than in the cells subjected to the action of nystatin alone. 24 hours after the combined physico-medicinal treatment of Candida the percentage of nonviable blastospores among them was 5-fold higher than that of such cells among Candida subjected to treatment with nystatin alone and more than 20-fold higher than among Candida subjected only to sonication. These data on the increased fungicidal effect of nystatin used in combination with sonication substantiate the expediency of the above-mentioned physico-medicinal treatment in cases of candidal lesions of the skin and its appendages, which is one of the ways for increasing the effectiveness of the treatment of this mycosis.

Candida albicans↗

Candida biofilms: antifungal resistance and emerging therapeutic options.

Intravascular catheter infections are a major cause of morbidity and mortality in hospitalized patients, accounting for the majority of the 200,000 nosocomial bloodstream infections occurring in the US annually. Of the intravenous lines that are culture-positive for Candida, 40% actually represent fungemia, which generally necessitates systemic treatment and line removal to affect cure. Until recently, the reason for the need for device removal was unclear. However, our research group and others have demonstrated a near-total resistance to antifungals by biofilm-associated Candida. Similar to bacterial species, Candida biofilm formation proceeds through early, intermediate and maturation phases. This process is associated with the generation of a polysaccharide extracellular matrix (ECM). Mature C. albicans biofilms have a heterogeneous architecture, in terms of distribution of fungal cells and ECM, and exhibit broad antimicrobial resistance. The mechanisms causing such profound antifungal resistance are beginning to be understood. Recent data indicate that resistance is phase-specific and multifactorial, involving efflux pumps and sterol synthesis (at early and mature biofilm phases, respectively). Neither metabolic quiescence nor the ECM appear to contribute substantially. Susceptibility testing and confocal scanning laser microscopy demonstrated that azoles failed to exert activity against mature Candida biofilms. However, sub-inhibitory concentrations of voriconazole impaired biofilm formation and caused cell morphological aberrations. In contrast, lipid-formulation amphotericins and the echinocandins uniquely exhibited activity against mature biofilms. The mechanisms underlying this ability are unknown. The role of other pharmacological (eg, catheter coatings, antimicrobial peptides and antibiotic locks) and non-pharmacological methods in the prevention and treatment of device-related biofilms is discussed in this review.

Animals↗

[Biofilm production and antifungal susceptibility patterns of Candida species].

In this study, biofilm production and antifungal susceptibility of various Candida species were examined and compared. A total number of 156 Candida species (94 C. albicans, 21 C. tropicalis, 18 C. glabrata, 12 C. parapsilosis, 9 C. krusei, 1 C. guilliermondii and 1 C. kefyr) isolated from different clinical specimens were included in the study. The biofilm production of the strains was searched by modified tube adherence and microplate methods. Their antifungal susceptibilities against fluconazole and amphotericin B were determined by microdilution method, according to NCCLS M27-A2 standards. Forty three (27.6%) and 26 (16.7%) of the strains were found to be slime producing by tube adherence and microplate methods, respectively. The agreement between the two methods were detected as 65 percent. The rate of biofilm formation by different species ranged between 17% and 55% by tube adherence test and 0 and 48% by microplate method. No significant difference was found between the biofilm production of C. albicans and non-albicans species by tube adherence test (p=0.29). However; a statistically important difference was found when microplate method was considered (p=0.04). MIC50 and MIC90 values for fluconazole ranged between 4-64 microg/ml and 32-->64 microg/ml for different Candida species while these values changed between 0.25-1 microg/ml and 0.5-2 microg/ml for amphotericin B, respectively. Forty-five (28.8%) and 23 (14.7%) of the isolates were found to be dose dependent susceptible and resistant to fluconazole, respectively. Eleven (6.7%) of the strains had MIC values >1 microg/ml for amphotericin B. When the relation between the biofilm production and the susceptibility categories of the strains for amphotericin B were searched, no statistical differences were found by any of the two methods (p=0.12 and p=0.50). A statistically important difference (p=0.03) was determined by tube adherence test and no important difference (p=0.11) was detected by microplate method when fluconazole susceptibility categories were considered. As a conclusion, it has been determined that biofilm production which is a potential virulence factor for Candida species seems to be in agreement with the antifungal susceptibility categories of the strains especially for amphotericin B when the planktonic cells were used for the susceptibility testing.

Amphotericin B↗

[Long terminal repeats of retroposons in Candida albicans].

25 Candida albicans strains have been analysed on Southern hybridization patterns with alpha, beta, gamma, kappa probes. The alpha, beta, gamma, kappa, elements can be used to distinguish the differences and relations between C. albicans strains. Chromosomal localization analysis indicated that the alpha, beta, gamma, kappa, elements were located on several different chromosomes in Candida albicans strains. Northern hybridization showed that alpha, beta, gamma were transcribed actively and regulated by different stimuli. The kappa was inactive. Our results indicated that in Candida albicans there were many kinds of retroposons whose numbers and distribution were different. These retroposons could be used to identify Candida albicans strains as moleculer markers.

Blotting, Northern↗

[Candida albicans adhesion to plastics during correction of removable dentures].

Colonisation of denture soft lining materials by Candida albicans can result in clinical problems. The presence of Candida albicans on the upper fitting surface of the denture is a major causative factor in denture-associated chronic atrophic candidosis (denture stomatitis). The fitting surface of denture can act as a reservoir of Candida albicans. The goal of our experiment was to determine of candidal adherence to two soft lining materials -- Ufi gel C temporary and Ufi gel P permanent. Results of experiment show that adherence of Candida albicans to the Ufi gel C temporary was significantly move than for Ufi gel P permanent.

Bacterial Adhesion↗

Isolation and characterization of Candida spp. in Jordanian cancer patients: prevalence, pathogenic determinants, and antifungal sensitivity.

The presence of Candida spp. in the oral cavity was evaluated in 95 cancer patients (57 in-patients and 38 out-patients) and in 65 healthcare workers in Amman, Jordan. Candida carriage occurred in 72.6% of cancer patients and 33.8% of healthcare workers, with Candida albicans being the species most commonly recovered, followed by C. glabrata. In-patients were found to harbor Candida spp. at significantly higher levels than out-patients (P = 0.0044). The number of adhered C. albicans cells and the secretion of extracellular proteinase was significantly higher in the in-patient group than in the out-patient group (P = 0.0016 and 0.00007, respectively); this significant difference was not observed regarding phospholipase secretion. Antifungal sensitivity testing data suggest that isolates were most sensitive to amphotericin B and nystatin, and least sensitive to miconazole and fluconazole, which are commonly used antifungal agents in Jordan.

Adult↗

Clinical features of patients showing Candida hypersensitivity: an observational study.

BACKGROUND: The significance of Candida albicans as an allergen is still unclear. This study aimed at investigating the clinical features of patients monosensitized to Candida. METHODS: Thirty-four adult patients monosensitized to the yeast Candida albicans selected from a population of >7000 subjects and referred for suspect respiratory allergy were studied. Ninety subjects monosensitized to different airborne allergens served as controls. Both patients and controls underwent a clinical examination at the ENT department to detect possible nasal polyps. RESULTS: Male and female patients were equally distributed (17/17). The mean age of the patients was 58.4 years (range 23-75 years; median 59 years) vs 29.9 years (range 9-62 years) in controls (p <0.001). At baseline examination, 15 (44%) patients vs 5/90 (6%) controls were diagnosed as having nasal polyposis (p< 0.001). Polyposis was bilateral in 13/15 (87%) patients; 3 had "massive" polyps, and 4 had a clinical history of prior surgical intervention to remove nasal polyps. Eight patients (24%) had asthma, previously diagnosed as intrinsic in six cases. No patient had a history of aspirin-induced asthma (i.e. ASA triad). After one year 1/11 (9%) patients without polyps at the baseline examination had developed bilateral nasal polyposis. CONCLUSION: Candida-hypersensitivity is uncommon, occurs in older ages, and is strongly associated with nasal polyposis.

Adolescent↗

Prevalence of Candida albicans and Trichomonas vaginalis in pregnant women in Havana City by an immunologic latex agglutination test.

We aimed to estimate the prevalence of Candida albicans and Trichomonas vaginalis in immunocompetent pregnant women living in Havana City, Cuba, with or without symptoms of vaginitis, using a sample of 640 women from 6 Gyneco-obstetrics hospitals, which represents 2.5% of total yearly pregnant women. Diagnosis was made using a new latex agglutination kit (Newvagin C-Kure, La Habana, Cuba). Clinical sensitivity and specificity of this assay were validated against culture method, with 467 and 489 clinical specimens for Candida albicans and Trichomonas vaginalis, respectively. Results showed that the kit clinical sensitivity was 100% for Candida albicans and 86.7% for Trichomonas vaginalis compared with a clinical specificity of 93.3% for Candida albicans and 95.1% for Trichomonas vaginalis by culture. The prevalence of candidiasis was determined to be 42.3% (95% confidence interval [CI] 3.8%); the prevalence of trichomoniasis was 9.84% (95% CI 2.3%). In our sample, 48.7% of the women tested negative with respect to both candidiasis and trichomoniasis. Only 6.41% of the cases yielded inconclusive results. The test has high sensitivity, and our results indicate a relatively high prevalence of both infections. However, a significant difference (P < .001) was also observed in candidiasis and trichomoniasis prevalence among hospitals corresponding to the quantity of women with clinical vaginitis. No difference was observed between diabetics and nondiabetics, probably due to the special care of diabetic pregnant women. We conclude that the method is useful for this kind of vaginitis prevalence study and that candidiasis and trichomoniasis prevalences in pregnant women of Havana are 38.5% to 46.2 % (95% CI) and 7.5% to 12.1% (95% CI), respectively.

Candida albicans↗

Candida tropicalis arthritis of the knee in a patient with acute lymphoblastic leukaemia: successful treatment with caspofungin.

Candida arthritis in patients with a haematological malignancy is rare. We report a case of Candida tropicalis arthritis of the knee that occurred in a patient with acute lymphoblastic leukaemia during the recovery phase of post-chemotherapy neutropenia. Although the Candida tropicalis isolates from synovial fluid and synovial tissue were sensitive to fluconazole in vitro, a 6-week course of oral treatment failed to produce clinical improvement. The arthritis resolved after 7 weeks of combination therapy with caspofungin, a new echinocandin class of antifungal agent that acts primarily on the cell wall. Eleven other reports of Candida arthritis in patients with a haematological malignancy were reviewed.

Antifungal Agents↗

Periodontal status and sulcular Candida albicans colonization in patients with primary Sjögren's Syndrome.

OBJECTIVE: The purpose of this study was to compare the periodontal status and prevalence of sulcular Candida albicans between subjects with primary Sjögren's Syndrome (SS-1) and healthy control subjects. MATERIAL AND METHODS: Ten SS-1 subjects and 10 age- and sex-matched control subjects were recruited. All subjects met the comprehensive European Community Criteria for primary Sjögren's Syndrome. Periodontal probing depth (PD), clinical attachment loss (CAL), plaque and gingivitis were scored on index teeth in each subject. Gingival crevicular fluid (GCF) volume was measured from the same teeth using Periopaper strips. Candida albicans presence was determined by plating paper strips directly into culture media tubes (Oricult kit). RESULTS: Despite having similar mean PD measures and gingivitis and plaque scores, SS-1 subjects who had Sjögren's Syndrome for a mean of 8.8 years had significantly more CAL (5.4 mm vs 2.7 mm; P < .01) and GCF (101.3 +/- 4.25 microL vs 33.0 +/- 1.91 microL; P < .001) than healthy control subjects. Candida albicans was detected in the sulci of only one SS-1 subject and in none of the control subjects. CONCLUSION: These data indicate that the cohort of the SS-1 patients in this particular study have significantly more gingival recession and GCF than do control subjects. The increased attachment loss in SS-1 patients is not attributed to an increase in colonization of the gingival sulci by Candida albicans organisms.

Adult↗

[In vitro study of oral Candida albicans in virulence from HIV-positive individuals].

OBJECTIVE: To study the influence of Candida albicans on human immunodeficiency virus (HIV)-positive individuals susceptible to oral candidiasis. METHODS: In vitro secreted aspartyl proteinase activities, adhesion to healthy buccal epithelial cells of Candida albicans isolates from oral cavities of subjects with and without HIV infection were measured. RESULTS: The pathogenetic isolates of Candida albicans from HIV-positive patients were significantly lower than that from HIV-negative subjects (P < 0.01) in secreted aspartyl proteinase activities and adhesion to buccal epithelial cells. There was no difference in commensals between these two groups. In the HIV-positive group, no difference was found between the pathogenetics and the commensals. However, in the HIV-negative group, the virulence of the pathogen was significantly higher than the commensals (P < 0.01). CONCLUSIONS: These results indicate that oral candidiasis was not correlated with some predominant strains of Candida albicans with higher virulence in HIV-positive subjects.

Acquired Immunodeficiency Syndrome↗

[Phospholipase activity of Candida species isolated from different clinical samples].

In this study, the phospholipase activity that was suggested to be important in the pathogenesis of Candida infections, has been investigated. A total of 109 Candida strains (80 Candida albicans, 10 C. tropicalis, 6 C. glabrata, 6 C. guilliermondii, 4 C. parapsilosis, 2 C. krusei, 1 C. kefyr) which were isolated from various clinical specimens (blood, cerebrospinal fluid, parasynthesis specimens, catheter samples, bronchoalveolar lavage fluid, tracheal aspirate, liver abscess) have been included in the study. Phospholipase activities were evaluated by modified plate method. Phospholipase activity (Pz) was determined as the ratio of colony diameter to the diameter of precipitation zone with the colony. While 61.3% (49/80) of C. albicans strains were found to be positive for phospholipase activity, none of the non-albicans Candida isolates exhibited phospholipase activity. The mean Pz coefficient value of phospholipase secreting isolates was calculated as 0.805 +/- 0.08. There was no statistically significant difference between the phospholipase activity of the isolates according to their isolation sites (chi2 = 5.5; p = 0.137).

Candida↗

A rapid PCR-based method for identification of four important Candida species.

The rapid detection and identification of Candida species in clinical laboratories are extremely important for the management of patients with hematogenous candidosis. Currently available culture and biochemical methods for detection and identification of Candida species are time-consuming. This study describes the use of a simple and rapid PCR method using species-specific oligonucleotides for the detection of clinical isolates of Candida species. These species-specific oligonucleotides are complementary to unique sequences within the intergenic transcribed spacer 2, located in between the 5.8S and 28S ribosomal DNA, and generated DNA fragments by both the conventional and hemi-nested PCR reactions. Conventional PCR produced a single DNA fragment of variable size in all isolates, while the hemi-nested PCR produced two discrete DNA fragments, both with the expected sizes of 111bp/57bp (C. albicans), 84bp/42bp (C. glabrata), 94bp/45bp (C. krusei) and 95bp/49bp (C. parapsilosis). In conclusion, the PCR-based method described in this study is fast and specific for the identification of clinically important Candida species.

Candida↗

[Decolorization of synthetic dyes with a new isolated yeast Candida krusei].

A new yeast isolate Y-G-1, identified as Candida krusei, capable of degrading Reactive Brilliant Red K-2BP, was obtained from soil by screening experiments. This strain gave a maximal decolorization (99%) for Reactive Brilliant Red K-2BP (200 mg/L) after incubation of 12 h. In order to get this decolorization effect, the optimal inoculation volume of Candida krusei was not less than 5%, the optimal pH of culture medium was within a range from 4 to 9, and the concentrations of (NH4)2SO4 and glucose were not lower than 0.1% and 0.5%, respectively. The research results on the mechanism of decolorization show that Candida krusei could biodegrade Reactive Brilliant Red K-2BP. In addition, Candida krusei could also decolorize 62% - 96% of another 9 dyes (50mg/ L). Specially for azo dyes, including Weak Acid Brilliant Red B, Reactive Black KN-B and Reactive Red M-3BE, their decolorization rates were over 90 %, and for triphenylmethane dye, Mordant Blue B, it was up to 93%. All these results indicate that this strain have potential application in dye wastewater treatment.

Azo Compounds↗

[The study of adhesion of Candida albicans to the selected acrylic resins].

The study has been performed on 3 acrylic resins used to fabricate removable dentures. Aim of the study was to detect possible differences in Candida albicans' adhesion within particular materials. Polished and non-polished samples were made, than these samples were sunk in precipitates containing Candida albicans material. Adhesion of Candida albicans to the surface of the materials occured within a concentration of 10. After 24 hours of incubation differences were found concerning the number of the plate cultures. Most of all plate cultures were observed on Lucitone 199, fewer on Zhermacryl, the poorest one was found on Palaxpress resin. Considerable number of plate cultures occured on non-polished samples relating to polished ones. After 48 hours of incubation further development of Candida albicans took place, with differences concerning various materials.

Acrylic Resins↗

Induction of experimental Candida arthritis in rats.

Experimental arthritis, caused by intravenously (IV) introduced Candida albicans, has been induced for the first time in rats. Four-week-old Sprague-Dawley rats were inoculated IV with three different strains of C. albicans and observed for 4 weeks. Each of the three strains tested was able to produce arthritis. The incidence of Candida arthritis increased in a dose-dependent manner and was more than 90% at sublethal doses. Joints of the limbs were affected predominantly, and at higher doses arthritis was produced in multiple (four or five) joints in individual animals, showing it to be polyarthritis. C. albicans was recovered from all cultures of affected limb joints, which were excised 12, 19 and 28 days after inoculation and showed different stages and degrees of joint swelling. Results of histopathology and radiography showed that the Candida arthritis involved not only periarticular inflammation but also changes in joint bones. In particular, metaphyseal enlargement, punched-out lesions at the diaphysis and the appearance of osteoclasts were the most prominent changes in affected bones. These pathological features are compared with those of Candida arthritis in humans.

Animals↗

[Vaginal candida infection in the third trimester of pregnancy].

The aim of this study is the determination of the frequency of vaginal Candida colonization in pregnant women in the third trimester, the status of the vaginal ecosystem, the grade and the subspecies of the candidal colonization, clinical manifestations and the therapeutic effect of the local antimycotic treatment. In this study it has been followed 172 pregnant women with a normal pregnancy at the end of the third trimester. It has been estimated that about 28.4% of all women get a vaginal yeast colonization - Candida spp. In 89.7% (44 women) of the cases, the colonization was caused by an overgrowth of the yeast Candida albicans. The remaining cases are caused by other subspecies of Candida - 5 cases (10.3%) - C. tropicalis /2/, C. parapsilosis /2/, C. glabrata/1/. The women in the first group were with symptoms of active candidosis (25.6%) and 88.3% of the cases were confirmed by microscopy, and 90.6% after a bacterial growth in a culture. In 7.7% of the cases was specified a mild to moderate colonization without a clinical signs of infection (II group). The local treatment with antimycotic vaginal globules and crème for 5 to 7 days alleviates the clinical symptoms. It was not observed a case of maternal - fetal transmission of this infection not a clinical manifestation in the early postpartal period.

Candida↗