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PubMedDate not supplied

The effect of complete dentures with a metal palate on candida species growth in HIV-infected patients.

PURPOSE: This in vivo investigation compared the oral candidal population between heat-cured acrylic resin and nickel-chromium-beryllium alloy in maxillary complete dentures in HIV-infected patients. MATERIALS AND METHODS: Split-palate maxillary complete dentures were fabricated for 19 HIV-infected patients: one-half of the palate was made in acrylic resin and the other half in nickel-chromium-beryllium. Patients were divided into low or high CD4+ lymphocyte count groups. Dentures were worn for 5 months. Palatal mucosa was clinically evaluated at baseline, 1, 3, and 5 months after denture insertion. Specimens were collected at 1, 3, and 5 months using a modified imprint culture method. Speciation of Candida was performed using a chromogenic culture medium. Two-sample t-test was employed to determine effects and significant interactions between the control and test groups and the low and high CD4+ lymphocyte groups. A chi(2) test analyzed and compared the results of the clinical evaluation (p < 0.05). RESULTS: Significant differences were observed in the colony counts between both materials during the third (p= 0.046) and fifth months (p= 0.039). The low CD4+ group demonstrated significant differences during the third (p= 0.03) and fifth months (p= 0.05). There were no significant differences between the species of Candida that colonized either material with the exception of Candida dubliniensis (p < 0.001) and "Others" (p < 0.001) during the first and fifth months. There were no significant differences on the clinical appearance of the palatal mucosa between both materials (p= 1.00). CONCLUSIONS: The metal base proved to be effective in decreasing the fungal growth typically present in complete dentures. Although overt clinical manifestations were not present, colony counts of Candida species were high in the acrylic resin denture bases of these patients. This investigation demonstrated that metal base complete dentures provide an important alternative dental service for edentulous HIV-positive and other patients who are particularly prone to higher incidences of fungal infections.

Acrylic Resins↗
PubMed2006

Candida biofilms on implanted biomaterials: a clinically significant problem.

In recent years there has been an increasing appreciation that microbial biofilms are ubiquitous, which has resulted in a number of studies on infectious diseases from a biofilm perspective. Biofilms are defined as structured microbial communities that are attached to a surface and encased in a matrix of exopolymeric material. A wide range of biomaterials used in clinical practice have been shown to support colonization and biofilm formation by Candida spp., and the increase in Candida infections in the last decades has almost paralleled the increase and widespread use of a broad range of medical implant devices, mainly in populations with impaired host defenses. Formation of Candida biofilms has important clinical repercussions because of their increased resistance to antifungal therapy and the ability of cells within biofilms to withstand host immune defenses. Further recognition and understanding of the role of Candida biofilms in human infection should help in the clinical management of these recalcitrant infections.

Biofilms↗
PubMed1995

Cleavage of human big endothelin-1 by Candida albicans aspartic proteinase.

A Candida albicans aspartic proteinase (CAP), one of the secretory proteinases of Candida albicans, is thought to be a possible virulence factor in Candida albicans infection. Whereas endothelin-1 is found as an endothelium-derived strong vasoconstrictive peptide, it is known to have a role in the maintenance of vascular homeostasis and tissue survival. Endothelin-1 is generated from a precursor form of endothelin-1, the so-called big endothelin-1. It has recently been reported that cathepsin D, E and pepsin, which are aspartic proteinases, convert big endothelin-1 to endothelin-1. In this study, the relationship between CAP and big endothelin-1 was studied. High performance liquid chromatography analysis revealed that big endothelin-1 was cleaved into several amino acid sites by CAP, but endothelin-1 was not converted from big endothelin-1. CAP cleaved big endothelin-1 at different sites when compared with that of other known aspartic proteinases, and it suppressed endothelin-1 production through the degradation of big endothelin-1. CAP may break homeostatic mechanism of endothelin-1 in Candida albicans infectious lesions.

Amino Acid Sequence↗
PubMed1996

Use of polymorphic short and clustered coding-region microsatellites to distinguish strains of Candida albicans.

We describe the identification of polymorphic microsatellite loci in the pathogenic yeast, Candida albicans. A search for all coding-region microsatellites with more than four repeats that can be found in Candida sequences in GenBank was conducted. Nine such microsatellite sequences consisting of trinucleotide motifs were found. Three of these were perfect microsatellites while the remaining six sequences were found in one imperfect microsatellite and two compound microsatellites. Because of the close proximity of some of these repeats, all could be assayed with six PCR primer pairs. All of these microsatellite sequences were found in five nuclear genes, ZNF1, CCN1, CPH1, EFG1, and MNT2. Except for a single (CTT)5 serine tract, all coded for polyglutamine tracts. Another locus with seven alleles, a region of the ERK1 protein kinase gene, was also examined, and may be a representative of a new class of highly polymorphic "clustered' microsatellites. Such loci, in which several non-contiguous but closely linked microsatellites are clustered together, may be a useful source of DNA polymorphisms in microorganisms in which long microsatellite sequences are unavailable. All seven regions amplified were polymorphic, having between two and seven variable length alleles in the 11 strains of Candida albicans examined. The results of this and similar searches will facilitate epidemiological and evolutionary studies of Candida and other microorganisms.

Alleles↗
PubMed1999

Modulation of neutrophil function in host defense against disseminated Candida albicans infection in mice.

Neutrophils (PMNs) constitute the main mechanism of host defense against acute invasive and disseminated candidiasis. Recent studies have demonstrated that tumor necrosis factor-alpha (TNFalpha), interleukin-6 (IL-6) and granulocyte colony-stimulating factor (G-CSF) play an important role in the recruitment of PMNs at the site of invasive Candida infection. In the absence of either TNFalpha or IL-6, the course of experimental disseminated candidiasis is more severe, due to defective PMN recruitment. Treatment of mice with recombinant G-CSF (rG-CSF) leads to a significantly reduced mortality during disseminated candidiasis. The outgrowth of Candida albicans from the organs of rG-CSF-treated mice is significantly decreased. Treatment with the combination of rG-CSF and fluconazole has an additive effect on the reduction of fungal load in the organs. In subacute or chronic disseminated Candida infection, rG-CSF is less effective, indicating that neutrophil recruitment and activation are crucial in acute, life-threatening candidiasis, whereas other host defense mechanisms control the outcome of less overwhelming invasive Candida infection.

Animals↗
PubMed1996

Genetic speciation of Candida isolates by arbitrarily primed polymerase chain reaction.

Candida species are opportunistic human pathogens capable of causing a variety of clinical diseases. Rapid and precise identification of Candida to species level is essential for effective treatment and management strategies. Conventional diagnosis of candidiasis is sometimes slow and variable. By using a random primer 5'-ACGGGCCAGT-3' in arbitrarily primed polymerase chain reaction, seven common Candida species (i.e., C. albicans, C. guilliermondii, C. parapsilosis, C. krusei, C. lipolytica, C. tropicalis and C. (Torulopsis) glabrata) produced characteristic DNA band patterns, which enabled rapid determination to species level among them. Further analysis of the nucleotide sequences of Candida specific fragments should improve our understanding of the molecular structures and possible functions of the gene regions involved.

Candida↗
PubMed2000

Cellular actin is affected by interaction with Candida albicans.

Attachment of Candida albicans, an important opportunistic pathogen, to host tissues is an initial step in the development of the infection. The events occurring in the fungal and in the host cells after interaction are poorly understood. In this study we concentrated on the events occurring in the mammalian cells after the interaction with Candida, with emphasis on the cytoskeleton actin. Human cell line cells (HEp2) were exposed to C. albicans or C. albicans-secreted material (culture filtrate) (actin-rearranging Candida-secreted factor, arcsf). The HEp2 cells were examined for cellular changes using confocal laser microscopy (CLSM), transmission and scanning electron microscopy (TEM and SEM). The CLSM studies, using fluorescein isothiocyanate-labeled C. albicans and rhodamine phalloidin actin staining, revealed yeasts adhering to the HEp2 cells or internalized into the cells, with actin surrounding the fungi. Furthermore, actin rearrangement from filamentous network to actin aggregates was noticed. Interaction between the HEp2 cells and C. albicans could be demonstrated also by SEM and TEM after a 2-4-h exposure of the cells to the fungus. Yeasts and hyphae were found attaching to the surface and within the cells. CLSM studies revealed that exposure of HEp2 cells to arcsf was also followed by cellular actin rearrangement, reduced membrane ruffling and decreased cellular motility. The effect was dose- and time-dependent. All these data indicate that the interaction of Candida with HEp2 cells involves signaling events and affects the cellular actin.

Actins↗
PubMed1997

Effects of tetracycline hydrochloride and chlorhexidine gluconate on Candida albicans. An in vitro study.

This study examined the effects of tetracycline hydrochloride (TCN) and chlorhexidine gluconate (CHX) on the growth and viability of Candida albicans. Subcultures of Candida albicans on Sabouraud's agar, were divided into 5 treatment groups: group 1, untreated control; group 2, 0.12% CHX; group 3, 3.0 mg/ml TCN adjusted to pH 4.5; groups 4 and 5, sodium azide free Tris buffer adjusted to pH 4.5 and pH 7.4, respectively. All groups were incubated for 10 days, and sampled and subcultured daily to determine the viability of each group. Additional samples from group 2 (day 4), group 4 (day 7) and all groups at day 10 were selected for SEM and TEM examination. Visual, SEM and TEM results showed that for groups 1, 3, 4, and 5 there was a heavy and constant uniform growth of Candida albicans throughout the period of the study. However, group 2 (CHX), showed decreasing viability and attachment from day 3 to day 10, with SEM and TEM revealing decreased blastospores and profound changes in the ultrastructural morphology, indicating inhibition of normal cell growth and replication. These results show that TCN even when used at high concentrations, in vitro, will allow uninhibited growth of Candida albicans whereas CHX inhibits cell growth and replication.

Adhesiveness↗
PubMed1990

Salivary levels of mutans streptococci, Lactobacillus, Candida, and Veillonella species in a group of Scottish adolescents.

Salivary levels of mutans streptococci, Lactobacillus, Candida, and Veillonella species were investigated on three occasions at annual intervals in a group of 372 Scottish adolescents. Counts of the micro-organisms studied were logarithmically distributed, with Candida spp. being isolated from approximately half the subjects. Counts of lactobacilli, mutans streptococci, and candida were significantly intercorrelated, while veillonella were associated consistently with mutans streptococci alone. Levels of each of the four micro-organisms were significantly correlated over the three examinations, with levels of the Candida spp. being the most stable over the period studied.

Adolescent↗
PubMed1998

Prevalence of Candida species in AIDS patients and HIV-free subjects in Thailand.

The purpose of this study was to examine the prevalence of Candida species among groups of HIV-infected and HIV-free subjects in Thailand and to ascertain whether particular Candida species were associated with HIV infection. Oral rinse specimens were collected from 45 AIDS patients (CDC stage IV), 74 HIV-free healthy subjects, and 42 HIV-free patients who had clinical candidiasis. Yeasts recovered in culture were identified and quantified. The mean ages of the cohorts were 30.75+/-8.19 years (AIDS group), 28.50+/-7.98 (HIV-free healthy group) and 41.83+/-12.25 years (HIV-free candidiasis group). Yeasts were isolated from 30/45 (66.66%, range 6.6x10(2)-5.7x10(6) CFU/ml) of the AIDS group, 8/74 (10.81%, range 8.0x10(1)-3.5x10(4) CFU/ml) of the HIV-free healthy group, and 24/42 (57.14%, range 1.0x10(2)-1.1x10(5) CFU/ml) of the HIV-free candidiasis group. There were statistically significant differences in the Candida colony counts between the AIDS group without oral candidiasis and the healthy group (P=0.0078) and between the AIDS group with candidiasis and the HIV-free, oral candidiasis group (P=0.0003). Candida albicans was the most common species recovered from AIDS patients (29 out of 30; 96.66%).

AIDS-Related Opportunistic Infections↗
PubMed2001

Malassezia and Candida infections in bull terriers with lethal acrodermatitis.

In 12 cases of lethal acrodermatitis (LAD), four sampling techniques (brush, swab, scrape and adhesive tape strip) were used to study the distribution of yeasts in various body sites and these results were compared with those from five cases of atopic dermatitis and those of 10 normal dogs. Malassezia was frequently isolated from lesional and non-lesional skin and haircoat, footpads, nails and mucous membranes from dogs with either LAD or atopic dermatitis, although, generally, more Malassezia organisms were isolated from LAD cases. In normal dogs, Malassezia was most frequently recovered from the ear canal and the perianal skin. Candida was isolated frequently from dogs with LAD, but only a single isolate of this yeast was found in the other two groups. Fungal hyphae and pseudohyphae, probably Candida albicans, could be detected in samples collected from the nails and footpads of dogs with LAD. Both Malassezia and Candida could be isolated using all four sampling techniques. The MacKenzie (toothbrush) technique and adhesive tape strip cultures proved simple methods for the semiquantitative evaluation of yeasts. The high recovery rate of Malassezia and Candida from dogs with LAD is probably related to immune dysfunction, particularly T-cell dysfunction, known to be present in these dogs. C albicans infection may in part be responsible for the pathogenic changes of the nails and footpads commonly seen in cases of LAD.

Acrodermatitis↗
PubMed2001

[In vitro assay method for augmention of anti-Candida activity of murine bone marrow cells by cytokines].

It is important to develop a sensitive assay method for evaluation of immunomodulating candidates including granulocyte-colony stimulating factor (G-CSF) which may augment host defense function against opportunistic infections. Effects of CSFs on anti-Candida activity of bone marrow cells (BMC) obtained from normal or cyclophosphamide-treated immunocompromised mice (CY-mice) were investigated. When BMC from CY-mice were preincubated for 24 hours in the presense of more than 0.005 ng/ml of G-CSF, anti-Candida activity was enhanced at 160 of effector (BMC) to target (C. albicans) ratio, whereas anti-Candida activity of BMC from CY-untreated mice was not changed at concentrations less than only by more than 0.5 ng/ml of G-CSF. Similar enhancement of activity was also observed in the presence of more than 0.05 ng/ml of granulocyte-macrophage colony stimulating factor (GM-CSF) in this assay using BMC from CY-mice. These findings suggest that this in vitro assay method can evaluate the activity of G-CSF and GM-CSF to augment leukocyte's anti-Candida activity.

Animals↗
PubMed2002

[Clinical utility of serum Candida mannan antigen detection kits using ELISA].

The clinical utility of two serum Candida mannan antigen detection kits with ELISA, UNIMEDI Candida and PLATERIA Candida Ag, was investigated. Thirty-four serum samples from 12 cases with candidemia diagnosed at Kawasaki Medical School Hospital in 1999 and 15 samples from 15 healthy volunteer were examined. The sensitivities and specificities of the two kits were 82.1% and 40.0%, 100% and 100% respectively. This sensitivity was higher than that achieved with the conventional methods. However, it was realized that the discrepancy between the sensitivity of these two kits was quite significant. This may have been caused by a difference in the reactivities of the respective kits against different species of Candida. A combined application of these methods and other supportive diagnostic methods, such as serum (1-->3)-beta-D-glucan detection, will improve their utility. A larger number of cases should be evaluated to clarify the characteristics of these new kits.

Adult↗
PubMed1980

High incidence of sensitivity to yeast killer toxins among Candida and Torulopsis isolates of human origin.

Among yeast strains of human origin belonging to the genera Candida, Cryptococcus, Torulopsis, and Rhodotorula which were examined for killer and sensitive characteristics with killer and sensitive strains of Cryptococcus, Hansenula, Kluyveromyces, Pichia, Saccharomyces, and Torulopsis as screening organisms, a high incidence of sensitivity to killer toxins was observed within the genera Candida and Torulopsis. Of 142 strains tested, 116 strains distributed over all Candida and Torulopsis species examined were sensitive to one or more killers. Several new intergeneric killer-sensitive relationships are described. Furthermore, killing activity was exhibited by six strains of Candida (C. krusei, C. guilliermondii) and three strains of Torulopsis (T. glabrata).

Candida↗
PubMed1980

In vitro activities of miconazole, miconazole nitrate, and ketoconazole alone and combined with rifampin against Candida spp. and Torulopsis glabrata recovered from cancer patients.

A total of 440 fresh clinical isolates of yeasts from cancer patients were tested by an agar dilution technique against miconazole, miconazole nitrate, and ketoconazole individually and combined with 5 micrograms of rifampin per ml. Most strains of Candida albicans were susceptible to 0.5 microgram or less of the imidazoles per ml. Candida tropicalis required 2 to 4 micrograms of miconazole and its nitrate base per ml for inhibition and was resistant to ketoconazole. The 100% minimal inhibitory concentration of the imidazoles for Candida krusei was 1 microgram/ml. Susceptibility to 4 micrograms of miconazole and miconazole nitrate per ml occurred in 73 and 87% of Torulopsis glabrata strains, respectively, and none was susceptible to ketoconazole. Miconazole was most effective against the Candida spp., whereas its nitrate base was most active against T. glabrata. Synergy was observed when rifampin was combined with miconazole and miconazole nitrate but was not observed when rifampin was combined with ketoconazole. Synergy occurred most frequently when rifampin was combined with miconazole nitrate.

Antifungal Agents↗
PubMed1994

Fluconazole susceptibilities of Candida species and distribution of species recovered from blood cultures over a 5-year period.

The distribution and fluconazole susceptibilities of Candida species isolated over a 5-year period were investigated. Susceptibilities were determined by using a new microtiter procedure and the National Committee for Clinical Laboratory Standards (NCCLS) proposed standard. The new method correlated well with the NCCLS proposed standard and gave very clear end points. Results indicate that there are species-related differences in MICs as reflected in the MICs for 90% of species tested. Candida albicans is most susceptible to fluconazole, while Candida glabrata is among the least susceptible. These findings coincided with the observation of a shift in distribution of yeast species recovered from blood cultures from 1987 to 1992. C. albicans was the predominant species (87%) in the pre- or early fluconazole years but decreased to only 31% of the isolates in 1992. Thus, Candida species for which MICs of fluconazole were higher have become more prominent in recent years. Significantly, throughout this period, MICs for each species did not change appreciably.

Candida↗
PubMed1995

Identification of the aminocatechol A-3253 as an in vitro poison of DNA topoisomerase I from Candida albicans.

The aminocatechol A-3253 is active against several pathogenic fungi, including Candida albicans, Cryptococcus albidus, and Aspergillus niger. A-3253 interferes with both the in vitro biosynthesis of (1,3)-beta-glucan and the activity of topoisomerases I isolated from Candida spp. It is likely that one or more of the enzymes involved in glucan biosynthesis rather than topoisomerase I is the primary intracellular target of A-3253, since a strain of Saccharomyces cerevisiae lacking topoisomerase I is as susceptible to A-3253 as cells containing wild-type levels of topoisomerase I. However, the interaction of A-3253 with topoisomerase I in vitro is of interest since the Candida topoisomerase is more susceptible to A-3253 than is the topoisomerase I isolated from human HeLa cells. A-3253 is both a reversible inhibitor of topoisomerase I catalysis and a reversible poison of topoisomerase I, and in both reactions the fungal topoisomerase I is more susceptible than the human topoisomerase I to A-3253. In contrast, an earlier study found that the human topoisomerase I is more susceptible than the fungal topoisomerase to camptothecin (J. M. Fostel, D. A. Montgomery, and L. L. Shen, Antimicrob. Agents Chemother. 36:2131-2138, 1992). Taken together with the response to camptothecin, the greater susceptibility of the Candida topoisomerase I to A-3253 suggests that there are structural differences between the human and fungal type I topoisomerases which can likely be exploited to allow for the development of antifungal agents which act against the fungal topoisomerase and which have minimal activity against the human enzyme.

Antifungal Agents↗
PubMed1997

Comparison of the in vitro activities of the echinocandin LY303366, the pneumocandin MK-0991, and fluconazole against Candida species and Cryptococcus neoformans.

Two new glucan synthesis inhibitors, the echinocandin LY303366 and the pneumocandin MK-0991 (formerly L-743,872), were studied for their antifungal activities in vitro in relation to each other and in relation to the activity of the triazole fluconazole. Systematic analysis of broth macrodilution testing by varying the starting inoculum size, medium composition, medium pH, temperature of incubation, length of incubation, or selection of endpoints failed to identify significant differences in antifungal activity for either LY303366 or MK-0991 in comparison to the activity under standard test conditions specified for other antifungal agents in National Committee for Clinical Laboratory Standards (NCCLS) document M27A. Under standardized conditions, both drugs exhibited prominent activity against Candida species including Candida glabrata and Candida krusei but showed little activity against Cryptococcus neoformans. This spectrum of activity differed from that of fluconazole, which exhibited marginal activity against C. glabrata and C. krusei but prominent activity against other Candida species and C. neoformans. For individual strains, broth microdilution MICs of LY303366 and MK-0991 were similar to but frequently higher than broth macrodilution results. In contrast, fluconazole broth microdilution MICs were often lower than broth microdilution results. We conclude that the test conditions specified in NCCLS document M27A are applicable to these two new glucan synthesis inhibitors and that systematic differences between broth microdilution procedures and the broth macrodilution reference standard will need to be addressed before the two test methods can be used interchangeably.

Anidulafungin↗