Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2002 Nov, 94(5), 589 - 92 Candida albicans adherence to resin-composite restorative dental material: influence of whole human saliva; Maza JL et al.; OBJECTIVE: Attachment of Candida albicans to oral surfaces is believed to be a critical event in the colonization of the oral cavity and in the development of oral diseases such as Candida-associated denture stomatitis . Although there is considerable information about the adhesion of C albicans to buccal epithelial cells and prosthetic materials, there is very little information about the adhesion of C albicans to composite restorative materials . The purpose of this study was to investigate the degree of adhesion of C albicans to a resin-composite restorative material (Herculite) . METHODS: The adhesion of 2 strains of C albicans, a germinative and a germ tube-deficient mutant, was studied by a visual method after incubating the fungus and the resin with and without human whole saliva . RESULTS: In absence of saliva, the adhesion of the C albicans germinative isolate to the resin showed an increase in parallel with the germination, reaching a maximum at the end of the experiment (120 minutes) . However, no significant differences were observed in the adhesion of the agerminative mutant during the period of time studied . In the presence of saliva, the adhesion of both isolates to the resin was significantly lowered . CONCLUSION: Germination and the presence of human whole saliva are important factors in the adhesion of C albicans to the resin-composite restorative material Herculite. Folia Microbiol (Praha), 2002, 47(4), 375 - 8 Antimicrobial activity of berberine--a constituent of Mahonia aquifolium; Cernakova M et al.; The antimicrobial activity of the protoberberine alkaloid, berberine, isolated from Mahonia aquifolium, was evaluated against 17 microorganisms including two Gram-negative bacteria--Pseudomonas aeruginosa and Escherichia coli (both resistant and sensitive), two Gram-positive bacteria--Bacillus subtilis and Staphylococcus aureus, Zoogloea ramigera, six filamentous fungi--Penicilium chrysogenum, Aspergillus niger, Aureobasidium pullulans (black and white strain), Trichoderma viride (original green strain and brown mutant), Fusarium nivale, Mycrosporum gypseum and two yeasts--Candida albicans and Saccharomyces cerevisiae . The IC50, minimum inhibitory concentration (MIC), minimum microbicidal concentration (MMC) and minimum microbistatic concentration (MMS) varied considerably depending on the microorganism tested, the sensitivity decreasing as follows: S . aureus > P . aeruginosa S (sensitive) > E . coli S > P . aeruginosa R (resistant) > E . coli R > B . subtilis > Z . ramigera > C . albicans > S . cerevisiae > A . pullulans B (black) > A . pullulans W (white) > T . viride Br (brown) > M . gypseum > A . niger > F . nivale > P . chrysogenum > T . viride G (green). Mycoses, 2002 Nov, 45(9-10), 389 - 92 Bacterial and Candida adhesion to intact and denatured collagen in vitro; Makihira S et al.; Several recent reports imply the possibility of cariogenicity and periodontal disease linked to denture plaque containing Candida albicans . Adhesion of oral bacteria and Candida species to the extracellular matrix, such as type I collagen, fibronectin and denatured type I collagen, was examined by using adenosine triphosphate (ATP) analysis . The adhesion of C . albicans to intact and denatured type I collagen was significantly greater than those of oral bacteria and other species of Candida . This result suggests that C . albicans possesses the ability to adhere specifically to extracellular matrix, as compared with other Candida species or oral bacteria. Mycoses, 2002 Nov, 45(9-10), 345 - 50 New molecular methods to study gene functions in Candida infections; Theiss S et al.; Candida albicans has become a model system for human pathogenic fungi in clinical research, mainly due to the increasing number of Candida infections . Molecular techniques to study C . albicans virulence properties have been improved over the last few years, despite difficulties in genetic manipulation of this fungus . Some of the recent achievements from our own laboratory or from other groups are described in this article . The molecular analysis of the recently identified ATP-dependent transporter Mlt1 using the green fluorescent protein (GFP) as reporter for protein localization and the dominant MPAR gene as a selection marker for gene inactivation provides an example for the study of gene functions in C . albicans. Pol Merkuriusz Lek, 2002 Aug, 13(74), 165 - 7 {Fungal infection in the course of acute liver failure}; Kups J et al.; Fungal infection is a common, serious and underestimated complication, which contributes significantly to high mortality in patients with acute liver injury . The features accounting for the incidence of fungal infection include defects of immune response, routine use of H2 antagonists, frequent use of broad-spectrum antibiotics and invasive monitoring . Clinical deterioration characterized by increasing coma grade after initial improvement, increasing prothrombin time, pyrexia unresponsive to antibiotics, renal failure and elevated white cell count make up the clinical picture of the disease which suggests coexistence of fungal infection in acute liver injury . Candida albicans is the principal etiological agent of fungal infection and this pathogen is frequently isolated from the respiratory tract within a week of admission . The mortality among untreated patients with acute liver injury complicated with mycotic infection reaches 100% . The early application of the specific treatment in cases suspected of mycotic infection in patients with liver injury could markedly reduce mortality in this group of patients. Arch Microbiol, 2002 Dec, 178(6), 428 - 36 Epub 2002 Sep 03. Validation of Cdc68p as a novel antifungal target; Buurman ET et al.; Candida albicans is the main cause of systemic fungal infections for which there is an urgent need for novel antifungal drugs . The CP (Cdc68p-Pob3p) complex, which is involved in transcription elongation, was evaluated as a putative antifungal target . In order to predict the consequences of inhibition of this complex, the largest CP subunit in Saccharomyces cerevisiae, Cdc68p, was the first novel target to be tested in GATE, a recently described, quantitative target inactivation system . Depletion of the cell's pool of Cdc68p led to rapid cell death . Subsequently, the C . albicans orthologue of CDC68, CaCDC68, was cloned . Attempts to disrupt both alleles were unsuccessful, thus suggesting an essential role of CaCDC68 in this fungus also . Furthermore, CDC68 was proven to be present in Neurospora crassa and Aspergillus nidulans, thus suggesting that the CP complex is widespread among fungi and could serve as a broad range antifungal target . Analysis of Cdc68p and Pob3p sequences indicated significant structural differences between fungal CP complexes and those present in higher eukaryotes . These results predict that, in principle, fungal-specific ligands of CP complexes could be identified that could subsequently serve as chemical starting points towards the development of new antifungal therapeutic agents. J Biol Chem, 2003 Jan 17, 278(3), 1713 - 20 Epub 2002 Nov 04. Inactivation of Kex2p diminishes the virulence of Candida albicans; Newport G et al.; Deletion of the kexin gene (KEX2) in Candida albicans has a pleiotropic effect on phenotype and virulence due partly to a defect in the expression of two major virulence factors: the secretion of active aspartyl proteinases and the formation of hyphae . kex2/kex2 mutants are highly attenuated in a mouse systemic infection model and persist within cultured macrophages for at least 24 h without causing damage . Pathology is modest, with little disruption of kidney matrix . The infecting mutant cells are largely confined to glomeruli, and are aberrant in morphology . The complex phenotype of the deletion mutants reflects a role for kexin in a wide range of cellular processes . Taking advantage of the specificity of Kex2p cleavage, an algorithm we developed to scan the 9168 open reading frames in Assembly 6 of the C . albicans genome identified 147 potential substrates of Kex2p . These include all previously identified substrates, including eight secreted aspartyl proteinases, the exoglucanase Xog1p, the immunodominant antigen Mp65, and the adhesin Hwp1p . Other putative Kex2p substrates identified include several adhesins, cell wall proteins, and hydrolases previously not implicated in pathogenesis . Kexins also process fungal mating pheromones; a modification of the algorithm identified a putative mating pheromone with structural similarities to Saccharomyces cerevisiae alpha-factor. Trends Microbiol, 2002 Nov, 10(11), 508 - 14 Fungi, dendritic cells and receptors: a host perspective of fungal virulence; Romani L et al.; An association between morphogenesis and virulence has long been presumed for dimorphic fungi that are pathogenic to humans, as one morphotype exists in the environment or during commensalism, and another within the host during the disease process . For Candida albicans, putative virulence factors include the ability to switch between saprophytic yeast and pathogenic, filamentous forms of the fungus . Dendritic cells sense either form in a specific way, resulting in distinct, T-helper-cell-dependent protective and non-protective immunities . Recent evidence suggests that the use of distinct recognition receptors contributes to the disparate patterns of reactivity observed locally in response to challenge with C . albicans . These findings offer new interpretive clues to the mechanisms of fungal virulence: rather than dimorphism per se, the engagement of different recognition receptors on dendritic cells might select the mode of fungal internalization and antigen presentation, condition the nature of the T-helper response and, ultimately, favor saprophytism or infection. J Allergy Clin Immunol, 2002 Nov, 110(5), 805 - 10 Isolation and biochemical characterization of a thaumatin-like kiwi allergen; Gavrovic-Jankulovic M et al.; BACKGROUND: Kiwi fruit allergy, as well as its association with hypersensitivity to other foods and to pollen, has been extensively reported in the last few years . Several IgE-binding components have been detected in kiwi extract, but only one 30- kd allergen has been isolated; it was identified as actinidin (Act c 1) . Recently, we have reported a 24-kd kiwi protein to be a potential major allergen in a group of patients with oral allergy syndrome (OAS) . OBJECTIVE: The aim of this study was to purify and characterize the 24-kd kiwi allergen biochemically . METHODS: Seven polysensitized patients with OAS to kiwi were used in this study . The kiwi allergen was isolated by using a combination of gel permeation, ion exchange, and immobilized metal ion affinity chromatography . Its biochemical characterization included determination of its isoelectric point, molecular weight, N-terminal sequencing, concanavalin A -binding ability, digestibility in simulated gastric fluid, and antifungal activity . Western blotting, 2-dimensional PAGE immunoblotting, and skin prick tests were performed to characterize the isolated protein immunochemically . RESULTS: All 7 patients recognized the isolated 24-kd kiwi protein as an allergen . The isolated protein consisted of 2 isoforms with isoelectric points of 9.4 and 9.5 migrated as one protein band of 20 kd after SDS-PAGE under nonreducing conditions or at 24 kd under reducing conditions . The partial N-terminal sequence revealed that it is a thaumatin-like protein (TLP) with concanavalin A -binding ability . The protein showed antifungal activity toward Saccharomyces carlsbergensis, and Candida albicans . The protein was degraded by the simulated gastric fluid within 1 minute . Both isoforms bound IgE from a pool of sera in a 2-dimensional PAGE immunoblot . The TLP elicited positive skin prick test responses in 4 (80 %) of 5 patients with OAS . CONCLUSION: This study reported isolation and full characterization of a new kiwi allergen, TLP (isoelectric points of 9.4 and 9.5 and molecular weight of 24 kd), which belongs to the family of pathogenesis-related proteins . The isolated protein expressed antifungal activity toward S carlsbergensis and C albicans. Mol Cell Biol, 2002 Dec, 22(23), 8199 - 203 Disseminated candidiasis and hepatic malarial infection in mannose-binding-lectin-A-deficient mice; Lee SJ et al.; To examine the physiological functions of mannose-binding lectin A (MBL-A), we generated mice that were deficient in MBL-A and examined their susceptibilities to the microbial pathogens Candida albicans and Plasmodium yoelii, an accepted experimental malaria model in mouse . We found no differences in the survival rates and fungal burdens of wild-type and MBL-A(-/-) mice with disseminated C . albicans infection . The two mouse strains were also similar in their abilities to resist hepatic accumulation of P . yoelii parasites . We conclude that MBL-A deficiency does not alter resistance to disseminated candidiasis or initial hepatic invasion by P . yoelii. Pediatrics . 2002 Nov;110(5):e65. Candida (amphotericin-sensitive) lens abscess associated with decreasing arterial blood flow in a very low birth weight preterm infant; Drohan L et al.; In this report, we review the case of a candidal lens abscess in a premature infant girl who was 28 weeks' gestational age at birth . The culture obtained from the lens abscess grew Candida albicans sensitive to amphotericin B but resistant to flucytosine . This case is unique in that the infant developed a fungal lens cataract at 34 weeks' postconceptional age during the last week of a 30-day course of amphotericin B . The embryonic hyaloid artery system, which perfuses the developing lens, regresses between 29 and 32 weeks of gestation; thus, the mechanism for an infection of the lens may be inoculation of the lens by Candida before hyaloid artery system regression, followed by developmental loss of this blood supply, which makes the lens inaccessible to antimicrobial penetration . Candidal endophthalmitis with lens abscess is an uncommon morbidity that requires prompt recognition and surgical intervention for effective management. Clin Diagn Lab Immunol, 2002 Nov, 9(6), 1282 - 94 NK cells mediate increase of phagocytic activity but not of proinflammatory cytokine (interleukin-6 {IL-6}, tumor necrosis factor alpha, and IL-12) production elicited in splenic macrophages by tilorone treatment of mice during acute systemic candidiasis; Gaforio JJ et al.; The participation of NK cells in the activation of splenic macrophages or in resistance to systemic candidiasis is still a matter of debate . We had previously reported that there is a correlation between natural killer cell activation and resistance to systemic candidiasis . In those experiments we had used tilorone to boost NK cell activity in mice . Here we show a mechanism elicited by tilorone in splenic macrophages which could explain their effect on mouse survival during acute disseminated Candida albicans infection . The results demonstrate that tilorone treatment elicits, by a direct effect, the production of proinflammatory cytokines (interleukin-6 {IL-6}, tumor necrosis factor alpha {TNF-alpha}, and IL-12) by splenic macrophages . In addition, it increases the capacity of splenic macrophages to phagocytize C . albicans through activation of NK cells . We also demonstrate that the presence of NK cells is essential for maintaining a basal level of phagocytic activity, which characterizes splenic macrophages of naive control mice . The results demonstrate that it is possible to identify two phenotypically and functionally peculiar cell populations among splenic macrophages: (i) . cells of the "stimulator/secretor phenotype," which show high levels of major histocompatibility complex (MHC) class II surface expression, are poorly phagocytic, and synthesize the proinflammatory cytokines IL-6, TNF-alpha, and IL-12, and (ii) . cells of the "phagocytic phenotype," which express low levels of MHC class II molecules, are highly phagocytic, and do not secrete proinflammatory cytokines. Shock, 2002 Nov, 18(5), 461 - 4 Murine beta-defensin-3 is an inducible peptide with limited tissue expression and broad-spectrum antimicrobial activity; Burd RS et al.; Beta-defensins are cationic peptides produced by epithelial cells that have been proposed to be an important component of immune function at mucosal surfaces . Similarities between mammalian beta-defensins may permit the use of murine models to further define the role of these peptides in innate host defense . Murine beta-defensin-3 (mBD-3) is a peptide that exhibits homology at the gene level to human beta-defensin-2 (hBD-2), one of four beta-defensins identified in man . The purpose of this study was to determine the antimicrobial activity of mBD-3, the tissue distribution of mBD-3 expression, and the effect of gram-negative bacterial infection on mBD-3 expression . Based on the sequence deduced from mBD-3 cDNA, a 40-amino acid peptide was assembled using automated {n-(9-fluorenyl)methoxycarbonyl} solid-phase synthesis . The antimicrobial activity of synthetic mBD-3 was evaluated in microdilution broth assays using bacterial and fungal organisms . mBD-3 mRNA expression was assayed by polymerase chain reaction (PCR) using cDNA derived from a panel of tissues . Expression of mBD-3 was also evaluated in tissues obtained from mice 24 h after intraperitoneal infection with Escherichia coli using reverse transcriptase (RT)-PCR . Synthetic mBD-3 inhibited the growth of E . coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans at concentrations from 25 to 50 microg/mL . Constitutive expression of mBD-3 mRNA was not consistently found in any organ using RT-PCR . In an E . coli peritonitis model, expression of mBD-3 mRNA was upregulated only in the esophagus and tongue . We conclude that mBD-3 is an inducible peptide with limited tissue expression during E . coli peritonitis . Because it exhibits broad-spectrum antimicrobial activity, this peptide may serve as an innate defense against microbial invasion at specific mucosal surfaces in the mouse. Akush Ginekol (Sofiia), 2002, 41 Suppl 1, 11 - 4 {Microbiological investigation of the vaginal flora during pregnancy}; Todorova M et al.; The infections complications during pregnancy and delivery are jet unsolved problem in obstetrics and neonatology . Most of them are due to anaerobic and aerobic organisms . The authors show the rate and distribution of the bacterial vaginal infections during pregnancy . 1330 pregnant women are investigated, 10% of them are with normal vaginal flora, 27% anaerobic organisms, 15% aerobic organisms, then Candida albicans and Gardnerella vaginalis . Those results are seen most frequently during the last trimester of pregnancy, which leads to the complications in delivery and postpartum. Curr Microbiol, 2002 Dec, 45(6), 394 - 9 Sodium azide reduces the thermotolerance of respiratively grown yeasts; Rikhvanov EG et al.; The effect of sodium azide in heat shock-induced cell death was studied in Debaryomyces vanrijiae, Candida albicans, and Saccharomyces cerevisiae yeasts . The results presented demonstrate that the azide addition induced a drastic decrease in the thermotolerance of glucose-grown D . vanrijiae . In contrast, glucose-grown S . cerevisiae and C . albicans cells treated with NaN(3) became more resistant to heat shock than control cells . Nevertheless, in galactose medium the decrease of thermotolerance of S . cerevisiae and C . albicans cells was observed in the presence of sodium azide . It was suggested that the decreasing effect of sodium azide on thermotolerance takes place only when the yeast cell is incapable of using fermentation for ATP synthesis and obtains energy via oxidative phosphorylation. Nippon Ishinkin Gakkai Zasshi, 2002, 43(4), 261 - 4 Histopathological examination of in vitro bone degeneration caused by a black yeast, Exophiala spinifera; Kishi F et al.; Exophiala spinifera, a black yeast, rarely causes systemic infection, and only a very few cases of its infection by the invasion of internal organs or bones have been reported . We examined the ability of E . spinifera to invade bone tissues in vitro . The fungus was inoculated on the surface of murine bones, and then these bones were incubated at 30 C for 2, 4, and 12 weeks on water agar plates and on brain heart infusion agar supplemented with 1%glucose (BHIA) plates . Histopathological examination demonstrated that the fungus was initially found in the non-calcified parts of the bone tissue, such as the growth plate and articular cartilage . Thereafter, the fungus invaded the calcified parts: cancellous and cortical bones . Our experiments showed that the capability of E . spinifera to invade bone tissue is higher than that of Candida albicans or other black fungi . E . spinifera grew in the mycelial form and C . albicans in the yeast form in these experiments . Our results suggest that E . spinifera may have a high potential to invade bone tissues, and that the mycelial form can invade bone more deeply than the yeast form . Therefore, bone degeneration should/ must be carefully monitored in any systemic infection with E . spinifera. Chem Biol, 2002 Oct, 9(10), 1119 - 28 Crystal structures of Candida albicans N-myristoyltransferase with two distinct inhibitors; Sogabe S et al.; Myristoyl-CoA:protein N-myristoyltransferase (Nmt) is a monomeric enzyme that catalyzes the transfer of the fatty acid myristate from myristoyl-CoA to the N-terminal glycine residue of a variety of eukaryotic and viral proteins . Genetic and biochemical studies have established that Nmt is an attractive target for antifungal drugs . We present here crystal structures of C . albicans Nmt complexed with two classes of inhibitor competitive for peptide substrates . One is a peptidic inhibitor designed from the peptide substrate; the other is a nonpeptidic inhibitor having a benzofuran core . Both inhibitors are bound into the same binding groove, generated by some structural rearrangements of the enzyme, with the peptidic inhibitor showing a substrate-like binding mode and the nonpeptidic inhibitor binding differently . Further, site-directed mutagenesis for C . albicans Nmt has been utilized in order to define explicitly which amino acids are critical for inhibitor binding . The results suggest that the enzyme has some degree of flexibility for substrate binding and provide valuable information for inhibitor design. Genetics, 2002 Oct, 162(2), 737 - 45 In Candida albicans, white-opaque switchers are homozygous for mating type; Lockhart SR et al.; The relationship between the configuration of the mating type locus (MTL) and white-opaque switching in Candida albicans has been examined . Seven genetically unrelated clinical isolates selected for their capacity to undergo the white-opaque transition all proved to be homozygous at the MTL locus, either MTLa or MTLalpha . In an analysis of the allelism of 220 clinical isolates representing the five major clades of C . albicans, 3.2% were homozygous and 96.8% were heterozygous at the MTL locus . Of the seven identified MTL homozygotes, five underwent the white-opaque transition . Of 20 randomly selected MTL heterozygotes, 18 did not undergo the white-opaque transition . The two that did were found to become MTL homozygous at very high frequency before undergoing white-opaque switching . Our results demonstrate that only MTL homozygotes undergo the white-opaque transition, that MTL heterozygotes that become homozygous at high frequency exist, and that the generation of MTL homozygotes and the white-opaque transition occur in isolates in different genetic clades of C . albicans . Our results demonstrate that mating-competent strains of C . albicans exist naturally in patient populations and suggest that mating may play a role in the genesis of diversity in this pernicious fungal pathogen. FEMS Microbiol Lett, 2002 Oct 8, 215(2), 267 - 72 Peptide-mediated delivery of green fluorescent protein into yeasts and bacteria; Rajarao GK et al.; Stringent microbial cell barriers limit the application of many substances in research and therapeutics . Carrier peptides that penetrate or translocate across cell membranes may help overcome this problem . To assess peptide-mediated delivery into two yeast and three bacterial species, a range of cell penetrating and signal peptide sequences were fused to green fluorescent protein (GFP), expressed in Escherichia coli, partially purified and incubated with growing cells . Fluorescence microscopy indicated several peptides that mediated delivery . In particular, VLTNENPFSDP efficiently delivered GFP into Candida albicans and Staphylococcus aureus, while YKKSNNPFSD was most efficient for Bacillus subtilis and CFFKDEL for Escherichia coli . Carrier peptides may improve delivery of certain large molecular mass molecules into microorganisms for research and therapeutic applications. J Nat Prod, 2002 Oct, 65(10), 1509 - 12 New bioactive peroxides from marine sponges of the family plakiniidae; Chen Y et al.; In our continuing program to identify compounds with antifungal properties, the ethanol extracts of two sponges of the family Plakinidae were found to inhibit the growth of the fungal pathogens Candida albicans and Aspergillus fumigatus . From these organisms three new compounds and five known compounds have been identified . A new 1,2-dioxane ring peroxide acid, 1, has been isolated from the sponge Plakortis halichondrioides along with five known compounds . Two new 1,2-dioxolane peroxide acids, 3 and 4, have been isolated from the sponge Plakinastrella onkodes . The structures were established by interpretation of spectral data . The three new compounds exhibit moderate activity against the fungal pathogen C . albicans with MICs of 5, 1.6, and 1.6 microg/mL respectively, for 1, 3, and 4 . Compound 1 also showed in vitro inhibition of the fungal pathogen A . fumigatus with an IC(90) value of 5.6 microg/mL. Microbiol Res, 2002, 157(3), 207 - 11 The antimicrobial activity of Aspergillus fumigatus is enhanced by a pool of bacteria; Furtado NA et al.; In a screening program for new antibiotic producers, a strain of Aspergillus fumigatus was isolated from Brazilian soil samples . A pool of autoclaved bacteria was added to part of the fungus culture on the second day of fermentation to increase antibiotic production . The chloroform extract from the culture broth to which the pool of autoclaved bacteria was added showed an increase of 55%, 63% and more than 100% in activity against Staphylococcus aureus, Candida albicans and Micrococcus luteus, respectively . Also, the HPLC chromatographic profiles of the chloroform extracts from both culture conditions were different . Two active compounds were isolated from the broth of the culture grown in the presence of pooled bacteria and were identified as 3,4-dimethoxyphenol and 1,3,5-trimethoxybenzene. Microbiol Res, 2002, 157(3), 201 - 6 Active substances against trypomastigote forms of Trypanosoma cruzi and microorganisms are produced in sequence by Talaromyces flavus; Freitas TP et al.; The conditions for the sequential production of antibiotic activity by Talaromyces flavus were determined . The highest level of activity against Trypanosoma cruzi was obtained from the aqueous extract of the Czapeck's fermentative culture after 48 hours, with lysis of 97.58% of the trypomastigote forms of Trypanosoma cruzi (red blood cells remained normal) . The antimicrobial activity was detected in the extracts of fermentative cultures from different media just after 144 hours of incubation . Maximum activities against Micrococcus luteus, Staphylococcus aureus and Candida albicans were present in chloroform, butanolic and water extracts, in this order, when Talaromyces flavus was cultivated at pH 5.0 . The minimal inhibitory concentration (MIC) of extracts of Takeuchi's cultures were determined. Proc Natl Acad Sci U S A, 2002 Nov 12, 99(23), 14907 - 12 Epub 2002 Oct 23. Metabolic specialization associated with phenotypic switching in Candidaalbicans; Lan CY et al.; Phase and antigenic variation are mechanisms used by microbial pathogens to stochastically change their cell surface composition . A related property, referred to as phenotypic switching, has been described for some pathogenic fungi . This phenomenon is best studied in Candida albicans, where switch phenotypes vary in morphology, physiology, and pathogenicity in experimental models . In this study, we report an application of a custom Affymetrix GeneChip representative of the entire C . albicans genome and assay the global expression profiles of white and opaque switch phenotypes of the WO-1 strain . Of 13,025 probe sets examined, 373 ORFs demonstrated a greater than twofold difference in expression level between switch phenotypes . Among these, 221 were expressed at a level higher in opaque cells than in white cells; conversely, 152 were more highly expressed in white cells . Affected genes represent functions as diverse as metabolism, adhesion, cell surface composition, stress response, signaling, mating type, and virulence . Approximately one-third of the differences between cell types are related to metabolic pathways, opaque cells expressing a transcriptional profile consistent with oxidative metabolism and white cells expressing a fermentative one . This bias was obtained regardless of carbon source, suggesting a connection between phenotypic switching and metabolic flexibility, where metabolic specialization of switch phenotypes enhances selection in relation to the nutrients available at different anatomical sites . These results extend our understanding of strategies used in microbial phase variation and pathogenesis and further characterize the unanticipated diversity of genes expressed in phenotypic switching. FEMS Microbiol Lett, 2002 Sep 24, 215(1), 57 - 62 Effect of Candida albicans metabolite(s) on cellular actin; Sandovsky-Losica H et al.; The present study describes experiments of the effect of Candida albicans metabolite(s) (arcsf) on cellular actin, and constitutes a continuation of our previous investigations regarding the effect of the fungus on actin . Western blot analysis of HEp2 cells exposed to arcsf or subfraction of arcsf (<100 kDa) revealed that the amount of soluble actin was decreased, and total actin increased, as compared to untreated cells . Transmission electron microscopy observations of HEp2 cells interacted with C . albicans or arcsf, and gold-labeled specifically for actin, revealed more intensive labeling, with labeled particles clustered in groups . Confocal laser scanning microscopy analysis has shown, as well, that exposure of HEp2 cells to the <100-kDa subfraction resulted in actin rearrangement, as did the unfractionated arcsf . Our results point to: (1) C . albicans metabolite(s) affects cellular actin by increasing the transition of soluble actin to the insoluble form; (2) the effect is associated with the subfraction of arcsf which is smaller than <100 kDa. J Hosp Infect, 2002 Oct, 52(2), 141 - 7 Spectrum of antimicrobial activity and user acceptability of the hand disinfectant agent Sterillium Gel; Kampf G et al.; The antimicrobial efficacy of alcohol-based hand gels has been shown to be significantly less than liquid hand rubs probably because of a lower concentration of alcohol . Sterillium Gel is the first hand gel with 85% ethanol . Its antimicrobial efficacy and user acceptability was studied . Bactericidal activity was tested according to prEN 12054 against Staphylococcus aureus, Enterococcus hirae, Pseudomonas aeruginosa and Escherichia coli (suspension test) and EN 1500 (15 volunteers; four replicates), fungicidal activity according to EN 1275 against Candida albicans and spores of Aspergillus niger (suspension test) and tuberculocidal activity against Mycobacterium terrae using the DGHM suspension test . Virucidal activity was determined in suspension tests based on reduction of infectivity with and without interfering substances (10% fetal calf serum; 0.3% erythrocytes and 0.3% bovine serum albumin) . Ninety-six healthcare workers in hospitals in France and the UK used the gel for four weeks and assessed it by filling out a questionnaire . The gel was bactericidal (a reduction factor of > 10(5)-fold), tuberculocidal (reduction factor > 10(5)) and fungicidal (reduction factor > 10(4)) in 30 s . Irrespective of interfering substances the gel inactivated orthopoxvirus and herpes simplex virus type 1 and 2 in 15 s, adenovirus in 2 min, poliovirus in 3 min and papovavirus in 15 min by a factor of > 10(4)-fold . Rotavirus and human immunodeficiency virus were inactivated in 30 s (without interfering substances) . Under practical use conditions it was as effective in 30 s as the reference alcohol in 60 s . Most users described the tackiness, aggregation, skin feeling after use and smell as positive or acceptable . A total of 65.6% assessed the new gel to be better than a comparator irrespective of its type (gel or liquid) . Overall Sterillium Gel had a unique spectrum of antimicrobial activity . It is probably the first alcohol-based hand gel to pass EN 1500 in 30 s . Due to the excellent acceptance by healthcare workers it may significantly improve compliance for hand hygiene and thereby help to reduce the incidence of nosocomial infection . Pathol Res Pract, 2002, 198(8), 537 - 42 Upregulation of human beta-defensin 2 peptide expression in oral lichen planus, leukoplakia and candidiasis . an immunohistochemical study; Abiko Y et al.; Human beta defensin 2 (hBD-2) is a major antimicrobial peptide that is produced by many types of epithelial cells, and is transcriptionally inducible by various proinflammatory agents, such as cytokines and bacteria . Although in vitro studies of the hBDs in oral epithelial cells have been well documented, only little is known about the in vivo pathological state of oral epithelium . We investigated the localization of hBD-2 peptide in tissue sections of oral lichen planus, leukoplakia, candidal leukoplakia and radicular cysts using immunohistochemistry . HBD-2 was stained in both the hyperkeratinized and the granular layers in cases of lichen planus with hyperkeratosis and leukoplakia . Expression in spinous and suprabasal layers was often strong in lichen planus . There were no significant differences in the number of S-100 positive dendritic cells between the widely stained areas and those with limited staining areas in lichen planus . In cases of candidal leukoplakia, the hyphae of candida were mainly detected on the surface of keratinization, which showed only negative or faint staining for hBD-2 . These results suggest that hBD-2 is vigorously induced by lichen planus-related inflammation and that it plays an important role in protection from Candida albicans infection; however, it is not a strong chemotactic attractant for Langerhans cells in pathological conditions of oral epithelium. East Afr Med J, 2002 Mar, 79(3), 143 - 5 Antifungal drug susceptibility of Candida albicans; Bii CC et al.; OBJECTIVE: To determine the susceptibility of clinical isolates of Candida albicans and to establish the minimum inhibitory concentrations (MIC) to commonly used antifungal drugs . DESIGN: Laboratory based experiment . SETTING: Mbagathi District Hospital, Nairobi, Kenya . SUBJECTS: Candida albicans isolated between 1998 and 2000 from the sputa of HIV/AIDS patients and throat swabs of children with acute respiratory infections (ARI) . METHODS: Susceptibility to amphotericin B, clotrimazole, nystatin, and 5-fluorocytosine was done using agar dilution method (NCCLS 1997) . RESULTS: Among the ARI isolates 29.3% and among HIV isolates 22.4% had MIC>0.5 microg/ml to amphotericin B . Over 80% of the ARI isolates had MICs > 1 microg/ml to clotrimazole . The MIC range of most isolates to nystatin was 4-16 microg/ml while most isolates were susceptible to 5-fluorocytosine . There were no significant differences in susceptibility between ARI and HIV isolates to commonly used antifungal drugs . CONCLUSION: Although fungal resistance has not been extensively studied, susceptibility tests showed some Candida albicans have increased MICs to commonly used antifungal drugs . The results call for further investigations on fungal resistance especially in the context of opportunistic infections in HIV/AIDS. Mol Biol Cell, 2002 Oct, 13(10), 3452 - 65 Transcription profiling of Candida albicans cells undergoing the yeast-to-hyphal transition; Nantel A et al.; The ability of the pathogenic fungus Candida albicans to switch from a yeast to a hyphal morphology in response to external signals is implicated in its pathogenicity . We used glass DNA microarrays to investigate the transcription profiles of 6333 predicted ORFs in cells undergoing this transition and their responses to changes in temperature and culture medium . We have identified several genes whose transcriptional profiles are similar to those of known virulence factors that are modulated by the switch to hyphal growth caused by addition of serum and a 37 degrees C growth temperature . Time course analysis of this transition identified transcripts that are induced before germ tube initiation and shut off later in the developmental process . A strain deleted for the Efg1p and Cph1p transcription factors is defective in hyphae formation, and its response to serum and increased temperature is almost identical to the response of a wild-type strain grown at 37 degrees C in the absence of serum . Thus Efg1p and Cph1p are needed for the activation of the transcriptional program that is induced by the presence of serum. Am J Physiol Cell Physiol, 2003 Jan, 284(1), C111 - 8 Epub 2002 Aug 28. Immunocompetence of macrophages in rats exposed to Candida albicans infection and stress; Rodriguez-Galan MC et al.; The integration of innate and adaptive immune responses is required for efficient control of Candida albicans . The present work aimed to assess, at the local site of the infection, the immunocompetence of macrophages in rats infected intraperitoneally with C . albicans and exposed simultaneously to stress during 3 days (CaS group) . We studied the 1) ability to remove and kill C . albicans, 2) tumor necrosis factor-alpha (TNF-alpha) release, 3) balance of the inducible enzymes NO synthase (iNOS) and arginase, and 4) expression of interleukin (IL)-1beta and IL-1 receptor antagonist (ra) mRNA . Compared with only infected animals (Ca group), the number of colony-forming units was significantly higher in CaS rats (P < 0.01), and the macrophage candidicidal activity was approximately 2.5-fold lower (P < 0.01) . Release of TNF-alpha was diminished in both unstimulated and heat-killed C . albicans restimulated macrophages of the CaS group (Ca vs . CaS, P < 0.03 and P < 0.05, respectively) . In Ca- and CaS-group rats, the rates for both the arginase activity and the NO synthesis were significantly enhanced . However, the stress exposure downregulated the activity of both enzymes (CaS vs . Ca, P < 0.05) . After in vitro restimulation, the IL-1ra/IL-1beta ratio was significantly diminished in CaS-group rats (P < 0.05) . Our results indicate that a correlation exists between early impairment of macrophage function and stress exposure. Rinsho Byori, 2002 Sep, 50(9), 853 - 9 {Mycoses}; Yamazumi T et al.; Antifungal susceptibility testing has developed rapidly during the last decade . Through the intensive collaborative work, the National Committee for Clinical Laboratory Standards (NCCLS) has published a standardized antifungal susceptibility method M27-A which included interpretive guidelines for 3 antifungal agents . Meaningful large-scale, longitudinal studies of antifungal susceptibility and resistance, based on standardized methodology and interpretive guidelines, have been published and serve as the basis for analysis of resistance trends . Resistant isolates have been further characterized using molecular biological techniques . Candida albicans and related species become resistant to antifungal agents, in particular triazoles, by expression of efflux pomps that reduce drug accumulation, alteration of the structure or concentration of antifungal target enzymes, and alteration of membrane sterol composition . On the other hand, there are several ongoing problems in antifungal susceptibility testing such as trailing phenomenon, ability to detect amphotericin B resistance, and application for other fungal pathogens . In this paper, we review studies which focused on the reliability of antifungal susceptibility testing, epidemiology of resistant isolates, and resistant mechanisms . Furthermore, we provide several recommendations for antifungal susceptibility testing in the clinical laboratory. Farmaco, 2002 Sep, 57(9), 771 - 5 Synthesis and microbiological activity of some novel N-{2-(p-substitutedphenyl)-5-benzoxazolyl}-cyclohexyl carboxamide, -cyclohexyl acetamide and -cyclohexyl propionamide derivatives; Arpaci OT et al.; The synthesis and microbiological activity of a new series of N-{2-(p-substitutedphenyl)-5-benzoxazolyl}-cyclohexyl carboxamide, -cyclohexyl acetamide and -cyclohexyl propionamide derivatives (4-11) is described . The in vitro microbiological activity of the compounds was determined against gram-positive, gram-negative bacteria and the yeast Candida albicans in comparison with standard drugs . Microbiological results indicated that the synthesized compounds possessed a broad spectrum of activity against the tested microorganisms. Antimicrob Agents Chemother, 2002 Nov, 46(11), 3617 - 20 Propranolol inhibits hyphal development in Candida albicans; Baker CA et al.; Propranolol was used to investigate the role of phosphatidic acid (PA) and diacylglycerol in the dimorphic transition in Candida albicans . Propranolol was able to inhibit the appearance of germ tubes without decreasing growth rate . Data suggest that inhibition of morphogenesis may be due to binding by propranolol of PA derived from PLD1 hydrolysis of phosphatidylcholine. Antimicrob Agents Chemother, 2002 Nov, 46(11), 3412 - 7 Evaluation of differential gene expression in fluconazole-susceptible and -resistant isolates of Candida albicans by cDNA microarray analysis; Rogers PD et al.; The opportunistic fungal pathogen Candida albicans is the major causative agent of oropharyngeal candidiasis (OPC) in AIDS . The development of azoles, such as fluconazole, for the treatment of OPC has proven effective except in cases where C . albicans develops resistance to fluconazole during the course of treatment . In the present study, we used microarray technology to examine differences in gene expression from a fluconazole-susceptible and a fluconazole-resistant well-characterized, clinically obtained matched set of C . albicans isolates to identify genes which are differentially expressed in association with azole resistance . Among genes found to be differentially expressed were those involved in amino acid and carbohydrate metabolism; cell stress, cell wall maintenance; lipid, fatty acid, and sterol metabolism; and small molecule transport . In addition to CDR1, which has previously been demonstrated to be associated with azole resistance, the drug resistance gene RTA3, the ergosterol biosynthesis gene ERG2, and the cell stress genes CRD2, GPX1, and IFD5 were found to be upregulated . Several genes, such as the mitochondrial aldehyde dehydrogenase gene ALD5, the glycosylphosphatidylinositol synthesis gene GPI1, and the iron transport genes FET34 and FTR2 were found to be downregulated . Further study of these differentially regulated genes is warranted to evaluate how they may be involved in azole resistance . In addition to these novel findings, we demonstrate the utility of microarray analysis for studying the molecular mechanisms of drug resistance in pathogenic organisms. Pediatr Dermatol, 2002 Sep-Oct, 19(5), 415 - 8 Antigliadin antibodies associated with chronic mucocutaneous candidiasis; Garcia YH et al.; Chronic mucocutaneous candidiasis (CMC) is a primary immunodeficiency disease clinically characterized by Candida infection of the skin, mucous membranes, or nails that is refractory to traditional treatment . We present a typical case of a 13-year-old boy with an onset of illness at 1 month of age in the form of oral thrush . At age 2-3 years the patient began to have external otitis caused by Candida albicans and recurrent upper respiratory tract infections . Analytical studies detected iron deficiency and circulating antigliadin antibodies . Immunologic findings excluded other possible immunodeficiencies . Significant clinical improvement was produced by therapy with orally administered fluconazole . The significance of antigliadin antibodies is discussed. J Med Chem, 2002 Oct 24, 45(22), 4903 - 12 Synthesis, antifungal activity, and molecular modeling studies of new inverted oxime ethers of oxiconazole; Rossello A et al.; Some new oxime ethers of types 7 and 8, in which the methyleneaminoxy group, C=N-O, of oxiconazole 6 is in an inverted atomic sequence, were synthesized and tested for their antifungal activities . Among them, the type 7 compounds, such as the N-ethoxy-morpholino-substituted derivatives 7l-o (Table 1), showed good antifungal properties against the Candida strains tested, with minimum inhibitory concentration (MIC) values similar to those of the reference drug 6 . A remarkable result was obtained with these types of azoles, which had shown a cidal character against Candida albicans, while the reference drug oxiconazole was only fungistatic in the same tests . This fact may be seen from a comparison of the MIC values with those of the minimum fungicidal concentration (MFC) values for most of the type 7 compounds assayed that have shown differences between the MIC and the MFC, which are lower than three double diluitions . A simple molecular modeling of the P450 14-alpha-sterol demethylase from C . albicans (Candida P450DM) was built in order to understand how the structural differences between type 7 compounds and oxiconazole 6 can induce different antifungal profiles . The results of this work seem to confirm that it is possible to reverse the atomic sequence of the methyleneaminoxy group, C=N-O, of 6, obtaining new imidazoles possessing good antifungal properties. FEMS Immunol Med Microbiol, 2002 Oct 11, 34(2), 153 - 7 Correlation between virulence of Candida albicans mutants in mice and Galleria mellonella larvae; Brennan M et al.; Candida albicans is a dimorphic human pathogen in which the yeast to hyphal switch may be an important factor in virulence in mammals . This pathogen has recently been shown to also kill insects such as the Greater Wax Moth Galleria mellonella when injected into the haemocoel of the insect larvae . We have investigated the effect of previously characterised C . albicans mutations that influence the yeast to hyphal transition on virulence in G . mellonella larvae . There is a good correlation between the virulence of these mutants in the insect host and the virulence measured through systemic infection of mice . Although the predominant cellular species detected in G . mellonella infections is the yeast form of C . albicans, mutations that influence the hyphal transition also reduce pathogenicity in the insect . The correlation with virulence measured in the mouse infection system suggests that Galleria may provide a convenient and inexpensive model for the in vivo screening of mutants of C . albicans. Acta Med Port, 2002 May-Jun, 15(3), 171 - 4 {Detection of phospholipidolytic Candida albicans isolated from saliva of children with Down's syndrome}; Ribeiro EL et al.; The childhood is one of the most propitious period of the life to the occurrence of infection by yeasts of the genus Candida . In children with Down's syndrome, besides the predispose factors to bucal candidiasis; macroglossia, bucal muscular incompetence, frequent respiratory diseases, motor difficulty and immunologic deficit are mentioned as additional elements for this fungus disease . It was verified that the children attacked by this syndrome have much more strains of Candida than other children . The aim of this study was to detect the prevalence of phospholipase producer, Candida on the saliva of children with Down's syndrome . Candida albicans was the only identified specie of Candida . The phospholipase production was found in isolated strains from both of study and control . However, the isolated strains of the group of children with Down's syndrome have strongly present phospholipidolitic. J Pharm Sci, 2002 Nov, 91(11), 2408 - 15 Effect of cyclodextrins on the solubility and antimycotic activity of sertaconazole: experimental and computational studies; Perdomo-Lopez I et al.; This study investigated the effects of the complexation of sertaconazole nitrate with different cyclodextrin (CD) derivatives (alpha-CD, beta-CD, gamma-CD, hydroxypropyl-beta-CD, and hydroxypropyl-gamma-CD) on the aqueous solubility and antimycotic activity of the drug . Phase solubility studies indicated that the solubility of sertaconazole in enzyme-free simulated gastric- and enzyme-free simulated enteric fluids was significantly increased in the presence of cyclodextrins . The observed order of solubility increasing effect was: gamma-CD > HPgamma-CD > HPbeta-CD > beta-CD > alpha-CD . Solid-state sertaconazole-cyclodextrin complexes were prepared by freeze drying, and characterized by X-ray powder difractometry, differential scanning calorimetry (DSC), and infrared spectroscopy (FTIR) . Freeze-dried complexes showed markedly higher solubility than both physical mixtures and sertaconazole alone . The antimycotic activities of sertaconazole-cyclodextrin complexes in solution were evaluated by inhibition zone assays with Candida albicans . The activity ranking agrees with the solubility ranking observed for these complexes, with the gamma-CD-sertaconazole complex showing the strongest antimycotic activity . Finally, molecular modeling studies were carried out using the MM2 force field method, for complexes in vacuum and in water . This enable indentification of the preferred orientation of sertaconazole in the gamma-CD cavity and of the main structural features responsible for the enhancement of its solubility and antimycotic activity . Infect Immun, 2002 Nov, 70(11), 6471 - 4 Parenteral administration of medium- but not long-chain lipid emulsions may increase the risk for infections by Candida albicans; Wanten GJ et al.; Intravenous administration to volunteers of an emulsion of medium-chain lipids, but not of an emulsion of pure long-chain lipids or a placebo, increased the growth of Candida albicans in serum and modulated Candida-induced cytokine production by mononuclear cells in a way suggesting that medium-chain, but not long-chain, triglycerides increase the risk for infections by Candida. Infect Immun, 2002 Nov, 70(11), 6319 - 29 Candida albicans killing by RAW 264.7 mouse macrophage cells: effects of Candida genotype, infection ratios, and gamma interferon treatment; Marcil A et al.; Phagocytic cells such as neutrophils and macrophages are potential components of the immune defense that protects mammals against Candida albicans infection . We have tested the interaction between the mouse macrophage cell line RAW 264.7 and a variety of mutant strains of C . albicans . We used an end point dilution assay to monitor the killing of C . albicans at low multiplicities of infection (MOIs) . Several mutants that show reduced virulence in mouse systemic-infection models show reduced colony formation in the presence of macrophage cells . To permit analysis of the macrophage-Candida interaction at higher MOIs, we introduced a luciferase reporter gene into wild-type and mutant Candida cells and used loss of the luminescence signal to quantify proliferation . This assay gave results similar to those for the end point dilution assay . Activation of the macrophages with mouse gamma interferon did not enhance anti-Candida activity . Continued coculture of the Candida and macrophage cells eventually led to death of the macrophages, but for the RAW 264.7 cell line this was not due to apoptotic pathways involving caspase-8 or -9 activation . In general Candida cells defective in the formation of hyphae were both less virulent in animal models and more sensitive to macrophage engulfment and growth inhibition . However the nonvirulent, hypha-defective cla4 mutant line was considerably more resistant to macrophage-mediated inhibition than the wild-type strain . Thus although mutants sensitive to engulfment are typically less virulent in systemic-infection models, sensitivity to phagocytic macrophage cells is not the unique determinant of C . albicans virulence. Ann Pharm Fr, 2002 Sep, 60(5), 348 - 51 {In vitro antimicrobial activity of new 1,10-phenantroline derivatives}; Druta I et al.; The antimicrobial and antifungical activities of some 1,10-phenanthroline derivatives are described . The test was performed using the diffusimetric method with stainless steel cylinders based on diffusion of the substances on the gelose surface for bacteria and Sabouraud field for Candida Albicans yeast . The comparative analysis of the obtained data leads to the following conclusions concerning the relation between structure and activity EMBO J, 2002 Oct 15, 21(20), 5448 - 56 Gcn4 co-ordinates morphogenetic and metabolic responses to amino acid starvation in Candida albicans; Tripathi G et al.; Candida albicans is a major fungal pathogen of humans . It regulates its morphology in response to various environmental signals, but many of these signals are poorly defined . We show that amino acid starvation induces filamentous growth in C.albicans . Also, starvation for a single amino acid (histidine) induces CaHIS4, CaHIS7, CaARO4, CaLYS1 and CaLYS2 gene expression in a manner reminiscent of the GCN response in Saccharomyces cerevisiae . These morphogenetic and GCN-like responses are both dependent upon CaGcn4, which is a functional homologue of S.cerevisiae Gcn4 . Like ScGcn4, CaGcn4 activates the transcription of amino acid biosynthetic genes via the GCRE element, and CaGcn4 confers resistance to the histidine analogue, 3-aminotriazole . CaGcn4 interacts with the Ras-cAMP pathway to promote filamentous growth, but the GCN-like response is not dependent upon morphogenetic signalling . CaGcn4 acts as a global regulator in C.albicans, co-ordinating both metabolic and morphogenetic responses to amino acid starvation. J Infect Chemother, 2002 Sep, 8(3), 237 - 41 Use of antifungal agents in febrile patients nonresponsive to antibacterial treatment: the current status in surgical and critical care patients in Japan; Aikawa N et al.; Disseminated candidiasis is difficult to diagnose and treat, and often becomes life-threatening in critically ill patients . However, guidelines or consensus views regarding the management of disseminated candidiasis do not exist in Japan . To develop feasible guidelines in Japan, we studied the current status of antifungal treatment in critically ill patients in Japan . From April 1999 to January 2000, critically ill patients from either surgical wards or critical care/intensive care units of 26 teaching hospitals were studied, using a prospective enrollment protocol . Patient enrollment criteria included persistent fever(> or =38 degrees C) for 3 days or more despite antibacterial agent administration . Data were entered at each institution and managed centrally using Clinware software . Of the 200 patients in the study, 68 (34%) received antifungal agents . Factors associated with antifungal treatment in the 68 patients included: central venous or pulmonary artery catheter, re-surgery, carbapenem or cephem administration, prolonged antibacterial agent administration, and high body temperature . Proven or probable disseminated candidiasis was presumed or diagnosed by culture in 34 patients, and by clinical signs and/or serological tests in 34 patients . Fungi isolated from blood included Candida albicans (57%), C . tropicalis (14%), C . parapsilosis (7%), C . glabrata (7%), and others (14%) . Treatment patterns were as follows: 65 patients (96%) were treated with fluconazole (60 as monotherapy and 5 with amphotericin B); 2 patients, with miconazole; and 1 patient, with amphotericin B . Excluding 6 unevaluable cases, antifungal treatment was efficacious in 75% (21/28) of the patients with positive fungal culture and in 68% (23/34) of patients diagnosed by other means. Biochem Biophys Res Commun, 2002 Oct 11, 297(5), 1350 - 3 Inhibition of Candida albicans secreted aspartic protease by a novel series of peptidomimetics, also active on the HIV-1 protease; Skrbec D et al.; Nineteen reduced amide, monohydroxy- or dihydroxyethylene-based transition-state peptidomimetics, known to be good inhibitors of the aspartic protease of HIV-1, were tested against a secreted aspartic protease (Sap2), purified from the culture medium of a virulent strain of Candida albicans . Ten of these compounds exhibited IC(50)s against Sap2 lower than 15 microM; the best inhibitor, Kyn-Val-Phe-Psi{OH-OH}-Phe-Val-Kyn, when added to the C . albicans culture, repressed the hydrolysis of bovine serum albumin (BSA), contained in the culture medium, and inhibited the growth of the fungus. Clin Transplant, 2002, 16 Suppl 7, 34 - 44 Thymoglobulin for induction or rejection therapy in pancreas allograft recipients: a single centre experience; Trofe J et al.; PURPOSE: To review the safety and efficacy of thymoglobulin in pancreas transplant patients receiving tacrolimus and mycophenolate mofetil . METHODS: Retrospective, single centre analysis of 45 patients transplanted between 1995 and 2000 who received 54 courses of thymoglobulin, including 36 courses in 29 solitary pancreas transplant recipients (16 pancreas alone, 13 pancreas after kidney transplants) and 18 courses in 16 simultaneous kidney-pancreas transplant patients . Thirty-two patients (71%) were primary pancreas transplants, 10 (22%) were second transplants and three (7%) were third transplants . Of the 54 treatment courses, 19 (35%) were for induction, 27 (50%) were for primary rejection and eight (15%) were rescue therapy for rejection . All rejection episodes were biopsy-proven in at least one organ . RESULTS: The median thymoglobulin dose was 1.5 mg/kg/d with a mean of six doses (range 3-10) . Dose reduction or interruption was required in 28 courses (52%), most often due to leukopenia (n = 24), fever (n = 2) and thrombocytopenia (n = 2) . Thymoglobulin was resumed in all but three patients, two with persistent fever and one with infection . Infectious complications (n = 25) occurred in 17 patients (38%) within 30 days and included bacterial (n = 16), cytomegalovirus (n = 4), polyoma (n = 1), fungal (Candida albicans, n = 1), toxoplasmosis (n = 1) and ehrlichiosis (n = 2) . Post-transplant lymphoproliferative disease occurred in two patients (4%) at a mean of 70 d post-thymoglobulin treatment . In the 19 patients that received thymoglobulin induction, one simultaneous kidney-pancreas transplant, two pancreas alone and four pancreas after kidney transplant recipients developed rejection (37% incidence), while all remaining patients followed by surveillance protocol biopsies were rejection-free . In the 35 patients that received thymoglobulin for rejection, reversal occurred in 26 of the patients (74%) . Rejection recurred within 30 d in five patients and post-treatment biopsies revealed persistent rejection in three of 20 pancreas and two of eight renal biopsies . After a mean follow-up of 6 months, the actual patient and pancreas graft survival rates were 93% and 71%, respectively . CONCLUSION: Thymoglobulin was effective as induction therapy in high-risk pancreas transplant recipients, and resulted in initial reversal of rejection in 74% of patients . Dose adjustments were required in over half the cases and were usually due to leukopenia . Infections occurring subsequent to thymoglobulin were not uncommon and reflected the immunosuppressive burden of the patient population. J Neuroendocrinol, 2002 Oct, 14(10), 824 - 8 In-vitro study of the effect of adrenaline on the functional capacity of human neutrophils: role during exercise; Malpica MI et al.; We studied the effect of adrenaline on the capacity of human neutrophils to attach, ingest and destroy Candida albicans . The neutrophils were incubated in vitro in the presence of an adrenaline concentration taken as basal (10-10 m), and another that is referred to as being reached following physical exercise (10-9 m) . Two higher concentrations (10-7 m and 10-5 m), which are seldom attained in blood but which can occur at specific locations in the organism, were tested as having a possible pharmacological application . At the two high concentrations (10-7 m and 10-5 m), the capacity to attach, ingest and destroy C . albicans was greater than at the physiological concentrations (10-10 m and 10-9 m) . Indeed, the capacity to attach and ingest C . albicans was significantly less after incubation with these physiological concentrations than the control values (incubation in the absence of adrenaline) . Hence, high concentrations of adrenaline seem to enhance neutrophils' phagocytic capacity compared to physiological plasma concentrations, whereas small variations such as those caused by physical exercise have no effect on this functional capacity. Arerugi, 2002 Aug, 51(8), 615 - 21 {Analysis of IgE reactivities of purified allergens from Candida albicans and Malassezia furfur among patients with atopic dermatitis}; Asako Y et al.; We analyzed the reactivities of a series of purified allergens from Candida albicans (C . albicans) and Malassezia furfur (M . furfur) with IgE antibodies in sera from patients with atopic dermatitis . We compared the specific IgE antibody levels to manganese superoxide dismutase (Mn SOD), cyclophilin, enolase, secretory aspartic protease (SAP 2) and type A mannan from C . albicans and Mn SOD, cyclophilin and Mal f 2 from M . furfur in 21 sera from patients with atopic dermatitis and 20 sera from patients with asthma without atopic dermatitis . The prevalence of IgE antibodies and the mean IgE antibody levels to all of the allergens tested were higher among patients with atopic dermatitis than among those with asthma without atopic dermatitis . More than 50% of patients with atopic dermatitis were IgE antibody-positive to Mn SOD, cyclophilin and type A mannan from C . albicans, and Mn SOD and cyclophilin from M . furfur . The availability of these purified allergens will facilitate studies on the contribution of fungal allergens to the development of atopic dermatitis. J Periodontal Res, 2002 Oct, 37(5), 333 - 9 Salivary IgA subclasses and bacteria-reactive IgA in patients with aggressive periodontitis; Hagewald S et al.; The local salivary immunoglobulin A (IgA) response in patients with aggressive periodontitis to oral microorganisms and its role for the pathogenesis has not been determined . This study investigated the hypothesis that aggressive periodontitis patients have impaired oral secretory immunity . Our test group was made-up of 19 aggressive periodontitis patients and 19 age- and gender-matched periodontally healthy controls . Total IgA, IgA subclass 1, IgA subclass 2 and IgA reactive to Actinobacillus actinomycetemcomitans Y4, Treponema denticola ATCC 35404 and Candida albicans DSM 3454 were determined by enzyme-linked immunosorbent assay in whole unstimulated and stimulated saliva . A statistically significantly lower concentration and secretion rate of total salivary IgA (P < 0.01) and IgA1 (P < 0.001) was found in the aggressive periodontitis group in resting and stimulated saliva . A decrease of IgA2 (P < 0.05) was seen in resting saliva . Although only minor differences were detected in the concentration and secretion of bacteria-reactive IgA in both groups, the proportion of bacteria-reactive IgA from the total IgA was significantly higher (P < 0.01) in the aggressive periodontitis group in all three microorganisms tested . Our results indicate an inhibition of total secretory IgA . In particular an IgA subclass 1-specific decrease in aggressive periodontitis was noted, while the bacteria-reactive humoral immune system in saliva was activated . The role of the decrease of IgA1 immunoglobulins in aggressive periodontitis with respect to susceptibility for periodontal diseases has to be elucidated. Mol Microbiol, 2002 Oct, 46(1), 269 - 80 Generation of conditional lethal Candida albicans mutants by inducible deletion of essential genes; Michel S et al.; The yeast Candida albicans is the most important fungal pathogen of humans and a model organism for studying fungal virulence . Sequencing of the C . albicans genome will soon be completed, allowing systematic approaches to analyse gene function . However, techniques to define and characterize essential genes in this permanently diploid yeast are limited . We have developed an efficient method to create conditional lethal C . albicans null mutants by inducible, FLP-mediated gene deletion . Both wild-type alleles of the CDC42 or the BEM1 gene were deleted in strains that carried an additional copy of the respective gene that could be excised from the genome by the site-specific recombinase FLP . Expression of a C . albicans-adapted FLP gene under the control of an inducible promoter generated cell populations consisting of > or = 99.9% null mutants . Upon plating, these cells were unable to form colonies, demonstrating that CDC42 and BEM1 are essential genes in C . albicans . The cdc42 null mutants failed to produce buds and hyphae and grew as large, round cells instead, suggesting that they lacked the ability to produce polarized cell growth . However, the cells still responded to hyphal inducing signals by aggregating and expressing hypha-specific genes, behaviours typical of the mycelial growth form of C . albicans . Budding cells and germ tubes of bem1 null mutants exhibited morphological abnormalities, demonstrating that BEM1 is essential for normal growth of both yeast and hyphae . Inducible, FLP-mediated gene deletion provides a powerful approach to generate conditional lethal C . albicans mutants and allows the functional analysis of essential genes. Microb Drug Resist, 2002 Fall, 8(3), 235 - 44 Detection of human P-glycoprotein-like molecule in azole-resistant Candida albicans from HIV+ patients; Stringaro A et al.; Azole resistance in Candida albicans may be due to several mechanisms . It has been demonstrated that C . albicans possesses sequences with a high degree of homology with the human MDR-1 gene coding for P-glycoprotein (P-gp), belonging to the ATP-binding cassette transporter (ABC) superfamily and responsible for the multidrug resistance (MDR) in tumor cells . On this basis, the expression and intracellular localization of human P-gp-like molecule in C . albicans strains showing different sensitivity to fluconazole were investigated by flow cytometry and immunoelectron microscopy . Post-embedding immunolabeling revealed that monoclonal antibody (mAb) MM4.17, which recognizes an external epitope of human P-gp, reacted with both fluconazole-sensitive (3153 and CO 23-1) and fluconazole-resistant (AIDS 68 and CO 23-2, isolated from AIDS patient and in vitro drug-selected, respectively) strains of C . albicans . However, the resistant strains displayed a number of MM4.17-reactive epitopes much higher than the drug-sensitive ones . The C . krusei ATCC 6458 strain, whose resistance is not mediated by the presence of ABC transporters, was not reactive at all with mAb MM4.17 . The specificity of the immunolabeling was confirmed by a competitive inhibition assay performed by using phage clone particles capable of mimicking the MM4.17-reactive epitope . The flow cytometric analysis confirmed a higher level of intracytoplasmic P-gp expression in azole-resistant strains of C . albicans . Both cyclosporin A and verapamil, which are well-known MDR inhibitors, strongly reduced the MICs for fluconazole and itraconazole of the tested azole-resistant AIDS 68 strain, while they did not influence the MICs of either the sensitive 3153 strain of C . albicans or the ATCC 6458 strain of C . krusei . Overall, our data suggest the existence of a P-gp-like drug efflux pump in C . albicans that may participate in the mechanisms of azole-resistance of this fungus. Am J Med, 2002 Sep, 113(4), 294 - 9 A randomized double-blind study of caspofungin versus fluconazole for the treatment of esophageal candidiasis; Villanueva A et al.; BACKGROUND: Candida esophagitis remains an important cause of morbidity in patients with advanced human immunodeficiency virus (HIV) infection . Fluconazole is widely regarded as the treatment of choice for this condition . METHODS: The efficacy and safety of caspofungin were compared with fluconazole in adult patients with Candida esophagitis in a double-blind randomized trial . Eligible patients had symptoms compatible with esophagitis, endoscopic demonstration of mucosal plaques, and microscopic demonstration of Candida from the esophageal lesions . Patients were randomly assigned to receive caspofungin (50 mg) or fluconazole (200 mg) intravenously once daily for 7 to 21 days . The primary endpoint was the combined response of symptom resolution and significant endoscopic improvement 5 to 7 days after discontinuation of treatment . Data were analyzed with a modified intention-to-treat analysis, which excluded 2 ineligible patients . RESULTS: Most patients (154/177; 87%) had HIV infection, with a median CD4 count of 30 cells/mm(3) . Candida albicans was the predominant isolate . Favorable response rates were achieved in 66 (81%) of the 81 patients in the caspofungin arm and in 80 (85%) of the 94 patients in the fluconazole arm (difference = -4%; 95% confidence interval: -15% to +8%) . Symptoms had resolved in >50% of patients in both groups by the fifth day of treatment . No patient in the caspofungin group developed a serious drug-related adverse event; therapy was only discontinued in 1 patient (receiving fluconazole) due to a drug-related adverse experience . Four weeks after stopping study drug, symptoms had recurred in 18 (28%) of 64 patients given caspofungin and in 12 (17%) of 72 patients given fluconazole (P = 0.19) . CONCLUSIONS: In this study, caspofungin appeared to be as efficacious and generally as well tolerated as fluconazole in patients with advanced HIV infection and documented Candida esophagitis. Aust Endod J, 2001 Dec, 27(3), 112 - 4 Antifungal effects of endodontic medicaments; Siqueira Junior JF et al.; The eradication of root canal infection is paramount in endodontic treatment . Because fungi are involved in some types of root canal infections, the purpose of this study was to investigate the antifungal effects of several medicaments against the following selected fungal species: Candida albicans, Candida glabrata, Candida guilliermondii, Candida parapsilosis, and Saccharomyces cerevisiae . The agar diffusion test was the method used . Calcium sulphate or zinc oxide in glycerin showed no inhibitory effects towards any selected fungal species . The pastes of calcium sulphate or calcium hydroxide in camphorated paramonochlorophenol (CPMC)/glycerin showed the most pronounced antifungal effects . Calcium hydroxide in glycerin or chlorhexidine, and chlorhexidine in a detergent also showed antifungal activity, which was, however, much lower than the pastes of calcium sulphate or calcium hydroxide in CPMC/glycerin . Strategies using medicaments that have antifungal effects may assist in the successful management of persistent or secondary endodontic infections caused by fungi. Biochem Biophys Res Commun, 2002 Oct 4, 297(4), 885 - 9 Influence on the plasma membrane of Candida albicans by HP (2-9)-magainin 2 (1-12) hybrid peptide; Lee DG et al.; A 20-residue hybrid peptide (HP (2-9)-MA (1-12): HP-MA), incorporating 2-9 residues of Helicobacter pyroli ribosomal protein L1 (HP) and 1-12 residues of magainin 2 (MA), has more potent antibacterial activity than parent peptide HP (2-20) and magainin 2 . In this study, the antifungal activity and its mechanism of HP-MA were investigated . HP-MA displayed a strong antifungal activity in an energy-dependent manner . To elucidate the antifungal mechanism(s) of HP-MA, FACScan analysis and the change in membrane dynamics using 1,6-diphenyl-1,3,5-hexatriene (DPH) as a membrane probe of Candida albicans were examined . The results indicated that the HP-MA exerts its antifungal effect by acting on the plasma membrane . Furthermore, the peptide induced remarkable morphological change when tested for membrane disrupting activity using liposomes (PC/Cholesterol; 10:1, w/w) . In C . albicans, dimorphism plays a crucial role in pathogenesis but HP-MA could disrupt the mycelial forms and exert its antifungal effect on the blastoconidia in 20% fetal bovine serum. Oral Microbiol Immunol, 2002 Oct, 17(5), 304 - 10 Persistence of oral Candida albicans carriage in healthy Portuguese schoolchildren followed for 3 years; Starr JR et al.; Little is known about carriage of Candida albicans, the predominant pathogenic yeast in oral infection, in children . We cultured buccal mucosal and gingival swabs from 150 Portuguese children to investigate the prevalence of C . albicans at baseline (before dental treatment), post-treatment, and 12, 24, and 36 months post-baseline . The children, aged 8 to 11 years at baseline, had no systemic disease or clinical symptoms of oral candidiasis . At each successive visit, respectively, 47, 32, 21, 27, and 28% of children were C . albicans positive, resulting in an almost 50% reduction in prevalence from baseline to post-treatment (P < 0.0005) . Children who carried C . albicans at one visit had 3 to 20 times greater odds of carrying C . albicans at another visit . C . albicans was cultured from 12 children at all time-points and from 10 children at four time-points . Children with oral C . albicans frequently maintained carriage over time, even with regular dental care. Cutis, 2002 Sep, 70(3), 185 - 92 Candida albicans intralesional injection immunotherapy of warts; Signore RJ; Often, the treatment of verrucae is frustrating for both the physician and patient . Treatment may be painful, scarring, ineffective, and costly . The object of this study was to compare the clinical outcomes and safety of Candida albicans intralesional injection immunotherapy (CI) versus conventional wart treatment . The results of a prospective, nonrandomized, open-label, comparison study are presented . CI is a novel, simple, and inexpensive modality for the treatment of verruca vulgaris (VV), including the plantar wart (PW) type . CI appears safe and well tolerated and is well suited for multiple warts on hands and fingers, PWs, and recalcitrant warts . Uninjected warts also may regress during CI . The new phenomenon of postimmunotherapy-revealed cicatrix (PIRC) is described . CI represents an off-label usage of Candida extract. Acta Derm Venereol, 2002, 82(3), 170 - 3 In vitro activity of phytosphingosines against Malassezia furfur and Candida albicans; Nenoff P et al.; Long-chain sphingoid bases, e.g . phytosphingosine, sphingosine and sphinganine, main constituents of the stratum corneum, can strongly inhibit the growth of microorganisms that are known to have undesirable effects on the skin . The aim of this study was to investigate the in vitro activity of different phytosphingosine preparations against Malassezia furfur, and, in comparison, against the common facultative pathogenic yeast Candida albicans . An agar dilution test for minimum inhibitory concentration (MIC) investigation of phytosphingosine base, phytosphingosine lactic acid salt, phytosphingosine HCl, and phytosphingosine glycolic acid salt was carried out using D.S.T . agar containing 2% olive oil and 0.2% Tween 80, to allow growth of the lipophilic yeast . M . furfur growth inhibition in vitro could be achieved only at extremely high phytosphingosine concentrations . Phytospingosine base had the lowest MIC value (mean 6,250 microg/ml, corresponding to 0.63% of phytospingosine in the agar) . For the different phytosphingosine salts--lactic acid salt, HCl and glycolic acid salt--4-8 fold higher MIC values were noted . Unexpectedly, there was a growth stimulating effect of Malassezia at lower phytosphingosine concentrations . In comparison, growth of Candida albicans strains was inhibited at phytosphingosine concentrations between 152 and 269 microg/ml. Biochim Biophys Acta, 2002 Oct 3, 1556(1), 73 - 80 Characterization of the mitochondrial respiratory pathways in Candida albicans; Helmerhorst EJ et al.; Candida albicans is an opportunistic oral pathogen . The flexibility of this microorganism in response to environmental changes includes the expression of a cyanide-resistant alternative respiratory pathway . In the present study, we characterized both conventional and alternative respiratory pathways and determined their ADP/O ratios, inhibitor sensitivity profiles and the impact of the utilization of either pathway on susceptibility to commonly used antimycotics . Oxygen consumption by isolated mitochondria using NADH or malate/pyruvate as respiratory substrates indicated that C . albicans cells express both cytoplasmic and matrix NADH-ubiquinone oxidoreductase activities . The ADP/O ratio was higher for malate/pyruvate (2.2+/-0.1), which generate NADH in the matrix, than for externally added NADH (1.4+/-0.2) . In addition, malate/pyruvate respiration was rotenone-sensitive, and an enzyme activity assay further confirmed that C . albicans cells express Complex I activity . Cells grown in the presence of antimycin A expressed the cyanide-insensitive respiratory pathway . Determination of the respiratory control ratio (RCR) and ADP/O ratios of mitochondria from these cells indicated that electron transport from ubiquinone to oxygen via the alternative respiratory pathway was not coupled to ATP production; however, an ADP/O ratio of 0.8 was found for substrates that donate electrons at Complex I . Comparison of antifungal susceptibility of C . albicans cells respiring via the conventional or alternative respiratory pathways showed that respiration via the alternative pathway does not reduce the susceptibility of cells to a series of clinically employed antimycotics (using Fungitest), or to the naturally occurring human salivary antifungal peptide, histatin 5. J Nat Prod, 2002 Sep, 65(9), 1353 - 6 Corticatic acids D and E, polyacetylenic geranylgeranyltransferase type I inhibitors, from the marine sponge Petrosia corticata; Nishimura S et al.; Two new polyacetylenic acids, corticatic acids D (2) and E (3), have been isolated from the marine sponge Petrosia corticata along with the known corticatic acid A (1) as geranylgeranyltransferase type I (GGTase I) inhibitors . Their structures were elucidated on the basis of spectroscopic and chemical methods . Compounds 1-3 inhibited GGTase I from Candida albicans with IC(50) values of 1.9-7.3 microM. Int Immunopharmacol, 2002 Jul, 2(8), 1109 - 22 Relationship between the physical properties of Candida albicans cell well beta-glucan and activation of leukocytes in vitro; Ishibashi K et al.; We previously reported that the fungal particle 1,3-beta-D-glucan derived from Candida albicans, a pathogenic fungus, was obtained by oxidation of the cell wall with sodium hypochlorite (NaClO) . It could be solubilized by treatment with dimethylsulfoxide (DMSO) . In the present study, we prepared Candida 1,3-beta-D-glucan having different physical properties, and examined the relationship between leukocyte activation and the physicochemical properties . Beta-glucan activated leukocytes significantly more effectively in a particulate than solubilized form in terms of TNF-alpha production by RAW 264.7 cells, hydrogen peroxide production by murine PEC and IL-8 production by human PBMC . Furthermore, we compared the biological activity of the glucan particles oxidized under various conditions . Interestingly, inactive and antagonistic particles were obtained under strong oxidation conditions . However, the inactive particles showed significant agonistic activity on dissolution in DMSO and following lyophilization . These facts strongly suggested that the solubility and assembly of the components influence the immunopharmacological activities of 1,3-beta-D-glucans. Biochem J, 2002 Nov 15, 368(Pt 1), 23 - 7 The cyclic dipeptide CI-4 {cyclo-(l-Arg-d-Pro)} inhibits family 18 chitinases by structural mimicry of a reaction intermediate; Houston DR et al.; Family 18 chitinases are attractive targets for the development of new inhibitors with chemotherapeutic potential against fungi, insects and protozoan/nematodal parasites . Although several inhibitors have been identified, these are based on complex chemistry, which hampers iterative structure-based optimization . Here we report the details of chitinase inhibition by the natural product peptide CI-4 { cyclo -(L-Arg-D-Pro)}, which possesses activity against the human pathogenic fungus Candida albicans, and describe a 1.7 A (0.17 nm) crystal structure of CI-4 in complex with the enzyme . The structure reveals that the cyclic dipeptide inhibits chitinases by structurally mimicking a reaction intermediate, and could, on the basis of its accessible chemistry, be a candidate for further optimization. Afr Women Health, 1994 Jul-Sep, 2(3), 5 - 8 Stubborn vaginal yeast infections. {Clinical evaluation of combined use of the spermicide Nonoxynol-9 and condoms} De Andrea Filho A, Marziona F. PIP: Condoms represent an efficient family planning method . Their use was 1st described by the Italian anatomist Fallopio in 1564 . Their effectiveness is considered to result in 0.5-2 births/100 years of marriage . 1st descriptions of vaginal contraceptives, by the Egyptians, date back to 1850 B.C . Their effectiveness is considered to be 5-10/100 years of marriage . A combined usage of condom and spermicides such as Nonoxynol-9 could thus elevate contraceptive effectiveness more than 20 times . A clinical test of such a combination product was conducted involving 2 groups consisting of 30 women each (1 control group) in order to evaluate possible alterations in vaginal mucus . By using questionnaires, women with a history of allergy to condoms or vaginal creams were excluded . However, those with symptoms of vulvovaginitis were not . The 2 groups were subjected to laboratory tests before and after usage: bacterioscopy, culture of vulvovaginal secretions, the saline drop method in order to diagnose Trichomonas, and the potassium hydroxide drop method in order to diagnose Gardnerella vaginalis and Candida albicans . Vaginal colposcopy and measuring of vulvovaginal pH were also performed . The results, before and after use, are listed for both groups in 3 tables, with reference to 2 clinical symptoms (itching of burning sensation), vaginal pH (normal, above, below), and various microorganisms being isolated . The tables do not allow for any interpretation of significant alterations resulting from the use of the combination product, e.g., the elevation of pH in some cases and 1 failure should be attributed to variations of flora not caused by the product, but being due to chance variations occurring in any given population . The absence of traumatic factors is due to the vaginal structure being functionally adapted, with numerous folds and wrinkles, to coitus . The effectiveness of the product is well documented in literature, and data listing decreased sperm motility is presented . It is concluded that no clinical adverse effects result with reference to the vulvovaginal epithelium or the penis . Contracept Fertil Sex (Paris), 1995 Apr, 23(4), 267 - 70 {Medical management of presumed sexual assault victims in Dakar, Senegal . Report of 25 cases}; Diouf A et al.; PIP: Between January 1989 and June 1992, interviews with and a medical examination of 25 rape victims (mean age, 12 years; range, 7-21 years) were conducted at the University Hospital in Dakar, Senegal . Females aged less than 18 represented 84% of cases, 25% of whom were less than 10 years old . None were married . Sexual abuse occurred during ovulation among 5 of the 11 victims who had reached menses, thus placing them at risk of pregnancy . Places where the rapes occurred were the dwelling of either the offender or the victim (56%), especially that of the victim (9/14 cases), or a public place (44%) . The victim knew the presumed offender in 80% of cases . Known offenders included fathers, priests, employers, ex-boyfriends, and men living in the vicinity . In five cases the female was gang-raped . 18 victims waited 72 hours before seeking care; 2 females waited 3 weeks . The long delays compromised cytologic exams and findings . None of the victims had ever had a child . One case had nine weeks of amenorrhea and tested positive for pregnancy . The only extragenital lesion was a bruise on the thigh . Genital lesions included bruises or lacerations of the large and small labia, lacerated hymen (sometimes ruptured hymen), fossa triangularis, and vaginal lacerations . There was no evidence of anal penetration . 3 of 15 samples tested positive for pathogens (1 for Escherichia coli; 2 for Candida albicans) . Sperm was found in only 1 case . In 7 cases, penetration had not occurred, probably due to immature genitals . It was not clear whether penetration had occurred or not in 3 other cases . Penetration clearly occurred in 15 cases . Physicians and allied health personnel should be sensitive and prepared to perform a complete physical exam so as to defend the interests of the victim and of society by obtaining proof to convict the sexual offender . Senegalese jurisprudence does not consider the distress of rape victims with an unwanted pregnancy . Legislation should include rape as a reason for legal abortion . Yeast, 2002 Oct, 19(14), 1243 - 59 Functional, comparative and cell biological analysis of Saccharomyces cerevisiae Kre5p; Levinson JN et al.; Saccharomyces cerevisiae kre5delta mutants lack beta-1,6-glucan, a polymer required for proper cell wall assembly and architecture . A functional and cell biological analysis of Kre5p was conducted to further elucidate the role of this diverged protein glucosyltransferase-like protein in beta-1,6-glucan synthesis . Kre5p was found to be a primarily soluble N-glycoprotein of approximately 200 kDa, that localizes to the endoplasmic reticulum . The terminal phenotype of Kre5p-deficient cells was observed, and revealed a severe cell wall morphological defect . KRE6, encoding a glucanase-like protein, was identified as a multicopy suppressor of a temperature-sensitive kre5 allele, suggesting that these proteins may participate in a common beta-1,6-biosynthetic pathway . An analysis of truncated versions of Kre5p indicated that all major regions of the protein are required for viability . Finally, Candida albicans KRE5 was shown to partially restore growth to S . cerevisiae kre5delta cells, suggesting that these proteins are functionally related . Proc Natl Acad Sci U S A, 2002 Oct 1, 99(20), 12969 - 74 Epub 2002 Sep 23. The CENP-A homolog CaCse4p in the pathogenic yeast Candida albicans is a centromere protein essential for chromosome transmission; Sanyal K et al.; The gene encoding CaCse4p, a homolog of the evolutionarily conserved histone H3-like kinetochore protein CENP-A, has been cloned from the human pathogenic diploid yeast Candida albicans . To study the phenotype of C . albicans diploid cells depleted of CaCse4p, we deleted one copy of CaCSE4 and brought the other copy under control of a regulated PCK1 promoter (repressed by glucose and induced by succinate) . Inability of this strain to grow on glucose medium indicates that CaCse4p is essential for cell viability . Shutdown of CaCSE4 expression resulted in a sharp decline of CaCse4p levels with concomitant loss of cell viability . Examination of these CaCse4p-depleted cells revealed a mitosis-specific arrest phenotype with accumulation of large-budded cells containing single G(2) nuclei at or near the bud neck along with short mitotic spindles . Subcellular localization of CaCse4p by anti-CaCse4p antibodies in both budding and filamentous C . albicans cells revealed an intense dot-like signal always colocalized with 4',6-diamidino-2-phenylindole-stained nuclei . Unlike higher eukaryotes but similar to the budding yeast Saccharomyces cerevisiae, centromere separation in the budding yeast form of C . albicans occurs before anaphase, at a very early stage of the cell cycle . In the filamentous mode of cell division, however, centromere separation appears to occur in early anaphase . Coimmunostaining with anti-CaCse4p and antitubulin antibodies shows that CaCse4p localizes near spindle pole bodies, analogous to the localization pattern observed for kinetochore proteins in S . cerevisiae . CaCse4p promises to be a highly useful reagent for the study of centromere/kinetochore structure in C . albicans. J Immunol Methods . 1997 Jan;14(1):19. Phagocytosis measured as inhibition of uridine uptake by Candida Albicans; Yamamura M et al.; Inhibition of 3H-uridine incorporation into Candida albicans can be used as a sensitive index of phagocytic function because: 1) there is a linear correlation between uridine incorporation and yeast number; 2) phagocytic cells do not incorporate significant amounts of uridine in short term cultures; and 3) C . albicans replicating inside phagocytic cells does not take up uridine from culture medium.Appropriate conditions for measuring phagocytic capacity of human polymorphonuclear cells (PMNs) were 5 x 10(5) C . albicans and 5 x 10(4) PMNs in 0.5 ml of medium containing 2.5% AB serum . This mixture was incubated for 30 min at 37 degrees C . Aliquots were then transferred into microtiter wells and incubated for a further 60 min in the presence of 3H-uridine.Under these conditions PMN luucocytes from 25 healthy individuals caused suppression of uridine incorporation ranging from 33 to 75% (50 +/- 12). Acta Reprod Turc, 1982 Oct, 4(2), 34 - 8 Intrauterine devices (IUDs) and their complications (clinical evaluation of 2013 women with IUD in-situ); Ayhan A et al.; PIP: IUD related events were evaluated at the Department of Obstetrics and Gynecology, Hacettepe University in Ankara, Turkey . The study population included 2213 fertile, healthy women who had an IUD in situ . The age range was 17-48 years . All IUDs were Lippes loop, size C and D, and they were inserted by an experienced physician and nurse on the 5th day of menstruation . The follow-up time was 1 year in 2013 women with IUDs . There was no follow-up on 200 women who were excluded from the study . Both physical and pelvic examinations were conducted on every women at 3 month intervals during the follow-up period . IUD related events were evaluated by using the Pearl index and life table method for some events . Of the 2013 women with IUD in situ, abnormal pelvic findings such as pelvic inflammatory disease and lower genital tract infection were seen in 85 (4.2%); PID was seen in 39 (1.9%) and lower genital tract infection caused by candida albicans and trichomonas vaginalis was seen in 46 (2.3%) . Persistent abnormal vaginal bleeding was seen in 77 women; persistent pain was seen in 10 women, 3.8 and 0.5/100 women years, respectively . The pregnancy rate associated with IUD use was 1.2, 1/2/100 women years of IUD use . Of the 25 total pregnancies that occurred, 2 were ectopic, 3 resulted in term delivery, and the 20 remaining were terminated by induced abortion . The expulsion rate was 1.6% (33 women), 1.6/100 women years of IUD use . The medical removal and uterine perforation rates per 100 women years of IUD use were 12 (240 women) and 0.15 (3 women), respectively . There was no mortality related to the IUD and its complications . J Antibiot (Tokyo), 2002 Jul, 55(7), 643 - 9 Phytotoxic arylethylamides from limnic bacteria using a screening with microalgae; Maskey RP et al.; N-Phenylethylamides 1a-1f, were isolated from cultures of three limnic strains GW90a, GW102a and GW73a . Strain GW102a delivered additionally the compound cyclo(isoleucyldehydroalanyl) (2) . The structure of these compounds were assigned by a detailed spectral analysis . Due to their potential use as herbicides, various related compounds 1a, 3, 4a and 4b were synthesized . The minimum inhibitory concentration (MIC) against Chlorella vulgaris, Chlorella sorokiniana, Chlorella salina and Scenedesmus subspicatus ranged from 100 to 12.5 microg/ml . All these amides were found to be inactive against Mucor miehei, Candida albicans, and some bacteria. Curr Mol Med, 2002 Sep, 2(6), 507 - 24 The interaction of fungi with dendritic cells: implications for Th immunity and vaccination; Claudia M et al.; Human beings are continuously exposed to fungi, yet they rarely get fungal diseases . The delicate balance between the host and these otherwise harmless pathogens may turn into a parasitic relationship, resulting in the development of severe infections . The ability to reversibly switch between unicellular and filamentous forms, all of which can be found in infected tissues, is thought to be important for virulence . Efficient responses to the different forms of fungi require different mechanisms of immunity . Dendritic cells (DC) are uniquely able at decoding the fungus-associated information and translating it in qualitatively different T helper (Th) immune responses, in vitro and in vivo . Myeloid DC phagocytosed yeasts and hyphae of Candida albicans and conidia and hyphae of Aspergillus fumigatus, both in vitro and in vivo . Phagocytosis occurred through distinct phagocytic morphologies, involving the engagement and cooperativity of distinct recognition receptors . However, receptor engagement and cooperativity were greatly modified by opsonization . The engagement of distinct receptors translated into disparate downstream signaling events, ultimately affecting cytokine production and costimulation . In vivo studies confirmed that the choice of receptor and mode of entry of fungi into DC was responsible for Th polarization and patterns of susceptibility or resistance to infection . Adoptive transfer of different types of DC activated protective, nonprotective and regulatory T cells, ultimately affecting the outcome of infection . The conclusions are that the selective exploitation of receptors and mode of entry into DC may determine the full range of host's immune relationships with fungi and have important implications in the design of vaccine-based strategies. Z Naturforsch {C}, 2002 Jul-Aug, 57(7-8), 624 - 8 GC-mS analysis and anti-microbial activity of acidic fractions obtained from Paeonia peregrina and Paeonia tenuifolia roots; Ivanova A et al.; Fourteen aromatic and 24 aliphatic acids were determined by GC-MS analysis of acidic fractions obtained from Paeonia peregrina and Paeonia tenuifolia roots . Benzoic acid and its monohydroxy-, dihydroxy- and trihydroxy-derivatives are the main acid components of both Paeonia species . Some fractions could serve as a source of benzoic, 4-hydroxybenzoic, vanillic and gallic acids, as well as of ethyl gallate . The fractions inhibited the growth of Staphylococcus aureus, Escherichia coli and Candida albicans. Z Naturforsch {C}, 2002 Jul-Aug, 57(7-8), 620 - 3 Composition and antimicrobial activity of essential oil and hexane-ether extract of Tanacetum santolinoides (dc.) Feinbr . and Fertig; El-Shazly A et al.; Tanacetum santolinoides, Essential Oil Composition, n-Hexane-Ether Extract Composition The essential oil of the aerial parts of Tanacetum santolinoides was analyzed by capillary GLC and GLC-MS . Altogether 30 components were identified . The main constituents were thymol (18%), trans-thujone (17.5%), trans-chrysanthenyl acetate (13.2%), cis-chrysanthenyl acetate (9.2%), umbellulone (9.7%) and 1,8-cineole (4.7%) . Similar essential oil pattern in addition to palmitic acid methyl ester, palmitic acid, stigmasterol, sitosterol and two flavonoidal aglycons were found in the n-hexane-ether extract . The oil showed strong in vitro activity against E . coli, Bacillus subtilis and Candida albicans. Z Naturforsch {C}, 2002 Jul-Aug, 57(7-8), 614 - 9 Structure of tyrolobibenzyl D and biological activity of tyrolobibenzyls from Scorzonera humilis; Zidorn C et al.; A novel tyrolobibenzyl derivative, 1-->beta-D-apiosyl-beta-D-glucopyranosyl 4-{2-(4-hydroxyphenyl)ethyl}benzofuran-2-carboxylate 3 (tyrolobibenzyl D) was isolated from Scorzonera humilis L . and its structure established by mass spectrometry and 1D- and 2D-NMR spectroscopy . The biological activities of the new compound and related tyrolobibenzyls A-C (1-2, 4) and the semi-synthetic peracetyl derivatives of tyrolobibenzyls B (2a) and C (4a) were assessed . The results revealed no cytotoxic activity against P388 cells and neither anti-bacterial activity against Bacillus subtilis nor antifungal activity against Candida albicans and Trichophyton mentagrophytes for any of the investigated compounds . An evaluation of potential chemopreventive activity of 2, 2a, 4, and 4a also revealed no pronounced activity in any of the employed assaying systems. Am J Obstet Gynecol, 2002 Sep, 187(3), 569 - 74 Prevalence of vulvovaginal candidiasis and susceptibility to fluconazole in women; Bauters TG et al.; OBJECTIVE: The purpose of this study was to determine the prevalence of vaginal colonization by Candida with the use of a rapid detection method, to examine the determinants of vaginal candidiasis, and to evaluate susceptibility for fluconazole . STUDY DESIGN: Vaginal swabs were collected from unselected women at the outpatient clinic of the Department of Obstetrics and Gynecology . A differentiation was made between patients with a positive and a negative potassium hydroxide examination . RESULTS: Six hundred twelve women were recruited, of whom 39 women (6.3%) had clinical candidiasis . The overall rate of yeast colonization was 20.1% . Candida albicans was isolated most frequently(68.3%), followed by C glabrata (16.3%) and C parapsilosis (8.9%) . Clinical candidiasis was related positively with the state of estrogen impregnation . In vitro susceptibility testing by the National Committee for Clinical Laboratory Standards method for fluconazole revealed that 21.1% of the isolates were resistant . CONCLUSION: More than 20% of the unselected women were colonized with Candida species . Hyperestrogenemia was associated with an increased vulvovaginal colonization by Candida . Surprisingly, 21% of the isolates was resistant to fluconazole, according to the National Committee for Clinical Laboratory Standards method. Antimicrob Agents Chemother, 2002 Oct, 46(10), 3236 - 42 Comparative evaluation of a new fluorescent carboxyfluorescein diacetate-modified microdilution method for antifungal susceptibility testing of Candida albicans isolates; Liao RS et al.; This report presents a fluorescent carboxyfluorescein diacetate (CFDA)-modified microdilution method used for the susceptibility testing of Candida albicans to amphotericin B, fluconazole, ketoconazole, itraconazole, voriconazole, and flucytosine . Four different broth microdilution susceptibility testing methods were simultaneously evaluated at 24 and 48 h . The MICs determined using the CFDA-modified method (MIC(cfda)) were compared to those obtained by the standard broth microdilution method (MIC(visual)) and a procedure employing the indicator Alamar blue (MIC(alamar)) . The reference MIC was determined visually as recommended by the NCCLS M27-A protocol, and then quantified spectrophotometrically following agitation (MIC(spec)) . The CFDA-modified microdilution method was demonstrated to effectively determine the MICs for all the antifungal drugs tested at both 24 and 48 h . The results from both the MIC(spec) and MIC(cfda) methods yielded >80% agreement within +/-1 dilution and >90% agreement within +/-2 dilutions at 24 h in comparison to the reference MIC(visual) method, respectively . The trailing growth phenomenon that occurs with azole antifungal drugs and many strains of C . albicans did not inhibit the effectiveness of the MIC(spec) and MIC(cfda) methods . The MIC(spec) and MIC(cfda) methods shared 92.8% agreement within +/-1 dilution at 24 h and 87.6% agreement within +/-1 dilution at 48 h. Antimicrob Agents Chemother, 2002 Oct, 46(10), 3175 - 9 Effect of prolonged fluconazole treatment on Candida albicans in diffusion chambers implanted into mice; Sohnle PG et al.; Fluconazole is an azole agent with primarily fungistatic activity in standard in vitro susceptibility tests . The present study was undertaken to develop a diffusion chamber model system in mice in order to study the in vivo effects of prolonged fluconazole treatment on Candida albicans . Chambers containing 100 C . albicans yeast cells were implanted subcutaneously on the flanks of C57BL/6 mice and were then retrieved 6 or 14 weeks later (after fluconazole treatment for 4 or 12 weeks, respectively) . Leukocyte counts demonstrated that implantation of the chambers did elicit an inflammatory response but that only small numbers of inflammatory cells were able to enter the chamber interior . Treatment with fluconazole at 10 mg/kg of body weight/day for 12 weeks not only reduced the numbers of viable organisms within the chambers compared to those in untreated mice (mean +/- standard deviation of log(10) CFU of 0.7 +/- 1.2 versus 2.3 +/- 2.0; P < 0.001 by the Bonferroni test) but also increased the numbers of chambers that became sterile over the treatment period (14 of 16 versus 6 of 19; P = 0.0009 by the chi-square test) . However, treatment for only 4 weeks had minimal effects on the numbers of chamber CFU, and none of the chambers became sterile during this period . Distribution of retrieved organisms between interior fluid and the chamber filters was approximately equal in all the treatment groups . This model system appears to be useful for evaluating the effects of antifungal drugs over prolonged periods in vivo . Its use in the present study demonstrates that fluconazole can increase the rate of sterilization of C . albicans foci that are protected from the host's inflammatory response. Antimicrob Agents Chemother, 2002 Oct, 46(10), 3113 - 7 Endogenous reactive oxygen species is an important mediator of miconazole antifungal effect; Kobayashi D et al.; We investigated the significance of endogenous reactive oxygen species (ROS) produced by fungi treated with miconazole . ROS production in Candida albicans was measured by a real-time fluorogenic assay . The level of ROS production was increased by miconazole at the MIC (0.125 micro g/ml) and was enhanced further in a dose-dependent manner, with a fourfold increase detected when miconazole was used at 12.5 micro g/ml . This increase in the level of ROS production was completely inhibited by pyrrolidinedithiocarbamate (PDTC), an antioxidant, at 10 micro M . In a colony formation assay, the decrease in cell viability associated with miconazole treatment was significantly prevented by addition of PDTC . Moreover, the level of ROS production by 10 clinical isolates of Candida species was inversely correlated with the miconazole MIC (r = -0.8818; P < 0.01) . These results indicate that ROS production is important to the antifungal activity of miconazole. Res Microbiol, 2002 Jul-Aug, 153(6), 373 - 8 Determination of the stability of protein pools from the cell wall of fungi; Ruiz-Herrera J et al.; Stability of the protein populations present in the cell wall of three ascomycetous fungi Candida albicans, Saccharomyces cerevisiae and Yarrowia lipolytica was investigated . Cell wall proteins were either labeled with biotin or radiolabeled with amino acids, and chased for a period of time representing several generations . Proteins linked by non-covalent or covalent bonds were separated and their turnover was analyzed . No significant turnover took place during the chase period, and in fact radioactive proteins were accumulated in the wall during the period possibly by transfer through the secretory pathway . This transfer did not involve de novo protein synthesis; it was inhibited by azide, and by incubation of a sec1 mutant of S . cerevisiae at the non-permissive temperature . It is concluded that proteins bound to the cell wall are stable and that there is no precursor-product relationship among those linked by non-covalent bonds and the covalently bound ones. AIDS Res Hum Retroviruses, 2002 Sep 1, 18(13), 903 - 8 Response and relapse rates of candidal esophagitis in HIV-infected patients treated with caspofungin; Dinubile MJ et al.; Caspofungin is a new antifungal drug of the echinocandin class . We analyzed the clinical efficacy of caspofungin (50 mg/day) in the treatment of HIV-infected adults with endoscopically documented Candida esophagitis and enrolled in four clinical trials of caspofungin . Symptoms were evaluated daily; a favorable outcome required complete resolution of all esophageal symptoms assessed at the time of discontinuation of therapy . Relapse was defined as recurrent symptoms during the subsequent 2 weeks . A multivariate logistic regression model was developed to identify potential factors (including severity of symptoms at presentation, CD4(+) cell count on entry, extent of disease {assessed endoscopically at baseline}, causative Candida species, duration of therapy {overall and after resolution of symptoms}, time on treatment before symptom resolution, and antifungal prophylaxis) that might predict symptomatic relapse in the 2 weeks following completion of therapy . The median CD4(+) lymphocyte count for the entire population was 31/mm(3) . Candida albicans was isolated from 109 of 110 patient samples cultured for the pathogen and constituted the sole isolate in 77% . Extensive esophageal involvement was present in 55% of patients at the time of pretreatment endoscopy . The duration of therapy ranged from 7 to 20 days (median, 12 days) . Symptoms resolved in 117 of 123 patients (95%; 95% confidence interval, 90-98%) with a median time of ~4 days . Response rates were 43 of 46 (93%) and 70 of 73 (96%) for patients with greater or fewer than 50 CD4(+) cells/mm(3), and 80 of 85 (94%) and 23 of 24 (96%) in infections caused by C . albicans alone or in association with non-albicans isolates, respectively . Symptoms recurred within 2 weeks of stopping caspofungin in 19 of 115 evaluable patients (17%), including 3 of 16 (19%) receiving antifungal prophylaxis . Relapse rates were similar for patients with greater or fewer than 50 CD4(+) cells/mm(3) . In this relatively small number of patients, only symptom severity and extent of disease judged endoscopically at baseline were significantly (p < 0.10) associated with early relapse in the multivariate model. J Invest Dermatol, 2002 Sep, 119(3), 600 - 8 Mechanisms underlying the suppression of established immune responses by ultraviolet radiation; Nghiem DX et al.; The ultraviolet radiation present in sunlight is immune suppressive . Recently we showed that solar-simulated ultraviolet radiation (ultraviolet A + B; 295-400 nm), applied after immunization, suppressed immunologic memory and the elicitation of delayed-type hypersensitivity to the common opportunistic pathogen, Candida albicans . Further, we found that wavelengths in the ultraviolet A region of the solar spectrum (320-400 nm), devoid of ultraviolet B, were equally effective in activating immune suppression as ultraviolet A + B radiation . Here we report on the mechanisms involved . Maximal immune suppression was found when mice were exposed to solar-simulated ultraviolet radiation 7-9 d post immunization . No immune suppression was found in ultraviolet-irradiated mice injected with monoclonal anti-interleukin-10 antibody, or mice exposed to solar-simulated ultraviolet radiation and injected with recombinant interleukin-12 . Suppressor lymphocytes were found in the spleens of mice exposed to ultraviolet A + B radiation . In addition, antigen-specific suppressor T cells (CD3+, CD4+, DX5+) were found in the spleens of mice exposed to ultraviolet A radiation . Applying liposomes containing bacteriophage T4N5 to the skin of mice exposed to solar-simulated ultraviolet A + B radiation, or mice exposed to ultraviolet A radiation, blocked immune suppression, demonstrating an essential role for ultraviolet-induced DNA damage in the suppression of established immune reactions . These findings indicate that overlapping immune suppressive mechanisms are activated by ultraviolet A and ultraviolet A + B radiation . Moreover, our findings demonstrate that ultraviolet radiation activates similar immunologic pathways to suppress the induction of, or the elicitation of, the immune response. Med Mycol, 2002 Aug, 40(4), 443 - 5 Prevalence of Candida dubliniensis in the BCCM/IHEM Biomedical Fungi/Yeasts culture collection (isolates before 1990); Martins-Nishikawa M et al.; The BCCM/IHEM Biomedical Fungi/Yeasts collection hosts 1200 Candida albicans strains of the Vanbreuseghem mycotheque isolated between 1951 and 1997 . From this collection, 469 freeze-dried C . albicans strains, producing chlamydospores, germ tubes and forming green colonies on CHROMagar, all isolated before 1990, were screened to identify the Candida dubliniensis isolates . Screening was performed in different steps using the growth at 45 degrees C, the assimilation of xylose, the intracellular beta-glucosidase activity test and C . dubliniensis-specific polymerase chain reaction (PCR) with primers from ACT1 intron sequence . Five isolates (1%) were identified as C . dubliniensis: one isolate was not documented, the others were of oropharyngeal origin of which two (1987 and 1990) were from proven human immunodeficiency virus patients. Med Mycol, 2002 Aug, 40(4), 393 - 7 Phagocytic and candidacidal activities of macrophages from suckling and adult mice pretreated with concanavalin-A; Moresco TR et al.; In this study, we investigated the effect of concanavalin-A (Con-A) on the activation of phagocytosis and killing of Candida albicans by peritoneal macrophages from suckling and adult mice . Pretreatment of adult mice with Con-A dose-dependently increased the percentage of macrophages phagocytosing C . albicans in vitro from 3.8 +/- 0.9 to 24.2 +/- 2.4 in the absence of serum opsonins . Addition of mannan (50 microg) and mannose (50 mM) to the incubation medium reduced phagocytosis from 21.5 +/- 1.3 to 4.7 +/- 1.9, suggesting that treatment with Con-A increased phagocytosis mediated by mannose receptors . Killing of C . albicans was also increased by increasing the dose of Con-A . Pretreatment of suckling mice with Con-A increased the macrophages' phagocytic and candidacidal activities by an amount similar to that observed in adult mice . Furthermore, suckling mice pretreated with Con-A survived an intraperitoneal inoculum of 5 x 10(7) C . albicans, whereas all control mice died within 24-48 h of infection . This suggested that increased phagocytosis and killing of C . albicans stimulated by the action of Con-A conferred early protection upon suckling mice experimentally infected with C . albicans. Med Mycol, 2002 Aug, 40(4), 359 - 75 Distinct protective host defenses against oral and vaginal candidiasis; Fidel PL Jr; Oral and vaginal candidiasis are the two most common forms of opportunistic fungal infections . However, the prevalence of each can be quite variable depending on the immune status of the host . While vulvovaginal candidiasis (VVC) is equally common in immunocompetent and immunocompromised women, oropharyngeal candidiasis (OPC) is infrequent except under immunocompromised states . Candida albicans, the causative agent in the majority of cases, is a commensal of the gastrointestinal and lower female reproductive tracts . Thus, most healthy individuals have protective Candida-specific immunity that normal