ß-lapachone and α-nor-lapachone modulate Candida albicans viability and virulence factors.

BACKGROUND: Candida albicans is the most important fungal pathogen that causes infections in humans, and the search for new therapeutic strategies for its treatment is essential. OBJECTIVE: The aim of this study was to evaluate the activity of seven naphthoquinones (ß-lapachone, ß-nor-lapachone, bromide-ß-lapachone, hydroxy-ß-lapachone, α-lapachone, α-nor-lapachone and α-xyloidone) on the growth of a fluconazole-resistant C. albicans oral clinical isolate and the effects of these compounds on the viability of mammalian cells, on yeast's morphogenesis, biofilm formation and cell wall mannoproteins availability. RESULTS: All the compounds were able to completely inhibit the yeast growth. ß-lapachone and α-nor-lapachone were the less cytotoxic compounds against L929 and RAW 264.7 cells. At IC50, ß-lapachone inhibited morphogenesis in 92%, while the treatment of yeast cells with α-nor-lapachone decreased yeast-to-hyphae transition in 42%. At 50µg/ml, ß-lapachone inhibited biofilm formation by 84%, whereas α-nor-lapachone reduced biofilm formation by 64%. The treatment of yeast cells with ß-lapachone decreased cell wall mannoproteins availability in 28.5%, while α-nor-lapachone was not able to interfere on this virulence factor. Taken together, data show that ß-lapachone and α-nor-lapachone exhibited in vitro cytotoxicity against a fluconazole-resistant C. albicans strain, thus demonstrating to be promising candidates to be used in the treatment of infections caused by this fungus.

A novel nerolidol-rich essential oil from Piper claussenianum modulates Candida albicans biofilm.

Candidiasis is a major opportunistic fungal infection in humans, and its incidence has increased steadily over the last two decades. Candida albicans, the main species of the genus, has a large arsenal of virulence attributes that contribute to successful infections, such as dimorphism and biofilm formation. The adverse effects of eukaryotic antimicrobial therapies associated with an increase in resistance to the compounds presently available have boosted efforts to improve the therapeutic arsenal against candidiasis with a newer and cheaper range of drugs. In this study, a novel nerolidol-rich essential oil (EO) derived from Piper claussenianum (Miq.) C. DC., Piperaceae, was tested on the growth, transition (yeast to hyphae), formation and stability of biofilms produced by C. albicans. Both inflorescence and leaf EOs were evaluated and revealed MIC values ranging from 0.04 to 0.1 % and 0.2 to 1.26 %, respectively. Furthermore, leaf EO managed to downregulate the yeast-to-hyphae transition by 81 %, as well as reducing biofilm formation by about 30 and 50 % after incubation for 24 and 48 h, respectively. The EO was also able to reduce the viability of pre-formed biofilm by 63.9 %. Finally, the association between the leaf EO and fluconazole was evaluated and revealed an interesting synergistic effect. Taken together, these results demonstrate that this novel compound could be a promising agent and could reinforce the arsenal of therapeutic alternatives for the treatment of candidiasis. Furthermore, it may represent a novel and natural source of nerolidol, which could be of interest pharmaceutically.

Ectophosphatase activity in Candida albicans influences fungal adhesion: study between HIV-positive and HIV-negative isolates.

OBJECTIVE: This study describes the expression of acidic ectophosphatase activity on twenty isolates of C. albicans from oral cavities of HIV-infected children (HIV+) and compares them with fifteen isolates from HIV-negative children (HIV-), as well as the fungal adhesion to epithelial cells and medical records. METHODS: The activities were measured in intact cells grown in BHI medium for 48 h at 37 degrees C. Phosphatase activity was assayed at pH 5.5 using 4-methylumbelliferyl phosphate. Yeast adhesion was measured using the MA 104 epithelial cell line. RESULTS: Mean values of ectophosphatase activity were 610.27 +/- 166.36 and 241.25 +/- 78.96 picomoles 4-methylumbelliferone/h/10(7) cells for HIV+ and HIV- group, respectively (P = 0.049). No correlation between C. albicans enzyme activity from HIV children with viral load and CD4 percentual was observed. Yeasts with high enzyme activity, isolated from HIV+ children showed greater adherence than yeasts with basal levels of ectophosphatases from HIV- (Spearman correlation, r = 0.8). Surface phosphatase activity was apparently involved in the adhesion to host cells, as the enhanced attachment of C. albicans to host epithelial cells was reversed by pretreatment of yeast with sodium orthovanadate (1 mM), an acid phosphatase inhibitor. CONCLUSION: These results show that C. albicans from HIV+ has an ectophosphatase activity significantly higher than the other isolates. Yeasts expressing higher levels of surface phosphatase activity showed greater adhesion to epithelial cells. So, the activity of acidic surface phosphatases on these cells may contribute to the early mechanisms required for disease establishment.

Cariogenic and erosive potential of the medication used by HIV-infected children: pH and sugar concentration.

OBJECTIVE: The aim of this work was to analyze pH and sugar concentration in seven antiretroviral and three antibacterial medications frequently prescribed to HIV infected paediatric patients. METHOD: Sugars (sucrose, glucose, lactose and fructose) and pH were measured from every one of ten medications with different serial numbers in two samples. The pH was determined by a previously calibrated digital pHmeter (Beckman). Analysis of free sugars was performed using thin-layer chromatography (TLC). The pH results and the amount of sugar originated from the two samples in each lot were added. The arithmetic mean of these results were computed. RESULTS: Two antiretrovirals (Zidovudin and Abacavir Sulphate) had pH below critical level (3.55 and 3.93, respectively). All three antibacterials analyzed had pH above 5.5, and one of them (Azithromycin) had the highest pH level of the ten medications examined (9.28). Sugar was present in seven out of 10 of the medications analyzed. The antibacterials contained the highest concentration of sucrose, ranging from 40% to 54%. Glucose was found in one of the ten, sucrose was present in seven of them and none showed lactose. Fructose was not observed with the technique used. CONCLUSIONS: A number of medications frequently used by HIV-infected children may cause a significant risk of both caries and dental erosion.

Differential recovery of Candida species from subgingival sites in human immunodeficiency virus-positive and healthy children from Rio de Janeiro, Brazil.

The prevalence of subgingival Candida species was studied in 52 human immunodeficiency virus (HIV)-positive and 42 HIV-negative children. Candida was cultured from 22 (42.3%) and 3 (7.1%) HIV-infected and control children, respectively. C. albicans was the most common Candida species isolated from HIV-infected children, followed by C. dubliniensis, C. glabrata, and C. tropicalis. In the HIV-positive group, the prevalence of Candida isolation was significantly higher in children who presented with low CD4(+)-T-lymphocyte counts, elevated viral loads, and gingivitis.

[Prevalence of caries and its correlation with clinical and immunological classification in HIV-infected children]. / Prevalência de cárie e sua correlação com a classificação clínica e imunológica em crianças infectadas pelo HIV.

This research aims to determine the relationship between the prevalence of caries and clinical and immunological classification in HIV-infected children. Ninety-two outpatients (42 male and 50 female subjects) with definitive diagnosis of HIV infection took part in this research. The patients were examined in order to determine the prevalence of caries (dmf and DMFT indexes), and medical data were collected from their medical records. The mean age of the subjects was 5.77 years. Although no statistical differences were found, young patients (up to 5 years old) had more caries when they were more clinically and immunologically compromised. The same fact was observed regarding older children.