(PhSe)2 and (pCl-PhSe)2 organochalcogen compounds inhibit Candida albicans adhesion to human endocervical (HeLa) cells and show anti-biofilm activities.

Adhesion capacity on biological surfaces and biofilm formation is considered an important step in the infection process by Candida albicans. The ability of (PhSe)2 and (pCl-PhSe)2, two synthetic organic selenium (organochalcogen) compounds, to act on C. albicans virulence factors related to adhesion to human endocervical (HeLa) cell surfaces and their anti-biofilm activities was analyzed. Both organochalcogen compounds inhibited C. albicans adhesion to HeLa cells, dependent on compound concentrations. (PhSe)2 (at 20 µM; p = 0.0012) was significantly more effective than (pCl-PhSe)2 (at 20 µM; p = 0.0183) compared with the control. (PhSe)2 inhibited biofilm formation and decreased biofilm viability in both early and mature biofilms more efficiently than (pCl-PhSe)2. Overall, the organochalcogen compounds, especially (PhSe)2, were demonstrated to be effective antifungal drugs against C. albicans virulence factors related to epithelial cell surface adhesion and the formation and viability of biofilms.

Photodynamic antimicrobial chemotherapy (PACT) using toluidine blue inhibits both growth and biofilm formation by Candida krusei.

Among non-albicans Candida species, the opportunistic pathogen Candida krusei emerges because of the high mortality related to infections produced by this yeast. The Candida krusei is an opportunistic pathogen presenting an intrinsic resistance to fluconazol. In spite of the reduced number of infections produced by C. krusei, its occurrence is increasing in some groups of patients submitted to the use of fluconazol for prophylaxis. Photodynamic antimicrobial chemotherapy (PACT) is a potential antimicrobial therapy that combines visible light and a nontoxic dye, known as a photosensitizer, producing reactive oxygen species (ROS) that can kill the treated cells. The objective of this study was to investigate the effects of PACT, using toluidine blue, as a photosensitizer on both growth and biofilm formation by Candida krusei. In this work, we studied the effect of the PACT, using TB on both cell growth and biofilm formation by C. krusei. PACT was performed using a light source with output power of 0.068 W and peak wavelength of 630 nm, resulting in a fluence of 20, 30, or 40 J/cm2. In addition, ROS production was determined after PACT. The number of samples used in this study varied from 6 to 8. Statistical differences were evaluated by analysis of variance (ANOVA) and post hoc comparison with Tukey-Kramer test. PACT inhibited both growth and biofilm formation by C. krusei. It was also observed that PACT stimulated ROS production. Comparing to cells not irradiated, irradiation was able to increase ROS production in 11.43, 6.27, and 4.37 times, in the presence of TB 0.01, 0.02, and 0.05 mg/mL, respectively. These results suggest that the inhibition observed in the cell growth after PACT could be related to the ROS production, promoting cellular damage. Taken together, these results demonstrated the ability of PACT reducing both cell growth and biofilm formation by C. krusei.

Photodynamic Antimicrobial Chemotherapy (PACT), using Toluidine blue O inhibits the viability of biofilm produced by Candida albicans at different stages of development.

BACKGROUND: Candida albicans is an opportunistic fungus producing both superficial and systemic infections, especially in immunocompromised individuals. It has been demonstrated that C. albicans ability to form biofilms is a crucial process for colonization and virulence. Furthermore, a correlation between the development of drug resistance and biofilm maturation at Candida biofilms has been shown. Photodynamic Antimicrobial Chemotherapy (PACT) is a potential antimicrobial therapy that combines visible light and a non-toxic dye, known as a photosensitizer, producing reactive oxygen species (ROS) that can kill the treated cells. The objective of this study was to investigate the effects of PACT, using Toluidine Blue O (TBO) on the viability of biofilms produced by C. albicans at different stages of development. METHODS: In this study, the effects of PACT on both biofilm formation and viability of the biofilm produced by C. albicans were studied. Biofilm formation and viability were determined by a metabolic assay based on the reduction of XTT assay. In addition, the morphology of the biofilm was observed using light microscopy. RESULTS: PACT inhibited both biofilm formation and viability of the biofilm produced by C. albicans. Furthermore, PACT was able to decrease the number of both cells and filamentous form present in the biofilm structure. This inhibitory effect was observed in both early and mature biofilms. CONCLUSIONS: The results obtained in this study demonstrated the potential of PACT (using TBO) as an effective antifungal therapy, including against infections associated with biofilms at different stages of development.

Diphenyl diselenide (PhSe)2 inhibits biofilm formation by Candida albicans, increasing both ROS production and membrane permeability.

PROJECT: The opportunistic fungal Candida albicans can produce superficial and systemic infections in immunocompromised patients. An essential stage to both colonization and virulence by C. albicans is the transition from budding yeast form to filamentous form, producing biofilms. PROCEDURE: In this work, we studied the effect of the organochalcogenide compound (PhSe)2 on both cell growth and biofilm formation by C. albicans. RESULTS: (PhSe)2 inhibited both growth and biofilm formation by C. albicans. The inhibitory effects of (PhSe)2 depended on the cell density and (PhSe)2 concentration. We have also observed that (PhSe)2 stimulated ROS production (67%) and increased cell membrane permeability (2.94-fold) in C. albicans. In addition, (PhSe)2 caused a marked decrease in proteinase activity (6.8-fold) in relation to non-treated group. CONCLUSIONS: (PhSe)2 decreased both cell growth and biofilm development, decreasing the release of extracellular proteinases, which is an important facet of C. albicans pathogenicity. The toxicity of (PhSe)2 towards C. albicans can be associated with an increase in ROS production, which can increase cell permeability. The permanent damage to the cell membranes can culminate in cell death.

Biofilm formation by Candida albicans is inhibited by 4,4-dichloro diphenyl diselenide (pCl-PhSe)2.

Candida species are the fourth most common cause of nosocomial bloodstream infections. An increase in the frequency of infections which have become refractory to standard antifungal therapyhave been observed. Recently, the effect of different organochalcogenide compounds reducing both growth and germ tube formation by Candida albicans was demonstrated. This work studied the effect of the organochalcogenide compound (pCl-PhSe)2 on both growth and biofilm formation by Candida albicans. A decrease in C. albicans growth in the presence of crescent concentrations of (pCl- PhSe)2 was observed, in a cell density dependent manner. The inhibition of Candida growth by 10µM (pCl-PhSe)2 was ~60, 57, 47 and 24%, in cell densities of 10(3), 10(4), 10(5) and 10(6) cells/ml, respectively. The compound (pCl-PhSe)2 was able to inhibit biofilm formation by Candida albicans, when biofilm was performed using a cell density of 10(6) cells/ml. In addition, an increase in both ROS production (96%) and cell membrane permeability (1.107-fold) by 10 µM (pCl-PhSe)2 was observed in C. albicans.These results demonstrate that the organochalcogenide compound (pCl-PhSe)2 presents a great potential to inhibit both growth and biofilm formation by C. albicans.

Low-level laser therapy (LLLT) reduces the COX-2 mRNA expression in both subplantar and total brain tissues in the model of peripheral inflammation induced by administration of carrageenan.

In the classical model of edema formation and hyperalgesia induced by carrageenan administration in rat paw, the increase in prostaglandin E2 (PGE2) production in the central nervous system (CNS) contributes to the severity of the inflammatory and pain responses. Prostaglandins are generated by the cyclooxygenase (COX). There are two distinct COX isoforms, COX-1 and COX-2. In inflammatory tissues, COX-2 is greatly expressed producing proinflammatory prostaglandins (PGs). Low-level laser therapy (LLLT) has been used in the treatment of inflammatory pathologies, reducing both pain and acute inflammatory process. Herein we studied the effect of LLLT on both COX-2 and COX-1 messenger RNA (mRNA) expression in either subplantar or brain tissues taken from rats treated with carrageenan. The experiment was designed as follows: A1 (saline), A2 (carrageenan-0.5 mg/paw), A3 (carrageenan-0.5 mg/paw + LLLT), A4 (carrageenan-1.0 mg/paw), and A5 (carrageenan-1.0 mg/paw + LLLT). Animals from the A3 and A5 groups were irradiated at 1 h after carrageenan administration, using a diode laser with an output power of 30 mW and a wavelength of 660 nm. The laser beam covered an area of 0.785 cm(2), resulting in an energy dosage of 7.5 J/cm(2). Both COX-2 and COX-1 mRNAs were measured by RT-PCR. Six hours after carrageenan administration, COX-2 mRNA expression was significantly increased both in the subplantar (2.2-4.1-fold) and total brain (8.65-13.79-fold) tissues. COX-1 mRNA expression was not changed. LLLT (7.5 J/cm(2)) reduced significantly the COX-2 mRNA expression both in the subplantar (~2.5-fold) and brain (4.84-9.67-fold) tissues. The results show that LLLT is able to reduce COX-2 mRNA expression. It is possible that the mechanism of LLLT decreasing hyperalgesia is also related to its effect in reducing the COX-2 expression in the CNS.

Photodynamic antimicrobial chemotherapy (PACT) inhibits biofilm formation by Candida albicans, increasing both ROS production and membrane permeability.

The opportunistic fungal Candida albicans is able to produce both superficial and systemic infections in immunocompromised patients. Photodynamic antimicrobial chemotherapy (PACT) is a process that combines visible light and a photosensitizer, producing reactive oxygen species (ROS) that can kill the treated cells and has been presented as a potential antimicrobial therapy. In this work, we study the effects of PACT, using toluidine blue (TB) as a photosensitizer drug, on ROS production and cell damage and the ability of C. albicans to form biofilm. A significant decrease was observed in the cell growth after PACT in a TB concentration-dependent manner. This effect was dependent on the incubation time after PACT. In addition, an increase in both the ROS production and cell permeability, after PACT, in a TB concentration-dependent manner was observed. PACT, using 0.1 mg/ml TB was able to reduce biofilm formation in 30, 50, and 62%, in cells submitted to incubation times of 1, 2, and 3 h, respectively. These results suggested that PACT, using TB, is able to decrease both growth and biofilm formation by C. albicans, possibly by a mechanism evolving both ROS production and the increase in the cell permeability.

Candida albicans growth and germ tube formation can be inhibited by simple diphenyl diselenides [(PhSe)2, (MeOPhSe)2, (p-Cl-PhSe)2, (F3CPhSe)2] and diphenyl ditelluride.

Candida species are the fourth most common cause of nosocomial bloodstream infections. An increase in the frequency of infections, which have become refractory to standard antifungal therapy, has been observed. Recent studies have shown that the pro-oxidant properties of diphenyl diselenide (PhSe)(2), a structurally simple organoselenium compound, can be toxic to yeast. The objective of this work was to study, under non-reactive oxygen species (ROS)-generating conditions, the effect of different organochalcogenide compounds [(PhSe)(2), (PhTe)(2), (MeOPhSe)(2), (p-Cl-PhSe)(2) and (F(3)CPhSe)(2)] on growth and germ tube formation by Candida albicans. A decrease in C. albicans growth in the presence of crescent concentrations of (PhSe)(2), (PhTe)(2) and (MeOPhSe)(2) was observed. The organochalcogenide compound concentration needed to inhibit 50% (IC50) of the Candida growth was 0.5-2 and 2-10 µmol l(-1), at a cell density of 10(5) and 10(6) cells ml(-1), respectively. The compounds (p-Cl-PhSe)(2) and (F(3)CPhSe)(2) were able to inhibit the cell growth, although the inhibition was considerably weaker than that by (PhSe)(2), (PhTe)(2) and (MeOPhSe)(2). In Candida suspensions incubated in a medium containing serum as an inducer of germ tube formation, the presence of either (PhSe)(2) or (MeOPhSe)(2) at 10 µmol l(-1) completely inhibited the number of cells which formed germ tubes. These results demonstrate the potential of organochalcogenide compounds to inhibit both C. albicans growth and germ tube formation.