Hormones modulate Candida vaginal isolates biofilm formation and decrease their susceptibility to azoles and hydrogen peroxide.

Vulvovaginal candidiasis (VVC) is an infection usually caused by Candida albicans and increasingly by Candida glabrata, which has an intrinsically high resistance to commonly used antifungals. Candida species possess virulence factors that contribute to VVC development, as the ability to form biofilms in vaginal walls and intrauterine devices. It is known that VVC is promoted by conditions that increase the hormones levels, during pregnancy, however, the effects of hormones on Candida cells are poorly studied, especially in C. glabrata. Thus, the influence of progesterone and ß-estradiol, at normal cycle and pregnancy concentrations, on biofilm formation and resistance of C. albicans and C. glabrata vaginal isolates, was analyzed using acidic conditions (pH 4). Biofilms of C. albicans developed in the presence of hormones presented reduced biomass (up to 65%) and impaired cells ability to produce filamentous forms. On the other hand, C. glabrata presented high adaptation to the presence of hormones, which did not affect its biofilm formation. Additionally, hormones impaired the susceptibility of C. albicans and C. glabrata cells to azoles, with potential clinical significance in the presence of pregnancy hormone levels. A similar result was obtained for the susceptibility to hydrogen peroxide, a biological vaginal barrier against Candida growth. Overall, the results of this study suggest that hormones may act as environmental cues promoting Candida protection from vaginal defenses and harmful conditions, what may have implications in Candida vaginal pathogenicity and treatment of VVC, especially in C. glabrata infections due to its high adaptability to vaginal conditions.

Application of 2'-OMethylRNA' Antisense Oligomer to Control Candida albicans EFG1 Virulence Determinant.

Antisense oligomers and their analogs have been successfully utilized to silence gene expression for the treatment of many human diseases; however, the control of yeast's virulence determinants has never been exploited before. In this sense, this work is based on the key hypothesis that if a pathogen's genetic sequence is a determinant of virulence, it will be possible to synthesize a nucleic acid mimic based on antisense therapy (AST) that will bind to the mRNA produced, blocking its translation into protein and, consequently, reducing the pathogen virulence phenotype. EFG1 is an important determinant of virulence that is involved in the regulation of the Candida albicans switch from yeast to filamentous form. Thus, our main goal was to design and synthesize an antisense oligonucleotide (ASO) targeting the EFG1 mRNA and to validate its in vitro applicability. The results show that the anti-EFG1 2'-OMethylRNA (2'OMe) oligomer was able to significantly reduce the levels of EFG1 gene expression and of Efg1p protein translation (both approximately 60%), as well as effectively prevent filamentation of C. albicans cells (by 80%). Moreover, it was verified that anti-EFG1 2'OMe keeps the efficacy in different simulated human body fluids. Undeniably, this work provides potentially valuable information for future research into the management of Candida infections, regarding the development of a credible and alternative method to control C. albicans infections, based on AST methodology.

Treino intervalado extensivo: comparação entre a corrida em plano horizontal e em plano inclinado / Long-interval training: comparison between level and uphill running

Embora o treino intervalado seja usualmente realizado em plano horizontal existe a possibilidade de o mesmo ser cumprido em plano inclinado, não obstante, neste caso, se colocarem dúvidas acerca da intensidade de treino mais adequada. Neste sentido, o objetivo deste estudo foi quantificar a diferença na velocidade de corrida em plano horizontal e em plano inclinado (4.2%) para uma mesma carga interna, em sessões de treino intervalado extensivo (10x 200 m) cumpridas por oito atletas do gênero masculino. Pela análise dos resultados, não se verificaram diferenças significativas entre as duas sessões de treino nos indicadores de carga interna usados (frequência cardíaca e lactatémia). Verificou-se, também, que a velocidade média de corrida em plano horizontal era significativamente superior à velocidade média de corrida em plano inclinado, (6.13 ± 0.06 m.s-1 e 5.61 ± 0.06 m.s-1), pese embora a diferença entre as velocidades de corrida nas duas situações foi encontrado uma correlação forte (r=0,955) entre a média da velocidade das repetições na situação de plano horizontal e a média da velocidade das repetições em plano inclinado o que permite concluímos, desta forma, que quando se pretende realizar este tipo de treino em plano inclinado (4.2%) deve adotar-se uma velocidade de corrida cerca de 8.5% inferior à adotada em plano horizontal, bem como tomar como bom indicador a percepção de cada um dos atletas sobre o impacto da carga.

Although the interval training is most often performed on level running it is also possible to perform it on uphill running. However, in the later situation it is more difficult to establish the proper exercise intensity. The aim of the present study was to identify differences on the running speed between level and uphill (4.2%) extensive interval training sessions (10x 200 m) with similar exercise intensity performed by eight male athletes. There were no significant differences between the two running conditions on the exercise intensity indicators that were used (heart rate and blood lactate). It was found that the mean running speed was significantly higher during level than during uphill running, beside that, we also find a great correlation (r=0,955), between the mean of running speed repetitions at ground level and the mean of running speed repetitions during uphill. It was concluded that when performing uphill extensive interval training (4.2% grade) the running speed should be 8.5% lower than the one that is used when performing the same type of training on a level grade.