Simultaneous Model Selection and Model Calibration for the Proliferation of Tumor and Normal Cells During In Vitro Chemotherapy Experiments.

In vitro experiments were conducted in this work to analyze the proliferation of tumor (DU-145) and normal (macrophage RAW 264.7) cells under the influence of a chemotherapeutic drug (doxorubicin). Approximate Bayesian Computation (ABC) was used to select among four competing models to represent the number of cells and to estimate the model parameters, based on the experimental data. For one case, the selected model was validated in a replicated experiment, through the solution of a state estimation problem with a particle filter algorithm, thus demonstrating the robustness of the ABC procedure used in this work.

Evaluation of 1,3-benzoxathiol-2-one Derivatives as Potential Antifungal Agents.

BACKGROUND: Over the last few years, fungal infections have emerged as a worrisome global public health problem. Candidiasis is a disease caused by Candida species and has been a problem worldwide mainly for immunosuppressed patients. Lately, the resistant strains and side effects have been reported as important issues for treating Candidiasis, which have to be solved by identifying new drugs. OBJECTIVE: The goal of this work was to synthesize a series of 1,3-benzoxathiol-2-one derivatives, XYbenzo[ d][1,3]oxathiol-2-ones, and evaluate their antifungal activity against five Candida species. METHODS: In vitro antifungal screening test and minimum inhibitory concentration determination were performed according to CLSI protocols using ketoconazole as the reference drug. The cytotoxicity of the most active compounds was evaluated by hemolysis and MTT (Vero cells) assays. RESULTS: Compounds 2 (XY = 6-hydroxy-5-nitro, MIC = 4-32 µg/mL) and 7 (XY = 6-acetoxy-5-nitro, MIC =16-64 µg/mL) showed good results when compared with current antifungals in CLSI values (MIC = 0.04-250 µg/mL). These compounds exhibited a safer cytotoxicity as well as a lower hemolytic profile than ketoconazole. CONCLUSION: Overall, the in vitro results pointed to the potential of compounds 2 and 7 as new antifungal prototypes to be further explored.

Signal transduction in human endothelial cells induced by their interaction with group B Streptococci.

The molecular mechanisms underlying entry of group B Streptococci (GBS) into human endothelial cells are not yet fully understood. This study is centered on the triggering of signaling cascade in human umbilical vein endothelial cells (HUVEC) during their interaction with different GBS serotypes/strains (type III: 80340-vagina and 90356-CSF and type V: 88641-vagina and 90186-blood). We have shown that the analyzed microorganisms adhere to HUVEC, but only those of the strains 90356-CSF, 88641-vagina and 90186-blood presented intracellular viability. Activation of PKC directly increased F-actin content and organization into stress fibers, and increased intracellular viability of GBS-III microorganisms. PKA inhibitor seems to promote surveillance of GBS type V microorganisms within HUVEC. These studies indicate that different molecules present at the cell surface of the GBS might induce different responses to HUVEC, interfering with the recruitment of cortical actin filaments.

Involvement of intercellular adhesion molecule-1 and beta1 integrin in the internalization process to human endothelial cells of group B Streptococcus clinical isolates.

The mechanism by which group B Streptococcus (GBS) interacts with human cells and disrupts physiological processes is an intriguing area of investigation and continues to unfold. The aim of this study was to investigate the adherence and intracellular viability within endothelial ECV304 cells of GBS serotypes Ia, III and V isolates from patients and asymptomatic carriers. The GBS isolates from patients (GBS-Ia 90222-urine, GBS-III 90356-liquor and GBS-V 90186-blood strains) exhibited a more efficient adherence and survival mechanisms to endothelial cells than those from asymptomatic carriers (GBS-Ia 85147-oropharynx, GBS-III 80340 and GBS-V 88641-vagina strains), independent of bacterial serotypes. Treatment of endothelial ECV304 cells with EDTA demonstrated that Ca2+-dependent molecules modulated the adherence and internalization process of GBS-Ia and III to ECV304 cells. SDS-PAGE analysis of samples of biotinylated ECV304 extracts treated with GBS clinical isolates (urine 90222-Ia, liquor 90356-III and blood 90186-V strains) revealed fragments ranging from approximately 61 to approximately 179 kDa. Results of immunoassays with ECV304 membrane proteins showed that ICAM-1 molecules interacted only with GBS-III liquor 90356 strain while beta1 integrin interacted with GBS-III liquor 90356 and GBS-V blood 90186 invasive strains. Thus, the interaction between ICAM-1 and beta1-integrin seems an additional means by which GBS exploits host endothelial cells during infection. These findings add to the current understanding of the roles played by multiple receptor-ligand systems in the uptake and pathogenesis of GBS infection.