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‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬This study aims to evaluate the in vitro antimicrobial and immunomodulatory activities and cytotoxicity of chlorhexidine (CHX) and synoeca‐MP peptide alone or in combination against Pseudomonas aeruginosa. The antimicrobial property was evaluated by the determination of minimal inhibitory concentration, minimum bactericidal concentration, and planktonic bacteria and biofilm inhibition. Immunomodulatory activity was determined by enzyme‐linked immunosorbent assay and nitric oxide production by the Griess reaction method. According to the results, synoeca‐MP combined with CHX demonstrated antimicrobial effectiveness compared with its isolated use, in addition to immunomodulatory activity (upregulating MPC‐1 and tumor necrosis factor‐α and downregulating nitric oxide and interleukin‐10). In this context, it is expected that the substances, together, could be capable of controlling bacterial infection and dissemination, besides potentiating macrophages' immune response against the studied microorganism. Moreover, reducing the CHX concentration by the addition of synoeca‐MP peptide may, in a beneficial way, minimize the undesirable effects of both, CHX and synoeca‐MP in a clinical setting. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a metabolic disorder that results in the impairment of the metabolism of carbohydrates, proteins and lipids. It can give rise to various complications, mainly caused by chronic exposure of cells to high glucose concentrations, including changes in the immune response processes. The aim of this study was to verify the chemokine and cytokines production profile in the presence of different glucose concentrations and infection/inflammatory stimuli. To this end, cell viability and the production of chemokines, cytokines and nitric oxide (NO) were analyzed in RAW 264.7 cell culture. Results demonstrated that there was no change in cell viability after 6, 24 and 72 h. Different stimuli were unable to modify the monocyte chemoattractant protein (MCP)-1 and tumor necrosis factor (TNF)-α production. Groups stimulated with lipopolysaccharides (LPS) and LPS and recombinant interferon (rIFN)-γ down-regulated interleukin (IL)-1α, IL-10 and IL-12 and up-regulated IL-6 production. NO production maintained a pattern of increase, according to the increase in glucose concentrations, reaching its peak at 72 h. In summary, the results demonstrated that high glucose concentrations alone may be sufficient to alter the in vitro mediators’ production of RAW 264.7 cells. [ABSTRACT FROM AUTHOR]

Fungal Candida species are commensals present in the mammalian skin and mucous membranes. Candida spp. are capable of breaching the epithelial barrier of immunocompromised patients with neutrophil and cell-mediated immune dysfunctions and can also disseminate to multiple organs through the bloodstream. Here we examined the action of innate defense regulator 1018 (IDR-1018), a 12-amino-acid-residue peptide derived from bovine bactenecin (Bac2A): IDR-1018 showed weak antifungal and antibiofilm activity against a Candida albicans laboratory strain (ATCC 10231) and a clinical isolate (CI) (MICs of 32 and 64 μg · ml -1 , respectively), while 8-fold lower concentrations led to dissolution of the fungal cells from preformed biofilms. IDR-1018 at 128 μg · ml -1 was not hemolytic when tested against murine red blood cells and also has not shown a cytotoxic effect on murine monocyte RAW 264.7 and primary murine macrophage cells at the tested concentrations. IDR-1018 modulated the cytokine profile during challenge of murine bone marrow-derived macrophages with heat-killed C. albicans (HKCA) antigens by increasing monocyte chemoattractant protein 1 (MCP-1) and interleukin-10 (IL-10) levels, while suppressing tumor necrosis factor alpha (TNF-α), IL-1β, IL-6, and IL-12 levels. Mice treated with IDR-1018 at 10 mg · kg -1 of body weight had an increased survival rate in the candidemia model compared with phosphate-buffered saline (PBS)-treated mice, together with a diminished kidney fungal burden. Thus, IDR-1018 was able to protect against murine experimental candidemia and has the potential as an adjunctive therapy., (Copyright © 2017 American Society for Microbiology.)