Evaluation of phytochemical composition, toxicity in Drosophila melanogaster and effects on antibiotics modulation of Plathymenia reticulata Benth extract.

Bacterial resistance is interfering with the action of antibiotics for clinical use in treating pathologies. The search for new substances capable of combating this resistance is necessary. An alternative to the search for these substances is in the extract of medicinal plants. Plathymenia reticulata, plant of the Fabaceae family, is a common tree species from the Brazilian cerrado, and is commonly used in areas of environmental degradation. This species is rich in phenolic compounds, such as flavonoids and tannins, compounds that are associated with various biological effects. A hydroethanolic extract from the bark of Plathymenia reticulata (HEPrB) was produced and then tests were carried out to verify the direct antibacterial activity, the modulatory effect of antibiotics for clinical use and their toxicity in Drosophila melanogaster flies. Through the analysis with UPLC, a wide variety of flavonoids contained in the HEPrB was observed. Direct antibacterial activity was observed for the standard strain of Staphylococcus aureus, however, the extract showed antagonistic activity or no significance in relation to the antibiotics tested in this study. As for toxicity, the HEPrB did not show significant damage in the proposed model. The results emphasize care when associating the consumption of teas with treatments with antibiotics for clinical use.

Antibacterial properties and modulation analysis of antibiotic activity of NaCe(MoO4)2 microcrystals.

This study reports the antibacterial properties and modulation analysis of antibiotic activity by NaCe(MoO4)2 microcrystals as well as their structural and morphological characterization. Evaluation of the antibacterial and antibiotic-modulating activity was carried out using the broth microdilution method. The Minimum Inhibitory Concentrations (MICs) of the compounds were expressed as the geometric mean of the triplicate values obtained through the use of Resazurin. Compound concentrations in the plates ranged from 512 to 0.5 µg/mL. Regarding its direct antibacterial activity, NaCe(MoO4)2 had a MIC ≥ 1024 µg/mL against all studied strains. As for its modulatory effect, it presented synergism with the antibiotic Gentamicin against the S. aureus strain and with Norfloxacin against E. coli, causing a reduction of 75% and 60%, respectively, in the antibiotic quantity required to have the same effect on the strain in study.

Modulation of antibiotic effect by Fe2(MoO4)3 microstrutures.

In this study, we report the antibacterial activity and modulation of antibiotic activity by Fe2(MoO4)3 microstructures obtained by the hydrothermal route without use of surfactants or organic additives. This material was characterized by X-ray diffraction (XRD), Raman spectroscopy and scanning electron microscopy (SEM) images. The XRD pattern showed that the Fe2(MoO4)3 crystallize in a monoclinic structure without secondary phases. Raman spectroscopy confirms the formation of Fe2(MoO4)3. SEM images show that the Fe2(MoO4)3 obtained have ball-of-yarn shaped morphology. In the antibacterial assays, strains of Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus were assayed by microdilution method to evaluate the antibacterial and modulatory-antibiotic activity with antibiotics as gentamicin, norfloxacin and imipenem. Against all bacteria, the Minimum Inhibitory Concentration (MIC) was Fe2(MoO4)3 ≥ 1024 µg/mL. This high MIC result must be associated with the fact of the iron be an essential microelement to the bacterial growth. However, when the Fe2(MoO4)3 was assayed in association with the antibiotics was observed an antagonistic effect demonstrated by an enhance of the MIC. This fact is associated directly with the pro-oxidative properties of metallic oxides. These compounds enhance the production of free radicals, as H2O2 and superoxide ions that can affect the cell structures as cell membrane and cell wall. Other effect is associated with the possible coordination of the metal, performing bonds with the chemical structure of the antibiotics, reducing their activity. Our results indicated that nanocompounds as Fe2(MoO4)3 can not be used as antimicrobial products for clinical usage, neither directly and neither in association with antibiotics.

Cholesterol and ergosterol affect the activity of Staphylococcus aureus antibiotic efflux pumps.

The aim of this study is to evaluate the effect of ergosterol on steroids and cholesterol efflux pumps in multidrug resistant strains of S. aureus. Were used RN4220 harboring plasmid pUL5054, which carries the gene encoding the MsrA macrolide efflux protein; and IS-58, which possesses the TetK tetracycline efflux protein; 1199B resists hydrophilic fluoroquinolones via a NorA-mediated mechanism and wild strain 1199B. The Minimal Inhibitory Concentration (MIC) was determined and the evaluation of possible inhibition of efflux pumps by reduction of MIC. Some of the detrimental effects on bacterial cells can be attributed to the detergent properties of cholesterol and ergosterol on account of their amphipathic structure. Besides the cholesterol did not affect directly the pump structure, a synergism was observed, maybe due the interaction with the cell membrane and interference in the lipid bilayer.

ß-Ag2MoO4 microcrystals: Characterization, antibacterial properties and modulation analysis of antibiotic activity.

This study reports the antibacterial properties and modulation analysis of antibiotic activity by ß-Ag2MoO4 microcrystals as well as their structural and vibrational characterization. The silver molybdate was obtained by the conventional hydrothermal method, and the structural, vibrational and morphological properties of the sample were determined using X-ray diffraction, Raman spectroscopy and scanning electron microscopy images. ß-Ag2MoO4 microcrystals obtained show spinel-type cubic structure (Fd-3m) with irregular shapes. The evaluation of antibacterial and modulatory-antibiotic activity was performed using the microdilution method to determine the Minimum Inhibitory Concentration (MIC) of the ß-Ag2MoO4 and antibiotics alone and associated with the silver molybdate. The ß-Ag2MoO4 modulates the antibiotic activity against all bacteria assayed in a synergistic (as the norfloxacin and gentamicin against S. aureus and gentamicin against E. coli) or an antagonistic form (as the norfloxacin against E.coli and P. aeruginosa). The reversion of antibiotic resistance by combinations with Ag2MoO4 could be a novel strategy to combat infections caused by multiple drug resistance (MDR) pathogens. Our results indicate that these silver molybdates present a clinically relevant antibacterial activity and enhanced the antibiotic activity of some antibiotics against MDR strain of S. aureus and E. coli, being an interesting alternative to combat antibiotic-resistant bacterial infectious agents.

Risk factors for imipenem-resistant Pseudomonas aeruginosa: a comparative analysis of two case-control studies in hospitalized patients.

Risk factors for acquisition of imipenem-resistant Pseudomonas aeruginosa by hospitalized patients were assessed at a tertiary care hospital. Two case-control studies with different control groups were used. In Study 1, patients with imipenem-resistant P. aeruginosa (IRPA) (case group) were compared with patients selected at random from the same unit. In Study 2, the case group was compared with patients with imipenem-susceptible P. aeruginosa (ISPA). Ninety-three patients with IRPA and 93 control patients were included in Study 1, and 93 IRPA patients and 65 patients with ISPA were included in Study 2. Carbapenem treatment [odds ratio (OR) 5.82], mechanical ventilation (OR 3.22) and hospital admission in the previous year (OR 2.59) were associated with IRPA in Study 1. An interaction between carbapenem and vancomycin was found to be a significant risk factor for IRPA (OR for carbapenem in patients with vancomycin use 43.71). In Study 2, carbapenem exposure (OR 12.82) and renal failure (OR 5.00) were associated with IRPA. Our study confirmed that carbapenem exposure is the main risk factor for IRPA, and found that the use of both carbapenem and vancomycin can increase this effect.

DNAzymes: from creation in vitro to application in vivo.

DNAzymes, also known as deoxyribozymes or DNA enzymes, refer to single-stranded DNA molecules with catalytic capabilities. DNAzymes are generated de novo by in vitro selection--a powerful and yet simple technique that has been routinely used to isolate extremely rare DNA or RNA sequences with a function of interest (e.g. ligand-binding or catalysis) from an extraordinarily large population of single-stranded DNA or RNA molecules. Since the report of the first DNAzyme nearly ten years ago, hundreds of DNA sequences have been isolated in many research laboratories around the world to facilitate many chemical transformations of biological importance. In recent years, considerable efforts have been undertaken to assess a variety of DNAzymes for innovation-driven applications ranging from biosensing to gene regulation. This article provides a review on several key aspects of DNAzyme-related research. We will first review in vitro selection techniques used for DNAzyme creation as well as some DNAzymes created for a few representative chemical transformations. We will then discuss recent progresses in studying and developing DNAzymes as reporter molecules for detection-oriented applications, and as therapeutic agents to regulate gene expression at the RNA level. Future outlook on efforts aimed to bring the wonder of catalytic DNA from laboratory curiosity to real world application are also discussed.

Selective modulation of chemokinesis, degranulation, and apoptosis in eosinophils through the PGD2 receptors CRTH2 and DP.

BACKGROUND: PGD(2) is the major prostanoid released by mast cells during an allergic response. Its role in the allergic response, however, remains unclear. OBJECTIVE: Because the accumulation of eosinophils is a feature of allergic reactions, we investigated the role of PGD(2) in the modulation of eosinophil function. METHODS: Circulating human eosinophils were isolated and challenged with PGD(2). The effects of PGD(2) on various eosinophil functions were then analyzed. RESULTS: PGD(2) binds with high affinity preferentially to 2 receptors, DP and chemoattractant receptor-homologous molecule expressed on T(H)2 cells (CRTH2). We show that both DP and CRTH2 are detectable on circulating eosinophils. We demonstrate that PGD(2) (1-10 nmol/L) induces a rapid change in human eosinophil morphology and an increase in chemokinesis and promotes eosinophil degranulation. These effects are induced by the CRTH2-selective agonist 13-14-dihydro-15-keto-PGD(2) (DK-PGD(2)) but not by the DP-selective agonist BW245C. These results suggest a role for CRTH2 in the modulation of eosinophil movement and in triggering the release of cytotoxic proteins. Finally, we demonstrate that BW245C, but not DK-PGD(2), can delay the onset of apoptosis in cultured eosinophils, presumably through interaction with DP. CONCLUSION: These data support the hypothesis that PGD(2) controls eosinophil functions through 2 pharmacologically distinct receptors with independent functions. Blockade of PGD(2)-mediated effects on human eosinophils may reduce the damage caused by these cells during an allergic response, but inhibition of both receptors may be required.

Acylation of indole under Friedel-Crafts conditions-an improved method to obtain 3-acylindoles regioselectively.

[reaction: see text]. The reaction of unsubstituted indole with different acylating agents such as acid chlorides, anhydrides, nitriles, and amino acid derivatives in the presence of Lewis acid is reported.