Modulatory role of α-MSH in hippocampal-dependent memory impairment, synaptic plasticity changes, oxidative stress, and astrocyte reactivity induced by short-term high-fat diet intake.

High-fat diet (HFD) consumption is associated with cognitive deficits and neurodegenerative diseases. Since the hippocampus is extremely sensitive to pathophysiological changes, neuroinflammation and the concomitant oxidative stress induced by HFD can significantly interfere with hippocampal-dependent functions related to learning and memory. The neuropeptide alpha-melanocyte stimulating hormone (α-MSH) mediates neuroprotective actions in the central nervous system and can reverse the effects of neuroinflammation in cognitive functions that depend on the hippocampus. In this study, we used male Wistar rats to evaluate the effect of short-term HFD intake (5 days) plus a mild immune challenge, Lipopolysaccharide (LPS 10 µg/kg) on contextual fear, changes in structural plasticity, oxidative stress, and astrocyte reactivation in the hippocampus. We also determined the possible modulatory role of α-MSH. HFD consumption was associated with an increase in markers of oxidative stress (Advanced oxidation protein products and Malondialdehyde) in the dorsal hippocampus (DH). We also found changes in hippocampal structural synaptic plasticity, observing a decrease in total spine in the DH after HFD plus LPS. We observed astrocyte proliferation and a significant increase in the percentage of the area occupied by GFAP. Treatment with α-MSH (0.1 µg/0.25 µl) in the DH reversed the effect of short-term HFD plus LPS on contextual fear memory, oxidative stress, and spine density. α-MSH also reduced astrocyte proliferation. Our present results indicate that HFD consumption for a short period sensitizes the central nervous system (CNS) to a subsequent immune challenge and impairs contextual fear memory and that α-MSH could have a modulatory protective effect.

Nanostructured Gold Coating for Prevention of Biofilm Development in Medical Devices.

Bacterial biofilms on medical devices (MDs) can cause deadly infections due to their resistance to antibiotics. Technology to prevent this kind of complication is urgently needed because they impact not only patients' lives but also hospital budgets. In this article, the creation and testing of an easy-to-produce antibiofilm (more precisely antibiofouling) coating are described for the first time. This coating can be applied to catheters, prostheses, and other plastic pieces, even after they have been manufactured. Rapid and ecofriendly synthesis of nanostructured gold coating was done in situ in just 15 minutes. Complete characterization and microbiological analysis of its antibiofouling capacity are presented. The coating prevents biofilm formation of pathogenic clinical isolates and ATCC strains on MDs, possibly due to its complex nanostructured gold surface. If the next generation of MDs is coated with this kind of antibiofouling technology, biofilm-related infections could be dramatically reduced. Graphical Abstract [Figure: see text].

Selective Photoinduced Antibacterial Activity of Amoxicillin-Coated Gold Nanoparticles: From One-Step Synthesis to in Vivo Cytocompatibility.

Photoinduced antibacterial gold nanoparticles were developed as an alternative for the treatment of antibiotic-resistant bacteria. Thanks to the amoxicillin coating, they possess high in vivo stability, selectivity for the bacteria wall, a good renal clearance, and are completely nontoxic for eukaryotic cells at the bactericidal concentrations. A simple one-step synthesis of amoxi@AuNP is described at mild temperatures using the antibiotic as both reducing and stabilizing agent. Time-resolved fluorescence microscopy proved these novel nano-photosensitizers, with improved selectivity, are bactericidal but showing excellent biocompatibility toward eukaryotic cells at the same dose (1.5 µg/mL) when co-cultures are analyzed. Their stability in biological media, hemocompatibility, and photo-antibacterial effect against sensitive and antibiotic-resistant Staphylococcus aureus were evaluated in vitro, whereas toxicity, renal clearance, and biodistribution were studied in vivo in male Wistar rats. The use of these nanoparticles to treat antibiotic-resistant infections is promising given their high stability and cytocompatibility.

Biocompatibility and photo-induced antibacterial activity of lignin-stabilized noble metal nanoparticles.

One-pot thermal and photochemical syntheses of lignin-doped silver and gold nanoparticles were developed and their antimicrobial properties were studied against Escherichia coli and Staphylococcus aureus. The nature of the lignin as well as the metal are directly involved in the antimicrobial activity observed in these nanocomposites. Whereas one of the nanocomposites is innocuous under dark conditions and shows photoinduced activity only against Staphylococcus aureus, the rest of the lignin-coated silver nanoparticles studied show antimicrobial activity under dark and light conditions for both bacteria strains. Additionally, only photoinduced activity is observed for lignin-coated gold nanoparticles. Importantly, the particles are non-cytotoxic towards human cells at the bactericidal concentrations. Preliminary assays show these silver nanoparticles as potential antimicrobial agents towards S. aureus biofilm eradication.

Enhanced inhibition of bacterial biofilm formation and reduced leukocyte toxicity by chloramphenicol:ß-cyclodextrin:N-acetylcysteine complex.

The purpose of this study was to improve the physicochemical and biological properties of chloramphenicol (CP) by multicomponent complexation with ß-cyclodextrin (ß-CD) and N-acetylcysteine (NAC). The present work describes the ability of solid multicomponent complex (MC) to decrease biomass and cellular activity of Staphylococcus by crystal violet and XTT assay, and leukocyte toxicity, measuring the increase of reactive oxygen species by chemiluminescence, and using 123-dihydrorhodamine. In addition, MC was prepared by the freeze-drying or physical mixture methods, and then characterized by scanning electron microscopy and powder X-ray diffraction. Nuclear magnetic resonance and phase solubility studies provided information at the molecular level on the structure of the MC and its association binding constants, respectively. The results obtained allowed us to conclude that MC formation is an effective pharmaceutical strategy that can reduce CP toxicity against leukocytes, while enhancing its solubility and antibiofilm activity.

Effect of antibiotics on cellular stress generated in Shiga toxin-producing Escherichia coli O157:H7 and non-O157 biofilms.

Shiga toxin-producing Escherichia coli (STEC) are important food-borne pathogens, with the main virulence factor of this bacterium being its capacity to secrete Shiga toxins (Stxs). Therefore, the use of certain antibiotics for the treatment of this infection, which induces the liberation of Stxs, is controversial. Reactive oxygen and nitrogen species are also involved in the pathogenesis of different diseases. The purpose of this study was to analyze the effects of antibiotics on biofilms of STEC and the relationships between cellular stress and the release of Stx. To this end, biofilms of reference and clinical strains were treated with antibiotics (ciprofloxacin, fosfomycin and rifaximin) and the production of oxidants, the antioxidant defense system and toxin release were evaluated. Ciprofloxacin altered the prooxidant-antioxidant balance, with a decrease of oxidant metabolites and an increase of superoxide dismutase and catalase activity, being associated with high-levels of Stx production. Furthermore, inhibition of oxidative stress by exogenous antioxidants was correlated with a reduction in the liberation of Stx, indicating the participation of this phenomenon in the release of this toxin. In contrast, fosfomycin and rifaximin produced less alteration with a minimal production of Stx. Our data show that treatment of biofilm-STEC with these antibiotics induces oxidative stress-mediated release of Stx.

Oxidative stress involved in the antibacterial action of different antibiotics.

Staphylococcus aureus and Escherichia coli sensitive to chloramphenicol incubated with this antibiotic suffered oxidative stress with increase of anion superoxide (O2-). This reactive species of oxygen was detected by chemiluminescence with lucigenin. S. aureus, E. coli, and Enterococcus faecalis sensitive to ciprofloxacin exhibited oxidative stress when they were incubated with this antibiotic while resistant strains did not show stimuli of O2-. Other bacteria investigated was Pseudomonas aeruginosa, strains sensitive to ceftazidime and piperacillin presented oxidative stress in presence of these antibiotics while resistant strains were not stressed. Higher antibiotic concentration was necessary to augment O2- in P. aeruginosa biofilm than in suspension, moreover old biofilms were resistant to oxidative stress caused by antibiotics. A ceftazidime-sensitive mutant of P. aeruginosa, coming from a resistant strain, exhibited higher production of O2- than wild type in presence of this antibiotic. There was relation between antibiotic susceptibility and production of oxidative stress.