The Efficacy of the Quorum Sensing Inhibitor FS8 and Tigecycline in Preventing Prosthesis Biofilm in an Animal Model of Staphylococcal Infection

We investigated the efficacy of tigecycline and FS8, alone or combined, in preventing prosthesis biofilm in a rat model of staphylococcal vascular graft infection. Graft infections were established in the back subcutaneous tissue of adult male Wistar rats by implantation of Dacron prostheses followed by topical inoculation with 2 × 10⁷ colony-forming units of Staphylococcus aureus, strain Smith diffuse. The study included a control group, a contaminated group that did not receive any antibiotic prophylaxis, and three contaminated groups that received: (i) intraperitoneal tigecycline, (ii) FS8-soaked graft, and (iii) tigecycline plus FS8-soaked graft, respectively. Each group included 15 animals. The infection burden was evaluated by using sonication and quantitative agar culture. Moreover, an in vitro binding-study was performed to quantify the how much FS8 was coated to the surface of the prosthesis. Tigecycline, combined with FS8, against the adherent bacteria showed MICs (2.00 mg/L) and MBCs (4.00 mg/L) four-fold lower with respect to tigecycline alone in in vitro studies. The rat groups treated with tigecycline showed the lowest bacterial numbers (4.4 × 10⁴ ± 1.2 × 10⁴ CFU/mL). The FS8-treated group showed a good activity and significant differences compared to control group with bacterial numbers of 6.8 × 10⁴ ± 2.0 × 10⁴ CFU/mL. A stronger inhibition of bacterial growth was observed in rats treated with a combined FS8 and tigecycline therapy than in those that were singly treated with bacterial numbers of 10¹ CFU/mL graft. In conclusion, the ability to affect biofilm formation as well, its property to be an antibiotic enhancer suggests FS8 as alternative or additional agent to use in conjunction with conventional antimicrobial for prevention of staphylococcal biofilm related infection.     

Thyroid Hormones and Antioxidant Systems: Focus on Oxidative Stress in Cardiovascular and Pulmonary Diseases

In previous works we demonstrated an inverse correlation between plasma Coenzyme Q₁₀ (CoQ₁₀) and thyroid hormones; in fact, CoQ₁₀ levels in hyperthyroid patients were found among the lowest detected in human diseases. On the contrary, CoQ₁₀ is elevated in hypothyroid subjects, also in subclinical conditions, suggesting the usefulness of this index in assessing metabolic status in thyroid disorders. A Low-T3 syndrome is a condition observed in several chronic diseases: it is considered an adaptation mechanism, where there is a reduction in pro-hormone T4 conversion. Low T3-Syndrome is not usually considered to be corrected with replacement therapy. We review the role of thyroid hormones in regulation of antioxidant systems, also presenting data on total antioxidant capacity and Coenzyme Q₁₀. Published studies suggest that oxidative stress could be involved in the clinical course of different heart diseases; our data could support the rationale of replacement therapy in low-T3 conditions.     

Interaction of silicon-based quantum dots with gibel carp liver: oxidative and structural modifications

Quantum dots (QDs) interaction with living organisms is of central interest due to their various biological and medical applications. One of the most important mechanisms proposed for various silicon nanoparticle-mediated toxicity is oxidative stress. We investigated the basic processes of cellular damage by oxidative stress and tissue injury following QD accumulation in the gibel carp liver after intraperitoneal injection of a single dose of 2 mg/kg body weight Si/SiO₂ QDs after 1, 3, and 7 days from their administration.QDs gradual accumulation was highlighted by fluorescence microscopy, and subsequent histological changes in the hepatic tissue were noted. After 1 and 3 days, QD-treated fish showed an increased number of macrophage clusters and fibrosis, while hepatocyte basophilia and isolated hepatolytic microlesions were observed only after substantial QDs accumulation in the liver parenchyma, at 7 days after IP injection.Induction of oxidative stress in fish liver was revealed by the formation of malondialdehyde and advanced oxidation protein products, as well as a decrease in protein thiol groups and reduced glutathione levels. The liver enzymatic antioxidant defense was modulated to maintain the redox status in response to the changes initiated by Si/SiO₂ QDs. So, catalase and glutathione peroxidase activities were upregulated starting from the first day after injection, while the activity of superoxide dismutase increased only after 7 days. The oxidative damage that still occurred may impair the activity of more sensitive enzymes. A significant inhibition in glucose-6-phosphate dehydrogenase and glutathione-S-transferase activity was noted, while glutathione reductase remained unaltered.Taking into account that the reduced glutathione level had a deep decline and the level of lipid peroxidation products remained highly increased in the time interval we studied, it appears that the liver antioxidant defense of Carassius gibelio does not counteract the oxidative stress induced 7 days after silicon-based QDs exposure in an efficient manner.     

Potential Mechanisms Linking Atherosclerosis and Increased Cardiovascular Risk in COPD: Focus On Sirtuins

The development of atherosclerosis is a multi-step process, at least in part controlled by the vascular endothelium function. Observations in humans and experimental models of atherosclerosis have identified monocyte recruitment as an early event in atherogenesis. Chronic inflammation is associated with ageing and its related diseases (e.g., atherosclerosis and chronic obstructive pulmonary disease). Recently it has been discovered that Sirtuins (NAD⁺-dependent deacetylases) represent a pivotal regulator of longevity and health. They appear to have a prominent role in vascular biology and regulate aspects of age-dependent atherosclerosis. Many studies demonstrate that SIRT1 exhibits anti-inflammatory properties in vitro (e.g., fatty acid-induced inflammation), in vivo (e.g., atherosclerosis, sustainment of normal immune function in knock-out mice) and in clinical studies (e.g., patients with chronic obstructive pulmonary disease). Because of a significant reduction of SIRT1 in rodent lungs exposed to cigarette smoke and in lungs of patients with chronic obstructive pulmonary disease (COPD), activation of SIRT1 may be a potential target for chronic obstructive pulmonary disease therapy. We review the inflammatory mechanisms involved in COPD-CVD coexistence and the potential role of SIRT1 in the regulation of these systems.     

LAS glass–ceramic scaffolds by three-dimensional printing

Highly porous (>60% open porosity) glass–ceramic scaffolds with remarkable mechanical properties (compression strength of ～15 MPa) were produced by indirect 3D printing. Precursor glass powders were printed into 3D ordered structures and then heat treated to sinter and develop crystalline phases. The final glass–ceramic contained a β-spodumene solid solution together with a secondary phase of lithium disilicate.The precision of the printed geometry and the density of the struts in the scaffold depended on several processing parameters (e.g. powder size and flowability, layer thickness) and were improved by increasing the binder saturation and drying time. Two types of powders with different particle size distribution (PSD) and flowability were used. Powders with a larger PSD, could be processed within a wider range of printing parameters due to their good flowability; however, the printing precision and the struts density were lower compared to the scaffolds printed using the powder in a smaller average PSD.     

A novel electron beam-based method for the immobilization of trypsin on poly(ethersulfone) and poly(vinylidene fluoride) membranes

A novel technique for the covalent immobilization of trypsin in a one-step reaction using low-energy electron beam is described. The enzyme immobilization was applied on poly(ethersulfone) and poly(vinylidene fluoride) microfiltration membranes. For this purpose, the membranes were dipped in an aqueous solution of trypsin followed by electron beam treatment.The effect of irradiation conditions on the immobilization was investigated, as well as the resulting membrane properties with respect to enzymatic activity, immobilized enzyme concentration, pure water flux, scanning electron microscopy, and porosimetry. This technique shall provide a simple, inexpensive method for enzyme immobilization on various polymer membranes and offer a tool for the application in enzymatic membrane reactors.     

Oxidative and carbonaceous patterning of Si surface in an organic media by scanning probe lithography

A simple top-down fabrication technique that involves scanning probe lithography on Si is presented. The writing procedure consists of a chemically selective patterning in mesitylene. Operating in an organic media is possible to perform local oxidation or solvent decomposition during the same pass by tuning the applied bias. The layer deposited with a positively biased tip with sub-100-nm lateral resolution consists of nanocrystalline graphite, as verified by Raman spectroscopy. The oxide pattern obtained in opposite polarization is later used as a mask for dry etching, showing a remarkable selectivity in SF₆ plasma, to produce Si nanofeatured molds.     

Rhodium‐Catalyzed Enantioselective Hydrogenation of (E)‐Enol Acetate Acids

The novel rhodium complex [Rh(S)‐Phanephos(cod)]‐catalyzed hydrogenation of disubstituted (E)‐enol acetate carboxylic acids is reported. The catalytic cycle works under 30 bar of hydrogen under conventional heating giving different 3‐acetoxy‐2,3‐disubstituted carboxylic acids with ee ≥90%. Hydrogenation occurred also under microwave dielectric heating without eroding the enantioselectivity but improving the overall efficiency of the process. With microwaves, hydrogen pressure and reaction time required for complete hydrogenation dropped to 5 bar and 30 min, respectively. The best performance of this catalyst under microwave irradiation was TON 100, TOF 196 h⁻¹ with ee 99% on a 6‐g scale.     

Direct Regio‐, Diastereo‐, and Enantioselective Vinylogous Michael Addition of Prochiral 3‐Alkylideneoxindoles to Nitroolefins

3‐Alkylidene‐2‐oxindoles represent a simple, yet enabling subfamily of indole alkaloids, and their ability to react as electron‐poor acceptors has largely been investigated. In contrast, their utility as pronucleophilic synthons remains elusive. In this context, the present article describes the successful execution of the direct, organocatalytic asymmetric Michael addition of prochiral 3‐alkylideneoxindoles to nitroolefins. A variety of γ‐substituted alkylideneoxindoles carrying two stereocenters at both the γ‐ and δ‐carbon sites was assembled with excellent stereoselectivity and without olefin isomerization or stereochemical ablation.