Design, Synthesis and Evaluation of Novel Molecular Hybrids between Antiglaucoma Drugs and H2S Donors

Glaucoma is a group of eye diseases consisting of optic nerve damage with corresponding loss of field vision and blindness. Hydrogen sulfide (H2S) is a gaseous neurotransmitter implicated in various pathophysiological processes. It is involved in the pathological mechanism of glaucomatous neuropathy and exerts promising effects in the treatment of this disease. In this work, we designed and synthetized new molecular hybrids between antiglaucoma drugs and H2S donors to combine the pharmacological effect of both moieties, providing a heightened therapy. Brinzolamide, betaxolol and brimonidine were linked to different H2S donors. The H2S-releasing properties of the new compounds were evaluated in a phosphate buffer solution by the amperometric approach, and evaluated in human primary corneal epithelial cells (HCEs) by spectrofluorometric measurements. Experimental data showed that compounds 1c, 1d and 3d were the hybrids with the best properties, characterized by a significant and long-lasting production of the gasotransmitter both in the aqueous solution (in the presence of L-cysteine) and in the intracellular environment. Because, to date, the donation of H2S by antiglaucoma H2S donor hybrids using non-immortalized corneal cells has never been reported, these results pave the way to further investigation of the potential efficacy of the newly synthesized compounds

Strontium titanate (SrTiO3) mesoporous coatings for enhanced strontium delivery and osseointegration on bone implants

The incorporation of strontium (Sr) in titania enhances surface bioactivity and has a positive effect on pre-osteoblastic cell attachment, proliferation, and differentiation. Strontium titanate mesoporous films (SrTiMFs) with 30% pore volume and a 20% Sr molar content have been prepared by the evaporation induced self-assembly method. SrTiMFs display a large internal surface area available for exchange of Sr, which is released in cell media up to 44% within the first 8 h. SrTiMFs improve attachment of MC3T3-E1 pre-osteoblastic cells, which show larger filopodia and more elongated features than cells attached to plain mesoporous titania films (MTFs). SrTiMFs also display improved cell proliferation and differentiation rates indicating that overall Sr incorporation into mesoporous titania coatings can lead to enhanced osseointegration during the early stages of bone tissue formation.Fil: Escobar, Ane. Centro de Investigación Cooperativa en Biomateriales; EspañaFil: Muzzio, Nicolás Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina. Centro de Investigación Cooperativa en Biomateriales; EspañaFil: Angelome, Paula Cecilia. Comisión Nacional de Energía Atómica. Gerencia del Área de Seguridad Nuclear y Ambiente. Gerencia de Química (CAC); Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bordoni, Andrea Veronica. Comisión Nacional de Energía Atómica. Gerencia del Área de Seguridad Nuclear y Ambiente. Gerencia de Química (CAC); Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Martínez, Angel. Centro de Investigación Cooperativa en Biomateriales; EspañaFil: Bindini, Elisa. Centro de Investigación Cooperativa en Biomateriales; EspañaFil: Coy, Emerson. Adam Mickiewicz University. Nanobiomedical Centre; PoloniaFil: Andreozzi, Patrizia. Centro de Investigación Cooperativa en Biomateriales; EspañaFil: Grzelczak, Marek. Donostia International Physic Center; . Basque Foundation for Science; EspañaFil: Moya, Sergio E.. Centro de Investigación Cooperativa en Biomateriales; Españ

Antibacterial mesoporous titania films with embedded gentamicin and surface modified with bone morphogenetic protein 2 to promote osseointegration in bone implants

Novel approaches are needed to avoid bacterial infections following implant surgery. Here the use of mesoporous titania films (MTFs) for gentamicin loading and delivery and the surface functionalization of MFTs with human recombinant bone morphogenetic protein 2 (hrBMP-2) are discussed. Gentamicin is incorporated into the MTF pores by immersion of the porous materials in gentamicin solution while hrBMP-2 is adsorbed on top of the MTF. Contact angle and X-ray photoelectron spectroscopy measurements are performed to prove gentamicin loading and hrBMP-2 functionalization. An initial burst release of gentamicin takes place in physiological media followed by a prolonged release that lasts weeks. Such a release profile is highly appealing for bone implants where a high concentration of antibiotics is necessary during implant surgery while a lower antibiotic concentration is needed until tissue is regenerated. The MTFs loaded with gentamicin and functionalized with hrBMP-2 are effective against Staphylococcus aureus colonization, and the presence of hrBMP-2 enhances MC3T3-E1 preosteoblastic cell attachment, proliferation, and differentiation.Fil: Escobar, Ane. Centro de Investigación Cooperativa en Biomateriales; EspañaFil: Muzzio, Nicolás Eduardo. Centro de Investigación Cooperativa en Biomateriales; España. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Coy, Emerson. Adam Mickiewicz University; PoloniaFil: Liu, Hui. Chinese Academy of Sciences; República de ChinaFil: Bindini, Elisa. Centro de Investigación Cooperativa en Biomateriales; EspañaFil: Andreozzi, Patrizia. Centro de Investigación Cooperativa en Biomateriales; EspañaFil: Wang, Guocheng. Chinese Academy of Sciences; República de ChinaFil: Angelome, Paula Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; ArgentinaFil: Delcea, Mihaela. University of Greifswald; AlemaniaFil: Grzelczak, Marek. Donostia International Physic Center; . Basque Foundation for Science; EspañaFil: Moya, Sergio E.. Centro de Investigación Cooperativa en Biomateriales; Españ

Impact of PEGylation on the degradation and pore organization in Mesoporous Silica Nanoparticles: a study of the inner mesoporous structure in physiologically relevant ionic conditions

The degradation of mesoporous silica nanoparticles (MSNs) in the biological milieu due to silica hydrolysis plays a fundamental role for the delivery of encapsulated drugs and therapeutics. However, little is known on the evolution of the pore arrangement in the MSNs in biologically relevant conditions. Small Angle X-ray scattering (SAXS) studies were performed on unmodified and PEGylated MSNs with a MCM-48 pore structure and average sizes of 140 nm, exposed to simulated body fluid solution (SBF) at pH 7.4 for different time intervals from 30 min to 24 h. Experiments were performed with silica concentrations below, at and over 0.14 mg/mL, the saturation concentration of silica in water at physiological temperature. At silica concentrations of 1 mg/mL (oversaturation), unmodified MSNs show variation in interpore distances over 6 h exposure to SBF, remaining constant thereafter. A decrease in radius of gyration is observed over the same time. Mesoporosity and radius of gyration of unmodified MSNs remain then unchanged up to 24 h. PEGylated MSNs at 1 mg/mL concentration show a broader diffraction peak but no change in the position of the peak is observed following 24 h exposure to SBF. PEGylated MSNs at 0.01 mg/mL show no diffraction peaks already after 30 min exposure to SBF, while at 0.14 mg/mL a small diffraction peak is present after 30 min exposure but disappears after 1 h.Fil: Ramirez, Maria de Los Angeles. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martin. Instituto de Nanosistemas; Argentina. Basque Research and Technology Alliance. CIC biomaGUNE; EspañaFil: Bindini, Elisa. Basque Research and Technology Alliance. CIC biomaGUNE; EspañaFil: Moretti, Paolo. Università Politecnica Delle Marche; ItaliaFil: Soler Illia, Galo Juan de Avila Arturo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martin. Instituto de Nanosistemas; ArgentinaFil: Amenitsch, Heinz. Graz University Of Technology.; AustriaFil: Andreozzi, Patrizia. Università degli Studi di Firenze; Italia. Basque Research and Technology Alliance. CIC biomaGUNE; EspañaFil: Ortore, Maria Grazia. Università Politecnica Delle Marche; ItaliaFil: Moya, Sergio E.. Basque Research and Technology Alliance. CIC biomaGUNE; Españ

The importance of a taste. A comparative study on wild food plant consumption in twenty-one local communities in Italy

A comparative food ethnobotanical study was carried out in twenty-one local communities in Italy, fourteen of which were located in Northern Italy, one in Central Italy, one in Sardinia, and four in Southern Italy. 549 informants were asked to name and describe food uses of wild botanicals they currently gather and consume. Data showed that gathering, processing and consuming wild food plants are still important activities in all the selected areas. A few botanicals were quoted and cited in multiple areas, demonstrating that there are ethnobotanical contact points among the various Italian regions (Asparagus acutifolius, Reichardia picroides, Cichorium intybus, Foeniculum vulgare, Sambucus nigra, Silene vulgaris, Taraxacum officinale, Urtica dioica, Sonchus and Valerianella spp.). One taxon (Borago officinalis) in particular was found to be among the most quoted taxa in both the Southern and the Northern Italian sites

Prescription appropriateness of anti-diabetes drugs in elderly patients hospitalized in a clinical setting: evidence from the REPOSI Register

Diabetes is an increasing global health burden with the highest prevalence (24.0%) observed in elderly people. Older diabetic adults have a greater risk of hospitalization and several geriatric syndromes than older nondiabetic adults. For these conditions, special care is required in prescribing therapies including anti- diabetes drugs. Aim of this study was to evaluate the appropriateness and the adherence to safety recommendations in the prescriptions of glucose-lowering drugs in hospitalized elderly patients with diabetes. Data for this cross-sectional study were obtained from the REgistro POliterapie-Società Italiana Medicina Interna (REPOSI) that collected clinical information on patients aged ≥ 65 years acutely admitted to Italian internal medicine and geriatric non-intensive care units (ICU) from 2010 up to 2019. Prescription appropriateness was assessed according to the 2019 AGS Beers Criteria and anti-diabetes drug data sheets.Among 5349 patients, 1624 (30.3%) had diagnosis of type 2 diabetes. At admission, 37.7% of diabetic patients received treatment with metformin, 37.3% insulin therapy, 16.4% sulfonylureas, and 11.4% glinides. Surprisingly, only 3.1% of diabetic patients were treated with new classes of anti- diabetes drugs. According to prescription criteria, at admission 15.4% of patients treated with metformin and 2.6% with sulfonylureas received inappropriately these treatments. At discharge, the inappropriateness of metformin therapy decreased (10.2%, P < 0.0001). According to Beers criteria, the inappropriate prescriptions of sulfonylureas raised to 29% both at admission and at discharge. This study shows a poor adherence to current guidelines on diabetes management in hospitalized elderly people with a high prevalence of inappropriate use of sulfonylureas according to the Beers criteria

EOSC-SYNERGY EU DELIVERABLE: D1.2 Diseemination and exploitation report

Summary of dissemination and exploitation activities during the first half of the project.This document presents a summary of the dissemination and exploitation activities during the first half of the project. A description of the dissemination activities with the measurable results, and how they fit the strategy designed at the beginning of the project is presented. The exploitation part covers the first results of the project and describes the canvas model adopted by EOSC-synergy for results exploitation.EOSC-SYNERGY receives funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 857647.Peer reviewe

Role of Biofilm in Protection of the Replicative Form of Legionella pneumophila

The dual nature of Legionella pneumophila enables its survival in free and intracellular environments and underpins its infection and spread mechanisms. Experiments using bacterial cultures and improved RTqPCR protocols were devised to gain fresh insights into the role of biofilm in protecting the replicative form of L. pneumophila. mip gene expression was used as a marker of virulence in sessile (biofilm-bound) and planktonic (free-floating) cells of L. pneumophila serotype 1 ATCC 33152. The ratio of mip gene expression to transcriptionally active Legionella cells increased both in sessile and free-floating cells demonstrating an up-regulation of mip gene under nutrient depletion. However, a different trend was observed between the two forms, in planktonic cells the mip gene expression/transcriptionally active Legionella cells increased until the end of the experiment, while in the biofilm such increase was observed at the end of the experiment. These findings suggest a possible association between the switch to the transmissive phase of Legionella and a mip up-regulation and a role for biofilm in preserving Legionella cells in replicative form. Moreover, it has been shown that improved RTqPCR protocols are valuable tools to explore bacterial virulence