Biodegradable and drug-eluting inorganic composites based on mesoporous zinc oxide for urinary stent applications

Conventional technologies for ureteral stent fabrication suffer from major inconveniences such as the development of encrustations and bacteria biofilm formation. These drawbacks typically lead to the failure of the device, significant patient discomfort and an additional surgery to remove and replace the stent in the worst cases. This work focuses on the preparation of a new nanocomposite material able to show drug elution properties, biodegradation and eventually potential antibacterial activity. Poly(2-hydroxyethyl methacrylate) or the crosslinked poly(2-hydroxyethyl methacrylate)-co-poly(acrylic acid) hydrogels were prepared by the radical polymerization method and combined with a biodegradable and antibacterial filling agent, i.e., flower-like Zinc Oxide (ZnO) micropowders obtained via the hydrothermal route. The physico-chemical analyses revealed the correct incorporation of ZnO within the hydrogel matrix and its highly mesoporous structure and surface area, ideal for drug incorporation. Two different anti-inflammatory drugs (Ibuprofen and Diclofenac) were loaded within each composite and the release profile was monitored up to two weeks in artificial urine (AU) and even at different pH values in AU to simulate pathological conditions. The addition of mesoporous ZnO micropowders to the hydrogel did not negatively affect the drug loading properties of the hydrogel and it was successfully allowed to mitigate undesirable burst-release effects. Furthermore, the sustained release of the drugs over time was observed at neutral pH, with kinetic constants (k) as low as 0.05 h-1. By exploiting the pH-tunable swelling properties of the hydrogel, an even more sustained release was achieved in acidic and alkaline conditions especially at short release times, with a further reduction of burst effects (k ≈ 0.01-0.02 h-1). The nanocomposite system herein proposed represents a new material formulation for preparing innovative drug eluting stents with intrinsic antibacterial properties

X-HESS: a large sample of highly accreting serendipitous AGN under the XMM-Newton microscope

The bulk of X-ray spectroscopic studies of active galactic nuclei (AGN) are focused on local ($z < 0.1$) sources with low-to-moderate ($< 0.3$) Eddington ratio ($\lambda_\mathrm{Edd}$). It is then mandatory to overcome this limitation and improve our understanding of highly accreting AGN. In this work we present the preliminary results from the analysis of a sample of $\sim70$ high-$\lambda_\mathrm{Edd}$ radio-quiet AGN at $0.06 \leq z \leq 3.3$, based on the 10th release of the XMM-Newton serendipitous source catalogue, that we named as XMM-Newton High-Eddington Serendipitous AGN Sample (X-HESS). Almost $\sim35\%$ of the X-HESS AGN have multi-epoch archival observations and $\sim70\%$ of the sources can rely on simultaneous OM optical data. First results reveal sources showing signatures of ultra-fast outflows and remarkable long- and short-term X-ray flux variations. Indeed in J095847.88+690532.7 ($z \sim 1.3$), one of the most densely monitored objects hosting a $\sim$$10^9\,M_\odot$ supermassive black hole, we discovered a variation of the soft X-ray flux by a factor of > 2 over approximately one week (rest-frame). Large variations in the power-law continuum photon index $\Gamma$ are also observed, questioning expectations from previously reported $\Gamma - \lambda_\mathrm{Edd}$ relations, for which $\Gamma \geq 2$ would be a ubiquitous hallmark of AGN with $\lambda_\mathrm{Edd} \sim 1$.Comment: 7 pages, 5 figures, proceedings of the XMM-Newton Workshop 2022 "Black hole accretion under the X-ray microscope". Accepted for publication in Astronomische Nachrichte

Effects of vanadyl complexes with acetylacetonate derivatives on non-tumor and tumor cell lines

Vanadium has a good therapeutic potential, as several biological effects, but few side effects, have been demonstrated. Evidence suggests that vanadium compounds could represent a new class of non-platinum, metal antitumor agents. In the present study, we aimed to characterize the antiproliferative activities of fluorescent vanadyl complexes with acetylacetonate derivates bearing asymmetric substitutions on the β-dicarbonyl moiety on different cell lines. The effects of fluorescent vanadyl complexes on proliferation and cell cycle modulation in different cell lines were detected by ATP content using the CellTiter-Glo Luminescent Assay and flow cytometry, respectively. Western blotting was performed to assess the modulation of mitogen-activated protein kinases (MAPKs) and relevant proteins. Confocal microscopy revealed that complexes were mainly localized in the cytoplasm, with a diffuse distribution, as in podocyte or a more aggregate conformation, as in the other cell lines. The effects of complexes on cell cycle were studied by cytofluorimetry and Western blot analysis, suggesting that the inhibition of proliferation could be correlated with a block in the G2/M phase of cell cycle and an increase in cdc2 phosphorylation. Complexes modulated mitogen-activated protein kinases (MAPKs) activation in a cell-dependent manner, but MAPK modulation can only partly explain the antiproliferative activity of these complexes. All together our results demonstrate that antiproliferative effects mediated by these compounds are cell type-dependent and involve the cdc2 and MAPKs pathway

Biodegradation and antimicrobial properties of zinc oxide–polymer composite materials for urinary stent applications

Research advancements in the field of urinary stents have mainly been in the selection of materials and coatings to address commonly faced problems of encrustation and bacterial adhesion. In this study, polylactic acid (PLA) and polypropylene (PP) were evaluated with zinc oxide (ZnO) coating to assess its ability to reduce or eliminate the problems of encrustation and bacteria adhesion. PLA and PP films were prepared via twin screw extrusion. ZnO microparticles were prepared using sol-gel hydrothermal synthesis. The as-prepared ZnO microparticles were combined in the form of a functional coating and deposited on both polymer substrates using a doctor blade technique. The ZnO-coated PP and PLA samples as well as their uncoated counterparts were characterized from the physicochemical standpoints, antibacterial and biodegradation properties. The results demonstrated that both the polymers preserved their mechanical and thermal properties after coating with ZnO, which showed a better adhesion on PLA than on PP. Moreover, the ZnO coating successfully enhanced the antibacterial properties with respect to bare PP/PLA substrates. All the samples were investigated after immersion in simulated body fluid and artificial urine. The ZnO layer was completely degraded following 21 days immersion in artificial urine irrespective of the substrate, with encrustations more evident in PP and ZnO-coated PP films than PLA and ZnO-coated PLA films. Overall, the addition of ZnO coating on PLA displayed better adhesion, antibacterial activity and delayed the deposition of encrustations in comparison to PP substrates

Comparative study of the biological behaviour in hamster of two isolates of leishmania characterized respectively as L. major-like and L. donovani

Hamster inoculated intraperitoneally with 1 x 10(7) parasites of L. donovani and L. major-like of the New World were studied in groups of 15, 30, 60 and 90 days of infection. The parasite load and density showed progressive increase with the evolution of the infection and was higher in the L. donovani groups than in the L. major-like groups. The L. major-like groups showed parasite density higher in the spleen than in the liver and was similar in both organs in L. donovani groups. The histopathology showed a diffuse marked hyperplasia and hypertrophy of the reticuloendothelial system with high parasitism in the L. donovani groups while there was focal involvement of these organs in L. major-like groups, forming nodules of macrophages that were scantly parasitised. The biological behaviour could be useful in the preliminary studies of Leishmania strain in regional laboratories and understanding the histopathology of lesions caused by different leishmania species.Experimentos utilizando-se hamsters inoculados intraperitonealmente com 1 x 10(7) parasitas de 2 cepas, L. donovani (MHOM/BR/72/LD 46) e L. major-like (MCAN/BR/73/LD 70) isoladas no Novo Mundo foram realizados e estudados em grupos de 15, 30, 60 e 90 dias de infecção. A carga e a densidade parasitária mostraram progressivo aumento com a evolução da infecção e foi maior nos grupos inoculados com L. donovani do que nos grupos inoculados com L. major-like. Os grupos inoculados com L. major-like mostraram densidade parasitária maior no baço que no fígado e foram semelhantes em ambos os órgãos nos grupos inoculados com L. donovani. A histopatologia mostrou intensa e difusa hyperplasia e hipertrofia do sistema reticuloendotelial com alto parasitismo nos grupos inoculados com L. donovani, enquanto foi encontrado envolvimento focai nestes órgãos nos grupos inoculados com L. major-like, formando nódulos de macrófagos discretamente parasitados. O comportamento biológico seria útil em estudos preliminares de identificação de cepas de Leishmania em laboratórios regionais e na compreensão da histopatologia das lesões causadas por diferentes espécimes de leishmanias

Long-Term Safety of Anti-TNF Adalimumab in HBc Antibody-Positive Psoriatic Arthritis Patients: A Retrospective Case Series of 8 Patients

Immunosuppressive drugs commonly used in the treatment of psoriatic arthritis make patients more susceptible to viral, bacterial, and fungal infections because of their mechanism of action. They not only increase the risk of new infections but also act altering the natural course of preexisting infections. While numerous data regarding the reactivation of tuberculosis infection are available in the literature, poor information about the risk of reactivation or exacerbation of hepatitis viruses B and C infections during treatment with biologics has been reported. Furthermore, reported series with biological therapy included short periods of followup, and therefore, they are not adequate to verify the risk of reactivation in the long-term treatment. Our study evaluated patients with a history of hepatitis B and psoriatic arthritis treated with adalimumab and monitored up to six years. During the observation period, treatment was effective and well tolerated in all patients, and liver function tests and viral load levels remained unchanged

The Ring Imaging Cherenkov detector (RICH) of the AMS experiment

The Alpha Magnetic Spectrometer (AMS) experiment to be installed on the International Space Station (ISS) will be equipped with a proximity focusing Ring Imaging Cherenkov (RICH) detector for measuring the electric charge and velocity of the charged cosmic particles. A RICH prototype consisting of 96 photomultiplier units, including a piece of the conical reflector, was built and its performance evaluated with ion beam data. Preliminary results of the in-beam tests performed with ion fragments resulting from collisions of a 158 GeV/c/nuc primary beam of Indium ions (CERN SPS) on a Pb target are reported. The collected data included tests to the final front-end electronics and to different aerogel radiators. Cherenkov rings for a large range of charged nuclei and with reflected photons were observed. The data analysis confirms the design goals. Charge separation up to Fe and velocity resolution of the order of 0.1% for singly charged particles are obtained.Comment: 29th International Conference on Cosmic Rays (Pune, India