Chelators confined into 80pvac-borax highly viscous dispersions for the removal of gypsum degradation layers

AbstractIn this paper a new method for the removal of gypsum degradation layers from carbonatic matrices in cultural heritage conservation, using aqueous Highly Viscous Polymeric Dispersions (HVPDs) based on partially hydrolyzed poly(vinyl acetate) and borax, embedded with chelators, is presented. Due to their interesting viscoelasticity, these systems guarantee a good adhesion to the treated surface and easiness of removal in one step, minimizing the residues. Thus, they can potentially overcome the "residue question" limit associated to traditional methodologies that use thickened solutions of chelators. Here the rheological properties of HVPDs containing different amounts of selected chelating agents are explored and their efficacy in the extraction of gypsum is verified through cleaning tests onto artificially sulfated travertine tiles. The homogeneous removal of gypsum across the surface was checked non-invasively via Fourier Transform Infrared Spectroscopy (FTIR) 2D Imaging. An analytical protocol for the pre-treatment and the analysis of HVPD samples by means of Ion Cromatography (IC) and Inductively Coupled Plasma Atomic Emission Spectroscopy (ICP-AES) was set up and the approximate amount of calcium sulfate removed was determined

Cathepsin B inhibition interferes with metastatic potential of human melanoma: an in vitro and in vivo study

<p>Abstract</p> <p>Background</p> <p>Cathepsins represent a group of proteases involved in determining the metastatic potential of cancer cells. Among these are cysteinyl- (e.g. cathepsin B and cathepsin L) and aspartyl-proteases (e.g. cathepsin D), normally present inside the lysosomes as inactive proenzymes. Once released in the extracellular space, cathepsins contribute to metastatic potential by facilitating cell migration and invasiveness.</p> <p>Results</p> <p>In the present work we first evaluated, by <it>in vitro </it>procedures, the role of cathepsins B, L and D, in the remodeling, spreading and invasiveness of eight different cell lines: four primary and four metastatic melanoma cell lines. Among these, we considered two cell lines derived from a primary cutaneous melanoma and from a supraclavicular lymph node metastasis of the same patient. To this purpose, the effects of specific chemical inhibitors of these proteases, i.e. CA-074 and CA-074Me for cathepsin B, Cathepsin inhibitor II for cathepsin L, and Pepstatin A for cathepsin D, were evaluated. In addition, we also analyzed the effects of the biological inhibitors of these cathepsins, i.e. specific antibodies, on cell invasiveness. We found that i) cathepsin B, but not cathepsins L and D, was highly expressed at the surface of metastatic but not of primary melanoma cell lines and that ii) CA-074, or specific antibodies to cathepsin B, hindered metastatic cell spreading and dissemination, whereas neither chemical nor biological inhibitors of cathepsins D and L had significant effects. Accordingly, <it>in vivo </it>studies, i.e. in murine xenografts, demonstrated that CA-074 significantly reduced human melanoma growth and the number of artificial lung metastases.</p> <p>Conclusions</p> <p>These results suggest a reappraisal of the use of cathepsin B inhibitors (either chemical or biological) as innovative strategy in the management of metastatic melanoma disease.</p

Differential redox state contributes to sex disparities in the response to influenza virus infection in male and female mice

Influenza virus replicates intracellularly exploiting several pathways involved in the regulation of host responses. The outcome and the severity of the infection are thus strongly conditioned by multiple host factors, including age, sex, metabolic, and redox conditions of the target cells. Hormones are also important determinants of host immune responses to influenza and are recently proposed in the prophylaxis and treatment. This study shows that female mice are less susceptible than males to mouse-adapted influenza virus (A/PR8/H1N1). Compared with males, PR8-infected females display higher survival rate (+36%), milder clinical disease, and less weight loss. They also have milder histopathological signs, especially free alveolar area is higher than that in males, even if pro-inflammatory cytokine production shows slight differences between sexes; hormone levels, moreover, do not vary significantly with infection in our model. Importantly, viral loads (both in terms of viral M1 RNA copies and tissue culture infectious dose 50%) are lower in PR8-infected females. An analysis of the mechanisms contributing to sex disparities observed during infection reveals that the female animals have higher total antioxidant power in serum and their lungs are characterized by increase in (i) the content and biosynthesis of glutathione, (ii) the expression and activity of antioxidant enzymes (peroxiredoxin 1, catalase, and glutathione peroxidase), and (iii) the expression of the anti-apoptotic protein Bcl-2. By contrast, infected males are characterized by high expression of NADPH oxidase 4 oxidase and phosphorylation of p38 MAPK, both enzymes promoting viral replication. All these factors are critical for cell homeostasis and susceptibility to infection. Reappraisal of the importance of the host cell redox state and sex-related effects may be useful in the attempt to develop more tailored therapeutic interventions in the fight against influenza

A multi-element psychosocial intervention for early psychosis (GET UP PIANO TRIAL) conducted in a catchment area of 10 million inhabitants: study protocol for a pragmatic cluster randomized controlled trial

Multi-element interventions for first-episode psychosis (FEP) are promising, but have mostly been conducted in non-epidemiologically representative samples, thereby raising the risk of underestimating the complexities involved in treating FEP in 'real-world' services