1,721,429 research outputs found

    Effetti dei Microcristalli di Urato Monosodico sull'apoptosi spontanea ed induzione di frammenti di DNA instabile nei sinoviociti

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    The deposition of Urate Monosodium crystals (MSU) in the articular and periarticular tissues is cause of the onset of inflammatory states associated to acute gout. Despite several and different pathogenetic hypotheses proposed, the molecular mechanism that controls the acute inflammatory attack induced by the microcrystals is still unknown. The aim of this study, through a model of acute inflammation in vitro mediated by MSU crystals , is verify the possible cito- and genotoxic effects induced on primary cultures of synoviocites derived from synovial fluid of 6 patients (3 affected by OA and 3 by AP). The purpose of this research is to determinate if the inflammation can influence the instability of genoma of the involved cells and what are the possible consequences in these cells concern the incidence of the apoptoss, proliferation, DNA integrity, formation of DNA unstable fragments and other aberrant figures as micronuclei. Experimentally the synoviocites primary cultures have been stimulated for 24 hours with different concentrations of MSU crystals (0,01 mg/ml; 0,025 mg/ml; 0,05 mg/ml; 0,075 mg/ml; 0,1 mg/ml, 0,25 mg/ml and 0,5 mg/ml). The same conditions have been repeated on CHO cells cultures, from Chinese Hamster, that represents one of the cellular systems more used and standardized for studies about in vitro mutagenesis.. For every experimental point the followings techniques have been applied: to) Tunel Test in order to analyze and quantify apoptotic cells b)In situ Incorporation of digoxigenin-dUTP for the staining of DNA breaks in the interphase nuclei and within the fragments of unstable DNA. c) cytological analysis for the determination of the mitotic index, of the defective mitoses and of other cytological parameters of genomic instability as presence of micronuclei, nuclear vesicles and anaphasic bridges. The stimulation for 24 hours of the CHO cell lines of Chinese Hamster has underlined as the presence of the MSU crystals induces on this cellular population a clastogenic effect. In fact the incidence of the cells marked by the digoxigenin-dUTP probe, that localizes in correspondence to free 3'-OH inside the DNA, increases in a dose dependent manner . The same results is noticed for other aberrations as the MN , aberrant mitotic figures, NPB and NBUD. Also the Mitotic index shows a meaningful decrease related on the MSU crystals dose used. The stimulation of the OA and AP derived synoviocytes primary cultures from confirm that , under these conditions, the MSU crystals induced a DNA damage in way analogous to how observed in precedence in CHO cell line used as control system. Nevertheless for all the types of DNA damage considered , the synoviocites derived from synovial fluid of patients with AP shows, from basal level as in presence of increasing stimulations of MSU crystals, a meaningful incidence of DNA damage greater in comparison to the synoviocites derived from OA. Such greater sensibility for the potentially genotoxic agents could derive from the fact that the primary cultures from AP originate from a synovial liquid, in general, more inflammatory in comparison to OA derived cells. In presence of stimulation with MSU crystals the frequency of apoptotic cells in CHO cells and OA primary cultures shows a meaningful decrement with values inferior to the 1% of incidence on the total population. Increasing the dose of stimulation the frequency of apoptotic cells increases in fucntion of the dose, in linear way for CHO cell line, while for the OA synoviocities , apoptosis increases. Subsequently for doses of MSU greater than 0,1mg/ml apoptosis slightly decreases. To basal level apoptosia of the AP synoviocites results very lower in comparison to the other cultures; nevertheless this primary culture cells respond in a very analogous way to the CHO cells and AP synoviocites in the presence of increasing doses of MSU crystals. Observing these data can be hypothesized that, relatively to apoptosis, the presence of MSU crystals, also already to concentrations of 0,01mg/ml acts with a " switch on/switch off "way, inhibiting a molecular apoptotic pathwayi for then subsequently activate an alternative for it in sensitive manner to the dose of stimulation. The data proposed in this study, even certainly still preliminary ,indicate that this simple experimental model can result very useful to appraise the DNA damage within joint tissues cell populations involved in the articular inflammatory pathologies and to characterize their behavior and evolution of it under these conditions. In perspective, analogous tests in vitro on cells obtained from the synovial fluid of patients with arthropathies could be predictive, also from the clinical point of view, in to preventively appraise the evolution of a date cellular population under conditions of chronic and acute inflammatory stress and in order to understand the degree of potential citotoxicity that a determined pharmacological treatment could induce to cellular level in a individual patient

    The translational value of calcium pyrophosphate deposition disease experimental mouse models

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    The deposition of calcium pyrophosphate (CPP) crystals in joint tissues causes acute and chronic arthritis that commonly affect the adult and elderly population. Experimental calcium pyrophosphate deposition disease (CPPD) models are divided into genetically modified models and crystal-induced inflammation models. The former do not reproduce phenotypes overlapping with the human disease, while in the latter, the direct injection of crystals into the ankles, dorsal air pouch or peritoneum constitutes a useful and reliable methodology that resembles the CPP induced-inflammatory condition in humans. The translational importance of the induced model is also strengthened by the fact that the key molecular and cellular mediators involved in inflammation are shared between humans and laboratory rodents. Although, in vivo models are indispensable tools for studying the pathogenesis of the CPPD and testing new therapies, their development is still at an early stage and major efforts are needed to address this issue. Here, we analyze the strenghts and limitations of each currently available CPPD in vivo model, and critically discuss their translational value

    Statins, fracture risk, and bone remodeling

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    Statins inhibit HMG-CoA reductase and reduce the intracellular formation of mevalonate. They are chemical compounds able to reduce total cholesterol by 15-40% and LDL cholesterol by 20-60%, and to increase HDL cholesterol by 5-15%. They also reduce triglycerides by 10- 30%. Statins, blocking the mevalonate pathway, inhibit the prenylation of proteins, which is essential to perform their biological function. A great deal of research has documented the positive effect of statins on bone formation and the importance of bone morphogenetic protein-2 (BMP-2) in mediating this effect. Statins are also able to decrease osteoblast apoptosis. The positive effect of statins on bone formation is accompanied by an inhibition of osteoclast activity, which gives statins the ability to uncouple the bone remodeling processes. Patients taking statins have a higher femoral bone density than those who do not. The lipophilic statins seem to be more effective than the hydrophilic statins in protecting bone. In several clinical trials, but not in all, the use of statins had been associated with a reduction in the fracture risk. In conclusion, statins have a positive effect on bone in vitro, but such an efficacy in humans has yet to be clearly demonstrated. Randomized, controlled trials are needed to provide a satisfactory answer on this issue

    Ni/CeO2-Al2O3 catalysts for the dry reforming of methane: the effect of CeAlO3 content and nickel crystallite size on catalytic activity and coke resistance

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    The catalytic performances of Ni/CeO2–Al2O3 catalysts for the dry reforming of CH4 (DRM) were investigated. Catalysts with different Ni dispersion and different amounts of CeAlO3 species were prepared by different methods and characterized by BET, XRD, XPS, Raman, TPR, and TPO techniques. Catalytic activity was studied during the time on stream in the range 873–1073K with a mixture of CH4:CO2:Ar = 40:40:20 vol.% and GHSV 90,000 cm3 g−1 h−1. The intrinsic catalytic activity increased with the increase of Ni crystallite size. Carbon was deposited as nano-fibers and graphite when catalysts worked at lower temperatures, and the largest amount was found on the catalyst with the largest Ni crystallite size. The formation of graphitic deposits is limited by the presence of CeAlO3 species formed during catalyst activation. CA preparation method results particularly attractive because it allows obtaining catalysts with small Ni crystallite size and high content of CeAlO3 species, which both have a role in suppressing the carbon deposition and therefore in obtaining stable catalytic performances

    Giuseppe Abate, Giovanni Luisetto. Codici e manoscritti della Biblioteca Antoniana col Catalogo delle miniature a cura di François Avril, Francesca d'Arcais, Giordana Mariani Canova

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    Bernardinello Silvio. Giuseppe Abate, Giovanni Luisetto. Codici e manoscritti della Biblioteca Antoniana col Catalogo delle miniature a cura di François Avril, Francesca d'Arcais, Giordana Mariani Canova. In: Scriptorium, Tome 33 n°2, 1979. pp. 314-316

    The catalytic activity of cobalt-exchanged mordenites for the abatement of NO with CH4 in the presence of excess O2

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    The abatement of NO with methane in the presence of oxygen was studied on various commercial MOR in the Na-form (Na-MOR) and H-form (H-MOR), or exchanged to various extents with cobalt (Co-MOR). The sodium and cobalt contents were determined by atomic absorption. Samples were characterized by FTIR and volumetric measurements of CO adsorption. Chemical analysis indicated that one cobalt species replaced two Brønsted acid sites in H-MOR and two Na + ions in Na-MOR. The IR analysis of the OH stretching region, evidencing an unexpected presence of Brønsted acid sites (band at 3610 cm-1) in Co-MOR, indicated that the exchange process had a more complex stoichiometry. The adsorption of CO at RT on Co-MOR, in addition to the bands of the corresponding H-MOR and Na-MOR matrices, yielded two types of CoII-carbonyls, the first type occupied the mordenite main channels, and the second one the mordenite smaller channels. Brønsted acid sites in mordenites were active for the selective catalytic reduction of NO with CH4. Co-MOR samples were far more active than Na-MOR and H-MOR samples, showing that acid protons play a negligible role when Co is present. Co-MOR catalysts showing the highest activity had the largest amount of Co II-carbonyls in the main channels. This result strongly suggests that CoII in the main channels of MOR are the active sites for the CH4 + NO + O2 reaction. © 2003 Elsevier B.V. All rights reserved

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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