Archivio istituzionale della ricerca - Università di Palermo


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    I tumori germinali maligni del testicolo rappresentano una evenienza rara. L'approccio chirurgico consiste nella orchiectomia radicale con eventuale esplorazione chirurgica dei linfonodi retroperitoneali doppo l'opportuna valutazione per imaging. vengono presentati i risultati di uno Studio Cooperativo Nazionale

    Optimization of a new lead promoting the readthrough of the nonsense mutations for CFTR rescue in human CF cells

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    Optimization of a new lead promoting the readthrough of the nonsense mutations for CFTR rescue in human CF cells Laura Lentini, Raffaella Melfi, Sara Baldassano, Marco Tutone, Aldo Di Leonardo, Andrea Pace, Ivana Pibiri Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo Background and rationale Cystic Fibrosis patients with nonsense mutations in the CFTR gene have a more severe form of the disease. Nonsense mutations represent about 10% of the mutations that affect the CFTR gene and they are frequently associated to the classical \uf044F508 mutation (1). A potential treatment for this genetic alteration is to promote the translational readthrough of premature termination codons (PTCs) by Translational Read-Through-Inducing Drugs (TRIDs) (2-4). Hypothesis and objectives Our objective is to evaluate the functionality of the CFTR channel after treatment with a new molecule that we individuated in a precedent FFC project, and the activity of new lead molecules in cells stably expressing a nonsense-CFTR-mRNA (ns CFTR) in CF cellular model systems. We want also to study the supramolecular interactions among TRIDs, CFTR mRNA and the ribosomal A-site to identify the biological target and the mechanism of action. Essential methods QSAR, carried out on the basis of our preliminary results, will allow to achieve lead optimization and synthesize then a small library of analogs to be tested and compared to the Lead. We will mutagenize the CFTR cDNA by introducing the most diffuse nonsense mutations. Subsequently, FRT cells engineered with the vector expressing mutagenized nsCFTR, and nonsense-CF-human broncoepithelial cells will be grown in the air-liquid culture system to reproduce in vitro the epithelial organization. CFTR expression after treatments with our molecule will be evaluated by biomolecular techniques. CFTR activity will be revealed by specific CFTR-functionality assays. Finally, in vitro-in vivo (Zebrafish model) analyses of the safety profile for the set of synthesized molecules will complete the study. Preliminary results We screened the activity of several molecules synthetized by us in a precedent FFC project, identifying some molecules that showed high readthrough activity associated to the expression of the CFTR protein in ns CF immortalized cells. Expected final results and their significance We are confident that our findings will provide the validation of molecules with readthrough activity for the recovery of the CFTR function. Moreover, our pre-clinical study will assess the presence of toxic effects caused by the molecules in vivo. References 1. Sermet-Gaudelus I, Boeck KD, Casimir GJ, Vermeulen F, Leal T, Mogenet A, Roussel D, Fritsch J, Hanssens L, Hirawat S, Miller NL, Constantine S, Reha A, Ajayi T, Elfring GL, Miller LL. Ataluren (PTC124) induces cystic fibrosis transmembrane conductance regulator protein expression and activity in children with nonsense mutation cystic fibrosis., Am J RespirCrit Care Med. 2010 Nov 15;182(10):1262-72. 2. Lentini L, Melfi R, Di Leonardo A, Spinello A, Barone G, Pace A, Palumbo Piccionello A, Pibiri I. Towards a rationale for the PTC124 (Ataluren) promoted read-through of premature stop codons: a computational approach and GFP-reporter cell-based assay. Mol. Pharm. 2014 11, 653-664. 3. Pibiri I, Lentini L, Melfi R, Gallucci G, Pace A, Spinello A, Barone G, Di Leonardo A. Enhancement of premature stop codon readthrough in the CFTR gene by Ataluren (PTC124) derivatives European Journal of Medicinal Chemistry 06/2015; 101. 4. Nagel-Wolfrum K, M\uf6ller F, Penner I, Baasov T4, Wolfrum U. Targeting Nonsense Mutations in Diseases with Translational Read-Through-Inducing Drugs (TRIDs), BioDrugs. 2016 Apr;30(2):49-74

    Existence results for parametric boundary value problems involving the mean curvature operator

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    In this note we propose a variational approach to a parametric differential problem where a prescribed mean curvature equation is considered. In particular, without asymptotic assumptions at zero and at infinity on the potential, we obtain an explicit positive interval of parameters for which the problem under examination has at least one nontrivial and nonnegative solution

    A min-max principle for non-differentiable functions with a weak compactness condition

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    A general critical point result established by Ghoussoub is extended to the case of locally Lipschitz continuous functions satisfying a weak Palais-Smale hypothesis, which includes the so-called non-smooth Cerami condition. Some special cases are then pointed out

    Sourdough and cereal-based foods: traditional and innovative products

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    Cereals represent the main crop of the five continents and contribute greatly to the diet of several populations. Cereals often undergo a fermentation before eating. This process is fundamental to confer high sensory quality, as well as to preserve and enhance the nutritional and safety aspects of the resulting products. Fermented cereal based foods are complex microbial ecosystems, mainly represented by lactic acid bacteria and yeasts. Among these products, sourdough is worldwide applied to produce breads. Sourdough technology is also used to improve the final characteristics of fortified and gluten\u2013free breads. This chapter focuses on the use of cereals to produce the most relevant fermented foods. The processes of fermentation and the microbial groups involved are analysed. Potentials and limits of sourdough to produce high quality fortified and gluten\u2013free breads are summarised. The technological parameters for the selection of the starter cultures are also reported

    The anion impact on the self-assembly of naphthalene diimide diimidazolium salts

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    Naphthalene diimide diimidazolium salts differing in the anion nature were synthesized and their properties as well as their self-assembly behaviour were investigated. In particular, we took into consideration the N,N0-bis-(1-octyl-3-propylimidazolium)-naphthalene diimide cations and anions differing in size, shape and coordination abilities like [I], [BF4] and [NTf2]. After determination of thermal behaviour, using differential scanning calorimetry and thermal gravimetric analysis, the electrochemical stability and redox properties were assessed using cyclic voltammetry. The self-assembly behaviour of the salts was investigated using concentration and temperature-dependent spectroscopic studies (UV-vis and fluorescence). Data collected demonstrate the ability of salts used to aggregate through an isodesmic pathway. Interestingly, the aggregation is featured by an enhanced emission event. The properties of aggregates were also investigated in the solid state using fluorescence measurements and scanning electron microscopy (SEM). On the whole, data collected show that the properties of salts and of aggregates that they are able to form are heavily dependent on the anion nature. Salts used combine the properties of a semiconductor, like the naphthalene diimide core, with the ones of imidazolium salts and could have interesting applications as materials for optoelectronic and conservation of energy

    Shear stress alterations in the celiac trunk of patients with a continuous-flow left ventricular assist device as shown by in-silico and in-vitro flow analyses

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    Background The use of left ventricular assist devices (LVADs) to treat advanced cardiac heart failure is constantly increasing, although this device leads to high risk for gastrointestinal bleeding. Methods Using in-silico flow analysis, we quantified hemodynamic alterations due to continuous-flow LVAD (HeartWare, Inc., Framingham, MA) in the celiac trunk and major branches of the abdominal aorta, and then explored the relationship between wall shear stress (WSS) and celiac trunk orientation. To assess outflow from the aortic branch, a 3-dimensional-printed patient-specific model of the celiac trunk reconstructed from an LVAD-supported patient was used to estimate echocardiographic outflow velocities under continuous-flow conditions, and then to calibrate computational simulations. Moreover, flow pattern and resulting WSS values were computed for 5 patients with LVAD implantation. Results Peak WSS values were estimated on the 3 branches of the celiac trunk and the LVAD cannula. The mean WSSs demonstrated that the left gastric artery underwent the highest WSS of 9.08 \uc2\ub1 5.45 Pa, with an average flow velocity of 0.57 \uc2\ub1 0.25 m/s compared with that of other vessel districts. The common hepatic artery had a less critical WSS of 4.58 \uc2\ub1 1.77 Pa. A positive correlation was found between the celiac trunk angulation and the WSS stress just distal to the ostium of the celiac trunk (R = 0.9), which may increase vulnerability of this vessel to bleeding. Conclusions Although further studies are needed to confirm these findings in a larger patient cohort, computational flow simulations may enhance the information of clinical image data and may have an application in clinical investigations of hemodynamic changes in LVAD-supported patients

    Microorganisms of food ice cubes and their transfer to drinks

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    The present work was carried out to investigate the microbiological characteristics of the ice cubes produced at different levels: 1) home-made (HM) from domestic freezers; 2) produced by ice machines in bars and pubs (BP); 3) produced by ice industries (IN). BP samples were collected from the box stocks. HM and BP samples were transferred into sterile stomacher bags. IN samples were provided in the manufacturers\u2019 plastic bags. Samples were transported into thermal insulated boxes. Five samples per each production level, forming a total of 15 samples (HM1-HM5, BP1-BP5, IN1-IN5), were collected in duplicate in two consecutive months. Each ice sample was thawed in 1 L sterile Dhuram\u2019s bottle at room temperature and subjected to the membrane filtration analyses. Total mesophilic microorganisms (TMM), total psychrotrophic microorganisms (TPM), pseudomonads, members of the Enterobacteriaceae family, coliforms, enterococci, yeasts and moulds were investigated. When the amounts of colonies were uncountable, 1 mL of sample was directly inoculated into agar media. All results were expressed as colony forming units (CFU)/100 mL of thawed ice. TMM were in the range 100-9600, 312-6300 and 130-4000 for HM, BP and IN samples, respectively. Three HM and two IN samples were negative for the presence of TPM. The highest concentration (960) was found for IN2. Pseudomonads were detected in all HM samples but the highest levels were registered for BP1 (390) and IN2 (384). Except IN4, Enterobacteriaceae were found in all samples. All INs and 4 HM samples did not displayed coliforms. By contrast, they were hosted in all BP samples, ranging from 1 to 184. Enterococci were never found in HM samples, but detected in two INs and 3 BPs. Except IN1, moulds were always registered, while yeasts developed from the majority of HM and IN samples and two BP samples. The colonies representative for the different morphologies were randomly picked up from plates, purified to homogeneity and subjected to a phenotypic grouping. Yeasts and bacteria were subjected to the genetic identification by sequencing of D1/D2 domains of 26S rRNA gene and partial sequencing of 16S rRNA gene, respectively, while moulds were identified phenotypically. So far, the species mostly represented among bacteria, as evaluated only by the forward 16S rRNA gene sequence, were Bacillus spp., Pseudomonas spp., Pantoea spp., Pantoea agglomerans, Enterococcus faecium, and Agrobacterium tumefaciens. Candida intermedia and Pichia guillermondii were identified among yeasts and Penicillium spp. among moulds. The work was also aimed to monitor the microbial transfer from ice to humans through drinks. To this purpose, each microorganism was inoculated singly in sterile mineral water to produce contaminated ice cubes using disposable ice cube trays. Inoculums occurred at the highest concentrations found in the ice cubes analysed. The concentrations of the microorganisms were followed in six different types of drinks, including alcoholic (vodka and whiskey), moderate alcoholic (Martini), sparkling (tonic water), sugary (peach tea) and sugary sparkling (coke) drinks. In order to simulate the contamination of drinks by ice during consumption, six ice cubes (corresponding to 60 mL) containing each microorganism were added to 100 mL of each drink (simulating a bar administration) in sterile cups and, after 1 h, the entire volume was analysed by membrane filtration. A physiological solution was used as control. So far, the tests were performed with Penicillium spp. and P. agglomerans. Penicillium was not influenced by the different drinks, since, after 1 h, its level did not change. Regarding P. agglomerans, which is an opportunistic pathogen causing urinary tract infections, its concentration in peach tea was superimposable to that found in physiological solution, while it decreased in all other drinks. In particular, the concentration of this bacterium almost halved in vodka, coke and tonic water, diminished consistently in Martini and completely disappeared in whiskey. Experimentations are in progress to determine the behaviour of the other microorganisms in these systems. These data evidenced that the worst hygienic characteristics were found in BP samples, while the majority of ice cubes produced in specialized industries were characterized by acceptable microbiological parameters. This work indicated that the concentration of P. agglomerans is reduced by alcohol and CO2, but further in vivo assays are necessary to better clarify their role on the other ice microorganisms

    Recensione di: Nunzia Donadio, Vadimonium e contendere in iure. Tra "certezza di tutela" e "diritto alla difesa", Milano, Giuffrè, 2011, pp. XI-526 [ISBN: 9788814172526 ]

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    Recensione critica del libro Nunzia Donadio, Vadimonium e contendere in iure. Tra "certezza di tutela" e "diritto alla difesa", Milano, Giuffr\ue8, 2011, pp. XI-526 [ISBN: 9788814172526 ]

    Degradation of polymer blends: A brief review

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    The usefulness of any material, including polymer blends, depends on its degradability and durability. The blend composition can significantly affect the degradative behavior of a polymer blend and can differ from the degradation routes of the pure components since the interactions among different species in the blends during degradation, and among the degradation products, can occur. These reactions can lead either to an acceleration of the degradation rate or to a stabilizing effect in comparison with the pure components. Thus, the additive rule cannot be often applied in case of degradation of polymer blends and, therefore, it is difficult to predict the degradative behavior of a polymer blend on the base of the properties of pure components. This review aims to report the status of the research on degradation of polymer blends focusing on thermal, thermomechanical and photo-oxidative degradation
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