Effects of Eltrombopag on In Vitro Macrophage Polarization in Pediatric Immune Thrombocytopenia

Immune Thrombocytopenia (ITP) is an autoimmune disease characterized by autoantibodies-mediated platelet destruction, a prevalence of M1 pro-inflammatory macrophage phenotype and an elevated T helper 1 and T helper 2 lymphocytes (Th1/Th2) ratio, resulting in impairment of inflammatory profile and immune response. Macrophages are immune cells, present as pro-inflammatory classically activated macrophages (M1) or as anti-inflammatory alternatively activated macrophages (M2). They have a key role in ITP, acting both as effector cells, phagocytizing platelets, and, as antigen presenting cells, stimulating auto-antibodies against platelets production. Eltrombopag (ELT) is a thrombopoietin receptor agonist licensed for chronic ITP to stimulate platelet production. Moreover, it improves T and B regulatory cells functions, suppresses T-cells activity, and inhibits monocytes activation. We analyzed the effect of ELT on macrophage phenotype polarization, proposing a new possible mechanism of action. We suggest it as a mediator of macrophage phenotype switch from the M1 pro-inflammatory type to the M2 anti-inflammatory one in paediatric patients with ITP, in order to reduce inflammatory state and restore the immune system function. Our results provide new insights into the therapy and the management of ITP, suggesting ELT also as immune-modulating drug.     

A simple and effective design strategy to increase power conversion efficiency of linear charge pumps

This paper introduces a simple design strategy to increase the power efficiency of linear charge pumps. The technique exploits a voltage amplitude of the clock signal lower than the supply voltage to reduce the power conversion losses. The nominal output voltage is maintained unaltered by increasing the number of stages.     

Corticosteroids in liver and urine in Sicilian cattle by a LC-MS/MS method

The presence of corticosteroid residues was assessed in urine and liver samples from livestock of Sicily. A total of 630 bovine samples were collected from farms and slaughterhouses. The samples were analysed using solid-phase extraction (SPE) coupled with ultra-performance liquid chromatography tandem mass spectrometry (UHPLC–MS/MS). All the corticosteroids found were under the maximum residue limit imposed by Commission Regulation (EC) 37/2010. About 4% of liver samples showed dexamethasone levels above the limit of detection (LOD), with a mean of 1.5 ± 0.2 µg kg^?1. Betamethasone was found only in seven liver samples, with a mean of 1.6 ± 0.1 µg kg^?1. Furthermore, prednisolone and prednisone were found only in urine and liver samples from slaughterhouse, probably related to the high rate of stress for bovines. These results suggest good control practices adopted by Sicilian farms, able to ensure the quality of food products.     

Design and analysis of a new wave energy converter based on a point absorber and a hydraulic system harvesting energy from waves near the shore in calm seas

The aim of this paper is to illustrate the design of a new wave energy converter, composed of a point absorber and a hydraulic system (power take off) and sized for recovering energy in calm seas from waves near the shore. The point absorber is consisting of a rectangular shaped buoy integrating a piston pump. The set buoy‐pump oscillates under the waves action and moves natural water in a closed circuit hydraulic system (power take off) composed of a piping connecting the piston pump itself, a pressurized reservoir, a hydraulic turbine and a discharge tank. The methodology adopted for designing the main constituents involves a 1D mathematical model, settled for understanding the motion of the buoy under the hypothesis of regular waves and fully developed sea, and a sizing procedure applied for the design of all the components of the hydraulic system. The project related to the Calabrian site of Cetraro (Mediterranean Sea—south Italy) led to designing a system with a 4 m large buoy, associated with a small 13 cm diameter micro Pelton turbine, so that more than 22 000 kWh could be recovered in a year.     

Structural models of critical regions in old-type r.c. frames with smooth rebars

Structural assessment of existing reinforced concrete constructions under gravity loads and seismic actions has a high social and economical impact; actually in many European countries, most of the buildings dates back to 1960s and 1970s and cannot ensure satisfactory seismic response, since many areas have been later classified as seismic or since design has been carried out according to obsolete codes. These structures are generally reinforced with smooth bars that exhibit poor bond and need specific anchoring end details. In the present paper, some key aspects of structural models of smooth reinforcement for old-type r.c. frame analysis are reported. Results of experimental tests on smooth reinforcement and circular hook anchoring devices are also used to discuss some aspects of behavioural models of beam to column critical regions.     

Development of an experimental test rig for cogeneration based on a Stirling engine and a biofuel burner

A system consisting of a last-generation Stirling engine (SE) and a fuel burner for distributed power generation has been developed and experimentally investigated. The heat generated by the combustion of two liquid fuels, a standard Diesel fuel and a rapeseed oil, is used as a heat source for the SE, that converts part of the thermal energy into mechanical and then electric energy. The hot head of the SE is kept in direct contact with the flame generated by the burner. The burner operating parameters, designed for Diesel fuel, were changed to make it possible to burn vegetable oils, not suitable for internal combustion engines. The possibility of adopting different configurations of the combustion chamber was taken into account to increase the system efficiency. The preliminary configurations adopted allowed to operate this integrated system, obtaining an electric power up to 4.4 kW_el with a net efficiency of 11.6%.     

Generation of Rho Zero Cells: Visualization and Quantification of the mtDNA Depletion Process

Human mitochondrial DNA (mtDNA) is located in discrete DNA-protein complexes, so called nucleoids. These structures can be easily visualized in living cells by utilizing the fluorescent stain PicoGreen^®. In contrary, cells devoid of endogenous mitochondrial genomes (ρ⁰ cells) display no mitochondrial staining in the cytoplasm. A modified restriction enzyme can be targeted to mitochondria to cleave the mtDNA molecules in more than two fragments, thereby activating endogenous nucleases. By applying this novel enzymatic approach to generate mtDNA-depleted cells the destruction of mitochondrial nucleoids in cultured cells could be detected in a time course. It is clear from these experiments that mtDNA-depleted cells can be seen as early as 48 h post-transfection using the depletion system. To prove that mtDNA is degraded during this process, mtDNA of transfected cells was quantified by real-time PCR. A significant decline could be observed 24 h post-transfection. Combination of both results showed that mtDNA of transfected cells is completely degraded and, therefore, ρ⁰ cells were generated within 48 h. Thus, the application of a mitochondrially-targeted restriction endonuclease proves to be a first and fast, but essential step towards a therapy for mtDNA disorders.