P2X7 receptor antagonist reduces fibrosis and inflammation in a mouse model of alpha-sarcoglycan muscular dystrophy

Limb-girdle muscular dystrophy R3, a rare genetic disorder affecting the limb proximal muscles, is caused by mutations in the α-sarcoglycan gene (Sgca) and aggravated by an immune-mediated damage, finely modulated by the extracellular (e)ATP/purinoceptors axis. Currently, no specific drugs are available. The aim of this study was to evaluate the therapeutic effectiveness of a selective P2X7 purinoreceptor antagonist, A438079. Sgca knockout mice were treated with A438079 every two days at 3 mg/Kg for 24 weeks. The P2X7 antagonist improved clinical parameters by ameliorating mice motor function and decreasing serum creatine kinase levels. Histological analysis of muscle morphology indicated a significant reduction of the percentage of central nuclei, of fiber size variability and of the extent of local fibrosis and inflammation. A cytometric characterization of the muscle inflammatory infiltrates showed that A438079 significantly decreased innate immune cells and upregulated the immunosuppressive regulatory T cell subpopulation. In α-sarcoglycan null mice, the selective P2X7 antagonist A438079 has been shown to be effective to counteract the progression of the dystrophic phenotype and to reduce the inflammatory response. P2X7 antagonism via selective inhibitors could be included in the immunosuppressant strategies aimed to dampen the basal immune-mediated damage and to favor a better engraftment of gene-cell therapies

Comparative analysis of co-processed starches prepared by three different methods

Co-processing is currently of interest in the generation of high-functionality excipients for tablet formulation. In the present study, comparative analysis of the powder and tableting properties of three co-processed starches prepared by three different methods was carried out. The co-processed excipients consisting of maize starch (90%), acacia gum (7.5%) and colloidal silicon dioxide (2.5%) were prepared by co-dispersion (SAS-CD), co-fusion (SAS-CF) and co-granulation (SAS-CG). Powder properties of each co-processed excipient were characterized by measuring particle size, flow indices, particle density, dilution potential and lubricant sensitivity ratio. Heckel and Walker models were used to evaluate the compaction behaviour of the three co-processed starches. Tablets were produced with paracetamol as the model drug by direct compression on an eccentric Tablet Press fitted with 12 mm flat-faced punches and compressed at 216 MPa. The tablets were stored at room temperature for 24 h prior to evaluation. The results revealed that co-granulated co-processed excipient (SAS-CG) gave relatively better properties in terms of flow, compressibility, dilution potential, deformation, disintegration, crushing strength and friability. This study has shown that the method of co-processing influences the powder and tableting properties of the co-processed excipient

Comparative analysis of co-processed starches prepared by three different methods

Co-processing is currently of interest in the generation of high-functionality excipients for tablet formulation. In the present study, comparative analysis of the powder and tableting properties of three co-processed starches prepared by three different methods was carried out. The co-processed excipients consisting of maize starch (90%), acacia gum (7.5%) and colloidal silicon dioxide (2.5%) were prepared by co-dispersion (SAS-CD), co-fusion (SAS-CF) and co-granulation (SAS-CG). Powder properties of each co-processed excipient were characterized by measuring particle size, flow indices, particle density, dilution potential and lubricant sensitivity ratio. Heckel and Walker models were used to evaluate the compaction behaviour of the three co-processed starches. Tablets were produced with paracetamol as the model drug by direct compression on an eccentric Tablet Press fitted with 12 mm flat-faced punches and compressed at 216 MPa. The tablets were stored at room temperature for 24 h prior to evaluation. The results revealed that co-granulated co-processed excipient (SAS-CG) gave relatively better properties in terms of flow, compressibility, dilution potential, deformation, disintegration, crushing strength and friability. This study has shown that the method of co-processing influences the powder and tableting properties of the co-processed excipient

Achievement of the planetary defense investigations of the Double Asteroid Redirection Test (DART) mission

NASA's Double Asteroid Redirection Test (DART) mission was the first to demonstrate asteroid deflection, and the mission's Level 1 requirements guided its planetary defense investigations. Here, we summarize DART's achievement of those requirements. On 2022 September 26, the DART spacecraft impacted Dimorphos, the secondary member of the Didymos near-Earth asteroid binary system, demonstrating an autonomously navigated kinetic impact into an asteroid with limited prior knowledge for planetary defense. Months of subsequent Earth-based observations showed that the binary orbital period was changed by –33.24 minutes, with two independent analysis methods each reporting a 1σ uncertainty of 1.4 s. Dynamical models determined that the momentum enhancement factor, β, resulting from DART's kinetic impact test is between 2.4 and 4.9, depending on the mass of Dimorphos, which remains the largest source of uncertainty. Over five dozen telescopes across the globe and in space, along with the Light Italian CubeSat for Imaging of Asteroids, have contributed to DART's investigations. These combined investigations have addressed topics related to the ejecta, dynamics, impact event, and properties of both asteroids in the binary system. A year following DART's successful impact into Dimorphos, the mission has achieved its planetary defense requirements, although work to further understand DART's kinetic impact test and the Didymos system will continue. In particular, ESA's Hera mission is planned to perform extensive measurements in 2027 during its rendezvous with the Didymos–Dimorphos system, building on DART to advance our knowledge and continue the ongoing international collaboration for planetary defense

Differential photosynthetic response of two Mediterranean species (Arbutus unedo and Viburnum tinus) to sulphur dioxide

The responses of young plants of Arbutus unedo and Viburnum tinus to long-term (80120 days) exposure of sulphur dioxide were investigated. Constant levels of the pollutant of 25 and 60 ppb were supplied to the plants, in comparison to charcoal-filtered air. At regular intervals, the photosynthetic responses were analyzed on fully expanded leaves developed during the fumigation. No visible symptoms were detected on the leaves of the treated plants. The photosynthetic activity and growth of A. unedo was markedly reduced in connection to a partial stomatal closure. In V. tinus, CO2 assimilation did not change although stomatal conductance significantly decreased at the end of treatment. A mechanism of repair was supposed. Results are discussed on the basis of natural drought stress resistance of plants typical of mediterrannean environments

A gas-exchange study of the differential response of Quercus species to long-term fumigations with a gradient of sulphur dioxide

Young oak plants (Quercus pubescens Willd. and Q. cerris L.) were exposed for 23 weeks to a gradient of sulphur dioxide concentrations (28, 61, 93 ppb in vol., compared with charcoal filtered-air ventilated controls) in fumigation chambers. Foliar gas exchange was analyzed by an IRGA methodology after 11 weeks and chlorophyll was assessed in a non-destructive way. At the end, foliar biomass produced during the experimental period was determined and its total sulphur and carbohydrate content analyzed. Visible foliar injury, as well as reduction in chlorophyll content was not observed. Carbon dioxide assimilation was linearly depressed by sulphur dioxide in both the species, with a maximum depression of 25% in Q. pubescens and 44% in Q. cerris. Stomatal conductance and transpiration were negatively affected only in Q. pubescens, with a linear trend. The two species showed a similar behaviour in water use efficiency, this parameter being reduced in a linear fashion. The intracellular/ambient carbon dioxide concentration ratio was affected in a differential way: while in Q. pubescens no alteration was evident, a linear increase was shown by Q. cerris. Total foliar sulphur content was dramatically increased in both the species. Average leaf area was unaffected in both the species. Reduction in foliar dry weight was only observed in Q. cerris (-30% at the highest sulphur dioxide concentration). We speculate that in Q. pubescens photosynthetic limitations are mainly of stomatal nature, and in Q. cerris the major constraints are probably associated with mesophyll disturbances. Foliar starch content was linearly increased by the pollutant