Antioxidant Supplementation in the Treatment of Aging-Associated Diseases

Oxidative stress is generally considered as the consequence of an imbalance between pro- and antioxidants species, which often results into indiscriminate and global damage at the organismal level. Elderly people are more susceptible to oxidative stress and this depends, almost in part, from a decreased performance of their endogenous antioxidant system. As many studies reported an inverse correlation between systemic levels of antioxidants and several diseases, primarily cardiovascular diseases, but also diabetes and neurological disorders, antioxidant supplementation has been foreseen as an effective preventive and therapeutic intervention for aging-associated pathologies. However, the expectations of this therapeutic approach have often been partially disappointed by clinical trials. The interplay of both endogenous and exogenous antioxidants with the systemic redox system is very complex and represents an issue that is still under debate. In this review a selection of recent clinical studies concerning antioxidants supplementation and the evaluation of their influence in aging-related diseases is analyzed. The controversial outcomes of antioxidants supplementation therapies, which might partially depend from an underestimation of the patient specific metabolic demand and genetic background, are presented

Local anaesthesia efficacy as postoperative analgesia for open shoulder instability surgery. a prospective randomised controlled study

Background and objectives: The aim of present study was to evaluate for the first time, the clinical effect of local anaesthetic infiltration as postoperative analgesia in open shoulder surgery for anterior-inferior instability. The comparison of the local infiltration and interscalenic brachial plexus block to a control group test the local anaesthetic efficacy in this surgery. Methods: 78 patients scheduled for open shoulder surgery were enrolled and randomly assigned to one of three groups: local infiltration anaesthesia (LIA), interscalenic brachial plexus block (IBPB) and control (C). All patients received standardized general anaesthesia and all injections were performed with the same dose and volume of anaesthetic. The number boluses delivered by a PCA pump applied at the end of surgery and the visual analogue score (VAS) at 0, 2, 4, 6, 12, 18 and 24 hours after intervention were recorded. A patient satisfaction score was also assessed. Results: Mean bolus consumption of the rescue analgesic, compared to C, was significantly less both in the LIA and IBPB groups (P<0.05). The IBPB group showed VAS scores that were significantly better than C group at all time points (P<0.05). The VAS scores for LIA group were clinically comparable to IBPB, and only at the 2 and 6 hours, postoperative time points there were no significant differences found in respect to the C group. IBPB and LIA showed comparable patient satisfaction scores. Conclusion: The local anaesthetic infiltration as postoperative analgesia appears to be a clinically valid alternative, statistically comparable to IBPB, with no clinical meaningful adverse effects

Modelling functional and structural impact of non-synonymous single nucleotide polymorphisms of the DQA1 gene of three Nigerian goat breeds

The DQA1 gene is a member of the highly polymorphic MHC class II locus that is responsible for the differences among individuals in immune response to infectious agents. In this study, the authors performed a comprehensive computational analysis of the functional and structural impact of non-synonymous or amino acid-changing single nucleotide polymorphisms (SNPs) (nsSNPs) that are deleterious to the DQA1 protein in Nigerian goats. A 310-bp fragment of exon 2 of the DQA1 gene was amplified and sequenced in 27 unrelated animals that are representative of three major Nigerian goat breeds (nine each of West African Dwarf, Red Sokoto, and Sahel of both sexes) using genomic DNA. Forty-two nsSNPs were identified from the alignment of the deduced amino acid sequences. Based on the PANTHER, PROVEAN and PolyPhen-2 algorithms, there was consensus in identifying the mutants I26D, E114V and V115F as being deleterious. Further, differences between the native and the mutant proteins in the subsequent molecular trajectory analysis (stabilizing and flexible residue composition, total grid energy, solvation energy, coulombic energy, solvent accessibility, and protein-protein interaction properties) revealed E114V and V115F to be highly deleterious. Combined mutational analysis comparing the amutant (I26D, E114V and V115F mutations collectively) with the native protein also showed changes that could affect protein function and structure. Further wet-lab confirmatory analysis in a pathological association study involving a larger population of goats is required at the DQA1 locus. This would lay a sound foundation for breeding disease-resistant individuals in the future. Keywords: Goats, in silico, mutants, protein, tropic

Signals of Warped Extra Dimensions at the LHC

We discuss the signatures of the spin-2 graviton excitations predicted by the Randall-Sundrum model with one warped extra dimension, in dilepton and diphoton production at LHC. By using a specific angular analysis, we assess the ranges in mass and coupling constant where such gravitons can be discriminated against competitor spin-1 and spin-0 objects, that potentially could manifest themselves in these processes with the same mass and rate of events. Depending on the value of the coupling constant to quarks and leptons, the numerical results indicate graviton identification mass ranges up to 1.1-2.4 TeV and 1.6-3.2 TeV for LHC nominal energy of 14 TeV and time-integrated luminosity of 10 and 100~${\rm fb}^{-1}$, respectively.Comment: 8 pages, Talk given at QCD@Work - International Workshop on QCD - Theory and Experiment, 20 - 23 June, 2010, Martina Franca Ital

Conservative upper limits on WIMP annihilation cross section from Fermi-LAT γ\gamma-rays

The spectrum of an isotropic extragalactic $\gamma$-ray background (EGB) has been measured by the Fermi-LAT telescope at high latitudes. Two new models for the EGB are derived from the subtraction of unresolved point sources and extragalactic diffuse processes, which could explain from 30% to 70% of the Fermi-LAT EGB. Within the hypothesis that the two residual EGBs are entirely due to the annihilation of dark matter (DM) particles in the Galactic halo, we obtain $conservative$ upper limits on their annihilation cross section \sigmav. Severe bounds on a possible Sommerfeld enhancement of the annihilation cross section are set as well. Finally, would {\sigmav} be inversely proportional to the WIMP velocity, very severe limits are derived for the velocity-independent part of the annihilation cross section.Comment: Proceedings of XII Taup Conference, Munich, September 201

Insulin resistance and HCV virologic response to peg-interferons (Peg-IFN) with ribavirin (RBV) in HIV/HCV co-infected patients

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Plastic Deformation of 2D Crumpled Wires

When a single long piece of elastic wire is injected trough channels into a confining two-dimensional cavity, a complex structure of hierarchical loops is formed. In the limit of maximum packing density, these structures are described by several scaling laws. In this paper it is investigated this packing process but using plastic wires which give origin to completely irreversible structures of different morphology. In particular, it is studied experimentally the plastic deformation from circular to oblate configurations of crumpled wires, obtained by the application of an axial strain. Among other things, it is shown that in spite of plasticity, irreversibility, and very large deformations, scaling is still observed.Comment: 5 pages, 6 figure