Decreased myocardial injury and improved contractility after administration of a peptide derived against the alpha-interacting domain of the L-type calcium channel.

BackgroundMyocardial infarction remains the leading cause of morbidity and mortality associated with coronary artery disease. The L-type calcium channel (IC a-L) is critical to excitation and contraction. Activation of the channel also alters mitochondrial function. Here, we investigated whether application of a alpha-interacting domain/transactivator of transcription (AID-TAT) peptide, which immobilizes the auxiliary β2 subunit of the channel and decreases metabolic demand, could alter mitochondrial function and myocardial injury.Methods and resultsTreatment with AID-TAT peptide decreased ischemia-reperfusion injury in guinea-pig hearts ex vivo (n=11) and in rats in vivo (n=9) assessed with uptake of nitroblue tetrazolium, release of creatine kinase, and lactate dehydrogenase. Contractility (assessed with catheterization of the left ventricle) was improved after application of AID-TAT peptide in hearts ex vivo (n=6) and in vivo (n=8) up to 12 weeks before sacrifice. In search of the mechanism for the effect, we found that intracellular calcium ([Ca(2+)]i, Fura-2), superoxide production (dihydroethidium fluorescence), mitochondrial membrane potential (Ψm, JC-1 fluorescence), reduced nicotinamide adenine dinucleotide production, and flavoprotein oxidation (autofluorescence) are decreased after application of AID-TAT peptide.ConclusionsApplication of AID-TAT peptide significantly decreased infarct size and supported contractility up to 12 weeks postcoronary artery occlusion as a result of a decrease in metabolic demand during reperfusion

Dark Monopoles in Grand Unified Theories

We consider a Yang-Mills-Higgs theory with gauge group $G=SU(n)$ broken to $G_{v} = [SU(p)\times SU(n-p)\times U(1)]/Z$ by a Higgs field in the adjoint representation. We obtain monopole solutions whose magnetic field is not in the Cartan Subalgebra. Since their magnetic field vanishes in the direction of the generator of the electromagnetic group $U(1)_{em}$, we call them Dark Monopoles. These Dark Monopoles must exist in some Grand Unified Theories (GUTs) without the need to introduce a dark sector. We analyze the particular case of $SU(5)$ GUT, where we obtain that their mass is $M = 4\pi v \widetilde{E}(\lambda/e^{2})/e$, where $\widetilde{E}(\lambda/e^{2})$ is a monotonically increasing function of $\lambda/e^{2}$ with $\widetilde{E}(0)=1.294$ and $\widetilde{E}(\infty)=3.262.$ We also give a geometrical interpretation to their non-abelian magnetic charge.Comment: 22 pages; added some comments on possible cosmological implications of Dark Monopoles in the last section and added some references. Published Versio

Primordial Gravitational Waves Enhancement

We reconsider the enhancement of primordial gravitational waves that arises from a quantum gravitational model of inflation. A distinctive feature of this model is that the end of inflation witnesses a brief phase during which the Hubble parameter oscillates in sign, changing the usual Hubble friction to anti-friction. An earlier analysis of this model was based on numerically evolving the graviton mode functions after guessing their initial conditions near the end of inflation. The current study is based on an equation which directly evolves the normalized square of the magnitude. We are also able to make a very reliable estimate for the initial condition using a rapidly converging expansion for the sub-horizon regime. Results are obtained for the energy density per logarithmic wave number as a fraction of the critical density. These results exhibit how the enhanced signal depends upon the number of oscillatory periods; they also show the resonant effects associated with particular wave numbers.Comment: 25 pages, 14 figure

Efficacy of first-line sodium thiosulphate administration in a case of potassium cyanide poisoning

Cyanide poisoning may occur following accidental fire-smoke inhalation or deliberate ingestion of salts. Hydroxocobalamin represents a first-line life-saving antidote. Although hydroxocobalamin represents a first-line lifesaving antidote, it is still not promptly available in the emergency department. Sodium thiosulfate can be administered in association with hydroxocobalamin whereas the delayed onset of clinical response makes sodium thiosulfate less suitable for emergency use. We describe a case of cyanide intoxication of a 43-year-old man who ingested an unknown amount of potassium cyanide, purchased via the Internet, in an attempted suicide. At admission to the emergency department, the patient presented GCS 3 with severe lactic acidosis. Orotracheal intubation, gastric lavage and oral activated charcoal were applied. Sodium thiosulfate was available in the emergency department and 10 grams were infused over a 30 minute period. Hydroxocobalamin was prescribed by the poison control centre and 5 grams were infused 2 hours after admission. Following sodium thiosulfate administration the patient was arousable and lactate concentration improved. No adverse effects were noted. Metabolic acidosis completely resolved 12 hours later. Cyanide concentration performed on blood samples collected at admission confirmed high cyanide blood levels (15 mg/L). This report highlights as the first-line administration of sodium thiosulfate, in rapid infusion, resulted effective and safe for cyanide poisoning. Our report suggests that sodium thiosulfate should be considered when hydroxocobalamin is not promptly available in an emergency settin

Preliminary study on electrophysiological changes after cellular autograft in age-related macular degeneration

Background: Evolving atrophic macular degeneration represents at least 80% of all macular degenerations and is currently without a standardized care. Autologous fat transplantation (AFT) efficacy was demonstrated by several studies, since these cells are able to produce growth factors. The aim of the work was to demonstrate possible therapeutic effect of the joined suprachoroidal graft of adipocytes, adipose derived stem-cells (ADSCs) in tissue adipose’s stromal vascular fractions (SVF), and platelet rich plasma (PRP). Methods: Twelve eyes in 12 dry age macular degeneration (AMD) patients, aged 71.25 (SD ± 6.8) between 62 and 80 years, were analyzed. A complete ocular evaluation was performed using: best corrected visual acuity (BCVA), retinographic analysis, spectral-domain optical coherence tomography, microperimetry, computerized visual field, and standard electroretinogram (ERG). Each eye received a cell in graft between choroid and sclera by means of the variant second Limoli, grafting of mature fat cells and ADSCs in SVF enriched with PRP (LRRT). In order to test if the differences pre- and post-treatment were significant the Wilcoxon signed rank test has been performed. Results: Adverse effects were not reported in the patients. After surgery with LRRT the most significant increase in the ERG values was recorded by scotopic rod-ERG (answer coming from the rods), from 41.26 to 60.83 μVolts (µV) with an average increase of 47.44% highly significant (p<0.05). Moderately significant was the one recorded by scotopic maximal ERG (answer coming from the rods and cones), from 112.22 to 129.68 μV with an average increase of 15.56% (p<0.1). Conclusions: Cell-mediated therapy based on growth factors used appears interesting because it can improve the retinal functionality responses in the short term. The ERG could, therefore, be used to monitor the effect of cell-mediated regenerative therapies

Reversibility of Red blood Cell deformation

The ability of cells to undergo reversible shape changes is often crucial to their survival. For Red Blood Cells (RBCs), irreversible alteration of the cell shape and flexibility often causes anemia. Here we show theoretically that RBCs may react irreversibly to mechanical perturbations because of tensile stress in their cytoskeleton. The transient polymerization of protein fibers inside the cell seen in sickle cell anemia or a transient external force can trigger the formation of a cytoskeleton-free membrane protrusion of micrometer dimensions. The complex relaxation kinetics of the cell shape is shown to be responsible for selecting the final state once the perturbation is removed, thereby controlling the reversibility of the deformation. In some case, tubular protrusion are expected to relax via a peculiar "pearling instability".Comment: 4 pages, 3 figure

Computing Matveev's complexity via crystallization theory: the boundary case

The notion of Gem-Matveev complexity has been introduced within crystallization theory, as a combinatorial method to estimate Matveev's complexity of closed 3-manifolds; it yielded upper bounds for interesting classes of such manifolds. In this paper we extend the definition to the case of non-empty boundary and prove that for each compact irreducible and boundary-irreducible 3-manifold it coincides with the modified Heegaard complexity introduced by Cattabriga, Mulazzani and Vesnin. Moreover, via Gem-Matveev complexity, we obtain an estimation of Matveev's complexity for all Seifert 3-manifolds with base $\mathbb D^2$ and two exceptional fibers and, therefore, for all torus knot complements.Comment: 27 pages, 14 figure

The Fine Structure Constant and the CMB Damping Scale

The recent measurements of the Cosmic Microwave Background anisotropies at arcminute angular scales performed by the ACT and SPT experiments are probing the damping regime of CMB fluctuations. The analysis of these datasets unexpectedly suggests that the effective number of relativistic degrees of freedom is larger than the standard value of Neff = 3.04, and inconsistent with it at more than two standard deviations. In this paper we study the role of a mechanism that could affect the shape of the CMB angular fluctuations at those scales, namely a change in the recombination process through variations in the fine structure constant. We show that the new CMB data significantly improve the previous constraints on variations of {\alpha}, with {\alpha}/{\alpha}0 = 0.984 \pm 0.005, i.e. hinting also to a more than two standard deviation from the current, local, value {\alpha}0. A significant degeneracy is present between {\alpha} and Neff, and when variations in the latter are allowed the constraints on {\alpha} are relaxed and again consistent with the standard value. Deviations of either parameter from their standard values would imply the presence of new, currently unknown physics.Comment: 4 pages, 1 figur