Toxicological evaluation of lactose and chitosan delivered by inhalation

These days, inhalation constitutes a promising administration route for many drugs. However, this route exhibits unique limitations, and formulations aimed at pulmonary delivery should include as few as possible additives in order to maintain lung functionality. The purpose of this work was to investigate the safety of lactose and chitosan to the pulmonary tissue when delivered by inhalation. The study was carried out with 18 Wistar rats divided in three groups receiving distilled water, lactose or chitosan. A solution of each excipient was administered by inhalation at a dose of 20 mg. The lungs were excised and processed to determine several biochemical parameters used as toxicity biomarkers. Protein and carbonyl group content, lipid peroxidation, reduced and oxidized glutathione ( GSSG), myeloperoxidase ( MPO), cooper/zinc and manganese superoxide dismutase, catalase, glutathione S-transferase and glutathione peroxidase were determined. Results of myeloperoxidase activity and glutathione disulfide lung concentrations showed a relevant decrease for chitosan group compared to control: 4.67 +/- 2.27 versus 15.10 +/- 7.27 ( P = 0.011) for MPO and 0.89 +/- 0.68 versus 2.02 +/- 0.22 ( P = 0.014) for GSSG. The other parameters did not vary significantly among groups. Lactose and chitosan administered by inhalation failed to show toxic effects to the pulmonary tissue. A protective effect against oxidative stress might even be attributed to chitosan, since some biomarkers had values significantly lower than those observed in the control group when this product was inhaled. Nevertheless, caution must be taken regarding chemical composition and technological processes applied to incorporate these products during drug formulation, in particular for dry powder inhalators

Constraints on dark matter particles from theory, galaxy observations and N-body simulations

Mass bounds on dark matter (DM) candidates are obtained for particles decoupling in or out of equilibrium with {\bf arbitrary} isotropic and homogeneous distribution functions. A coarse grained Liouville invariant primordial phase space density $\mathcal D$ is introduced. Combining its value with recent photometric and kinematic data on dwarf spheroidal satellite galaxies in the Milky Way (dShps), the DM density today and $N$-body simulations, yields upper and lower bounds on the mass, primordial phase space densities and velocity dispersion of the DM candidates. The mass of the DM particles is bound in the few keV range. If chemical freeze out occurs before thermal decoupling, light bosonic particles can Bose-condense. Such Bose-Einstein {\it condensate} is studied as a dark matter candidate. Depending on the relation between the critical($T_c$)and decoupling($T_d$)temperatures, a BEC light relic could act as CDM but the decoupling scale must be {\it higher} than the electroweak scale. The condensate tightens the upper bound on the particle's mass. Non-equilibrium scenarios that describe particle production and partial thermalization, sterile neutrinos produced out of equilibrium and other DM models are analyzed in detail obtaining bounds on their mass, primordial phase space density and velocity dispersion. Light thermal relics with $m \sim \mathrm{few} \mathrm{keV}$ and sterile neutrinos lead to a primordial phase space density compatible with {\bf cored} dShps and disfavor cusped satellites. Light Bose condensed DM candidates yield phase space densities consistent with {\bf cores} and if $T_c\gg T_d$ also with cusps. Phase space density bounds from N-body simulations suggest a potential tension for WIMPS with $m \sim 100 \mathrm{GeV},T_d \sim 10 \mathrm{MeV}$.Comment: 27 pages 8 figures. Version to appear in Phys. Rev.

Epitaxial growth and magnetic properties of Sr2CrReO6 thin films

The double perovskite Sr2CrReO6 is an interesting material for spintronics, showing ferrimagnetism up to 635 K with a predicted high spin polarization of about 86%. We fabricated Sr2CrReO6 epitaxial films by pulsed laser deposition on (001)-oriented SrTiO3 substrates. Phase-pure films with optimum crystallographic and magnetic properties were obtained by growing at a substrate temperature of 700 degree C in pure O2 of 6.6x10-4 mbar. The films are c-axis oriented, coherently strained, and show less than 20% anti-site defects. The magnetization curves reveal high saturation magnetization of 0.8 muB per formula unit and high coercivity of 1.1 T, as well as a strong magnetic anisotropy.Comment: accepted for publicatio

Human ApoD, an apolipoprotein up-regulated in neurodegenerative diseases, extends lifespan and increases stress resistance in Drosophila

Apolipoprotein D (ApoD) expression increases in several neurological disorders and in spinal cord injury. We provide a report of a physiological role for human ApoD (hApoD): Flies overexpressing hApoD are long-lived and protected against stress conditions associated with aging and neurodegeneration, including hyperoxia, dietary paraquat, and heat stress. We show that the fly ortholog, Glial Lazarillo, is strongly up-regulated in response to these extrinsic stresses and also can protect in vitro-cultured cells in situations modeling Alzheimer's disease (AD) and Parkinson's disease (PD). In adult flies, hApoD overexpression reduces age-associated lipid peroxide accumulation, suggesting a proximal mechanism of action. Similar data obtained in the mouse [Ganfornina, M.D., et al., (2008) Apolipoprotein D is involved in the mechanisms regulating protection from oxidative stress. Aging Cell 10.1111/j.1474-9726.2008.00395.] as well as in plants (Charron et al., personal communication) suggest that ApoD and its orthologs play an evolutionarily conserved role in response to stress, possibly managing or preventing lipid peroxidation

Milky Way potentials in CDM and MOND. Is the Large Magellanic Cloud on a bound orbit?

We compute the Milky Way potential in different cold dark matter (CDM) based models, and compare these with the modified Newtonian dynamics (MOND) framework. We calculate the axis ratio of the potential in various models, and find that isopotentials are less spherical in MOND than in CDM potentials. As an application of these models, we predict the escape velocity as a function of the position in the Galaxy. This could be useful in comparing with future data from planned or already-underway kinematic surveys (RAVE, SDSS, SEGUE, SIM, GAIA or the hypervelocity stars survey). In addition, the predicted escape velocity is compared with the recently measured high proper motion velocity of the Large Magellanic Cloud (LMC). To bind the LMC to the Galaxy in a MOND model, while still being compatible with the RAVE-measured local escape speed at the Sun's position, we show that an external field modulus of less than $0.03 a_0$ is needed.Comment: Accepted for publication in MNRAS, 13 pages, 7 figures, 3 table

Soil and leaf mineral element contents in mediterranean vineyards: bioaccumulation and potential soil pollution

The study reported here concerns the geochemical distributions of macro- and trace elements (including potentially toxic elements, PTEs) in the vineyard soils of Alcubillas, which is one of the oldest, albeit not world-renowned, wine-growing areas in La Mancha (Central Spain). Soil and leaf samples were analyzed by X-ray fluorescence spectrometry to ascertain the levels of various elements in the soil and the plant. The potential toxicity of the elements was assessed with regard to the development of the vineyard. Despite the fact that fertilizers and pesticides are employed in the vineyards in this area, the results showed that the levels of trace elements in the soil samples did not exceed the reference values according the pedogeochemical values for the region and Spain. This finding suggests that the study area is not polluted, and therefore, there are hardly any traces of anthropogenic contamination. The Biological Absorption Coefficient (BAC) was calculated to assess the assimilation of various elements from the soil to the leaves, and differences were found in the element absorption capacity of the vines. Some elements were not taken up by Vitis vinifera despite elements like Zr and Rb being present in relatively high concentrations in the soil. The production in these soils does not represent a threat to human health or the ecosystem, because the farmers in this area are extremely careful to preserve the environment and they only farm to achieve moderate yields of grapes per hectar

An Explanation for the Observed Weak Size Evolution of Disk Galaxies

Surveys of distant galaxies with the Hubble Space Telescope and from the ground have shown that there is only mild evolution in the relationship between radial size and stellar mass for galactic disks from z~1 to the present day. Using a sample of nearby disk-dominated galaxies from the Sloan Digital Sky Survey (SDSS), and high redshift data from the GEMS (Galaxy Evolution from Morphology and SEDs) survey, we investigate whether this result is consistent with theoretical expectations within the hierarchical paradigm of structure formation. The relationship between virial radius and mass for dark matter halos in the LCDM model evolves by about a factor of two over this interval. However, N-body simulations have shown that halos of a given mass have less centrally concentrated mass profiles at high redshift. When we compute the expected disk size-stellar mass distribution, accounting for this evolution in the internal structure of dark matter halos and the adiabatic contraction of the dark matter by the self-gravity of the collapsing baryons, we find that the predicted evolution in the mean size at fixed stellar mass since z~1 is about 15-20 percent, in good agreement with the observational constraints from GEMS. At redshift z~2, the model predicts that disks at fixed stellar mass were on average only 60% as large as they are today. Similarly, we predict that the rotation velocity at a given stellar mass (essentially the zero-point of the Tully-Fisher relation) is only about 10 percent larger at z~1 (20 percent at z~2) than at the present day.Comment: 13 pages, 6 figures, accepted for publication in ApJ. Revised in response to referee's comments to improve clariry. Results are unchange