Absorption Enhancing Excipients in Systemic Nasal Drug Delivery

Intranasal drug delivery is becoming an increasingly important form of drug administration for chronic and chronic-intermittent diseases. Important new applications in development include drugs for diabetes, osteoporosis, obesity, certain types of convulsive disorders, migraine headaches, symptomatic pain relief, nausea, and anxiety, among others. Transmucosal absorption across the nasal mucosa is generally limited to molecules under 1,000 Da in size. Systemic delivery of molecules larger than this requires formulation with a suitable transmucosal absorption enhancer. More than one hundred potential transmucosal absorption enhancing excipients have been tested to date.  Nearly all have failed to be practical due to poor effectiveness or unacceptable toxicity to mucosal tissue. Alkylsaccharides, cyclodextrins, and chitosan's have emerged as the leading candidates for potential broad clinical applications and are allowing development of convenient, patient-friendly, needle free formulations of small molecule drugs, as well as peptide and protein drugs that can be administered at home, at work, or in other public and private settings outside of the doctor’s office or hospital environment

FUV variability of HD 189733. Is the star accreting material from its hot Jupiter?

Hot Jupiters are subject to strong irradiation from the host stars and, as a consequence, they do evaporate. They can also interact with the parent stars by means of tides and magnetic fields. Both phenomena have strong implications for the evolution of these systems. Here we present time resolved spectroscopy of HD~189733 observed with the Cosmic Origin Spectrograph (COS) on board to HST. The star has been observed during five consecutive HST orbits, starting at a secondary transit of the planet ($\phi$ ~0.50-0.63). Two main episodes of variability of ion lines of Si, C, N and O are detected, with an increase of line fluxes. Si IV lines show the highest degree of variability. The FUV variability is a signature of enhanced activity in phase with the planet motion, occurring after the planet egress, as already observed three times in X-rays. With the support of MHD simulations, we propose the following interpretation: a stream of gas evaporating from the planet is actively and almost steadily accreting onto the stellar surface, impacting at $70-90\deg$ ahead of the sub-planetary point.Comment: 35 pages, 19 Figures. Accepted for publication to Ap

Fingerprint of dynamical charge/spin correlations in the tunneling spectra of colossal magnetoresistive manganites

We present temperature-dependent scanning tunneling spectroscopy measurements on $La_{1-x}Ca_{x}MO_{3}$ ($x\sim0.33$) films with different degrees of biaxial strain. A depletion in normalized conductance around the Fermi level is observed both above and below the insulator-to-metal transition temperature $T_{MI}$, for weakly as well as highly-strained films. This pseudogap-like depletion globally narrows on cooling. The zero-bias conductance decreases on cooling in the insulating phase, reaches a minimum close to $T_{MI}$ and increases on cooling in the metallic phase, following the trend of macroscopic conductivity. These results support a recently proposed scenario in which dynamical short-range antiferromagnetic/charge order correlations play a preeminent role in the transport properties of colossal magnetoresistive manganites [R. Yu \textit{et al}., Phys. Rev. B \textbf{77}, 214434 (2008)].Comment: 9 pages, 4 figure

Scaling laws of solar and stellar flares

In this study we compile for the first time comprehensive data sets of solar and stellar flare parameters, including flare peak temperatures T_p, flare peak volume emission measures EM_p, and flare durations t_f from both solar and stellar data, as well as flare length scales L from solar data. Key results are that both the solar and stellar data are consistent with a common scaling law of EM_p ~ T_p^4.7, but the stellar flares exhibit ~250 times higher emission measures (at the same flare peak temperature). For solar flares we observe also systematic trends for the flare length scale L(T_p) ~ T_p^0.9 and the flare duration t_F(T_p) ~ T_p^0.9 as a function of the flare peak temperature. Using the theoretical RTV scaling law and the fractal volume scaling observed for solar flares, i.e., V(L) ~ L^2.4, we predict a scaling law of EM_p ~ T_p^4.3, which is consistent with observations, and a scaling law for electron densities in flare loops, n_p ~ T_p^2/L ~ T_p^1.1. The RTV-predicted electron densities were also found to be consistent with densities inferred from total emission measures, n_p=(EM_p/q_V*V)^1/2, using volume filling factors of q_V=0.03-0.08 constrained by fractal dimensions measured in solar flares. Our results affect also the determination of radiative and conductive cooling times, thermal energies, and frequency distributions of solar and stellar flare energies.Comment: 9 Figs., (paper in press, The Astrophsycial Journal

Sambucus nigra L. (fam. Viburnaceae) in Sicily: Distribution, Ecology, Traditional Use and Therapeutic Properties

Sambucus nigra, the elderberry, has long been used for its medicinal properties in treating numerous diseases. Based on this traditional knowledge, its different pharmacological activities have been the focus of active research. All parts of the tree have long been used in traditional medicine, that is, the bark, the leaves, the flowers and the fruit. This study, carried out in Sicily (Italy), concerns the traditional uses of elder against human diseases. In order to trace the history of man's interaction with elder on the island, multidisciplinary research was carried out, aiming at (1) presenting a comprehensive overview of elderberry's applications and activities and (2) bridging traditional knowledge (uses and beliefs) with modern science, i.e., the most recent scientific findings in the biomedical and pharmacological fields. A rigorous literature review of scientific (and other local) reports on the elderberry tree and its application in food, health and household applications was undertaken. This article also provides a synthetic and updated picture of the ecology and distribution of S. nigra in Sicily. The elderberry is quite widespread in Sicily, yet its distribution is discontinuous. It prefers hedges, riparian woodlands, forest margins and clearings and is rather common along the watercourses flowing in the canyons of the Hyblaean Plateau, in the Madonie Mts. and in Enna province. Indeed, many old plants are often found near sacred places and rural houses, suggesting that in the past, it was extensively planted on purpose for its multiple uses. The complementary data obtained from multidisciplinary research confirm the usefulness of this approach in building a comprehensive and correct picture of the distribution of the most common woody species, for which the available knowledge is often fragmentary and imprecise

Polysorbates, peroxides, protein aggregation, and immunogenicity – a growing concern

Aggregation can have a number of deleterious effects on biotherapeutics including the loss of efficacy, the induction of unwanted immunogenicity, altered pharmacokinetics, and reduced shelf life. Aggregation is ameliorated by the inclusion of surfactants in biotherapeutics formulations, typically non-ionic polymeric ether surfactants. The most commonly used examples are Tween® 20 (Polysorbate 20) and Tween® 80 (Polysorbate 80). Others include Triton™ X-100, Pluronic® F-68, Pluronic® F-88, Pluronic® F-127 (poloxamers), and Brij 35 (polyoxyethylene alkyl ether). The usefulness of polysorbates, in particular in preventing protein aggregation in biotherapeutic formulations, is well accepted. However, polysorbates contain ether linkages and unsaturated alkyl chains that have been shown to auto-oxidize in aqueous solution to protein-damaging peroxides and reactive aldehydes including formaldehyde and acetaldehyde. The peroxides principally affect methionine and tryptophan moieties. The aldehydes react with primary amino groups on proteins and are known to induce immunogenicity of proteins in the absence of aggregation or adjuvants. Detection of protein aggregation and prevention of aggregation using polysorbates is relatively straightforward using light scattering or size exclusion chromatography methods. Detection of oxidative damage to amino acyl moieties or increased immunogenicity resulting from the reaction of biotherapeutics with the degradation products of polysorbates is considerably more difficult and has generally been ignored in the scientific literature. As an increasing number of biotherapeutic agents come into use in common clinical practice, including both as innovator and as biosimilar products, these latter issues will come under increased scrutiny. Substitution of non-ionic, non-ether-based surfactants, could offer significant improvements in stability, reduced immunogenicity, and shelf life, and represents a significant unmet need in the field of biotherapeutics formulation

Vortex Structure in Superconducting Stripe States

The vortex structure in superconducting stripe states is studied according to the Bogoliubov-de Gennes theory on the two-dimensional Hubbard model with nearest-neighbor sites pairing interaction. The vortex is trapped at the outside region of the stripe line, where the superconductivity is weak. The superconducting coherence length along the stripe direction becomes long. There are no eminent low-energy electronic states even near the vortex core. These characters resemble the Josephson vortex in layered superconductors under a parallel field.Comment: LaTeX 5 pages (using jpsj macros) with 3 figure

Anti-phase Modulation of Electron- and Hole-like States in Vortex Core of Bi2Sr2CaCu2Ox Probed by Scanning Tunneling Spectroscopy

In the vortex core of slightly overdoped Bi2Sr2CaCu2Ox, the electron-like and hole-like states have been found to exhibit spatial modulations in anti-phase with each other along the Cu-O bonding direction. Some kind of one-dimensionality has been observed in the vortex core, and it is more clearly seen in differential conductance maps at lower biases below +-9 mV

The Stock Genetic Structure of Two Sparidae Species, Diplodus vulgaris and Lithognathus mormyrus, in the Mediterranean Sea.

Polyacrilamide gel electrophoresis (PAGE) of allozymes was used to investigate the intraspecies genetic variation and the genetic stock structure of Diplodus vulgaris and Lithognathus mormyrus captured from eight localities in the Mediterranean Sea. Twenty-two and 20 putative enzyme-coding loci were examined, respectively, in D. vulgaris and L. mormyrus. Polymorphic loci at the 95% level were used to assess the allozyme variability in D. vulgaris (AAT-2, EST-1, GLDH, PEPB-2, PGI-2, PGM, SDH) and L. mormyrus (AAT-2, EST-1, GLDH, MDH-2, PGI-2, PGM). The proportion of polymorphic loci in both species ranged from 0.31 (D. vulgaris) to 0.30 (L. mormyrus), and the observed and expected mean heterozygosity varied between 0.082 and 0.093 (D. vulgaris) and between 0.069 and 0.072 (L. mormyrus). The mean value of observed heterozygosity in D. vulgaris showed a deficit of heterozygosites, thereby indicating a Wahlund effect in the samples examined. Significant genetic differentiation (mean value of θ = 0.013, p < 0.005) was found in D. vulgaris indicating an intraspecific genetic substructure among the samples examined, whereas the mean value of θ = 0.001, p > 0.05 found in L. mormyrus showed a high degree of genetic homogeneity. The results showed the presence of distinct subpopulations of D. vulgaris among the sampled sites, and suggested that analysis of allozymes may provide important information on the genetic stock structure of these two sparids to ensure sustainable management of these species