Pharmacokinetic study on pradofloxacin in the dog – Comparison of serum analysis, ultrafiltration and tissue sampling after oral administration

Background: Pradofloxacin, a newly developed 8-cyano-fluoroquinolone, show enhanced activity against Grampositive organisms and anaerobes to treat canine and feline bacterial infections. The purpose of this cross-over study was to measure the unbound drug concentration of pradofloxacin in the interstitial fluid (ISF) using ultrafiltration and to compare the kinetics of pradofloxacin in serum, ISF and tissue using enrofloxacin as reference. Results: After oral administration of enrofloxacin (5 mg/kg) and pradofloxacin (3 mg/kg and 6 mg/kg, respectively), serum collection and ultrafiltration in regular intervals over a period of 24 h were performed, followed by tissue sampling at the end of the third dosing protocol (pradofloxacin 6 mg/kg). Peak concentrations of pradofloxacin (3 mg/kg) were 1.55±0.31 μg/ml in the ISF and 1.85±0.23 μg/ml in serum and for pradofloxacin (6 mg/kg) 2.71±0.81 μg/kg in the ISF and 2.77±0.64 μg/kg in serum; both without a statistical difference between ISF and serum. Comparison between all sampling approaches showed no consistent pattern of statistical differences. Conclusions: Despite some technical shortcomings the ultrafiltration approach appears to be the most sensitive sampling technique to estimate pharmacokinetic values of pradofloxacin at the infection site. Pharmacokinetics – Pradofloxacin – Ultrafiltration – Dog – Oral Administration

The Biological Standard of Living in the two Germanies.

Physical stature is used as a proxy for the biological standard of living in the two Germanies before and after unification in an analysis of a cross-sectional sample (1998) of adult heights, as well as among military recruits of the 1990s. West Germans tended to be taller than East Germans throughout the period under consideration. Contrary to official proclamations of a classless society, there were substantial social differences in physical stature in East-Germany. Social differences in height were greater in the East among females, and less among males than in the West. The difficulties experienced by the East-German population after 1961 is evident in the increase in social inequality of physical stature thereafter, as well as in the increasing gap relative to the height of the West-German population. After unification, however, there is a tendency for East-German males, but not of females, to catch up with their West-German counterparts

Critical Susceptibility Exponent Measured from Fe/W(110) Bilayers

The critical phase transition in ferromagnetic ultrathin Fe/W(110) films has been studied using the magnetic ac susceptibility. A statistically objective, unconstrained fitting of the susceptibility is used to extract values for the critical exponent (gamma), the critical temperature Tc, the critical amplitude (chi_o) and the range of temperature that exhibits power-law behaviour. A fitting algorithm was used to simultaneously minimize the statistical variance of a power law fit to individual experimental measurements of chi(T). This avoids systematic errors and generates objective fitting results. An ensemble of 25 measurements on many different films are analyzed. Those which permit an extended fitting range in reduced temperature lower than approximately .00475 give an average value gamma=1.76+-0.01. Bilayer films give a weighted average value of gamma = 1.75+-0.02. These results are in agreement with the -dimensional Ising exponent gamma= 7/4. Measurements that do not exhibit power-law scaling as close to Tc (especially films of thickness 1.75ML) show a value of gamma higher than the Ising value. Several possibilities are considered to account for this behaviour.Comment: -Submitted to Phys. Rev. B -Revtex4 Format -6 postscript figure

First principles calculation of structural and magnetic properties for Fe monolayers and bilayers on W(110)

Structure optimizations were performed for 1 and 2 monolayers (ML) of Fe on a 5 ML W(110) substrate employing the all-electron full-potential linearized augmented plane-wave (FP-LAPW) method. The magnetic moments were also obtained for the converged and optimized structures. We find significant contractions ($\sim$ 10 %) for both the Fe-W and the neighboring Fe-Fe interlayer spacings compared to the corresponding bulk W-W and Fe-Fe interlayer spacings. Compared to the Fe bcc bulk moment of 2.2 $\mu_B$, the magnetic moment for the surface layer of Fe is enhanced (i) by 15% to 2.54 $\mu_B$ for 1 ML Fe/5 ML W(110), and (ii) by 29% to 2.84 $\mu_B$ for 2 ML Fe/5 ML W(110). The inner Fe layer for 2 ML Fe/5 ML W(110) has a bulk-like moment of 2.3 $\mu_B$. These results agree well with previous experimental data

The helicase HAGE prevents interferon-a-induced PML expression in ABCB5+ malignant melanoma-initiating cells by promoting the expression of SOCS1

The tumour suppressor PML (promyelocytic leukaemia protein) regulates several cellular pathways involving cell growth, apoptosis, differentiation and senescence. PML also has an important role in the regulation of stem cell proliferation and differentiation. Here, we show the involvement of the helicase HAGE in the transcriptional repression of PML expression in ABCB5 + malignant melanoma-initiating cells (ABCB5 + MMICs), a population of cancer stem cells which are responsible for melanoma growth, progression and resistance to drug-based therapy. HAGE prevents PML gene expression by inhibiting the activation of the JAK-STAT (janus kinase-signal transducers and activators of transcription) pathway in a mechanism which implicates the suppressor of cytokine signalling 1 (SOCS1). Knockdown of HAGE led to a significant decrease in SOCS1 protein expression, activation of the JAK-STAT signalling cascade and a consequent increase of PML expression. To confirm that the reduction in SOCS1 expression was dependent on the HAGE helicase activity, we showed that SOCS1, effectively silenced by small interfering RNA, could be rescued by re-introduction of HAGE into cells lacking HAGE. Furthermore, we provide a mechanism by which HAGE promotes SOCS1 mRNA unwinding and protein expression in vitro

A hysteresis model with dipole interaction: one more devil-staircase

Magnetic properties of 2D systems of magnetic nanoobjects (2D regular lattices of the magnetic nanoparticles or magnetic nanostripes) are considered. The analytical calculation of the hysteresis curve of the system with interaction between nanoobjects is provided. It is shown that during the magnetization reversal system passes through a number of metastable states. The kinetic problem of the magnetization reversal was solved for three models. The following results have been obtained. 1) For 1D system (T=0) with the long-range interaction with the energy proportional to $r^{-p}$, the staircase-like shape of the magnetization curve has self-similar character. The nature of the steps is determined by interplay of the interparticle interaction and coercivity of the single nanoparticle. 2) The influence of the thermal fluctuations on the kinetic process was examined in the framework of the nearest-neighbor interaction model. The thermal fluctuations lead to the additional splitting of the steps on the magnetization curve. 3) The magnetization curve for system with interaction and coercivity dispersion was calculated in mean field approximation. The simple method to experimentally distinguish the influence of interaction and coercivity dispersion on the magnetization curve is suggested.Comment: 22 pages, 8 figure

Measurement of the charm structure function F_{2,c)^{γ} of the photon at LEP

The production of charm quarks is studied in deep-inelastic electron–photon scattering using data recorded by the OPAL detector at LEP at nominal e⁺e⁻ centre-of-mass energies from 183 to 209 GeV. The charm quarks have been identified by full reconstruction of charged D* mesons using their decays into D⁰π with the D⁰ observed in two decay modes with charged particle final states, Kπ and Kπππ. The cross-section σ^{D*} for production of charged D* in the reaction e⁺e⁻→e⁺e⁻D*Χ is measured in a restricted kinematical region using two bins in Bjorken x, 0.00140.1 the perturbative QCD calculation at next-to-leading order agrees perfectly with the measured cross-section. For x<0.1 the measured cross-section is 43.8±14.3±6.3±2.8 pb with a next-to-leading order prediction of 17.0⁺²·⁹_₂.₃ pb