The Phenion (R) Full-Thickness Skin Model for Percutaneous Absorption Testing

In recent years many efforts have been made to replace dermal toxicity testing of chemicals in the animal by in vitro assays. As a member of a German research consortium, we have previously contributed to the validation of an in vitro test protocol for percutaneous absorption studies on the basis of reconstructed human epidermis and both human and pig skin ex vivo. Aiming to assess the barrier properties of a newly developed reconstructed skin model, this protocol has now been transferred to the Phenion (R) Full-Thickness Skin Model (FT model). The permeation of testosterone and caffeine was quantified in parallel to that of pig skin using Franz-type diffusion cells. In addition, the permeation of benzoic acid and nicotine was studied. As expected, the FT model is more permeable than pig skin, yet its barrier properties are well in accordance with those of reconstructed human epidermis when compared to previous data. In fact, the FT model most efficiently retards testosterone as the compound of highest lipophilicity, which can be explained by an additional uptake by a reservoir formed by the dermis equivalent. Thus, the structure closely parallels human skin. In consequence, the Phenion FT model appears to be suitable for percutaneous absorption studies in hazard analysis and should be subjected to a catch-up validation study. Copyright (C) 2009 S. Karger AG, Base

Clinical assessment of retinal changes by spectral-domain OCT.

Purpose: To evaluate optical coherence tomography changes in patients with retinal thinning at the posterior pole. Methods: In this cross-sectional and retrospective study, 648 files were reviewed, and 67 patients were selected. Optical coherence tomography images that showed an area with a retinal thickness reduction at the macular region by using the Asymmetry Analysis Map in Heidelberg Spectralis were selected. The presence of hemisphere asymmetry in the same eye and asymmetry between the paired eyes were calculated and used for the analysis. Retinal thickness was measured in 3 different retinal areas (squares): (1) the area (square) involved by the pathology (IA), (2) the specular area (square) in the opposite hemifield (SA), and (3) the corresponding IA in the contralateral eye (CIA) (area used to recruit the patients). Retinal layer morphology was analyzed observing the Spectralis screen. Results: The thickness of the IA was 235.54 \ub1 39.95 \u3bcm (mean \ub1 standard deviation), while it was 269.84 \ub1 36.16 \u3bcm and 293.81 \ub1 37.52 \u3bcm for SA and CIA, respectively. Conclusions: Different retinal layers could be involved in reduction of the retinal thickness: a reduction of the inner layers was related to disease in which ciliary or retinal arterial vessel flow was involved, while a reduction of the outer retinal layer was related to pathologies related to choroidal flow diseases

Correlation Between the Transdermal Permeation of Ketoprofen and its Solubility in Mixtures of a pH 6.5 Phosphate Buffer and Various Solvents

The passage of a drug through the skin is directly proportional to the concentration of the drug in the donor phase and to the permeability coefficient constant Kp. Kp is determined essentially by two factors: the dissolution of the drug in the stratum corneum (measured by the partition coefficient P) and the diffusion in the same stratum (measured by the diffusion constant D). In our study, several saturated solutions of ketoprofen in mixtures of a pH 6.5 phosphate buffer and various co-solvents were studied to find correlations between the solubility of the ketoprofen in the mixtures and its permeation parameters in in vitro permeation studies with Franz cells. The results show that D does not change in the different mixtures; the diffusion of the drug into the stratum corneum is not influenced by the presence of the co-solvents, whereas the partition coefficient is strongly influenced. In particular, Kp and P were found to be inversely proportional to solubility, meaning that when the co-solvent increases the solubility, the partition of the drug and consequently Kp decrease. These findings were confirmed in some developed gels, and the developed gels were found to enhance the ketoprofen permeation with respect to the formulation in a commercial Fastum gel

Measurement of Measurement of V 0 Production Ratios in pp Collisions at ps = 0.9 and 7TeV

The \bar{\Lambda} / \Lambda and \bar{\Lambda} / K^0_\mathrm{S} production ratios are measured by the LHCb detector from 0.3\,\mathrm{nb}^{-1} of pp collisions delivered by the LHC at \sqrt{s} = 0.9\,TeV and 1.8\,\mathrm{nb}^{-1} at \sqrt{s} = 7\,TeV. Both ratios are presented as a function of transverse momentum, p_\mathrm{T}, and rapidity, y, in the ranges {0.15 \u3c p_\mathrm{T} \u3c 2.50\,\mathrm{GeV}/c} and {2.0

Search for the Lepton Number Violating Decays B+ → π- μ+μ+ and B+→ K-μ+ μ+

A search is performed for the lepton number violating decay B^{+}\rightarrow h^- \mu^+ \mu^+, where h^- represents a K^- or a \pi^-, using data from the LHCb detector corresponding to an integrated luminosity of 36pb^{-1}. The decay is forbidden in the Standard Model but allowed in models with a Majorana neutrino. No signal is observed in either channel and limits of B(B^{+} \rightarrow K^- \mu^+ \mu^+) \u3c 5.4\times 10^{-8} and B(B^{+} \rightarrow \pi^- \mu^+ \mu^+) \u3c 5.8\times 10^{-8} are set at the 95% confidence level. These improve the previous best limits by factors of 40 and 30, respectively

First Observation of Bs -\u3e J/psi f0(980) Decays

Using data collected with the LHCb detector in proton-proton collisions at a centre-of-mass energy of 7 TeV, the hadronic decay Bs -\u3e J/psi f0(980) is observed. This CP eigenstate mode could be used to measure mixing-induced CP violation in the B_s system. Using a fit to the pi+ pi- mass spectrum with interfering resonances gives R_{f0/phi} = [Gamma(Bs -\u3e J/psi f0, f0 -\u3e pi+ pi-)]/[Gamma(Bs -\u3e J/psi phi, phi -\u3e K+K-)] = 0.252^{+0.046+0.027}_{-0.032-0.033}, where the uncertainties are statistical and systematic, respectively

Measurements of the Branching Fractions for B_(s) -\u3e D_(s)πππ and Λ_b^0 -\u3e Λ_c^+πππ

Branching fractions of the decays H_b\to H_c\pi^-\pi^+\pi^- relative to H_b\to H_c\pi^- are presented, where H_b (H_c) represents B^0-bar(D^+), B^- (D^0), B_s^0-bar (D_s^+) and \Lambda_b^0 (\Lambda_c^+). The measurements are performed with the LHCb detector using 35{\rm pb^{-1}} of data collected at \sqrt{s}=7 TeV. The ratios of branching fractions are measured to be B(B^0-bar -\u3e D^+\pi^-\pi^+\pi^-)/ B(B^0-bar -\u3e D^+\pi^-) = 2.38\pm0.11\pm0.21 B(B^- -\u3e D^0\pi^-\pi^+\pi^-) / B(B^- -\u3e D^0\pi^-) = 1.27\pm0.06\pm0.11 B(B_s^0-bar -\u3e D_s^+\pi^-\pi^+\pi^-) / B(B_s^0-bar -\u3e D_s^+\pi^-) = 2.01\pm0.37\pm0.20 B(\Lambda_b^0-\u3e\Lambda_c^+\pi^-\pi^+\pi^-) / B(\Lambda_b^0 -\u3e \Lambda_c^+\pi^-) = 1.43\pm0.16\pm0.13. We also report measurements of partial decay rates of these decays to excited charm hadrons. These results are of comparable or higher precision than existing measurements

Measurements of the Branching Fractions for B(s) → D(s)πππ and Λb0 → Λc+πππ

Branching fractions of the decays H_b\to H_c\pi^-\pi^+\pi^- relative to H_b\to H_c\pi^- are presented, where H_b (H_c) represents B^0-bar(D^+), B^- (D^0), B_s^0-bar (D_s^+) and \Lambda_b^0 (\Lambda_c^+). The measurements are performed with the LHCb detector using 35{\rm pb^{-1}} of data collected at \sqrt{s}=7 TeV. The ratios of branching fractions are measured to be B(B^0-bar -\u3e D^+\pi^-\pi^+\pi^-)/ B(B^0-bar -\u3e D^+\pi^-) = 2.38\pm0.11\pm0.21 B(B^- -\u3e D^0\pi^-\pi^+\pi^-) / B(B^- -\u3e D^0\pi^-) = 1.27\pm0.06\pm0.11 B(B_s^0-bar -\u3e D_s^+\pi^-\pi^+\pi^-) / B(B_s^0-bar -\u3e D_s^+\pi^-) = 2.01\pm0.37\pm0.20 B(\Lambda_b^0-\u3e\Lambda_c^+\pi^-\pi^+\pi^-) / B(\Lambda_b^0 -\u3e \Lambda_c^+\pi^-) = 1.43\pm0.16\pm0.13. We also report measurements of partial decay rates of these decays to excited charm hadrons. These results are of comparable or higher precision than existing measurements

Measurement of the Inclusive phi Cross-Section in pp Collisions at Sqrt(s) = 7 TeV

The cross-section for inclusive phi meson production in pp collisions at a centre-of-mass energy of sqrt(s) = 7 TeV has been measured with the LHCb detector at the Large Hadron Collider. The differential cross-section is measured as a function of the phi transverse momentum p_T and rapidity y in the region 0.6 \u3c p_T \u3c 5.0 GeV/c and 2.44 \u3c y \u3c 4.06. The cross-section for inclusive phi production in this kinematic range is sigma(pp -\u3e phi X) = 1758 pm 19(stat) ^{+43}_{-14}(syst) pm 182(scale) microbarn, where the first systematic uncertainty depends on the p_T and y region and the second is related to the overall scale. Predictions based on the Pythia 6.4 generator underestimate the cross-section