Localization of dexamethasone within dendritic core-multishell (CMS) nanoparticles and skin penetration properties studied by multi-frequency electron paramagnetic resonance (EPR) spectroscopy

The skin and especially the stratum corneum (SC) act as a barrier and protect epidermal cells and thus the whole body against xenobiotica of the external environment. Topical skin treatment requires an efficient drug delivery system (DDS). Polymer-based nanocarriers represent novel transport vehicles for dermal application of drugs. In this study dendritic core-multishell (CMS) nanoparticles were investigated as promising candidates. CMS nanoparticles were loaded with a drug (analogue) and were applied to penetration studies of skin. We determined by dual-frequency electron paramagnetic resonance (EPR) how dexamethasone (Dx) labelled with 3-carboxy-2,2,5,5-tetramethyl-1-pyrrolidinyloxy (PCA) is associated with the CMS. The micro-environment of the drug loaded to CMS nanoparticles was investigated by pulsed high-field EPR at cryogenic temperature, making use of the fact that magnetic parameters (g-, A-matrices, and spin-lattice relaxation time) represent specific probes for the micro-environment. Additionally, the rotational correlation time of spin-labelled Dx was probed by continuous wave EPR at ambient temperature, which provides independent information on the drug environment. Furthermore, the penetration depth of Dx into the stratum corneum of porcine skin after different topical applications was investigated. The location of Dx in the CMS nanoparticles is revealed and the function of CMS as penetration enhancers for topical application is shown

The similarity problem for JJ-nonnegative Sturm-Liouville operators

Sufficient conditions for the similarity of the operator $A := 1/r(x) (-d^2/dx^2 +q(x))$ with an indefinite weight r(x)=(\sgn x)|r(x)| are obtained. These conditions are formulated in terms of Titchmarsh-Weyl $m$-coefficients. Sufficient conditions for the regularity of the critical points 0 and $\infty$ of $J$-nonnegative Sturm-Liouville operators are also obtained. This result is exploited to prove the regularity of 0 for various classes of Sturm-Liouville operators. This implies the similarity of the considered operators to self-adjoint ones. In particular, in the case r(x)=\sgn x and $q\in L^1(R, (1+|x|)dx)$, we prove that $A$ is similar to a self-adjoint operator if and only if $A$ is $J$-nonnegative. The latter condition on $q$ is sharp, i.e., we construct $q\in \cap_{\gamma <1} L^1(R, (1+|x|)^\gamma dx)$ such that $A$ is $J$-nonnegative with the singular critical point 0. Hence $A$ is not similar to a self-adjoint operator. For periodic and infinite-zone potentials, we show that $J$-positivity is sufficient for the similarity of $A$ to a self-adjoint operator. In the case $q\equiv 0$, we prove the regularity of the critical point 0 for a wide class of weights $r$. This yields new results for "forward-backward" diffusion equations.Comment: 36 pages, LaTeX2e, version 2; addresses of the authors added, the reference [38] update

Land use and soil development in Southern chile: Effects on physical properties

Different physical properties of volcanic ash soils were investigated along a transect of 120 km from the western slope of the Central Cordilleras (40°20’S, 72°06’W) to the eastern slope of the Costal Cordillera (39°39’S, 73°11’W) in southern Chile with respect to the degree of soil development (Arenosol versus Andosol stage; Arenosol: young volcanic ash soil, free of clay, tephric properties, Andosol: older volcanic soil, clayey). The Andosols show a higher total pore volume and a higher field capacity, especially due to an increase in fine pores, than the Arenosols. Furthermore, the precompression stress (Pc) as a parameter for the mechanical soil strength is higher for Andosols despite of a lower bulk density. A land use (cropland, meadow, forest) dependent variation of the investigated parameters was less distinct for Andosols. A reduction of macropores and saturated hydraulic conductivity (ks) due to agriculture could be determined in the field, but in general the values are still on a high level with ks-values >100 cm d-1. However, at higher stresses using an oedometer test the ks-values of the Andosols are highly negatively affected with values <10 cm d-1. Aggregation is of major importance for soil stability of Andosols, whereas a homogenization of soil structure will lead to a distinct decrease of Pc of approx. 50%.DFG/HO 911/45-1DFG/BA 1359/12-

Wasserhaushalt und Schrumpfungsverhalten von organischen Böden im Grundwasserabsenkbereich eines Wasserwerkes in Norddeutschland

Auenüberflutungsmoore sind geprägt durch eine heterogene Substratverteilung. Kleinräumig wechselnd finden sich in Stillwasserbereichen der ehemals mäandrierenden Vorfluter gebildete Mudden sowie Auensande und sukzessiv aufgewachsene Niedermoortorfe. Künstliche Entwässerung mittels Drainagen, verstärkt durch die Grundwasserförderung eines Wasserwerkes, hat aufgrund unterschiedlicher Empfindlichkeiten der Substrate im Hinblick auf austrocknungsabhängige Volumenveränderungen zur Ausbildung einer die landwirtschaftliche Grünlandnutzung erschwerenden Sackungsmorphologie ("Buckelwiese") im untersuchten Niedermoor geführt. Vor diesem Hintergrund wurden an zwei Standorten Wasserhaushaltsuntersuchungen durchgeführt und zwei organische (Niedermoortorf, organo-mineralische Mudde) und ein anorganisches Substrat (Auensand) im Hinblick auf ihr Schrumpfungsverhalten untersucht. Der Einfluss von Unterschieden im Wasserhaushalt auf die oberflächennahe Bodenfeuchteverteilung und damit einhergehende Schrumpfungsintensitäten der verschiedenen Substrate wurde erfasst

Abstract kinetic equations with positive collision operators

We consider "forward-backward" parabolic equations in the abstract form $Jd \psi / d x + L \psi = 0$, $0< x < \tau \leq \infty$, where $J$ and $L$ are operators in a Hilbert space $H$ such that $J=J^*=J^{-1}$, $L=L^* \geq 0$, and $\ker L = 0$. The following theorem is proved: if the operator $B=JL$ is similar to a self-adjoint operator, then associated half-range boundary problems have unique solutions. We apply this theorem to corresponding nonhomogeneous equations, to the time-independent Fokker-Plank equation $\mu \frac {\partial \psi}{\partial x} (x,\mu) = b(\mu) \frac {\partial^2 \psi}{\partial \mu^2} (x, \mu)$, $0<x<\tau$, $\mu \in \R$, as well as to other parabolic equations of the "forward-backward" type. The abstract kinetic equation $T d \psi/dx = - A \psi (x) + f(x)$, where $T=T^*$ is injective and $A$ satisfies a certain positivity assumption, is considered also.Comment: 20 pages, LaTeX2e, version 2, references have been added, changes in the introductio

C/EBPβ regulates homeostatic and oncogenic gastric cell proliferation

Cancer of the stomach is among the leading causes of death from cancer worldwide. The transcription factor C/EBPβ is frequently overexpressed in gastric cancer and associated with the suppression of the differentiation marker TFF1. We show that the murine C/EBP{beta} knockout stomach displays unbalanced homeostasis and reduced cell proliferation and that tumorigenesis of human gastric cancer xenograft is inhibited by knockdown of C/EBPβ. Cross-species comparison of gene expression profiles between C/EBPβ-deficient murine stomach and human gastric cancer revealed a subset of tumors with a C/EBPβ signature. Within this signature, the RUNX1t1 tumor suppressor transcript was down-regulated in 38% of gastric tumor samples. The RUNX1t1 promoter was frequently hypermethylated and ectopic expression of RUNX1t1 in gastric cancer cells inhibited proliferation and enhanced TFF1 expression. These data suggest that the tumor suppressor activity of both RUNX1t1 and TFF1 are mechanistically connected to C/EBPβ and that cross-regulation between C/EBPβ-RUNX1t1-TFF1 plays an important role in gastric carcinogenesis

Five years MIQE guidelines: The case of the Arabian countries

The quantitative real time polymerase chain reaction (qPCR) has become a key molecular enabling technology with an immense range of research, clinical, forensic as well as diagnostic applications. Its relatively moderate instrumentation and reagent requirements have led to its adoption by numerous laboratories, including those located in the Arabian world, where qPCR, which targets DNA, and reverse transcription qPCR (RT-qPCR), which targets RNA, are widely used for region-specific biotechnology, agricultural and human genetic studies. However, it has become increasingly apparent that there are significant problems with both the quality of qPCR-based data as well as the transparency of reporting. This realisation led to the publication of the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines in 2009 and their more widespread adoption in the last couple of years. An analysis of the performance of biomedical research in the Arabian world between 2001-2005 suggests that the Arabian world is producing fewer biomedical publications of lower quality than other Middle Eastern countries. Hence we have analysed specifically the quality of RT-qPCR-based peer-reviewed papers published since 2009 from Arabian researchers using a bespoke iOS/Android app developed by one of the authors. Our results show that compliance with 15 essential MIQE criteria was low (median of 40%, range 0-93%) and few details on RNA quality controls (22% compliance), assays design (12%), RT strategies (32%), amplification efficiencies (30%) and the normalisation process (3%). These data indicate that one of the reasons for the poor performance of Arabian world biomedical research may be the low standard of any supporting qPCR experiments and identify which aspects of qPCR experiments require significant improvements

Imatinib Treatment Induces CD5+ B Lymphocytes and IgM Natural Antibodies with Anti-Leukemic Reactivity in Patients with Chronic Myelogenous Leukemia

Imatinib mesylate is a first line treatment of Chronic Myelogenous Leukemia and of a rare form of gastrointestinal stromal cancer, where the response to the drug is also linked to the immune system activation with production of antineoplastic cytokines. In this study, forty patients in the chronic phase of disease, treated with imatinib mesylate, were analyzed. Bone marrow aspirates were drawn at diagnosis, after 3, 6, 12, 18 months for haematological, cytofluorimetric, cytogenetic, biomolecular evaluation and cytokine measurement. Responder and non responder patients were defined according to the European LeukemiaNet recommendations. In responder patients (n = 32), the percentage of bone marrow CD20+CD5+sIgM+ lymphocytes, and the plasma levels of IgM, were significantly higher, at 3 months and up to 9 months, than in non responders. These IgM reacted with O-linked sugars expressed by leukemic cells and could induce tumor cell apoptosis. In responeìder patients the stromal-derived factor-1 and the B-lymphocyte-activating factor of the tumor necrosis factor family significantly raised in the bone marrow after imatinib administration, together with the bone morphogenetic proteins-2 and −7. All patients with high number of CD20+CD5+sIgM+ cells and high stromal-derived factor-1 and B lymphocyte activating factor levels, underwent complete cytogenetic and/or molecular remission by 12 months. We propose that CD20+CD5+sIgM+ lymphocytes producing anti-carbohydrate antibodies with anti-tumor activity, might contribute to the response to imatinib treatment. As in multivariate analysis bone marrow CD20+CD5+sIgM+ cells and stromal-derived factor-1 and B-lymphocyte-activating factor levels were significantly related to cytogenetical and molecular changes, they might contribute to the definition of the pharmacological response