Optical probes of intradiskal processes in rod photoreceptors I: Light-scattering study of ATP-dependent dark reactions.

ATP can cause dramatic structural changes in the outer segment of rod photoreceptors. These changes can be visualized by means of a concomitant light-scattering signal AD, a decrease in scattered light intensity of over 20%. The large size of the signal suggests that the major structural changes occur. The underlying molecular events may reflect an important, yet still unknown, part of the photoreceptor machinery. AD signals reflect ATPase-driven transmembrane events which occur in and at the disk membrane. Their only structural prerequisite is the structural integrity of the disk compartment. The angular dependence of AD, which can be mimicked by an osmotically-induced disk-swelling, suggests that the disk compartment swells during the production of the AD signal. AD signals proceed with first-order kinetics (half-life = 1 min at 20 °C and ATP concentrations of greater than 100 /gmM) and are accompanied by the hydrolysis of approximately 4 mol ATP (mol rhodopsin)−1. The AD signal is inhibited by a number of transport ATPase inhibitors (quercetin, NBD·Cl, vanadate, DCCD), but not by oligomycin, azide and ouabain. The sensitivity to DCCD, together with the fact that except magnesium no other cation has to be present, points to a proton translocation. This proton transport appears to be electrogenic, since AD signals require the presence of a permeant anion. In physiological saline this is chloride, and the chloride flux is facilitated by a DIDS-sensitive anion transport unit in the disk membrane

Sirolimus inhibits key events of restenosis in vitro/ex vivo: evaluation of the clinical relevance of the data by SI/MPL- and SI/DES-ratio's

<p>Abstract</p> <p>Background</p> <p>Sirolimus (SRL, Rapamycin) has been used successfully to inhibit restenosis both in drug eluting stents (DES) and after systemic application. The current study reports on the effects of SRL in various human in vitro/ex vivo models and evaluates the theoretical clinical relevance of the data by SI/MPL- and SI/DES-ratio's.</p> <p>Methods</p> <p>Definition of the SI/MPL-ratio: relation between <b>s</b>ignificant <b>i</b>nhibitory effects in vitro/ex vivo and the <b>m</b>aximal <b>p</b>lasma <b>l</b>evel after systemic administration in vivo (6.4 ng/ml for SRL). Definition of the SI/DES-ratio: relation between <b>s</b>ignificant <b>i</b>nhibitory effects in vitro/ex vivo and the drug concentration in <b>DES </b>(7.5 mg/ml in the ISAR drug-eluting stent platform). Part I of the study investigated in cytoflow studies the effect of SRL (0.01–1000 ng/ml) on TNF-α induced expression of intercellular adhesion molecule 1 (ICAM-1) in human coronary endothelial cells (HCAEC) and human coronary smooth muscle cells (HCMSMC). Part II of the study analysed the effect of SRL (0.01–1000 ng/ml) on cell migration of HCMSMC. In part III, IV, and V of the study ex vivo angioplasty (9 bar) was carried out in a human organ culture model (HOC-model). SRL (50 ng/ml) was added for a period of 21 days, after 21 and 56 days cell proliferation, apoptosis, and neointimal hyperplasia was studied.</p> <p>Results</p> <p>Expression of ICAM-1 was significantly inhibited both in HCAEC (SRL ≥ 0.01 ng/ml) and HCMSMC (SRL ≥ 10 ng/ml). SRL in concentrations ≥ 0.1 ng/ml significantly inhibited migration of HCMSMC. Cell proliferation and neointimal hyperplasia was inhibited at day 21 and day 56, significance (p < 0.01) was achieved for the inhibitory effect on cell proliferation in the media at day 21. The number of apoptotic cells was always below 1%.</p> <p>Conclusion</p> <p>SI/MPL-ratio's ≤ 1 (ICAM-1 expression, cell migration) characterize inhibitory effects of SRL that can be theoretically expected both after systemic and local high dose administration, a SI/MPL-ratio of 7.81 (cell proliferation) represents an effect that was achieved with drug concentrations 7.81-times the MPL. SI/DES-ratio's between 10^-6and 10^-8indicate that the described inhibitory effects of SRL have been detected with micro to nano parts of the SRL concentration in the ISAR drug-eluting stent platform. Drug concentrations in DES will be a central issue in the future.</p

Chemodynamics, transport behaviour and treatment of phthalic acid esters in municipal landfill leachates

Large amounts of phthalic acid esters (PAEs) are leached from plastics dumped at municipal landfills. This leachate transports PAEs either adsorbed on particulate matter or in dissolved phase. Dissolved organic macromolecules, mainly humic-like substances, enhance the solubility of PAEs. In the biochemical environments of municipal landfills short chain PAEs can be degraded by base-catalyzed hydrolysis or by microorganisms which enzymatically split the side chains. However, there is no cleavage of the aromatic ring. Long chain PAEs like di-(2-ethylhexyl) phthalate are neither degraded abiotically nor by microorganisms. Hence, these PAEs can be leached and washed out of leaky landfills into the groundwater and thus continue to be a threat to the aquatic environment. Only a combined UV radiation/ozonation treatment is capable of fully destroying PAEs.</jats:p

Psychosoziale Versorgung von Flüchtlingen in Deutschland

Die etwa 1,2 Mio. seit Herbst 2014 in Deutschland registrierten Flüchtlinge werden häufig als Herausforderung für das hiesige medizinische Versorgungssystem wahrgenommen, da akut ein hoher Versorgungsbedarf auf nicht ausreichende Versorgungskapazitäten getroffen ist. Diese Versorgungssituation ist in der Tat neu für ein westeuropäisches Gesundheitssystem, stellt jedoch für in der Not- und Entwicklungshilfe im Ausland tätige Nichtregierungsorganisationen eine typische Ausgangslage dar, für die zahlreiche erfolgreicher Lösungsstrategien entwickelt und aus denen Handlungsempfehlungen abgeleitet worden sind. Aus unserer Sicht stellen die in der Entwicklungshilfe zentral formulierten Grundprinzipien der Gleichbehandlung, Partizipation von Betroffenen, das Beachten des Nichtschadensprinzips, die Betonung einer Ressourcen- statt einer Defizitorientierung sowie das Einfordern integrierter und gestufter Gesundheitsleistungen eben nicht nur in Krisenregionen weltweit, sondern auch in der gegenwärtigen Situation in Deutschland wichtige und beachtenswerte allgemeingültige Prinzipien dar