Freiwillige Aufnahme von Kokain und Morphin im Tiermodell bei gemeinsamer und getrennter Darbietung sowie deren Beeinflussung durch eine vorangehende, erzwungene Aufnahme

Während der letzten Jahrzehnte finden Probleme des gleichzeitigen Mißbrauchs mehrerer psychoaktiver Drogen zunehmend Beachtung. Die vorliegende Arbeit geht der Frage nach, ob Drogen wie Morphin und Kokain in gleichem Maß als Belohnung empfundene Reaktionen auslösen können. Die Frage wurde im Tierexperiment mit männlichen Sprague-Dawley-Ratten untersucht. Dazu wurde das Modell der „Zwei- oder Drei-Flaschenwahl“ benutzt, bei dem die Versuchstiere die Drogen Morphin und Kokain über das Trinkwasser aufnehmen. Drei Teilaspekte der obigen Frage standen im Mittelpunkt: 1. Beeinflusst eine zum freien Konsum angebotene psychoaktive Substanz die freiwillige Aufnahme einer anderen? 2. Welche Folgen hat ein temporärer Aufnahmezwang für den nachfolgenden freiwilligen Konsum? 3. Welche Bedeutung hat es, wenn die Drogen parallel nebeneinander oder kombiniert als Gemisch angeboten werden? Vier Versuche lieferten die nachfolgend genannten Ergebnisse, die zu einem besseren Verständnis der eingesetzten Methode und zu Antworten auf die zentrale Frage führten. Ergebnisse zum experimentellen Vorgehen: 1. Ratten konsumieren freiwillig Morphin und Kokain, wenn diese Stoffe parallel nebeneinander oder als Gemisch angeboten werden. 2. Der freiwillige Konsum von Morphin und Kokain wies bei männlichen Sprague-Dawley-Ratten große interindividuelle Schwankungen auf, ist jedoch intraindividuell recht konstant. 3. Die tägliche Flüssigkeitsaufnahme wurde durch Morphin und Kokain nicht beeinflusst, wenn die Drogen zum freiwilligen Gebrauch parallel oder als Gemisch oder unter Zwang aufgenommen wurden. 4. Die Zugabe von Saccharin zur Maskierung des Drogengeschmackes führte dauerhaft zu keiner statistisch relevanten Änderung der freiwilligen Aufnahme von Morphin oder Kokain. 5. Die Zugabe von Saccharin zur Trinklösung in Konkurrenz zu Morphin und Kokain veränderte nicht die Aufnahme von Morphin, führte jedoch zu einer größeren Aufnahme von Kokain. 6. Die Positionierung der Trinkflaschen im Käfig führte zu keiner nennenswerten Änderung der freiwilligen Aufnahme von Morphin oder Kokain. Diese Befunde belegen die Brauchbarkeit des eingeschlagenen experimentellen Vorgehens zur Untersuchung von Fragen der freiwilligen Aufnahme von Drogen. Resultate zu Wirkungen der Testsubstanzen: 1. Bei parallelem Angebot war der freiwillige Konsum von Kokain größer als der von Morphin. 2. Bei Angebot einer Morphin-Kokain-Lösung blieb der freiwillige Konsum von Morphin etwa gleich, der Konsum von Kokain nahm dagegen ab. 3. Bei alleinigem Angebot von Morphin oder Kokain im Sinne eines Aufnahmezwanges erhöhte sich die Aufnahme beider Drogen entsprechend der täglichen Gesamtflüssigkeitsaufnahme. 4. Ein temporärer Aufnahmezwang von Morphin erhöhte nachfolgend die freiwillige Aufnahme von Morphin. Die freiwillige Aufnahme von Kokain wurde dagegen vermindert. 5. Ein temporärer Aufnahmezwang von Kokain erhöhte nachfolgend den freiwilligen Konsum von Kokain und Morphin praktisch nicht. Damit wird deutlich, daß Kokain besser angenommen wird als Morphin. Die freiwillige Aufnahme von Kokain wird jedoch durch Morphin supprimiert. Offenbar sind belohnende Wirkungen, die Morphin stimulieren kann stärker ausgeprägt als diejenigen von Kokain. Diese Befunde können die Annahme stützen, daß verschiedene „Belohnungssysteme“ angesprochen werden, wobei das „Morphinzentrum“ das „Kokainzentrum“ dominiert

An electrostatic elliptical mirror for neutral polar molecules

Focusing optics for neutral molecules finds application in shaping and steering molecular beams. Here we present an electrostatic elliptical mirror for polar molecules consisting of an array of microstructured gold electrodes deposited on a glass substrate. Alternating positive and negative voltages applied to the electrodes create a repulsive potential for molecules in low-field-seeking states. The equipotential lines are parallel to the substrate surface, which is bent in an elliptical shape. The mirror is characterized by focusing a beam of metastable CO molecules and the results are compared to the outcome of trajectory simulations.Comment: 5 pages, 4 figure

Expression and regulation of CCL18 in synovial fluid neutrophils of patients with rheumatoid arthritis

Rheumatoid arthritis (RA) is characterized by the recruitment of leukocytes and the accumulation of inflammatory mediators within the synovial compartment. Release of the chemokine CCL18 has been widely attributed to antigen-presenting cells, including macrophages and dendritic cells. This study investigates the production of CCL18 in polymorphonuclear neutrophils (PMN), the predominant cell type recruited into synovial fluid (SF). Microarray analysis, semiquantitative and quantitative reverse transcriptase polymerase chain reaction identified SF PMN from patients with RA as a novel source for CCL18 in diseased joints. Highly upregulated expression of other chemokine genes was observed for CCL3, CXCL8 and CXCL10, whereas CCL21 was downregulated. The chemokine receptor genes were differentially expressed, with upregulation of CXCR4, CCRL2 and CCR5 and downregulation of CXCR1 and CXCR2. In cell culture experiments, expression of CCL18 mRNA in blood PMN was induced by tumor necrosis factor α, whereas synthesis of CCL18 protein required additional stimulation with a combination of IL-10 and vitamin D3. In comparison, recruited SF PMN from patients with RA were sensitized for CCL18 production, because IL-10 alone was sufficient to induce CCL18 release. These results suggest a release of the T cell-attracting CCL18 by PMN when recruited to diseased joints. However, its production is tightly regulated at the levels of mRNA expression and protein synthesis

A Planetary Companion around a Metal-Poor Star with Extragalactic Origin

We report the detection of a planetary companion around HIP 13044, a metal-poor star on the red Horizontal Branch. The detection is based on radial velocity observations with FEROS, a high-resolution spectrograph at the 2.2-m MPG/ESO telescope, located at ESO La Silla observatory in Chile. The periodic radial velocity variation of P = 16.2 days can be distinguished from the periods of the stellar activity indicators. We computed a minimum planetary mass of 1.25 MJup and an orbital semi-major axis of 0.116 AU for the planet. This discovery is unique in three aspects: First, it is the first planet detection around a star with a metallicity much lower than few percent of the solar value; second, the planet host star resides in a stellar evolutionary stage that is still unexplored in the exoplanet surveys; third, the star HIP 13044 belongs to one of the most significant stellar halo streams in the solar neighborhood, implying an extragalactic origin of the planetary system HIP 13044 in a disrupted former satellite of the Milky Way.Comment: Part of PlanetsbeyondMS/2010 proceedings http://arxiv.org/html/1011.660

Increased Osteoclastogenesis in Mice Lacking the Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1

Alterations in bone remodeling are a major public health issue, as therapeutic options for widespread bone disorders such as osteoporosis and tumor-induced osteolysis are still limited. Therefore, a detailed understanding of the regulatory mechanism governing bone cell differentiation in health and disease are of utmost clinical importance. Here we report a novel function of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), a member of the immunoglobulin superfamily involved in inflammation and tumorigenesis, in the physiologic regulation of bone remodeling. Assessing the expression of all members of the murine Ceacam family in bone tissue and marrow, we found CEACAM1 and CEACAM10 to be differentially expressed in both bone-forming osteoblasts and bone-resorbing osteoclasts. While Ceacam10-deficient mice displayed no alteration in structural bone parameters, static histomorphometry demonstrated a reduced trabecular bone mass in mice lacking CEACAM1. Furthermore, cellular and dynamic histomorphometry revealed an increased osteoclast formation in Ceacam1-deficient mice, while osteoblast parameters and the bone formation rate remained unchanged. In line with these findings, we detected accelerated osteoclastogenesis in Ceacam1-deficient bone marrow cells, while osteoblast differentiation, as determined by mineralization and alkaline phosphatase assays, was not affected. Therefore, our results provide in vivo and in vitro evidence for a physiologic role of CEACAM1 in the regulation of osteoclastogenesis

Driving Under the Influence of Drugs, Alcohol and Medicines in Europe — findings from the DRUID project

The ‘state of the art’ review presents the results of the largest research project ever carried out in the EU on Driving under the influence of drugs, alcohol and medicines (the ‘DRUID’ project), which ran between 2006 and 201

Different Involvement of Vimentin during Invasion by Listeria monocytogenes at the Blood–Brain and the Blood–Cerebrospinal Fluid Barriers In Vitro

The human central nervous system (CNS) is separated from the blood by distinct cellular barriers, including the blood–brain barrier (BBB) and the blood–cerebrospinal fluid (CFS) barrier (BCSFB). Whereas at the center of the BBB are the endothelial cells of the brain capillaries, the BCSFB is formed by the epithelium of the choroid plexus. Invasion of cells of either the BBB or the BCSFB is a potential first step during CNS entry by the Gram-positive bacterium Listeria monocytogenes (Lm). Lm possesses several virulence factors mediating host cell entry, such as the internalin protein family—including internalin (InlA), which binds E-cadherin (Ecad) on the surface of target cells, and internalin B (InlB)—interacting with the host cell receptor tyrosine kinase Met. A further family member is internalin (InlF), which targets the intermediate filament protein vimentin. Whereas InlF has been shown to play a role during brain invasion at the BBB, its function during infection at the BCSFB is not known. We use human brain microvascular endothelial cells (HBMEC) and human choroid plexus epithelial papilloma (HIBCPP) cells to investigate the roles of InlF and vimentin during CNS invasion by Lm. Whereas HBMEC present intracellular and surface vimentin (besides Met), HIBCPP cells do not express vimentin (except Met and Ecad). Treatment with the surface vimentin modulator withaferin A (WitA) inhibited invasion of Lm into HBMEC, but not HIBCPP cells. Invasion of Lm into HBMEC and HIBCPP cells is, however, independent of InlF, since a deletion mutant of Lm lacking InlF did not display reduced invasion rates

A patient empowerment program for primary immunodeficiency improves quality of life in children and adolescents.

Aim: To assess a patient empowerment program (PEP) for children/adolescents with primary immunodeficiency (PID) on IgG replacement therapy regarding quality of life (QoL) in patients and proxy. Patients & methods: Health-related QoL was assessed using KIDSCREEN-27 and DISABKIDS-37 before and 6 months after PID-PEP kids in 19 children/adolescents and their parents. Results: The following three dimensions of the KIDSCREEN-27 significantly increased in children/adolescents after PID-PEP kids as compared with baseline: Psychological Well-Being, Parents & Autonomy and School Environment. Total DISABKIDS-37 index, as well as 5 of the 6 DISABKIDS-37 dimensions, significantly increased, in other words, Independence, Emotion, Social Inclusion, Social Exclusion and Physical. Evaluation of proxy instruments showed comparable results. Conclusion: PID-PEP kids significantly improved QoL in patients with PID

Pre-ALMA observations of GRBs in the mm/submm range

GRBs generate an afterglow emission that can be detected from radio to X-rays during days, or even weeks after the initial explosion. The peak of this emission crosses the mm/submm range during the first hours to days, making their study in this range crucial for constraining the models. Observations have been limited until now due to the low sensitivity of the observatories in this range. We present observations of 10 GRB afterglows obtained from APEX and SMA, as well as the first detection of a GRB with ALMA, and put them into context with all the observations that have been published until now in the spectral range that will be covered by ALMA. The catalogue of mm/submm observations collected here is the largest to date and is composed of 102 GRBs, of which 88 had afterglow observations, whereas the rest are host galaxy searches. With our programmes, we contributed with data of 11 GRBs and the discovery of 2 submm counterparts. In total, the full sample, including data from the literature, has 22 afterglow detections with redshift ranging from 0.168 to 8.2. GRBs have been detected in mm/submm wavelengths with peak luminosities spanning 2.5 orders of magnitude, the most luminous reaching 10^33erg s^-1 Hz^-1. We observe a correlation between the X-ray brightness at 0.5 days and the mm/submm peak brightness. Finally we give a rough estimate of the distribution of peak flux densities of GRB afterglows, based on the current mm/submm sample. Observations in the mm/submm bands have been shown to be crucial for our understanding of the physics of GRBs, but have until now been limited by the sensitivity of the observatories. With the start of the operations at ALMA, the sensitivity will be increased by more than an order of magnitude. Our estimates predict that, once completed, ALMA will detect up to 98% of the afterglows if observed during the passage of the peak synchrotron emission.Comment: 23 pages, 14 figures, 5 tables (one big one!), Accepted for publication in A&A. Includes the first observation of a GRB afterglow with ALM

Cross-sectional seroprevalence surveys of SARS-CoV-2 antibodies in children in Germany, June 2020 to May 2021

The rate of SARS-CoV-2 infections in children remains unclear due to many asymptomatic cases. We present a study of cross-sectional seroprevalence surveys of anti-SARS-CoV-2 IgG in 10,358 children recruited in paediatric hospitals across Germany from June 2020 to May 2021. Seropositivity increased from 2.0% (95% CI 1.6, 2.5) to 10.8% (95% CI 8.7, 12.9) in March 2021 with little change up to May 2021. Rates increased by migrant background (2.8%, 4.4% and 7.8% for no, one and two parents born outside Germany). Children under three were initially 3.6 (95% CI 2.3, 5.7) times more likely to be seropositive with levels equalising later. The ratio of seropositive cases per recalled infection decreased from 8.6 to 2.8. Since seropositivity exceeds the rate of recalled infections considerably, serologic testing may provide a more valid estimate of infections, which is required to assess both the spread and the risk for severe outcomes of SARS-CoV-2 infections