Einfluss von Alkoholabstinenz und sozialen Alkoholgewohnheiten auf die Schwankung des CDT und anderer einschlägiger Laborparameter innerhalb der Normgrenzen

In dieser Studie sollte untersucht werden, inwieweit gängige Laborparameter in der Alkoholdiagnostik (GOT, GPT, GGT, MCV und CDT), auch innerhalb der Normwertgrenzen Aussagen über den Alkoholkonsum im Rahmen des „sozialen Trinkverhaltens“ erlauben. Insgesamt 23 Proband/innen haben sich an der insgesamt viermonatigen Studie beteiligt, Diese war in vier Phasen von jeweils vier Wochen aufgeteilt. In der ersten Phase sollte das normale Trinkverhalten genau protokolliert werden. Diese Angaben ermöglichten eine Berechnung der Alkoholdosis pro Woche/kg Körpergewicht. Die untersuchten Laborparameter konnten dann in Korrelation zu diesen Alkoholmengen gesetzt werden. (Querschnittsdarstellung) Hier zeigte sich kein signifikanter Zusammenhang zwischen Konzentration bzw. Aktivität der Laborparameter und Höhe der eingenommenen Alkoholmenge. Die zweite Phase war eine komplette Alkoholabstinenzphase. Der erwartete Abfall der Laborparameter GOT, GPT, GGT und CDT konnte nicht nachgewiesen werden. Der Mittelwert des CDT lag knapp über 1%, also über dem Cut-off-Wert, der oft zur Bestätigung einer Alkoholabstinenz herangezogen wird. In Phase 3 und 4 wurden jeweils genau definierte Alkoholmengen eingenommen. In Phase 4 war dies die doppelte Menge im Vergleich zu Phase 3. Es waren aber immer nur geringe Alkoholmengen. Auch hier zeigte sich kein eindeutiger Anstieg der Laborparameter. Es konnte also weder eine Korrelation von Transaminasen, MCV und CDT zu den Alkoholmengen, die in den Trinkprotokollen angegeben waren, hergestellt werden, noch gerichtete Reaktionen der Parameter auf Änderungen des Trinkverhaltens aufgezeigt werden. Vor dem Hintergrund der hohen Anforderungen an die Aussagekraft der Veränderung der Laborparameter, die im Rahmen von Begutachtungen gestellt werden, kann man von der Höhe der Parameter und ihrer Entwicklung in der Längsschnittbeobachtung keine Rückschlüsse auf das Trinkverhalten ziehen. Am Ende von Phase 4 lag der Mittelwert des CDT-Wert mit 1,246% des Gesamt-transferrins deutlich über dem Cut-off-Wert. CDT-Werte im sogenannten Graubereich zwischen 1,0% und 1,7% lassen also nicht auf einen übermäßigen Alkoholkonsum schließen. Selbst nach einer Abstinenzphase lag der Mittelwert noch über 1%, sodass ein CDT-Wert im Graubereich auch nicht unbedingt darauf rückschließen lässt, dass eine Alkoholabstinenz nicht eingehalten wurde. Ein verkehrsmedizinisches Gutachten, das darlegen soll, dass kein übermäßiger Alkoholkonsum erfolgt ist, kann sich nicht allein auf einen CDT-Wert stützen. Wichtig ist die Verlaufsbeobachtung verschiedener Parameter über einen längeren Zeitraum

FTY720 Reduces Post-Ischemic Brain Lymphocyte Influx but Does Not Improve Outcome in Permanent Murine Cerebral Ischemia

BACKGROUND: The contribution of neuroinflammation and specifically brain lymphocyte invasion is increasingly recognised as a substantial pathophysiological mechanism after stroke. FTY720 is a potent treatment for primary neuroinflammatory diseases by inhibiting lymphocyte circulation and brain immigration. Previous studies using transient focal ischemia models showed a protective effect of FTY720 but did only partially characterize the involved pathways. We tested the neuroprotective properties of FTY720 in permanent and transient cortical ischemia and analyzed the underlying neuroimmunological mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: FTY720 treatment resulted in substantial reduction of circulating lymphocytes while blood monocyte counts were significantly increased. The number of histologically and flow cytometrically analyzed brain invading T- and B lymphocytes was significantly reduced in FTY720 treated mice. However, despite testing a variety of treatment protocols, infarct volume and behavioural dysfunction were not reduced 7d after permanent occlusion of the distal middle cerebral artery (MCAO). Additionally, we did not measure a significant reduction in infarct volume at 24 h after 60 min filament-induced MCAO, and did not see differences in brain edema between PBS and FTY720 treatment. Analysis of brain cytokine expression revealed complex effects of FTY720 on postischemic neuroinflammation comprising a substantial reduction of delayed proinflammatory cytokine expression at 3d but an early increase of IL-1β and IFN-γ at 24 h after MCAO. Also, serum cytokine levels of IL-6 and TNF-α were increased in FTY720 treated animals compared to controls. CONCLUSIONS/SIGNIFICANCE: In the present study we were able to detect a reduction of lymphocyte brain invasion by FTY720 but could not achieve a significant reduction of infarct volumes and behavioural dysfunction. This lack of neuroprotection despite effective lymphopenia might be attributed to a divergent impact of FTY720 on cytokine expression and possible activation of innate immune cells after brain ischemia

Alcohol consumption and liver phenotype of individuals with alpha‐1 antitrypsin deficiency

Background and Aims: Alpha‐1 antitrypsin deficiency is an inherited disorder caused by alpha‐1 antitrypsin (AAT) mutations. We analysed the association between alcohol intake and liver‐related parameters in individuals with the heterozygous/homozygous Pi*Z AAT variant (Pi*MZ/Pi*ZZ genotype) found in the United Kingdom Biobank and the European Alpha1 liver consortium. Methods: Reported alcohol consumption was evaluated in two cohorts: (i) the community‐based United Kingdom Biobank (17 145 Pi*MZ, 141 Pi*ZZ subjects, and 425 002 non‐carriers [Pi*MM]); and (ii) the European Alpha1 liver consortium (561 Pi*ZZ individuals). Cohort (ii) included measurements of carbohydrate‐deficient transferrin (CDT). Results: In both cohorts, no/low alcohol intake was reported by &gt;80% of individuals, while harmful consumption was rare (~1%). Among Pi*MM and Pi*MZ individuals from cohort (i), moderate alcohol consumption resulted in a &lt;30% increased rate of elevated transaminases and ~50% increase in elevated gamma-glutamyl transferase values, while harmful alcohol intake led to an at least twofold increase in the abnormal levels. In Pi*ZZ individuals from both cohorts, moderate alcohol consumption had no marked impact on serum transaminase levels. Among Pi*ZZ subjects from cohort (ii) who reported no/low alcohol consumption, those with increased CDT levels more often had signs of advanced liver disease.Conclusions: Pi*MZ/Pi*ZZ genotype does not seem to markedly aggravate the hepatic toxicity of moderate alcohol consumption. CDT values might be helpful to detect alcohol consumption in those with advanced fibrosis. More data are needed to evaluate the impact of harmful alcohol consumption.<br/

Lenalidomide/melphalan/dexamethasone in newly diagnosed patients with immunoglobulin light chain amyloidosis: results of a prospective phase 2 study with long-term follow up

Chemotherapy in light chain amyloidosis aims to normalize the involved free light chain in serum, which leads to an improvement, or at least stabilization of organ function in most responding patients. We performed a prospective single center phase 2 trial with 50 untreated patients not eligible for high-dose treatment. The treatment schedule comprised 6 cycles of oral lenalidomide, melphalan and dexamethasone every 4 weeks. After 6 months, complete remission was achieved in 9 patients (18%), very good partial remission in 16 (32%) and partial response in 9 (18%). Overall, organ response was observed in 24 patients (48%). Hematologic and cardiac toxicities were predominant adverse events. Mortality at 3 months was low at 4% (n=2) despite the inclusion of 36% of patients (n=18) with cardiac stage Mayo 3. After a median follow-up of 50 months, median overall and event-free survival were 67.5 months and 25.1 months, respectively. We conclude that the treatment of lenalidomide, melphalan and dexamethasone is very effective in achieving a hematologic remission, organ response and, consecutively, a long survival in transplant ineligible patients with light chain amyloidosis. However, as toxicity and tolerability are the major problems of a 3-drug regimen, a strict surveillance program is necessary and sufficient to avoid severe toxicities. clinicaltrials.gov Identifier: 00883623 (Eudract2008-001405-41)

An overview of the Amazonian Aerosol Characterization Experiment 2008 (AMAZE-08)

The Amazon Basin provides an excellent environment for studying the sources, transformations, and properties of natural aerosol particles and the resulting links between biological processes and climate. With this framework in mind, the Amazonian Aerosol Characterization Experiment (AMAZE-08), carried out from 7 February to 14 March 2008 during the wet season in the central Amazon Basin, sought to understand the formation, transformations, and cloud-forming properties of fine- and coarse-mode biogenic aerosol particles, especially as related to their effects on cloud activation and regional climate. Special foci included (1) the production mechanisms of secondary organic components at a pristine continental site, including the factors regulating their temporal variability, and (2) predicting and understanding the cloud-forming properties of biogenic particles at such a site. In this overview paper, the field site and the instrumentation employed during the campaign are introduced. Observations and findings are reported, including the large-scale context for the campaign, especially as provided by satellite observations. New findings presented include: (i) a particle number-diameter distribution from 10 nm to 10 Î1/4m that is representative of the pristine tropical rain forest and recommended for model use; (ii) the absence of substantial quantities of primary biological particles in the submicron mode as evidenced by mass spectral characterization; (iii) the large-scale production of secondary organic material; (iv) insights into the chemical and physical properties of the particles as revealed by thermodenuder-induced changes in the particle number-diameter distributions and mass spectra; and (v) comparisons of ground-based predictions and satellite-based observations of hydrometeor phase in clouds. A main finding of AMAZE-08 is the dominance of secondary organic material as particle components. The results presented here provide mechanistic insight and quantitative parameters that can serve to increase the accuracy of models of the formation, transformations, and cloud-forming properties of biogenic natural aerosol particles, especially as related to their effects on cloud activation and regional climate. © 2010 Author(s)

High-Resolution Melting Curve Analysis for Identification of Pasteurellaceae Species in Experimental Animal Facilities.

Pasteurellaceae are among the most prevalent bacterial pathogens isolated from mice housed in experimental animal facilities. Reliable detection and differentiation of Pasteurellaceae are essential for high-quality health monitoring. In this study, we combined a real-time PCR assay amplifying a variable region in the 16S rRNA sequence with high-resolution melting curve analysis (HRM) to identify and differentiate among the commonly isolated species Pasteurella pneumotropica biotypes "Jawetz" and "Heyl", Actinobacillus muris, and Haemophilus influenzaemurium. We used a set of six reference strains for assay development, with the melting profiles of these strains clearly distinguishable due to DNA sequence variations in the amplicon. For evaluation, we used real-time PCR/HRM to test 25 unknown Pasteurellaceae isolates obtained from an external diagnostic laboratory and found the results to be consistent with those of partial 16S rRNA sequencing. The real-time PCR/HRM method provides a sensitive, rapid, and closed-tube approach for Pasteurellaceae species identification for health monitoring of laboratory mice

PR - FINANCIAL RATIOS AS INDICATORS OF ECONOMIC SUSTAINABILITY: SYNERGIES AND TRADE-OFFS FOR SWISS DAIRY FARMS

The presented analysis of synergies and trade-offs between indicators of economic sustainability used a large sample of panel data of Swiss dairy farms ranging from the years 2003 to 2014. Using these data, six common financial ratios are used to calculate economic indicators representing profitability, liquidity and stability. The correlation analysis shows a strong positive correlation (i.e. synergy) between the two financial ratios for profitability. Between the financial ratios for liquidity and stability, synergies and trade-offs exist to various extents. The financial ratios are then normalized and harmonized to get an overall coherent picture and to construct an aggregate indicator of economic performance. The results are a promising starting point for analysing additional factors that should be considered in quantitative sustainability assessments