Do common genetic variants in endotoxin signaling pathway contribute to predisposition to alcoholic liver cirrhosis?

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta), produced by endotoxin-activated Kupffer cells, play a key role in the pathogenesis of alcoholic liver cirrhosis (ALC). Alleles TNFA -238A, IL1B -31T and variant IL1RN*2 of repeat polymorphism in the gene encoding the IL-1 receptor antagonist increase production of TNF-alpha and IL-1beta, respectively. Alleles CD14 -159T, TLR4 c.896G and TLR4 c.1196T modify activation of Kupffer cells by endotoxin. We confirmed the published associations between these common variants and genetic predisposition to ALC by means of a large case-control association study conducted on two Central European populations. METHODS: The study population comprised a Czech sample of 198 ALC patients and 370 controls (MONICA project), and a German sample of 173 ALC patients and 331 controls (KORA-Augsburg), and 109 heavy drinkers without liver disease. RESULTS: Single locus analysis revealed no significant difference between patients and controls in all tested loci. Diplotype [IL1RN 2/ 2; IL1B -31T+] was associated with increased risk of ALC in the pilot study, but not in the validation samples. CONCLUSIONS: Although cytokine mediated immune reactions play a role in the pathogenesis of ALC, hereditary susceptibility caused by variants in the corresponding genes is low in Central European populations.

Formflexible Werkzeuge für den Spritzguss – Lösungsansatz zur wirtschaftlichen Anwendung des Spritzgießens bei kleinen Losgrößen

Die derzeitige Marktentwicklung hin zu individualisierten Produkten führt auch im Werkzeug- und Formenbau zu reduzierten Stückzahlen. Die Wirtschaftlichkeit des Spritz- oder Druckgießens ist eingeschränkt durch hohe Werkzeugkosten, die teilweise nur auf eine geringe Anzahl von Bauteilen umgelegt werden können. Lösungsmöglichkeiten durch Modularisierung bzw. Standardisierung von Werkzeugsegmenten bieten nur eine eingeschränkte Wiederverwendbarkeit der Werkzeuge. Aus dieser Situation heraus werden am iwb (Institut für Werkzeugmaschinen und Betriebswissenschaften) Anwenderzentrum Augsburg der Technischen Universität München (TUM) formflexible Werkzeuge für den Spritzguss entwickelt, die dem Anspruch genügen, verschiedene Geometrien mit dem gleichen Werkzeug abzuformen. Bei dem im Folgenden beschriebenen Ansatz wird die Formflexibilität durch ein einstellbares Nadelpaket realisiert, das beliebig oft justiert werden kann. Die so gewonnene Wiederverwendbarkeit des Werkzeugkonzepts garantiert den wirtschaftlichen Einsatz des Spritzgießens bei kleinen Losgrößen und stellt eine neue Möglichkeit des Prototypenwerkzeugbaus im Anwendungsgebiet Spritzgießen dar.

No evidence for an association of posttraumatic stress disorder with circulating levels of CRP and IL-18 in a population-based study.

Several studies have shown associations of posttraumatic stress disorder (PTSD) with the development of cardiometabolic diseases. The underlying psychopathological mechanisms, including potential links to inflammatory processes, have been discussed but remain elusive. Therefore, the aim of the present study was to evaluate the association of PTSD symptoms with the inflammatory biomarkers C-reactive protein (CRP) and interleukin-18 (IL-18). The study population consisted of 3012 participants aged 32-81years drawn from the population-based KORA F4 study conducted in 2006-08 in the Augsburg region (Southern Germany). PTSD symptoms were measured by the Impact of Event Scale, the Posttraumatic Diagnostic Scale and interview data and classified as no, partial or full PTSD. The associations of PTSD with CRP and IL-18 concentrations were estimated by multiple regression analyses with adjustments for age, sex and cardiometabolic risk factors. Linear regression analyses showed no significant association between PTSD and CRP or IL-18 concentration: adjusted for age and sex, the geometric mean concentrations in participants with full PTSD was for CRP 9% lower and for IL-18 1% higher than in participants with no PTSD (p values 0.53 and 0.89). However, further analyses indicated that individuals with partial PTSD had an increased chance of belonging to the highest quartile of the IL-18 concentration. No significant association was observed for any of the three subscales intrusion, avoidance or hyperarousal with CRP or IL-18 concentration. This large, population-based study could not find an association of full PTSD with CRP and IL-18 concentrations. Further research is needed to analyse these relationships.