The shunt from the cyclooxygenase to lipoxygenase pathway in human osteoarthritic subchondral osteoblasts is linked with a variable expression of the 5-lipoxygenase-activating protein

Osteoarthritis (OA) is characterized by articular cartilage degradation and hypertrophic bone changes with osteophyte formation and abnormal bone remodeling. Two groups of OA patients were identified via the production of variable and opposite levels of prostaglandin E(2 )(PGE(2)) or leukotriene B(4 )(LTB(4)) by subchondral osteoblasts, PGE(2 )levels discriminating between low and high subgroups. We studied whether the expression of 5-lipoxygenase (5-LO) or 5-LO-activating protein (FLAP) is responsible for the shunt from prostaglandins to leukotrienes. FLAP mRNA levels varied in low and high OA groups compared with normal, whereas mRNA levels of 5-LO were similar in all osteoblasts. Selective inhibition of cyclooxygenase-2 (COX-2) with NS-398-stimulated FLAP expression in the high OA osteoblasts subgroup, whereas it was without effect in the low OA osteoblasts subgroup. The addition of PGE(2 )to the low OA osteoblasts subgroup decreased FLAP expression but failed to affect it in the high OA osteoblasts subgroup. LTB(4 )levels in OA osteoblasts were stimulated about twofold by 1,25-dihydroxyvitamin D(3 )(1,25(OH)(2)D(3)) plus transforming growth factor-β (TGF-β), a situation corresponding to their effect on FLAP mRNA levels. Treatments with 1,25(OH)(2)D(3 )and TGF-β also modulated PGE(2 )production. TGF-β stimulated PGE(2 )production in both OA osteoblast groups, whereas 1,25(OH)(2)D(3 )alone had a limited effect but decreased the effect of TGF-β in the low OA osteoblasts subgroup. This modulation of PGE(2 )production was mirrored by the synthesis of COX-2. IL-18 levels were only slightly increased in a subgroup of OA osteoblasts compared with normal; however, no relationship was observed overall between IL-18 and PGE(2 )levels in normal and OA osteoblasts. These results suggest that the shunt from the production of PGE(2 )to LTB(4 )is through regulation of the expression of FLAP, not 5-LO, in OA osteoblasts. The expression of FLAP in OA osteoblasts is also modulated differently by 1,25(OH)(2)D(3 )and TGF-β depending on their endogenous low and high PGE(2 )levels

L'étude du "cross-talk" des voies de synthèse des prostaglandines E₂ et des leucotriènes B₄ dans le fonctionnement altéré des ostéoblastes sous-chondraux humains arthrosiques

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal

Thinking and Doing: Challenge, Agency, and the Eudaimonic Experience in Video Games

The nascent growth of videogames has led to great leaps in technical understanding in how to create a functional and entertaining play experience. However, the complex, mixed-affect, eudaimonic entertainment experience that is possible when playing a video game—how it is formed, how it is experienced and how to design for it, has been investigated far less than hedonistic emotional experiences focusing on fun, challenge and ‘enjoyment.’ Participants volunteered to be interviewed about their mixed-affect emotional experiences of playing avant-garde videogames. New conceptions of agency emerged (Actual, Interpretive, Fictional, Mechanical) from the analysis of transcripts and were used to produce a framework of four categories of agency. This new framework offers designers and researchers the extra nuance in conversations around agency, and contributes to the discussion of how we can design video games that allow for complex, reflective, eudaimonic emotional experiences

Phenomenology of Neutrino Oscillations

This review is focused on neutrino mixing and neutrino oscillations in the light of the recent experimental developments. After discussing possible types of neutrino mixing for Dirac and Majorana neutrinos and considering in detail the phenomenology of neutrino oscillations in vacuum and matter, we review all existing evidence and indications in favour of neutrino oscillations that have been obtained in the atmospheric, solar and LSND experiments. We present the results of the analyses of the neutrino oscillation data in the framework of mixing of three and four massive neutrinos and investigate possibilities to test the different neutrino mass and mixing schemes obtained in this way. We also discuss briefly future neutrino oscillation experiments.Comment: 109 pages. Final version to be published in Progress in Particle and Nuclear Physics, Volume 43. Typos correcte

Social Media as part of Online-Marketing-Mix : Webpresence of one premium brand (Rolex) and non-premium brand (Swatch) in the social network Facebook

Die vorliegende Arbeit beschäftigt sich mit den neuen Nutzungsmöglichkeiten des Web 2.0, die eine menschliche Kommunikation mit Interaktion zulassen. Durch die rasanten Zuwachsraten von Social Media gewinnt das weltweit größte Social Network Facebook auch als Marketingkanal für Unternehmen eine immer größere Bedeutung. In einer vergleichenden Fallstudie der Premiummarke Rolex und Non-Premiummarke Swatch werden die jeweiligen Facebook Fanpages hinsichtlich der Markenaktivitäten und der Resonanz der Kunden untersucht. Die aufgestellte These der Auswirkung auf eine positive Kaufentscheidung einer Facebook Präsenz wird empirisch anhand einer Umfrage mit 136 Swatch Kunden und 45 Rolex Kunden validiert. Die Ergebnisse der Untersuchung werden abschließend in einem Fazit zusammengefasst

L'étude du "cross-talk" des voies de synthèse des prostaglandines E₂ et des leucotriènes B₄ dans le fonctionnement altéré des ostéoblastes sous-chondraux humains arthrosiques

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal

Prevalence of proMMP-1, MMP-3, proMMP-13, TIMP-1, TIMP-2, C2C and CPII in plasma and synovial fluid from patients with knee joint injury and osteoarthritis

Fragestellung: Ziel dieser Arbeit war es, die Prävalenz selektierter Matrix- modulierender Proteasen, Protease-Inhibitoren und Knorpelmetaboliten bei traumatischer und chronischer Kniegelenksschädigung (OA) zu evaluieren. Zudem wurde die Prävalenz dieser Faktoren bei chronischer Kniegelenksschädigung bei unterschiedlichem Erkrankungsalter und die Korrelation dieser Marker im Serum und in der Synovia untersucht. Material und Methoden: 69 Patienten, die einer Kniegelenksendoprothese bedurften wurden in folgende Gruppen unterteilt: 50–59 Jahre Frühe-OA-Gruppe (FOA), 60–69 Jahre Mittlere-OA-Gruppe (MOA) und 70–80 Jahre Späte-OA-Gruppe (SOA). Daneben wurden 61 Patienten nach traumatischer Kniegelenksschädigung (Trauma-Gruppe) untersucht. Mittels Sandwich-ELISA wurden die Konzentrationen von MMP-3, pro-MMP-1, pro-MMP-13, TIMP-1 und TIMP-2 aus Synovia und Serum ermittelt. CPII diente als Marker für den Knorpelaufbau und C2C für den Knorpelabbau. Daneben wurde das Serum CRP und die Leukozyten bestimmt. Präoperative Röntgenbilder wurden nach Kellgren & Lawrence klassifiziert, das subjektive Krankheitsempfinden mittels Knee Injury and Osteoarthritis Outcome Score bewertet und der Body-Mass-Index bestimmt. Ergebnisse: In der Trauma-Gruppe war verglichen mit der OA-Gruppe MMP-3 und pro-MMP-1 in der Synovia signifikant erhöht und pro-MMP-13 signifikant erniedrigt. In der Trauma-Gruppe korrelierten MMP-3 mit pro-MMP-1 und -13 sowie pro-MMP-1 mit pro-MMP-13 jeweils signifikant. In der OA-Gruppe korrelierte MMP-3 mit pro-MMP-1. In der Trauma-Gruppe war TIMP-2 in der Synovia signifikant höher als in der OA-Gruppe und TIMP-1 korrelierte umgekehrt proportional mit C2C. In der OA-Gruppe korrelierte TIMP-1 mit MMP-3 signifikant. In der FOA war TIMP-2 signifikant niedriger als in der MOA und SOA. Eine niedrige Prävalenz von TIMP-2 korrelierte in der Synovia signifikant mit einem niedrigen Erkrankungsalter. Eine Korrelation zwischen Serum und Synovia konnte nicht beobachtet werden. Schlussfolgerung: Die niedrigeren Werte von pro-MMP-13 in der Trauma-Gruppe im Vergleich zur OA-Gruppe sind möglicherweise durch das unterschiedliche Ausmaß des Knorpelschadens bedingt, bei dem gemäß bisheriger Untersuchungen eine erhöhte Prävalenz von pro-MMP-13 eher mit einem fortgeschrittenen Knorpelschaden assoziiert ist. Eine erhöhten Prävalenz von MMP-3 und pro-MMP-1 scheint eher zu einer früheren Erkrankung einer endgradigen chronischen Kniegelenksschädigung zu führen. Die Assoziation niedriger TIMP-2 Konzentrationen mit früherem Erkrankungsalter in der OA- Gruppe, sowie niedrige TIMP-1 mit hohen C2C Konzentrationen in der Trauma- Gruppe, lassen die Vermutung zu, dass TIMP-1 bei traumatischer sowie TIMP-2 bei der chronischen Kniegelenksschädigung eine Rolle spielt. Ob eine höhere Konzentration von TIMP-2 in der Synovia das Eintreten einer endgradigen chronischen Knieschädigung verzögert, ist durch weiterführende prospektive Studien zu untersuchen. Die Prävalenz der Biomarker in der Synovia korrespondiert nicht mit dem Serum.Objective: To compare activity levels of selected matrix metalloproteinases, tissue inhibitors of matrix metalloproteinases and cartilage metabolism between patients after knee injury and osteoarthritis (OA). Furthermore, to investigate the prevalence in diverse ages of osteoarthritis. To determine a correlation of these biomarkers between plasma and synovial fluid. Methods: 69 patients who underwent total knee arthroplasty were subdivided into 3 groups: 50-59 years early-onset (FOA), 60-69 years middle-onset (MOA) and 70-80 years late-onset (SOA). Also, 61 patients were surveyed after knee injury (trauma group). Plasma and synovial fluid levels of MMP-3, proMMP-1, proMMP-13, TIMP-1, TIMP-2, CPII and C2C were obtained and measured by sandwich enzyme immunoassays. CRP and leukocytes were determined in plasma. Preoperative radiographs were classified by the Kellgren & Lawrence score. Knee disabilities were assessed with the Knee Injury and Osteoarthritis Outcome Score. Furthermore, the Body-Mass-Index was assessed. Results: MMP-3 and proMMP-1 activities were significantly elevated in the trauma group in comparison to the OA group and proMMP-13 was demeaned. In the trauma group MMP-3 correlated significantly with proMMP-1 and -13 as well as proMMP-1 with proMMP-13. MMP-3 correlated significantly with proMMP-1 in the OA group. TIMP-2 levels were significantly higher in the trauma group as in OA group and TIMP-1 correlated reciprocally proportionally with C2C. TIMP-1 correlated significantly with MMP-3 in the OA group. Synovial fluid TIMP-2 levels were significantly lower in the FOA group as in MOA and SOA. Low TIMP-2 synovial fluid levels correlated significantly with an early disease onset. A correlation between plasma and synovial fluid levels could not be verified. Conclusions: Low levels of proMMP-13 in the trauma group in comparison to the OA group are potentially due to differing extent of articular degradation. In accordance with previous studies, high levels of proMMP-13 are associated with advanced articular damage. Patients with high levels of MMP-3 and proMMP-1 appear to suffer from early-onset OA. Low levels of TIMP-2 in the OA group are associated with early-onset OA and low levels of TIMP-1 are associated with high levels of C2C. Thus the assumption can be made that after trauma TIMP-1 and in OA TIMP-2 is of relevance. Further prospective studies have to be investigated if higher levels of TIMP-2 in synovial fluid can prevent an early onset of OA. The prevalence of the examined markers in synovial fluid do not correspond with Serum markers