Potent Cardioprotective Effect of the 4-Anilinoquinazoline Derivative PD153035: Involvement of Mitochondrial KATP Channel Activation

Background: The aim of the present study was to evaluate the protective effects of the 4-anilinoquinazoline derivative PD153035 on cardiac ischemia/reperfusion and mitochondrial function. Methodology/Principal Findings: Perfused rat hearts and cardiac HL-1 cells were used to determine cardioprotective effects of PD153035. Isolated rat heart mitochondria were studied to uncover mechanisms of cardioprotection. Nanomolar doses of PD153035 strongly protect against heart and cardiomyocyte damage induced by ischemia/reperfusion and cyanide/aglycemia. PD153035 did not alter oxidative phosphorylation, nor directly prevent Ca(2+) induced mitochondrial membrane permeability transition. The protective effect of PD153035 on HL-1 cells was also independent of AKT phosphorylation state. Interestingly, PD153035 activated K(+) transport in isolated mitochondria, in a manner prevented by ATP and 5-hydroxydecanoate, inhibitors of mitochondrial ATP-sensitive K(+) channels (mitoK(ATP)). 5-Hydroxydecanoate also inhibited the cardioprotective effect of PD153035 in cardiac HL-1 cells, demonstrating that this protection is dependent on mitoK(ATP) activation. Conclusions/Significance: We conclude that PD153035 is a potent cardioprotective compound and acts in a mechanism involving mitoK(ATP) activation

Stromal Down-Regulation of Macrophage CD4/CCR5 Expression and NF-κB Activation Mediates HIV-1 Non-Permissiveness in Intestinal Macrophages

Tissue macrophages are derived exclusively from blood monocytes, which as monocyte-derived macrophages support HIV-1 replication. However, among human tissue macrophages only intestinal macrophages are non-permissive to HIV-1, suggesting that the unique microenvironment in human intestinal mucosa renders lamina propria macrophages non-permissive to HIV-1. We investigated this hypothesis using blood monocytes and intestinal extracellular matrix (stroma)-conditioned media (S-CM) to model the exposure of newly recruited monocytes and resident macrophages to lamina propria stroma, where the cells take up residence in the intestinal mucosa. Exposure of monocytes to S-CM blocked up-regulation of CD4 and CCR5 expression during monocyte differentiation into macrophages and inhibited productive HIV-1 infection in differentiated macrophages. Importantly, exposure of monocyte-derived macrophages simultaneously to S-CM and HIV-1 also inhibited viral replication, and sorted CD4+ intestinal macrophages, a proportion of which expressed CCR5+, did not support HIV-1 replication, indicating that the non-permissiveness to HIV-1 was not due to reduced receptor expression alone. Consistent with this conclusion, S-CM also potently inhibited replication of HIV-1 pseudotyped with vesicular stomatitis virus glycoprotein, which provides CD4/CCR5-independent entry. Neutralization of TGF-β in S-CM and recombinant TGF-β studies showed that stromal TGF-β inhibited macrophage nuclear translocation of NF-κB and HIV-1 replication. Thus, the profound inability of intestinal macrophages to support productive HIV-1 infection is likely the consequence of microenvironmental down-regulation of macrophage HIV-1 receptor/coreceptor expression and NF-κB activation

Individuelle und strukturelle Faktoren der Mitgliederbindung im Sportverein

This article analyses the conditions influencing the commitment of members of sports clubs. It focuses not only on individual characteristics of members, but also on the corresponding structural conditions of sports clubs related to the individual decision to quit or continue their membership. The influences of both the individual and context levels on the commitment of members are estimated in different multi-level models. Results of these multi-level analyses indicate that commitment of members is not just an outcome of individual characteristics such as strong commitment to the club, positively perceived communication and cooperation, satisfaction with sports clubsʼ offers, or voluntary engagement. It is also influenced by club-specific structural conditions: commitment is more probable in rural sports clubs, and clubs who explicitly support sociability, whereas success-oriented sporting goals in clubs have a destabilizing effect.In diesem Beitrag werden Bedingungen analysiert, die die Mitgliederbindung in Sportvereinen beeinflussen. Neben individuellen Merkmalen interessieren dabei auch die Strukturbedingungen der Sportvereine, die im Zusammenhang mit der individuellen Wahlhandlung zwischen stabiler Mitgliedschaft oder Austritt stehen. Der Einfluss der Individual- und Kontextebene auf die Mitgliederbindung in Sportvereinen wird anhand unterschiedlicher Mehrebenenmodelle geschätzt. Die Analysen machen deutlich, dass sich die dauerhafte Mitgliedschaft in Sportvereinen nicht allein auf individuelle Merkmale der Mitgliedschaft, wie eine ausgeprägte Verbundenheit, ein positiv wahrgenommenes soziales Miteinander, die Zufriedenheit mit der Vereinsarbeit sowie die ehrenamtliche Mitarbeit zurückführen lässt. Darüber hinaus nehmen vereinsspezifische Strukturbedingungen Einfluss auf die Mitgliederbindung, wobei in ländlich geprägten Sportvereinen und in Vereinen, die Geselligkeit explizit fördern und in denen das Vereinsziel sportlicher Erfolg eher eine untergeordnete Rolle spielt, die Austrittswahrscheinlichkeit geringer ist

Polyphenolics of African multipurpose trees and shrubs and their effects in ruminant nutrition

.Von westafrikanischen Futterbaumarten (n=72) aus Niger, Nigeria und Benin waren wertvoll: Boscia angustifolia, B. senegalesis, Maerua crassifolia, M. angolensis, Balanites aegyptiaca u. einige Akazienarten (z.B. A. senegal) in der semi-ariden Zone, Pterocarpus erinaceous, Afzelia africana, Lonchocarpus laxiflora u. Mikamia cordata in der subhumiden Zone, Moringa oleifera, Millettia thonningii, Phyllantus discoideus, Ficus thonningii, Spondias mombis u. Antaris africana in der humiden Zone. Der Futterwert von "Browse" kann hinsichtlich der Proteinabbaubarkeit im Pansen mit hoher Wahrscheinlichkeit aus den Polyphenolgehalten vorhergesagt werden. Bei Schafen war der Futterwert von Acacia albida, A. seyal und B. aegyptiaca gleichSIGLEAvailable from: D-70599 Hohenheim Univ., Stuttgart (Germany). Universitaetsbibliothek, Garbenstr. 15 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman