Mafieux ou héros ? Mythes et motifs tragiques dans Le Parrain et Le Parrain II de Francis Ford Coppola

Le Parrain et Le Parrain II de Francis Ford Coppola constituent l’une des principales sources d’information sur la mafia dont disposent les spectateurs du monde entier. La caractérisation tragique attribuée aux personnages de la saga des Corleone et aux événements dont ils sont les protagonistes ont contribué à rendre iconique et légendaire le stéréotype du chef mafieux et à consolider le mythe d’une « bonne mafia » exprimant les valeurs traditionnelles de la famille patriarcale et dotée d’un sens aigu de la justice et de l’honneur. Cet article souhaite expliciter les principaux motifs tragiques de la saga et les relier aux stéréotypes sur la mafia largement répandus auprès du public. On soulignera notamment que Cosa Nostra elle-même a fini par s'approprier l’image de la mafia proposée dans les films de Coppola, en la considérant opératoire pour la mythologie ésotérique et exotérique de l’organisation.Il Padrino e Il Padrino II di Francis Ford Coppola costituiscono tutt’oggi una delle principali fonti d’informazione sulla mafia per il pubblico mondiale. La caratterizzazione tragica conferita ai personaggi della saga dei Corleone e alle vicende di cui sono protagonisti hanno contribuito a rendere iconica e leggendaria la figura del capomafia e a consolidare il mito di una « mafia buona », espressione dei valori tradizionali della famiglia patriarcale e dotata di un acuto senso della giustizia e dell’onore. Questo saggio si ripropone di esplicitarne i principali motivi tragici e di metterli in relazione con gli stereotipi sulla mafia diffusi presso gli spettatori. In particolare si sottolineerà come la stessa Cosa Nostra abbia finito per impadronirsi dell’immagine della mafia proposta dai film di Coppola, considerandola funzionale alla mitologia esoterica ed essoterica dell’organizzazione

Wortmannin, a Potent Antineutrophil Agent, Exerts Cardioprotective Effects in Myocardial Ischemia/Reperfusion 1

ABSTRACT Ischemia followed by reperfusion in the presence of polymorphonuclear leukocytes (PMNs) results in a marked cardiac contractile dysfunction. Wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase, suppresses superoxide production from PMNs. Therefore, we hypothesized that wortmannin could attenuate PMN-induced cardiac dysfunction by suppression of superoxide production from PMNs. We examined the effects of wortmannin in isolated ischemic (20 min) and reperfused (45 min) rat hearts perfused with PMNs. Wortmannin at 10, 20, or 40 nM given to hearts during the first 5 min of reperfusion, significantly improved left ventricular developed pressure (P Ͻ .01), and the maximal rate of development of left ventricular developed pressure (P Ͻ .01) compared with ischemic/reperfused hearts perfused with PMNs in the absence of wortmannin. In addition, wortmannin significantly reduced PMN infiltration into the myocardium by 50 to 75% (P Ͻ .001). Superoxide radical release also was significantly reduced in N-formylmethionyl-leucylphenylalanine-stimulated PMNs pretreated with 10 or 40 nM wortmannin by 70 and 95%, respectively (P Ͻ .001 versus untreated PMNs). Rat PMN adherence to rat superior mesenteric artery endothelium exposed to 2 U/ml thrombin was significantly attenuated by 10 to 40 nM wortmannin compared with untreated vessels (P Ͻ .001). These results provide evidence that wortmannin can significantly attenuate PMN-induced cardiac contractile dysfunction in the ischemic/reperfused rat heart via attenuation of PMN infiltration into the myocardium and suppression of superoxide release by PMNs. Myocardial ischemia followed by reperfusion results in a marked degree of cardiac contractile dysfunction and myocardial cell injury PMNs induce endothelium and myocardial injury by releasing cytotoxic substances such as oxygen-derived free radicals, inflammatory cytokines, and proteolytic enzyme

Essential Role of P-Selectin in the Initiation of the Inflammatory Response Induced by Hemorrhage and Reinfusion

Resuscitation from hemorrhage induces profound pathophysiologic alterations and activates inflammatory cascades able to initiate neutrophil accumulation in a variety of tissues. This process is accompanied by acute organ damage (e.g., lungs and liver). We have previously demonstrated that significant leukocyte–endothelium interactions occur very early in other forms of ischemia/reperfusion (i.e., splanchnic ischemia/reperfusion and traumatic shock) which are largely mediated by increased expression of the adhesion molecule, P-selectin, on the vascular endothelium. Here we postulated that increased endothelial expression of P-selectin in the microvasculature would play an essential role in initiating the inflammatory signaling of hemorrhagic shock. Using intravital microscopy, we found that hemorrhagic shock significantly increased the number of rolling and adherent leukocytes in the mouse splanchnic microcirculation. In contrast, mice genetically deficient in P-selectin, or wild-type mice given either an anti–P-selectin monoclonal antibody or a recombinant soluble P-selectin glycoprotein ligand (PSGL)-1 immunoglobulin, exhibited markedly attenuated leukocyte–endothelium interaction after hemorrhagic shock. Thus, activation of P-selectin protein on the microvascular endothelium is essential for the initial upregulation of the inflammatory response occurring in hemorrhagic shock. Moreover, endogenous levels of PSGL-1 mRNA were significantly increased in the lung, liver, and small intestine of wild-type mice subjected to hemorrhagic shock. Since PSGL-1 promotes adhesive interactions largely through P-selectin expressed on the vascular endothelium, this result further supports the crucial role played by P-selectin in the recruitment of leukocytes during hemorrhagic shock

Adiponectin inhibits tumor necrosis factor-α-induced vascular inflammatory response via caveolin-mediated ceramidase recruitment and activation.

RATIONALE: Anti-inflammatory and vascular protective actions of adiponectin are well recognized. However, many fundamental questions remain unanswered. OBJECTIVE: The current study attempted to identify the adiponectin receptor subtype responsible for adiponectin\u27s vascular protective action and investigate the role of ceramidase activation in adiponectin anti-inflammatory signaling. METHODS AND RESULTS: Adiponectin significantly reduced tumor necrosis factor (TNF)α-induced intercellular adhesion molecule-1 expression and attenuated TNFα-induced oxidative/nitrative stress in human umbilical vein endothelial cells. These anti-inflammatory actions were virtually abolished by adiponectin receptor 1 (AdipoR1-), but not AdipoR2-, knockdown (KD). Treatment with adiponectin significantly increased neutral ceramidase (nCDase) activity (3.7-fold; P87% of adiponectin-induced nCDase activation was lost. Whereas adiponectin treatment failed to inhibit TNFα-induced intercellular adhesion molecule-1 expression, treatment with sphingosine-1-phosphate or SEW (sphingosine-1-phosphate receptor agonist) remained effective in Cav1-KD cells. AdipoR1 and Cav1 colocalized and coprecipitated in human umbilical vein endothelial cells. Adiponectin treatment did not affect this interaction. There is weak basal Cav1/nCDase interaction, which significantly increased after adiponectin treatment. Knockout of AdipoR1 or Cav1 abolished the inhibitory effect of adiponectin on leukocyte rolling and adhesion in vivo. CONCLUSIONS: These results demonstrate for the first time that adiponectin inhibits TNFα-induced inflammatory response via Cav1-mediated ceramidase recruitment and activation in an AdipoR1-dependent fashion

Bifidobacterium affects antitumor efficacy of oncolytic adenovirus in a mouse model of melanoma

Gut microbiota plays a key role in modulating responses to cancer immunotherapy in melanoma patients. Oncolytic viruses (OVs) represent emerging tools in cancer therapy, inducing a potent immunogenic cancer cell death (ICD) and recruiting immune cells in tumors, poorly infiltrated by T cells. We investigated whether the antitumoral activity of oncolytic adenovirus Ad5D24-CpG (Ad-CpG) was gut microbiota-mediated in a syngeneic mouse model of melanoma and observed that ICD was weakened by vancomycin-mediated perturbation of gut microbiota. Ad-CpG efficacy was increased by oral supplementation with Bifidobacterium, reducing melanoma progression and tumor-infiltrating regulatory T cells. Fecal microbiota was enriched in bacterial species belonging to the Firmicutes phylum in mice treated with both Bifidobacterium and Ad-CpG; furthermore, our data suggest that molecular mimicry between melanoma and Bifidobacterium-derived epitopes may favor activation of cross-reactive T cells and constitutes one of the mechanisms by which gut microbiota modulates OVs response

Mafieux ou héros ? Mythes et motifs tragiques dans Le Parrain et Le Parrain II de Francis Ford Coppola

Le Parrain et Le Parrain II de Francis Ford Coppola constituent l’une des principales sources d’information sur la mafia dont disposent les spectateurs du monde entier. La caractérisation tragique attribuée aux personnages de la saga des Corleone et aux événements dont ils sont les protagonistes ont contribué à rendre iconique et légendaire le stéréotype du chef mafieux et à consolider le mythe d’une « bonne mafia » exprimant les valeurs traditionnelles de la famille patriarcale et dotée d’un sens aigu de la justice et de l’honneur. Cet article souhaite expliciter les principaux motifs tragiques de la saga et les relier aux stéréotypes sur la mafia largement répandus auprès du public. On soulignera notamment que Cosa Nostra elle-même a fini par s'approprier l’image de la mafia proposée dans les films de Coppola, en la considérant opératoire pour la mythologie ésotérique et exotérique de l’organisation