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Objectives: Macrophage migration inhibitory factor (MIF) has been recognized as a potent proinflammatory mediator that may induce myocardial dysfunction. Mechanisms by which MIF affects cardiac function are not completely elucidated; yet, some macrophage migration inhibitory effects have been related to changes in cytoskeleton architecture. We hypothesized that MIF-induced myocardial dysfunction and mitochondrial respiration deficit could be related to cardiac cell microtubule dynamics alterations., Design: Prospective, randomized study., Setting: Experimental Cardiovascular Laboratory, University Hospital., Subjects: Human myocardial (atrial) trabeculae., Interventions: Atrial trabeculae were obtained at the time of cardiac surgery. Isometrically contracting isolated human right atrial trabeculae were exposed to MIF (100 ng/mL) for 60 minutes, in the presence or not of pretreatment with colchicine (10 µM), a microtubule-depolymerizing agent, or paclitaxel (10 µM) a microtubule-stabilizing agent., Measurements and Main Results: Maximal active isometric tension curve and developed isometric force were studied. Trabeculae were then permeabilized for mitochondrial respiration studies using high-resolution oxygraphy. Heart fiber electron microscopy and visualization of βIV tubulin and polymerized actin by confocal microscopy were used to evaluate sarcomere and microtubule disarray. Compared with controls, MIF elicited cardiac contractile and mitochondrial dysfunction, which were largely prevented by pretreatment with colchicine, but not by paclitaxel. Pretreatment with colchicine prevented MIF-induced microtubule network disorganization, excessive tubulin polymerization, and mitochondrial fragmentation. Compound-C, an inhibitor of AMP-activated protein kinase (AMPK), partially prevented contractile dysfunction, suggesting that cardiac deleterious effects of MIF were related to AMPK activation., Conclusions: MIF depresses human myocardial contractile function and impairs mitochondrial respiration. Changes in microtubule network likely promote MIF-induced cardiac dysfunction by 1) altering with mitochondrial tubular assembly and outer membrane permeability for adenine nucleotides leading to energy deficit, 2) excessive tubulin polymerization that may impede cardiomyocyte viscosity and motion, and 3) interfering with AMPK pathway.

The blood-brain barrier (BBB) is a dynamic cellular complex that is responsible for the maintenance of brain homeostasis. To understand the BBB's key cellular and molecular mechanisms, in vitro models combining endothelial cells and astrocytes can be used to reproduce most of the barrier's in vivo features (low paracellular permeability and the expression of specific transporters). However, these models lack pericytes - a poorly characterized cell type which appears to be of crucial importance to understand BBB's function in healthy and diseased states. The present study sought to identify and characterize this cell population - which lacks a specific marker - by comparing its phenotype with that of vascular smooth muscle cells. Even if pericytes and smooth muscle cells shared many markers in vitro, our results showed that they could be distinguished by their different P-glycoprotein expression and γ-glutamyltranspeptidase activity. Two different three-cell-type culture models were described, including pericytes to mimic the neurovascular unit. In the first model, endothelial cells were cultured alone on a filter, away from glial cells and pericytes, allowing endothelial cell phenotype characterization. In the second model, glial cells were at the bottom of the well while pericytes and endothelial cells were cultured together in the filter: close interactions were observed in peg-and-socket contacts. In both models low paracellular permeability and P-glycoprotein functionality were demonstrated. These models are likely to be useful tools for understanding the pericytes' role in BBB physiology and could be of value in investigating the pericytes' influence on BBB in diseased states.

The ability of inhibitors of transcription and translation to prevent glucocorticoid-induced apoptosis has been interpreted to indicate that the cell death machinery requires de novo protein synthesis. The transcriptional inhibitors actinomycin D (Act D) and DRB as well as the translational inhibitors CHX and puromycin inhibited early loss of mitochondrial membrane integrity in a dose-dependent manner. This effect was not observed with the transcriptional inhibitor α-amanitin suggesting they may have additional effects. Their role in the glucocorticoid receptor (GR) intracellular trafficking was therefore investigated. Here, we show that Act D and CHX reduced glucocorticoid binding, GR turnover and impaired GR nuclear translocation. We performed the same experiments in different thymocyte subpopulations of Balb/c mice. At the highest dose tested, actinomycin D and cycloheximide abolished glucocorticoid-induced cell death of CD4+CD8+ and CD4+CD8-. In all subsets, Act D, DRB, as well as CHX and puromycin prevented receptor nuclear translocation, indicating a general alteration of GR trafficking. Overall, our data support a direct effect of macromolecular inhibitors on GR activation and trafficking. Finally, direct alterations of the functional properties of the glucocorticoid receptor might be responsible for cell death prevention by actinomycin D, DRB, cycloheximide and puromycin., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Since the first descriptions by McBride and then Stewart, and later reports by wegener, numerous publications have contained data emphasizing the diagnostic and classification difficulties of these affections, 450 cases having been documented up to the present times. Findings clearly demonstrate that mediofacial necrosis differs greatly by its pathological, etiopathogenic and out come features, and particularly the localization of the lesions. Eight case were investigated, and conclusions drawn that it was important to identify the different affections grouped under the term "mediofacial necrosis", in order to isolate cases of pure malignant centrofacial granuloma, which have no detectable etiology and cannot be integrated in another nosological framework.

A brief historical survey is completed by the presentation of a technique for immediate prosthetic rehabilitation during facial hemiresections for malignant tumors. The method presents multiple advantages when compared to typical drainage procedures from the physiological, mechanical and psychological points of view. A detailed description of the introduction of this prosthesis is followed by a brief summary of postoperative sequelae and the advantages the method supplies due to its extreme simplicity in application.

Authors present a case of primary oesophageal lymphoma, in view of the great rarity of the neoplasm in this place.