Multiphoton microscopy for pre-clinical evaluation of flow-diverter stents for treating aneurysms

BackgroundConventional histological analyses are the gold standard for the study of aneurysms and vascular pathologies in pre-clinical research. Over the past decade, in vivo and ex vivo imaging using multiphoton microscopy have emerged as powerful pre-clinical tools for detailed tissue analyses that can assess morphology, the extracellular matrix (ECM), cell density and vascularisation. Multiphoton microscopy allows for deeper tissue penetration with minor phototoxicity.ObjectiveThe present study aimed to demonstrate the current status of multimodality imaging, including multiphoton microscopy, for detailed analyses of neo-endothelialisation and ECM evolution after flow-diverter stent (FDS) treatment in an experimental rabbit model of aneurysms.MethodsMultiphoton microscopy tools for assessing autofluorescence and second harmonic generation (SHG) signals from biological tissues were used to evaluate the endovascular treatment of intracranial aneurysms in an animal model of aneurysms (pig, rabbit). Results from multiphoton microscopy were compared to those from standard histology, electronic and bright field microscopy.ConclusionsThe present study describes novel evaluation modes based on multiphoton microscopy for visualising tissue morphology (e.g., collagen, elastin, and cells) to qualify and quantify the extent of neo-intimal formation of covered arteries and device integration into the arterial wall using a rabbit model of intracranial aneurysms treated with FDS.     

Patency of the supraclinoid internal carotid artery branches after flow diversion treatment. A meta-analysis

Background and purpose

Placement of flow-diverters across the ostia of major ICA branches carries a risk of arterial occlusion. We determined the rate of occlusion of the supraclinoid ICA branches and the related symptoms, following coverage with flow-diverters.

Immature dendritic cell transdifferentiation into osteoclasts: a novel pathway sustained by the rheumatoid arthritis microenvironment

Dendritic cells (DCs), the mononuclear cells that initiate immune response, and osteoclasts, the multinucleated bone-resorbing cells, are derived from monocyte/macrophage precursor cells. Granulocyte-macrophage colony-stimulating factor and macrophage colony-stimulating factor (M-CSF) reciprocally regulate the differentiation of both lineages in mice. Using human monocyte-derived DCs generated in vitro, we show that immature DCs transdifferentiate into functional osteoclasts (OCs) in the presence of M-CSF and receptor activator of nuclear factor-kappaB ligand (RANKL). Transdifferentiation operates through fusion of intermediate adherent bipolar fusiform mononuclear cells expressing CD14, CD1a, and RANKL and able to induce RANKL(+) T-cell proliferation. Surprisingly, DC fusion in vitro is faster and more efficient than monocyte fusion to form multinucleated giant cells. The transdifferentiation process reported here supports the existence of a high cellular plasticity within differentiated myeloid phagocytes. Importantly, this process is greatly enhanced by rheumatoid arthritis synovial fluid and involves proinflammatory cytokines such as interleukin 1 or tumor necrosis factor alpha, as well as components of the extracellular matrix such as hyaluronic acid. Our data therefore suggest that DC-derived OCs may be directly involved in the osteolytic lesions observed in human inflammatory bone diseases such as rheumatoid arthritis or in particular forms of Langerhans cell histiocytosis, characterized by accumulation of immature skin DCs and chronic lytic bone lesions.     

Care and prejudice: moving beyond mistrust in the care relationship with addicted patients

Social representations of addiction and the resulting stigmatization have been widely described and studied in the literature, but their effects are no less problematic. These representations, which also occur in care settings, generate a climate of distrust which damages the therapeutic relationship, and its ethical quality. This article, combining clinical experience and an ethical stance, offers an original, innovating approach to the existence of distrust in care relationships in the area of addiction. Pragmatic approaches deriving from the human sciences and analytical philosophy provide an invitation to escape from the demanding climate of mistrust, and to take the gamble on trust so as to improve the quality of interactions between protagonists in care. In complementary fashion, a sociology of action can combat the disquiet generated by distrust through a new commitment to innovating forms of action. This “poetic” mode of action is legitimized by the reflection that backs it up, and by its presentation to peers qualified to approve it. Finally, continental moral philosophy underlines the importance of a carefully weighed commitment on the part of caregivers and addicted patients towards promises aiming to support a sincere care relationship, without damaging the therapeutic dynamic or the ethical quality by providing too many safety nets. This reflection is intended to achieve better identification of the clinical and ethical issues raised by mistrust, and inclusion of these aspects in the training of personnel and in care provision planning.