6,825 research outputs found

    Intracapillary leucocyte accumulation as a novel antihaemorrhagic mechanism in acute pancreatitis in mice

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    Background: Pancreatic infiltration by leucocytes represents a hallmark in acute pancreatitis. Although leucocytes play an active role in the pathophysiology of this disease, the relation between leucocyte activation, microvascular injury and haemorrhage has not been adequately addressed.Methods: We investigated intrapancreatic leucocyte migration, leucocyte extravasation and pancreatic microperfusion in different models of oedematous and necrotising acute pancreatitis in lys-EGFP-ki mice using fluorescent imaging and time-lapse intravital microscopy.Results: In contrast to the current paradigm of leucocyte recruitment, the initial event of leucocyte activation in acute pancreatitis was represented through a dose- and time-dependent occlusion of pancreatic capillaries by intraluminally migrating leucocytes. Intracapillary leucocyte accumulation (ILA) resulted in dense filling of almost all capillaries close to the area of inflammation and preceded transvenular leucocyte extravasation. ILA was also initiated by isolated exposure of the pancreas to interleukin 8 or fMLP, demonstrating the causal role of chemotactic stimuli in the induction of ILA. The onset of intracapillary leucocyte accumulation was strongly inhibited in LFA-1-/- and ICAM-1-/- mice, but not in Mac-1-/- mice. Moreover, prevention of intracapillary leucocyte accumulation led to the development of massive capillary haemorrhages and transformed mild pancreatitis into lethal haemorrhagic disease.Conclusions: ILA represents a novel protective and potentially lifesaving mechanism of haemostasis in acute pancreatitis. This process depends on expression of LFA-1 and ICAM-1 and precedes the classical steps of the leucocyte recruitment cascade

    Two-photon microscopy : sequential imaging studies in vivo

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    Microscopists have always desired to look inside various organ tissues to study structure, function and dysfunction of their cellular constituents. In the past, this has frequently required tissue extraction and histological preparation to gain access. Traditional optical microscopy techniques, which use linear (one-photon) absorption processes for contrast generation, are limited to use near the tissue surface (< 80 µm) because at greater depths strong and multiple light scattering blurs the images. Scattering particularly strongly affects signal strength in confocal microscopy, which achieves three-dimensional resolution and optical sectioning with a detection pinhole that rejects all light that appears not to originate from the focus. New optical microscopy techniques have been developed that use nonlinear light-matter interactions to generate signal contrast only within a thin raster-scanned plane. Since its first demonstration over a decade ago, two-photon microscopy has been applied to a variety of imaging tasks and has now become the technique of choice for fluorescence microscopy in thick tissue preparations and in live animals. The gain in resolution over conventional in vivo imaging techniques has been several orders of magnitude. Neuroscientists have used it to measure calcium dynamics deep in brain slices and in live animals, blood flow measurement, neuronal plasticity and to monitor neurodegenerative disease models in brain slices and in live rodents. These types of applications define the most important niche for two-photon microscopy - high-resolution imaging of physiology, morphology and cell-cell interactions in intact tissue. Clearly the biggest advantage of two-photon microscopy is in longitudinal monitoring of rodent models of disease or plasticity over days to weeks. The aim of this article is to discuss some methodological principles, and show some applications of this technique obtained from our laboratory in the area of acute experimental stroke research.peer-reviewe

    Animal models of ischaemic stroke and characterisation of the ischaemic penumbra

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    Over the past forty years, animal models of focal cerebral ischaemia have allowed us to identify the critical cerebral blood flow thresholds responsible for irreversible cell death, electrical failure, inhibition of protein synthesis, energy depletion and thereby the lifespan of the potentially salvageable penumbra. They have allowed us to understand the intricate biochemical and molecular mechanisms within the ‘ischaemic cascade’ that initiate cell death in the first minutes, hours and days following stroke. Models of permanent, transient middle cerebral artery occlusion and embolic stroke have been developed each with advantages and limitations when trying to model the complex heterogeneous nature of stroke in humans. Yet despite these advances in understanding the pathophysiological mechanisms of stroke-induced cell death with numerous targets identified and drugs tested, a lack of translation to the clinic has hampered pre-clinical stroke research. With recent positive clinical trials of endovascular thrombectomy in acute ischaemic stroke the stroke community has been reinvigorated, opening up the potential for future translation of adjunctive treatments that can be given alongside thrombectomy/thrombolysis. This review discusses the major animal models of focal cerebral ischaemia highlighting their advantages and limitations. Acute imaging is crucial in longitudinal pre-clinical stroke studies in order to identify the influence of acute therapies on tissue salvage over time. Therefore, the methods of identifying potentially salvageable ischaemic penumbra are discussed

    Synthetic Aperture Anomaly Imaging

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    Previous research has shown that in the presence of foliage occlusion, anomaly detection performs significantly better in integral images resulting from synthetic aperture imaging compared to applying it to conventional aerial images. In this article, we hypothesize and demonstrate that integrating detected anomalies is even more effective than detecting anomalies in integrals. This results in enhanced occlusion removal, outlier suppression, and higher chances of visually as well as computationally detecting targets that are otherwise occluded. Our hypothesis was validated through both: simulations and field experiments. We also present a real-time application that makes our findings practically available for blue-light organizations and others using commercial drone platforms. It is designed to address use-cases that suffer from strong occlusion caused by vegetation, such as search and rescue, wildlife observation, early wildfire detection, and sur-veillance

    The Effect of Interfacial Chemical Bonding in TiO2-SiO2 Composites on their Photocatalytic NOx Abatement Performance

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    The authors gratefully acknowledge funding from the UK Engineering and Physical Sciences Research Council (Grant Ref: EP/M003299/1) and the Natural Science Foundation of China (No. 51461135005) International Joint Research Project (EPSRC-NSFC).Peer reviewedPublisher PD

    Leukocyte margination in alveolar capillaries: Interrelationship with functional capillary geometry and microhemodynamics

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    The pulmonary capillary microvasculature harbors a large pool of intravascularly marginated leukocytes. In this study, we investigated the interrelationship of leukocyte margination with characteristics of functional capillary geometry and microhemodynamics in alveolar capillary networks. In 22 anesthetized rabbits we assessed functional capillary density, average capillary length, red blood cell velocity and leukocyte kinetics in alveolar capillary networks in vivo by intravital fluorescence microscopy. In alveolar wall areas of 12,800 +/- 1,800 mu m(2), we detected 3.6 +/- 0.5 sticking leukocytes and 21.0 +/- 1.9 functional capillary segments with an average capillary length of 35.7 +/- 2.1 mu m. We calculated that approximately 15% of functional capillary segments are blocked by marginated leukocytes. Leukocyte margination was predominantly observed in capillary networks characterized by a high functional capillary density, short capillary segments and low red blood cell velocities. The multitude of interconnected capillary channels in these networks may allow alveolar blood flow to bypass marginated leukocytes. Hence, this interrelationship may be relevant for maintenance of adequate alveolar perfusion and low capillary network resistance despite excessive leukocyte margination in the pulmonary microvasculature. Local microhemodynamic factors may play a regulatory role in the spatial distribution of leukocyte margination
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