1,228 research outputs found
The Effects of 6-Chromanol SUL-138 during Hypothermic Machine Perfusion on Porcine Deceased Donor Kidneys
Diminishing ischemia-reperfusion injury (IRI) by improving kidney preservation techniques offers great beneficial value for kidney transplant recipients. Mitochondria play an important role in the pathogenesis of IRI and are therefore interesting targets for pharmacological interventions. Hypothermic machine perfusion (HMP), as a preservation strategy, offers the possibility to provide mitochondrial–targeted therapies. This study focuses on the addition of a mitochondrial protective agent SUL—138 during HMP and assesses its effect on kidney function and injury during normothermic reperfusion. In this case, 30 min of warm ischemia was applied to porcine slaughterhouse kidneys before 24 h of non–oxygenated HMP with or without the addition of SUL—138. Functional assessment was performed by 4 h normothermic autologous blood reperfusion. No differences in renal function or perfusion parameters were found between both groups. ATP levels were lower after 30 min of warm ischemia in the SUL–138 group (n.s, p = 0.067) but restored significantly during 24 h of HMP in combination with SUL—138. Aspartate aminotransferase (ASAT) levels were significantly lower for the SUL—138 group. SUL—138 does not influence renal function in this model. Restoration of ATP levels during 24 h of HMP with the addition of SUL in combination with lower ASAT levels could be an indication of improved mitochondrial function
Exploring Porcine Precision-Cut Kidney Slices as a Model for Transplant-Related Ischemia-Reperfusion Injury
Marginal donor kidneys are more likely to develop ischemia-reperfusion injury (IRI), resulting in inferior long-term outcomes. Perfusion techniques are used to attenuate IRI and improve graft quality. However, machine perfusion is still in its infancy, and more research is required for optimal conditions and potential repairing therapies. Experimental machine perfusion using porcine kidneys is a great way to investigate transplant-related IRI, but these experiments are costly and time-consuming. Therefore, an intermediate model to study IRI would be of great value. We developed a precision-cut kidney slice (PCKS) model that resembles ischemia-reperfusion and provides opportunities for studying multiple interventions simultaneously. Porcine kidneys were procured from a local slaughterhouse, exposed to 30 min of warm ischemia, and cold preserved. Subsequently, PCKS were prepared and incubated under various conditions. Adenosine triphosphate (ATP) levels and histological tissue integrity were assessed for renal viability and injury. Slicing did not influence tissue viability, and PCKS remained viable up to 72 h incubation with significantly increased ATP levels. Hypothermic and normothermic incubation led to significantly higher ATP levels than baseline. William’s medium E supplemented with Ciprofloxacin (and Amphotericin-B) provided the most beneficial condition for incubation of porcine PCKS. The porcine PCKS model can be used for studying transplant IR
Morphology and density of post-CME current sheets
Eruption of a coronal mass ejection (CME) drags and "opens" the coronal
magnetic field, presumably leading to the formation of a large-scale current
sheet and the field relaxation by magnetic reconnection. We analyze physical
characteristics of ray-like coronal features formed in the aftermath of CMEs,
to check if the interpretation of this phenomenon in terms of reconnecting
current sheet is consistent with the observations. The study is focused on
measurements of the ray width, density excess, and coronal velocity field as a
function of the radial distance. The morphology of rays indicates that they
occur as a consequence of Petschek-like reconnection in the large scale current
sheet formed in the wake of CME. The hypothesis is supported by the flow
pattern, often showing outflows along the ray, and sometimes also inflows into
the ray. The inferred inflow velocities range from 3 to 30 km s,
consistent with the narrow opening-angle of rays, adding up to a few degrees.
The density of rays is an order of magnitude larger than in the ambient corona.
The density-excess measurements are compared with the results of the analytical
model in which the Petschek-like reconnection geometry is applied to the
vertical current sheet, taking into account the decrease of the external
coronal density and magnetic field with height. The model results are
consistent with the observations, revealing that the main cause of the density
excess in rays is a transport of the dense plasma from lower to larger heights
by the reconnection outflow
Generalization of cylindrical spheromak solution to finite beta and large reversed shear
Magnetoluminescence
Pulsar Wind Nebulae, Blazars, Gamma Ray Bursts and Magnetars all contain
regions where the electromagnetic energy density greatly exceeds the plasma
energy density. These sources exhibit dramatic flaring activity where the
electromagnetic energy distributed over large volumes, appears to be converted
efficiently into high energy particles and gamma-rays. We call this general
process magnetoluminescence. Global requirements on the underlying, extreme
particle acceleration processes are described and the likely importance of
relativistic beaming in enhancing the observed radiation from a flare is
emphasized. Recent research on fluid descriptions of unstable electromagnetic
configurations are summarized and progress on the associated kinetic
simulations that are needed to account for the acceleration and radiation is
discussed. Future observational, simulation and experimental opportunities are
briefly summarized.Comment: To appear in "Jets and Winds in Pulsar Wind Nebulae, Gamma-ray Bursts
and Blazars: Physics of Extreme Energy Release" of the Space Science Reviews
serie
Recent Advances in Understanding Particle Acceleration Processes in Solar Flares
We review basic theoretical concepts in particle acceleration, with
particular emphasis on processes likely to occur in regions of magnetic
reconnection. Several new developments are discussed, including detailed
studies of reconnection in three-dimensional magnetic field configurations
(e.g., current sheets, collapsing traps, separatrix regions) and stochastic
acceleration in a turbulent environment. Fluid, test-particle, and
particle-in-cell approaches are used and results compared. While these studies
show considerable promise in accounting for the various observational
manifestations of solar flares, they are limited by a number of factors, mostly
relating to available computational power. Not the least of these issues is the
need to explicitly incorporate the electrodynamic feedback of the accelerated
particles themselves on the environment in which they are accelerated. A brief
prognosis for future advancement is offered.Comment: This is a chapter in a monograph on the physics of solar flares,
inspired by RHESSI observations. The individual articles are to appear in
Space Science Reviews (2011
Differentiation and Glucocorticoid Regulated Apopto-Phagocytic Gene Expression Patterns in Human Macrophages. Role of Mertk in Enhanced Phagocytosis
The daily clearance of physiologically dying cells is performed safely mainly by cells in the mononuclear phagocyte system. They can recognize and engulf dying cells utilizing several cooperative mechanisms. In our study we show that the expression of a broad range of apopto-phagocytic genes is strongly up-regulated during differentiation of human monocytes to macrophages with different donor variability. The glucocorticoid dexamethasone has a profound effect on this process by selectively up-regulating six genes and down-regulating several others. The key role of the up-regulated mer tyrosine kinase (Mertk) in dexamethasone induced enhancement of phagocytosis could be demonstrated in human monocyte derived macrophages by gene silencing as well as blocking antibodies, and also in a monocyte-macrophage like cell line. However, the additional role of other glucocorticoid induced elements must be also considered since the presence of autologous serum during phagocytosis could almost completely compensate for the blocked function of Mertk
Macrophages Recognize Size and Shape of Their Targets
Recognition by macrophages is a key process in generating immune response against invading pathogens. Previous studies have focused on recognition of pathogens through surface receptors present on the macrophage's surface. Here, using polymeric particles of different geometries that represent the size and shape range of a variety of bacteria, the importance of target geometry in recognition was investigated. The studies reported here reveal that attachment of particles of different geometries to macrophages exhibits a strong dependence on size and shape. For all sizes and shapes studied, particles possessing the longest dimension in the range of 2–3 µm exhibited highest attachment. This also happens to be the size range of most commonly found bacteria in nature. The surface features of macrophages, in particular the membrane ruffles, might play an important role in this geometry-based target recognition by macrophages. These findings have significant implications in understanding the pathogenicity of bacteria and in designing drug delivery carriers
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