1,078 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 mitochondrialâtargeted therapies. This study focuses on the addition of a mitochondrial protective agent SULâ138 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 nonâoxygenated HMP with or without the addition of SULâ138. 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 SULâ138 group (n.s, p = 0.067) but restored significantly during 24 h of HMP in combination with SULâ138. Aspartate aminotransferase (ASAT) levels were significantly lower for the SULâ138 group. SULâ138 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
Quantitative assessment of the asphericity of pretherapeutic FDG uptake as an independent predictor of outcome in NSCLC
Background The aim of the present study was to evaluate the predictive value
of a novel quantitative measure for the spatial heterogeneity of FDG uptake,
the asphericity (ASP) in patients with non-small cell lung cancer (NSCLC).
Methods FDG-PET/CT had been performed in 60 patients (15 women, 45 men; median
age, 65.5 years) with newly diagnosed NSCLC prior to therapy. The FDG-PET
image of the primary tumor was segmented using the ROVER 3D segmentation tool
based on thresholding at the volume-reproducing intensity threshold after
subtraction of local background. ASP was defined as the relative deviation of
the tumorâs shape from a sphere. Univariate and multivariate Cox regression as
well as Kaplan-Meier (KM) analysis and log-rank test with respect to overall
(OAS) and progression-free survival (PFS) were performed for clinical
variables, SUVmax/mean, metabolically active tumor volume (MTV), total lesion
glycolysis (TLG), ASP and âsolidityâ, another measure of shape irregularity.
Results ASP, solidity and âprimary surgical treatmentâ were significant
independent predictors of PFS in multivariate Cox regression with binarized
parameters (HR, 3.66; pâ<â0.001, HR, 2.11; pâ=â0.05 and HR, 2.09; pâ=â0.05),
ASP and âprimary surgical treatmentâ of OAS (HR, 3.19; pâ=â0.02 and HR, 3.78;
pâ=â0.01, respectively). None of the other semi-quantitative PET parameters
showed significant predictive value with respect to OAS or PFS. Kaplan-Meier
analysis revealed a probability of 2-year PFS of 52% in patients with low ASP
compared to 12% in patients with high ASP (pâ<â0.001). Furthermore, it showed
a higher OAS rate in the case of low versus high ASP (1-year-OAS, 91% vs. 67%:
pâ=â0.02). Conclusions The novel parameter asphericity of pretherapeutic FDG
uptake seems to provide better prognostic value for PFS and OAS in NCSLC
compared to SUV, metabolic tumor volume, total lesion glycolysis and solidity
Disparities in dialysis treatment and outcomes for Dutch and Belgian children with immigrant parents
BACKGROUND: In Belgium and the Netherlands, up to 40% of the children on dialysis are children with immigrant parents of non-Western European origin (non-Western). Concerns exist regarding whether these non-Western patients receive the same quality of care as children with parents of Western European origin (Western). We compared initial dialysis, post-initial treatment, and outcomes between non-Western and Western patients on dialysis. METHODS: All children <19 years old on chronic dialysis in the Netherlands and Belgium between September 2007 and May 2011 were included in the study. Non-Western patients were defined as children of whom one or both parents were born in non-Western countries. RESULTS: Seventy-nine of the 179 included patients (44%) were non-Western children. Compared to Western patients, non-Western patients more often were treated with hemodialysis (HD) instead of peritoneal dialysis (PD) as first dialysis mode (52 vs. 37%, p = 0.046). Before renal transplantation, non-Western patients were on dialysis for a median (range) of 30 (5-99) months, vs. 15 (0-66) months in Western patients (p = 0.007). Renal osteodystrophy was diagnosed in 34% of non-Western vs. 18% of Western patients (p = 0.028). The incidence rate ratio [95% confidence interval] for acute peritonitis was 2.44 [1.43-4.17] (p = 0.032) for non-Western compared to Western patients. CONCLUSIONS: There are important disparities between children on chronic dialysis with parents from Western European origin and those from non-Western European origin in the choice of modality, duration, and outcomes of dialysis therapy
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
Physics of Solar Prominences: II - Magnetic Structure and Dynamics
Observations and models of solar prominences are reviewed. We focus on
non-eruptive prominences, and describe recent progress in four areas of
prominence research: (1) magnetic structure deduced from observations and
models, (2) the dynamics of prominence plasmas (formation and flows), (3)
Magneto-hydrodynamic (MHD) waves in prominences and (4) the formation and
large-scale patterns of the filament channels in which prominences are located.
Finally, several outstanding issues in prominence research are discussed, along
with observations and models required to resolve them.Comment: 75 pages, 31 pictures, review pape
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
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