670 research outputs found
Biomarkers in acute coronary syndromes and their role in diabetic patients
Diabetic patients with acute coronary syndromes
are at high risk for cardiovascular complications
but risk stratification in these patients remains
challenging. Regularly, diabetic patients have a less typical
clinical presentation, which could lead to delayed
diagnosis and subsequent delayed initiation of treatment.
Since diabetic patients derive particular benefit
from aggressive anti-platelet therapy, early diagnostic
and therapeutic risk stratification of these patients is of
critical importance to improve their adverse outcome.
Although the electrocardiogram remains a pivotal
diagnostic tool in the evaluation of patients suspected of
having an acute coronary syndrome, only significant STsegment
changes provide reasonable prognostic information.
Therefore, repeated assessment of circulating
protein biomarkers represents a valuable diagnostic tool
for improving efficacy and safety of decision-making in
these patients. The combined use of biomarkers reflecting
distinct pathophysiological aspects, such as myocardial
necrosis, vascular inflammation, oxidative stress
and neurohumoral activation, may significantly improve
triage of patients with chest pain. These tools may identify
those patients that are at particularly high risk for
short-term and/or long-term cardiovascular events.
Eventually, tailored medical and interventional treatment
of diabetic patients should help to prevent these cardiac
events in a cost-effective manner
Разработка и исследование асинхронного электропривода с наблюдателем состояния
Выпускная квалификационная работа 109 с., 35 рис., 18 табл., 47 источников, 5 прил.
Объектом исследования является дискретная математическая модель наблюдателя состояния полного порядка асинхронного двигателя.
Цель работы – Разработка и исследование асинхронного электропривода с наблюдателем состояния
В процессе исследования проводилось имитационное моделирование разработанной дискретной математической модели асинхронного двигателя и разработанной дискретной математической модели наблюдателя состояния полного порядкаFinal qualifying work 109 p., 35 fig., 18 tab., 47 sources, 5 adj.
The object of research is a discrete mathematical model of the observer status of full order of the induction motor.
Objective - Development and research of the asynchronous electric drive with observer status
The study was conducted simulations developed discrete mathematical model of the induction motor and the developed mathematical model of discrete observer of full order stat
Matrix metalloproteinases at key junctions in the pathomechanism of stroke
Matrix metalloproteinases play a crucial role in the remodelling of the extracellular matrix through direct degradation of its structural proteins and control of extracellular signaling. The most common cause of ischemic brain damage is an atherothrombotic lesion in the supplying arteries. The progress of the atherosclerotic plaque development and the related thrombotic complications are mediated in part by matrix metalloproteinases. In addition to their role in the underlying disease, various members of this protease family are upregulated in the acute phase of ischemic brain damage as well as in the post-ischemic brain recovery following stroke. This review summarizes the current understanding of the matrix metalloproteinase-related molecular events at three stages of the ischemic cerebrovascular disease (in the atherosclerotic plaque, in the neurovascular unit of the brain and in the regenerating brain tissue)
Plasticity and cardiovascular applications of multipotent adult progenitor cells
Cardiovascular disease is the leading cause of death worldwide, which
has encouraged the search for new therapies that enable the treatment of
patients in palliative and curative ways. In the past decade, the potential
benefit of transplantation of cells that are able to substitute for the injured
tissue has been studied with several cell populations, such as stem cells.
Some of these cell populations, such as myoblasts and bone marrow cells,
are already being used in clinical trials. The laboratory of CM Verfaillie has
studied primitive progenitors, termed multipotent adult progenitor cells,
which can be isolated from adult bone marrow. These cells can differentiate
in vitro at the single-cell level into functional cells that belong to the three
germ layers and contribute to most, if not all, somatic cell types after
blastocyst injection. This remarkably broad differentiation potential makes
this particular cell population a candidate for transplantation in tissues
in need of regeneration. Here, we focus on the regenerative capacity of
multipotent adult progenitor cells in several ischemic mouse models, such
as acute and chronic myocardial infarction and limb ischemia
Comparative transcriptome analysis of embryonic and adult stem cells with extended and limited differentiation capacity
Comparison of the transcriptomes of pluripotent embryonic stem cells, multipotent adult progenitor cells and lineage restricted mesenchymal stem cells identified a unique gene expression profile of multipotent adult progenitor cells
uPA deficiency exacerbates muscular dystrophy in MDX mice
Duchenne muscular dystrophy (DMD) is a fatal and incurable muscle degenerative disorder. We identify a function of the protease urokinase plasminogen activator (uPA) in mdx mice, a mouse model of DMD. The expression of uPA is induced in mdx dystrophic muscle, and the genetic loss of uPA in mdx mice exacerbated muscle dystrophy and reduced muscular function. Bone marrow (BM) transplantation experiments revealed a critical function for BM-derived uPA in mdx muscle repair via three mechanisms: (1) by promoting the infiltration of BM-derived inflammatory cells; (2) by preventing the excessive deposition of fibrin; and (3) by promoting myoblast migration. Interestingly, genetic loss of the uPA receptor in mdx mice did not exacerbate muscular dystrophy in mdx mice, suggesting that uPA exerts its effects independently of its receptor. These findings underscore the importance of uPA in muscular dystrophy
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Increased Cardiac Myocyte PDE5 Levels in Human and Murine Pressure Overload Hypertrophy Contribute to Adverse LV Remodeling
Background: The intracellular second messenger cGMP protects the heart under pathological conditions. We examined expression of phosphodiesterase 5 (PDE5), an enzyme that hydrolyzes cGMP, in human and mouse hearts subjected to sustained left ventricular (LV) pressure overload. We also determined the role of cardiac myocyte-specific PDE5 expression in adverse LV remodeling in mice after transverse aortic constriction (TAC). Methodology/Principal Findings: In patients with severe aortic stenosis (AS) undergoing valve replacement, we detected greater myocardial PDE5 expression than in control hearts. We observed robust expression in scattered cardiac myocytes of those AS patients with higher LV filling pressures and BNP serum levels. Following TAC, we detected similar, focal PDE5 expression in cardiac myocytes of C57BL/6NTac mice exhibiting the most pronounced LV remodeling. To examine the effect of cell-specific PDE5 expression, we subjected transgenic mice with cardiac myocyte-specific PDE5 overexpression (PDE5-TG) to TAC. LV hypertrophy and fibrosis were similar as in WT, but PDE5-TG had increased cardiac dimensions, and decreased dP/dtmax and dP/dtmin with prolonged tau (P<0.05 for all). Greater cardiac dysfunction in PDE5-TG was associated with reduced myocardial cGMP and SERCA2 levels, and higher passive force in cardiac myocytes in vitro. Conclusions/Significance: Myocardial PDE5 expression is increased in the hearts of humans and mice with chronic pressure overload. Increased cardiac myocyte-specific PDE5 expression is a molecular hallmark in hypertrophic hearts with contractile failure, and represents an important therapeutic target
Placenta Growth Factor-1 Exerts Time-Dependent Stabilization of Adherens Junctions Following VEGF-Induced Vascular Permeability
Increased vascular permeability is an early event characteristic of tissue ischemia and angiogenesis. Although VEGF family members are potent promoters of endothelial permeability the role of placental growth factor (PlGF) is hotly debated. Here we investigated PlGF isoforms 1 and 2 and present in vitro and in vivo evidence that PlGF-1, but not PlGF-2, can inhibit VEGF-induced permeability but only during a critical window post-VEGF exposure. PlGF-1 promotes VE-cadherin expression via the trans-activating Sp1 and Sp3 interaction with the VE-cadherin promoter and subsequently stabilizes transendothelial junctions, but only after activation of endothelial cells by VEGF. PlGF-1 regulates vascular permeability associated with the rapid localization of VE-cadherin to the plasma membrane and dephosphorylation of tyrosine residues that precedes changes observed in claudin 5 tyrosine phosphorylation and membrane localization. The critical window during which PlGF-1 exerts its effect on VEGF-induced permeability highlights the importance of the translational significance of this work in that PLGF-1 likely serves as an endogenous anti-permeability factor whose effectiveness is limited to a precise time point following vascular injury. Clinical approaches that would pattern nature's approach would thus limit treatments to precise intervals following injury and bring attention to use of agents only during therapeutic windows
Circulating endothelial cells are an early predictor in renal cell carcinoma for tumor response to sunitinib
<p>Abstract</p> <p>Background</p> <p>Tyrosine kinase inhibitors (TKI) have enriched the therapeutic options in patients with renal cell carcinoma (RCC), which frequently induce morphological changes in tumors. However, only little is known about the biological activity of TKI. Circulating endothelial cells (CEC) have been associated with endothelial damage and, hence, may serve as a putative marker for the biological activity of TKI. The main objective of our study was to evaluate the predictive value of CEC, monocytes, and soluble vascular endothelial growth factor receptor (sVEGFR)-2 in RCC patients receiving sunitinib treatment.</p> <p>Methods</p> <p>Analyses of CEC, monocytes, and sVEGFR-2 were accomplished for twenty-six consecutive patients with metastatic RCC who received treatment with sunitinib (50 mg, 4 wks on 2 wks off schedule) at our institution in 2005 and 2006.</p> <p>Results</p> <p>In RCC patients CEC are elevated to 49 ± 44/ml (control 8 ± 8/ml; P = 0.0001). Treatment with sunitinib is associated with an increase in CEC within 28 days of treatment in patients with a Progression free survival (PFS) above the median to 111 ± 61 (P = 0.0109), whereas changes in patients with a PFS below the median remain insignificant 69 ± 61/ml (P = 0.1848). Monocytes and sVEGFR2 are frequently altered upon sunitinib treatment, but fail to correlate with clinical response, defined by PFS above or below the median.</p> <p>Conclusions</p> <p>Sunitinib treatment is associated with an early increase of CEC in responding patients, suggesting superior endothelial cell damage in these patients as a putative predictive biomarker.</p
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