Relapsing Urinary Catheter Bleeding with Triple Antithrombotic Therapy in an ...CrimsonPublishersAICS
Relapsing Urinary Catheter Bleeding with Triple Antithrombotic Therapy in an Elderly Patient with ACS, PCI and A-fib: A Case Report by Michael AB Naafs* in Advancements in Case Studies
Relapsing Urinary Catheter Bleeding with Triple Antithrombotic Therapy in an ...CrimsonPublishersAICS
Relapsing Urinary Catheter Bleeding with Triple Antithrombotic Therapy in an Elderly Patient with ACS, PCI and A-fib: A Case Report by Michael AB Naafs* in Advancements in Case Studies
The role of the endothelium as a mediator of critical illnessSMACC Conference
Endothelium was once thought to be an inert organ. However, it plays an important role in multiple functions. These include coagulation, inflammation and determination of vascular permeability.
He then gives a brief overview of the endothelial arrangement, function of the glycocalyx layer and how an injury causing a loss of the protective layer results in holes in the endothelium. The inflammatory cells enter via these holes and causes oedema in the affected organs leading to multiple pathologies.
Danny then explains the role of endothelium in controlling cell barrier function.
Activation of cortactin protein and the myosin light-chain kinase (MLCK) enzymes activate stress fibres resulting in pulling of endothelial cells thereby increasing its permeability.
Danny discusses the role of endothelial dysfunction in acute respiratory distress syndrome (ARDS) at macrovascular, microvascular and molecular levels. Macrovascular thrombosis is related to an increase in severity of ARDS, pulmonary hypertension, and mortality.
At a microvascular level there is a loss of vascularity and increased blood vessel thickness. At a microscopic level, endothelial cells appear swollen and damaged in ARDS. Endothelial dysfunction drives organ dysfunction and mortality. Changes in various endothelial markers like increased von Willebrand factor (vWF), decreased protein C and increased pulmonary dead space correlate with increased mortality.
Studies show that endothelial dysfunction is a more specific and sensitive method to predict mortality of critically ill patients when compared to SOFA score, SAPS 2 score and WCC. Danny discusses ventilator strategies for endothelial cells in ARDS patients. Lowering the tidal volume of ventilators and employing recruitment manoeuvres are such strategies.
Both of these cause a decrease in oedema by reducing endothelial permeability. He then shares the various potential pharmacological treatments for treating endothelial damage. These include statins and spingosine-1-phosphate (S1P). Different studies on the effect of statins in ARDS show contradicting result.
However, targeted therapies can be designed by studying the phenotypes and molecular basis of ARDS in each patient.
The role of the endothelium as a mediator of critical illness by Danny McAuley
Finally, for more like this, head to our podcast page. #CodaPodcast
Role of Plasma Exchange in ABO-incompatible Kidney TransplantationApollo Hospitals
In the past, ABO incompatibility was an absolute contraindication for solid organ transplantation. However,
multiple recent trials have suggested strategies for overcoming the reactions between graft antigens and recipient antibodies that cause graft rejection.
Introduction: Aging-associated vascular stiffening augments cardiovascular disease risk in the elderly. Research to identify targetable cellular and molecular mechanisms is of key interest as no current therapies are available to specifically target vascular stiffening. In this context, enzymes that mediate remodeling of the vascular matrix and those that promote cellular dysfunction are attractive targets. In pre-clinical models, pulse wave velocity (PWV), the gold standard measure of in vivo vascular stiffness, can be measured longitudinally and non-invasively, to make inroads towards the discovery and validation of potential targets.
A novel target and model: We have identified a central role for tissue transglutaminase (TG2) in vascular stiffening during aging. TG2 is a multifunctional protein of the transglutaminase family, whose primary function is to assist in the formation of a strong and stable matrix by catalyzing crosslinking of matrix proteins. Recent studies have shown that TG2 has putative crosslinking-independent functions in aging-associated vascular stiffening and dysfunction. The crosslinking independent mechanisms of TG2 remain incompletely understood due to the lack of pre-clinical models and specific inhibitors that can selectively inhibit a single function of TG2. Thus, we developed a novel knock-in mouse, the TGM2-C277S mouse, by mutating the active site cysteine of TG2 using the CRISPR-Cas9 gene editing technology to selectively target its crosslinking function.
Results and conclusion: We first validated the TGM2-C277S mouse and confirmed that this mutation removes TG2’s crosslinking function but retains its crosslinking independent functions. We next compared PWV wild type (WT), global TG2 knockout (TG2-/-), and the TGM2-C277S mice, to identify the contributions of the crosslinking-dependent and crosslinking-independent functions of TG2 to vascular aging in vivo. PWV increased significantly with age in WT mice, and to a much lower magnitude in the TGM2-C277S mice. TG2-/- mice were further protected against aging associated increase in PWV. Together, these studies show that TG2 contributes significantly to overall vascular stiffening in aging through both crosslinking dependent and crosslinking independent functions.
The learning objectives are:
To understand changes in pulse wave velocity (PWV) with age in mouse models
To determine the specific role of tissue transglutaminase (TG2) in vascular aging
To evaluate the role of vascular matrix vs. VSMCs to overall in vivo stiffness described by PWV
The role of the endothelium as a mediator of critical illnessSMACC Conference
Endothelium was once thought to be an inert organ. However, it plays an important role in multiple functions. These include coagulation, inflammation and determination of vascular permeability.
He then gives a brief overview of the endothelial arrangement, function of the glycocalyx layer and how an injury causing a loss of the protective layer results in holes in the endothelium. The inflammatory cells enter via these holes and causes oedema in the affected organs leading to multiple pathologies.
Danny then explains the role of endothelium in controlling cell barrier function.
Activation of cortactin protein and the myosin light-chain kinase (MLCK) enzymes activate stress fibres resulting in pulling of endothelial cells thereby increasing its permeability.
Danny discusses the role of endothelial dysfunction in acute respiratory distress syndrome (ARDS) at macrovascular, microvascular and molecular levels. Macrovascular thrombosis is related to an increase in severity of ARDS, pulmonary hypertension, and mortality.
At a microvascular level there is a loss of vascularity and increased blood vessel thickness. At a microscopic level, endothelial cells appear swollen and damaged in ARDS. Endothelial dysfunction drives organ dysfunction and mortality. Changes in various endothelial markers like increased von Willebrand factor (vWF), decreased protein C and increased pulmonary dead space correlate with increased mortality.
Studies show that endothelial dysfunction is a more specific and sensitive method to predict mortality of critically ill patients when compared to SOFA score, SAPS 2 score and WCC. Danny discusses ventilator strategies for endothelial cells in ARDS patients. Lowering the tidal volume of ventilators and employing recruitment manoeuvres are such strategies.
Both of these cause a decrease in oedema by reducing endothelial permeability. He then shares the various potential pharmacological treatments for treating endothelial damage. These include statins and spingosine-1-phosphate (S1P). Different studies on the effect of statins in ARDS show contradicting result.
However, targeted therapies can be designed by studying the phenotypes and molecular basis of ARDS in each patient.
The role of the endothelium as a mediator of critical illness by Danny McAuley
Finally, for more like this, head to our podcast page. #CodaPodcast
Role of Plasma Exchange in ABO-incompatible Kidney TransplantationApollo Hospitals
In the past, ABO incompatibility was an absolute contraindication for solid organ transplantation. However,
multiple recent trials have suggested strategies for overcoming the reactions between graft antigens and recipient antibodies that cause graft rejection.
Introduction: Aging-associated vascular stiffening augments cardiovascular disease risk in the elderly. Research to identify targetable cellular and molecular mechanisms is of key interest as no current therapies are available to specifically target vascular stiffening. In this context, enzymes that mediate remodeling of the vascular matrix and those that promote cellular dysfunction are attractive targets. In pre-clinical models, pulse wave velocity (PWV), the gold standard measure of in vivo vascular stiffness, can be measured longitudinally and non-invasively, to make inroads towards the discovery and validation of potential targets.
A novel target and model: We have identified a central role for tissue transglutaminase (TG2) in vascular stiffening during aging. TG2 is a multifunctional protein of the transglutaminase family, whose primary function is to assist in the formation of a strong and stable matrix by catalyzing crosslinking of matrix proteins. Recent studies have shown that TG2 has putative crosslinking-independent functions in aging-associated vascular stiffening and dysfunction. The crosslinking independent mechanisms of TG2 remain incompletely understood due to the lack of pre-clinical models and specific inhibitors that can selectively inhibit a single function of TG2. Thus, we developed a novel knock-in mouse, the TGM2-C277S mouse, by mutating the active site cysteine of TG2 using the CRISPR-Cas9 gene editing technology to selectively target its crosslinking function.
Results and conclusion: We first validated the TGM2-C277S mouse and confirmed that this mutation removes TG2’s crosslinking function but retains its crosslinking independent functions. We next compared PWV wild type (WT), global TG2 knockout (TG2-/-), and the TGM2-C277S mice, to identify the contributions of the crosslinking-dependent and crosslinking-independent functions of TG2 to vascular aging in vivo. PWV increased significantly with age in WT mice, and to a much lower magnitude in the TGM2-C277S mice. TG2-/- mice were further protected against aging associated increase in PWV. Together, these studies show that TG2 contributes significantly to overall vascular stiffening in aging through both crosslinking dependent and crosslinking independent functions.
The learning objectives are:
To understand changes in pulse wave velocity (PWV) with age in mouse models
To determine the specific role of tissue transglutaminase (TG2) in vascular aging
To evaluate the role of vascular matrix vs. VSMCs to overall in vivo stiffness described by PWV
Primary hyperaldosteronism is characterized by an increase in
the adrenal production of aldosterone. It is critical for its treatment to determine whether it is caused by unilateral or bilateral overproduction of aldosterone. When imaging studies are ambiguous, adrenal venous sampling is the choice to confirm lateralization. It consists in dosing plasma aldosterone and cortisol in both adrenal veins simultaneously with the femoral vein, and establishing the aldosterone/cortisol ratio. On the affected side this ratio is at least 2 times higher than the femoral vein’s.
Functional genomics has led to an improvement of our understanding of CVD and can be translated to clinical utility. Gene-based pre-symptomatic prediction of illness, finer diagnostic sub-classifications and improved risk assessment tools will permit earlier and more targeted intervention. Pharmacogenetics will guide our therapeutic decisions and monitor response to therapy. Personalised medicine requires the integration of clinical information, stable and dynamic genomics and molecular phenotyping.
It is now possible to systematically search the entire human genome for common variants that are associated with a particular phenotype. (HGP, HAP MAP)
Comparison of clinical, radiological and outcome characteristics of ischemic ...MIMS Hospital
Here is the latest publication from the department of Neurology in the Journal of Neurology Research, titled, ’Comparison of Clinical, Radiological and Outcome Characteristics of Ischemic Strokes in Different Vascular Territories’ authored by Ashraf V Valappila, c, Dhanya T Janardhanana, Praveenkumar Raghunatha, Abdulla Cherayakkatb, Girija ASa
Comparison of clinical, radiological and outcome characteristics of ischemic ...
SPUR final abstract
1. Kathryn Repp – Wake Forest University
John LaDisa, PhD
Department of BiomedicalEngineering
UNDERSTANDING MECHANICAL STIMULI ASSOCIATED WITH TWO DIFFERENT CARDIOVASCULAR DISEASES
Wall shear stress (WSS) resulting from the frictional force of blood flow on endothelial cells can alter vascular
structure and homeostasis. Sites of atherosclerosis are known to correlate with low time-averaged WSS and
non-uniform WSS gradients. The success of coronary intervention to atherosclerosis using drug eluting stents
(DES) is limited by restenosis in ~10% of patients, but mechanisms are not fully understood. This study aims to
quantify the response of endothelial cells to WSS experienced after stenting for eventual use in understanding
whether the elution agents from DES impact the known relationship between cellular proliferation and WSS.
Using a syringe pump and Hele-Shaw flow chamber to impose WSS variability, rat endothelial cells were
subjected to a range of WSS from stenting (1.7-17 dyne/cm2). TNF-α in the media (0.3 ng/mL) simulated the
inflammation present with atherosclerosis. The number of cells positively stained for Ki67 served as a
surrogate for restenosis and decreased as WSS increased (y=11.02e-0.519x; R2 = 0.99; n=3). Prior attempts by
various laboratory researchers with this setup failed to show differences in WSS along the length of the
chamber. The current favorable findings are attributed to changes in the protocol influenced by extensive
literature research. This important advancement sets the stage to now quantify the influence of elution agents
from DES on the inverse relationship between restenosis and WSS.
Coarctation of the aorta (CoA) is one of the most common congenital cardiovascular diseases. It consis ts of a
constriction in the proximal descending thoracic aorta, which causes elevated blood pressure (BP) above, and
a BP gradient across, the coarctation. Even after corrective surgery, complications such as hypertension still
exist, leading to a reduced life expectancy. It is likely that CoA patients undergo changes in gene expression
due to the mechanical stimuli (i.e. elevated BP) introduced by the coarctation. In order to better understand
the mechanisms of coarctation pathology in humans, this study used a rabbit model of untreated and
corrected CoA. Comparing microarray data from this rabbit model and RNAseq data of 6 human patients with
CoA, we were able to quantify differentially expressed genes from the region of elevated BP as compared to
regions experiencing normal BP. We observed that the Natriuretic Peptide Receptor 3 (NPR3) gene was
downregulated in the proximal (elevated BP) region of rabbits and humans with CoA. To confirm these
findings, a PCR assay was first run with human control aortic samples to determine the level of NPR3
expression relative to GAPDH for eventual comparison with similar data from the CoA patients. This
experiment revealed 2.5 ng is a sufficient input cDNA when validating the level of NPR3 expression. NPR3
expression in CoA patients can now be more carefully studied using a paired aorta PCR assay. Future studies
will then be performed to understand the functional relevance of the decreased NPR3 expression in CoA
patients.