PUBLICATIONS Continued
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Nov 2019
[This corrects the article DOI: 10.1371/journal.pmed.1002522.].
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Oct 2019
What we already know about this topic: Sevoflurane has antiinflammatory properties, but less is known about effects on infectious inflammationSevoflurane effects on macrophage function in inflammation are not well understood WHAT THIS ARTICLE TELLS US THAT IS NEW: In a lipopolysaccharide model of inflammation, sevoflurane increased mouse macrophag...
Poster
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May 2019
Article
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Feb 2019
Aims: Increases in hydrostatic pressure results in endothelial hyperpermeability via eNOS-dependent pathways. Ropivacaine is known to inhibit eNOS activation and to attenuate lung injury. Herein, we sought to determine if ropivacaine regulates pressure-induced lung endothelial hyperpermeability. Main methods: The effects of ropivacaine on lung perm...
The GTPase Rab1 Is Required for NLRP3 Inflammasome Activation and Inflammatory Lung Injury
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Nov 2018
Uncontrolled inflammatory response during sepsis predominantly contributes to the development of multiorgan failure and lethality. However, the cellular and molecular mechanisms for excessive production and release of proinflammatory cytokines are not clearly defined. In this study, we show the crucial role of the GTPase Ras-related protein in brai...
Heparan sulfate proteoglycans regulate aortic response to vasoactive agents
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Nov 2018
Glypican-1 mediates endothelial hyperpermeability in a model of acute heart failure
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Nov 2018
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Oct 2018
Aims: Acute increases in left ventricular end diastolic pressure (LVEDP) can induce pulmonary edema (PE). The mechanism(s) for this rapid onset edema may involve more than just increased fluid filtration. Lung endothelial cell permeability is regulated by pressure-dependent activation of nitric oxide synthase (NOS). Herein, we demonstrate that pres...
Emergency Intubation: Early Identification and Strategic Management (Can) Save Lives
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Jun 2018
Article
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Mar 2018
Background Trauma is the leading cause of death and disability in patients aged 1–46 y. Severely injured patients experience considerable blood loss and hemorrhagic shock requiring treatment with massive transfusion of red blood cells (RBCs). Preclinical and retrospective human studies in trauma patients have suggested that poorer therapeutic effic...
Data
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Mar 2018
Raw data presented in Figs 1–6. (XLSX)
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Jul 2017
Hypercapnic acidosis (HCA) has beneficial effects in experimental models of lung injury by attenuating inflammation and decreasing pulmonary edema. However, HCA increases pulmonary vascular pressure that will increase fluid filtration and worsen edema development. To reconcile these disparate effects, we tested the hypothesis that HCA inhibits endo...
Heparanase promotes neuroinflammatory response during subarachnoid hemorrhage in rats
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Jul 2017
Background Heparanase, a mammalian endo-β-D-glucoronidase that specifically degrades heparan sulfate, has been implicated in inflammation and ischemic stroke. However, the role of heparanase in neuroinflammatory response in subarachnoid hemorrhage (SAH) has not yet been investigated. This study was designed to examine the association between hepara...
Isoflurane promotes phagocytosis of apoptotic neutrophils through AMPK-mediated ADAM17/Mer signaling
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Jul 2017
A patient's recovery from lung inflammatory injury or development of multi-system organ failure is determined by the host's ability to resolve inflammation and repair tissue damage, both of which require the clearance of apoptotic neutrophils by macrophages (efferocytosis). Here, we investigated the effects of isoflurane on macrophage efferocytosis...
Goal-Directed Fluid Therapy: What the Mind Does Not Know, the Eye Cannot See
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Mar 2017
ACE Phenotyping as a Guide Toward Personalized Therapy with ACE Inhibitors
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Jan 2017
Background: Angiotensin-converting enzyme (ACE) inhibitors (ACEI) are widely used in the management of cardiovascular diseases but with significant interindividual variability in the patient's response. Objectives: To investigate whether interindividual variability in the response to ACE inhibitors is explained by the "ACE phenotype"-for example...
The Role of HMGB1 in Pial Arteriole Dilating Reactivity following Subarachnoid Hemorrhage in Rats
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Dec 2016
High-mobility group box 1 protein (HMGB1) has been implicated in inflammatory responses, and is also associated with cerebral vasospasm after subarachnoid hemorrhage (SAH). However, there are no direct evident links between HMGB1 and cerebral vasospasm. We therefore investigated the effects of HMGB1 on pial arteriole reactivity following SAH in rat...
Lysozyme and bilirubin bind to ACE and regulate its conformation and shedding
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Oct 2016
Angiotensin I-converting enzyme (ACE) hydrolyzes numerous peptides and is a critical participant in blood pressure regulation and vascular remodeling. Elevated tissue ACE levels are associated with increased risk for cardiovascular and respiratory disorders. Blood ACE concentrations are determined by proteolytic cleavage of ACE from the endothelial...
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Oct 2016
The Biomechanical Effects of Resuscitation Colloids on the Compromised Lung Endothelial Glycocalyx
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Jun 2016
Background: The endothelial glycocalyx is an important component of the vascular permeability barrier, forming a scaffold that allows serum proteins to create a gel-like layer on the endothelial surface and transmitting mechanosensing and mechanotransduction information that influences permeability. During acute inflammation, the glycocalyx is deg...
Rab11a Mediates Vascular Endothelial-Cadherin Recycling and Controls Endothelial Barrier Function
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Dec 2015
Objective: Vascular endothelial (VE)-cadherin is the predominant component of endothelial adherens junctions essential for cell-cell adhesion and formation of the vascular barrier. Endocytic recycling is an important mechanism for maintaining the expression of cell surface membrane proteins. However, little is known about the molecular mechanism o...
Propofol increases morbidity and mortality in a rat model of sepsis
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Dec 2015
Severe sepsis is associated with approximately 50% mortality and accounts for tremendous healthcare costs. Most patients require ventilatory support and propofol is commonly used to sedate mechanically ventilated patients. Volatile anesthetics have been shown to attenuate inflammation in a variety of different settings. We therefore hypothesized th...
Tissue Specificity of Human Angiotensin I-Converting Enzyme
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Nov 2015
Background: Angiotensin-converting enzyme (ACE), which metabolizes many peptides and plays a key role in blood pressure regulation and vascular remodeling, as well as in reproductive functions, is expressed as a type-1 membrane glycoprotein on the surface of endothelial and epithelial cells. ACE also presents as a soluble form in biological fluids...
Role of Integrin β4 in Lung Endothelial Cell Inflammatory Responses to Mechanical Stress
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Nov 2015
Simvastatin, an HMG-CoA reductase inhibitor, has lung vascular-protective effects that are associated with decreased agonist-induced integrin β4 (ITGB4) tyrosine phosphorylation. Accordingly, we hypothesized that endothelial cell (EC) protection by simvastatin is dependent on these effects and sought to further characterize the functional role of I...
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Nov 2015
Background Matrix-metalloproteinases (MMP) and cancer cell invasion are crucial for solid tumour metastasis. Important signalling events triggered by inflammatory cytokines, such as tumour necrosis factor α (TNFα), include Src-kinase-dependent activation of Akt and focal adhesion kinase (FAK) and phosphorylation of caveolin-1. Based on previous stu...
The glycocalyx and Trauma: A Review
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Oct 2015
In the United States trauma is the leading cause of mortality among those under the age of 45, claiming approximately 192,000 lives each year. Significant personal disability, lost productivity and long term healthcare needs are common and contribute 580 billion dollars in economic impact each year. Improving resuscitation strategies and the early...
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Mar 2015
The integrity of the lung alveolar epithelial barrier is required for the gas exchange and is important for immune regulation. Alveolar epithelial barrier is composed of flat type I cells, which make up approximately 95% of the gas-exchange surface, and cuboidal type II cells, which secrete surfactants and modulate lung immunity. p120-catenin (p120...
Testosterone induces leukocyte migration by NADPH oxidase-driven ROS- and COX2-dependent mechanisms
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Feb 2015
The mechanisms whereby testosterone increases cardiovascular risk are not clarified. However, oxidative stress and inflammation seem to be determinant. Herein, we sought to determine whether exogenous testosterone, in physiological levels, induces leukocyte migration, a central feature in immune and inflammatory responses, and the mediating mechani...
Chapter
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Jan 2015
The case discusses a pharmacodynamic reaction between halothane and epinephrine resulting in arrhythmias.
Chapter
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Jan 2015
This case discusses the pharmacokinetic interaction between codeine and quinidine. Codeine is a prodrug, metabolized to the active compound morphine by CYP2D6, quinidine is a 2D6 inhibitor.
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Jan 2015
This chapter discusses the genetics, metabolic actions, substrates, inducers, and inhibitors of cytochrome P450 2E1.
The Worry That’s Always With Us: Afternoon Nap
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Jan 2015
This case discusses the pharmacodynamic interaction between oxycodone and diazepam resulting in apnea and decreased level of consciousness in a patient with chronic back pain.
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Jan 2015
This chapter discusses the genetics, metabolic actions, substrates, and inhibitors of cytochrome P450 2D6.
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Jan 2015
This case discusses a pharmacokinetic interaction between methadone and ciprofloxacin resulting in increased sedative and analgesic effects of methadone. Methadone is a cytochrome P450 3A4 substrate and ciprofloxacin is a 3A4 inhibitor.
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Jan 2015
This case discusses the pharmacokinetic interaction between pomegranate juice and sildenafil, resulting in priapism. Sildenafil is a cytochrome P450 3A4 substrate and pomegranate juice is a 3A4 inhibitor.
There’s Just Not Enough Roc in the World
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Jan 2015
This case discusses the pharmacokinetic interaction between rocuronium and carbamazepine, resulting in shortened duration of neuromuscular blockade.
Chapter
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Jan 2015
This chapter discusses the genetics, metabolic actions, substrates, inducers, and inhibitors of P450 CYP2C9.
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Jan 2015
This chapter discusses the genetics, metabolic actions, substrates, inducers, and inhibitors of cytochrome P450 2B6.
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Jan 2015
This case discusses a pharmacokinetic interaction between budesonide and itraconazole, resulting in Cushing’s disease. Budesonide is a cytochrome P450 3A4 substrate and itraconazole is a 3A4 inhibitor.
Chapter
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Jan 2015
This chapter discusses the genetics, metabolic actions, substrates, inducers, and inhibitors of cytochrome P450 3A4.
Chapter
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Jan 2015
This case discusses an interaction between tacrolimus and nicardipine. Tacrolimus is a cytochrome P450 3A4 substrate and nicardipine is a 3A4 inhibitor. The interaction resulted in tacrolimus toxicity. The pharmacokinetics of nicardipine are also discussed.
Chapter
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Jan 2015
This chapter discusses the genetics, metabolic actions, substrates, inducers, and inhibitors of cytochrome P450 2C9.
Chapter
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Jan 2015
This chapter discusses the genetics, metabolic actions, substrates, inducers, and inhibitors of cytochrome P450 1A2
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Jan 2015
This case discusses a ketamine/theophylline interaction of unknown etiology resulting in decreased seizure threshold.
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Jan 2015
This case discusses the interaction between clopidogrel and omeprazole. Clopidogrel is a prodrug metabolized to an intermediate compound by cytochrome P450 2C19. Omeprazole is a 2C19 inhibitor.
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Jan 2015
This chapter discusses the essential terms and concepts of drug–gene interactions or how genetics affect pharmacology. This subset of pharmacology is also known as pharmacogenomics.
Conference Paper
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Jun 2014
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May 2014
The inflammatory response is a primary mechanism in the pathogenesis of ventilator-induced lung injury. Autophagy is an essential, homeostatic process by which cells break down their own components. We explored the role of autophagy in the mechanisms of mechanical ventilation-induced lung inflammatory injury. Mice were subjected to low (7 ml/kg) or...
The Endothelial Glycocalyx: Emerging Concepts in Pulmonary Edema and Acute Lung Injury
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Jul 2013
The endothelial glycocalyx is a dynamic layer of macromolecules at the luminal surface of vascular endothelium that is involved in fluid homeostasis and regulation. Its role in vascular permeability and edema formation is emerging but is still not well understood. In this special article, we highlight key concepts of endothelial dysfunction with re...
Conference Paper
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May 2013
HYALURONAN MODULATES VASCULAR MECHANOTRANSDUCTION IN THE INTACT LUNG
Conference Paper
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May 2013
Conference Paper
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May 2013
Inflammation, wound healing, and infection
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Mar 2013
Sevoflurane reduces clinical disease in a mouse model of multiple sclerosis
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Dec 2012
Background Inhalational anesthetics have been shown to influence T cell functions both in vitro and in vivo, in many cases inducing T cell death, suggesting that exposure to these drugs could modify the course of an autoimmune disease. We tested the hypothesis that in mice immunized to develop experimental autoimmune encephalomyelitis (EAE), a well...
Article
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May 2012
Numerous cardiopulmonary, autoimmune, and inflammatory diseases, as well as cigarette smoke and dietary suppressants, induce significant oxidative stress resulting in endothelial cell dysfunction, hyperproliferation, and vasoocclusive vascular disease. Maintenance of normal endothelial cell function is thought to be mediated in part via tight contr...
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Apr 2012
Reflectance interference contrast microscopy (RICM) was used to study the mechanics of the endothelial glycocalyx. This technique tracks the vertical position of a glass microsphere probe that applies very light fluctuating loads to the outermost layer of the bovine lung microvascular endothelial cell (BLMVEC) glycocalyx. Fluctuations in probe vert...
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Dec 2011
Lung endothelial cells respond to changes in vascular pressure through mechanotransduction pathways that alter barrier function via non-Starling mechanism(s). Components of the endothelial glycocalyx have been shown to participate in mechanotransduction in vitro and in systemic vessels, but the glycocalyx's role in mechanosensing and pulmonary barr...
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Sep 2011
Endogenous agonists of transient receptor potential vanilloid-1 (TRPV1) (endovanilloids) are implicated as mediators of lung injury during inflammation. This study tested the hypothesis that endovanilloids produced following lipopolysaccharide (LPS) treatment activate TRPV1 and cause endoplasmic reticulum stress/GADD153 expression in lung cells, re...
Article
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Aug 2011
Studies show that LL-37 is a naturally occurring urinary defensin peptide that is up-regulated during urinary tract infections. Although normal urinary LL-37 levels are antimicrobial, we propose that increased LL-37 may trigger bladder inflammation. We further suggest that anti-inflammatory sulfated polysaccharides known as semi-synthetic glycosami...
Mechano-Transduction and Barrier Regulation in Lung Microvascular Endothelial Cells
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Jul 2011
Alterations in endothelial permeability are a hallmark of inflammation as well as the underlying cause of many clinical syndromes. Quantifying changes in endothelial barrier properties to water and macromolecules can be an important means of assessing the degree of cellular injury and, conversely, the effect of therapies to attenuate the inflammato...
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Jun 2011
The mechanical properties of endothelial glycocalyx were studied using atomic force microscopy with a silica bead (diameter ∼18 μm) serving as an indenter. Even at indentations of several hundred nanometers, the bead exerted very low compressive pressures on the bovine lung microvascular endothelial cell (BLMVEC) glycocalyx and allowed for an avera...
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Mar 2011
Complications of intrauterine growth restriction (IUGR) include increased pulmonary morbidities and impaired alveolar development. Normal alveolar development depends upon elastin expression and processing, as well as the formation and deposition of elastic fibers. This is true of the human and rat. In this study, we hypothesized that uteroplacenta...
Article
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Oct 2010
Pulmonary edema and the associated increases in vascular permeability continue to represent a significant clinical problem in the intensive care setting, with no current treatment modality other than supportive care and mechanical ventilation. Therapeutic compound(s) capable of attenuating changes in vascular barrier function would represent a sign...
Article
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Aug 2009
Acute changes in lung capillary permeability continue to complicate procedures such as cardiopulmonary bypass, solid organ transplant, and major vascular surgery and precipitate the more severe disease state Adult Respiratory Distress Syndrome (ARDS). To date there is no treatment targeted directly to the lung microvasculature. We hypothesized that...
Fluorescence correlation spectroscopy can probe albumin dynamics inside lung endothelial glycocalyx
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Sep 2007
The endothelial glycocalyx is believed to play a major role in capillary permeability by functioning as a macromolecular barrier overlying the intercellular junction. Little is known about the functional attributes of the glycocalyx (i.e., porosity and permeability) or which constituents contribute to its overall structure-function relationship. In...
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Jul 2007
We investigated the nonlinear dynamics of the pressure vs. hydraulic conductivity (L(p)) relationship in lung microvascular endothelial cells and demonstrate that heparan sulfates, an important component of the endothelial glycocalyx, participate in pressure-sensitive mechanotransduction that results in barrier dysfunction. The pressure vs. L(p) re...
The Role of Endothelial Glycocalyx Components in Mechanotransduction of Fluid Shear Stress
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Apr 2007
The surface of endothelial cells is decorated with a wide variety of membrane-bound macromolecules that constitute the glycocalyx. These include glycoproteins bearing acidic oligosaccharides with terminal sialic acids (SA), and proteoglycans with their associated glycosaminoglycan that include: heparan sulfate (HS), chondroitin sulfate (CS), and hy...
Chapter
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Dec 2006
Genetic engineering offers the opportunity to design and construct various mutant hemoglobins possessing conformational and functional characteristics that render them suitable for use as therapeutic agents in a variety of clinical situations. Problems related to the use of Hb solutions for transfusion are the rapid loss of Hb through the kidney's...
Article
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Apr 2006
We have developed an automated, digital imaging system, controlled by two virtual instruments, to measure hydraulic conductivity (Lp) of cultured endothelial monolayers. Live digital images of multiple independent experiments were captured by custom-designed video processing software running in National Instruments LabVIEW 6.1. Fluid displacement d...
Vascular smooth muscle cell glycocalyx influences shear stress-mediated contractile response
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Feb 2005
This study addressed the influence of the rate of shear stress application on aortic smooth muscle cell (SMC) contraction and the role of specific glycosaminoglycans in this mechanotransduction. Rat aortic SMCs were exposed to either a step increase in shear stress (0 to 25 dyn/cm(2)) or a ramp increase in shear stress (0 to 25 dyn/cm(2) over 5 min...
Quantitative assessment of hemoglobin-induced endothelial barrier dysfunction
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Dec 2004
Hemoglobin (Hb)-based O2 carriers (HBOC) are undergoing extensive development as potential "blood substitutes." A major problem associated with these molecules is an increase in microvascular permeability and peripheral vascular resistance. In this paper, we utilized bovine lung microvascular endothelial cell monolayers and simultaneously measured...
Article
Full-text available
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Dec 2003
The endothelial glycocalyx is believed to play a major role in microvascular permeability. We tested the hypothesis that specific components of the glycocalyx, via cytoskeletal-mediated signaling, actively participate in barrier regulation. With the use of polymers of arginine and lysine as a model of neutrophil-derived inflammatory cationic protei...
Heparan Sulfate Proteoglycan Is a Mechanosensor on Endothelial Cells
Article
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Dec 2003
The objective of this study was to test whether a glycosaminoglycan component of the surface glycocalyx layer is a fluid shear stress sensor on endothelial cells (ECs). Because enhanced nitric oxide (NO) production in response to fluid shear stress is a characteristic and physiologically important response of ECs, we evaluated NOx (NO2- and NO3-) p...
Leukocyte-induced microvascular permeability: how contractile tweaks lead to leaks
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Jul 2002
Leukocyte-Induced Microvascular Permeability: How Contractile Tweaks Lead to Leaks
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Jun 2002
Neutrophil infiltration into tissues, a hallmark of acute inflammation, is a complex process requiring an intricate orchestration of signals between microvascular endothelial cells and both circulating and adherent neutrophils. Cytokines and inflammatory mediators elaborated during injury or infection activate both endothelial cells and circulating...
Polycation induced changes in endothelial cytoskeleton and cell permeability
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Apr 2002
Article
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Apr 2001
Vascular endothelial growth factor (VEGF) was originally discovered as vascular permeability factor because of its ability to increase microvascular permeability to plasma proteins. Since then, it has been shown to induce proliferation and migration in endothelial cells. Placenta growth factor (PlGF) is a member of the VEGF family of growth factors...
Article
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Apr 2000
Vascular endothelial growth factor (VEGF) is a potent enhancer of microvascular permeability in vivo. To date, its effects on hydraulic conductivity (L(p)) and diffusive albumin permeability (P(e)) of endothelial monolayers have not been thoroughly assessed in vitro. We hypothesized that VEGF affects endothelial transport properties differently dep...
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Mar 2000
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Article
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Jan 1999
Unlabelled: Adjuvants such as opioids or epinephrine are commonly added in small volumes to multicomponent spinal anesthetic solutions. In this study, we tested the hypothesis that final adjuvant concentrations vary depending on the devices and techniques used to prepare the anesthetic solution. We compared two aspiration devices, the filter needl...
Variations in the Composition of Spinal Anesthetic Solutions
Article
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Dec 1998
Adjuvants such as opioids or epinephrine are commonly added in small volumes to multicomponent spinal anesthetic solutions. In this study, we tested the hypothesis that final adjuvant concentrations vary depending on the devices and techniques used to prepare the anesthetic solution. We compared two aspiration devices, the filter needle and the fil...
Article
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Dec 1998
Evaluation of the composition of spinal anesthetic solutions prepared with a filter straw
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Sep 1997
Article
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Jan 1996
There is a correlation between the location of early atherosclerotic lesions and the hemodynamic characteristics at those sites. Circulating monocytes are key cells in the pathogenesis of atherosclerotic plaques and localize at sites of atherogenesis. The hypothesis that the distribution of monocyte adhesion to the vascular wall is determined in pa...
Hemodynamic Forces in Relation to Mechanosensitive Ion Channels in Endothelial Cells
Chapter
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Dec 1993
Hemodynamic forces and vascular cell communication in arteries
Article
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Jan 1993
As the interface between the blood and the rest of the vessel wall, the endothelium is directly affected by hemodynamic shear stress (frictional) forces that locally regulate vascular tone and are implicated in the localization of atherosclerosis. There are many diverse responses of endothelial cells to hemodynamically related mechanical stresses r...
Article
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Nov 1992
Intracellular free calcium ([Ca2+]i) was measured in single cells of a confluent endothelial monolayer subjected to defined flow. Flow medium containing adenosine triphosphate (ATP) was used to study the influence of flow forces upon agonist-response coupling as mediated via the P2y-purinoceptor. [Ca2+]i responses were highly sensitive to the fluid...
Flow modulation of agonist (ATP)-response (Ca2+) coupling in vascular endothelial cells
Article
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Aug 1991
ATP-induced increases of intracellular calcium concentration ([Ca2+]i) were measured as a function of flow rate in single cell recordings within a confluent endothelial cell monolayer. Although flow and its associated shear stress did not per se significantly alter basal [Ca2+]i, ATP-induced [Ca2+]i was exquisitely sensitive to flow. Step increases...
Endothelial albumin permeability is shear dependent, time dependent, and reversible
Article
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Jul 1991
Altered permeability of vascular endothelium to macromolecules may play a role in vascular disease as well as vascular homeostasis. Because the shear stress of flowing blood on the vascular wall is known to influence many endothelial cell properties, an in vitro system to measure transendothelial permeability (Pe) to fluorescein isothiocyanate conj...
Article
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Jun 1991
An in vitro model of the endothelial transport barrier was developed using bovine aortic endothelial cell monolayers cultured on a porous polycarbonate substrate. Hydraulic conductivity (Lp) was measured by a bubble tracking technique at varying pressure differentials and albumin concentrations. The effective albumin permeability (Pc) was determine...
How Does the Arterial Endothelium Sense Flow? Hemodynamic Forces and Signal Transduction
Article
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Feb 1990
The focal nature of atherosclerotic lesions is associated with patterns of altered blood flow in the major arteries (1–3), although the precise nature of the flow in such regions is unclear. At the interface between flowing blood and the arterial wall, a confluent monolayer of endothelial cells operates as a signal-transduction system for hemodynam...
Chapter
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Jan 1990
Endothelial cells regulate transmural volume flux and permeability of the vascular wall to macromolecules. Alteration of wall permeability may be an early event in atherogenesis. In order to study transport properties of the endothelial monolayer in isolation from the underlying structures of the arterial wall, we developed an in vitro model employ...
Antihistamines reverse blood-ocular barrier breakdown in experimental diabetes
Article
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Mar 1988
Retinal and other tissue histamine synthesis is increased in experimental diabetes; histamine infusion causes blood-ocular barrier breakdown in nondiabetic rats. We have examined the hypothesis that antihistamines prevent blood-ocular barrier breakdown in streptozotocin diabetes using male Sprague-Dawley rats held 28 days. During the last 7 days th...
Effect of chronic histamine infusion on the permeability of the blood retinal barrier
Article
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Jan 1986