Open Access. Powered by Scholars. Published by Universities.®
- Discipline
-
- Cellular and Molecular Physiology (41)
- Medicine and Health Sciences (30)
- Biochemistry, Biophysics, and Structural Biology (16)
- Neuroscience and Neurobiology (12)
- Physical Sciences and Mathematics (11)
-
- Medical Sciences (10)
- Molecular and Cellular Neuroscience (10)
- Applied Mathematics (8)
- Biophysics (8)
- Other Physiology (8)
- Diseases (7)
- Molecular Biology (6)
- Pharmacology, Toxicology and Environmental Health (6)
- Systems and Integrative Physiology (6)
- Cardiovascular Diseases (5)
- Cell and Developmental Biology (5)
- Endocrinology (5)
- Medical Specialties (5)
- Behavioral Neurobiology (4)
- Cell Biology (4)
- Exercise Physiology (4)
- Laboratory and Basic Science Research (4)
- Ordinary Differential Equations and Applied Dynamics (4)
- Pharmacology (4)
- Animal Experimentation and Research (3)
- Chemicals and Drugs (3)
- Exercise Science (3)
- Immunology and Infectious Disease (3)
- Keyword
-
- Ischemia (6)
- Nitric oxide (6)
- Electrophysiology (5)
- Hypertension (5)
- Medicine (5)
-
- Mitochondria (5)
- Other (5)
- Oxygen consumption (5)
- Bile acids (4)
- Hemoglobin (4)
- Inflammation (4)
- Reperfusion (4)
- Atherosclerosis (3)
- Doxorubicin (3)
- MMP-1 (3)
- Microcirculation (3)
- Motility (3)
- Oxygen (3)
- PIP2 (3)
- PKC (3)
- Porphyromonas gingivalis (3)
- Preeclampsia (3)
- Signaling (3)
- Sildenafil (3)
- Smooth Muscle (3)
- Smooth muscle (3)
- 5-HT2A (2)
- AMPK (2)
- Akt (2)
- Angiogenesis (2)
- Publication Year
- Publication
- Publication Type
Articles 91 - 120 of 186
Full-Text Articles in Physiology
Spatial Distribution And Modulation Of Nitric Oxide Synthase In A Hypertensive Rat Model, Andrew Yannaccone
Spatial Distribution And Modulation Of Nitric Oxide Synthase In A Hypertensive Rat Model, Andrew Yannaccone
Theses and Dissertations
There are gaps in the fundamental understanding of the expression of nitric oxide synthases (NOS) in the microvasculature. We examined co-localization of NOS1 (nNOS), NOS2 (iNOS) and NOS3 (eNOS) in the spinotrapezius muscle of young adult male Wistar-Kyoto (WKY) and Spontaneously Hypertensive (SHR) rats according to fiber type using immunohistochemistry and brightfield microscopy. Data regarding fiber distribution, population and morphology data were collected. Alkaline phosphatase staining was used to determine capillary density and average number of capillaries around a fiber. Gel electrophoresis and Western blot techniques were used to compare myosin heavy chain (MHC) protein expression with fiber type population …
Epigenetic Regulation Of Genes Involved In Vascular Dysfunction In Preeclamptic Women, Ahmad Mousa
Epigenetic Regulation Of Genes Involved In Vascular Dysfunction In Preeclamptic Women, Ahmad Mousa
Theses and Dissertations
DNA methylation is the most recognizable epigenetic mechanism. In general, DNA hypomethylation is associated with increased gene expression whereas DNA hypermethylation is associated with decreased gene expression. To date, little is known about the role of DNA methylation in the pathophysiology of preeclampsia. In this study, we examined the differences in DNA methylation in omental arteries of normal pregnant and preeclamptic women using the high throughput Illumina HumanMethylation27 BeadChip assay. We found 1,685 genes with a significant difference in DNA methylation at a false discovery rate of < 10% with many inflammatory genes having reduced methylation. The thromboxane synthase gene was the most hypomethylated gene in preeclamptic women as compared to normal pregnant women. When we examined the expression of thromboxane synthase in omental arteries of normal pregnant and preeclamptic women we found it to be significantly increased in preeclamptic women. The increased expression was observed in vascular smooth muscle cells, endothelial cells and infiltrating neutrophils. Experimentally induced DNA hypomethylation increased the expression of thromboxane synthase in the neutrophil-like HL-60 cell line, whereas tumor necrosis factor α (TNFα), a neutrophil product, increased its expression in cultured human vascular smooth muscle cells (VSMC). These finding suggest that DNA methylation and release of TNFα by infiltrating neutrophils could contribute to the increased expression of thromboxane synthase in systemic blood vessels of preeclamptic women, contributing to the hypertension and coagulation abnormalities. We also explored the possible contribution of DNA methylation to the altered expression of genes involved in collagen metabolism in preeclampsia. Several matrix metalloproteinase (MMP) genes, including MMP1 and MMP8, were significantly less methylated in preeclamptic women, whereas TIMP and COL genes were either significantly more methylated or had no significant change in their DNA methylation status. Experimentally induced DNA hypomethylation increased the expression of MMP-1, but not TIMP-1 or COL1A1, in cultured VSMCs and increased the expression of MMP-1 and MMP-8 in HL-60 cells. These findings suggest that DNA methylation contributes to the imbalance in genes involved in collagen metabolism in blood vessels of preeclamptic women.
Association Between T Cells-Related Gene Expression And Fibrosis Progression In Hcv Recurrence Disease., Alexander Philip
Association Between T Cells-Related Gene Expression And Fibrosis Progression In Hcv Recurrence Disease., Alexander Philip
Theses and Dissertations
Hepatitis C virus (HCV) is the major cause of chronic hepatitis worldwide and a leading cause for liver transplant. Unfortunately, graft HCV infection is a universal phenomenon despite of pre-transplant prophylactic strategies. Acute HCV infection and innate immune responses elicit an inflammatory scenario that triggers the recruitment of adaptive immune response cells. Of those chronically infected, 30% experience accelerated fibrosis with concomitant cirrhosis development within 5 years post-LT and require re-transplant. With many patients responding unfavorably to antivirals and ineffective vaccines, much attention is now placed on T cell immunity in controlling HCV infection. This study represents a retrospective analysis …
Molecular Pathways Involved In Calcineurin Inhibitor Nephrotoxicity In Kidney Allograft Transplants, Huong Nguyen
Molecular Pathways Involved In Calcineurin Inhibitor Nephrotoxicity In Kidney Allograft Transplants, Huong Nguyen
Theses and Dissertations
ABSTRACT MOLECULAR MECHANISMS AND GENE SIGNATURES INVOVLED IN CALCINEURIN INHIBITOR NEPHROTOXICITY IN KIDNEY ALLOGRAFT By Huong Le Diem Nguyen, M.S. A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science in Physiology at Virginia Commonwealth University. Virginia Commonwealth University, 2011. Major Director: Valeria Mas, Ph.D. Associate Professor, Department of Surgery and Pathology Director of Molecular Transplant Research Laboratory, Division of Transplant Calcineurin inhibitors (CNI), cyclosporin A and tacrolimus, are potent immunosuppressive agents but induce toxicities causing damages and graft dysfunction, and have been suggested to contribute to late-term loss of graft in kidney transplant …
Opioid Addiction Treatments During Pregnancy And Their Effects On Axonal Growth And Myelination In The Developing Central Nervous System, Manisha Magar
Theses and Dissertations
Treatment with buprenorphine represents a promising alternative for pregnant opioid addicts but there is a need to understand potential effects on nervous system development. We previously showed effects of perinatal exposure to buprenorphine on axonal caliber and myelination in 26-day-old rat corpus callosum. These changes, detected at the end of rapid brain myelination and accompanied by earlier oligodendrocyte maturation, suggested interference with mechanisms coordinating axonal growth and myelination. To better understand buprenorphine actions and to establish whether these effects extend to the spinal cord, we analyzed the corpus callosum and corticospinal tract at 16 days of age, just before the …
Quantitative Analysis Of Contactin-Associated Protein And Voltage-Gated Sodium Channel Isoform 1.6 Following Experimental Diffuse Traumatic Brain Injury, Daniel Gardiner
Quantitative Analysis Of Contactin-Associated Protein And Voltage-Gated Sodium Channel Isoform 1.6 Following Experimental Diffuse Traumatic Brain Injury, Daniel Gardiner
Theses and Dissertations
Traumatic axonal injury (TAI) contributes to the mortality and morbidity following diffuse traumatic brain injury (TBI). Previous work has shown that following TBI, alterations in the molecular domains of axons result in TAI. It is currently posited that injury induced ionic flux is responsible for activating deleterious proteolytic cascades, resulting in altered distributions of axonal components. However, the underlying mechanism of this progressive pathology remains elusive. This study further explores the hypothesis that altered molecular domains contributes to the progressive intra-axonal changes that characterize TAI. Using a rodent model of impact acceleration TBI we examined the expression of nodal and …
Receptor Influences In Girk Current Activation And Desensitization, Gyu Park
Receptor Influences In Girk Current Activation And Desensitization, Gyu Park
Theses and Dissertations
G protein-coupled receptors (GPCRs) are seven-transmembrane domain receptors that sense extracellular signal and activate intracellular signaling pathways. Metabotropic glutamate receptor 2 (mGluR2) is one of the GPCRs coupled to Gi/o proteins whose Gβγ subunits stimulate G protein-gated inwardly rectifying K+ channels (GIRKs). Previous experiments demonstrated that in planar lipid bilayer both active forms of G proteins [Gα (GTPγS-stimulated) and Gβγ subunits] were required to activate GIRK channels in the absence of the receptor, but surprisingly, the Gβγ subunit alone could activate GIRK channel in the presence of GPCR. Currently, it is not clear whether GPCRs play a role beyond catalyzing …
Kinase Pathways Underlying Muscarinic Activation Of Colonic Longitudinal Muscle, Charles Dudley Anderson Jr.
Kinase Pathways Underlying Muscarinic Activation Of Colonic Longitudinal Muscle, Charles Dudley Anderson Jr.
Theses and Dissertations
The longitudinal muscle layer in gut is the functional opponent to the circular muscle layer during the peristalsis reflex. Differences in innervation of the layers allow for the contraction of one layer that corresponds with the simultaneous relaxation of the other, enabling the passage of gut contents in a controlled fashion. Differences in development have given the cells of the two layers differences in receptor populations, membrane lipid handling, and calcium handling profiles/behaviors. The kinase signaling differences between the two layers is not as well characterized. Upon activation of cells from the circular muscle layer, it is known that Rho …
Differential Regulation Of Mlc20 Phosphorylation In Tonic And Phasic Smooth Muscles Of The Stomach, Othman Al-Shboul
Differential Regulation Of Mlc20 Phosphorylation In Tonic And Phasic Smooth Muscles Of The Stomach, Othman Al-Shboul
Theses and Dissertations
Gastrointestinal (GI) smooth muscle possesses distinct regional and functional properties that distinguish it from other types of visceral and vascular smooth muscle. On the basis of electrical properties and contractile phenotype, GI smooth muscles have been classified into phasic (non-sphinteric) and tonic (sphinteric) smooth muscles. The biochemical basis of phasic and tonic phenotypes of smooth muscle is not clear and is the major question of inquiry of the present study. Phosphorylation of Ser19 on the 20 kDa myosin light chain (MLC) is essential for acto-myosin interaction and contraction in both phasic and tonic muscles. The levels of MLC20 phosphorylation are …
Characterization Of The Expression Of Bdnf And Cgrp And Their Regulatory Pathways In Dorsal Root Ganglion During Cystitis., Sharon Yu
Theses and Dissertations
Interstitial cystitis is a chronic debilitating disease that causes pain and increased frequency of micturition, amongst other symptoms, without any identifiable cause. This disease affects a large number of the population, yet the etiology is still unknown. The present study aimed to characterize BDNF and CGRP—two neuropeptides that have both been proven to play an important role in the transmission of pain as well as in hypersensitivity. The signaling pathways regulating the expression of the two neuropeptides were also examined. Results revealed that BDNF protein expression levels increased in both L1 and L6 DRG following 48 hours post CYP-induced cystitis. …
The Characterization Of Pg0228 In Porphyromonas Gingivalis W83, Courtney Schlenker
The Characterization Of Pg0228 In Porphyromonas Gingivalis W83, Courtney Schlenker
Theses and Dissertations
Periodontitis affects 10 to 15 percent of most adult populations and can contribute to numerous systemic diseases. Porphyromonas gingivalis, a gram-negative anaerobic bacterium, is a recognized prime causative agent in periodontitis. Studies have shown a number of small non-coding RNAs (sRNAs) have been related to bacterial virulence. Many of these sRNAs require the facilitation of the bacterial Sm-like protein, Hfq, for optimum function. Hfq is a RNA chaperone involved in RNA stability, sRNA function, and polyadenylation. Mutants lacking in Hfq often show pleiotropic phenotypes, although the extent and severity of hfq null phenotypes is often species-specific. Hfq has been encoded …
Changes In The Expression Of Thin Filament-Associated Proteins In Colonic Smooth Muscle From Mice During Inflammation, Reem Alkahtani
Changes In The Expression Of Thin Filament-Associated Proteins In Colonic Smooth Muscle From Mice During Inflammation, Reem Alkahtani
Theses and Dissertations
The contractility of smooth muscle in inflammatory bowel disease and experimental colitis is reduced due to inhibition of neurotransmitter release and a decrease in the response of smooth muscle to contractile agonists. We and others have shown that inflammation induced by TNBS treatment alters the expression and/or activity of signaling molecules involved in the regulation of Ca2+ mobilization, MLC20 phosphorylation and contraction in colonic smooth muscle. Although, thin filament- associated proteins such as calponin, caldesmon, tropomyosin and smoothelin do not directly participate in contraction, they regulate acto-myosin interaction and thus, muscle contraction. Calponin, caldesmon and tropomyosin inhibit actomyosin interaction and …
Renal Epithelial Sodium Channel (Enac) Regulation Of Pregnancy Mediated Hemodynamic Adaptations: Mechanistic Insights, Crystal West
Renal Epithelial Sodium Channel (Enac) Regulation Of Pregnancy Mediated Hemodynamic Adaptations: Mechanistic Insights, Crystal West
Theses and Dissertations
Pregnancy-mediated sodium (Na) retention is required to provide an increase in plasma volume for the growing fetus. The mechanisms responsible for this Na retention are not clear. In the first study, we generated a renal tubule protein profile indicating α ENaC as the only sodium transport protein upregulated in mid and late pregnancy. To determine the in vivo activity of ENaC we conducted in vivo studies in late pregnant rats (day 18-20) and virgin rats to measure the natriuretic response to ENaC blockade (with benzamil). The in vivo activity of ENaC (UNaV post benzamil - UNaV post vehicle) was markedly …
Systemic And Microcirculatory Effects Of Hboc-201: A Hemoglobin-Based Oxygen Carrier, Bjorn Song
Systemic And Microcirculatory Effects Of Hboc-201: A Hemoglobin-Based Oxygen Carrier, Bjorn Song
Theses and Dissertations
Top-loading This study compared the effects on oxygen (O2) transport of four fluids: 5.9% human serum albumin (HSA) a non-O2 carrying iso-oncotic solution (volume control);HBOC-201 (Hemopure, Biopure Corp., Cambridge, MA); MP50, HBOC-201 with a P50 of 18 mmHg; and lastly LP50, an HBOC-201 with P50 of 17 mmHg and higher viscosity (4 cP). It has been proposed that HBOC with a higher O2 affinity and a viscosity closer to that of whole blood will cause less vasoconstriction and thus a lower MAP than Hemopure (P50 = 40 mmHg and 2.2 cP). Intravital microscopic measurements were made on the spinotrapezius muscle …
The Expression Of Matrix Metalloproteinase-9 And -2 In Olfactory Injury And Recovery, Stephen Bakos
The Expression Of Matrix Metalloproteinase-9 And -2 In Olfactory Injury And Recovery, Stephen Bakos
Theses and Dissertations
The olfactory system has the remarkable capacity for neurogenesis following injury. However, the molecular mechanisms important for reinnervation of the olfactory bulb (OB) remain unknown. The matrix metalloproteinases (MMPs) are important components in many central nervous system (CNS) injury paradigms, yet remain unexplored in olfactory injury and recovery. To address the role of MMPs, the temporal expressions of MMP-9 and MMP-2 were examined in 3 olfactory injury models: nerve transection (NTx), methyl bromide gas (MeBr) exposure, and nerve transection with Teflon barrier (NTx-TB). Each injury model represents a different degree of olfactory injury and neuronal recovery. In NTx, sensory axons …
In Vivo Measurement Of Rat Skeletal Muscle Oxygen Consumption Following Brief Periods Of Ischemia With Reperfusion As Assessed By Phosphorescence Quenching Microscopy, William Nugent
Theses and Dissertations
Brief periods of skeletal muscle ischemia (ischemic pre-conditioning) alter cellular metabolism in a way that confers protection over subsequent ischemic episodes. The mechanisms behind this effect have been studied indirectly through assays for the byproducts of ATP synthesis and in vitro studies of cellular signaling cascades and ROS generation. There have been no direct, in vivo assessments of the changes in respiration during reperfusion. We employed phosphorescence quenching microscopy in conjunction with a flow-arrest technique to assess the influences of external, pressure-induced 1- to 10-min focal ischemia on interstitial oxygenation (PISFO2) and the consumption of oxygen (VO2) in spinotrapezius muscles …
Discovery Of A Novel Ccr5 Antagonist As An Effective Therapeutic Agent For Prostate Cancer, Tasrif Ahmed
Discovery Of A Novel Ccr5 Antagonist As An Effective Therapeutic Agent For Prostate Cancer, Tasrif Ahmed
Theses and Dissertations
Previously, the CCR5 receptor was found to be a good target for treating prostate cancer (PCa). Dr. Yan Zhang’s laboratory designed several CCR5 antagonists, which were screened for their inhibitory effect on the growth and invasion of the M12, DU145 and PC-3 PCa cell lines. Primary in vitro screening showed one compound (Drug 17) significantly inhibited the proliferation of PCa cells at 1μM concentration, with a half-maximal inhibitory concentration of 237.68 nM. Further in vitro assays including a proliferation, cytotoxicity and invasion assay confirmed the inhibitory effect of drug 17. The physiological effect of drug 17 was tested by the …
Characterization And Crystallization Of The Mycobacterium Tuberculosis Trmd, Zohal Hamidi
Characterization And Crystallization Of The Mycobacterium Tuberculosis Trmd, Zohal Hamidi
Theses and Dissertations
One third of the world’s population is affected by Tuberculosis (TB), a disease caused by infection with Mycobacterium tuberculosis (MtB). The emergence of multidrug-resistant MtB makes this disease a major public health concern. New agents are needed to treat TB infections in a manner that circumvents existing pathways of resistance. One strategy is to target the organism at the translational level by inhibiting vital modifications of RNA. One gene responsible for these modifications is the tRNA (guanosine-1)-methyltransferase, trmD, which has been shown to be essential in several bacteria. The eukaryotic and bacterial m1G methyltransferases are structurally dissimilar, making this enzyme …
The Effect Of Cobalt Protoporphyrin And Cobalt Chloride On Heme Oxygenase Expression And Protection From Deoxycholate-Induced Apoptosis, Tina Lawson
Theses and Dissertations
The inner surface of the stomach is lined by a mucous membrane known as the gastric mucosa. The integrity of the gastric mucosa is critical for protecting the stomach from the low pH and proteolytic environment within the lumen. Both clinically and experimentally, exposure of gastric mucosal cells to bile salts is known to cause injury. Bile salts present in duodenogastric reflux are thought to play a significant role in gastric ulcer formation and alkaline gastritis. In vitro, studies using physiologic concentrations of the secondary bile salt, deoxycholic acid, indicate that bile salts can induce apoptosis in cultured human gastric …
Molecular Mechanisms Involved Involved In The Interaction Effects Of Hcv And Ethanol On Liver Cirrhosis, Ryan Fassnacht
Molecular Mechanisms Involved Involved In The Interaction Effects Of Hcv And Ethanol On Liver Cirrhosis, Ryan Fassnacht
Theses and Dissertations
The leading causes of liver disease are Hepatitis C virus infection and chronic alcohol abuse. Alcohol accelerates liver disease in HCV but the mechanisms are poorly understood. The identification of molecular gene expression profiles on human liver tissue was performed using microarrays. Samples were obtained from alcoholic-cirrhotic, HCV-cirrhotic, HCV/alcohol-cirrhotic and control non-cirrhotic liver tissue. Probe set expression summaries were calculated using RMA. Probe set level linear models were fit where probe set expression was modeled by HCV status, alcohol status, and the interaction between HCV and Alcohol. HCV cirrhosis was associated with up-regulation of genes related to viral and immune …
Role Of Capsule In The Interaction Of Porphyromonas Gingivalis With Host, Amrita Singh
Role Of Capsule In The Interaction Of Porphyromonas Gingivalis With Host, Amrita Singh
Theses and Dissertations
Periodontal disease is a chronic oral disease that is triggered by bacteria. One of these bacteria is Porphyromonas gingivalis. Some strains of P. gingivalis produce capsule, however, so far the role of capsule in the interactions with host cells in P. gingivalis is not well understood. Here, we investigated the contribution of capsule to triggering host response as well as its protective role on bacterial internalization by host cells with subsequent killing. qRT-PCR analysis showed more upregulation of expression of various groups of genes in macrophages challenged with the non-capsulated strain than in those challenged with the capsulated one with …
Signaling Pathways Coupled To Melatonin Receptor Mt1 In Gastric Smooth Muscle, Rashad Ahmed
Signaling Pathways Coupled To Melatonin Receptor Mt1 In Gastric Smooth Muscle, Rashad Ahmed
Theses and Dissertations
The Melatonin, a close derivative of serotonin, is involved in physiological regulation of circadian rhythms. In the gastrointestinal (GI) system, melatonin exhibits endocrine, paracrine and autocrine actions and is implicated in the regulation of GI motility. Generally, melatonin actions oppose the stimulatory actions of serotonin on motility. However, it is not known whether melatonin can also act directly on GI smooth muscle cells. The aim of the present study was to determine the expression of melatonin receptors in smooth muscle and identify their signaling pathways. Muscle cells were isolated from rabbit distal stomach by enzymatic digestion, filtration and centrifugation and …
The Clinical Utility Of Cardiopulmonary Exercise Testing In Patients With Suspected Myocardial Ischemia, Sherry Pinkstaff
The Clinical Utility Of Cardiopulmonary Exercise Testing In Patients With Suspected Myocardial Ischemia, Sherry Pinkstaff
Theses and Dissertations
Heart disease is a major cause of morbidity and mortality in the United States with coronary artery disease (CAD) representing more than half of all cardiovascular events. Stable patients presenting with symptoms suggestive of CAD are likely to undergo either an exercise ECG and/or imaging study as a first line diagnostic assessment. A cardiopulmonary exercise test (CPX) is an ECG stress test plus ventilatory gas analysis. Recently CPX has been used to detect exercise-induced myocardial ischemia suggestive of underlying CAD. Currently there are a number of diagnostic tests available for the identification of CAD with the most widely used being …
Opioid Addiction And Pregnancy: Potential Effects Of Substitution Therapies On Developmental Myelination, Andrew Eschenroeder
Opioid Addiction And Pregnancy: Potential Effects Of Substitution Therapies On Developmental Myelination, Andrew Eschenroeder
Theses and Dissertations
While most cells of the central nervous system (CNS) express opioid receptors, the role of the endogenous opioid system in CNS development remains poorly understood. Identification of opioid functions during brain maturation is particularly crucial in light of the increasing trend in opioid abuse and the use of opioid drugs during pregnancy. New substitution therapies in pregnant opioid addicts include buprenorphine, a mu opioid receptor partial agonist and kappa opioid receptor antagonist. However, while clinical studies demonstrated buprenorphine efficacy in reducing neonatal withdrawal symptoms, there is a lack of information on the potential effects of this drug on brain development. …
Effect Of Hyaluronidase Treatment On The Structural Integrity Of The Endothelial Glycocalyx Layer, Kristin Simmons
Effect Of Hyaluronidase Treatment On The Structural Integrity Of The Endothelial Glycocalyx Layer, Kristin Simmons
Theses and Dissertations
The endothelial glycocalyx plays an important role as part of the permeability barrier between the blood and the interstitium. In this study, we used different sized fluorescently labeled dextran molecules to determine the size of the macromolecular exclusion zone in capillaries. The width of the exclusion zone was calculated as one half the difference between the anatomic luminal diameter, as determined by transillumination, and the width of a fluorescent dextran column. During the first hour after systemic injection of labeled dextrans, neither 70 kDa dextran (Dextran 70) nor 500 kDa dextran (Dextran 500) labeled with the anionic fluorescein isothiocyanate (FITC) …
Role Of Neutrophils In Enhancing Vascular Reactivity To Angiotensin Ii In Preeclampsia, Nikita Mishra
Role Of Neutrophils In Enhancing Vascular Reactivity To Angiotensin Ii In Preeclampsia, Nikita Mishra
Theses and Dissertations
Women with preeclampsia have enhanced vascular reactivity to Angiotensin II (Ang II) and extensive vascular infiltration of neutrophils. The primary mechanism to enhance vessel reactivity is RhoA kinase that phosphorylates MYPT1 to inhibit myosin light chain (MLC) phosphatase. Therefore, MLCs remain phosphorylated and increase sensitivity to calcium. Neutrophils release reactive oxygen species (ROS), which can activate this pathway, so we hypothesized that neutrophils would enhance vessel reactivity to Ang II. Omental vessels from normal pregnant women were used to study vascular reactivity. Ang II dose response (0.001-10µM) was significantly enhanced with perfusion of neutrophils (<2000/mm3, activated with IL-8) or ROS. Addition of superoxide dismutase (SOD)/Catalase to quench ROS or 3µM Y-27632, a specific RhoA kinase inhibitor, blocked enhancement. Vascular smooth muscle expression of pMYPT1 and pMLC in cell culture was significantly increased by neutrophils or ROS. The increase was prevented by Y-27632. RhoA kinase activity assay showed a 3-fold increase in RhoA kinase activity in omental vessels treated with ROS. Similarly, ROS also enhanced vessel reactivity to another vasoconstrictor, norepinephrine, via RhoA kinase. In preeclamptic women, increased neutrophil infiltration is associated with increased vascular expression and production of matrix metalloproteinase-1 (MMP-1). MMP-1 activates protease activated receptor-1 (PAR-1), which could cause endothelial endothelin-1 release, so we considered a novel hypothesis that MMP-1 might cause vasoconstriction and enhance vessel reactivity to Ang II via PAR-1. Omental vessels perfused with activated MMP-1 (0.025-25ng/ml) showed dose-dependent vasoconstriction. Perfusion of activated MMP-1 (2.5ng/ml) significantly enhanced dose response to angiotensin II. MMP-1 mediated vasoconstriction and enhanced vessel reactivity to Ang II was abolished by co-perfusion of 10µM SCH-79797, a specific PAR-1 blocker, and by 5µM BQ-123, a specific endothelin-1 type A receptor blocker. These data are the first to show that activated neutrophils enhance vascular reactivity to Ang II via ROS and the RhoA kinase pathway. They are also the first to show that MMP-1 induces vasoconstriction and enhances vessel reactivity to Ang II. Thus, vascular neutrophil infiltration leading to ROS and MMP-1 generation could be an important mechanism for hypertension in preeclampsia.
Scribble: A Potential Dual Kinase Inhibitor, Steven Christofakis
Scribble: A Potential Dual Kinase Inhibitor, Steven Christofakis
Theses and Dissertations
Extracellular signal-regulated kinases (ERKs) modulate cellular activities in response to extracellular stimuli and play important biological roles. Thus, perturbed kinase pathways induce pathological conditions, such as tumor development. Rit, a novel member of the Ras family GTPases, activase ERK6, and its over-expression confers tumorigenicity. We hypothesized the presence of scaffolding molecules specific to ERK6, similar to other known MAP kinases. We performed yeast two-hybrid assays using ERK6 as bait, and Scribble was identified as a binding partner. Scribble contains 16 LRR domains and four PDZ domains. We performed immunoprecipitation (IP) assays and discovered ERK2 as another binding partner. Surprisingly, no …
The Development Of A Novel Multi-Dimensional Product For Wound Healing Applications, Necrisha Roach
The Development Of A Novel Multi-Dimensional Product For Wound Healing Applications, Necrisha Roach
Theses and Dissertations
A characteristic feature of chronic wounds is a prolonged inflammatory response as well as susceptibility to infection. Studies have shown that during the inflammatory response, there is a significant increase in the levels of neutrophil-derived enzymes. The purpose of this work was to determine whether the anionic macromolecule polystyrene sulfonate (PSS) and five of its salt forms, namely PSS-calcium, PSS-chlorhexidine, PSS-doxycycline, PSS-glutathione and PSS-silver are able to inhibit the activity of three of the enzymes whose levels are elevated in chronic wounds: elastase, cathepsin G and myeloperoxidase. In addition to the enzyme inhibition study, the various formulations’ antimicrobial properties were …
Neutrophil Products Control The Expression Of Progesterone Receptors And Matrix Metalloproteinase-1 In The Decidual And Myometrium And Are Possible Regulators Of Premature Labor, Anna Solotskaya
Theses and Dissertations
Neutrophils infiltrate myometrium and decidual tissue prior to parturition. Activated neutrophils release reactive oxygen species (ROS) and tumor necrosis factor α (TNFα), which might increase expression of pro-labor genes such as matrix metalloproteinase-1 (MMP-1), progesterone receptor (PR) A/B ratio, and cause demethylation of DNA. These changes might cause labor. Decidual tissue was obtained from consented, healthy women at term (37+ weeks of gestation) not in labor (no contractions, without cervical effacement), term labor and preterm labor (under 37 weeks of pregnancy). Decidual and myometrial cells in culture were treated with (1) ROS, (2) TNFα, or (3) 5-aza-2’-deoxycytidine. Total RNA was …
Small Molecule Inhibitors Of Mapk And Pi3k Pathways Enhance Mda-7 Lethality In Renal Cell Carcinoma, Patrick Eulitt
Small Molecule Inhibitors Of Mapk And Pi3k Pathways Enhance Mda-7 Lethality In Renal Cell Carcinoma, Patrick Eulitt
Theses and Dissertations
Renal cell carcinoma accounted for an estimated 57,760 new cases and estimated 12,980 deaths in the United States in 2009. Current treatment options for systemic renal cell carcinoma yield markedly low response percentages; however, recent cytokine therapy experiments have produced promising results. A novel adenovirus, Ad.5/3-mda-7, has been synthesized to efficiently infect renal cancer cells with the mda-7 gene. This gene encodes for the cytokine MDA-7/IL-24 that has the ability to specifically target transformed cells. Assays performed with this adenovirus resulted in an increased percentage of cell death in renal cancer cells when compared to infection with Ad.5/3-cmv empty vector. …