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2010

Inflammation

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Role Of Amyloid Beta Assembly State In The Human Immune Response, Deepa Viswanathan Dec 2010

Role Of Amyloid Beta Assembly State In The Human Immune Response, Deepa Viswanathan

Dissertations

Alzheimer’s disease (AD) is a slowly progressing neurodegenerative disease that leads to dementia. Histopathological hallmarks that characterize AD are senile plaques formed by extracellular deposition of Amyloid beta (Aβ) peptide and intracellular aggregates of hyperphosphorylated tau protein. The plaques, which are found in the brain parenchyma, comprise both 40 and 42 residue Aβ. Aggregation of Aβ is an established pathogenic mechanism in AD, but little is known about the initiation of this process in vivo. Several studies have revealed significant inflammatory markers such as activated microglia and cytokines surrounding the plaques. Plaques are a hallmark of AD, but they are …


The Role Of Muc1 Splice Variants In Dry Eye And Inflammation., Yoannis Imbert-Fernandez Dec 2010

The Role Of Muc1 Splice Variants In Dry Eye And Inflammation., Yoannis Imbert-Fernandez

Electronic Theses and Dissertations

Mucin 1 (MUC1) is a plasma membrane-bound glycoprotein that plays a protective role in corneal epithelial cells. Two full-length splice variants of MUCl: MUCl/B and MUCl/A, that differ by the inclusion of 27 bp from intron 1 and a SNP in MUCl/A, but have identical C-terminal cytoplasmic domain (CD) sequences, were identified in human conjunctival tissue. I tested the hypothesis that MUC1 splice variants are key immunoregulators that act on the ocular surface to protect the ocular surface from inflammation and that their expression correlates with dry eye status. The expression of MUC1/A and MUCl/B splice variant was examined in …


Acetate Causes Alcohol Hangover Headache In Rats., Christina R Maxwell, Rebecca Jay Spangenberg, Jan B Hoek, Stephen D Silberstein, Michael L Oshinsky Dec 2010

Acetate Causes Alcohol Hangover Headache In Rats., Christina R Maxwell, Rebecca Jay Spangenberg, Jan B Hoek, Stephen D Silberstein, Michael L Oshinsky

Department of Neurology Faculty Papers

BACKGROUND: The mechanism of veisalgia cephalgia or hangover headache is unknown. Despite a lack of mechanistic studies, there are a number of theories positing congeners, dehydration, or the ethanol metabolite acetaldehyde as causes of hangover headache.

METHODS: We used a chronic headache model to examine how pure ethanol produces increased sensitivity for nociceptive behaviors in normally hydrated rats.

RESULTS: Ethanol initially decreased sensitivity to mechanical stimuli on the face (analgesia), followed 4 to 6 hours later by inflammatory pain. Inhibiting alcohol dehydrogenase extended the analgesia whereas inhibiting aldehyde dehydrogenase decreased analgesia. Neither treatment had nociceptive effects. Direct administration of acetate …


Dietary Milk Fat Globule Membrane Reduces The Incidence Of Aberrant Crypt Foci In Fischer-344 Rats And Provides Protections Against Gastrointestinal Stress In Mice Treated With Lipopolysaccharide, Dallin R. Snow Dec 2010

Dietary Milk Fat Globule Membrane Reduces The Incidence Of Aberrant Crypt Foci In Fischer-344 Rats And Provides Protections Against Gastrointestinal Stress In Mice Treated With Lipopolysaccharide, Dallin R. Snow

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Milk fat globule membrane surrounds the fat droplets of milk. It is a biopolymer containing primarily membrane glycoproteins and polar lipids which contribute to its properties as a possible neutraceutical. The aims of the studies were to determine if dietary milk fat globule membrane: (1) confers protection against colon carcinogenesis; and (2) promotes gut mucosal integrity while decreasing inflammation compared to diets containing corn oil or anhydrous milk fat.

Aim 1. Three dietary treatments differing only in the fat source were formulated: (1) AIN-76A, corn oil; (2) AIN-76A, anhydrous milk fat; and (3) AIN-76A, 50% milk fat globule membrane, 50% …


Tobacco-Induced Changes To Porphyromonas Gingivalis Gene Expression, Phenotype And Host-Pathogen Interactions., Juhi Bagaitkar Dec 2010

Tobacco-Induced Changes To Porphyromonas Gingivalis Gene Expression, Phenotype And Host-Pathogen Interactions., Juhi Bagaitkar

Electronic Theses and Dissertations

Tobacco smoke is a strong and independent risk factor for several chronic systemic diseases and also increases susceptibility to a multitude of bacterial infections, including periodontal infections. Periodontitis is a chronic inflammatory disease of the supporting tissues of the periodontium caused by its chief etiological agent, Porphyromonas gingivalis . Smokers are more prone to persistent infections by P. gingivalis , and harbor higher numbers of P. gingivalis than non-smokers. However, smokers show reduced clinical signs of inflammation compared to non-smokers, making diagnosis of periodontal disease in smokers problematic. While several studies delineate the different mechanisms of how tobacco smoke alters …


A Combined Phase I And Ii Open Label Study On The Effects Of A Seaweed Extract Nutrient Complex On Osteoarthritis, Stephen P. Myers, Joan O'Connor, J Helen Fitton, Lyndon O. Brooks, Margaret Rolfe, Paul A. Connellan, Hans Wohlmuth, Phillip A. Cheras, Carol A. Morris Nov 2010

A Combined Phase I And Ii Open Label Study On The Effects Of A Seaweed Extract Nutrient Complex On Osteoarthritis, Stephen P. Myers, Joan O'Connor, J Helen Fitton, Lyndon O. Brooks, Margaret Rolfe, Paul A. Connellan, Hans Wohlmuth, Phillip A. Cheras, Carol A. Morris

Dr Lyndon O Brooks

Background: Isolated fucoidans from brown marine algae have been shown to have a range of anti-inflammatory effects. Purpose: This present study tested a Maritech® extract formulation, containing a blend of extracts from three different species of brown algae, plus nutrients in an open label combined phase I and II pilot scale study to determine both acute safety and efficacy in osteoarthritis of the knee. Patients and methods: Participants (n = 12, five females [mean age, 62 ± 11.06 years] and seven males [mean age, 57.14 ± 9.20 years]) with a confirmed diagnosis of osteoarthritis of the knee were randomized to …


T-Lymphocyte Responses To Intestinally Absorbed Antigens Can Contribute To Adipose Tissue Inflammation And Glucose Intolerance During High Fat Feeding, Yuehui Wang, Jianing Li, Lihua Tang, Yu Wang, Richard Charnigo, Willem De Villiers, Erik Eckhardt Nov 2010

T-Lymphocyte Responses To Intestinally Absorbed Antigens Can Contribute To Adipose Tissue Inflammation And Glucose Intolerance During High Fat Feeding, Yuehui Wang, Jianing Li, Lihua Tang, Yu Wang, Richard Charnigo, Willem De Villiers, Erik Eckhardt

Internal Medicine Faculty Publications

BACKGROUND: Obesity is associated with inflammation of visceral adipose tissues, which increases the risk for insulin resistance. Animal models suggest that T-lymphocyte infiltration is an important early step, although it is unclear why these cells are attracted. We have recently demonstrated that dietary triglycerides, major components of high fat diets, promote intestinal absorption of a protein antigen (ovalbumin, "OVA"). The antigen was partly transported on chylomicrons, which are prominently cleared in adipose tissues. We hypothesized that intestinally absorbed gut antigens may cause T-lymphocyte associated inflammation in adipose tissue.

METHODOLOGY/PRINCIPAL FINDINGS: Triglyceride absorption promoted intestinal absorption of OVA into adipose tissue, …


Activation Of The Innate Immune Response By The Alzheimer's Amyloid Beta Protein Via Toll-Like Receptors, Udan Lourdes Maria Oct 2010

Activation Of The Innate Immune Response By The Alzheimer's Amyloid Beta Protein Via Toll-Like Receptors, Udan Lourdes Maria

Dissertations

Alzheimer’s Disease (AD) is the most common form of neurodegenerative disease characterized by the generation and deposition of amyloid beta plaques and the formation of neurofibrillary tangles. A wealth of data now demonstrate that inflammation is a prominent feature in AD pathology and a potential therapeutic target for the treatment and prevention of the disease. The emergence of evidence linking amyloid beta protein (Aβ), the primary component of senile plaques, to inflammation has led to new insights into understanding AD pathology. Aβ, a protein fragment resulting from cleavage of human amyloid precursor protein (APP), primarily exists in two forms: a …


Proteoglycans In Health And Disease: Novel Regulatory Signaling Mechanisms Evoked By The Small Leucine-Rich Proteoglycans., Renato V. Iozzo, Liliana Schaefer Oct 2010

Proteoglycans In Health And Disease: Novel Regulatory Signaling Mechanisms Evoked By The Small Leucine-Rich Proteoglycans., Renato V. Iozzo, Liliana Schaefer

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The small leucine-rich proteoglycans (SLRPs) are involved in many aspects of mammalian biology, both in health and disease. They are now being recognized as key signaling molecules with an expanding repertoire of molecular interactions affecting not only growth factors, but also various receptors involved in controlling cell growth, morphogenesis and immunity. The complexity of SLRP signaling and the multitude of affected signaling pathways can be reconciled with a hierarchical affinity-based interaction of various SLRPs in a cell- and tissue-specific context. Here, we review this interacting network, describe new relationships of the SLRPs with tyrosine kinase and Toll-like receptors and critically …


Association Between Chronic Liver And Colon Inflammation During The Development Of Murine Syngeneic Graft-Versus-Host Disease, Jason Anthony Brandon, Jacqueline Perez-Rodriguez, C. Darrell Jennings, Donald A. Cohen, Vishal J. Sindhava, Subbarao Bondada, Alan M. Kaplan, J. Scott Bryson Sep 2010

Association Between Chronic Liver And Colon Inflammation During The Development Of Murine Syngeneic Graft-Versus-Host Disease, Jason Anthony Brandon, Jacqueline Perez-Rodriguez, C. Darrell Jennings, Donald A. Cohen, Vishal J. Sindhava, Subbarao Bondada, Alan M. Kaplan, J. Scott Bryson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The murine model of cyclosporine A (CsA)-induced syngeneic graft-versus-host disease (SGVHD) is a bone marrow (BM) transplantation model that develops chronic colon inflammation identical to other murine models of CD4+ T cell-mediated colitis. Interestingly, SGVHD animals develop chronic liver lesions that are similar to the early peribiliary inflammatory stages of clinical chronic liver disease, which is frequently associated with inflammatory bowel disease (IBD). Therefore, studies were initiated to investigate the chronic liver inflammation that develops in the SGVHD model. To induce SGVHD, mice were lethally irradiated, reconstituted with syngeneic BM, and treated with CsA. All of the SGVHD animals …


Synthesis And In Vitro Binding Of N,N-Dialkyl-2-Phenylindol-3-Ylglyoxylamides For The Peripheral Benzodiazepine Binding Sites, T. P. Homes, F. Mattner, Paul A. Keller, A. Katsifis Aug 2010

Synthesis And In Vitro Binding Of N,N-Dialkyl-2-Phenylindol-3-Ylglyoxylamides For The Peripheral Benzodiazepine Binding Sites, T. P. Homes, F. Mattner, Paul A. Keller, A. Katsifis

Paul Keller

A series of N,N-dialkyl-2-phenylindol-3-ylglyoxylamides bearing the halogens iodine and bromine were synthesised and their binding affinity for the peripheral benzodiazepine binding sites (PBBS) in rat kidney mitochondrial membranes were evaluated using [3H]-PK11195. Central benzodiazepine receptor (CBR) affinities were also evaluated in rat cortices using 3H-flumazenil to determine their selectivity for PBBS over CBR. The tested compounds had PBBS binding affinities (IC50) ranging from 7.86 nM to 618 nM, with all compounds showing high selectivity over the CBR (CBR IC50 > 5000 nM). Among the 12 compounds tested, those with a diethylamide group were the most potent. The highest affinity iodinated PBBS …


Polymorphisms In The Macrophage Migration Inhibitory Factor Gene And Bone Loss In Postmenopausal Women, George A. Kuchel, Anne M. Kenny Aug 2010

Polymorphisms In The Macrophage Migration Inhibitory Factor Gene And Bone Loss In Postmenopausal Women, George A. Kuchel, Anne M. Kenny

UCHC Articles - Research

Osteoporosis is a severe condition in postmenopausal women and a common cause of fracture. Osteoporosis is a complex disease with a strong genetic impact, but susceptibility is determined by many genes with modest effects and environmental factors. Only a handful of genes consistently associated with osteoporosis have been identified so far. Inflammation affects bone metabolism by interfering with the interplay between bone resorption and formation, and many inflammatory mediators are involved in natural bone remodeling. The cytokine macrophage migration inhibitory factor (MIF) has been shown to affect bone density in rodents, and polymorphisms in the human MIF promoter are associated …


Marital Behavior, Oxytocin, Vasopressin, And Wound Healing, Jean-Phillipe Gouin, Jeffrey R. Stowell, C. Sue Carter, Hossein Pournajafi-Nazarloo, Ronald Glasser, William B. Malarkey, Timothy J. Loving, Janice K. Kiecoltglaser Aug 2010

Marital Behavior, Oxytocin, Vasopressin, And Wound Healing, Jean-Phillipe Gouin, Jeffrey R. Stowell, C. Sue Carter, Hossein Pournajafi-Nazarloo, Ronald Glasser, William B. Malarkey, Timothy J. Loving, Janice K. Kiecoltglaser

Jeffrey R. Stowell

Animal studies have implicated oxytocin and vasopressin in social bonding, physiological stress responses, and wound healing. In humans, endogenous oxytocin and vasopressin levels covary with perceptions of relationship quality, marital behaviors, and physiological stress responses. To investigate relationships among marital behavior, oxytocin, vasopressin, and wound healing, and to determine the characteristics of individuals with the highest neuropeptide levels, 37 couples were admitted for a 24-hour visit in a hospital research unit. After small blister wounds were created on their forearm, couples participated in a structured social support interaction task. Blister sites were monitored daily following discharge to assess wound repair …


Transcriptional Suppression Of Mir-29b-1/Mir-29a Promoter By C-Myc, Hedgehog, And Nf-Kappab., Justin L. Mott, Satoshi Kurita, Sophie C. Cazanave, Steven F. Bronk, Nathan W. Werneburg, Martin E. Fernandez-Zapico Aug 2010

Transcriptional Suppression Of Mir-29b-1/Mir-29a Promoter By C-Myc, Hedgehog, And Nf-Kappab., Justin L. Mott, Satoshi Kurita, Sophie C. Cazanave, Steven F. Bronk, Nathan W. Werneburg, Martin E. Fernandez-Zapico

Journal Articles: Biochemistry & Molecular Biology

MicroRNAs regulate pathways contributing to oncogenesis, and thus the mechanisms causing dysregulation of microRNA expression in cancer are of significant interest. Mature mir-29b levels are decreased in malignant cells, and this alteration promotes the malignant phenotype, including apoptosis resistance. However, the mechanism responsible for mir-29b suppression is unknown. Here, we examined mir-29 expression from chromosome 7q32 using cholangiocarcinoma cells as a model for mir-29b downregulation. Using 5' rapid amplification of cDNA ends, the transcriptional start site was identified for this microRNA locus. Computational analysis revealed the presence of two putative E-box (Myc-binding) sites, a Gli-binding site, and four NF-kappaB-binding sites …


Marital Behavior, Oxytocin, Vasopressin, And Wound Healing, Jean-Phillipe Gouin, Jeffrey R. Stowell, C. Sue Carter, Hossein Pournajafi-Nazarloo, Ronald Glasser, William B. Malarkey, Timothy J. Loving, Janice K. Kiecoltglaser Aug 2010

Marital Behavior, Oxytocin, Vasopressin, And Wound Healing, Jean-Phillipe Gouin, Jeffrey R. Stowell, C. Sue Carter, Hossein Pournajafi-Nazarloo, Ronald Glasser, William B. Malarkey, Timothy J. Loving, Janice K. Kiecoltglaser

Faculty Research and Creative Activity

Animal studies have implicated oxytocin and vasopressin in social bonding, physiological stress responses, and wound healing. In humans, endogenous oxytocin and vasopressin levels covary with perceptions of relationship quality, marital behaviors, and physiological stress responses. To investigate relationships among marital behavior, oxytocin, vasopressin, and wound healing, and to determine the characteristics of individuals with the highest neuropeptide levels, 37 couples were admitted for a 24-hour visit in a hospital research unit. After small blister wounds were created on their forearm, couples participated in a structured social support interaction task. Blister sites were monitored daily following discharge to assess wound repair …


Arsenic In Drinking Water Causes Gene Expression Changes In The Liver Related To Inflammation And Metabolic Dysfunction And Accelerates Atherosclerosis In Apoe-/-Mice, Matthew R. Zajack Aug 2010

Arsenic In Drinking Water Causes Gene Expression Changes In The Liver Related To Inflammation And Metabolic Dysfunction And Accelerates Atherosclerosis In Apoe-/-Mice, Matthew R. Zajack

Electronic Theses and Dissertations

Arsenic exposure in drinking-water is a significant worldwide health problem. It causes adverse human health effects, such as cancer, increases the risks for others such as cardiovascular disease, and accelerates atherosclerosis. In this study, we analyze arsenic-induced gene expression changes in the liver of ApoE-knockout mice given 49 ppm arsenic in drinking-water. We hypothesize chronic arsenic exposure accelerates atherosclerosis by disrupting liver homeostasis, causing aberrant gene expression changes. Networks revealed hubs on 3 stress-response MAP kinase pathways, ERK, JNK, and p38. Pathways revealed mitochondrial dysfunction and oxidative phosphorylation enrichment from the gene set. Transcription factor binding site analysis revealed specific …


Delayed Wound Healing: Can Exercise Accelerate It?, K Todd Keylock, Hilary Young Jul 2010

Delayed Wound Healing: Can Exercise Accelerate It?, K Todd Keylock, Hilary Young

International Journal of Exercise Science

Poorly healing wounds affect millions around the world, yet preventive methods and low-cost, effective treatments are few. Wounds heal quickly through well-coordinated phases in those who are healthy and active but can become chronically nonhealing as a result of disease and inactivity. Recently it has been reported that moderate aerobic exercise accelerated healing rates in the aged. High levels of inflammation are known to delay wound healing, and aging and disease are associated with chronically increased inflammation. Therefore, exercise may help speed healing by reducing inflammation to healthier levels not only in the aged, but also in other populations with …


Prolongation Of Carrageenan-Induced Inflammation In Human Colonic Epithelial Cells By Activation Of An Nfκb-Bcl10 Loop, Alip Borthakur, Sumit Bhattacharyya, Arivarasu N. Anbazhagan, Anoop Kumar, Pradeep K. Dudeja, Joanne K. Tobacman Jul 2010

Prolongation Of Carrageenan-Induced Inflammation In Human Colonic Epithelial Cells By Activation Of An Nfκb-Bcl10 Loop, Alip Borthakur, Sumit Bhattacharyya, Arivarasu N. Anbazhagan, Anoop Kumar, Pradeep K. Dudeja, Joanne K. Tobacman

Clinical & Translational Sciences

Carrageenan, a sulfated polysaccharide that is widely used as a food additive, induces inflammatory responses in animal models and human cells. The carrageenan-induced inflammatory cascades involve tolllike receptor (TLR)4- and B-cell leukemia/lymphoma (BCL)10-dependent activation of NF-κB, leading to increased IL-8 production. Translocations involving BCL10 in the mucosa-associated lymphoid tissue (MALT) lymphomas are associated with constitutive activation of NF-κB. This report presents a mechanism by which carrageenan exposure leads to prolonged activation of both BCL10 and NF-κB in human colonic epithelial cells. Study findings demonstrate that nuclear RelA and RelB bind to an NF-κB binding motif in the BCL10 promoter in …


The Relationship Between Fam5c Snp (Rs10920501) Variability, Metabolic Syndrome, And Inflammation, In Women With Coronary Heart Disease, Jennifer L. Cline Jun 2010

The Relationship Between Fam5c Snp (Rs10920501) Variability, Metabolic Syndrome, And Inflammation, In Women With Coronary Heart Disease, Jennifer L. Cline

USF Tampa Graduate Theses and Dissertations

The leading cause of death among women is coronary heart disease (CHD), a multifactorial disease with polygenic heritability estimated at 50%. Polymorphisms in the family with sequence similarity 5, member C’ (

FAM5C) gene have been associated with myocardial infarction (MI), and one single-nucleotide polymorphism (SNP) has partially accounted for linkage in an acute coronary syndrome subset. The linkage peak on FAM5C corresponds directly with a quantitative trait locus for the inflammatory biomarker monocyte chemoattractant protein 1, as well as a linkage peak to metabolic syndrome (MetS). Metabolic syndrome increases the risk of developing CHD, and MI has been positively …


The Relationship Between Fam5c Snp (Rs10920501) Variability, Metabolic Syndrome, And Inflammation, In Women With Coronary Heart Disease, Jennifer L. Cline Jun 2010

The Relationship Between Fam5c Snp (Rs10920501) Variability, Metabolic Syndrome, And Inflammation, In Women With Coronary Heart Disease, Jennifer L. Cline

USF Tampa Graduate Theses and Dissertations

The leading cause of death among women is coronary heart disease (CHD), a multifactorial disease with polygenic heritability estimated at 50%. Polymorphisms in the family with sequence similarity 5, member C' (FAM5C) gene have been associated with myocardial infarction (MI), and one single-nucleotide polymorphism (SNP) has partially accounted for linkage in an acute coronary syndrome subset. The linkage peak on FAM5C corresponds directly with a quantitative trait locus for the inflammatory biomarker monocyte chemoattractant protein 1, as well as a linkage peak to metabolic syndrome (MetS). Metabolic syndrome increases the risk of developing CHD, and MI has been …


Lifecourse Socioeconomic Trajectories And C-Reactive Protein Levels In Young Adults: Findings From A Brazilian Birth Cohort, Aydin Nazmi, I. O. Oliveira, Bernardo L. Horta, D. P. Gigante, Cesar G, Victora May 2010

Lifecourse Socioeconomic Trajectories And C-Reactive Protein Levels In Young Adults: Findings From A Brazilian Birth Cohort, Aydin Nazmi, I. O. Oliveira, Bernardo L. Horta, D. P. Gigante, Cesar G, Victora

Aydin Nazmi

Socioeconomic factors are associated with cardiovascular disease. C-reactive protein (CRP) is increasingly implicated as a candidate linking conventional risk factors and atherosclerosis. The impact of early- and later-life socioeconomic status (SES) on CRP levels has not been widely investigated and a handful of studies from high-income countries are inconsistent. We set out to examine the associations between lifecourse socioeconomic indicators (family income at birth, maternal education, family income at age 23 and own education) on CRP levels in young adults belonging to the 1982 Pelotas (Brazil) Birth Cohort Study (n = 5914). Early-life SES showed significant and graded associations with …


Acid-Sensing Ion Channels And Pain, Qihai Gu, Lu-Yuan Lee May 2010

Acid-Sensing Ion Channels And Pain, Qihai Gu, Lu-Yuan Lee

Physiology Faculty Publications

Pathophysiological conditions such as inflammation, ischemia, infection and tissue injury can all evoke pain, and each is accompanied by local acidosis. Acid sensing ion channels (ASICs) are proton-gated cation channels expressed in both central and peripheral nervous systems. Increasing evidence suggests that ASICs represent essential sensors for tissue acidosis-related pain. This review provides an update on the role of ASICs in pain sensation and discusses their therapeutic potential for pain management.


Damage-Induced Inflammation And Nociceptive Hypersensitivity In Drosophila Larvae, Daniel T. Babcock May 2010

Damage-Induced Inflammation And Nociceptive Hypersensitivity In Drosophila Larvae, Daniel T. Babcock

Dissertations & Theses (Open Access)

Mounting an effective response to tissue damage requires a concerted effort from a number of systems, including both the immune and nervous systems. Immune-responsive blood cells fight infection and clear debris from damaged tissues, and specialized pain receptors become hypersensitive to promote behavior that protects the damaged area while it heals. To uncover the cellular and molecular mechanisms underlying these processes, we have developed a genetically tractable invertebrate model of damage-induced inflammation and pain hypersensitivity using Drosophila larvae.

To study wound-induced inflammation, we generated transgenic larvae with fluorescent epidermal cells and blood cells (hemocytes). Using live imaging, we monitored the …


Synthesis Of Novel Cannabinoid Ligands And Their Use As Anti-Glioma And Anti-Inflammatory Agents, Steven Neal Gurley May 2010

Synthesis Of Novel Cannabinoid Ligands And Their Use As Anti-Glioma And Anti-Inflammatory Agents, Steven Neal Gurley

Theses and Dissertations (ETD)

Following the discovery of the cannabinoid receptors, research in the field of cannabinoids has grown exponentially over the last two decades. Cannabinoids have been shown to have tremendous therapeutic potential in the treatment of several pathological conditions ranging from inflammation to asthma, multiple sclerosis, Parkinson’s disease, epilepsy, glaucoma, septic shock, hemorrhagic shock, and cancer. Our research has focused on two major conditions for which cannabinoids hold great promise for drug development, namely, cancer and inflammation.

Our focus in the field of cancer has been on the devastatingly lethal brain tumor glioblastoma multiforme. Due to the high expression of the CB2 …


Preeclampsia, Autoimmunity And The At1 Receptor, Roxanna A. Irani May 2010

Preeclampsia, Autoimmunity And The At1 Receptor, Roxanna A. Irani

Dissertations & Theses (Open Access)

Preeclampsia (PE) is a disease of late pregnancy characterized by maternal hypertension and proteinuria. It is associated with preterm delivery and significant perinatal morbidity and mortality. Despite affecting ~7% of first pregnancies, there is no effective screening method to identify women at risk, nor is there a definitive treatment other than delivery of the baby and placenta. Though the pathogenesis of PE remains unclear, an imbalance in the renin-angiotensin and immune systems are thought to be major contributors. Bridging these two concepts, it has recently been shown that women with PE harbor specific autoantibodies: the angiotensin II type 1 receptor …


Effects Of Long-Term Pioglitazone Treatment On Peripheral And Central Markers Of Aging, Eric M. Blalock, Jeremiah T. Phelps, Tristano Pancani, James L. Searcy, Katie L. Anderson, John C. Gant, Jelena Popovic, Margarita G. Avdiushko, Don A. Cohen, Kuey-Chu Chen, Nada M. Porter, Olivier Thibault Apr 2010

Effects Of Long-Term Pioglitazone Treatment On Peripheral And Central Markers Of Aging, Eric M. Blalock, Jeremiah T. Phelps, Tristano Pancani, James L. Searcy, Katie L. Anderson, John C. Gant, Jelena Popovic, Margarita G. Avdiushko, Don A. Cohen, Kuey-Chu Chen, Nada M. Porter, Olivier Thibault

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: Thiazolidinediones (TZDs) activate peroxisome proliferator-activated receptor gamma (PPARgamma) and are used clinically to help restore peripheral insulin sensitivity in Type 2 diabetes (T2DM). Interestingly, long-term treatment of mouse models of Alzheimer's disease (AD) with TZDs also has been shown to reduce several well-established brain biomarkers of AD including inflammation, oxidative stress and Abeta accumulation. While TZD's actions in AD models help to elucidate the mechanisms underlying their potentially beneficial effects in AD patients, little is known about the functional consequences of TZDs in animal models of normal aging. Because aging is a common risk factor for both AD and …


Lifecourse Socioeconomic Trajectories And C-Reactive Protein Levels In Young Adults: Findings From A Brazilian Birth Cohort, Aydin Nazmi, I. O. Oliveira, Bernardo L. Horta, D. P. Gigante, Cesar G, Victora Apr 2010

Lifecourse Socioeconomic Trajectories And C-Reactive Protein Levels In Young Adults: Findings From A Brazilian Birth Cohort, Aydin Nazmi, I. O. Oliveira, Bernardo L. Horta, D. P. Gigante, Cesar G, Victora

Food Science and Nutrition

Socioeconomic factors are associated with cardiovascular disease. C-reactive protein (CRP) is increasingly implicated as a candidate linking conventional risk factors and atherosclerosis. The impact of early- and later-life socioeconomic status (SES) on CRP levels has not been widely investigated and a handful of studies from high-income countries are inconsistent. We set out to examine the associations between lifecourse socioeconomic indicators (family income at birth, maternal education, family income at age 23 and own education) on CRP levels in young adults belonging to the 1982 Pelotas (Brazil) Birth Cohort Study (n = 5914). Early-life SES showed significant and graded associations …


Stuck Together: Searching For A Model Of Peritoneal Adhesions Using The August Rat, James W. Bathe Apr 2010

Stuck Together: Searching For A Model Of Peritoneal Adhesions Using The August Rat, James W. Bathe

Honors Theses

Fibrous adhesions, a by-product of the healing process, often appear post-surgically as a result of peritonitis related to the surgery. These adhesions can be either primarily "scar tissue" or excess "healthy tissue," and are the leading cause of intestinal obstruction in modern medicine. Shockingly, adhesions occur in up to 96% of patients undergoing intra-abdominal surgery. Adhesions can lead to multiple complications other than obstructions such as inadvertent enterotomy at the time of adhesiolysis, chronic pain, and female infertility. Additional complications arise from the adhesions preventing the free movement of organs and causing strangulations. The causes of the peritonitis, and therefore …


Bone Marrow Stromal Cells Use Tgf-Β To Suppress Allergic Responses In A Mouse Model Of Ragweed-Induced Asthma, K. Nemeth, A. Keane-Myers, J. M. Brown, D. D. Metcalfe, J. D. Gorham Mar 2010

Bone Marrow Stromal Cells Use Tgf-Β To Suppress Allergic Responses In A Mouse Model Of Ragweed-Induced Asthma, K. Nemeth, A. Keane-Myers, J. M. Brown, D. D. Metcalfe, J. D. Gorham

Dartmouth Scholarship

Bone marrow stromal cells [BMSCs; also known as mesenchymal stem cells (MSCs)] effectively suppress inflammatory responses in acute graft-versus-host disease in humans and in a number of disease models in mice. Many of the studies concluded that BMSC- driven immunomodulation is mediated by the suppression of pro- inflammatory Th1 responses while rebalancing the Th1/Th2 ratio toward Th2. In this study, using a ragweed induced mouse asthma model, we studied if BMSCs could be beneficial in an allergic, Th2- dominant environment. When BMSCs were injected i.v. at the time of the antigen challenge, they protected the animals from the majority of …


Determination Of The Pharmacokinetics And Oral Bioavailability Of Salicylamine, A Potent Γ-Ketoaldehyde Scavenger, By Lc/Ms/Ms, Irene Zagol-Ikapitte, Elena Matafonova, Venkataraman Amarnath, Christopher L. Bodine, Olivier Boutaud, Rommel G. Tirona, John A. Oates, L. Jackson Roberts, Sean S. Davies Mar 2010

Determination Of The Pharmacokinetics And Oral Bioavailability Of Salicylamine, A Potent Γ-Ketoaldehyde Scavenger, By Lc/Ms/Ms, Irene Zagol-Ikapitte, Elena Matafonova, Venkataraman Amarnath, Christopher L. Bodine, Olivier Boutaud, Rommel G. Tirona, John A. Oates, L. Jackson Roberts, Sean S. Davies

Paediatrics Publications

Levels of reactive γ-ketoaldehydes derived from arachidonate increase in diseases associated with inflammation and oxidative injury. To assess the biological importance of these γ-ketoaldehydes, we previously identified salicylamine as an effective γ-ketoaldehyde scavenger in vitro and in cells. To determine if salicylamine could be administered in vivo, we developed an LC/MS/MS assay to measure salicylamine in plasma and tissues. In mice, half-life (t1/2) was 62 minutes. Drinking water supplementation (1-10 g/L) generated tissue concentrations (10-500 μM) within the range previously shown to inhibit γ-ketoaldehydes in cells. Therefore, oral administration of salicylamine can be used to assess the contribution of γ-ketoaldehydes …