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Search Results: 1 - 10 of 463931 matches for " Keith A Sharkey "
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Helminth Parasites and the Modulation of Joint Inflammation
Chelsea E. Matisz,Jason J. McDougall,Keith A. Sharkey,Derek M. McKay
Journal of Parasitology Research , 2011, DOI: 10.1155/2011/942616
Abstract: There is an urgent need to develop better therapeutics for autoimmune and autoinflammatory diseases, of which musculoskeletal disorders such as rheumatoid arthritis are particularly prevalent and debilitating. Helminth parasites are accomplished masters at modifying their hosts' immune activity, and so attention has focused on rodent-helminth model systems to uncover the workings of the mammalian immune response to metazoan parasites, with the hope of revealing molecules and/or mechanisms that can be translated into better treatments for human autoimmune and idiopathic disorders. Substantial proof-of-principal data supporting the concept that infection with helminth parasites can reduce the severity of concomitant disease has been amassed from models of mucosal inflammation. Indeed, infection with helminth parasites has been tried as a therapy in inflammatory bowel disease, and there are case reports relating to other conditions (e.g., autism); however, the impact of infection with parasitic helminths on musculoskeletal diseases has not been extensively studied. Here, we present the view that such a strategy should be applied to the amelioration of joint inflammation and review the literature that supports this contention. 1. Introduction Infection with helminth parasites results in a conserved series of immune events that are orchestrated and dominated by T helper cell type 2 (Th2) events [1]. Given the reciprocity in immune regulation where, for example, Th2 cell-derived mediators inhibit the activity of Th1 cells, the hypothesis arises that individuals infected with helminth parasites could be less susceptible to other inflammatory diseases. By extrapolation, infection with helminth parasites could be used to treat disease driven by Th1 cells. Many species of parasitic helminths reside at mucosal surfaces, and it has repeatedly been shown that infection with trematode, cestode, or nematode parasites can reduce the severity of colitis and airway inflammation in murine models [2]. The impact of infection with helminths on organs outside the parasite’s location has received less attention. Here, we review the effect of infection with helminth parasites on joint inflammation. The last four decades have seen an alarming increase in the prevalence of autoimmune diseases such as inflammatory bowel disease (IBD), diabetes, multiple sclerosis, and rheumatoid arthritis (RA) in Western societies. Rheumatoid arthritis is a painful and debilitating disease that affects ~1% of the North American population [3]. The socioeconomic burden of this disease is
A unique therapeutic approach to emesis and itch with a proanthocyanidin-rich genonutrient
Mark JS Miller, Brian K Reuter, John L Wallace, Keith A Sharkey
Journal of Translational Medicine , 2008, DOI: 10.1186/1479-5876-6-3
Abstract: Emesis was induced in ferrets with morphine-6-glucuronide (0.05 mg/kg sc) in the presence of Zangrado (3 mg/kg, ip) and the cannabinoid receptor 1 antagonist, AM 251 (5 mg/kg, ip). Topical Zangrado (1%) was assessed for anti-pruretic actions in the 5-HT-induced scratching model in rats and evaluated in capsaicin-induced gastric hyperemia as measured by laser doppler flow. In the ApcMinmouse model of precancerous adenomatosis polyposis, mice received Zangrado (100 μg/ml in drinking water) from the age of 6 – 16 weeks for effects on polyp number. In RAW 264.7 cells Zangrado was examined for effects on lipopolysaccharide-induced nitrite production.Zangrado was a highly effective anti-emetic, reducing morphine-induced vomiting and retching by 77%. These benefits were not associated with sedation or hypothermia and were not reversed by cannabinoid receptor antagonism. Itch responses were blocked in both the morphine and 5-HT models. Zangrado did not exacerbate the ApcMincondition rather health was improved. Capsaicin-induced hyperemia was blocked by Zangrado, which also attenuated the production of nitric oxide by activated macrophages.Zangrado is an effective anti-emetic and anti-itch therapy that is devoid of common side-effects, cannabinoid-independent and broadly suppresses sensory afferent nerve activation. This complementary medicine represents a promising new approach to the management of nausea, itch and irritable bowel syndrome.The latex of the Amazonian traditional medicine Croton palanostigma and related Croton species is traditionally used in the treatment of inflammation, pain, itch, and a number of gastrointestinal afflictions that are common in the rainforest [1]. This traditional medicine is derived from a fast growing tree that is known by different names in various countries: in Peru it is called sangre de grado and in Ecuador, sangre de drago. We have found substantial scientific support for a number of these ethnomedical applications [2-4]. A central
Gastrointestinal Viral Load and Enteroendocrine Cell Number Are Associated with Altered Survival in HIV-1 Infected Individuals
Guido van Marle, Keith A. Sharkey, M. John Gill, Deirdre L. Church
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0075967
Abstract: Human immunodeficiency virus type 1 (HIV-1) infects and destroys cells of the immune system leading to an overt immune deficiency known as HIV acquired immunodeficiency syndrome (HIV/AIDS). The gut associated lymphoid tissue is one of the major lymphoid tissues targeted by HIV-1, and is considered a reservoir for HIV-1 replication and of major importance in CD4+ T-cell depletion. In addition to immunodeficiency, HIV-1 infection also directly causes gastrointestinal (GI) dysfunction, also known as HIV enteropathy. This enteropathy can manifest itself as many pathological changes in the GI tract. The objective of this study was to determine the association of gut HIV-1 infection markers with long-term survival in a cohort of men who have sex with men (MSM) enrolled pre-HAART (Highly Active Antiretroviral Therapy). We examined survival over 15-years in a cohort of 42 HIV-infected cases: In addition to CD4+ T cell counts and HIV-1 plasma viral load, multiple gut compartment (duodenum and colon) biopsies were taken by endoscopy every 6 months during the initial 3-year period. HIV-1 was cultured from tissues and phenotyped and viral loads in the gut tissues were determined. Moreover, the tissues were subjected to an extensive assessment of enteroendocrine cell distribution and pathology. The collected data was used for survival analyses, which showed that patients with higher gut tissue viral load levels had a significantly worse survival prognosis. Moreover, lower numbers of serotonin (duodenum) and somatostatin (duodenum and colon) immunoreactive cell counts in the gut tissues of patients was associated with significant lower survival prognosis. Our study, suggested that HIV-1 pathogenesis and survival prognosis is associated with altered enteroendocrine cell numbers, which could point to a potential role for enteroendocrine function in HIV infection and pathogenesis.
The role of the purinergic P2X7 receptor in inflammation
Martin F Lister, John Sharkey, Deborah A Sawatzky, Joseph P Hodgkiss, Donald J Davidson, Adriano G Rossi, Keith Finlayson
Journal of Inflammation , 2007, DOI: 10.1186/1476-9255-4-5
Abstract: Inflammation is an important physiological reaction which occurs in response to a wide variety of injurious agents (e.g. bacterial infection or physical trauma) ultimately aiming to perform the dual function of limiting damage and promoting tissue repair [1]. The inflammatory process is often viewed as being comprised of three closely linked phases: – initiation, propagation and resolution, with current anti-inflammatory therapies designed to limit or prevent the initiation and propagation phases. However, it is increasingly recognised that therapies aimed at enhancing the resolution phase will be important in limiting the damage associated with persistent inflammatory disease states such as rheumatoid arthritis, chronic obstructive pulmonary diseases and artherosclerosis [2].In recent years, the role of ATP and its cognate receptors in the inflammatory process has been recognised. In particular, the P2X7 receptor (P2X7R) which is expressed primarily (though not exclusively) on cells of haemopoietic origin [3] is thought to play an important role in macrophage/microglial and granulocyte function by regulating cytokine production and apoptosis. Moreover, as the P2X7R is known to be up-regulated during inflammation, antagonists of this receptor may serve as novel anti-inflammatory agents. In this review we summarise recent advances in the understanding of the role of the P2X7R in inflammatory processes and highlight the potential of P2X7R ligands for the treatment of chronic inflammatory diseases, focusing particularly on tuberculosis and cancer.Extracellular ATP is known to activate two classes of membrane-bound receptors; the metabotropic P2Y (P2Y1, P2Y2, P2Y4, P2Y6 and P2Y11–14), and ionotropic P2X (P2X1–7) receptors with the pharmacology, distribution and putative functions of these receptors extensively reviewed [4-6]. Of the P2 receptors, the P2X7R has attracted considerable interest as a consequence of its unique biological properties. Brief activation of the P
Local Barriers and Solutions to Improve Care-Seeking for Childhood Pneumonia, Diarrhoea and Malaria in Kenya, Nigeria and Niger: A Qualitative Study
K. Juliet A. Bedford, Alyssa B. Sharkey
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0100038
Abstract: We present qualitative research findings on care-seeking and treatment uptake for pneumonia, diarrhoea and malaria among children under 5 in Kenya, Nigeria and Niger. The study aimed to determine the barriers caregivers face in accessing treatment for these conditions; to identify local solutions that facilitate more timely access to treatment; and to present these findings as a platform from which to develop context-specific strategies to improve care-seeking for childhood illness. Kenya, Nigeria and Niger are three high burden countries with low rates of related treatment coverage, particularly in underserved areas. Data were collected in Homa Bay County in Nyanza Province, Kenya; in Kebbi and Cross River States, Nigeria; and in the Maradi and Tillabéri regions of Niger. Primary caregivers of children under 5 who did not regularly engage with health services or present their child at a health facility during illness episodes were purposively selected for interview. Data underwent rigorous thematic analysis. We organise the identified barriers and related solutions by theme: financial barriers; distance/location of health facilities; socio-cultural barriers and gender dynamics; knowledge and information barriers; and health facility deterrents. The relative importance of each differed by locality. Participant suggested solutions ranged from community-level actions to facility-level and more policy-oriented actions, plus actions to change underlying problems such as social perceptions and practices and gender dynamics. We discuss the feasibility and implications of these suggested solutions. Given the high burden of childhood morbidity and mortality due to pneumonia, diarrhoea and malaria in Kenya, Nigeria and Niger, this study provides important insights relating to demand-side barriers and locally proposed solutions. Significant advancements are possible when communities participate in both problem identification and resolution, and are engaged as important partners in improving child health and survival.
Imaging Proteolytic Activity in Live Cells and Animal Models
Stefanie Galbán, Yong Hyun Jeon, Brittany M. Bowman, James Stevenson, Katrina A. Sebolt, Lisa M. Sharkey, Michael Lafferty, Benjamin A. Hoff, Braeden L. Butler, Susan S. Wigdal, Brock F. Binkowski, Paul Otto, Kris Zimmerman, Gediminas Vidugiris, Lance P. Encell, Frank Fan, Keith V. Wood, Craig J. Galbán, Brian D. Ross, Alnawaz Rehemtulla
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0066248
Abstract: In addition to their degradative role in protein turnover, proteases play a key role as positive or negative regulators of signal transduction pathways and therefore their dysregulation contributes to many disease states. Regulatory roles of proteases include their hormone-like role in triggering G protein-coupled signaling (Protease-Activated-Receptors); their role in shedding of ligands such as EGF, Notch and Fas; and their role in signaling events that lead to apoptotic cell death. Dysregulated activation of apoptosis by the caspase family of proteases has been linked to diseases such as cancer, autoimmunity and inflammation. In an effort to better understand the role of proteases in health and disease, a luciferase biosensor is described which can quantitatively report proteolytic activity in live cells and mouse models. The biosensor, hereafter referred to as GloSensor Caspase 3/7 has a robust signal to noise (50–100 fold) and dynamic range such that it can be used to screen for pharmacologically active compounds in high throughput campaigns as well as to study cell signaling in rare cell populations such as isolated cancer stem cells. The biosensor can also be used in the context of genetically engineered mouse models of human disease wherein conditional expression using the Cre/loxP technology can be implemented to investigate the role of a specific protease in living subjects. While the regulation of apoptosis by caspase's was used as an example in these studies, biosensors to study additional proteases involved in the regulation of normal and pathological cellular processes can be designed using the concepts presented herein.
Using multiple household food inventories to measure food availability in the home over 30 days: a pilot study
Cheree Sisk, Joseph R Sharkey, William A McIntosh, Jenna Anding
Nutrition Journal , 2010, DOI: 10.1186/1475-2891-9-19
Abstract: After the development and pre-testing of the 251-item home observation guide that used direct observation to determine the presence and amount of food items in the home (refrigerator, freezer, pantry, elsewhere), two trained researchers recruited a convenience sample of 9 households (44.4% minority); administered a baseline questionnaire (personal info, shopping habits, food resources, and food security); and conducted 5 in-home assessments (7-day interval) over a 30-day period. Each in-home assessment included food-related activities since the last assessment, and an observational survey of types and amounts of foods present.Complete data were collected from all 9 women (32.8 y ± 6.0; 3 married; 4 ± 1.6 adults/children in household; 4 received food assistance; and 6 had very low food security) and their households. Weekly grocery purchases (place, amount, and purpose) varied from once (n = 1) to every week (n = 5); 4 used fast food 2-3 times/wk for 4 weeks. The weekly presence and amounts of fresh and processed fruits and vegetables and dairy varied.The feasibility of conducting multiple in-home assessments was confirmed with 100% retention of participants through 5 in-home assessments, which paid particular attention to the intra-monthly changes in household availability in type and amount of foods. This study contributes to research on home food availability by identifying the importance of multiple measures, presence of certain foods in the home, and the feasibility of comprehensive in-home assessments.Obesity and overweight continue to present broad-scale problems throughout the world, with high obesity rates in the United States among African American and Hispanic populations [1-6], persons with low income and educational attainment [7], and individuals living in rural areas [8,9]. There is very little argument that food choice, which is influenced by food available in the home, affects nutritional health [10]. In fact, Rasmussen and colleagues report home foo
Ponderosa Pine Family Growth Comparisons in the Central Great Plains of Kansas  [PDF]
Wayne A. Geye, Keith D. Lynch
Open Journal of Forestry (OJF) , 2011, DOI: 10.4236/ojf.2011.12004
Abstract: Ponderosa pine (Pinus ponderosa Laws.) has been planted widely in the Great Plains. Recommendations based on a 1968 study were to use material from south central South Dakota and north central Nebraska. A second test to further delineate seed sources (provenance/families) in this region was established in 1986. This paper reports results for survival, height, diameter, and D2H measurements in Kansas at 15 years. Results identify a wide range of suitable families within the Great Plains region.A majority of the tested sources performed well especially those from central Nebraska. Those sources from eastern Montana and western Nebraska performed poorly where environmental or geographic conditions were the poorest, thus verifying the original recommendations.
Osteonecrosis: The perils of steroids. A review of the literature and case report  [PDF]
Ben J. Brooker, Prue P. A. Keith
Case Reports in Clinical Medicine (CRCM) , 2012, DOI: 10.4236/crcm.2012.12008
Abstract: Non-traumatic osteonecrosis is a cause of joint pain and deformity, not uncommonly caused by corticosteroid use. Despite this, corticosteroid induced osteonecrosis is poorly represented in the literature. We performed a detailed review of corticosteroid induced osteonecrosis, including aetiology, prevention, screening, clinical presentation, investigations, staging systems and treatment. We present this in the context of a patient at our institution who developed bilateral hip, shoulder and knee osteonecrosis following high dose corticosteroid therapy for dermatomyositis.
Can We Praxize Second Language Teacher Education? An Invitation to Join a Collective, Collaborative Challenge*
íkala, Revista de Lenguaje y Cultura , 2009,
Abstract: the purpose of this essay is to begin a conversation on how we might make praxis, or ''praxizing,'' i.e., fostering and sustaining an ongoing dialogical relationship between theory and practice, an integral part of second language teacher education. this project is firmly located in critical sociocultural theories of, and approaches to, language learning and teaching, and requires active, participatory and collaborative inquiries by teacher educators and teacher learners across the multiple levels and stages of teacher learning from entry level courses to teaching practica and beyond. examples of praxis/praxizing are included as well as some of the challenges to doing this work.
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