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Neuroprotective Effects of a Novel Apple Peel Extract AF4 in a Mouse Model of Hypoxic-Ischemic Brain InjuryDunlop, Kate 12 July 2011 (has links)
The neuroprotective effects of AF4, a flavonoid-enriched extract derived from the
peel of Northern Spy apples (containing quercetin-3-O-glucoside, quercetin-3-O-galactoside,
quercetin-3-O-rhamnoside, quercetin-3-O-rutinoside, epicatechin, and
cyanidin-3-O-galactoside) were examined by assessing neuronal loss and motor
impairment resulting from hypoxic-ischemic (HI) brain injury in adult C57BL/6 mice.
Relative to vehicle treatment (water, 10mL/kg/day), oral administration of AF4 (50
mg/kg/day) for 3 days reduces HI-induced neuronal loss in the striatum and
hippocampus, motor impairments, and reduces the ability of LPS to stimulate the
production of TNF-alpha in whole blood. Pretreatment with AF4 (1 ug/mL) decreased the
death of mouse primary cortical neurons subjected to oxygen glucose deprivation (12
hours) in comparison to vehicle (DMSO) or the same concentration of quercetin or its
metabolites. Taken together these findings indicate that AF4 reduces HI-induced brain
injury and motor deficits by increasing the resistance of vulnerable neurons to ischemic
cell death and decreasing the production of inflammatory cytokines.
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Neuregulin’s role in regulating the anti-inflammatory pathwayNash, Michelle January 2009 (has links)
Inflammation can be up-regulated by microglia and macrophages through the release of pro-inflammatory cytokines such as tumour necrosis factor-alpha (TNF-α). Excess production of TNF-α can lead to a variety of diseases and even tissue necrosis. Recently, the expression of alpha seven acetylcholine receptors (α7AChR) by microglia have been shown to decrease the amount of TNF-α released. This anti-inflammatory pathway has been studied extensively where researchers are able to reduce TNF-α concentration through α7AChR expression and increases in the concentration of its ligand. I have shown that Neuregulin is able to increase the expression of α7AChR in microglia and macrophages.
Using three immortalized cell lines, BV-2, EOC-20 and RAW 264.7, and primary microglial cells harvest from mice I investigated the role that neuregulin plays in the anti-inflammatory process. Neuregulin signals through the ErbB receptors, a family of tyrosine kinase receptors, to facilitate the effects on ACh expression. My results show that ErbB4 is expressed in BV-2, EOC-20 and RAW 264.7 cell lines while ErbB2-4 receptors are expressed in primary microglia. As well, I was able to show that ErbB4 became phosphorylated upon binding to NRG in immortalized cell lines.
Using an Enzyme Linked Immunsorbent Assay to analyze TNF- α concentration in microglia and macrophages, I was able to demonstrate that increased levels of α7AChRs did not result in a reduction in TNF-α concentration. These results showed that NRG is able to increase α7AChRs in microglia and macrophages after the phosphorylation of the ErbB4 receptors. As well, this increase in α7AChR does not relate to a reduction in TNF-α, thus under these experimental conditions does not have an effect on the anti-inflammatory pathway.
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Neuregulin’s role in regulating the anti-inflammatory pathwayNash, Michelle January 2009 (has links)
Inflammation can be up-regulated by microglia and macrophages through the release of pro-inflammatory cytokines such as tumour necrosis factor-alpha (TNF-α). Excess production of TNF-α can lead to a variety of diseases and even tissue necrosis. Recently, the expression of alpha seven acetylcholine receptors (α7AChR) by microglia have been shown to decrease the amount of TNF-α released. This anti-inflammatory pathway has been studied extensively where researchers are able to reduce TNF-α concentration through α7AChR expression and increases in the concentration of its ligand. I have shown that Neuregulin is able to increase the expression of α7AChR in microglia and macrophages.
Using three immortalized cell lines, BV-2, EOC-20 and RAW 264.7, and primary microglial cells harvest from mice I investigated the role that neuregulin plays in the anti-inflammatory process. Neuregulin signals through the ErbB receptors, a family of tyrosine kinase receptors, to facilitate the effects on ACh expression. My results show that ErbB4 is expressed in BV-2, EOC-20 and RAW 264.7 cell lines while ErbB2-4 receptors are expressed in primary microglia. As well, I was able to show that ErbB4 became phosphorylated upon binding to NRG in immortalized cell lines.
Using an Enzyme Linked Immunsorbent Assay to analyze TNF- α concentration in microglia and macrophages, I was able to demonstrate that increased levels of α7AChRs did not result in a reduction in TNF-α concentration. These results showed that NRG is able to increase α7AChRs in microglia and macrophages after the phosphorylation of the ErbB4 receptors. As well, this increase in α7AChR does not relate to a reduction in TNF-α, thus under these experimental conditions does not have an effect on the anti-inflammatory pathway.
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NSAID effect on prostanoids in fishes prostaglandin E2 levels in bluntnose minnows (Pimephales notatus) exposed to ibuprofen /Bhandari, Khageshor. Venables, Barney J., January 2009 (has links)
Thesis (M.S.)--University of North Texas, Aug., 2009. / Title from title page display. Includes bibliographical references.
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Development of a Novel Biodegradable Drug Polymer for the Modification of Inflammatory ResponseKhor, Sara 30 July 2008 (has links)
The first objective of this thesis was to assess the feasibility of designing a “smart”
degradable polymer that can release anti-inflammatory drugs in response to inflammatory-related enzymes. The drug polymer was synthesized using diisocyanates, poly(caprolactone)diols, and oxaceprol (OC) biomonomers. Biodegradation studies demonstrated that the trimethylhexamethylene diisocyanate-based drug polymer responded to an inflammatory enzyme to release more OC, while a 1, 12-diisocyanatododecane analog demonstrated minimal drug release. The drug delivery response was believed to be a direct function of the molecular structure and distribution of the hard segment.
The second objective of this thesis was to elucidate the anti-inflammatory mechanisms of OC by investigating its effects on cytokine-induced monocytic-cells adhesion
in human umbilical vein endothelial cells (HUVECs) in vitro. Results showed that OC had
no direct effect on the monocyte-endothelium adhesion, suggesting that OC may mediate
inflammation by mechanisms other than those suggested by the literature.
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Neuroprotective Effects of a Novel Apple Peel Extract AF4 in a Mouse Model of Hypoxic-Ischemic Brain InjuryDunlop, Kate Elizabeth 12 July 2011 (has links)
The neuroprotective effects of AF4, a flavonoid-enriched extract derived from the
peel of Northern Spy apples (containing quercetin-3-O-glucoside, quercetin-3-O-galactoside,
quercetin-3-O-rhamnoside, quercetin-3-O-rutinoside, epicatechin, and
cyanidin-3-O-galactoside) were examined by assessing neuronal loss and motor
impairment resulting from hypoxic-ischemic (HI) brain injury in adult C57BL/6 mice.
Relative to vehicle treatment (water, 10mL/kg/day), oral administration of AF4 (50
mg/kg/day) for 3 days reduces HI-induced neuronal loss in the striatum and
hippocampus, motor impairments, and reduces the ability of LPS to stimulate the
production of TNF-alpha in whole blood. Pretreatment with AF4 (1 ug/mL) decreased the
death of mouse primary cortical neurons subjected to oxygen glucose deprivation (12
hours) in comparison to vehicle (DMSO) or the same concentration of quercetin or its
metabolites. Taken together these findings indicate that AF4 reduces HI-induced brain
injury and motor deficits by increasing the resistance of vulnerable neurons to ischemic
cell death and decreasing the production of inflammatory cytokines.
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Biological activity of nanostructured silverNadworny, Patricia L Unknown Date
No description available.
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The efficacy of a local action transcutaneous flurbiprofen patch, in the treatment of lateral epicondylitisOehley, Darryl Bruce Somerset January 2002 (has links)
Thesis (M.Tech.: Chiropractic)- Dept. of Chiropractic, Durban Institute of Technology, 2002 xii, 90 leaves / The purpose of this study was to determine the relative efficacy of topical flurbiprofen in the form of a local action transcutaneous patch (LAT), in the treatment of lateral epicondylitis.
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Development of a Novel Biodegradable Drug Polymer for the Modification of Inflammatory ResponseKhor, Sara 30 July 2008 (has links)
The first objective of this thesis was to assess the feasibility of designing a “smart”
degradable polymer that can release anti-inflammatory drugs in response to inflammatory-related enzymes. The drug polymer was synthesized using diisocyanates, poly(caprolactone)diols, and oxaceprol (OC) biomonomers. Biodegradation studies demonstrated that the trimethylhexamethylene diisocyanate-based drug polymer responded to an inflammatory enzyme to release more OC, while a 1, 12-diisocyanatododecane analog demonstrated minimal drug release. The drug delivery response was believed to be a direct function of the molecular structure and distribution of the hard segment.
The second objective of this thesis was to elucidate the anti-inflammatory mechanisms of OC by investigating its effects on cytokine-induced monocytic-cells adhesion
in human umbilical vein endothelial cells (HUVECs) in vitro. Results showed that OC had
no direct effect on the monocyte-endothelium adhesion, suggesting that OC may mediate
inflammation by mechanisms other than those suggested by the literature.
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Biological activity of nanostructured silverNadworny, Patricia L 06 1900 (has links)
Although nanocrystalline silver is used commercially to treat burns and wounds, the mechanisms of action (MOA) for its activity are not clear. The purposes of this work were to determine if nanocrystalline silver has anti-inflammatory activity, determine physicochemical properties critical for its MOA, and develop nanocrystalline silver-derived solutions for use in the treatment of lung diseases, including ARDS and pneumonia. In a porcine contact dermatitis model, nanocrystalline silver had anti-inflammatory activity independent of antimicrobial activity, with increased apoptosis induction in inflammatory cells, but not keratinocytes; decreased expression of TNF-, TGF-, IL-8, and MMPs; and increased expression of IL-4, EGF, KGF, and KGF-2. Treatment with AgNO3 (Ag+) increased inflammation, and caused apoptosis induction in keratinocytes. Thus, nanocrystalline silver releases additional species, perhaps Ag^(0)-containing clusters, resulting in anti-inflammatory activity. SIMS analysis showed significant deposition of Ag-clusters after nanocrystalline silver, but not AgNO3, treatment. Nanocrystalline silver had a systemic effect, despite SIMS analysis showing minimal skin penetration by silver, suggesting that nanocrystalline silver interacts with cells near tissue surfaces that release signals altering the inflammatory cascade. Relative to various Ag+-releasing dressings, nanocrystalline silver had significantly enhanced antimicrobial activity, Ag+-resistant bacteria kill, and was not prone to development of resistant bacteria, indicating that nanocrystalline silver releases antimicrobial species additional to Ag+, and has multiple bactericidal MOA. Single silver nanocrystals are inactive, and heat treatment of nanocrystalline silver resulting in crystallites over ~30 nm caused loss of antimicrobial activity, soluble silver, silver oxide, and oxygen. This indicates a poly-nanocrystalline silver structure is necessary for optimal antimicrobial activity, as is having silver oxide to pin the nanostructure, preventing its growth. While oxygen is necessary during sputtering to produce silver oxide, too much oxygen reduces antimicrobial activity, as silver oxide is predominantly deposited. Sufficient total silver, modifiable with current and time, is also important for activity. Nanocrystalline silver-derived solution properties vary significantly with dissolution conditions. Solutions generated at pH 4-6 have stronger antimicrobial activity, and solutions generated at pH 9 have stronger anti-inflammatory activity. Overall, nanocrystalline silver-derived solutions have biological properties similar to nanocrystalline silver, indicating that they may be useful in a variety of medical applications.
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