135 research outputs found
The cyanide catalyzed dimerization of 2,3 naphthalenedicarboxaldehyde: a unique oxidative condensation product and derivatives
Thesis (M.S.) University of Alaska Fairbanks, 20052,3 Naphthalenedicarboxaldehyde (NDA), in the presence of cyanide, is commonly used for the derivitization of amino acids and peptides to fluorescent 2-substituted 1-cyanobenzo[f]isoindoles, providing high sensitivity in capillary electrophoresis (CE) and high performance liquid chromatography (HPLC) separations. CE studies of the neurotransmitters glutamate and aspartate have shown the formation of a number of competitive side products. Although mentioned in the literature, these side products have not been characterized. The product, 15-hydroxybenzo[g]benzo [6, 7]isochromeno[4,3-c]isochromen- 7(15H)-one (2), is reported here, as a dimerization of NDA in the presence of cyanide and atmospheric oxygen. The structure is confirmed by IR, LRFAB-MS, IRMS, and NMR spectra. Possible mechanisms for the formation of 2, its air oxidation, and an alternative benzoin condensation product are discussed. 15-hydroxybenzo[g]benzo [6,7]isochromeno[4,3-c]isochromen-7(15H)-one (2) is easily converted to full acetals via reflux in an alcohol solvent in the presence of an acid catalyst. Oxidation by NaOCI (aq) yields 3-(3-chloro-1,4-dioxo-3,4-dihydro-1H-benzo[g]isochromen-3-yl)-2-napthaldahyde (4) by capturing hypochlorite at the position æ the enolate. Oxidation by pyridinium chlorochromate (PCC) yields naptho[2,3-c]furan-1,3-dione (5) by multiple oxidations and the formation of the anhydride
Biologically relevant secondary metabolites of Vaccinium uliginosum: bioassay-directed natural products identification of anti-neuroninflammatory agents in the Alaska bog blueberry
Thesis (M.S.) University of Alaska Fairbanks, 2010Dietary blueberry supplementation has demonstrated numerous health benefits including improved learning and memory in aging and neurodegenerative models, neuroprotection from ischemic events, anti-diabetic properties, and modulation of multiple inflammatory cascades. Despite previous research on antioxidant components prevalent in blueberries, no adequate explanation for a molecular mechanism for the benefits of blueberry supplementation has been proposed. Vaccinium uliginosum, the Alaska bog blueberry, possesses higher concentrations of antioxidant components than commercial varietals, and exhibits a greater oxygen radical scavenging capacity, making it an excellent candidate for the identification of biologically relevant secondary metabolites. An approach of bioassay-directed natural products identification was utilized to identify compounds in the Alaska bog blueberry responsible for the inhibition of both a magnesium-dependent neutral sphingomyelinase and NADPH oxidase in TNF-[alpha]-induced SH-SY5Y human neuroblastomas. Five relevant metabolites were identified: ß-sitosterol (1), ursolic acid (2), 3-0-(4-hydroxyphenylcarboxylic acid) 4-0-(ß-D-glucopyranosyl) gallic acid (3), malic acid (4), and 2,3-dihydroxybutane-1,2,3,4-tetracarboxylic acid (5). Neither compounds 3 or 5 had been previously described as a natural product in the literature. The identification of these compounds in the Alaska bog blueberry provides new explanations as to the benefits of blueberry consumption and offers new avenues of research for nutraceutical treatment of neuroinflammation.1.0. Introduction -- 1.1. Relevance of Vaccinium uliginosum, the Alaskan bog blueberry -- 1.2. Bioassay directed fractionation for the identification of biologically relevant compounds in complex extracts -- 1.3. Review of the literature : Whole berry supplementation and the relevance of NADPH oxidase and neutral sphingomyelinase modulation -- 1.3.1. Blueberry supplementation and neuroprotection : implications in learning and memory -- 1.3.1.1. Psychomotor performance and cognition improvements in the context of neuronal signaling and oxidative insult -- 1.3.1.2. The presence of blueberry anthocyanins and polyphenols in neuronal tissue -- 1.3.1.3. Modulation of IGF-1 and activation of MAPK signaling cascades, CREB, and BDNF -- 1.3.1.4. Protection in alzheimer's models : involvement of MAPK, CREB, AChE, and GSH -- 1.3.1.5. Effects on inflammatory cytokines and ceramides -- 1.3.2. Blueberry related neuroprotection in ischemia -- 1.3.3. Anti-diabetic properties of blueberries -- 1.3.4. NADPH oxidase as a target for blueberry research -- 1.3.5. Neutral sphingomyelinase regulation of ceramide release as a target for blueberry research -- 2.0. Methods -- 2.1. Evaluation of modulation of nSMase and NOX activation by Alaska bog blueberry components -- 2.2. Materials -- 2.3. Preparation of crude blueberry extract -- 2.4. Primary fractionation of crude extract pre-treatment procedures -- 2.5. Secondary fractionation of pre-treated samples -- 2.6. Tertiary fractionation : isolation of DPG and blueberric acid -- 2.7. Tertiary fractionation : isolation of malic acid -- 2.8. Tertiary fractionation : isolation of ursolic acid -- 2.9. Isolation of ß-sitosterol -- 3.0. Results -- 3.1. Initial evidence of anti-inflammatory components in the Alaska bog blueberry : whole extract inhibition of nSMase and NOX -- 3.2. Fractionation of Alaska bog blueberry and identification of biologically relevant secondary metabolites : tracking via inhibition of nSMase and NOX -- 3.3. ß-Sitosterol : structure and analysis of NMR -- 3.4. Ursolic acid : structure and analysis of NMR -- 3.5. 3-O-(4-hydroxyphenylcarboxylic acid) 4-O-(ß-D-glucopyranosyl) gallic acid or dimeric protocatechuic acid glycoside (DPG) : structure and analysis of NMR -- 3.6. Dimeric protocatechuic acid (DPG) : discussion of MS -- 3.7. Malic acid : determination of structure via NMR -- 3.8. 2,3-dihydroxybutane-1,2,3,4-tetracarboxylic acid or blueberric acid (BBA) : structure and analysis of NMR -- 3.9. Mass spectroscopy of BBA -- 4.0. Discussion -- 4.1. Ursolic acid -- 4.2. ß-sitosterol -- 4.3. Polyphenols : DPG in context -- 4.4. Malic acid -- 4.5. Blueberric acid -- 4.6. Future directions -- 5.0. References -- 6.0. Appendices
Consequences of removing cheap, super-strength beer and cider: a qualitative study of a UK local alcohol availability intervention.
OBJECTIVES: Increasingly, English local authorities have encouraged the implementation of an intervention called 'Reducing the Strength' (RtS) whereby off-licences voluntarily stop selling inexpensive 'super-strength' (≥6.5% alcohol by volume (ABV)) beers and ciders. We conceptualised RtS as an event within a complex system in order to identify pathways by which the intervention may lead to intended and unintended consequences. DESIGN: A qualitative study including a focus group and semistructured interviews. SETTING: An inner-London local authority characterised by a high degree of residential mobility, high levels of social inequality and a large homeless population. Intervention piloted in three areas known for street drinking with a high alcohol outlet density. PARTICIPANTS: Alcohol service professionals, homeless hostel employees, street-based services managers and hostel dwelling homeless alcohol consumers (n=30). RESULTS: Participants describe a range of potential substitution behaviours to circumvent alcohol availability restrictions including consuming different drinks, finding alternative shops, using drugs or committing crimes to purchase more expensive drinks. Service providers suggested the intervention delivered in this local authority missed opportunities to encourage engagement between the council, alcohol services, homeless hostels and off-licence stores. Some participants believed small-scale interventions such as RtS may facilitate new forms of engagement between public and private sector interests and contribute to long-term cultural changes around drinking, although they may also entrench the view that 'problem drinking' only occurs in certain population groups. CONCLUSIONS: RtS may have limited individual-level health impacts if the target populations remain willing and able to consume alternative means of intoxication as a substitute for super-strength products. However, RtS may also lead to wider system changes not directly related to the consumption of super-strengths and their assumed harms
Reducing the Strength: a mixed methods evaluation of alcohol retailers' willingness to voluntarily reduce the availability of low cost, high strength beers and ciders in two UK local authorities.
BACKGROUND: Reducing the Strength is an increasingly popular intervention in which local authorities ask retailers to stop selling 'super-strength' beers and ciders. The intervention cannot affect alcohol availability, nor consumption, unless retailers participate. In this paper, we ask whether and why retailers choose or refuse to self-impose restrictions on alcohol sales in this way. METHODS: Mixed method assessment of retailers' participation in Reducing the Strength in two London (UK) local authorities. Compliance rates and the cheapest available unit of alcohol at each store were assessed. Qualitative interviews with retailer managers and staff (n = 39) explored attitudes towards the intervention and perceptions of its impacts. RESULTS: Shops selling super-strength across both areas fell from 78 to 25 (18 % of all off-licences). The median price of the cheapest unit of alcohol available across all retailers increased from £0.29 to £0.33 and in shops that participated in Reducing the Strength it rose from £0.33 to £0.43. The project received a mixed response from retailers. Retailers said they participated to deter disruptive customers, reduce neighbourhood disruptions and to maintain a good relationship with the local authority. Reducing the Strength participants and non-participants expressed concern about its perceived financial impact due to customers shopping elsewhere for super-strength. Some felt that customers' ability to circumvent the intervention would limit its effectiveness and that a larger scale compulsory approach would be more effective. CONCLUSIONS: Reducing the Strength can achieve high rates of voluntary compliance, reduce availability of super-strength and raise the price of the cheapest available unit of alcohol in participating shops. Questions remain over the extent to which voluntary interventions of this type can achieve wider social or health goals if non-participating shops attract customers from those who participate
A Nonpolar Blueberry Fraction Blunts NADPH Oxidase Activation in Neuronal Cells Exposed to Tumor Necrosis Factor-α
Inflammation and oxidative stress are key to the progressive neuronal degeneration common to chronic pathologies, traumatic injuries, and aging processes in the CNS. The proinflammatory cytokine tumor necrosis factor-alpha (TNF-α) orchestrates cellular stress by stimulating the production and release of neurotoxic mediators including reactive oxygen species (ROS). NADPH oxidases (NOX), ubiquitously expressed in all cells, have recently emerged as pivotal ROS sources in aging and disease. We demonstrated the presence of potent NOX inhibitors in wild Alaska bog blueberries partitioning discretely into a nonpolar fraction with minimal antioxidant capacity and largely devoid of polyphenols. Incubation of SH-SY5Y human neuroblastoma cells with nonpolar blueberry fractions obstructed the coalescing of lipid rafts into large domains disrupting NOX assembly therein and abolishing ROS production characteristic for TNF-α exposure. These findings illuminate nutrition-derived lipid raft modulation as a novel therapeutic approach to blunt inflammatory and oxidative stress in the aging or diseased CNS
Mechanosensory Neuron Aging: Differential Trajectories with Lifespan-Extending Alaskan Berry and Fungal Treatments in Caenorhabditis elegans
Removal of cheap, super-strength beer and cider to address alcohol-related harms: a qualitative study of a local alcohol availability intervention
Working with the National Framework for Inclusion: a guide for teacher educators
This companion resource accompanies the National Framework for Inclusion 3rd edition and was developed by the Scottish Universities Inclusion Group (SUIG) and edited by Di Cantali (SUIG Chair). SUIG is a working group of the Scottish Council of Deans of Education
National framework for inclusion
Inclusive education is the cornerstone of Scottish education and, as such, must be of the highest priority for the Scottish Government and for all those involved in education in Scotland. There is clear recognition of the fact that teachers need to be well prepared and appropriately supported throughout their careers if they are to succeed in developing and sustaining the desired inclusive practice which will enable them to meet the increasingly diverse needs of all children within schools in Scotland
Working with the National Framework for Inclusion: a guide for teacher educators
This companion resource accompanies the National Framework for Inclusion 3rd edition and was developed by the Scottish Universities Inclusion Group (SUIG) and edited by Di Cantali (SUIG Chair). SUIG is a working group of the Scottish Council of Deans of Education
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