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Dive into the research topics where Norma Frizzell is active.

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Featured researches published by Norma Frizzell.


Diabetologia | 2004

Substrates modified by advanced glycation end-products cause dysfunction and death in retinal pericytes by reducing survival signals mediated by platelet-derived growth factor

Alan W. Stitt; S.-J. Hughes; Paul Canning; O. Lynch; O. Cox; Norma Frizzell; Suzanne R. Thorpe; Thomas G. Cotter; Tim M. Curtis; T. A. Gardiner

Aims/hypothesisPremature death of retinal pericytes is a pathophysiological hallmark of diabetic retinopathy. Among the mechanisms proposed for pericyte death is exposure to AGE, which accumulate during diabetes. The current study used an in vitro model, whereby retinal pericytes were exposed to AGE-modified substrate and the mechanisms underlying pericyte death explored.MethodsPericytes were isolated from bovine retinal capillaries and propagated on AGE-modified basement membrane (BM) extract or non-modified native BM. The extent of AGE modification was analysed. Proliferative responses of retinal pericytes propagated on AGE-modified BM were investigated using a 5-bromo-2-deoxy-uridine-based assay. The effect of extrinsically added platelet-derived growth factor (PDGF) isoforms on these proliferative responses was also analysed alongside mRNA expression of the PDGF receptors. Apoptotic death of retinal pericytes grown on AGE-modified BM was investigated using terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling labelling, mitochondrial membrane depolarisation and by morphological assessment. We also measured both the ability of PDGF to reverse Akt dephosphorylation that was mediated by AGE-modified BM, and increased pericyte apoptosis.ResultsRetinal pericytes exposed to AGE-modified BM showed reduced proliferative responses in comparison to controls (p<0.05–0.01), although this effect was reversed at low-AGE modifications. PDGF mRNA levels were differentially altered by exposure to low and high AGE levels, and AGE-modified BM caused significantly increased apoptosis in retinal pericytes. Pre-treatment of AGE-modified BM with PDGF-AA and -BB reversed the apoptosis (p<0.05–0.001) and restored Akt phosphorylation in retinal pericytes.Conclusions/interpretationEvidence suggests that substrate-derived AGE such as those that occur during diabetes could have a major influence on retinal pericyte survival. During diabetic retinopathy, AGE modification of vascular BM may reduce bioavailability of pro-survival factors for retinal pericytes.


International Congress Series | 2002

Role of dyslipidemia and AGE/ALE formation in the progression of nephropathy and retinopathy in STZ-diabetic rats

Suzanne R. Thorpe; Nathan L. Alderson; Mark Chachich; Andrzej Januszweski; Nancy N. Youssef; Stephanie M Jimenez; T. A. Gardiner; Norma Frizzell; Paul Canning; Agnieszka Lichanska; John W. Baynes; Alan W. Stitt

Abstract We hypothesized that the beneficial effects of a variety of pharmacological agents on the progression of diabetic complications were mediated by a common pathway limiting the formation of advanced glycation and advanced lipoxidation end products (AGEs/ALEs) on protein. We studied the effects of the AGE/ALE inhibitor pyridoxamine (PM), the antioxidant vitamin E (VE) and the ACE inhibitor enalapril (EP) on the development of nephropathy and retinopathy in STZ-induced diabetic rats over 29 weeks. Blood glucose and glycohemoglobin were similar in all diabetic groups. Plasma lipids rose continuously in diabetic animals and only PM significantly attenuated this increase. Early nephropathy was indicated by increased plasma creatinine, and urinary albumin, protein and TGF-β excretion in untreated rats. While all interventions limited renal damage to some extent, PM was the most effective, although the increased expression of renal laminin β1 and fibronectin mRNA was normalized by all therapies. Measurement of retinal damage (acellular capillaries, vascular basement membrane-associated laminin) showed that only PM significantly limited signs of early retinopathy in diabetic rats. Only PM limited the increases in the AGE/ALEs in renal and retinal tissue, and in skin collagen, of diabetic rats. Our results suggest that limiting both dyslipidemia and AGE/ALE formation is required for maximum protection of renal and retinal function in the STZ-diabetic rat.


Investigative Ophthalmology & Visual Science | 2003

The role of advanced glycation end products in retinal microvascular leukostasis.

Tara Moore; Jonathan E. Moore; Yuichi Kaji; Norma Frizzell; Tomohiko Usui; V. Poulaki; Iain L. Campbell; Alan W. Stitt; Tom A. Gardiner; Desmond B. Archer; Anthony P. Adamis


Investigative Ophthalmology & Visual Science | 2002

A Modulatory Role for Advanced Glycation End-Products (AGEs) in Retinal Microvascular Leukostasis

Tb McMullen; Norma Frizzell; John E. Moore; V. Poulaki; Iain L. Campbell; Na Afshari; Yuichi Kaji; Alan W. Stitt; Desmond B. Archer; Anthony P. Adamis


Archive | 2013

Atherosclerosis, diabetes and neurodegenerative diseases are more commonly associated with accumulation of iron in tissues, including both vascular and neurodegenerative plaque.

Norma Frizzell; John W. Baynes


Archive | 2007

Simultaneous Determination of Ascorbic and Dehydroascorbic Acids using Newly Developed HILIC Stationary Phases and Tandem Mass Spectrometry

William E. Cotham; Michael D. Walla; Audrey M Howard; Norma Frizzell; John W. Baynes; Matthew Przybyciel


Annals of the New York Academy of Sciences | 2005

Characterization of a Glycoaldehyde-Modified Model of the Diabetic Basement Membrane: Relevance to Pathological Responses during Diabetes.

Norma Frizzell; Alan W. Stitt; Suzanne R. Thorpe


Annals of the New York Academy of Sciences | 2005

Quantification of Advanced Glycation End Products in Diabetic Animal Tissues by RP-HPLC: An Investigation of the Role of Pyridoxamine

Norma Frizzell; Alan W. Stitt; Suzanne R. Thorpe


Archive | 2002

The Role of Advanced Glycation End-Products (AGEs) in Retinal Microvascular Leukostasis

Tara Moore; Johnny Moore; Yuichi Kaji; Norma Frizzell; Tomohiko Usui; Poulaki; Iain L. Campbell; Na Asfhari; Alan W. Stitt; Desmond B. Archer; Anthony P. Adamis


Archive | 2002

Basement Membrane Immobilised AGEs Induce Capillary Endothelial Dycfunction and Apoptosis

Norma Frizzell; Tom A. Gardiner; Tara Moore; Thorpe; Brown; Alan W. Stitt

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Alan W. Stitt

Queen's University Belfast

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Desmond B. Archer

Queen's University Belfast

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Suzanne R. Thorpe

University of South Carolina

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Anthony P. Adamis

Massachusetts Eye and Ear Infirmary

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John W. Baynes

University of South Carolina

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Paul Canning

Queen's University Belfast

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Tom A. Gardiner

Queen's University Belfast

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Tomohiko Usui

Massachusetts Eye and Ear Infirmary

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V. Poulaki

Massachusetts Eye and Ear Infirmary

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