The presence of the age pigment lipofuscin is associated with numerous age-related diseases. In the retina lipofuscin is located within the pigment epithelium where it is exposed to high oxygen and visible light, a prime environment for the generation of reactive oxygen species. Although we, and others, have demonstrated that retinal lipofuscin is a photoinducible generator of reactive oxygen species it is unclear how this may translate into cell damage. The position of lipofuscin within the lysosome infers that irradiated lipofuscin is liable to cause oxidative damage to either the lysosomal membrane or the lysosomal enzymes. We have found that illumination of lipofuscin with visible light is capable of extragranular lipid peroxidation, enzyme inactivation, and protein oxidation. These effects, which were pH-dependent, were significantly reduced by the addition of the antioxidants, superoxide dismutase and 1,4-diazabicyclo(2,2,2)-octane, confirming a role for both the superoxide anion and singlet oxygen. We postulate that lipofuscin may compromise retinal cell function by causing loss of lysosomal integrity and that this may be a major contributory factor to the pathology associated with retinal light damage and diseases such as age-related macular degeneration.The age pigment lipofuscin accumulates within the lysosomal system of a variety of postmitotic cells throughout life and is considered to be a biomarker of cell aging. Evidence has shown that the rate of lipofuscin accumulation corresponds to the aging rates in different species, being influenced by both metabolic activity and extent of oxidative stress (1). However, a causal role for lipofuscin in the aging process or development of age-related diseases such as neuronal ceroid lipofuscinosis, age-related macular degeneration, Ménière's disease, and cardiac hypertrophy has yet to be established (see Refs. 2 and 3). Unlike other cells in the body, in which lipofuscin occurs through the autophagic breakdown of intracellular organelles (2), the major substrate for lipofuscin in the retinal pigment epithelium (RPE) 1 of the eye is the undegradable end product resulting from the phagocytosis of photoreceptor outer segments (4, 5) that are rich in polyunsaturated fatty acids and vitamin A.Ocular lipofuscin may have a unique role to play in aging of the RPE, a tissue that is continually exposed to visible light (400 -700 nm) and high oxygen tensions (ϳ70 mm Hg). Studies have shown this type of lipofuscin to be a photoinducible generator of superoxide ions, singlet oxygen, hydrogen peroxide, and lipid peroxides (6 -9), all of which are reactive oxygen species implicated in general aging processes. These species can adversely affect cell function by damaging proteins, carbohydrates, DNA, and lipids (10). The position of lipofuscin within the lysosome infers that the first site of oxidative damage will be either the lysosomal membrane or the lysosomal enzymes. To test this hypothesis we have assessed the effect of photoactivated lipofuscin on (i) lipid peroxidat...
Summary Backgound : Patients being investigated for symptoms of abdominal pain, diarrhoea and or weight loss often undergo small bowel radiology as part of their diagnostic workup mainly to exclude inflammatory bowel disease. Aim : To assess and compare the utility of a single faecal calprotectin estimation to barium follow through as well as conventional inflammatory markers such as erythrocyte sedimentation rate and C‐reactive protein in exclusion of intestinal inflammation. Methods : Seventy‐three consecutive cases undergoing barium follow through for investigation of symptoms of diarrhoea and or abdominal pain with or without weight loss were studied. The control group comprised 25 cases with known active Crohn's disease (positive controls), 26 normal healthy volunteers (negative controls) and 25 cases of irritable bowel syndrome diagnosed by Rome II criteria. Symptoms, erythrocyte sedimentation rate and C‐reactive protein were recorded at recruitment and a single stool sample assayed for calprotectin within 7 days prior to or after barium follow through. Results : The median calprotectin value in the active Crohn's group, irritable bowel syndrome group and normal volunteers was 227 μg/g of stool, 19 and 10 μg/g respectively (P < 0.0001). A faecal calprotectin above a cut‐off value of 60 μg/g was able to predict all nine cases with an abnormal barium follow through as well as all six cases with a normal barium follow through but with organic intestinal disease. The negative predictive value of a single calprotectin result below 60 μg/g of stool was 100% compared with 91% each for erythrocyte sedimentation rate > 10 mm and C‐reactive protein > 6 mg/L and 84% for a combination of erythrocyte sedimentation rate and C‐reactive protein in predicting absence of organic intestinal disease. Conclusion : A single stool calprotectin value < 60 μg/g of stool obviates the need for further barium radiology of the small bowel, is more accurate than measurement of erythrocyte sedimentation rate or C‐reactive protein and effectively excludes Crohn's disease or non‐functional gastrointestinal disease.
Background Gastroenterologists are often hampered by the lack of a reliable, non-invasive index of bowel inflammation when establishing a differential diagnosis for patients presenting with chronic diarrhoea. Investigations aim to distinguish between inflammatory bowel disease (IBD) (e.g. Crohn's disease, ulcerative colitis) and irritable bowel syndrome (IBS). As an acute phase protein, faecal calprotectin measurement may be useful in this context.
Background: Calprotectin is an acute-phase protein used extensively in the assessment of gastrointestinal inflammation. It can readily be measured by enzyme-linked immunoassay (ELISA) and recently by point-of-care testing (POCT). We evaluated the Quantum Blue w POCT in this study and compared it with our existing ELISA method. Methods: The method comparison study used faecal samples (n ¼ 47) sent to the laboratory for routine calprotectin analysis. Linearity was assessed by serial dilution of extracted faeces (n ¼ 4). Extraction efficiency was determined by repeat extraction of three different stools. The variation in results as a consequence of reading the POCT cartridges either side of the recommended 12 min was also assessed. Results: The assay was linear across the range stated by the manufacturer. When multiple samples were taken from the same stool, results varied from 231.3% to þ31.5%. For the clinical arm of our study, strictly applying the 50 mg/g cut-off recommended for both assays as positive for gastrointestinal inflammation, there were four patients where results fell a different side of the clinical cut-off; two patients had results higher by Quantum Blue w and two higher by ELISA. Conclusions: In our hands, the Quantum Blue w method was a suitable screening test for excluding inflammatory bowel disease. It may be of value to laboratories wishing to offer calprotectin but who do not have sufficient numbers to warrant ELISA methodology or in 'one stop' gastrointestinal clinics where an immediate result is required.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.