| Increased sulfatation of orbital glycosaminoglycans in Graves' ophthalmopathy. | |
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MedLine Citation:
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PMID: 10199787 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Accumulation of interstitial glycosaminoglycans (GAG) in orbital tissue of patients with Graves' ophthalmopathy (GO) leads to edema, increased orbital pressure, and proptosis. In this study, a new, highly sensitive, high performance liquid chromatography method was developed to determine the altered concentration and biochemical composition of different GAG polymers in orbital connective tissue of 27 GO patients and 18 controls. GAG were isolated by tissue homogenization and digestion, followed by sequential enzymatic GAG hydrolysis and high performance liquid chromatographic analysis of the resulting alpha,beta-unsaturated disaccharides. High recovery rates of 78 +/- 6% (mean +/- SE) and a detection limit of 4.0 microg/L (0.01 micromol/L) were obtained. Total tissue GAG amounted to 254 +/- 16 microg/g wet tissue wt in patients and 150 +/- 13 microg/g (P < 0.0001) in controls. Regarding the GAG polymers, marked differences were detected between patients and controls (chondroitin sulfate, 127 +/- 13 vs. 47 +/- 5 microg/g; hyaluronic acid, 56 +/- 5 vs. 34 +/- 4 microg/g; both P < 0.0001; dermatan sulfate, 77 +/- 6 vs. 69 +/- 6 microg/g; P < 0.05). In patients, chondroitin sulfate was the major GAG component (48 +/- 6 vs. 31 +/- 5% of total GAG in controls), whereas dermatan sulfate was dominant in controls (46 +/- 8% vs. 30 +/- 5%). The sulfated disaccharide digestion products were markedly increased (P < 0.0001) in patients, and the ratio of sulfated vs. total disaccharide content was 85 +/- 6% vs. 65 +/- 5% (P < 0.05) in patients and controls, respectively. As accumulation of negatively charged sulfate residues in GAG disaccharides results in enhanced water-binding capacity, beside inflammation and increased volume of the orbital adipose tissue, the altered structure and nature of sulfated GAG units in the orbit may be responsible for the pathogenic changes in Graves' ophthalmopathy. |
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Authors:
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C Hansen; R Rouhi; G Förster; G J Kahaly |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: The Journal of clinical endocrinology and metabolism Volume: 84 ISSN: 0021-972X ISO Abbreviation: J. Clin. Endocrinol. Metab. Publication Date: 1999 Apr |
Date Detail:
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Created Date: 1999-04-21 Completed Date: 1999-04-21 Revised Date: 2005-11-17 |
Medline Journal Info:
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Nlm Unique ID: 0375362 Medline TA: J Clin Endocrinol Metab Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1409-13 Citation Subset: AIM; IM |
Affiliation:
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Department of Endocrinology/Metabolism, Gutenberg-University Hospital, Mainz, Germany. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Aged, 80 and over Chromatography, High Pressure Liquid Female Glycosaminoglycans / metabolism* Graves Disease / metabolism* Humans Male Middle Aged Orbit / metabolism* Sulfates / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Glycosaminoglycans; 0/Sulfates |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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