Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purposes of these experiments were to measure the influence of 14 trace elements on cataractogenesis and to test if these trace elements could prevent cataracts induced by selenium. On days 5-9 postpartum, suckling white rats received daily subcutaneous injections of either selenium (0.15 mumoles Se, as Na2SeO3, per pup) or selenium plus one of 14 other trace elements (separate subcutaneous injection) at one to five times the molar concentration of selenium. The frequency and severity of cataracts at three locations in the lens were assessed by slit-lamp examination on day 26-28 postpartum. Seven ions were found to be effective in preventing selenium-induced cataracts (% protection): mercuric (100%), silver (80%), cyanide (75%), arsenite (75%), cadmium (60%), and cupric (44%). Tellurite ion offered only 20% protection, while ferrous, zinc, lead, chromic, molybdate, tungstate, and vanadate ions provided no protection against selenium-induced cataract. No significant differences were found between the concentration of selenium in the lenses of control and cataractous lenses when measured approximately three weeks after selenium injection. Except for selenium, none of the trace minerals alone caused cataracts under our experimental conditions. In addition to subcutaneous injection of selenium, oral administration of this element was also found to cause cataract. It was concluded that among the ions studied, selenite was a powerful and rapid promoter of nuclear cataract formation, and that the protection ions may serve as useful probes for elucidating the mechanism of selenium-induced cataracts.
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PMID:Influence of selenite and fourteen trace elements on cataractogenesis in the rat. 683 14

Cigarette smoking is a main source of cyanide in human body, which can be taken as a risk factor of cataract formation. In this study, combined gas chromatography and mass spectrum (GC/MS) was used to determine the amino acid hydantoin after the incubation of soluble human lens gamma-crystallins with cyanate. The carbamylated amino acids obtained by this procedure are alanine and glycine, which are N-terminal amino acids of gamma-crystallin, and leucine. The aggregate, which can be observed in carbamylated gamma 1-crystallin on SDS-PAGE, may be related to the formation of disulfide and non-disulfide covalent bonds, and it seems that gamma 2 and gamma 3-crystallins can not be aggregated to any great extend. The results in this study indicate that the GC/MS is an effective method for analyzing the carbamylation of lens proteins; gamma-crystallin may play a very important role in the formation of cataract associated with accumulation of cyanate in human body, such as heavy smoking.
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PMID:Carbamylation of human lens gamma-crystallins: relevance to cataract formation. 816 8

Oxidative stress is thought to play a major role in cataract formation. The present experiments are aimed at gaining a better understanding of the systems that protect the lens from damage by reactive oxygen species. The aqueous humor normally contains hydrogen peroxide (H2O2), a compound capable of generating reactive oxygen species. The systems protecting the ocular lens from oxidative damage are primarily confined to the epithelium, a single layer of cells on the anterior side of the organ directly beneath the lens capsule. When cultured rabbit lenses were challenged with a single dose of 0.2 mM H2O2, cells in the peripheral region of the epithelium survived; those in the central region died. Here we investigate the histochemical and immunoperoxidase distributions of catalase, an enzyme which detoxifies H2O2, in cells from the peripheral and central regions of the epithelium on flat mount preparations of the epithelium. In a flat mount, the entire population of lens epithelial cells can be viewed on one preparation. The reaction product for catalase activity and its immunoperoxidase localization were more intense in peripheral epithelial cells than in cells throughout the central epithelium. Treatment of cultured lens epithelial cells or rabbit lenses with 3-aminotriazole or potassium cyanide, inhibitors of catalase, reduced or abolished the histochemical reaction product. Ultrastructural cytochemistry confirmed the presence of catalase in microperoxisomes of the epithelial cells from whole lenses. The decreased level of catalase throughout the central epithelium may account for the increased susceptibility of these cells to H2O2-induced cell death.
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PMID:Regional differences in the distribution of catalase in the epithelium of the ocular lens. 869 57

Cyano(2-oxo-2,3-dihydroindol-3-yl)acetic acid derivatives were synthesized and tested as a novel class of aldose reductase (ALR2) inhibitors. Each compound was evaluated as a diastereomeric mixture, due to tautomeric equilibria in solution. The parent compound 39 exhibited a good inhibitory activity with an IC(50) value of 0.85 microM, similar to that of the well-known ARI sorbinil (IC(50) 0.50 microM). The concurrent introduction of a halogen and a lipophilic group in the 5- and in the 1-positions, respectively, of the indole nucleus of 39, gave compound 55, cyano[5-fluoro-1-(4-methylbenzyl)-2-oxo-2,3-dihydroindol-3-yl]acetic acid, which displayed the highest activity (IC(50) 0.075 microM, very close to that of tolrestat IC(50) 0.046 microM), with a good selectivity toward ALR2 compared with aldehyde reductase (ALR1) (16.4-fold), and no appreciable inhibitory properties against sorbitol dehydrogenase (SD), or glutathione reductase (GR). The isopropyl ester 59, a prodrug of 55, was found to be almost as effective as tolrestat in preventing cataract development in severely galactosemic rats when administered as an eye drop solution. Docking simulation of 55 into a three-dimensional model of human ALR2 made it possible to formulate the hypothesis that the 2-hydroxy tautomer was the active species binding into the catalytic site of the enzyme. This was fully consistent with the structure-activity relationships within this series of cyanooxoindolylacetic acid derivatives.
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PMID:Novel, highly potent aldose reductase inhibitors: cyano(2-oxo-2,3-dihydroindol-3-yl)acetic acid derivatives. 1267 41