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)

Aqueous fluid was withdrawn from eyes of patients undergoing cataract extraction at various intervals after administration of two drops of 2% pilocarpine HCl in a standard manner. Determination of aqueous pilocarpine concentration was made both by spectroscopy of a ferric hydroxylamine complex and by gas-liquid chromatography. Results of both methods were consistent in indicating that concentration does not rise at any time following such topical instillation beyond 5 microgram/ml, with an average of 1.67 microgram/ml, representing a flux efficiency of 0.03%. These findings correlate well with previous investigations of transcorneal flux of pilocarpine for the rabbit in a transport chamber system, in which comparable low flux efficiency was found after simulated drop administration. This serves in some measure to validate an extrapolation of other findings in chamber experiments to the living human eye.
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PMID:Transcorneal flux of topical pilocarpine to the human aqueous. 43 53

Aqueous fluid was withdrawn from eyes of patients undergoing cataract extraction at various intervals after administration of two drops 2% pilocarpine-HCl in a standard manner. Determination of aqueous pilocarpine concentration was made both by spectroscopy of a ferric hydroxylamine complex and by gas-liquid chromatography. These methods were consistent in indicating that concentration does not rise beyond 5 micrograms/ml at any time following topical instillation. The mean of 71 GLC determinations of aqueous tapped between 2 and 32 minutes after drops was 1.67 micrograms/ml. With assumption of a total chamber volume of 400 microliter, the average total pilocarpine in aqueous in these circumstances is less than 1 microgram. These findings correlate well with investigations of transcorneal flux of pilocarpine for the rabbit in a partial in vitro transport chamber system, with which comparable low flux efficiency was found after simulated drop administration. This serves to validate in some measure in extrapolation of other findings in chamber experiments to the living human eye. The combined in vitro and in vivo experimental results suggest that two distinct mechanisms govern the flux of pilocarpine across the cornea. High doses, comparable to those in standard clinical use, whether administered in drops or in constant flow, are transported inefficiently with kinetics indicating a diffusional mechanism and are associated with intracorneal retention or degradation of a substantial moiety. Low doses, if continuously applied, are much more efficiently transported. Hydrogel polymer vehicles appear to mobilize this low-dose mechanism by retaining drug against mechanical dissipation and elution by tear flow, but also by retaining drug against the capability of the cornea to take up more pilocarpine than can be transported to produce an intracorneal drug "depot." Although the exact nature of the "depot" is not clear, it is not elutable as pharmacologically active drug. It is consistently associated with the relatively poor flux efficiency found with high doses, and thus may act in some manner to disable a more efficient mechanism. The flux efficiency found with hydrogel mediation is more than double the best found in constant flow determinations. Vehicular mediated flux is rate limited by the cornea, independent of dose, linear with time despite exponentially secreasing available drug, and not associated with an intracorneal drug "depot." These features are consistent with carrier mediation of some type.
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PMID:Flux of topical pilocarpine to the human aqueous. 75 81

Cataract is the world's leading cause of blindness and a disease for which no efficacious medical therapy is available. To screen potential anti-cataract agents, a lens organ culture model system was used. Opacification of lenses maintained in culture was induced by specific insults including H(2)O(2) or the cataractogenic sugar xylose. Potential anti-cataract agents were added to the culture medium and their ability to inhibit opacification and certain biochemical changes associated with the opacification were assessed. Among the compounds tested, Tempol-H, the hydroxylamine of the nitroxide Tempol, gave the most promising results. It significantly inhibited opacification of rat lenses in an H(2)O(2)-induced cataract system as well as opacification of rhesus monkey lenses induced by xylose. Tempol-H inhibited the loss of glutathione, the leakage of protein, and decreases in the ability of cultured lenses to accumulate (3)H-choline from the medium, all of which were associated with the development of lens opacification. The antioxidative activity of Tempol-H and its ability to re-dox cycle make it an attractive candidate as a therapeutic agent for the prevention of aging-related cataract.
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PMID:Tempol-H inhibits opacification of lenses in organ culture. 1460 18