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Aqueous fluid was withdrawn from eyes of patients undergoing cataract extraction at various intervals after administration of two drops of 2% pilocarpine HCl in a standard manner.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Aqueous fluid was withdrawn from eyes of patients undergoing cataract extraction at various intervals after administration of two drops 2% pilocarpine-HCl in a standard manner.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

Pretreatment with topical nonsteroidal anti-inflammatory drugs is common practice to maintain maximal pupil dilation for cataract surgery. Most surgeons also inject a cholinergic agent intracamerally for miosis after intraocular lens insertion. We evaluated the effects of topical suprofen and flurbiprofen on the miosis induced by anterior chamber irrigation with either acetylcholine or carbachol. One eye of 30 pigmented rabbits was dilated with cyclopentolate HCl and phenylephrine HCl. Three groups, each composed of ten eyes, received flurbiprofen, suprofen, or a control. In each group, five eyes received acetylcholine by anterior chamber irrigation and five received carbachol. Pupil diameters were measured with calipers before and five minutes after irrigation by an observer unaware of the treatment regimen. Irides irrigated with carbachol constricted less than those irrigated with acetylcholine (P = .016). In anterior chambers irrigated with carbachol, suprofen was associated with less miosis than either tears (P = .005) or flurbiprofen (P = .009); however, if the infusion was performed with acetylcholine, no differences between the three groups were noted (P = .44).
J Cataract Refract Surg 1991 Nov
PMID:Effects of topical suprofen and flurbiprofen on the miosis produced by anterior chamber irrigation with cholinergic agonists. 177 49

To assess the effect of aspirin on cataractogenesis, we compared the stability of individual, native protein fractions alpha L, beta H, beta L, beta s, beta B2, gamma-II, gamma-III and gamma-IV with that of their acetylated counterparts. The conformational stabilities of native fractions beta B2 and beta s, which were not reported earlier, were determined first from their thermal and a thermal denaturation behaviour. Since alpha L, beta H and beta L fractions are oligomeric, no thermodynamic analysis of these fractions was attempted. The thermal stability of beta s and beta B2 is rather low; their melting temperature (T1/2) range is 58-60 degrees C compared with 67-75 degrees C for the gamma-crystallins. Furthermore, except for alpha L, which remains stable even at 100 degrees C, and beta B2, all crystallins aggregate at temperatures slightly above T1/2. The Gibbs free energy of unfolding, delta GH2OD, calculated from guanidine HCl (GdnHCl) denaturation, is surprising low (3-9 kcal mol-1) for all crystallin fractions. The low values of delta GH2OD indicate that the structural destabilization of these proteins, which may lead to cataract formation, could result from a slight disturbance of a particular kind (sugar, UV light, oxidation, and other factors). The overall effect of acetylation on the individual crystallin fractions is mixed. The thermal stability of beta B2 increased, tended to decrease in the case of gamma-crystallins, but remained virtually unchanged for other proteins. Delta GH2OD values of the native crystallin fractions do not differ significantly from those of their acetylated counterparts.
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PMID:Effect of acetylation by aspirin on the thermodynamic stability of lens crystallins. 226 81

The conformational stabilities of bovine lens gamma-crystallin fractions II, IIIA, IIIB, and IVA and those modified with glutathione were compared by studying the thermal and guanidine hydrochloride (Gdn-HCl) denaturation behavior. The conformational state was monitored by both far-UV CD and fluorescence measurements. All the gamma-crystallins studied showed a sigmoidal order-disorder transition with varied melting temperatures. The thermal denaturation of these proteins is reversible up to a temperature 3 or 4 degrees C above T 1/2; above this temperature, irreversible aggregation occurs. The validity of a two-state approximation of both thermal and Gdn-HCl denaturation was tested for all four crystallins, and the presence of one or more intermediates was evident in the unfolding of IVA. delta GDH2O values of these crystallins range from 4 to 9 kcal/mol. Upon glutathione treatment IVA showed the maximum decrease in T 1/2 by approximately 9 degrees C and in delta GDH2O value by 29%; the smallest decrease in T 1/2 was for IIIA by 2 degrees C and in delta GDH2O by 15%. We have demonstrated that the glutathione reaction can dramatically reduce the conformational stability of gamma-crystallins and, thus, that the thermodynamic quantities of the unreacted crystallins can be used to evaluate the stability of these proteins when modified during cataract formation.
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PMID:Thermodynamics of thermal and athermal denaturation of gamma-crystallins: changes in conformational stability upon glutathione reaction. 230 85

A new method has been devised for the complete hydrolysis of proteins with an extremely low level of racemization of amino acids. Proteins are incubated in 10 M HCl at a low temperature to obtain partial hydrolysis. They are then incubated with pronase and finally with leucine aminopeptidase and peptidyl-D-amino-acid hydrolase from Loligo vulgaris. The proposed method ensures the total hydrolysis of either purified proteins or proteins contained in a crude homogenate of animal or vegetable tissue. In both cases, the racemization of amino acids (expressed as rate of D form/D + L form X 100) was lower than 0.015% for aspartic acid and lower than 0.01% for other amino acids. D-Amino acids released from peptides or proteins were estimated with enzymatic methods based on the use of octopus D-aspartate oxidase or hog kidney D-amino acid oxidase; with these enzymes, 0.05 nmol of a D-amino acid was determined in the presence of up to 20 mumols of a mixture of L-amino acids (ratio %D/D + L = 0.00025). The method allows the determination of D-amino acids either in tissues in which they are present in high concentrations (as human cataract lenses, tooth enamel, etc.) or in those with low enantiomer content (as brain, erythrocytes, etc.). Using the method described, we hydrolyzed several synthetic peptides consisting of D- and L-amino acids and determined the amount of D-amino acids. In addition, we totally hydrolyzed all the nuclear proteins of human cataractous lenses. The amount of D-aspartic acid was 0.026 mumols/mg in lenses of women aged between 71 and 76 years and 0.0256 mumols/mg in lenses of men aged between 55 and 72 years. The D-aspartic acid measured corresponds to about 12% with respect to total aspartic acid.
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PMID:Total hydrolysis of proteins with strongly reduced racemization of amino acids. 230 73

Because the cholesterol concentration of lens fiber cell membrane in general and lens intercellular junctions in particular is comparatively high, it is likely that it plays a major role in maintaining these structures. In addition, the high concentration of cholesterol in fiber cell membrane is also likely to influence membrane fluidity. Subcutaneous injections of U18666A (3 beta-(2-diethylaminoethoxy) androst-5-en-17-one HCl) into rats effects: (1) a blockade of sterolgenesis in the lens; (2) a depletion of lens fiber cell membrane cholesterol; and (3) the development of irreversible nuclear cataracts. In the present study we have analyzed the ultrastructure of lens fiber cell membrane in adult rats, these by the freeze-etch technique. Whereas it has been previously demonstrated that intercellular junctions comprise approximately one-third of the intermediate cortical fiber cell membrane in adult rats, these junctions were completely absent between comparable fiber cells taken from opaque regions of the U18666A cataractous lenses. There was also a concomitant increase in the extracellular space between the opaque fiber cells and a substantial redistribution of intramembrane proteins in the exoplasmic and protoplasmic faces of these cells. These findings support a "hypothesis" that inhibition of endogenous lens cholesterol production leads to damage and/or degeneration of lens fiber cell membrane in general and in intercellular junctions in particular, resulting in the production of an irreversible nuclear cataract.
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PMID:An ultrastructural analysis of plasma membrane in the U18666A cataract. 333 83

The level of lipid peroxidation products (LPP) was determined in the aqueous humor from the anterior chamber of patients with cataract and donor eyes. The content of LPP in senile cataract aqueous humor was shown to be significantly increased. To determine the possible mechanism of LPP increase in aqueous humor, human lenses at different stages of cataract as well as transparent human and rabbit lenses were incubated for 3 hours in 3.0 ml medium containing liposomes (0.5 mg/ml) prepared from phospholipids from the egg yolk and 0.14 M NaCl + 0.01 M TRIS-HCl buffer, pH 7.4). Corrections were made for phospholipid autooxidation. The level of LPP accumulation in the medium was determined by MDA assay. The rate of LPP production increased significantly in transparent lenses and in early senile cataract, as compared to controls and advanced (mature) cataracts. EDTA (1 mM), superoxide dismutase (114 u/sample), catalase (900 u/sample), chelated iron (III): Fe3+-ADP addition to the incubation medium depressed the level of LPP accumulation. This suggests the participation of Fe2+, O2-., H2O2 in the mechanism of LPP production in the lens. The induction of lipid peroxidation in the lens can be significant for leukotriene and prostaglandin synthesis in the eye.
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PMID:[Crystalline lens induction of lipid peroxidation]. 380 49

Fifty patients in a double-blind study received in randomized fashion either etidocaine HCl (Duranest) 1% or lidocaine HCl (Xylocaine) 2% with epinephrine 1:200,000 in a retrobulbar block for cataract surgery. Two parallel groups of 25 patients each were studied comparing the clinical properties of the drugs. The onset time for sensory and motor blocks of both drugs was essentially the same (3 minutes). The duration of action of etidocaine was considerably longer than lidocaine and less postoperative pain medication was required by patients blocked with etidocaine.
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PMID:Etidocaine used for retrobulbar block: a comparison with lidocaine. 699 10

Opacification of the posterior lens capsule, (secondary cataract), is one of the major complications of extracapsular cataract extraction. The lens epithelial cells remaining after surgery migrate and proliferate along posterior capsule, and give rise to structures such as pearls and cells with contractile properties, which considerably hamper vision. One pharmacological approach aimed at limiting this phenomenon would be to stop this cell migration, thus inhibiting their proliferation. It has been shown that cells adhere and migrate on their support via adhesion molecules such as integrins. Generally, the tripeptide sequence Arg-Gly-Asp (RGD) is the recognition motif for these receptors. In this study, cell adhesion inhibition in the presence of RGD peptides and derivatives was measured on extracellular matrix and lens capsule. One of these compounds, the [N alpha-acetyl-NG(H+)-arginyl]-glycyl-[C beta (H)-C alpha -benzyl]-aspartamid- HCl] (LCM 1910), significantly inhibited cell migration at millimolar concentrations, and could be of interest in prevention of secondary cataract.
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PMID:Inhibition of cell adhesion to lens capsule by LCM 1910, an RGD-derived peptide. 771 6


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