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)

Both hypertension and cataract formation have been associated with reductions in sodium pump activity, possibly as a result of an endogenous inhibitor. The objective of the present study was to answer 4 closely related questions: (1) Is the lens sodium pump effectively inhibited by a labile, digitalis-like factor we have identified in the peritoneal dialysate from hypertensive patients in end-stage renal failure? (2) How does that inhibition compare to that induced by ouabain? (3) Does sodium pump isoform distribution determine the degree of lens sodium pump inhibition? (This question was precipitated by the unanticipated finding that the labile DLF was more effective in inhibiting lens sodium pump than was anticipated.) (4) Is sodium pump activity altered in lens in response to increased salt intake, a maneuver known to increase endogenous digitalis-like factor? We found that whereas ouabain produced equivalent or significantly less inhibition of lens Na(+), K(+)-ATPase from calf or rabbit, respectively, compared with brain, labile digitalis-like factor preferentially inhibited lens compared with brain. Analysis of whole-lens preparations from rabbit, calf, and normal human lens revealed substantial alpha2- and alpha3-isoforms of the sodium pump but little alpha1-isoform. Ouabain inhibition of whole-lens Na(+),K(+)-ATPase from rabbit and calf were comparable: for rabbit lens, K(i)=5.2x10(-7) mol/L; for calf lens, K(i)=1.0x10(-6) mol/L. Limited quantities of labile digitalis-like factor prohibited similar determinations; however, its concentration-activity profile paralleled that of ouabain. Na(+), K(+)-ATPase activity, measured in the 3 major anatomic regions of lens and normalized to nucleus, was greatest in epithelium (56. 9+/-17.9) compared with cortex (5.8+/-1.4) and nucleus (1.0+/-0.0; P=0.01). Immunohistochemistry of rabbit lens found abundant alpha2- and alpha3-isoforms in epithelium and limited alpha3 but undetectable alpha1 in cortex and nucleus. Finally, rats randomized to a high Na diet showed significantly reduced lens Na(+), K(+)-ATPase activity compared with those on a low Na diet, consistent with the effects of a sodium pump inhibitor. In conclusion, the present study suggests that digitalis-like factor may provide a link between hypertension and cataract formation.
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PMID:Sodium pump inhibition and regional expression of sodium pump alpha-isoforms in lens. 1056

A population-based cross-sectional study (n = 2,873) was conducted near Sydney, Australia, from January 1992 to January 1994 to assess the relation between dietary sodium intake and risk of cataract. Photographs of subjects' lenses were graded for cortical, nuclear, and posterior subcapsular cataracts. Dietary sodium intake was assessed with a food frequency questionnaire. The study found that higher sodium intakes were associated with greater risk of posterior subcapsular cataract (p for trend = 0.006). The adjusted relative risk was 2.0 (95% confidence interval: 1.2, 3.4) for subjects in the highest versus the lowest quintile of sodium intake. These findings suggest that a high-salt diet may increase the risk of posterior subcapsular cataract.
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PMID:Dietary sodium intake and cataract: the Blue Mountains Eye Study. 1073 45

Understanding aqueous protein-protein interactions is crucial for the development of a molecular-thermodynamic model for salt-induced protein precipitation. In addition, protein interactions are important in many disease states, including cataract formation and alpha-amyloid diseases. Fluorescence anisotropy provides a means to measure intermolecular interactions. In this work, monomer-dimer equilibrium of the peptide T4 LYS(11-36) was studied by fluorescence anisotropy over the pH range 4-7 and the NaCl concentration range 0.0-1.0 M, in a 25 mM sodium phosphate buffer. This 26 amino-acid peptide is derived from the beta-sheet region of the T4 lysozyme molecule and has the potential to form amyloid fibrils. The association constant for dimerization increases with rising pH and ionic strength. The potential of mean force for peptide-peptide interactions was calculated from these association constants. Circular-dichroism measurements show that the peptide becomes more structured as the pH rises, possibly contributing to increased association.
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PMID:Interactions of proteins in aqueous electrolyte solutions from fluorescence anisotropy and circular-dichroism measurements. 1079 32

Metal ions, which are present in ocular fluids, can significantly decrease the bioavailability of fluoroquinolones. This in vitro study investigated the bioavailability of ofloxacin and ciprofloxacin in the presence of two balanced salt solutions, BSS-Plus and AMO Endosol, commonly used as irrigants in cataract surgery. Minimum inhibitory concentrations (MICs) and antibiotic susceptibility were determined through broth dilution methods and a standard disk diffusion bioassay with Escherichia coli. Although neither solution affected the in vitro antimicrobial activity of ofloxacin, both markedly decreased that of ciprofloxacin. In BSS-Plus and AMO Endosol, the MICs of ciprofloxacin for several ocular isolates were increased, indicating decreased susceptibility to that drug; the activity of ciprofloxacin against E. coli was also decreased. Because the composition of BSS-Plus is similar to that of human aqueous humor, the clinical efficacy of ofloxacin may be unaffected by the ionic composition of the aqueous humor. In contrast, because the antimicrobial activity of ciprofloxacin was diminished in BSS-Plus, the clinical efficacy of this fluoroquinolone against deep ocular infections may not be as great as indicated by standard laboratory antibiotic susceptibility testing.
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PMID:Effect of two balanced salt solutions on the bioavailability of ofloxacin and ciprofloxacin. 1091 95

Agricultural evaporation basins are used as a means to dispose of highly saline underground-tile-drainage water in the San Joaquin Valley (California, USA). The hypersaline water conditions encourage high aquatic invertebrate production, primarily brine shrimp (Artemia franciscana), which attract birds to these sites. Cool winter temperatures (< 4 C) and hypersaline water conditions (> 70,000 mumhos/cm) resulted in feather salt encrustation and salt toxicosis in ruddy ducks (Oxyura jamaicensis). During December 1998 and January 1999, approximately 200 dead and sick ruddy ducks were collected from an evaporation basin and five healthy control ruddy ducks were collected from a freshwater wetland. Brains contained > or = 1,890 ppm sodium (wet tissue mass) in seven dead birds and contained < or = 1,150 ppm sodium in the control birds. Liver arsenic, lead, and mercury concentrations were < 1 ppm in all birds examined. Manganese, molybdenum, and copper liver concentrations did not differ significantly (P > 0.05) between the two groups of ducks. The dead ducks had significantly higher liver selenium, cadmium, iron, and zinc than the controls, but the concentrations were not sufficient to cause toxicity. Significant gross and microscopic lesions in most of the dead birds included conjunctivitis, lens opacity and cataract formation, vascular congestion in various organs most notably in the meninges of the brain, and myocardial and skeletal muscle degeneration.
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PMID:Salt toxicosis in ruddy ducks that winter on an agricultural evaporation basin in California. 1183 3

Dietary sugar and salt represent etiological risk factors of human cataract. To verify etiological data on the basis of histological findings, 9 pigs with a body weight of 40 kg, 3 months of age, in groups of 3 were continuously fed with 5% of refined dietary sugar (sucrose - C(12)H(22)O(11)), 0.5% of salt (NaCl) and a sugar-salt mixture (2.5 + 0.25% accordingly) in their crude (unboiled) meal food during 3 months, which resulted in minor cataractous changes in the lens. In the second experiment, 10 weight- and age-matched animals were fed a chronic sugar and intermittent salt diet during 6 months; the other 10 animals served as controls. During the second experiment, crystallin leakage into the aqueous humor of the lens was detected, and a marked swelling of the lens fibers and fiber tips was noticed, indicating that excessive amounts of dietary sugar and salt are risk factors for the development of cataract in normal (nondiabetic) animals.
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PMID:Dietary sugar and salt represent real risk factors for cataract development. 1279 39

The study results showed a principle possibility to fragmentize the most dense lens nuclei by means of a nylon cutting loop. The safety and efficiency of applying a loop fragmentizer in phacoemulsification of high-density cataract were equally demonstrated. The method advantages are conditioned by that a preliminary splitting of the nucleus into fragments without trenches being shaped cuts essentially the total capacity and duration of ultrasound impact, thus, the irrigation time and the needed volume of balance salt solution also decrease intraoperatively: it, naturally, diminishes the generally-known traumatic aftermaths of surgical intervention.
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PMID:[A new method of macrofragmentation of dense nuclei by using loop fragmentizer]. 1511 21

Low-salt diets have potential for prevention and treatment of hypertension, and may also reduce risk for stroke, left ventricular hypertrophy, osteoporosis, renal stones, asthma, cataract, gastric pathology, and possibly even senile dementia. Nonetheless, the fact that salt restriction evokes certain counter-regulatory metabolic responses-- increased production of renin and angiotensin II, as well as increased sympathetic activity--that are potentially inimical to vascular health, has suggested to some observers that salt restriction might not be of unalloyed benefit, and might in fact be contraindicated in some "salt-resistant" subjects. Current epidemiology indicates that lower-salt diets tend to reduce coronary risk quite markedly in obese subjects, whereas the impact of such diets on leaner subjects (who are less likely to be salt sensitive) is equivocal--seemingly consistent with the possibility that salt restriction can exert countervailing effects on vascular health. There is considerable evidence that sodium chloride, rather than sodium per se, is responsible for the known adverse effects of dietary salt. Other non-halide sodium salts, such as sodium citrate or bicarbonate, do not raise plasma volume, increase blood pressure, boost urinary calcium loss, or promote stroke in stroke-prone rats. Nonetheless, these compounds have been shown to blunt the impact of salt restriction on renin, angiotensin II, and sympathetic activity in humans. This may rationalize limited clinical evidence that organic sodium salts can decrease blood pressure in salt-restricted hypertensives. Furthermore, organic sodium salts have an alkalinizing metabolic impact favorable to bone health. These considerations suggest that restricting dietary salt to the extent feasible, while encouraging consumption of organic sodium salts in mineral waters, soft drinks, or other nutraceuticals--preferably in conjunction with organic potassium salts and taurine--may represent a superior strategy for controlling blood pressure, promoting vascular health, and preserving bone density. Further clinical studies should determine whether a moderately salt-restricted diet supplemented with organic sodium salts has a better and more uniform impact on hypertension than salt restriction alone, while rodent studies should examine the comparative impact of these regimens on rodents prone to vascular disease.
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PMID:Should we restrict chloride rather than sodium? 1519 67

Medarex is developing MDX-RA, an immunotoxin, for the potential prevention of secondary cataracts. It entered phase III clinical trials in December 1997. The phase III studies will involve 680 patients undergoing primary cataract surgery at approximately 60 sites in the US [272814]. The immunotoxin consists of a murine monoclonal antibody (4197X) that binds specifically to human lens epithelial cells conjugated to a polypeptide toxin, ricin A (RA) chain toxin. MDX-RA is formulated as a salt solution which will be injected into the eye following the removal of the natural opaque lens and the insertion of a clear plastic intraocular lens. The specificity of the antibody directs the agent to the target where RA will exert its cytotoxic activity. The linkage technology used in the manufacture of MDX-RA is proprietary to Sanofi SA and was licensed exclusively to Medarex for use in ophthalmic therapeutics [193106]. Results from a placebo-controlled phase I/II clinical trial demonstrated that patients treated with 50 units of MDX-RA experienced substantially less opacification than patients on placebo [272814]. There was less lens capsule opacification in the treated group than in the placebo group even at this early stage. The company expected to complete additional interim analyses during the two-year follow-up. MDX-RA has also been in phase II trials in patients undergoing bilateral cataract surgery. Santen will fund the clinical development of MDX-RA, at a cost of some US $8 million over six years, in return for an exclusive marketing licence for Japan [204883]. Houston Biotechnology, which was acquired by Medarex in 1997, holds an exclusive worldwide license to patents from the Baylor College of Medicine, to which most of the early patents relating to the immunotoxin are assigned [193106]. Medarex estimates that there will be 1.8 million primary cataract procedures performed in the US in 1998, with the number performed elsewhere equalling this figure. The projected worldwide market potential for MDX-RA, based on these figures, is US $450 to 600 million [193106].
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PMID:MDX-RA Medarex Inc. 1846 81

Cataract, the opacification of eye lens, is the leading cause of blindness worldwide. At present, the only remedy is surgical removal of the cataractous lens and substitution with a lens made of synthetic polymers. However, besides significant costs of operation and possible complications, an artificial lens just does not have the overall optical qualities of a normal one. Hence it remains a significant public health problem, and biochemical solutions or pharmacological interventions that will maintain the transparency of the lens are highly required. Naturally, there is a persistent demand for suitable biological models. The ocular lens would appear to be an ideal organ for maintaining culture conditions because of lacking blood vessels and nerves. The lens in vivo obtains its nutrients and eliminates waste products via diffusion with the surrounding fluids. Lens opacification observed in vivo can be mimicked in vitro by addition of the cataractogenic agent sodium selenite (Na(2)SeO(3)) to the culture medium. Moreover, since an overdose of sodium selenite induces also cataract in young rats, it became an extremely rapid and convenient model of nuclear cataract in vivo. The main focus of this review will be on selenium (Se) and its salt sodium selenite, their toxicological characteristics and safety data in relevance of modelling cataractogenesis, either under in vivo or in vitro conditions. The studies revealing the mechanisms of lens opacification induced by selenite are highlighted, the representatives from screening for potential anti-cataract agents are listed.
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PMID:Different experimental approaches in modelling cataractogenesis: An overview of selenite-induced nuclear cataract in rats. 2121 65


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