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)

Abnormalities in glucose metabolism are thought to be among the main causes of cataract formation. We have taken noninvasive biochemical measurements of the lens which provides us with information concerning glucose metabolism in the lens epithelium. The autofluorescence of reduced pyridine nucleotides (PN) and oxidized flavoproteins (Fp) in the rat lens epithelium was measured noninvasively as a function of time using redox fluorometry. The oscillations of the metabolic ratio, PN/Fp, were measured in vivo, in situ, and in the organ-cultured lens. The PN/Fp ratio in the organ-cultured lens ranged from 1.05 to 2.57 within a period of 60-90 minutes (mean +/- SD = 1.52 +/- 0.36). This PN/Fp ratio increased by 23% when a respiratory inhibitor (8 mM KCN) was applied to the lens. However, it decreased by 10% in the presence of a complete metabolic inhibitor (8 mM iodoacetamide). The presence of metabolic oscillations in the in vivo, in situ and cultured lens indicates that this oscillation is a local phenomenon. In cell-free extract systems, oscillations of several intermediates in the glycolytic pathway have been previously demonstrated and this PN/Fp oscillation is thought to be a reflection of glycolytic oscillation.
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PMID:Glycolytic oscillation and effect of metabolic inhibitor on rat lens. 146 67

Four different methods for transferring conjunctival fluid to stix test pads were studied. One hundred and twenty eyes from 120 cataract-extracted patients (35 in the operated eye 0-5 days post-operatively and 85 in the contralateral eye) were included in the study. Transfer of fluid by a glass rod from the lateral part of the inferior fornix was demonstrated to be the most suitable method, showing the highest sensitivity to leucocyte-esterase (83%, N = 120, p < 0.05) and with a specificity equal to that of the other methods tested (cotton, spongostan, Schirmer paper strip). The glass rod method is suitable for detecting blood, nitrite, albumin, pH, and glucose, and is a both quick and unintrusive procedure. All four transferring methods may, however, cause an increased desquamation of epithelial cells and an increased amount of mucus.
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PMID:Sampling methods for tear stix tests. 148 83

Congenital cataract occurs in 90-95% of diabetic rat fetuses. The pathogenetic mechanism is triggered by fetal hyperglycemia and presents the following steps: (1) a high glucose concentration in the lens; (2) reduction of glucose to sorbitol by aldose reductase; (3) accumulation of sorbitol into the fibers of the lens creating a hyperosmotic effect, leading to (4) an infusion of liquid into the fibers, which (5) become hydropic and degenerate (vacuolization). This series of manifestations might also occur in fetuses of pregnant diabetic mothers. Post birth glycemia diminishes rapidly, and this favorable condition which decreases vacuolization is perhaps the reason why such degeneration has not yet been observed. Since the fibers of the lens are permanent cells, damage in the fetal period might later bring about negative consequences. We hope that someone will study whether this ocular pathology occurs in human infants born to diabetic mothers.
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PMID:Damage to the crystalline lens in infants of diabetic mothers: a pathology so far neglected? 151 48

The purpose of this study was to investigate the physiological effects of irradiation in the spectral range 295-340 nm in cultured rabbit lenses. Ultraviolet B cataract was produced in lenses exposed to low levels of irradiation, 1-2 mW/cm2. Opacification was assessed by laser transmittance measurements. The changes observed during lens culture after a 1 hr dose (4 J/cm2) include a gradual increase in hydration, sodium concentration, and calcium levels. Loss in membrane voltage and a rise in 36Cl accumulation indicate that membrane permeability was increased. The cation pump was impaired within 20 hr of irradiation, as concluded by an observed fall in 22Na efflux. Availability of glucose for cation transport was diminished based on the reduced rate of uptake of tritiated 3-o-methylglucose in irradiated lenses, but this reduced accumulation was observed much later than was sodium elevation. Ionic imbalances and opacification required less than 1 d of culture for 4-12-wk-old lenses and required nearly 7 d of culture for 100-wk-old lenses.
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PMID:Physiological effects of UVB irradiation on cultured rabbit lens. 155 78

In tissues susceptible to damage from chronic diabetes, excess glucose is metabolized by aldose reductase (AR) to sorbitol. Originally, AR-catalyzed sorbitol formation (and accumulation) was found in the diabetic lens; the cataractogenicity of this process was proven by preventing cataract formation with an AR inhibitor (ARI). These findings were extended to the hypothesis that, in diabetic tissues, excessive intracellular sorbitol formation initiates a cascade of metabolic abnormalities which gradually progress to loss of functional and structural integrity. The pivotal role of AR as a trigger for such abnormalities was established by preventing their occurrence in diabetic animals treated with an ARI. By inference, this led to the concept that inhibition of AR should prevent, arrest, and, possibly, reverse the development of late diabetic sequelae. In addition to motivating drug-oriented research, the ARI concept provided a rationale for the use of ARIs as experimental tools to probe the pathogenesis of diabetic complications. By helping to elucidate the metabolic, functional, and structural ramifications of the AR-catalyzed disposal of excess glucose in diabetic schemes, and in addition, by helping to define the applicability of animal models for the study of early functional pathogenic alterations occurring in diabetic subjects, ARIs may enable the discrimination in diabetic tissue of arrestible and reversible from the irreversible abnormalities.
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PMID:Aldose reductase inhibitors as pathobiochemical probes. 156 55

Evidence from epidemiological, in vitro and animal studies has accumulated to support the idea that aspirin, ibuprofen and paracetamol protect against cataract. In this study rats made diabetic with streptozotocin were given these drugs in their drinking solution for up to 160 days. All three drugs delayed cataract formation assessed by slit-lamp examination for a large part of this time. Blood glucose levels were a little lower in diabetic rats treated with aspirin and ibuprofen than in untreated diabetic rats although all groups remained diabetic. Similarly, the increased glycation (non-enzymic glycosylation) of lens proteins caused by diabetes was less in the diabetic rats treated with aspirin and ibuprofen. The fall in glutathione induced by diabetes was also alleviated by aspirin and ibuprofen. Paracetamol appeared to afford similar protection against the biochemical changes but its effect was not statistically significant. The decrease in glutathione and increase in glycation were related to the progression of lens opacification. The greatest loss of glutathione occurred at an early stage, whereas glycation had its greatest change at the later stages--nuclear and mature cataract. These results encourage the view that ibuprofen, aspirin and paracetamol could protect against cataract in man: a hypothesis that could be tested in a properly-conducted clinical trial.
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PMID:Prevention of cataract in diabetic rats by aspirin, paracetamol (acetaminophen) and ibuprofen. 162 37

The effects of a new aldose reductase inhibitor, 7-fluoro-2-(N-methyl-N-carboxymethyl)sulfamoyl xanthone (BAL-ARI8, CAS 124066-40-6), on the diabetic complications of streptozotocin-induced diabetic rats were studied. The daily administration of BAL-ARI8 throughout the 8-week course of the experiment sharply decreased the sorbitol accumulation in the lens of the diabetic rats. The incidence of cataract formation was also reduced, being detected in only 45% of BAL-ARI8 treated animals, against the 100% of diabetic controls showing cataract after 8 weeks from diabetes onset. On the other hand, the serum glucose levels remained unchanged. In diabetic controls, there was about a 2.5-fold increase of the total protein urinary excretion during the 24 h. Treatment with BAL-ARI8 prevented up to 70% of this increase. Individual protein components were examined by polyacrylamide gel electrophoresis and quantitated by laser densitometric analysis. Diabetic-induced proteinuria primarily resulted from excretion of newly detected proteins with molecular weight in the range 30,000-60,000 D, together with an increase of albumin (25% of the total excretion) and the presence of new higher molecular weight proteins (greater than 66,000 D). BAL-ARI8 administration resulted in a shift of the protein profile back toward normality i.e. 73% of proteins with molecular weight below 30,000 D, 7.5% albumin and no proteins above 66,000 D. These results suggest that BAL-ARI8 may represent a therapeutic approach for the management of diabetic complications.
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PMID:Effects of a new aldose reductase inhibitor on diabetic complications in rats. 181 Feb 61

We conducted a randomised prospective controlled study to determine the effects of a glucose glutathione bicarbonate solution (BSS Plus) and a citrate acetate bicarbonate solution (S-MA2) on the corneal endothelium in patients undergoing extracapsular cataract extraction with posterior chamber lens implantation. One eye of each patient was randomly assigned to receive BSS Plus, and the other eye to receive S-MA2. BSS Plus caused significantly less corneal swelling on the first postoperative day than did S-MA2. There was no difference between the two solutions in their effect on corneal thickness one week and one month postoperatively. Computer assisted morphometric analysis of wide-field specular microscopic photographs demonstrated minimal changes in endothelial morphological characteristics in the eyes irrigated with BSS Plus. By comparison S-MA2, caused a significant loss of endothelial cells and a marked reduction in the figure coefficient. These results indicated that BSS Plus has a clinical advantage over S-MA2 with respect to the corneal endothelium.
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PMID:Comparison of the effects of intraocular irrigating solutions on the corneal endothelium in intraocular lens implantation. 187 66

We studied the plasma catecholamine, plasma glucose and cardiovascular responses to cataract surgery in 20 elderly patients allocated randomly to receive either general anaesthesia or local anaesthesia by retrobulbar block. Local anaesthesia prevented the increase in plasma noradrenaline, adrenaline and glucose concentrations found in those patients who received general anaesthesia and also improved cardiovascular stability. The results show the beneficial effects of local anaesthesia in preventing the hormonal, metabolic and cardiovascular changes found when cataract surgery is conducted under general anaesthesia.
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PMID:Plasma catecholamine response to cataract surgery: a comparison between general and local anaesthesia. 188 69

FR74366 (FK366) ([3-(4-bromo-2-fluorobenzyl)-7-chloro-2,4-dioxo-1,2,3,4- tetrahydroquinazolin-1-yl] acetic acid) is a chemically novel aldose reductase (AR) inhibitor. It exhibited a highly potent, reversible, and mixed type inhibition of partially purified AR from the rat sciatic nerve (IC50 = 3.6 nmol/L) and rat lens (IC50 = 4.4 nmol/L). FR74366 inhibited sorbitol accumulation in the isolated human erythrocyte (IC50 = 1.6 mumol/L), rat lens (IC50 = 39 mumol/L), and rat sciatic nerve (IC50 = 17 mumol/L) incubated with high glucose concentrations. The oral administration of FR74366 to streptozotocin (STZ)-induced diabetic rats for 2 weeks decreased sorbitol levels (ED50 = 3.7 mg/kg for sciatic nerve, 23 mg/kg for lens, 52 mg/kg for retina, and 62 mg/kg for renal cortex). Administration of FR74366 to diabetic rats for 17 weeks delayed cataract formation and admixture of 0.028% FR74366 in the diet completely inhibited the cataract formation. Moreover, the recovery of reduced motor nerve conduction velocity by FR74366 in diabetic rats was demonstrated in prevention and reversal experiments. This recovery effect correlated well with reduction of accumulated sorbitol and fructose levels and normalization of decreased myoinositol levels. The duration and tissue specificity of inhibitory effects of FR74366 on sorbitol accumulation also correlated well with the levels of FR74366 in various tissues of diabetic rats. These data indicate that both decreases in tissue sorbitol levels and improvement of functional defects reflect FR74366 levels in tissue rather than plasma in diabetic rats. These results, taken together, suggest that FR74366, which is currently undergoing clinical trials in Japan and the United States, will be a useful therapeutic agent for diabetic complications.
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PMID:Characterization of a novel aldose reductase inhibitor, FR74366, and its effects on diabetic cataract and neuropathy in the rat. 189 18


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