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 purpose of the present study was to examine the effects on cataractogenesis of daily sc administration of the Ca2+ antagonist drug verapamil to diabetic rats. Streptozotocin-induced diabetic rats were given verapamil half-way through the 8-week experimental period or during the full 8 weeks of diabetes. Verapamil administration had no effect on the high blood glucose values, low circulating insulin levels, or elevated triglyceride and cholesterol concentrations in the diabetic rats. Untreated diabetic rats had a 90% incidence of cataracts. Four weeks of verapamil administration reduced this incidence to 41%, and a full 8 weeks of drug treatment further lowered the incidence to 20%. Diltiazem, another Ca2+ antagonist, lowered the incidence of cataracts in the diabetic rats to a similar extent. Verapamil administration to the diabetic animals also partially protected against the presence of retinal microangiopathy in the diabetic animals. Lenticular hydration and lipid accumulation were only indirectly related to cataractogenesis in the diabetic rats and its protection by verapamil treatment. Lenticular electrolyte imbalance, particularly Ca2+, in the diabetic animals was closely correlated with cataract formation, and verapamil significantly reduced the alterations in these ion concentrations. The present results demonstrate the efficacy of verapamil as a protective agent against cataractogenesis and some retinal damage in diabetic animals. Most importantly, this occurs in the absence of any change in the glycemic status of the diabetic animals. The findings strongly support a role for lenticular Ca2+ imbalance in cataract development in diabetes and provide initial evidence to suggest its clinical use in the diabetic population at risk for blindness.
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PMID:Cataract formation is prevented by administration of verapamil to diabetic rats. 275 74

The clinical, biochemical and radiological features of spontaneously occurring hypoparathyroidism in 13 patients (mean age 9 years, range 4 months to 20 years) are highlighted. Nine patients presented with a history of generalised seizures and 2 were in acute hypocalcemic crisis at the time of admission. Ocular involvement (corneal opacities, cataract) was present in 3 patients and vitiligo in 1 patient. The serum calcium level was low (mean 5.46 mg/dl, range 5.0-7.2) and serum phosphorus level was high (mean 8.49 mg/dl, range 6-14 mg/dl) in all the patients. Six patients had elevated serum alkaline phosphatase (greater than 20 KAU). Radiological examination revealed osteopenia in 3 patients. Nine patients underwent a head CT scan; 5 had evidence of basal ganglia calcification. The findings of elevated serum alkaline phosphatase and osteopenia are at variance with existing literature and may possibly reflect pre-existing vitamin D deficiency.
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PMID:Spontaneous hypoparathyroidism: clinical, biochemical and radiological features. 280 54

The purpose of this experiment was to assess the roles of free, intracellular calcium and calcium-dependent neutral protease (calpain II, EC.34.22.17) in selenite nuclear cataract. Free calcium ion concentrations within lens nuclear fibers during selenite cataractogenesis increased to 3 microM on day 2 post-injection (clear lens) and to 108 microM at day 4 (nuclear cataract). Calpain II is known to be activated in vitro by calcium levels above 50 microM. Calpain II activity was present in the lens nucleus at time periods preceding formation of selenite cataract. These data suggested that after selenite injection, calpain II was activated by elevated free calcium in the nucleus, and that calpain II-induced proteolysis of nuclear proteins was an important mechanism in selenite cataract. Calpain II levels were also observed to decrease in the nucleus during selenite cataractogenesis, probably due to autolysis. This was supported by the finding that incubation of purified lens calpain II with 100 microM calcium caused partial inactivation of the protease.
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PMID:Regional distribution of free calcium in selenite cataract: relation to calpain II. 282 Aug 91

The role of the plasma membrane in the regulation of lens fiber cell cytosolic Ca2+ concentration has been examined using a vesicular preparation derived from calf lenses. Calcium accumulation by these vesicles was ATP dependent, and was releasable by the ionophore A23187, indicating that calcium was transported into a vesicular space. Calcium accumulation was stimulated by Ca2+ (K1/2 = 0.08 microM Ca2+) potassium (maximally at 50 mM K+), and cAMP-dependent protein kinase; it was inhibited by both vanadate (IC50 = 5 microM) and the calmodulin inhibitor R24571 (IC50 = 5 microM), indicating that this pump was plasma-membrane derived and likely calmodulin dependent. Valinomycin, in the presence of K+, stimulated calcium uptake, suggesting that the calcium pump either countertransports K+, or is regulated in an electrogenic fashion. Inhibition of calcium uptake by selenite and p-chloromercuribenzoate demonstrates the presence of an essential -SH group(s) in this enzyme. Calcium release from calcium-filled lens vesicles was enhanced by Na+, demonstrating that these vesicles also contain a Na:Ca exchange carrier. p-Chloromercuribenzoate and p-chloromercuribenzoate sulfonic acid also promoted calcium release from calcium-filled vesicles, suggesting that this release, like calcium uptake, is in part mediated by a cysteine-containing protein. We conclude that lens fiber cell cytosolic Ca2+ concentration could be regulated by a number of plasma membrane processes. The sensitivity of both calcium uptake and release to -SH reagents has implications in lens cataract formation, where oxidation of lens proteins has been proposed to account for the elevated cytosolic Ca2+ in this condition.
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PMID:Calcium regulation by lens plasma membrane vesicles. 284 Aug 57

Microelectrode studies of fresh human and rabbit lens epithelia revealed stable membrane potentials [VR (human) = -36 mV; VR (rabbit) = -45 mV] and low input resistances [Ri (human) = 10 M omega; Ri (rabbit) = 20 M omega]. Coupling studies, using two voltage microelectrodes, demonstrated that the low input resistance of the fresh epithelial tissue was due to electrotonic coupling, which was found to be extremely labile and sensitive to perfusion of the apical (fibrefacing) surface of the epithelium. The intercellular coupling could be stabilized by raising the calcium concentration of the perfusate. Studies performed on confluent monolayers of cultured human lens epithelial (HLE) cells demonstrated a membrane potential (VR = -33 mV) and input resistance (Ri = 29 M omega) similar to their fresh counterparts. The intercellular coupling of these cells was found to be much more robust. Ultrastructural studies revealed that the apical junction of cultured HLE cells was less complex than that found in fresh tissue, the latter exhibiting multiple interdigitations and folds. The cultured monolayer was dissociated into single cells by a variety of methods and the membrane properties of individual cells were studied. Single cells were found to have a lower membrane potential (-20 to -25 mV) and an input resistance in the range 110-170 M omega, depending on the method of dissociation. Channel blocking and ion replacement studies revealed significant conductance pathways for potassium, sodium and chloride and a cell-attached patch clamp investigation revealed three distinct channel types. Of the two channels with inward currents at the resting potential, one, with a conductance of 25 pS, is identified as a non-selective cation channel, and the other, with a conductance of 14 pS and reversal potential of - 14 mV, is a possible candidate for a chloride channel but has yet to be characterized. A third channel with an outward current at the resting potential is identified as a potassium channel with a conductance of 49 pS. A link between epithelial uncoupling and certain types of cataract is proposed.
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PMID:Fresh and cultured human lens epithelial cells: an electrophysiological study of cell coupling and membrane properties. 284 35

Myotonic dystrophy (MyD) is a multisystemic disorder characterized by muscle atrophy, myotonia and cataract. Although a number of reports have been accumulated showing the presence of bone changes in MyD patients, there are few published papers in which calcium metabolism was precisely examined. In the previous paper, we reported that intestinal calcium absorption was increased in MyD patients due to the elevation of plasma 1,25(OH)2D level. The present study was designed to elucidate the mechanism of increased level of serum 1,25(OH)2D concentration in MyD patients. Calcium tolerance tests were performed in 13 patients with MyD, 13 patients with other neuromuscular disorders (non-MyD) and 12 healthy control subjects according to the method of Broadus et al. Immunoreactive PTH (iPTH) levels and cyclic AMP (cAMP) levels were measured using commercially available RIA kits. The basal plasma calcium levels in MyD were slightly higher than those in the other two groups, but the difference was not statistically significant. The plasma 1,25(OH)2D levels, calcemic responses and calciuric responses in MyD were significantly higher than those in the other two groups. Serum iPTH levels in MyD (0.462 +/- 0.320 ng/ml, Mean +/- SD) were significantly higher than those in the other two groups (normal subjects 0.175 +/- 0.092, non-MyD 0.200 +/- 0.111; p less than 0.02). Nephrogenous cyclic AMP (NcAMP) levels in MyD (2.094 +/- 3.244 nmol/100 ml GF) were also higher than those in normal subjects (0.907 +/- 0.212, p less than 0.05) and in non-MyD (0.929 +/- 0.335, p less than 0.05). There was a significant correlation between serum iPTH levels and NcAMP levels, and therefore it might be possible to accept that these two measurements reflect the level of parathyroid function.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Abnormal calcium metabolism in myotonic dystrophy (II): Increased level of nephrogenous cyclic AMP and serum immunoreactive parathyroid hormone]. 285 65

The precise factors responsible for the cataract formation are not known. The role of Na+-K+-ATPase in maintaining ionic concentration of lens and lens membrane permeability and its involvement in the formation of cataracts has been of recent interest. Thus the present study was undertaken to study the effect of pre-treatment with Ouabain, a known Na-K-ATPase inhibitor, on the intra-lenticular ionic concentration and the rule of lens membrane permeability in cataractogenesis. Fresh goat lenses were used for the experimental work. Isolated lens culture technique was used. The electrolytes were estimated before and 24 hours after Ouabain pre-treatment. The electrolyte pattern showed significant changes after pre-treatment with Ouabain. Lens sodium ion concentration increased significantly with a concommitant decrease in potassium ion concentration. Intra-lenticular chloride concentration also showed a significant increase as compared to control. Calcium and magnesium ion concentrations also showed slight increase after the inhibition of Na+-K+-ATPase system by Ouabain.
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PMID:Effect of inhibition of lens membrane Na+-K+ ATPase by ouabain pre-treatment--an in vitro study. 285 21

The specificity of the action of low-molecular-weigh heparin promotes its prevention use in ophthalmological surgery, where any hemorrhage, even if not of vital consequence, can reduce and even cancel out the results of the surgery. Consequently, we subjected 63 patients (21 male, 42 female) aged 54 to 93 to preventive treatment with Fraxiparine (CY 216) as per the conventional indications of risk factors: essentially venous insufficiency [23], varicose veins [29], a history of phlebitis [20] or pulmonary embolism [12]. A first group of 31 patients (protocol P 1) was given the first injection 2 hours prior to surgery (D 0). A second group of 32 patients (P 2) was given the injection at 10 p.m. on the eve of surgery (D-1). P 1 and P 2 were given CY 216 (0.3 ml, one injection at 6 a.m.) each day from D 1 to D 7 (and 7 patients from P 1 until D 10). The type of surgery concerned was: cataract [46], retinal detachment [11], glaucoma [3]; fifteen patients had already undergone surgery and 6 were given CY 216 twice. P 2 was compared with a control group T of 20 patients (7 male, 13 females, mean age 71.8) in the same department given calcium heparin sc (3 x 0.2 ml daily, D 1 to D 7). In P 1 and P 2, as well as in the T group, no clinical thromboembolic complications were observed. Tolerance, however, differed. In P 1: 2 cases of hyphema and one of choroidal hematoma. In P 2: no significant hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Tolerability in ophthalmologic surgery of CY 216 in preventing venous thrombosis of the leg]. 285 75

Selenite-cataracts incorporated many morphological characteristics observed in human senile catracts. Progressive elevation of sodium, marked loss of potassium, several fold increment of calcium; considerable loss of magnesium levels, a dose-response reduction of total-ATPase activity and significant hydration are the important features observed in the lens during the progressive treatment of selenite. The sodium-potassium imbalance is found to be a secondary effect during the development of cataract and is suggested to bring about by an abnormal accumulation of calcium ions and inactivation of transport enzyme. The calcium activated proteases could be the promoting factor for the proteolysis and insolubilization of lens proteins in the inducement of selenite cataract. The impact of selenite on the SH containing ATPase anzymes could be the cause of impairment in energy metabolism, derangement of electrolytes and osmotic imbalance which, in turn, accelerate the cortical involvement of lens opacities.
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PMID:State of electrolytes, osmotic balance and the activity of ATPase in the lenses of selenite--induced cataracts. 297 78

This study focused on whether changes in lens levels of glutathione and calcium, early events associated with cataract formation, were related or that one might cause the other. The first part of the investigation was concerned with the extent to which an increase in levels of intracellular calcium might alter GSH levels in lens fiber and epithelial cells. The results demonstrate that calcium accumulation, either at 19 degrees C or 37 degrees C, did not diminish the concentration of GSH. More importantly, GSH levels did not decline in opaque regions of a calcium-loaded lens. The reciprocal part of the problem focused on whether a decline in lens thiol might lead to an increase in levels of calcium and subsequent opacification. In particular, it was shown that treatment of lenses with parachloromercuribenzene sulphonic acid (PCMBS), a nonpenetrating sulphydryl probe, resulted in a 10-30% loss of membrane SH groups in the epithelium. Diminished numbers of SH groups was accompanied by chloride fluxes and an increase in membrane permeability to sodium and calcium with an influx of sodium and calcium leading to opacities. It is important to note that these changes occurred in the absence of any change in cellular levels of soluble protein-SH or GSH. Additional experiments suggest that calcium transport was not impaired, as evidenced by lack of inhibition of Ca-ATPase activity in lenses treated with PCMBS. The results suggest that one explanation for opacification is that oxidative insults, which diminish GSH levels, leads to a loss of important membrane SH groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The importance of membrane sulfhydryl groups to calcium homeostasis in the lens. 299 53


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