Giovanni Iuliano

Effect of vitamin E on glutathione content in red blood cells, aqueous humor and lens of humans and other species

High doses of orally administered vitamin E have been given to humans, rabbits and rats. Placebo has been given to control groups. At the end of the treatment period, enhanced levels of reduced glutathione (GSH) were found in the red blood cells (humans and rabbits), aqueous humor (humans and rabbits) and lens (rabbits and rats) of treated subjects and animals. The percentage of GSH converted to oxidized glutathione (GSSG) was the same in both vitamin E-supplied and control groups. The GSSG--GSH ratio remained unchanged. The plasma levels of vitamin E were significantly higher in treated than in control subjects and animals. At the end of the study, the levels of vitamin E in aqueous humor and lens of rabbit were the same in animals which received vitamin E and in animals which received placebo. Lastly, vitamin E administration did not influence ascorbic-acid levels in plasma (humans and rabbits), aqueous humor, lens and vitreous body (rabbits).

Systemic human diseases as oxidative risk factors in cataractogenesis. I. Diabetes.

In this study we have investigated the oxidative metabolism of red blood cells (RBC), plasma, serum, aqueous humor, and lens of healthy subjects and of age-matched cataractous patients with and without diabetes. Reduced and oxidized glutathione (GSH GSSG) levels in RBC were similar among the three groups. Plasma levels of GSSG were higher in diabetics than in cataractous and control subjects. No differences in plasma content of GSH were noted among the three groups. The activity of the enzyme glucose-6-phosphate dehydrogenase was significantly diminished in diabetic patients. Controls and cataractous patients showed similar levels of malondialdehyde (MDA). Although not significant the MDA content in RBC from diabetics was elevated. No differences in plasma levels of vitamin E were noted among the three groups. The biological liquid oxidant activity of serum in diabetic patients was significantly higher than in controls and cataractous patients. GSH levels in aqueous humor were similar in diabetic and nondiabetic cataractous patients. The content of GSSG in aqueous humor was highest in diabetic patients. Control clear lenses showed low levels of MDA. The MDA levels in cataractous lenses from nondiabetic patients were significantly higher than those of controls. In diabetic patients the content of MDA in the lens was approximately twice as high as the cataractous values. Our results seem to demonstrate that oxidative damage could play a role in the pathogenesis of cataract in diabetes.

Effect of topical ketanserin administration on intraocular pressure.

The effect of topical ketanserin on intraocular pressure (IOP) in normotensive and hypertensive eyes was evaluated. The study was performed on 10 healthy volunteers and 10 glaucomatous patients. Systolic arterial blood pressure (SBP), diastolic arterial blood pressure (DBP), heart rate (HR), IOP, tonographic outflow facility, pupil diameter, corneal thickness, and tear secretion were recorded at baseline and at 1 hour intervals for 12 hours after topical administration of 0.5% ketanserin or placebo, given in a randomised, double masked, crossover fashion. The alternative treatment was given 1 week later. In all subjects ketanserin significantly lowered IOP, while no variations in SBP, DBP, HR, pupil diameter, corneal thickness, and tear secretion were found. When subjects received placebo no significant variations of IOP occurred. Total outflow facility, measured by conventional tonography, increased significantly after drug administration in all subjects. Ketanserin is effective up to 6 hours in control subjects and 9 hours in glaucomatous patients. The placebo did not induce any change in this component of the aqueous humour dynamic in normal or in glaucomatous eyes. The findings indicate that topical ketanserin might be added to the list of antiglaucomatous agents.

Systemic human diseases as oxidative risk factors in cataractogenesis. II.Chronic renal failure

In this study we have investigated the oxidative metabolism of red cells (RBC), plasma, serum and aqueous humour of healthy subjects and of age-matched cataractous patients with and without chronic renal failure (CRF). Reduced glutathione (GSH) levels in RBC were lower in CRF patients than in the other groups. Oxidized glutathione (GSSG) plasma levels in CRF patients were higher than those of controls and cataractous subjects. The activity of the enzyme glucose-6-phosphate dehydrogenase in RBC was significantly reduced in CRF patients with respect to the other two groups. The levels of malondialdehyde (MDA) in RBC and in lens were about twice in CRF patients compared with the other two groups. The plasma levels of vitamin E were diminished in CRF patients; on the contrary, the biological liquid oxidant activity (BLOA) of serum in CRF patients was significantly higher than in controls and in cataractous patients without CRF. Cataractous patients with and without CRF showed similar levels of GSH in aqueous humour; on the contrary, the content of GSSG was significantly higher in CRF patients. Our findings seem to demonstrate that CRF patients are exposed to oxidative stresses that could probably act synergistically with uraemia and carbamylation of lens proteins. This synergism could explain why CRF represents a relatively high risk factor for cataract.

Effect of Topical Glucocorticoid Administration on the Protein and Nonprotein Sulfhydryl Groups of the Rabbit Lens

The effects of topical administration of glucocorticoids on rabbit lenses are described. Animals were divided into three groups. The first group (A) served as control, the second (B) and the third (C) group were treated with betamethasone and fluorometholone, respectively. After 40 days of treatment there was a significant fall in the levels of nonprotein sulfhydryl (-SH) groups (group A: 3.82 +/- 0.21; group B: 2.61 +/- 0.11; group C: 1.93 +/- 0.13 mumol/lens) and of protein -SH groups (group A: 8.215 +/- 1.023; group B: 4.120 +/- 0.631; group C: 4.068 +/- 0.538 mumol/lens). Also ascorbic acid levels showed a significant decrease both in lens and in aqueous humor. No differences were noted in the reduced glutathione content in aqueous humor. The fall in nonprotein and protein -SH could be the first event in the well-known biochemical changes that occur in steroid-induced cataract. The mechanism underlying steroid-induced damage could be due to a conformational change of lens crystallins which results in an unmasking of -SH groups with a consequent increased susceptibility to oxidation. The decrease of ascorbic acid should represent an effect of the fall in the glutathione system. Lastly, it is hypothesized that the protective effect exerted by some substances, such as vitamin E and ascorbic acid, occurs by counteracting this oxidation.

In vivo Measurement of Human Lens Aging using the Lens Opacity Meter

Lens aging has been measured in vivo using a new instrument: the lens opacity meter 701 (Interzeag, Schlieren, Switzerland). Statistical analyses have been performed to verify the occurrence of the phenomenon, the sex differences and the reproducibility of the obtained results. The findings demonstrate an increase in the light scattering in the normal lens with aging, which is similar in both sexes. The instrument detects this process and the measurements have a high degree of reproducibility.

Quantification and Measurement of Human Lens Opacities Using the Lens Opacity Meter

Lens opacity was quantified in 85 cataractous patients, using a new instrument: the lens opacity meter 701 (LOM; Interzeag, Schlieren, Switzerland). Cataracts were classified as nuclear, cortical, subcapsular and mixed forms. Sensitivity, specificity and reproducibility of the results were evaluated by statistical analysis. Visual acuity was correlated with LOM values in patients with nuclear and mixed cataracts. Moreover, the instrument gave a good degree of reproducibility only in patients who presented these forms of lens opacities. Our findings demonstrate that the LOM 701 is able to detect and to measure only lens opacities which affect the central area of the lens.

Influence of lens opacities on visual field indices

This report presents the results of a study designed to verify the influence of lens opacities on the visual field indices. Four age-matched groups of subjects were considered: healthy volunteers, glaucomatous patients without lens opacities, cataractous patients without glaucoma and glaucomatous patients with lens opacities. The quantification of lens opacities was performed with the Lens Opacity Meter 701 instrument. The visual field indices were obtained automatically from the G1 program of the Octopus system. The statistical analysis of the results (coefficient of correlation) has shown that only the visual field indices that correspond to uniform and diffuse loss of light sensitivity were influenced by the presence of cataract. On the contrary, the visual field indices that indicate local irregularities of the threshold were not significantly influenced by the presence of lens opacities.

EFFECTS OF KETANSERIN ON INTRAOCULAR-PRESSURE

SummaryThere is evidence that some antihypertensive drugs, such as beta blockers, are effective in reducing intraocular pressure (IOP) and are commonly used in the medical treatment of glaucoma. The aim of this study was to evaluate the effects of the anti-serotonergic agent ketanserin, which has associated alpha1-blocking properties, on IOP in normotensive and hypertensive eyes. The first part of the study was performed in six arterial hypertensive patients (mean ± SD blood pressure 156/102 ± 10/6 mmHg) with a pretreatment IOP in the normal range (15.7 ±1mmHg). Both blood pressure and IOP were measured at baseline and at 1 hour intervals up to 3 hours following the oral administration of ketanserin 20 mg or placebo, given in a randomized manner. Three hours after ketanserin treatment, mean systolic and diastolic blood pressures dropped by 10/5 mmHg and mean IOP was reduced by 2.7 mmHg; after placebo, no change was observed in these variables. Thereafter, four normotensive patients with chronic open-angle glaucoma (IOP=22.8 mmHg) were given 20 mg ketanserin orally. Three hours after administration, a 22% reduction in mean IOP occurred (-5.8 mmHg), with a concomitant reduction in mean systolic blood pressure of 13.0 mmHg. These results indicate that ketanserin treatment reduces IOP and systemic blood pressure. Further, long-term studies are needed in order to confirm the efficacy of ketanserin in the medical treatment of ocular hypertension.

Inhibition of rat lens aldose reductase by bendazac-L-lysine salt

Authors describe the in vitro effect of bendazac-L-lysine salt on the activity of enzyme aldose reductase from rat lens. In the presence of bendazac the activity of the tested enzyme was inhibited. Lineweaver-Burk plot demonstrated that the inhibition was noncompetitive. The possible curative effects on diabetic cataract together with a better way of administration are pointed out.