Biomedical subjects

S A Gandolfi

Publications and source records attributed to S A Gandolfi.

At least 19 recordsLinked to original sources

PubMed1997

5-fluorouracil in combined trabeculectomy and clear-cornea phacoemulsification with posterior chamber intraocular lens implantation. A one-year randomized, controlled clinical trial.

PURPOSE: To test the effect of postoperative subconjunctival 5-fluorouracil (5-FU) on the pressure outcome in combined procedure (limbus-based trabeculectomy + clear-cornea phacoemulsification). METHODS: Prospective randomized, controlled clinical trial; n = 24 eyes (24 patients) with concurrent open-angle glaucoma and cataract; 12 eyes per treatment group; sample size adjusted for a minimal expected difference in the event rate between the 2 treatment groups = 50%, control rate = 20%; type I error = 0.05; power = 95%. Uncomplicated limbus-based trabeculectomy + uncomplicated clear-cornea phacoemulsification + posterior chamber intraocular lens. The 5-FU group = five subconjunctival injections of 5 mg 5-FU, starting from day 8 after surgery, one injection per week. Control group = no injections. The groups were matched for age, preoperative intraocular pressure (IOP), duration of preoperative antiglaucoma treatment, preoperative pilocarpine and adrenergics, preoperative laser trabeculoplasty, and beta-blockers in the fellow eye. The IOP less than or equal to 15 mmHg without treatment 1 year after surgery (IOP = average of the two highest values measured in the diurnal curve, 8 AM to 6 PM, one reading every 2 hours). RESULTS: Each patient completed a 1-year follow-up. Ten of 12 eyes of the 5-FU group showed an IOP less than or equal to 15 mmHg at the end of follow-up versus 1 of 12 eyes in the control group (Fisher's exact test, P = 0.00064). The IOP range was 10 to 17 mmHg in the 5-FU group and 14 to 22 mmHg in the control group. CONCLUSION: Postoperative 5-FU may improve the 1-year success rate of trabeculectomy combined with clear-cornea phacoemulsification.

Antimetabolites↗

PubMed1996

Effect of a YAG laser iridotomy on intraocular pressure in pigment dispersion syndrome.

PURPOSE: To determine whether an iridotomy can prevent an increase in intraocular pressure (IOP) in patients with pigment dispersion syndrome. METHODS: Consecutive subjects (n = 21) recruited into this randomized, controlled clinical trial in a hospital-based outpatient referral center, had pigment dispersion syndrome in both eyes, and underwent a YAG laser iridotomy in one eye (randomly chosen); no intervention was performed in the fellow eye. A significant elevation of IOP was arbitrarily defined as an increase of more than 5 mmHg. RESULTS: Eleven (52.3%) untreated eyes versus 1 (4.7%) treated eye showed a significant elevation of IOP during the 2-year follow-up. The IOP difference between the untreated and the fellow treated eye at the end of the 2-year follow-up period is inversely related to the age of each patient. CONCLUSION: YAG laser iridotomy may reduce the incidence of ocular hypertension in eyes affected by pigment dispersion syndrome. This effect, being less pronounced after 40 years of age, may be of clinical relevance in young subjects.

Adult↗

PubMed1996

Serial administration of adrenergic antagonist and agonist ("pulsatile therapy") reduces the incidence of long-term drift to timolol in humans.

PURPOSE: To test whether the incidence of long-term drift to timolol can be reduced by a "pulsatile" treatment (6 months timolol-2 months dipivefrin). METHODS: In a randomized clinical trial, 100 consecutive subjects with ocular hypertension or high-tension primary open-angle glaucoma in at least one eye were randomly assigned to either group A, which was administered timolol 0.5% twice a day (b.i.d.), or to group B, which was administered timolol 0.5% b.i.d. (6 months) alternated with 0.1% dipivefrin b.i.d. (2 months). Diurnal intraocular pressure (IOP) was measured at recruitment, 1 month later during timolol administration ("reference value"), and every 6 months in group A or at the end of each pulse in group B. In bilateral cases, the right eye only was considered for the analysis. Length of follow-up was 54 months. Long-term drift was diagnosed if the IOP on timolol increased by at least 5 mm Hg over the reference value and was followed by a </ = 2mm Hg increase after withdrawing timolol for 2 weeks. RESULTS: Reference values were comparable in both groups (16.4+/-1.2 mm Hg in group A, 15.9+/-1.7 mm Hg in group B). Eleven subjects (four in group A and seven in group B) did not complete follow-up because IOP increased >5 mm Hg in the study eye without detectable drift to the beta-blocker. The actual 54-month incidence of long-term drift was 45% (21/46) in group A versus 7% (3/43) in group B (P<0.01). In group B, IOP was always higher during dipivefrin pulse than on timolol (paired samples t-test, P<0.01). However, dipivefrin proved more effective through follow-up; IOP was 21.1+/-1.2 mm Hg at month 8 (first "pulse") and 18.6+/-0.95 mm Hg at month 48 (last "pulse") (paired samples t-test, P<0.01). CONCLUSIONS: Serial administration of adrenergic antagonist and agonist can reduce the incidence of long-term drift to the beta-blockade in ocular hypertension and primary open angle glaucoma.

Adrenergic Agonists↗

PubMed1995

Decrease of intraocular pressure after subconjunctival injection of mitomycin in human glaucoma.

OBJECTIVE: To investigate the effects of a subconjunctival injection of mitomycin on the intraocular pressure in human eyes affected by glaucoma. DESIGN: Consecutive case series, prospective study, intraocular pairwise comparison (paired samples Student's t test adopted). SETTING: Hospital-based glaucoma clinic. PATIENTS: Twelve consecutive patients with bilateral glaucoma and monolateral blindness, intraocular pressure greater than 30 mm Hg in the blind eye (mean of the two highest values of the diurnal curve, confirmed at 96-hour interval), and no previous bulbar surgery. INTERVENTION: Subconjunctival injection of 0.5 mL of 0.2% mitomycin in the upper temporal quadrant, preceded and followed by treatment with topical indomethacin. MAIN OUTCOME MEASURE: Analysis of the variance of the mean intraocular pressure before and after the injection of mitomycin in each eligible eye. RESULTS: An intraocular pressure decrease was observed in each eligible eye the day after the treatment (mean [+/- SD] decrease, 7.15 +/- 1.46 mm Hg). The effect was still detectable at the end of the 60 days of follow-up (mean [+/- SD] decrease, 5.67 +/- 1.61 mm Hg). No change of intraocular pressure, in the meantime, was observed in the fellow eye. CONCLUSIONS: Topically applied mitomycin induces a decrease of intraocular pressure in human glaucomatous eyes. Our data confirm previous results obtained in albino rabbits and support the hypothesis that mitomycin exerts a still unknown direct effect on aqueous humor dynamics in the eye.

Adult↗

PubMed1994

Calmodulin antagonists induce changes in lens permeability and transparency.

Calmodulin has been shown to perform several important functions in the lens including regulation of the plasma membrane Ca(2+)-ATPase. This study investigated the effects of a variety of different CaM antagonists on rat lens membrane potential, membrane resistance, intracellular Na+ and Ca2+ content and transparency, in order to examine the role of CaM in control of lens membrane permeability. W7, calmidazolium and trifluoperazine caused biphasic changes in lens membrane electrical characteristics. Phase 1 consisted of a depolarization of the membrane potential and an increase in resistance, indicating that K+ channels were being blocked. This was confirmed by application of the K+ channel antagonist, quinine, which inhibited Phase 1 changes. Phase 2 was a further depolarization coupled with a decrease in resistance, indicating the activation of a cation conductance. Application of W7 in low Na+ medium slowed the Phase 2 depolarization and decrease in resistance indicating that Na+ is the main charge carrier through the activated conductance. The CaM inhibitors also led to a large increase in the Na+ and Ca2+ contents of the lens. W5, a less potent analogue of W7, caused a depolarization and increase in membrane resistance, but no Phase 2 changes were observed. Na+ and Ca2+ contents were similar to control lenses after 4 hours incubation in 200 microM W5. In addition, exposure to W7, TFP and calmidazolium resulted in a loss of transparency, while W5 treated lenses remained clear. It appears, therefore, that CaM is involved in control of lens membrane permeability. Loss of control of these channels leads to catastrophic changes in the intracellular ionic environment and hence opacification of the lens.

Animals↗

PubMed1993

Lens sodium channels are inactivated by anti-MIP26 antibodies.

Sodium-specific channels can be functionally identified in phosphatidylcholine liposomes incorporating detergent-solubilized membrane proteins from pig lens epithelium and outer cortex. The transport of sodium is saturable, specific and protease-sensitive. MIP26 was identified in the solubilized membrane fraction and in the liposomes by means of Western blot analysis. Pre-treatment of liposomes with anti-MIP26 antiserum abolished the transport of sodium. These data indicate that MIP26 is associated to a sodium selective transport activity.

Animals↗

PubMed1992

Low-molecular-weight sodium hyaluronate in the treatment of bacterial corneal ulcers.

A double-blind clinical trial was performed on 26 patients suffering from corneal ulcers of proven (i.e., culture-positive) bacterial etiology. After their recruitment, the subjects were randomly assigned to one of the following treatment protocols: (1) tobramycin (15 mg/ml) in saline applied at 1 drop/h or (2) tobramycin (15 mg/ml) in low-molecular-weight hyaluronic acid applied at 1 drop/h. The sample size was adjusted according to a type I error of 0.01 and type a II error of 0.05 for a minimal expected difference of 35%. The healing time was calculated from the beginning of treatment to the day on which a follow-up fluorescein test proved to be negative. The mean healing time (+/- SD) was 3.5 +/- 0.9 days in the sodium hyaluronate group and 5.9 +/- 1.5 days in the saline group (P less than 0.001). These results suggest that treatment with an antibiotic dissolved in low-molecular-weight sodium hyaluronate can further shorten the clinical course of a bacterial corneal ulcer.

Adolescent↗

PubMed1992

Evidence for a Na(+)-Cl(-)-H(+)-HCO3- exchange system in the mammalian lens.

36Cl- efflux was studied in the isolated rat lens under two conditions that are known to decrease internal pH. The first follows exposure to a pulse of ammonium chloride (50 mM) and the second accompanies exposure to an acidified propionate (20 mM) solution. Under acidifying conditions, a stimulation in 36Cl- efflux was observed, that was abolished on removing external Na+ and also on removing external Cl- and HCO3-. In the absence of external Cl-, the presence of HCO3- (16 mM) resulted in an increase in 36Cl- efflux during internal acidification. In the absence of internal acidification, the addition of 0.1 mM dibutyrylcAMP or 0.5 mM IBMX to the external medium produced a rapid increase in 36Cl- efflux. This stimulation was reduced by 0.2 mM SITS. Neither cAMP or IBMX had any significant effect on the electrical resistance of the lens membranes. It is suggested that a coupled SITS-sensitive, Na(+)-Cl(-)-H(+)-HCO3- exchange mechanism is activated when the lens internal pH falls and further that cAMP may play a role in regulating this mechanism.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗

PubMed1991

Increased ion traffic through non-specific cation pathways in the ageing human lens. Evidence from radiotracer fluxes studies.

86Rb efflux studies were carried out on normal human lenses in vitro. The data confirmed previous studies showing that 86Rb efflux increases with age. Removal of Ca2+ from the lens perifusate increased 86Rb efflux at all ages. The fractional increase above baseline was highest in the younger lenses, while the net increase of the 86Rb efflux induced by a Ca(2+)-free medium increased with age. This study supports the idea that Ca(2+)-sensitive, non-specific cation channels are present in the human lens and that their contribution to membrane permeability increases as the lens ages.

Aging↗

PubMed1990

Mammalian lens inter-fiber resistance is modulated by calcium and calmodulin.

The relationship between Ca2+ and lens fiber cell communication was investigated in the isolated intact rat lens by using radiotracer and electrophysiological techniques. The lens internal calcium was increased by adding the SH oxidant diamide (1 mM), by incubating in a sodium-free (n-methylglucamine) solution or by increasing external calcium from 1 to 10 mM. A 12 hours incubation in diamide produced a ten-fold increase in 45Ca uptake into the lens which was accompanied by a ten-fold increase in internal resistance. Incubation in Na-free solution or in 10 mM Ca2+ both produced a 5-fold increase in 45Ca content, while the increase in internal resistance was five and six fold respectively. This uncoupling was prevented in the diamide and Na-free treated lenses by omitting Ca2+ from the incubation medium. Fiber cell uncoupling was noticed in each of these experimental conditions after approximately 5 hours incubation, and good recovery was obtained in the high calcium solution if the stress was removed. The calmodulin antagonists calmidazolium (3 microM) and W7 (100 microM) both prevented uncoupling in the high calcium solution, provided there was a 2 hours preincubation period in calcium-free solution containing antagonist before the stress was applied. These data indicate that lens fiber cell communication is required by Ca2+ and calmodulin.

Animals↗

PubMed1990

Restoring sensitivity to timolol after long-term drift in primary open-angle glaucoma.

In a prospective randomized single-masked study lasting 6 months, 39 eyes with primary open-angle glaucoma showing a long-term drift with 0.5% timolol were put on a "timolol holiday" lasting 30 or 60 days. Twenty-three of them were enrolled with dipivefrin 0.1% twice daily during the holiday. When timolol therapy was restored, the dipivefrin-treated group showed a more pronounced decrease of intraocular pressure (IOP) (8.2 +/- 1.5), whereas the IOP decrease in the nondipivefrin-treated group was lower (3.9 +/- 1.2) and of shorter duration (less than 60 days). Among the dipivefrin-treated group, the response to timolol was more prolonged in the eyes treated for 60 days: the IOP of these eyes was less than 23 mmHg throughout the follow-up.

Aged↗

PubMed1989

Human lens membrane cation permeability increases with age.

Parallel studies of the ionic balance and membrane permeability characteristics of normal human lenses were carried out in three countries (USA, England and Italy). Similar age-related changes were found in each laboratory. The lens membrane potential and resistance declined markedly with age while internal Na+ and free Ca2+ increased. There was a concomitant stimulation of Na+ and K+ transmembrane fluxes. These data indicate that in the ageing process there is an increasing contribution to membrane ion traffic from a channel, or channels, that permit Na+, K+ and Ca2+ to pass. The increase in permeability coincides exactly with the increase in optical density that occurs in the ageing human lens.

Adult↗

PubMed1988

Diamide alters membrane Na+ and K+ conductances and increases internal resistance in the isolated rat lens.

The voltage and conductance of the isolated rat lens were measured using a two-internal-microelectrode technique and the potassium permeability was calculated by applying Goldman theory to 86Rb efflux data. The SH oxidizing agent diamide induces a multiphasic response in lens voltage, conductance and potassium permeability. The initial response (less than or equal to 30 min) to 1 mM diamide consists of a small depolarization (approximately 10 mV) of membrane potential accompanied by a significant decrease in conductance. The 86Rb efflux and permeability data also show an initial decrease. As this initial response is abolished by TEA (20 mM) it is probably due to an inactivation of voltage-sensitive potassium channels. After 30 min exposure to 1 mM diamide both the electrical conductance and the rate of depolarization increase. The 86Rb permeability also increases. Since the conductance increase is abolished by replacing Na+ by methyl glucamine and as it is reduced by amiloride (10(-4) M) the second phase is probably due to the activation of nonspecific cation channels. The third phase is only apparent after prolonged (approximately 12 hr) incubation in 1 mM diamide and consists of a marked increase in the bulk resistance component of the lens impedance. It is suggested that this component arises from an increase in the resistance of the fibre cell gap junctions. This cellular uncoupling may be due to calcium entering the lens through the nonspecific cation channels.

Amiloride↗

PubMed1988

Oxidative cross-linking of fodrin parallels a membrane conductance increase in the mammalian lens.

An oxidative cross-linking of the lens spectrin-like protein fodrin was induced by incubating WKY-rat lenses in the presence of the SH-reagent diamide. The oxidation of fodrin was paralleled by an increase in lens membrane conductance. The time relationship between these two events as well as the reversibility of both, achieved by incubating the lens in the presence of dithiothreitol, indicate that normal permeability characteristics of the lens membranes require the integrity of the membrane attached cytoskeleton.

Animals↗

PubMed1987

Multicomponent analysis of amino acid transport System L in normal and virus-transformed fibroblasts.

Amino acid transport System L in both normal Balb/c 3T3 cells and in those transformed with simian virus 40 (SV 3T3) was analysed kinetically under two different experimental conditions. Under 'zero-trans' conditions the results for both types of cell could be interpreted satisfactorily in terms of System L consisting of two components (L1 and L2) characterized by different Km values. This conclusion is in agreement with previous reports. However, under 'infinite-trans' conditions, the experimental data could not be accounted for in terms of only two components; the introduction of a third component (L3) was necessary to provide a satisfactory fit. Viral transformation affects only the L1 component, either by modification or by replacement, giving it a higher 'affinity' (lower Km) but a lower 'capacity' (lower Vmax).

Amino Acids↗

PubMed1986

Cytoskeleton abnormalities in human senile cataract.

The cytoskeletal pattern of the most superficial layers (cortex and epithelium) of senile cataractous lenses has been analyzed by PAGE-SDS. While the nuclear type of cataract and age-matched transparent human lenses have superimposable protein patterns, lenses with cortical cataract demonstrate appreciable modifications of their cytoskeletal composition. The most evident change is the decrease of fodrin and the marked reduction or even the absence of the 98 Kd band. Fodrin may be completely removed from the water insoluble fraction (WIF) of cortical cataract by extraction in low ionic strength buffer, a treatment which only partially solubilizes this protein in transparent control lenses.

Aged↗

PubMed1986

Interaction of beta-adrenergic antagonists with local anaesthetic acceptor sites.

H3-dihydroalprenolol (H3-DHA) binding in isolated smooth muscle cells has been studied. Two different binding sites have been detected: a high affinity (highly specific) and a low affinity (nonspecific) binding site. Local anaesthetics are able to displace H3-DHA from nonspecific sites with a rank order of potency that mirrors their local anaesthetic activity. This finding correlates, at the molecular level, with the local anaesthetic properties of beta-blockers, as concluded from classical pharmacological experiments.

Adrenergic beta-Antagonists↗

PubMed1985

The effect of the intracellular sodium level on the activity of amino acid transport systems L and A in SV40 3T3 cells.

The rate of transport of phenylalanine and leucine, pertinent amino acids of System L, has been measured in SV40 3T3 cells as a function of the presence of Na+ ions during the reloading phase that precedes the influx determination. The presence of Na+ ions during the reloading phase resulted in an increase of the subsequent substrate influx through System L. This effect was related to the intracellular Na+ level and was found to be independent by the presence of a chemical sodium gradient outside-inside during influx determination; furthermore, this effect could not be ascribed to a difference between control and Na+-treated cells in the internal levels of those amino acids that participate in the exchange phenomena of transport System L. The transport of phenylalanine appeared to have the ability to accept Li+ for Na+ substitution in the 'trans' position. The presence of Na+ ions in the 'trans' position was not required to optimize the transport of System A-reactive substrates, whose influxes are dependent on the presence of the cation in 'cis' position. Analysis of the relationship between influx and substrate concentration indicated that the Na+-dependent increase of substrate influx was associated with an enlarged capacity of the high-affinity component of transport System L.

3-O-Methylglucose↗