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Biomedical subjects

J Santafé

Publications and source records attributed to J Santafé.

15 recordsLinked to original sources
PubMed1999

The effect of topical diltiazem on ocular hypertension induced by water loading in rabbits.

The aim of this work was to assess the effect of topical diltiazem on the ocular hypertension induced by water loading in rabbits. The effect of three different concentrations of diltiazem on the intraocular pressure rise produced by oral administration of tap water (60 ml/kg) was tested in groups of nine or ten rabbits each. When applied at the lowest concentration studied, topical diltiazem was found to enhance the intraocular pressure rise after water loading. In contrast, when applied at the highest concentration, diltiazem counteracted the ocular hypertension caused by water loading. Although diltiazem, and probably other calcium channel blockers, may be useful in the management of ocular hypertension, the data obtained suggest that these drugs may have complex actions on aqueous humor dynamics; therefore further studies in animal models for glaucoma should be carried out before their clinical evaluation in humans.

Animals↗
PubMed1999

Aqueous humor dynamics in alpha-chymotrypsin-induced ocular hypertensive rabbits.

Aqueous humor dynamics were studied in alpha-chymotrypsin-induced ocular hypertensive rabbits either by tonographic or two-level constant pressure perfusion techniques. A significant correlation was obtained between the values of outflow facility in alpha-chymotrypsin-induced ocular hypertensive rabbits as determined by tonography and constant pressure perfusion. The mean value of tonographic outflow facility in ocular hypertensive rabbits was not statistically different from that found in ocular normotensive rabbits. On the contrary, the estimated rate of aqueous inflow in ocular hypertensive rabbits was about 1.5-fold higher than that of ocular normotensive ones. While topical timolol lowered intraocular pressure and aqueous humor inflow in ocular hypertensive rabbits, pilocarpine did not produce any significant effect. Aqueous humor protein was significantly increased in ocular hypertensive eyes. The results of this study show that accurate measurements of outflow facility can be obtained in alpha-chymotrypsin-induced ocular hypertensive rabbits by tonographic technique. Our data suggest that the long-term ocular hypertension induced by alpha-chymotrypsin in albino rabbits may be secondary to an increase in the rate of aqueous humor inflow, likely produced by a breakdown of the blood-aqueous barrier. This finding strongly conflicts with the hypothesis of trabecular blockage as the cause of alpha-chymotrypsin-induced ocular hypertension in this species.

Animals↗
PubMed1999

Topical verapamil lowers outflow facility in the rabbit eye.

Results of studies examining the mechanism of the ocular hypotensive effect of topical calcium channel blockers are controversial. Whereas evidence obtained in perfused human eyes indicates that these drugs lower intraocular pressure by increasing the aqueous humor outflow, tonographic studies in rabbits have revealed that they reduce both the aqueous humor outflow and inflow. In order to clarify such a discrepancy, the aim of this study was to assess whether the effect of topical verapamil on the facility of aqueous humor outflow in the rabbit eye was dose-related. Total outflow facility was determined by two-level constant pressure perfusion in anesthetized rabbits. The effect of 5 different concentrations on aqueous humor outflow at 60 minutes postdrug was studied in groups of 10 rabbits each. Baseline outflow facility was also determined in a group of 15 rabbits. In order to check the reliability of the method for detecting drug-induced changes in aqueous outflow, the effect of pilocarpine was also tested. Topical verapamil was shown to lower outflow facility in the rabbit eye in a dose-related fashion. On the contrary, topical pilocarpine was found to significantly increase outflow facility. Our data indicate that topical verapamil reduces outflow facility in the rabbit eye.

Administration, Topical↗
PubMed1998

The effect of topical dihydroergocristine on the intraocular pressure in alpha-chymotrypsin-induced ocular hypertensive rabbits.

Having previously reported that topical dihydroergocristine dose-dependently reduces intraocular pressure in ocular normotensive rabbits with a maximum response and potency higher than those of timolol and pilocarpine, the aim of the present work was to assess the effect of this drug in alpha-chymotrypsin-induced ocular hypertensive rabbits. Intraocular pressure was measured with a pneumatonometer. The experiments examining the effects of dihydroergocristine on intraocular pressure were conducted in 10 albino rabbits in which ocular hypertension was induced by intracameral injection of alpha-chymotrypsin. Intraocular pressure responses to drug vehicle and 5 different doses of topical dihydroergocristine were studied in order to obtain a dose-response curve. Tonographies were also performed in ocular hypertensive rabbits 2 h after vehicle and dihydroergocristine instillation to ascertain the actions of this drug on aqueous humor dynamics. Topical dihydroergocristine was found to lower intraocular pressure in alpha-chymotrypsin-induced ocular hypertensive rabbits in a dose-related manner, with the ED50 of the concentration-response curve very similar to that previously obtained in ocular normotensive rabbits. Data from tonographic studies indicate that dihydroergocristine reduces intraocular pressure in this animal model for glaucoma by decreasing the aqueous humor inflow. Our findings suggest that topical dihydroergocristine may be useful in the treatment of ocular hypertension.

Administration, Topical↗
PubMed1998

The effect of topical diltiazem on the intraocular pressure in betamethasone-induced ocular hypertensive rabbits.

The effect of calcium channel blockers (CCBs) on intraocular pressure (IOP) remains still controversial, although some preliminary reports suggest that these drugs may be effective in the management of ocular hypertension and low-tension glaucoma. The aim of the present work was to assess the effect of topical diltiazem on IOP in an animal model for glaucoma, the betamethasone-induced ocular hypertension in rabbits. IOP was measured with a manometrically calibrated applanation pneumatonograph. Ocular hypertension was produced in 120 rabbits by weekly subconjunctival injection of a betamethasone suspension into the left eye. The experiments examining the ocular actions of diltiazem were carried out in two stages. In the first one, the ability of topical diltiazem to prevent the rise in IOP induced by betamethasone was studied. In a second phase, the effect of topical diltiazem on IOP in betamethasone-induced ocular hypertensive rabbits was assessed. Diltiazem was topically applied once daily for 5 days a week into the left eye. The effect of five different concentrations of diltiazem was evaluated to obtain dose-response curves. Topical diltiazem was found to prevent in a dose-related fashion the betamethasone-induced IOP rise as well as to reduce IOP in rabbits made ocular hypertensive by weekly subconjunctival injection of betamethasone. Unilateral topical administration did not produce a clear effect on IOP in the untreated eye. This is the first report describing the ocular hypotensive action CCBs in animal model for glaucoma. These findings are in agreement with preliminary evidence suggesting that CCBs may have a beneficial effect in human ocular hypertension.

Administration, Topical↗
PubMed1997

A long-lasting hypotensive effect of topical diltiazem on the intraocular pressure in conscious rabbits.

The effect of calcium channel blockers on intraocular pressure and aqueous humor dynamics remains still controversial, although preliminary evidence suggests that these drugs may be beneficial in the management of ocular hypertension and low-tension glaucoma. Having previously reported the ocular hypotensive effect of topical nifedipine and verapamil in albino rabbits, the original aim of the present work was to evaluate the effect of topical diltiazem on aqueous humor dynamics in this species. Intraocular pressure was measured with a manual applanation tonometer. The experiments examining the ocular actions of diltiazem were carried out in two stages. In the first one, short term effects of topical diltiazem on intraocular pressure were studied in groups of 13 albino rabbits receiving 8 different doses of the drug in order to obtain a dose-response curve. Tonographies were performed in 13 anaesthetized animals before and 90 min after drug instillation. In a second phase, the persistence of the effect of diltiazem on intraocular pressure was examined in 6 groups of 10 rabbits each receiving three different doses of the drug. Topical diltiazem was found to lower intraocular pressure in a dose-related fashion. The maximum response to diltiazem was greater and the ED50 lower than those previously reported for nifedipine and verapamil. In the tonographic study, diltiazem was shown to reduce the facility of aqueous humor outflow and inflow. Diltiazem exhibited a long lasting effect on intraocular pressure that was again dose-related. Depending on the dose administered, the calculated time necessary for the peak effect to be halved ranged from 0.6 to 7.0 days. Due to the intensity and the persistence of its intraocular pressure-lowering effect, diltiazem shows great potential for the treatment of glaucoma, since a daily or less frequent administration may be enough to control ocular hypertension.

Administration, Topical↗
PubMed1997

Betamethasone-induced ocular hypertension in rabbits.

The effect of subconjunctivally injected betamethasone on intraocular pressure (IOP) was studied in 85 albino New Zealand rabbits. IOP was measured with a Mentor Model 30 classic pneumatonograph that was manometrically calibrated to the rabbit eye. Ocular hypertension was induced by weekly subconjunctival injections of a betamethasone suspension into the left eye. In one experiment, 70 rabbits were given betamethasone for 4 weeks, while a second group of 10 rabbits received betamethasone for 11 weeks. The short-term effects of subconjunctival injections of betamethasone on IOP were also recorded in a third group of 5 rabbits. Weekly injections over 4 weeks resulted in an increase in IOP in the treated eye, which was prolonged to 11 weeks by repeated weekly injections. A sustained increase in IOP was observed in the treated eye for a period of 7 weeks. During the early hours after betamethasone injection, a transient decrease in IOP was registered in both eyes. The results show that weekly subconjunctival injections of betamethasone cause a predictable increase in IOP in the treated eye which may be suitable for testing the short- and long-term effects of antiglaucoma drugs. Evidence suggesting that endogenous glucocorticoids may play a role in the development of ocular hypertension in humans strengthens the potential value of this glaucoma model.

Animals↗
PubMed1996

A complex interaction between topical verapamil and timolol on intraocular pressure in conscious rabbits.

Calcium channel blockers have complex actions on aqueous humour dynamics that seem to depend on the route of drug administration. When applied topically, verapamil and nifedipine effectively lower intraocular pressure. However, these drugs also produce a slight reduction in aqueous humor outflow through the trabecular meshwork whereby they could modify the effect of other drugs on intraocular pressure. As calcium channel blockers could be effective in the management of ocular hypertension and low-tension glaucoma, the aim of the present work was to assess the interaction between verapamil and timolol when both drugs are topically applied to the eye of albino rabbits. Intraocular pressure was measured with a manual applanation tonometer. The effects of 5-6 different doses of each drug alone and the effects of five mixtures of both drugs at fixed concentration ratios (timolol: verapamil 4:1, 2:1, 1:1, 1:2 and 1:4) were evaluated. After measuring baseline intraocular pressure, one 50 microliters drop of the different solutions was instilled in the left eye. Measures of the intraocular pressure were repeated at intervals of 30 min until the maximal effect was reached. Each set of experiments was carried out in a group of 9-11 rabbits. Dose-response curves were fitted with a nonlinear regression microcomputer programme. The median effect plot was constructed as proposed by Chou and Talalay (1981, 1983, 1984). In order to analyse the nature of the interaction between both drugs, the observed effect was compared with the theoretically expected one and the combination indices, that relate the doses of verapamil and timolol present in the mixtures with the doses of both drugs separately which are equieffective with the combination, were calculated. The effects of verapamil and timolol followed the principle of the mass action law when administered alone. Nevertheless, no adequate dose-response relationship was obtained when the mixtures of both drugs were applied. In general, the observed effects were lower than the expected ones. Combination indices also indicate the presence of antagonism, except for the lowest concentrations of mixtures where verapamil predominates. In this case, combination indices suggest summation of effects or synergy. Both drugs seem to decrease intraocular pressure by reducing aqueous humor secretion through different mechanisms. However, due to the reduction of aqueous humor outflow caused by verapamil, the ocular hypotensive effect of timolol may be antagonized when high doses of verapamil are administered.

Administration, Topical↗
PubMed1993

The topical application of verapamil and nifedipine lowers intraocular pressure in conscious rabbits.

1. The time-course of the ocular effects of topical verapamil and nifedipine as well as the dose-response relationship, were studied in conscious, normotensive rabbits. 2. Both drugs caused a dose-dependent fall of intraocular pressure, which lasted 4 hr or more. 3. Log dose-response curves of both drugs show a similar peak response, but the potency of verapamil was greater that of nifedipine. 4. A fall in the intraocular pressure in the untreated eye was also observed. 5. Verapamil and nifedipine induced a reduction of the tonographic outflow facility in the treated eye.

Administration, Topical↗
PubMed1978

Significance of a new isovolumetric technique for the study of the myometrial dynamics in vitro.

Above usual values for active tension are measured in 10 uterine horns of rat under electric stimulation through an original isovolumetric technique. At the maximum length increase attained were 1.79 +/- 0.2 kg/cm2, with passive tension from 9--10% total tension. These values are within the range for other smooth and striated muscles. The isometric techniques efficacy to record total uterine tension, as well as the application of isometric activity to the analyse of uterine dynamics are discussed.

Animals↗
PubMedDate not supplied

Modification of rat plasma lipoproteins induced by acute immobilization stress.

To determine the influence of acute stress on plasma lipids and lipoproteins, 66 Wistar rats (31 males and 35 females) were immobilized for 10 hours. Previously, these animals were deprived of food for another 10 hours. Because immobilization involves forced fasting, the control group consisted of 58 rats (30 males and 28 females) that fasted for 20 hours. The immobilized animals showed gastric lesions (94% of the males and 83% of the females). Plasma lipoproteins were separated by ultracentrifugation in the following densities: less than 1.006 g/ml (very low-density lipoproteins (VLDL)), 1.006 to 1.040 g/ml (low-density lipoproteins (LDL)), 1.040 to 1.063 g/ml (high-density lipoproteins fraction 1 (HDL1)), and 1.063 to 1.210 g/ml (HDL2). Measurements were adjusted according to hematocrit value. In male rats, immobilization caused a rise in total plasma cholesterol as a consequence of increases in the VLDL, LDL, and HDL1 fractions. In female rats, however, no significant variations were observed in plasma cholesterol, although there was a slight, but significant, increase in VLDL and LDL cholesterol. Immobilization caused hypertriglyceridemia in both sexes as a result of an increase in triglycerides in all classes of lipoproteins, except in HDL2 in both sexes and VLDL in males. Finally, the protein content of VLDL and LDL increased both in male and female rats; HDL2 levels decreased in female rats. These changes suggest an atherogenic character of stress caused by continuous immobilization during 10 hours.

Animals↗