... TO CETYLPYRIDINIUM CHLORIDE KEITH GREEN, Ph.D., D. Sc. * KAREN A. BOWMAN R. DAVID ELIJAH, BS ... more ... TO CETYLPYRIDINIUM CHLORIDE KEITH GREEN, Ph.D., D. Sc. * KAREN A. BOWMAN R. DAVID ELIJAH, BS Medical College of Georgia Augusta, Georgia R. MERMELSTEIN, Ph. D. R. W. KILPPER, Ph.D. Xerox Corporation Rochester. New York Abstract ...
A steroid antagonist applied to one eye of 18 young pigmented rabbits during a 10-week period cau... more A steroid antagonist applied to one eye of 18 young pigmented rabbits during a 10-week period caused a statistically significant fall in IOP, but no statistically significant nor clinically relevant change in the rate of aqueous humor turnover. The pressure change is therefore ascribed to an alteration in outflow channels. No changes occurred in a parallel group of 5 animals in which one eye was treated with vehicle and the contralateral eye was untreated. The drug effects became evident after two weeks of application, suggesting that a slow turnover pathway is involved.
Rabbit corneal endothelial pH and electrical potential have both been determined using tracer dis... more Rabbit corneal endothelial pH and electrical potential have both been determined using tracer distribution techniques. Intercellular pH was measured using the dimethyloxazolidine-dione method and intracellular potential was measured using tetraphenylphosphonium bromide. Intracellular pH was determined as 7.10 in an ambient solution of pH 7.5. The only solution variations which altered intracellular pH were variations in the external solution pH, bathing in sodium-free or bicarbonate-free solution, incubation for 3 hours with 10(-6) or 10(-4) M ouabain or for 1 hour with 10(-4) M ouabain or in a high (60 mM) bicarbonate solution. The data indicate a close correlation between sodium and bicarbonate needs for the endothelium which corresponds with known effects of these ions on transendothelial ion fluxes. Intracellular potentials were measured of -34 mV, which were stable in the face of all environmental perturbations except 1 mM acetazolamide and 10(-6) M ouabain exposure for 3 hours. These newer techniques may be employed to provide some clues into the mechanism of endothelial transport systems.
One group of 5 pigmented rabbits, during a period of 10 weeks, and two groups of 8 albino rabbits... more One group of 5 pigmented rabbits, during a period of 10 weeks, and two groups of 8 albino rabbits, during 16 weeks, showed a fall in aqueous turnover rate and outflow facility of about 30%. A fall in intraocular pressure also occurred of about 10 mm Hg. The biochemical correlative mechanism, systemic and/or local, is conjectural (reduction of "stress"; homeostasis). Empirically a parallel completely untreated control group should accompany any longitudinal study group in order to differentiate these temporal trends from experimental effects.
Relatively selective beta 1- and beta 2-adrenergic agonists (tazolol and terbutaline) and antagon... more Relatively selective beta 1- and beta 2-adrenergic agonists (tazolol and terbutaline) and antagonists (metoprolol and butoxamine) were topically applied to albino rabbit eyes and to isolated ciliary epithelium. The beta 2-agonist, terbutaline, was the most effective agent in reducing intraocular pressure although all compounds induced changes in aqueous humor formation rate and pseudofacility. The effects on the isolated ciliary epithelium were determined on tissues derived from both normal and superior cervical ganglionectomized eyes. The beta 1- and beta 2-agonists as well as the beta 1-antagonist induced large permeability increases while the beta 2-antagonist induced a small permeability increase in normal tissues. In ganglionectomized tissues the beta 1-antagonist effect was decreased and the beta 2-antagonist effect enhanced while the agonist effects were almost unchanged. The results show that both beta 1- and beta 2-receptors exist in the ciliary epithelium and that stimulation of either receptor leads to an increase in fluid permeability and alterations in aqueous dynamics.
Further studies have been made with water soluble marihuana-derived material (MDM). Neither adren... more Further studies have been made with water soluble marihuana-derived material (MDM). Neither adrenergic, cholinergic, aldosterone, dopamine or serotonin antagonism affected the fall in intraocular pressure induced by MDM. Partial blockade was obtained with galactose, glucose, or mannose, but not arabinose, when the latter were given at intravenous concentrations of 1 gm/animal and MDM was given at 25 micrograms animal, suggesting that these sugars may be involved at the active site of the MDM glycoproteins. Dexamethasone was without effect on either intravenous or intravitreal MDM indicating that the MDM effect is not a non-specific response to a protein. A similar plant glycoprotein, larch arabinogalactan, at 200 micrograms/animal was without effect on intraocular pressure. Aqueous humor flow rate was increased 3 hours after MDM administration, a period corresponding to the intraocular pressure increase caused by MDM, and fell to 20% of control values when the fall in intraocular pressure occurred. Blood flow through the iris was increased at both one and six hours after intravenous MDM injection indicating a vasodilation which could contribute to the initial increase in intraocular pressure. Intravitreal injection of MDM in rabbit and rhesus monkey caused a fall in intraocular pressure only after a 24 hour delay: the unilateral response indicated that systemic metabolism was not required for activity and the delay was likely caused by the diffusion time to the ciliary processes from the mid-vitreal injection site. The changes in beta-receptors, adenylate cyclase and carbonic anhydrase in the ciliary processes are minimal indicating a possible vascular mechanism of action of MDM.
A water soluble material, isolated from Cannabis sativa, has been tested in albino and pigmented ... more A water soluble material, isolated from Cannabis sativa, has been tested in albino and pigmented rabbits and rhesus monkeys for both ocular and systemic effects. Intravenous administration produced a dose-related fall in intraocular pressure in both albino and pigmented rabbits with concentrations as low as 0.005 mg/animal being effective, but no response was found in monkeys. High concentrations (0.2 to 1 mg/animal) induced a hypertensive phase in intraocular pressure prior to the ocular hypotension; higher concentrations (2 or 5 mg/animal) also induced antidiuresis and general relaxation. Tachyphylaxis was found to repeated daily injections. Alpha and beta-adrenergic antagonists caused some reduction of the hypertensive phase but had no effect on the hypotensive phase. Superior cervical ganglionectomy did not influence the time course of the intraocular pressure response. Indomethacin inhibited the hypertensive intraocular pressure phase but was ineffective against the hypotensive phase. Systemic blood pressure was unchanged following intravenous administration of 0.2 mg material/animal. Aqueous tumor protein concentration was increased at both 1 and 6 hours after intravenous administration, becoming greater at the later time. Aqueous humor turnover rate was substantially reduced reaching a minimum 8.75 hours after administration. Topical administration was ineffective in eyes when the epithelium was removed in rabbits with and without pretreatment with aspirin. Neither gastric nor suppository administration of large quantities (10 mg or greater) of material had any influence on intraocular pressure.
... TO CETYLPYRIDINIUM CHLORIDE KEITH GREEN, Ph.D., D. Sc. * KAREN A. BOWMAN R. DAVID ELIJAH, BS ... more ... TO CETYLPYRIDINIUM CHLORIDE KEITH GREEN, Ph.D., D. Sc. * KAREN A. BOWMAN R. DAVID ELIJAH, BS Medical College of Georgia Augusta, Georgia R. MERMELSTEIN, Ph. D. R. W. KILPPER, Ph.D. Xerox Corporation Rochester. New York Abstract ...
A steroid antagonist applied to one eye of 18 young pigmented rabbits during a 10-week period cau... more A steroid antagonist applied to one eye of 18 young pigmented rabbits during a 10-week period caused a statistically significant fall in IOP, but no statistically significant nor clinically relevant change in the rate of aqueous humor turnover. The pressure change is therefore ascribed to an alteration in outflow channels. No changes occurred in a parallel group of 5 animals in which one eye was treated with vehicle and the contralateral eye was untreated. The drug effects became evident after two weeks of application, suggesting that a slow turnover pathway is involved.
Rabbit corneal endothelial pH and electrical potential have both been determined using tracer dis... more Rabbit corneal endothelial pH and electrical potential have both been determined using tracer distribution techniques. Intercellular pH was measured using the dimethyloxazolidine-dione method and intracellular potential was measured using tetraphenylphosphonium bromide. Intracellular pH was determined as 7.10 in an ambient solution of pH 7.5. The only solution variations which altered intracellular pH were variations in the external solution pH, bathing in sodium-free or bicarbonate-free solution, incubation for 3 hours with 10(-6) or 10(-4) M ouabain or for 1 hour with 10(-4) M ouabain or in a high (60 mM) bicarbonate solution. The data indicate a close correlation between sodium and bicarbonate needs for the endothelium which corresponds with known effects of these ions on transendothelial ion fluxes. Intracellular potentials were measured of -34 mV, which were stable in the face of all environmental perturbations except 1 mM acetazolamide and 10(-6) M ouabain exposure for 3 hours. These newer techniques may be employed to provide some clues into the mechanism of endothelial transport systems.
One group of 5 pigmented rabbits, during a period of 10 weeks, and two groups of 8 albino rabbits... more One group of 5 pigmented rabbits, during a period of 10 weeks, and two groups of 8 albino rabbits, during 16 weeks, showed a fall in aqueous turnover rate and outflow facility of about 30%. A fall in intraocular pressure also occurred of about 10 mm Hg. The biochemical correlative mechanism, systemic and/or local, is conjectural (reduction of "stress"; homeostasis). Empirically a parallel completely untreated control group should accompany any longitudinal study group in order to differentiate these temporal trends from experimental effects.
Relatively selective beta 1- and beta 2-adrenergic agonists (tazolol and terbutaline) and antagon... more Relatively selective beta 1- and beta 2-adrenergic agonists (tazolol and terbutaline) and antagonists (metoprolol and butoxamine) were topically applied to albino rabbit eyes and to isolated ciliary epithelium. The beta 2-agonist, terbutaline, was the most effective agent in reducing intraocular pressure although all compounds induced changes in aqueous humor formation rate and pseudofacility. The effects on the isolated ciliary epithelium were determined on tissues derived from both normal and superior cervical ganglionectomized eyes. The beta 1- and beta 2-agonists as well as the beta 1-antagonist induced large permeability increases while the beta 2-antagonist induced a small permeability increase in normal tissues. In ganglionectomized tissues the beta 1-antagonist effect was decreased and the beta 2-antagonist effect enhanced while the agonist effects were almost unchanged. The results show that both beta 1- and beta 2-receptors exist in the ciliary epithelium and that stimulation of either receptor leads to an increase in fluid permeability and alterations in aqueous dynamics.
Further studies have been made with water soluble marihuana-derived material (MDM). Neither adren... more Further studies have been made with water soluble marihuana-derived material (MDM). Neither adrenergic, cholinergic, aldosterone, dopamine or serotonin antagonism affected the fall in intraocular pressure induced by MDM. Partial blockade was obtained with galactose, glucose, or mannose, but not arabinose, when the latter were given at intravenous concentrations of 1 gm/animal and MDM was given at 25 micrograms animal, suggesting that these sugars may be involved at the active site of the MDM glycoproteins. Dexamethasone was without effect on either intravenous or intravitreal MDM indicating that the MDM effect is not a non-specific response to a protein. A similar plant glycoprotein, larch arabinogalactan, at 200 micrograms/animal was without effect on intraocular pressure. Aqueous humor flow rate was increased 3 hours after MDM administration, a period corresponding to the intraocular pressure increase caused by MDM, and fell to 20% of control values when the fall in intraocular pressure occurred. Blood flow through the iris was increased at both one and six hours after intravenous MDM injection indicating a vasodilation which could contribute to the initial increase in intraocular pressure. Intravitreal injection of MDM in rabbit and rhesus monkey caused a fall in intraocular pressure only after a 24 hour delay: the unilateral response indicated that systemic metabolism was not required for activity and the delay was likely caused by the diffusion time to the ciliary processes from the mid-vitreal injection site. The changes in beta-receptors, adenylate cyclase and carbonic anhydrase in the ciliary processes are minimal indicating a possible vascular mechanism of action of MDM.
A water soluble material, isolated from Cannabis sativa, has been tested in albino and pigmented ... more A water soluble material, isolated from Cannabis sativa, has been tested in albino and pigmented rabbits and rhesus monkeys for both ocular and systemic effects. Intravenous administration produced a dose-related fall in intraocular pressure in both albino and pigmented rabbits with concentrations as low as 0.005 mg/animal being effective, but no response was found in monkeys. High concentrations (0.2 to 1 mg/animal) induced a hypertensive phase in intraocular pressure prior to the ocular hypotension; higher concentrations (2 or 5 mg/animal) also induced antidiuresis and general relaxation. Tachyphylaxis was found to repeated daily injections. Alpha and beta-adrenergic antagonists caused some reduction of the hypertensive phase but had no effect on the hypotensive phase. Superior cervical ganglionectomy did not influence the time course of the intraocular pressure response. Indomethacin inhibited the hypertensive intraocular pressure phase but was ineffective against the hypotensive phase. Systemic blood pressure was unchanged following intravenous administration of 0.2 mg material/animal. Aqueous tumor protein concentration was increased at both 1 and 6 hours after intravenous administration, becoming greater at the later time. Aqueous humor turnover rate was substantially reduced reaching a minimum 8.75 hours after administration. Topical administration was ineffective in eyes when the epithelium was removed in rabbits with and without pretreatment with aspirin. Neither gastric nor suppository administration of large quantities (10 mg or greater) of material had any influence on intraocular pressure.
Uploads