Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a randomized, double-masked, parallel study, one drop of 0.003% (1 microgram; n = 9) or 0.01% (3 micrograms; n = 10) PhXA34, a new phenyl-substituted prostaglandin F2 alpha analogue (13,14-dihydro-15[R,S]-17-phenyl-18,19,20-trinor-prostaglandin F2 alpha-1-isopropyl ester), or its vehicle (n = 10) was applied topically twice daily for 6 days to one eye in each of 29 patients with ocular hypertension. Compared with either baseline, contralateral, or vehicle control values, PhXA34 caused a significant (P < .001) dose-dependent reduction of intraocular pressure. The reduction lasted at least 12 hours after each drop and 24 to 48 hours after the last drop, with a significant (P < .0001) mean +/- SEM reduction of as much as 10 +/- 1 mm Hg (40%). Conjunctival hyperemia was not produced by 0.003% PhXA34, but was noted in some eyes treated with 0.01% PhXA34, and after repeated tonometry with either concentration. The prostaglandin analogue did not produce clinically obvious miosis, anterior chamber flare or cellular response, or any subjective adverse effects. PhXA34 is a potent, effective, and well-tolerated ocular hypotensive agent based on our results in this small, short-term study. Its potential as a new drug for glaucoma therapy warrants further investigation in long-term, larger studies.
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PMID:Intraocular pressure reduction with PhXA34, a new prostaglandin analogue, in patients with ocular hypertension. 146 14

Selective alpha 2-adrenergic agonists UK14304-18 and B-HT 920 were evaluated in the eyes of cynomolgus monkeys. In normal monkeys, unilateral topical application of 0.3%, 0.5%, or 1% UK14304-18 or B-HT 920 reduced (P less than .05) intraocular pressure bilaterally up to 9.9 +/- 1.2 mm Hg (mean +/- SEM) and 8.4 +/- 1.4 mm Hg in treated and contralateral eyes, respectively. Five-day twice-daily 0.5% UK14304-18 administration reduced (P less than .05) intraocular pressure up to 49% in eight glaucomatous monkeys. In eight normal monkeys, 0.5% B-HT 920 and 0.5% UK14304-18 produced no alterations in outflow facility. Following unilateral application of 0.5% B-HT 920 or 0.5% UK14304-18, fluorophotometrically measured aqueous humor production was reduced (P less than .05) bilaterally up to 67% compared with baseline values. Also, 0.5% UK14304-18 reduced (P less than .025) systolic and diastolic blood pressure. UK14304-18 and B-HT 920 seem to reduce intraocular pressure by decreasing aqueous production. They are potential new agents for the treatment of glaucoma.
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PMID:Selective alpha 2-adrenergic agonists B-HT 920 and UK14304-18. Effects on aqueous humor dynamics in monkeys. 167 57

The effect of exercise conditioning on elevated intraocular pressure has not been previously described among sedentary individuals. We prospectively observed intraocular pressure for nine sedentary subjects suspected of having glaucoma before and after 3 months of aerobic exercise training. Mean (+/- SEM) aerobic capacity, as assessed by maximal oxygen uptake, increased 6.3 +/- 1.6 mL.kg-1.min-1 (30%) (P less than .02). Mean intraocular pressure decreased 4.6 +/- 0.4 mmHg (20%) (P less than .001) at the end of the conditioning period. With cessation of exercise and subsequent detraining, intraocular pressure returned to elevated preconditioning levels by 3 weeks. Regular aerobic exercise is associated with a reduction in elevated intraocular pressure and may represent an effective nonpharmacologic intervention for patients suspected of having glaucoma.
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PMID:Exercise training reduces intraocular pressure among subjects suspected of having glaucoma. 186 51

Measurements of pulsatile ocular blood flow (POBF) have been recorded in a group of healthy, ocular normotensive volunteers and ocular hypertensive patients recruited from outpatients. Use of a pneumotonometric probe linked to a Langham ocular blood flow system enabled readings of intraocular pressure and its variation with heart rate (ocular pulse) to be taken in erect and supine positions. Pulsatile ocular blood flow was calculated from these values by means of the pressure-volume relationship previously described for living human eyes. Assumption of the supine posture was accompanied by a significant rise in intraocular pressure; in normal eyes (mean, with SEM) (3.1 (0.4) mmHg, p less than 0.0001) and to a greater extent in ocular hypertensive eyes (4.7 (0.6) mmHg, p less than 0.0001). The POBF did not differ significantly between normotensive and ocular hypertensive groups in either the erect or supine postures. In both groups, however, assumption of the supine posture was accompanied by a significant fall in POBF (normals: -121 (21) microliters/min, p less than 0.0001; ocular hypertensives: -75 (16) microliters/min, p less than 0.0002). These reductions in POBF represent decrements of 27.5 (3.0)% and 17.1 (3.8)% respectively. Pulsatile ocular blood flow is reduced in the supine posture, and this may result in tissue hypoxia in subjects at risk of developing glaucoma. A companion paper describes the measurement of POBF in a group of patients with chronic open angle glaucoma treated with topical timolol 0.25%.
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PMID:Postural studies in pulsatile ocular blood flow: I. Ocular hypertension and normotension. 199 45

The pulsatile ocular blood flow (POBF) has been recorded in 15 patients with chronic open angle glaucoma. Measurements were performed during regular treatment with timolol 0.25% eyedrops, two weeks after withdrawal of this treatment, and then a further two weeks after its reinstitution. Readings were taken with subjects in both the erect and supine positions by means of a pneumotonometric probe to measure intraocular pressure (IOP), linked to a Langham ocular blood flow system. Assumption of the supine posture was associated with a significant increase in IOP in all phases of the study. Treatment with timolol lowered the mean IOP in comparison with the untreated phase (-4.4 (SEM 0.6) mmHg, p less than 0.001) but had no effect on the postural change. A significant reduction in POBF was recorded on assumption of the supine posture (-66 (SEM 18) microliters/min, p less than 0.001), representing a mean decrement of 19%. However, there were no significant differences in POBF between treated and untreated phases of the study. Comparison of the values obtained in patients with glaucoma (COAG) after withdrawal of treatment with those in subjects with ocular hypertension revealed that there was no significant difference in intraocular pressure between the two groups. However, both POBF (-68 (SEM 29) microliters/min) and the pulse amplitude of the intraocular pressure (ocular pulse: -0.45 (SEM) 0.14 mmHg) were significantly lower in the COAG patients. Pulsatile ocular blood flow is significantly lower in patients with chronic open angle glaucoma. Furthermore, the POBF and the postural response of these patients is not improved by the use of topical timolol therapy.
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PMID:Postural studies in pulsatile ocular blood flow: II. Chronic open angle glaucoma. 199 46

Effects of topical administration of a single dose of timolol maleate on intraocular pressure (IOP) and pupil diameter were evaluated in normotensive eyes of 11 clinically normal dogs over 12 hours (7:00 AM to 7:00 PM). Mean (+/- SEM) normal IOP was 15.5 (+/- 1.1) mm of Hg and diurnal fluctuation was observed, with the highest IOP seen in the morning. Mean normal pupil diameter was 8.5 (+/- 0.3) mm. Topical treatment with 0.5% timolol resulted in reduction of IOP in the treated and nontreated eyes. Mean reduction of IOP in the treated eye was 2.5 mm of Hg, a reduction of 16.1%, with maximal reduction of 3.7 mm of Hg. Mean reduction of IOP in the nontreated eye was 1.4 mm of Hg, a reduction of 9.0%. The treated eye had reduced pupil diameter at 30 minutes after treatment, which persisted throughout the 12 hours of the study. Mean reduction of pupil diameter in the treated eye was 2.9 mm, a reduction of 34.1%. In addition, a contralateral effect on pupil diameter was seen in the nontreated eye, with mean reduction of 1.2 mm, a reduction of 14.1%. Topical administration of timolol maleate resulted in reduction of IOP and pupil diameter in treated and contralateral eyes, thus supporting the use of timolol for treatment of glaucoma in dogs. Miosis indicates possible beta-adrenergic inhibition or alpha-adrenergic activation of the sphincter muscle. beta-Adrenergic blockade would then result in miosis.
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PMID:Effects of topical administration of timolol maleate on intraocular pressure and pupil size in dogs. 203 17

Effects of topical administration of a single dose of timolol maleate, a nonselective beta-adrenergic blocking agent, on intraocular pressure (IOP) and pupil diameter were evaluated in the normotensive eyes of 10 clinically normal cats over 12 hours. Mean (+/- SEM) normal IOP was 17.1 (+/- 1.1) mm of Hg and diurnal fluctuation was observed, with the highest IOP seen in the evening. Mean (+/- SEM) normal pupil diameter was 10.1 (+/- 0.5) mm. Topical treatment with 0.5% timolol resulted in reduction of IOP in treated and nontreated eyes. This effect was time-dependent and was first observed at 6 hours after treatment. Mean reduction of IOP was 22.3% in the treated eye and 16.3% in the nontreated eye. The treated eye had reduced pupil diameter at 30 minutes after treatment, and miosis persisted throughout the 12 hours of the study. Mean reduction of pupil diameter was 38.7%. A contralateral effect on pupil diameter was not seen in the nontreated eye. Topical administration of timolol maleate results in a reduction of IOP in treated and contralateral eyes, which supports the use of timolol for treatment of glaucoma in cats. In addition, the treated eye becomes miotic. This effect may indicate beta-adrenergic inhibition or alpha-adrenergic activation of the iris sphincter muscle. beta-Adrenergic blockade would then result in miosis.
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PMID:Effects of topical administration of timolol maleate on intraocular pressure and pupil size in cats. 203 18

Effects of topical administration of a single dose of 2% pilocarpine on intraocular pressure (IOP) and pupil diameter were evaluated in normotensive eyes of 10 clinically normal cats over 12 hours. Mean (+/- SEM) normal IOP was 17.1 (+/- 1.1) mm of Hg and, diurnal fluctuation was observed, with the highest IOP seen in the evening. Mean (+/- SEM) normal pupil diameter was found to be 10.1 (+/- 0.5) mm. Topical treatment with pilocarpine resulted in reduction of IOP in treated and nontreated eyes. This effect was time-dependent and was first observed at 4 hours after treatment. Mean reduction of IOP was 15.2% in the treated eye and 9.3% in the nontreated eye. The treated eye had reduced pupil diameter at 30 minutes after treatment, and miosis persisted throughout the 12 hours of the study. Mean reduction in pupil diameter was 28.5% in the treated eye and 14.2% in the nontreated eye. Topically administered pilocarpine results in reduction of IOP and pupil diameter in treated and contralateral eyes, which supports the use of pilocarpine for treatment of glaucoma in cats.
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PMID:Effects of topical administration of 2.0% pilocarpine on intraocular pressure and pupil size in cats. 203 19

Atrial natriuretic factor (ANF) concentration in the aqueous humor (AH) was studied in rabbits with experimental glaucoma induced by injecting alpha-chymotrypsin into the posterior chamber. In normal rabbit eyes, the ANF concentration in AH was 3.1 +/- 1.2 pg/ml (mean +/- SEM; n = 12), ranging from 0 to 5.8 pg/ml, whereas it was significantly higher in AH from glaucomatous rabbit eyes, being 81.0 +/- 9.8 pg/ml (n = 12). These findings were correlated with intraocular pressure (IOP), which was 13.0 +/- 2.4 mmHg (n = 12) in normal rabbit eyes and significantly greater in glaucomatous eyes: 24.4 +/- 3.0 mmHg (n = 12). Our data indicate that enhanced ANF release in AH during experimental glaucoma may play an important physiological role in modulating IOP.
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PMID:Immunoreactive atrial natriuretic factor in aqueous humor: its concentration is increased with high intraocular pressure in rabbit eyes. 214 92

L-671,152, a new potent water-soluble inhibitor of human carbonic anhydrase II in vitro, was applied topically to cynomolgus monkey eyes in which glaucoma had been produced by argon laser photocoagulation of the trabecular mesh-work. Intraocular pressure was measured at 0 hours, 0.5 hours, and hourly for 8 hours in eight eyes for 2 baseline days, 1 day receiving the vehicle and 5 days receiving therapy with 2% L-671,152 twice a day, after initial single-dose trials of various concentrations. Intraocular pressure was not significantly different comparing baseline and vehicle-treated days. Significant intraocular pressure reductions occurred from 1 to 8 hours after the first dose, and lasted for at least 16 hours after the second dose. The reduction in intraocular pressure became more pronounced from day 1 to day 5 at each time interval. The mean (+/- SEM) maximum reduction in intraocular pressure was 7.8 +/- 2.1 mm Hg on day 1 and 10.1 +/- 2.4 mm Hg on day 5 at 3 hours after administration, comparing the intraocular pressure in drug-treated and vehicle-treated eyes. L-671,152 has a longer duration of action than does previously studied MK-927 in glaucomatous monkeys. It appears to have great clinical potential.
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PMID:The ocular hypotensive effect of the topical carbonic anhydrase inhibitor L-671,152 in glaucomatous monkeys. 232 52


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