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)

The effect of a single instillation of topical carteolol on iridial tissue circulation of pigmented rabbits was studied. The blood flow rate and a quantitative index of tissue blood velocity (NBiris) were measured simultaneously, using the microsphere technique and the laser speckle method, before and 2 hours after the instillation of 20 microliters of 2% carteolol or the vehicle. Consecutive changes of intraocular pressure and NBiris were also studied at 30-minute intervals for 2.5 hours after a single instillation of 2% carteolol in one eye and the vehicle in the contralateral eye. To provide a control, intraocular pressure and NBiris were measured according to the same schedule after the vehicle instillation in both eyes. Two hours after carteolol instillation, iridial blood flow rate and NBiris significantly increased to 127 +/- 8% and 122 +/- 9% (mean +/- SEM, n = 8) of the baseline. Unilateral instillation of carteolol significantly reduced intraocular pressure by about 9 mm Hg in both the carteolol- and vehicle-treated eyes (P < 0.001, analysis of variance); and NBiris was significantly increased by about 20% in both eyes (P < 0.001, analysis of variance), compared with control eyes.
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PMID:Effect of topical carteolol on iridial circulation in pigmented rabbit eyes. 969 Aug 95

An aqueous humor draining device, with size comparable to that of the Krupin tube, was constructed by using poly-HEMA material. Deposits were found on the surface of poly-HEMA when contacted in vitro with the aqueous humor of the rabbit's eye. A fibrous structure, probably composed of proteins and other macromolecules, developed on poly-HEMA surface in 15 days after the draining device was implanted into the rabbit's eye. The draining device was still in function 250 days after its implantation. SEM analysis of the retrieved poly-HEMA draining device indicated that the poly-HEMA tube opening was not blocked by any substance. These results suggest that poly-HEMA could be used as a biomaterial for construction of the aqueous humor draining device to relieve the intraocular pressure of glaucoma patients. Its long-term application awaits further investigation.
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PMID:A poly-HEMA based aqueous humor draining device. 1017 Nov

We have compared the effect of rocuronium and succinylcholine on intraocular pressure (IOP) during rapid sequence induction of anaesthesia using propofol and fentanyl, in a randomized double-blind study. We studied 30 adult patients, allocated to one of two groups. Anaesthesia was induced with fentanyl 2 micrograms kg-1 and propofol until loss of verbal response. This was followed by succinylcholine 1.5 mg kg-1 (group S; n = 15) or rocuronium 0.9 mg kg-1 (group R; n = 15). Laryngoscopy was performed 60 s later. IOP, mean arterial pressure (MAP) and heart rate (HR) were measured before induction, immediately before intubation and every minute after intubation for 5 min. A Keeler Pulsair air impulse tonometer was used to measure IOP and the mean of two readings obtained in the right eye at each measurement time was recorded. Intubating conditions were evaluated according to a simple scoring system. IOP in the succinylcholine group was significantly greater than that in the rocuronium group (mean 21.6 (SEM 1.4) mm Hg vs 13.3 (1.4) mm Hg; P < 0.001). Intubating conditions were equally good in both groups. We conclude that with rapid sequence induction of anaesthesia using propofol and fentanyl, rocuronium did not cause as great an increase in IOP as succinylcholine and may be an alternative in open eye injury cases.
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PMID:Effect of rocuronium compared with succinylcholine on intraocular pressure during rapid sequence induction of anaesthesia. 1069 Jan 55

Our group recently demonstrated that autoimmune T cells directed against central nervous system-associated myelin antigens protect neurons from secondary degeneration. We further showed that the synthetic peptide copolymer 1 (Cop-1), known to suppress experimental autoimmune encephalomyelitis, can be safely substituted for the natural myelin antigen in both passive and active immunization for neuroprotection of the injured optic nerve. Here we attempted to determine whether similar immunizations are protective from retinal ganglion cell loss resulting from a direct biochemical insult caused, for example, by glutamate (a major mediator of degeneration in acute and chronic optic nerve insults) and in a rat model of ocular hypertension. Passive immunization with T cells reactive to myelin basic protein or active immunization with myelin oligodendrocyte glycoprotein-derived peptide, although neuroprotective after optic nerve injury, was ineffective against glutamate toxicity in mice and rats. In contrast, the number of surviving retinal ganglion cells per square millimeter in glutamate-injected retinas was significantly larger in mice immunized 10 days previously with Cop-1 emulsified in complete Freund's adjuvant than in mice injected with PBS in the same adjuvant (2,133 +/- 270 and 1,329 +/- 121, respectively, mean +/- SEM; P < 0.02). A similar pattern was observed when mice were immunized on the day of glutamate injection (1,777 +/- 101 compared with 1,414 +/- 36; P < 0.05), but not when they were immunized 48 h later. These findings suggest that protection from glutamate toxicity requires reinforcement of the immune system by antigens that are different from those associated with myelin. The use of Cop-1 apparently circumvents this antigen specificity barrier. In the rat ocular hypertension model, which simulates glaucoma, immunization with Cop-1 significantly reduced the retinal ganglion cell loss from 27.8% +/- 6.8% to 4.3% +/- 1.6%, without affecting the intraocular pressure. This study may point the way to a therapy for glaucoma, a neurodegenerative disease of the optic nerve often associated with increased intraocular pressure, as well as for acute and chronic degenerative disorders in which glutamate is a prominent participant.
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PMID:Vaccination for protection of retinal ganglion cells against death from glutamate cytotoxicity and ocular hypertension: implications for glaucoma. 1124 90

Two independent, prospective trials were recently conducted to assess the efficacy of latanoprost in reducing intraocular pressure (IOP) in patients with primary angle-closure glaucoma (PACG). The first study was a 2-week, randomized, double-masked comparison of latanoprost treatment and timolol treatment in patients with PACG. Patients were randomized to one of two parallel treatment groups, receiving either placebo in the morning and latanoprost 0.005% in the evening, or timolol 0.5% twice daily. The mean IOP reduction in latanoprost group was 8.8 +/- 1.1 mm Hg (mean +/- SEM, p < 0.001; 34.2%) from a mean baseline IOP of 25.7 +/- 0.9 mm Hg, and the corresponding figures for the timolol group were 5.7 +/- 0.9 mm Hg (p < 0.001; 22.6%) from a mean baseline IOP of 25.2 +/- 1.1 mm Hg. A significantly greater IOP reduction of 3.1 +/- 1.5 mm Hg (95% confidence interval: 0.1 to 6.0) was achieved in the latanoprost group compared to the timolol treatment group (p = 0.04). In the second study, latanoprost 0.005% once a day was added adjunctively to PACG patients with persistently elevated IOP after iridectomy, despite treatment with beta-blockers and pilocarpine. The IOP decreased by about 21% during the first 3 months, and showed a reduction of about 36% at the end of 1 year. At the 1-year follow-up, IOP was <20 mm Hg in all eyes. In both studies, latanoprost was well tolerated with few adverse events. These results demonstrate that latanoprost is effective in reducing IOP in patients with PACG.
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PMID:Efficacy of latanoprost in reducing intraocular pressure in patients with primary angle-closure glaucoma. 1220 8

The objective of this study was to evaluate the changes in intraocular pressure (IOP) in glaucomatous dogs after instillations of 0.2% brimonidine once, twice and three times daily in single day studies, and after twice and three times daily for 4 days in multiple dose studies. We studied eight Beagles with inherited primary open angle glaucoma. Applanation tonometry (IOP), pupil size (PS) and heart rate (HR) measurements were obtained at 8 am, 10 am, 1 pm, 3 pm and 5 pm. The studies were divided into: eight glaucoma dogs and five of the eight dogs that demonstrated greater response to 0.2% brimonidine. Single-dose drug studies are divided into placebo (0.5% methylcellulose), 0.2% brimonidine administered once daily (8 am); twice daily (8 am and noon); and three times daily (8 am, noon and 5 pm). The 5-day multiple-dose studies included: day 1, no drug; and 4 days, 0.2% brimonidine instillations either twice daily (8 am and 2 pm) or three times daily (8 am, 2 pm and 9 pm). Statistical comparisons between drug groups included control (nondrug) and treated (placebo/0.2% brimonidine) eyes for both single- and multiple-dose studies. The mean +/- SEM diurnal decrease in IOP in the eight glaucomatous Beagles for the control and placebo eyes were 3.4 +/- 4.7 and 5.4 +/- 2.8 mmHg, respectively. The mean +/- SEM diurnal decrease in IOP after 0.2% brimonidine once, twice and three times daily was 6.4 +/- 3.5, 8.0 +/- 6.1 and 9.8 +/- 8.1 mmHg, respectively; this trend was not significant statistically. Significant miosis occurred starting 2 h postinstillations, and the resultant mean +/- SD pupil size was 2.7 +/- 0.3 mm. A significant decrease in heart rate also occurred (12%). In the five most responsive dogs the changes in PS and HR during these studies were similar to the larger group, but significant decreases in IOP occurred at most measurement times. In the multiple-dose study with 0.2% brimonidine twice daily the mean +/- SEM decrease in IOP for day 1 to day 4 was 5.0 +/- 1.3, 5.7 +/- 1.3, 1.4 +/- 3.3 and 4.9 +/- 1.3 mmHg, respectively. When 0.2% brimonidine was instilled three times daily the mean +/- SEM diurnal IOP decrease was from day 1 to day 4 and was 0.75 +/- 1.3, 2.4 +/- 1.5, 1.2 +/- 2.7 and 1.4 +/- 1.8 mmHg, respectively. The mean change in pupil diameter was 1.3 +/- 0.5 mm. Decrease in HR averaged 22%. In the same single-dose studies with the five most responsive dogs, PS and HR were similar, but the decreases in IOP were significant at more measurement intervals. We conclude that 0.2% brimonidine produces a decrease in IOP in dogs, a statistically significant miosis, and a reduced heart rate (12-22%). However, because of the limited drug-induced ocular hypotension, brimonidine should be combined with other drugs when used for the glaucomas in the dog.
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PMID:Effect of single and multiple doses of 0.2% brimonidine tartrate in the glaucomatous Beagle. 1244 95

The changes in intraocular pressure and pupil size in glaucomatous dogs were evaluated after instillations of 0.03% bimatoprost (Lumigan, Allergan, Irvine, CA USA) once in the morning, or once in the evening, or twice daily in five day multiple dose studies. Applanation tonometry (IOP) and pupil size (PS) measurements were obtained at 8 am, 10 am, 12 noon, 2 pm, and 4 pm in 8 glaucoma dogs. Methylcellulose (0.5% as placebo) was instilled in the control eye, and 0.03% bimatoprost was instilled in the opposite drug eye. Methylcellulose (0.5%) and 0.03% bimatoprost were instilled the second through the fifth days with instillations in the morning (8:30 am), or evening (8 pm), or twice daily (8:30 am and 8 pm). The mean +/- SEM diurnal changes in IOP from baseline values after 0.03% bimatoprost at 8 am once daily for the next four days were 25.0 +/- 3.2 mm Hg, 25.6 +/- 2.9 mm Hg, 25.5 +/- 3.0 mm Hg, and 26.0 +/- 3.2 mm Hg respectively, and were significantly different from the control eye. After bimatoprost was instilled at 8 pm, the mean +/- SEM changes in IOP from baseline values in the drug eyes were 27.3 +/- 2.4 mm Hg, 26.6 +/- 2.2 mm Hg, 27.2 +/- 2.5 mm Hg, and 27.3 +/- 2.6 mm Hg respectively. When 0.03% bimatoprost was instilled twice daily, the mean +/- SEM changes in IOP from baseline values were 39.1 +/- 2.3 mm Hg, 39.9 +/- 2.2 mm Hg, 39.9 +/- 2.3 mm Hg, and 39.6 +/- 2.1 mm Hg respectively, and were significantly different from the control eyes. Miosis of varying duration was frequent during the three studies. Bimatoprost instilled once daily (am or pm) as well as twice daily produces significant decreases in IOP and PS in the glaucomatous Beagle.
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PMID:Effect of different dose schedules of bimatoprost on intraocular pressure and pupil size in the glaucomatous Beagle. 1253 79

The aim of the study was to evaluate the efficacy of replacing current dual local therapy (timolol and pilocarpine) with latanoprost 0.005% in 71 pseudoexfoliation glaucoma patients with controlled intraocular pressure (IOP). 39 patients switched to latanoprost 0.005%) and 32 patients continued timolol-pilocarpine therapy. Mean diurnal (IOP) was measured at baseline, after 0.5, 1, 3 and 6 months of treatment. After 6 months 38 patients with latanoprost and 30 patients with timolol-pilocarpine had completed the study. At baseline the mean diurnal IOP was 20.4 +/- 2.0 mmHg for patients in latanoprost treatment group and 21.4 +/- 2.1 mmHg for patients in timolol-pilocarpine group. At the end of the study, after 6 months of treatment, the mean diurnal IOP values were 16.6 +/- 2.4 and 17.9 +/- 2.0 mmHg respectively. IOP was statistically significantly reduced from baseline (p < 0.001). The mean diurnal IOP change from baseline was -3.3 +/- 0.5 mmHg (mean +/- SEM, ANCOVA) for the patients treated with latanoprost and -3.2 +/- 0.4 mmHg for the patients treated with timolol + pilocarpine. This difference in IOP reduction between groups was not statistically significant (z = 0.69; p = 0.49). This study showed that combination therapy (timolol plus pilocarpine) in pseudoexfoliation glaucoma can effectively be replaced by latanoprost monotherapy.
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PMID:A study of replacement of timolol-pilocarpine with latanoprost in pseudoexfoliation glaucoma. 1474 65

To evaluate the effect of CS-088, an angiotensin AT1 receptor antagonist, on intraocular pressure (IOP) in monkey eyes with unilateral laser-induced glaucoma. A multiple-dose study was performed in 8 glaucomatous monkey eyes. One 50 microl drop of CS-088, 2% or 4%, was topically applied to the glaucomatous eye at 9:30 a.m. and 3:30 p.m. for 5 consecutive days. IOP was measured hourly for 6 hours beginning at 9:30 a.m. for one baseline day, one vehicle-treated day, and daily for 5 days of treatment with CS-088. The washout period between the two drug concentrations was at least 2 weeks. Twice daily administration of 2 % CS-088 for 5 days did not reduce the IOP until the third dose on day 2 of the treatment regimen. A significant (p<0.02) reduction in IOP began 1 hour after the third dose, and lasted for 3 hours. The maximum reduction in IOP was 5.3+/- 0.8 (mean+/-SEM) mmHg (15%) (p<0.001), with the longest duration of IOP reduction of at least 6 hours after dosing on day 5. The 4% dose of CS-088 reduced (p<0.05) IOP from 1 to 5 hours after the first dose. The maximum reduction in IOP was 6.9+/-1.0 mmHg (20%), with the longest duration of IOP reduction of at least 18 hours after administration on day 5. Both 2% and 4% CS-088 showed enhancement of the ocular hypotensive effect with repeated dosing. 4% CS-088 produced greater (p<0.05) IOP reduction with longer duration of action than 2%. Topically applied CS-088, a new antagonist drug at the angiotensin AT1 receptor, reduced IOP in glaucomatous monkey eyes in a dose-dependent manner.
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PMID:Effect of CS-088, an angiotensin AT1 receptor antagonist, on intraocular pressure in glaucomatous monkey eyes. 1586 69

Glaucoma is the second leading cause of blindness in the world. Loss of vision in glaucomatous optic neuropathy is caused by the selective degeneration of retinal ganglion cells (RGCs). Ocular hypertension is a major risk factor in glaucoma, but visual field defects continue to progress in some patients despite the use of drugs that lower intraocular pressure. At present, there are no effective neuroprotective strategies for the treatment of this disease. The extracellular signal-regulated kinase (Erk) 1/2 pathway is an evolutionarily conserved mechanism used by several peptide factors to promote cell survival. Here we tested if selective activation of Erk1/2 protected RGCs in a rat model of experimental glaucoma. We used recombinant adeno-associated virus to transduce RGCs with genes encoding constitutively active or wild-type MEK1 (approved gene symbol MAP2K1), the upstream activator of Erk1/2. MEK1 gene transfer into RGCs markedly increased neuronal survival: 1366 +/- 70 RGCs/mm(2) (mean +/- SEM) were alive in the dorsal retina at 5 weeks after ocular hypertension surgery, a time when only 680 +/- 86 RGCs/mm(2) of these neurons remained in control eyes. We conclude that the Erk1/2 pathway plays a key role in the protection of RGCs from ocular hypertensive damage. This study identifies a novel gene therapy strategy in which selective activation of the Erk1/2 signaling pathway effectively slows cell death in glaucoma.
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PMID:Activation of the extracellular signal-regulated kinase 1/2 pathway by AAV gene transfer protects retinal ganglion cells in glaucoma. 1597 50


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