{"title":"Adrenergic regulation of aqueous outflow.","authors":"K Erickson, L Liang, P Shum, J A Nathanson","doi":"10.1089/jop.1994.10.241","DOIUrl":"https://doi.org/10.1089/jop.1994.10.241","url":null,"abstract":"<p><p>Epinephrine increased outflow facility and cyclic AMP in the in vitro perfused human anterior segment with a maximal facility increase of 44% occurring at approximately 2 x 10(-5) M. Cyclic AMP measured in the perfusate from anterior segments increased by 12-14 fold after administration of 10(-5) M epinephrine. Both the facility increase and cyclic AMP rise were blocked by the beta-2 selective antagonist, ICI118,551. While there was a correlation between the facility increase and elevation in cyclic AMP levels, the rise in cyclic AMP preceded the facility increase by about 1 hour, suggesting that the ultimate effect of epinephrine involved a rather slow event such as synthesis and release of prostaglandins or protein synthesis. Subsequent perfusion studies showed that very large concentrations of indomethacin were necessary to block the outflow facility effect of epinephrine, suggesting that prostaglandin synthesis did not underlie the facility effect in this system. However, 5 x 10(-5) M cyclohexamide blocked the effect on outflow facility of both epinephrine and forskolin, but did not block the rise in cyclic AMP. These studies suggest that protein synthesis may play a role in the epinephrine-induced facility increase at some point beyond the second messenger level.</p>","PeriodicalId":16638,"journal":{"name":"Journal of ocular pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/jop.1994.10.241","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18909545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Modulation of retinal aromatic L-amino acid decarboxylase by light and neuroactive drugs.","authors":"N H Neff, M Hadjiconstantinou","doi":"10.1089/jop.1994.10.265","DOIUrl":"https://doi.org/10.1089/jop.1994.10.265","url":null,"abstract":"","PeriodicalId":16638,"journal":{"name":"Journal of ocular pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/jop.1994.10.265","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18909546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M Sharir, T J Zimmerman, R G del Negro, S F Ball, K S Kooner
{"title":"A comparison of the efficacy of various metipranolol-pilocarpine combinations in patients with ocular hypertension and primary open-angle glaucoma.","authors":"M Sharir, T J Zimmerman, R G del Negro, S F Ball, K S Kooner","doi":"10.1089/jop.1994.10.411","DOIUrl":"https://doi.org/10.1089/jop.1994.10.411","url":null,"abstract":"<p><p>We compared the ocular hypotensive effects of four fixed-dose metipranolol-pilocarpine combinations in nineteen ocular hypertensive subjects and glaucoma patients. Each patient was tested with all of the study medications: vehicle alone, 0.1% metipranolol HCl + 2% pilocarpine HCl, 0.1% metipranolol HCl + 4% pilocarpine HCl, 0.3% metipranolol HCl + 2% pilocarpine HCl, and 0.3% metipranolol HCl + 4% pilocarpine HCl, in a single dose, randomized, double-masked, cross-over placebo-controlled trial. In addition, another eight age and baseline intraocular pressure (IOP)-matched subjects received 0.1% or 0.3% metipranolol HCl, while a similar group of 14 volunteers received 2% or 4% pilocarpine HCl. A two week washout period was instituted between the various groups of treatments. All four metipranolol-pilocarpine combinations were more effective than placebo or either medication alone in reducing the average IOP for up to 8 hours (p < 0.05 for each treatment group). Metipranolol HCl 0.3%, regardless of the pilocarpine concentration, demonstrated the most significant IOP lowering effect, reducing the IOP by 4.9 mm Hg or about 20% from baseline. However, 0.1% metipranolol HCl in combination with 4% pilocarpine HCl was found almost as effective with a 18.5% reduction in IOP from baseline, but a shorter duration of action. In conclusion, all metipranolol-pilocarpine combinations were more efficacious than either medication alone in a single-dose trial. Additional multiple-dose studies are needed to determine the long-term effectiveness and tolerance of combining 0.3% metipranolol HCl with either 2% or 4% pilocarpine HCl.</p>","PeriodicalId":16638,"journal":{"name":"Journal of ocular pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/jop.1994.10.411","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18915569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Studies on prostanoid receptors in ocular tissues.","authors":"P Bhattacherjee, C A Paterson","doi":"10.1089/jop.1994.10.167","DOIUrl":"https://doi.org/10.1089/jop.1994.10.167","url":null,"abstract":"<p><p>Cyclooxygenase products of arachidonic acid, for example prostaglandins (PGs), prostacyclin, and thromboxane A2, mediate a wide range of physiological actions. Vasodilation, increased vascular permeability, platelet aggregation and its inhibition, and immunomodulation are some of the important biological actions of cyclooxygenase products (1). Depending on type and dose, PGs cause vasodilation, increase or decrease intraocular pressure, and disrupt the blood-aqueous barrier (2, 3). These actions also vary qualitatively and quantitatively with the animal species. Prostaglandins, like any biological molecule, must act by binding with their specific receptors. Coleman and coworkers (4, 5), from a series of studies with PG agonists and antagonists in vascular and non-vascular smooth muscle preparations, classified PG receptors. This classification led to a greater appreciation of the relationship between PG actions and specific PG receptors in various tissues. Ocular actions of PGs linked with specific PG receptors are far from being clear. In this communication we will review our work on PG binding sites in ocular tissues and PG receptors coupled to adenylyl cyclase or phosphoinositidase C signal transduction pathways in ocular tissues of various animal species.</p>","PeriodicalId":16638,"journal":{"name":"Journal of ocular pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/jop.1994.10.167","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19196951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"S-adenosyl-L-methionine-mediated enzymatic methylations in the rat retinal membranes.","authors":"B V Sastry, P S Vidaver, V E Janson, J J Franks","doi":"10.1089/jop.1994.10.253","DOIUrl":"https://doi.org/10.1089/jop.1994.10.253","url":null,"abstract":"<p><p>Enzymatic step-wise methylation of membrane phosphatidylethanolamine (PE) to phosphatidyl-N-methylethanolamine (PME) and then phosphatidyl-choline (PC) has been known to alter membrane properties and responsiveness of cells for activation of receptors by chemical transmitters. Conversion of PE to PME and PME to PC in the presence of S-adenosyl-L-methionine (SAM) are catalyzed by two phospholipid N-methyltransferases, PMT I and PMT II, of which PMT I is the rate limiting enzyme. Retina is a good neuronal model for chemical transmission. However, retina was not studied for PMT activity. Therefore, we studied the rat retina for PMT I activity. Methylation of PE in the rat retinal sonicates was assayed using 3H-SAM (2 microM) at 37 degrees C in Tris-glycylglycine buffer (50 mM, pH 8.0) and methylated phospholipids were extracted with chloroform/methanol/HCl (2/1/0.02, v/v) and separated by thin layer chromatography on Silica Gel G plates. Chromatograms were developed in a solvent system of propionic acid/n-propyl alcohol/chloroform/water (2/2/1/1, v/v). This study gave the following results: (a) the total methylated phospholipids were (M +/- SE, N = 5) 19.90 +/- 4.03 fmol/mg protein/min; (b) the major methylated phospholipid was PME (4.21 +/- 0.68 fmol/mg protein/min; (c) the fatty acid methylesters formed by fatty acid carboxymethylase (FACM) which accumulated in the solvent front amounted to 18.82 +/- 2.84 fmol/mg protein/min. Both PMT I and FACM were inhibited by S-adenosyl-L-homocysteine (I50, 1.2-5 microM). These observations indicate that rat retina contains both PMTs and FACM.</p>","PeriodicalId":16638,"journal":{"name":"Journal of ocular pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/jop.1994.10.253","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19197494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S A Elgebaly, D Miano, W Ehlers, F Rahhal, E Tyles, A F el-Kerm
{"title":"The induction of anterior chamber inflammation by factors released from hydrogen peroxide-injured corneas: effect of dexamethasone and indomethacin.","authors":"S A Elgebaly, D Miano, W Ehlers, F Rahhal, E Tyles, A F el-Kerm","doi":"10.1089/jop.1994.10.295","DOIUrl":"https://doi.org/10.1089/jop.1994.10.295","url":null,"abstract":"<p><p>Studies from our laboratory have demonstrated the release of high levels of neutrophil chemotactic factors (NCF) from isolated rabbit corneas injured by hydrogen peroxide (H2O2). The purpose of the present study was to determine the biological activity of these factors and to test the hypothesis that the intracameral injection of these factors can induce inflammation of the anterior segment. Under sterile conditions, the epithelial surfaces of isolated rabbit corneas were incubated with a 300 ul mixture of glucose (G) (1mg/ml) and glucose oxidase (GO) (20 U/ml) at 37 degrees C for 6 hours. This supernatant solution was collected and a 100 ul sample containing NCF, but not H2O2, was injected into the anterior chamber of anesthetized rabbit eyes (n = 8). Anterior chamber inflammation, characterized by moderate corneal edema associated with a fibrinous anterior chamber reaction, was evident 2 and 4 hours after injection. Aqueous humor analysis revealed the presence of fibrin and a large number of neutrophils (32 +/- 5 x 10(4) cells/ml). Control eyes, on the other hand, showed normal morphology and low levels of neutrophils after the injection of 100 ul minimum essential medium (MEM) (n = 8) (1.2 +/- 0.14 x 10(4) cells/ml), G/GO mixture (n = 8) (5 +/- 0.86 x 10(4) cells/ml), or supernatant solutions collected from MEM-treated corneas (n = 8) (15 +/- 2 x 10(4) cells/ml). To determine whether the inflammatory reaction observed was due to a direct effect of the chemoattractants or mediated through stimulation of arachidonic acid (AA) metabolites, we pretreated rabbit eyes with a sterile solution of 0.1% dexamethasone (n = 8 eyes) or with a sterile solution of 3.4% indomethacin (n = 8 eyes) three times a day, for one day, prior to the injection of NCF supernatant solution. Examination 2 hours and 4 hours after injection revealed inflammation characterized by mild-to-moderate corneal edema associated with a fibrinous anterior chamber reaction was observed with or without prior treatment with AA metabolite inhibitors. No difference in the degree of inflammation was detected clinically. Results of these studies suggest that NCF released from H2O2-injured corneas can directly induce inflammation of the anterior segment, and that metabolites of AA are not mediating the observed in vivo response.</p>","PeriodicalId":16638,"journal":{"name":"Journal of ocular pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/jop.1994.10.295","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19198742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Platelet-activating factor antagonists and ocular inflammation.","authors":"H E Bazan, Y Tao, J S Hurst","doi":"10.1089/jop.1994.10.319","DOIUrl":"https://doi.org/10.1089/jop.1994.10.319","url":null,"abstract":"","PeriodicalId":16638,"journal":{"name":"Journal of ocular pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/jop.1994.10.319","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19198744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Treatment of glaucoma with 3 alpha, 5 beta-tetrahydrocortisol: a new therapeutic modality.","authors":"A L Southren, T Wandel, G G Gordon, B I Weinstein","doi":"10.1089/jop.1994.10.385","DOIUrl":"https://doi.org/10.1089/jop.1994.10.385","url":null,"abstract":"<p><p>The effectiveness of 3 alpha, 5 beta-tetrahydrocortisol (3 alpha, 5 beta-THF), a metabolite of cortisol, in lowering intraocular pressure (IOP) in rabbits made ocular hypertensive with glucocorticoids suggested its use in patients with Primary Open Angle Glaucoma (POAG). Patients with well-documented POAG were treated with a 1% suspension of 3 alpha, 5 beta-THF administered to one eye four times daily for up to six weeks. Eight out of nine patients experienced an appreciable decrease in IOP in the treated eye (average decrease 4.9 mm Hg). There was no conjunctival irritation, corneal pathology, visual field changes, alteration in liver or renal function tests or blood count during the treatment period. The present study demonstrates that 3 alpha, 5 beta-THF, a naturally occurring steroid metabolite, is effective in lowering IOP in patients with POAG. Antiglucocorticoids may represent a new therapeutic modality for the management of POAG.</p>","PeriodicalId":16638,"journal":{"name":"Journal of ocular pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/jop.1994.10.385","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19198749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J M Yanni, D J Stephens, D W Parnell, J M Spellman
{"title":"Preclinical efficacy of emedastine, a potent, selective histamine H1 antagonist for topical ocular use.","authors":"J M Yanni, D J Stephens, D W Parnell, J M Spellman","doi":"10.1089/jop.1994.10.665","DOIUrl":"https://doi.org/10.1089/jop.1994.10.665","url":null,"abstract":"<p><p>Emedastine [1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)- benzimidazole difumarate] was evaluated for topical ocular anti-histaminic activity in histamine and antigen stimulated conjunctivitis models. Concentration-dependent inhibition of histamine induced vascular permeability changes occurring in the conjunctiva was observed when the time interval between topical ocular administration and histamine challenge ranged from 1 min to 8 hr. The calculated ED50 values obtained using intervals of 1 min, 30 min, 2, 4 and 8 hr were 0.0002%, 0.000035%, 0.0029%, 0.019% and 0.19%, w/v, respectively. Comparisons of relative potency 30 min post dosing between emedastine and other anti-histamines demonstrated that emedastine is equipotent to ketotifen, and 7, 7, 10, 10, 100, 357, 3333, and 5813 times more potent than brompheniramine, chlorpheniramine, clemastine, pyrilamine, levocabastine, pheniramine, diphenhydramine, and antazoline, respectively. Emedastine (0.1%) failed to significantly attenuate either serotonin or platelet-activating-factor induced vascular permeability changes indicating high selectivity for the histamine H1 receptor. In a passive conjunctival anaphylaxis model in guinea pigs, significant inhibition of the allergic response was observed following topical ocular administration of emedastine 5 min or 30 min prior to antigen challenge (ED50s 0.0046% and 0.00022%, respectively). These data clearly indicate that emedastine has potential as a topical ocular anti-histamine for treating allergic conjunctivitis.</p>","PeriodicalId":16638,"journal":{"name":"Journal of ocular pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/jop.1994.10.665","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18715909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}