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":"10 1","pages":"295-306"},"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":"10 1","pages":"319-27"},"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":"10 1","pages":"385-91"},"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}
{"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":"10 1","pages":"241-52"},"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":"10 1","pages":"265-71"},"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}
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":"10 4","pages":"665-75"},"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}
{"title":"Intravitreal delivery of ganciclovir in rabbits by transscleral iontophoresis.","authors":"T T Lam, J Fu, R Chu, K Stojack, E Siew, M O Tso","doi":"10.1089/jop.1994.10.571","DOIUrl":"https://doi.org/10.1089/jop.1994.10.571","url":null,"abstract":"<p><p>To avoid the side effects of systemic administration of ganciclovir (GCV) for the treatment of cytomegalovirus (CMV) retinitis, we studied transscleral iontophoresis of GCV into rabbit eyes. After a single application with 20% (w/w) aqueous solution of GCV at 1.0 mA for 15 min gave a vitreal/retinal level of GCV at 74 +/- 17 micrograms/ml at 2 hours as determined by HPLC. At 24 hours after iontophoresis the vitreal/retinal level was above therapeutic level at 4.2 +/- 0.6 micrograms/ml. At 72 hours, there was still detectable level in the vitreous/retina. Hence, transscleral iontophoresis is able to deliver effective dose of GCV into the vitreous. Multiple applications of iontophoresis should be examined as a possible means of CMV treatment.</p>","PeriodicalId":16638,"journal":{"name":"Journal of ocular pharmacology","volume":"10 3","pages":"571-5"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/jop.1994.10.571","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18836998","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":"Synthesis of 12(R)- and 12(S)-hydroxyeicosatetraenoic acid by porcine ocular tissues.","authors":"T Asakura, M Matsuda, S Matsuda, H Shichi","doi":"10.1089/jop.1994.10.525","DOIUrl":"https://doi.org/10.1089/jop.1994.10.525","url":null,"abstract":"<p><p>Microsomal fractions from porcine ocular tissues synthesized 12(S)-5,8,10,14-hydroxyeicosatetraenoic acid [12(S)-HETE] from arachidonic acid by a membrane-bound lipoxygenase and 12(R)-HETE by the cytochrome P450-dependent monooxygenase system. Both activities were the highest in corneal microsomes. The 12(R)-HETE synthesizing activity of corneal microsomes was dependent on NADPH and inhibited by 0.1 mM SKF-525A, an inhibitor of P450 enzymes. The activity to form 12(R)-enantiomer was significantly enhanced by treatment of corneal epithelium with 3-methylcholanthrene or clofibrate. The induced activity was suppressed by cycloheximide, indicating that the induction of enzyme activities involved a translational process. The effect of these inducers on 12(R)-HETE synthesizing activity appeared to be additive. The activity to form 12(S)-enantiomer was markedly stimulated by 3 mM CaCl2. The 12-lipoxygenase of corneal microsomes was capable of oxygenating linoleic acid in addition to arachidonic acid, a characteristic of 12-lipoxygenases of the leukocyte type. 12(R)-HETE at 10(-6) M inhibited almost completely the Na,K-ATPase of corneal epithelium but had little or no effect on ciliary epithelial enzymic activity. 12(S)-HETE at 10(-6) M also inhibited corneal enzymic activity but to a lesser extent, and had no significant effect on ciliary epithelial Na,K-ATPase activity.</p>","PeriodicalId":16638,"journal":{"name":"Journal of ocular pharmacology","volume":"10 3","pages":"525-35"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/jop.1994.10.525","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18837044","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":"10 2","pages":"411-20"},"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}