Journal of ocular pharmacology最新文献_第3页

Relevance of drug-melanin interactions to ocular pharmacology and toxicology. 药物-黑色素相互作用与眼部药理学和毒理学的相关性。

Journal of ocular pharmacology Pub Date : 1994-01-01 DOI: 10.1089/jop.1994.10.217

M M Salazar-Bookaman, I Wainer, P N Patil

{"title":"Relevance of drug-melanin interactions to ocular pharmacology and toxicology.","authors":"M M Salazar-Bookaman, I Wainer, P N Patil","doi":"10.1089/jop.1994.10.217","DOIUrl":"https://doi.org/10.1089/jop.1994.10.217","url":null,"abstract":"In melanocytes, the biosynthesis of L-dopa derived indole polymer, melanin, is accelerated by tyrosinase and related enzymes. The brown to black pigment is characterized by a stable free-radical property. In humans, a pigment dependent slow onset of ocular actions of ephedrine, atropine, cocaine, pilocarpine and related medications was observed. Extensive accumulation of drugs by melanin appears to be the most important factor governing the long term therapeutic/toxicological activities. Drugs crossing placental circulation are localized in the mouse fetal eye. Thus, drugs exhibit a high binding capacity for melanin containing tissues. Studies on synthetic melanin and melanin granules also indicated a high binding capacity of many therapeutic classes of drugs, including psychotropics. In addition to the liposoluble property of the molecule, there is a definite relationship between chemical structure and the affinity of drugs for melanin. For example, the affinity of chlorpromazine for melanin is higher than that of chlorprothixene. NMR studies, with soluble melanins indicate that there is a steric preference among ephedrine enantiomers. A high binding capacity indicates that more than two molecules of (-)-ephedrine may complex with one indole unit of melanin. Ocular drug development calls for the study of qualitative and quantitative aspects of drug-melanin interaction.","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.1994.10.217","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19197493","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}

引用次数: 70

Effect of metabolic inhibitors on arachidonic acid metabolism in the corneal epithelium: evidence for cytochrome P450-mediated reactions. 代谢抑制剂对角膜上皮花生四烯酸代谢的影响:细胞色素p450介导反应的证据。

Journal of ocular pharmacology Pub Date : 1994-01-01 DOI: 10.1089/jop.1994.10.307

R A Stoltz, M S Conners, M W Dunn, M L Schwartzman

{"title":"Effect of metabolic inhibitors on arachidonic acid metabolism in the corneal epithelium: evidence for cytochrome P450-mediated reactions.","authors":"R A Stoltz, M S Conners, M W Dunn, M L Schwartzman","doi":"10.1089/jop.1994.10.307","DOIUrl":"https://doi.org/10.1089/jop.1994.10.307","url":null,"abstract":"The corneal epithelium of several species, has the capacity to metabolize arachidonic acid (arachidonic acid) via an NADPH-dependent cytochrome P450 mechanism. The major metabolites are 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) and 12-hydroxy-5,8,14-eicosatrienoic acid (12-HETrE), both of which exist in stereoisomeric configurations. However, the R enantiomers are predominantly produced by this enzyme system and exhibit potent biological activities. 12(R)-HETE inhibits Na-K-ATPase, increases corneal thickness and reduces intraocular pressure. 12(R)-HETrE causes vasodilation, neutrophil chemoattraction and angiogenesis. The formation of these metabolites is unaffected by cyclooxygenase and lipoxygenase inhibitors (indomethacin, diclofenac and BW755C) but inhibited by cytochrome P450 enzyme inhibitors such as carbon monoxide, SKF-525A and clotrimazole. The capacity of the normal corneal epithelium to metabolize arachidonic acid via cytochrome P450 is very low although under certain conditions this enzymatic pathway may become greatly induced. Corneal epithelial hypoxia in response to contact lens wear results in the time-dependent formation of NADPH-cytochrome P450-dependent arachidonate metabolites, 12(R)-HETE and 12(R)-HETrE. Under this condition, metabolite production correlates strongly with the in situ inflammatory response and inhibition of their formation significantly attenuates inflammation. It is evident that the cytochrome P450 arachidonate metabolites should be added to the realm of cyclooxygenase and lipoxygenase-derived eicosanoids as possible inflammatory mediators. Therefore, studies to evaluate eicosanoid involvement in inflammation should examine inhibitors of this pathway in addition to the classically studied non-steroidal antiinflammatory drugs (NSAIDs).","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.1994.10.307","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19198743","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}

引用次数: 23

Steroidal and nonsteroidal drugs in endotoxin-induced uveitis. 内毒素性葡萄膜炎的甾体和非甾体药物治疗。

Journal of ocular pharmacology Pub Date : 1994-01-01 DOI: 10.1089/jop.1994.10.329

P S Kulkarni

{"title":"Steroidal and nonsteroidal drugs in endotoxin-induced uveitis.","authors":"P S Kulkarni","doi":"10.1089/jop.1994.10.329","DOIUrl":"https://doi.org/10.1089/jop.1994.10.329","url":null,"abstract":"Various classes of anti-inflammatory compounds like steroids (dexamethasone), cyclooxygenase inhibitors (indomethacin and flurbiprofen), 5-lipoxygenase inhibitors (BWA 218C and BWA 4C), immunosuppressive drugs (cyclosporin and rapamycin) and cod liver oil were tested for their antiinflammatory activities in endotoxin-induced uveitis model in rabbits. Intraocular inflammation was assessed in terms of two inflammatory responses i.e. breakdown of blood-aqueous barrier (BAB) and leukocyte infiltration into aqueous humor and iris ciliary body (ICB). Prostaglandin (PG) E2 and leukotriene (LT) B4 release into aqueous humor was also measured. Indomethacin significantly inhibited PGE2 release without affecting leukocyte or BAB response. Flurbiprofen prevented leukocyte, PGE2 and LTB4 release into aqueous humor but not ICB chemotaxis. BWA 218C and BWA 4C also significantly inhibited leukocyte and LTB4 release but not BAB responses. Dexamethasone (2mg/kg, i.m.) and cyclosporin A (25 mg/kg i.m.) significantly inhibited leukocyte infiltration into aqueous humor and ICB, and PGE2 release but they failed to inhibit breakdown of BAB and LTB4 release. On the other hand, rapamycin (10mg/kg i.m.) and cod liver oil (1 ml daily i.m. up to 15 days) significantly prevented leukocyte and BAB response. Cod liver oil also significantly inhibited PGE2 and LTB4 release but rapamycin affected only PGE2 release into aqueous humor. It is concluded that arachidonic acid metabolites may not play a vital role in this uveitis model and additional proinflammatory mediators like cytokines may be involved.","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.1994.10.329","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19198745","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}

引用次数: 16

The effect of pilocarpine on ocular levobunolol absorption from ophthalmic solutions. 匹洛卡平对眼液中左旋布诺尔吸收的影响。

Journal of ocular pharmacology Pub Date : 1994-01-01 DOI: 10.1089/jop.1994.10.605

D D Tang-Liu, J B Richman

引用次数: 1

Review: pharmacological manipulation of docosahexaenoic-phospholipid biosynthesis in photoreceptor cells: implications in retinal degeneration. 综述:光感受器细胞中二十二碳六烯烷磷脂生物合成的药理学操作:视网膜变性的意义。

Journal of ocular pharmacology Pub Date : 1994-01-01 DOI: 10.1089/jop.1994.10.591

N G Bazan, E B Rodriguez de Turco

{"title":"Review: pharmacological manipulation of docosahexaenoic-phospholipid biosynthesis in photoreceptor cells: implications in retinal degeneration.","authors":"N G Bazan, E B Rodriguez de Turco","doi":"10.1089/jop.1994.10.591","DOIUrl":"https://doi.org/10.1089/jop.1994.10.591","url":null,"abstract":"Docosahexaenoic acid (22:6n-3, DHA) is derived in vertebrate animals from n-3 fatty acids present in the diet (i.e., alpha-linolenic acid, 18:3n-3 and/or other n-3-long chain polyunsaturated fatty acids) and is found in very high concentrations in phospholipids from membranes of the central nervous system. Disk membranes of photoreceptor outer segments and synaptic terminals display a preferential enrichment in DHA-phospholipids that appears to be necessary for normal excitable membrane functions. Because of the relevance of adequate DHA-phospholipid synthesis and sorting toward new assembled disk membranes and synaptic terminals, as well as the pathophysiological implications of abnormal DHA metabolism (including its synthesis, delivery to the retina, and incorporation into lipids by de novo and turnover pathways), we reviewed recent studies of: a) the preferential uptake and retention of DHA by photoreceptors and its metabolism as it is activated to DHA-CoA and incorporated preferentially into phospholipids; b) pharmacological manipulations using amphiphilic cationic drugs (i.e., propranolol) to show an active esterification of DHA into lipids via de novo synthesis; and c) perturbations in DHA metabolism in retinas from dogs with progressive rod-cone degeneration (prcd).","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.1994.10.591","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18837001","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}

引用次数: 35

Effect of ascorbic acid 2-O-alpha-glucoside on hydrocortisone-induced cataract formation in developing chick embryos: II. Influence on glutathione and lipid peroxide contents in the lens. 抗坏血酸2- o - α -葡萄糖苷对氢化可的松诱导的发育中的鸡胚白内障形成的影响对晶状体中谷胱甘肽和过氧化脂质含量的影响。

Journal of ocular pharmacology Pub Date : 1994-01-01 DOI: 10.1089/jop.1994.10.537

M Nagata, M Hikida, H Mibu, N Muto, I Yamamoto

引用次数: 6

Low dose cyclosporin-A therapy in Behçet's disease. 小剂量环孢素a治疗behaperet病。

Journal of ocular pharmacology Pub Date : 1994-01-01 DOI: 10.1089/jop.1994.10.553

H Sajjadi, M Soheilian, H Ahmadieh, K Hassanein, M Parvin, M Azarmina, V Ehyaee, B Amiransari

{"title":"Low dose cyclosporin-A therapy in Behçet's disease.","authors":"H Sajjadi, M Soheilian, H Ahmadieh, K Hassanein, M Parvin, M Azarmina, V Ehyaee, B Amiransari","doi":"10.1089/jop.1994.10.553","DOIUrl":"https://doi.org/10.1089/jop.1994.10.553","url":null,"abstract":"The effect of systemic low dose cyclosporin-A (5 mg/kg/day as initial dose) combined with 0.2 to 0.6 mg/kg/day prednisolone (when necessary) in clinical course of 22 patients suffering from severe forms of Behçet's disease are reviewed. All the patients had received other drugs previously and had either no response to them or developed intolerable side effects, therefore, pre treatment visual acuity (VA) was compared to post treatment VA as \"self control\". The average age of our patients was 30.6 years (range 19-51 years). The average duration of our therapy was 19.5 months (range 4-32 months). Improvement or stabilization of vision was achieved in 21 patients (95%). The intraocular inflammation was controlled in all of the eyes and most of the non-ocular signs and symptoms were also improved. Serious side effects included rise in creatinine in 10 (45%) of the patients, rise in bilirubin in 6 (27%) and hypertension in 1 (4.5%). These side effects disappeared as the dose of cyclosporin-A was tapered. We believe this form of therapy is of great value in the management of severe forms of Behçet's disease.","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.1994.10.553","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18837047","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}

引用次数: 38

Ocular effects of alpha 2-adrenoceptor activation in anesthetized cats. 麻醉猫α 2-肾上腺素能受体激活对眼部的影响。

Journal of ocular pharmacology Pub Date : 1994-01-01 DOI: 10.1089/jop.1994.10.149

M C Koss, T Gherezghiher

引用次数: 7

Ganciclovir ophthalmic gel in herpes simplex virus rabbit keratitis: intraocular penetration and efficacy. 更昔洛韦眼用凝胶治疗兔单纯疱疹病毒性角膜炎:眼内渗透及疗效观察。

Journal of ocular pharmacology Pub Date : 1994-01-01 DOI: 10.1089/jop.1994.10.439

N Castela, N Vermerie, F Chast, H Sauvageon-Martre, J Denis, V Godard, P Goldschmidt, Y Pouliquen

{"title":"Ganciclovir ophthalmic gel in herpes simplex virus rabbit keratitis: intraocular penetration and efficacy.","authors":"N Castela, N Vermerie, F Chast, H Sauvageon-Martre, J Denis, V Godard, P Goldschmidt, Y Pouliquen","doi":"10.1089/jop.1994.10.439","DOIUrl":"https://doi.org/10.1089/jop.1994.10.439","url":null,"abstract":"A chronic administration of three ganciclovir gels (0.2%, 0.05%, 0.0125%) was compared with a placebo gel and a 3% acyclovir ophthalmic ointment in the treatment of HSV-1 rabbit keratitis. All the ganciclovir gels showed a clinical efficacy: a significant reduction of the corneal ulcer area, clouding and vascularization (p < 0.05) and a fast inhibition of HSV isolates into tear film with the 0.2% and 0.05% ganciclovir gels. However the efficacy was slower than using acyclovir ointment. No significant difference could be shown between the 0.2% and 0.05% ganciclovir gels or the 0.05% ganciclovir gel and the acyclovir treatment on viral isolation, when it was performed on pooled samples. The distribution of ganciclovir and acyclovir into the rabbit eyes (HPLC methods), were similar but markedly higher in solid tissues than ocular fluids. It might explain the recovery from tissue damages. The mean corneal ganciclovir concentrations were largely higher than ED 50 of ganciclovir for HSV-1. No toxicity was expected, due to very limited systemic availability. This study suggests a comparable activity on HSV-1 superficial keratitis between 0.05%, 0.2% ganciclovir gels and 3% acyclovir ointment. Higher concentration of ganciclovir gels are probably necessary in order to treat the HSV-1 kerato-uveitis.","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.1994.10.439","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19076669","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}

引用次数: 45

Facilitation of retinal function recovery by natural products after temporary ischemic occlusion of central retinal artery. 视网膜中央动脉暂时性缺血性闭塞后天然产物促进视网膜功能恢复。

Journal of ocular pharmacology Pub Date : 1994-01-01 DOI: 10.1089/jop.1994.10.493

G C Chiou, B H Li, M S Wang

引用次数: 19