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1. |
Possible Mechanisms Underlying the Differential Effects of Selective Inhibitors of Type A and Type B Monoamine Oxidase on Intraocular Pressure in the Cat |
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Journal of Ocular Pharmacology and Therapeutics,
Volume 2,
Issue 1,
1986,
Page 1-8
BRENDA K. COLASANTI,
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摘要:
ABSTRACTIntraocular pressure and facility of aqueous outflow were measured in adult cats after topical application of clorgyline, a selective inhibitor of type A monoamine oxidase (MAO), or deprenyl, a selective inhibitor of type B of the enzyme. Clorgyline produced a dose-related lowering of intraocular pressure which was associated with a dose-related increase in outflow facility. Sympathetic denervation markedly reduced both these effects of clorgyline. Both effects, on the other hand, persisted after death of the animals. Deprenyl did not lower intraocular pressure; in fact, a tendency toward pressure elevation was apparent 2 hours after its administration. Outflow facility was not significantly changed. These results suggest that an endogenous substrate of type A MAO, presumably norepinephrine, is responsible for the ocular tension lowering effect of clorgyline. Because cessation of circulation after death did not abolish the effect, it is assumed that the trabecular meshwork is the site of action and that sympathetic innervation normally supplies an adrenergic neurotransmitter to the meshwork area. The tendency toward rise in intraocular pressure produced by deprenyl is probably due to alteration of aqueous humor formation rather than to a change in outflow resistance.
ISSN:8756-3320
DOI:10.1089/jop.1986.2.1
年代:1986
数据来源: MAL
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2. |
The Ocular Effects of Xylazine in Rabbits, Cats, and Monkeys |
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Journal of Ocular Pharmacology and Therapeutics,
Volume 2,
Issue 1,
1986,
Page 9-21
JAMES A. BURKE,
DAVID E. POTTER,
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摘要:
ABSTRACTXylazine is an agent frequently used in combination with ketamine to anesthetize rabbits. Xylazine is also related pharmacologically to clonidine, a relatively selective α2-agonist. In the present studies, xylazine was examined for its effects on intraocular pressure (IOP) and pupil diameter (PD) in rabbits, cats and monkeys and on noradrenergic function in the cat nictitating membrane (CNM) preparation. Topical and unilateral administration of xylazine (1.0 mg) lowered IOP bilaterally in normal, unanesthetized rabbits, cats and monkeys and caused unilateral miosis in rabbits and cats. These ocular effects of xylazine were attenuated in superior cervical ganglionectomized (SX) cats and rabbits. In addition, intra-arterially administered xylazine (10, 33 and 100 μg) produced dose-related inhibition of contractions of the CNM elicited by electrically stimulating the pre- and postganglionic sympathetic trunks without altering the response to i.a. norepinephrine (10 μg). These data suggest that ocular effects of xylazine are mediated, in part, by alteration of sympathetic neuron function. Xylazine suppressed ocular hypertension induced by water loading and IOP recovery rate following hypertonic saline infusion in rabbits suggesting that aqueous flow was inhibited. Topical pretreatment with 0.05 mg of timolol caused potentiation of the ocular hypotensive response to 0.05 mg of xylazine in rabbits. These results indicate that xylazine lowers IOP, in part, by suppressing sympathetic neuronal function which causes a reduction in aqueous flow. The augmented response to timolol and xylazine, as compared with either agent alone, suggests a rational basis for combining a prejunctionally active agent with a postjunctionally active o
ISSN:8756-3320
DOI:10.1089/jop.1986.2.9
年代:1986
数据来源: MAL
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3. |
Effects of Topical Diclofenac Sodium in a Rabbit Model of Ocular Inflammation and Leukotaxis |
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Journal of Ocular Pharmacology and Therapeutics,
Volume 2,
Issue 1,
1986,
Page 23-29
J. MARK ROWLAND,
CATHERINE J. FORD,
RICHARD A. DELLA PUCA,
WILLIAM D. CASH,
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摘要:
ABSTRACTA useful model that combines paracentesis with administration of a leukotactic factor was developed in order to study the effects of topical diclofenac sodium on various aspects of ocular inflammation. The increases in intraocular pressure (IOP) and secondary aqueous humor protein concentration induced in rabbits by anterior chamber paracentesis, as well as leukocyte accumulation in the anterior chamber induced by formyl-methionyl-leucyl-phenylalanine, were significantly reduced by topical application of diclofenac sodium at concentrations of 2 mM (0.064%, w/v) and higher. Lower doses consistently affected only IOP and secondary protein concentrations. A slight paracentesis-induced miosis was refractory to diclofenac sodium. That this potent inhibitor of prostaglandin synthesis can reduce important signs of ocular inflammation is well supported in this model.
ISSN:8756-3320
DOI:10.1089/jop.1986.2.23
年代:1986
数据来源: MAL
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4. |
Effects of Ocular Inflammation on Tear Proteins. I. Thiol Protease Inhibitors |
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Journal of Ocular Pharmacology and Therapeutics,
Volume 2,
Issue 1,
1986,
Page 31-40
WENDY L. DAVIS,
JANET A. ANDERSON,
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摘要:
ABSTRACTConcentrations of protease inhibitors found in tears have been observed to vary during ocular inflammation. Possible stimuli for these variations were tested for by studying thiol protease inhibitor concentrations in models of ocular inflammation. Inflammatory responses were elicited either by topical application of arachidonic acid (AA), or compound 48/80. For each model, four rabbits were treated in one eye with the inflammatory stimulant and tear samples were collected before and up to five hours following treatment. Control animals were treated with buffer. When compared to pretreatment values, tears from AA-treated eyes showed decreased inhibitor at one and two hours and an increased inhibitor concentration at three hours. In the 48/80 model, inhibitory activity and protein levels were elevated when compared over time to the control group (p ≥ 0.02, p ≥ 0.0001 respectively). When compared to pretreatment values, inhibitor values were elevated at all times after treatment and protein values were elevated at one and three hours in this model. Serum proteins were also increased in the tears of rabbits treated with 48/80. The results suggest that one or more of the mediators released by basophil or mast cell degranulation stimulate increased tear protease inhibitory activity and tear serum prote
ISSN:8756-3320
DOI:10.1089/jop.1986.2.31
年代:1986
数据来源: MAL
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5. |
Adrenergic Induction of HSV-1 Ocular Shedding in Rabbits |
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Journal of Ocular Pharmacology and Therapeutics,
Volume 2,
Issue 1,
1986,
Page 41-54
KEVIN C. ABBOTT,
EARL F. McLENDON,
LOUIS P. GANGAROSA,
JAMES M. HILL,
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摘要:
ABSTRACTFour groups of latently infected rabbits were induced to shed HSV-1 into the tear film by a one-time ocular iontophoresis of 6-hydroxydopamine (6-HD) followed 3 days later by five consecutive days of twice daily topical epinephrine (Epi). Groups 1 and 4 had both eyes inoculated and Groups 2 and 3 had only one eye inoculated. Groups 1 and 2 had eyes swabbed to detect HSV-1, and Groups 3 and 4 had eyes washed. Group 1 was iontophoresed with1.0%6-HD at 0.5 mAmp for 5 min, and Groups 2, 3 and 4 were iontophoresed with0.1%6-HD at 0.75 mAmp for 5 min. Group 1 received topical2.0% Epi, and Groups 2, 3, and 4 received topical1.0%Epi. Inoculated eyes in all groups shed HSV-1 during the induction period. The peak of HSV-1 shedding occurred on the last day of Epi application for Groups 1 and 2, and on the day after the last Epi application for Groups 3 and 4. The ratio of total positive tear film samples to total samples for inoculated eyes that received 6-HD and Epi were 53/119 (45%), 38/87 (44%), 24/66 (36%), and 14/33 (42%) for Groups 1, 2, 3, and 4, respectively. Therefore, even reduced concentrations of 6-HD and Epi, as well as beginning Epi 3 days after 6-HD, induced HSV-1 ocular shedding.
ISSN:8756-3320
DOI:10.1089/jop.1986.2.41
年代:1986
数据来源: MAL
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6. |
Ocular Hyperuricosis in the Rabbit Following Hyperuricemia and Topical Epinephrine |
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Journal of Ocular Pharmacology and Therapeutics,
Volume 2,
Issue 1,
1986,
Page 55-58
CHARLES H. BONNEY,
KWOK-WAI LAM,
DONALD FONG,
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摘要:
ABSTRACTSources for the high levels of uric acid reported in the aqueous humor from human glaucoma eyes were studied in the rabbit model.A hyperuricemia was produced by oxonic acid blockade of uricase prior to a systemic administration of uric acid. These animals showed no increase in aqueous humor uric acid.Topical medication of eyes with 1% epinephrine produced a statistically significant (P<0.001) rise in the level of uric acid in aqueous humor of treated eyes. Mean urate levels increased from 0.44 mg/dl to 0.82 mg/dl. Topical glaucoma medication appears to be the source of ocular hyperuricosis.
ISSN:8756-3320
DOI:10.1089/jop.1986.2.55
年代:1986
数据来源: MAL
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7. |
Stimulation of the Hexose Monophosphate Shunt in Bovine Ciliary Body under Oxidative Stress |
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Journal of Ocular Pharmacology and Therapeutics,
Volume 2,
Issue 1,
1986,
Page 59-66
HITOSHI SHICHI,
WILLIAM A. HODDER,
FRANK J. GIBLIN,
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摘要:
ABSTRACTThe effect of t-butyl hydroperoxide (TBHP) on the oxidation of C1-radiolabeled glucose and C6-radiolabeled glucose by bovine ciliary body was investigated in the presence and absence of the glutathione reductase inhibitors nitrofurantoin (NF) and 1,3-bis(2-chloroethyl)-1-nitrosourea [BCNU].14CO2production from 1-14C-glucose was markedly stimulated by TBHP and inhibited by BCNU. Using tissue extracts, BCNU was shown to inhibit both glutathione reductase and glucose-6-phosphate dehydrogenase. These results support the hypothesis that bovine ciliary body has high NADPH regenerating capacity by the hexose monophosphate shunt.
ISSN:8756-3320
DOI:10.1089/jop.1986.2.59
年代:1986
数据来源: MAL
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8. |
Topical Ocular Drug Delivery: Recent Developments and Future Challenges |
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Journal of Ocular Pharmacology and Therapeutics,
Volume 2,
Issue 1,
1986,
Page 67-108
VINCENT H.L. LEE,
JOSEPH R. ROBINSON,
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摘要:
ABSTRACTExisting ocular drug delivery systems are fairly primitive and inefficient, but the stage is set for the rational design of newer and significantly improved systems. The focus of this review is on recent developments in topical ocular drug delivery systems relative to their success in overcoming the constraints imposed by the eye and to the improvements that have yet to be made. In addition, this review attempts to place in perspective the importance of pharmacokinetic modeling, ocular drug pharmacokinetic and bioavailability studies, and choice of animal models in the design and evaluation of these delivery systems. Five future challenges are perceived to confront the field. These are: (a) The extent to which the protective mechanisms of the eye can be safely altered to facilitate drug absorption, (b) Delivery of drugs to the posterior portion of the eye from topical dosing, (c) Topical delivery of macromolecular drugs including those derived from biotechnology, (d) Improved technology which will permit non-invasive monitoring of ocular drug movement, and (e) Predictive animal models in all phases of ocular drug evaluation.The design of ocular drug delivery systems is undergoing a gradual transition from an empirical to a rational base. This is partly due to a better understanding of the constraints on drug disposition in the eye and partly due to improved approaches in animal and clinical assessment of ocular drugs and drug delivery systems. Undoubtedly, interest in the broad area of ocular drug delivery has increased in recent years due to an increased understanding of a number of ocular physiological processes and pathological conditions, including aqueous humor dynamics, inflammation, corneal wound healing, and cataractogenesis, with a parallel increase in the number of drugs and drug candidates that have a beneficial effect in these conditions. Some of these compounds are rather potent and, at the same time, possess unfavorable aqueous solubility, stability, and lipophilicity characteristics. The inevitable result is that the formulation of these compounds for optimal topical delivery to the eye is increasingly challenging, much more so for the posterior than for the anterior portion of the eye. Coincidentally, the design of ocular drug delivery systems is becoming more sophisticated, partly due to a better understanding of the constraints in ocular drug disposition and partly due to the availability of polymers with a wide range of properties including biodegradability and bioadhesiveness.A number of recent reviews (1-5) have provided excellent background information on corneal drug transport mechanisms, ocular drug bioavailability, and ocular drug pharmacokinetics. Although a portion of each of these reviews also deals with the subject of ocular drug delivery, either directly or indirectly, a comprehensive current review of this subject does not appear to be available in the literature, hence the purpose of this article. Specifically, this paper will first review and describe (a) the constraints in topical ocular drug delivery, (b) mechanisms and constraints of ocular drug absorption, and (c) mathematics and modelling of ocular drug disposition in order to set the stage for understanding (a) the approaches that can be taken to optimize ocular drug delivery, (b) the suitability of rabbits as an animal model to evaluate ocular drug delivery systems, and (c) new challenges in ocular drug delivery system design.To provide a framework for subsequent discussions, it is useful to describe typical boundaries that are encountered in topical drug application. It is common to see approximately 1% or less of an applied dose absorbed across the cornea to reach anterior segment tissues of the eye. This, therefore, is an extremely inefficient process that also signals a substantial systemic drug load. Obviously, subsequent movement of this absorbed drug to the posterior segment of the eye will occur for only a tiny fraction of that which is in the anterior segment. In addition to the fraction of dose absorbed, the issue of residence time in the living eye is also important. Typically, an instilled aqueous solution will be eliminated from the precorneal area within 90 seconds. All things considered, improving the fraction of dose absorbed, achieving relatively high drug concentrations in the posterior segment, and maintaining drug in the front of the eye for several hours to several days are considerable challenges in ocular drug delivery.
ISSN:8756-3320
DOI:10.1089/jop.1986.2.67
年代:1986
数据来源: MAL
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