摘要:

ABSTRACTTreatment with topical anesthetics was reported to increase corneal permeability and improve ocular drug bioavailability. These changes were attributed to the loss of reflex blinking, reduction of tear secretion and appearance of superficial corneal epithelial lesions.A recent report showed that pretreatment with Ophthetic (0.5% proparacaine HC1) (OPH) in pentobarbital-anesthetized rabbits significantly increased the permeability of the lipophobic carbonic anhydrase inhibitor (CAI) benzolamide (B) and transformed it to a highly active ocular hypotensive drug. This did not affect the permeability and activity of other, more lipophilic, CAI like methazolamide and ethoxzolamide (E). Similar experiments in awake rabbits using other CAI failed to reproduce the finding reported for B. We compared the ocular drug levels and the Intraocular pressure lowering (ΔIOP) with and without application of Ophthetic prior to 1 drop of 2% suspensions, in groups of anesthetized and conscious albino rabbits.In unanesthetized rabbits pretreatment with Ophthetic, lidocaine or benzalkonium had minimal and insignificant effects on ocular drug levels and ΔIOP of B as well as E. On the other hand, Ophthetic or lidocaine pretreatment in anesthetized rabbits led to a highly significant increase in both ocular drug levels and hypotensive activity of B. We conclude that the error introduced by pretreatment with OPH occurs only in the presence of pentobarbital anesthesia and has little relevance to the normal, unanesthetized conditio

ISSN:8756-3320    

DOI:10.1089/jop.1988.4.1

年代:1988

数据来源: MAL

摘要:

ABSTRACTThis was a double-masked, randomized, paired comparison with vehicle trial of a topically administered prostaglandin (PG)E2in healthy human volunteers. A statistically significant decrease of the intraocular pressure in these non-glaucomatous volunteers occurred at six hours following one drop of 0.02% solution that persisted to the last measurement of IOP at the 24 hour examination. Significant elevation in the intraocular pressure was present at one and two hours following the eye drop instillation. All volunteers reported transient ocular side effects related to drug administration, including mild eye ache and intermittent photophobia for a duration of 2 to 4 hours. These symptoms were associated with a transient conjunctival vasodilation, but with no evidence of anterior chamber cells and flare or ciliary flush as determined by slit lamp examination. The results of this study suggest that PGE2, or a derivative, may offer a new class of topically effective ocular hypotensive agents useful in lowering the intraocular pressure of glaucoma patients.

ISSN:8756-3320    

DOI:10.1089/jop.1988.4.13

年代:1988

数据来源: MAL

摘要:

ABSTRACTLY141865 (LY), an ergoline derivative, was investigated for ocular effects in rabbits and monkeys. LY lowered intraocular pressure (IOP) bilaterally in monkeys and rabbits, prevented the bilateral rise in IOP caused by oral waterloading in rabbits and slowed the rate of IOP recovery bilaterally in rabbits. The ocular hypotensive activity of LY in rabbits was inhibited by sympathectomy and pretreatment with sulpiride. Since LY has cardiovascular effects that are centrally mediated, ocular responses may also be mediated, in part, by an action in the CNS.

ISSN:8756-3320    

DOI:10.1089/jop.1988.4.19

年代:1988

数据来源: MAL

摘要:

ABSTRACTThe binding characteristics of3H-timolol to bovine iris melanin were determined by using a ligand binding assay. The association and dissociation kinetics were performed using 100 nM3H-timolol and 0.5 mg/ml melanin at 37 °C. The effects of pH, ethanol, 2.5 μM isoxuprine and 1 μM d- and 1-propranolol on 100 nM3H-timolol binding were also determined. In saturation experiments3H-timolol (from 1.25 nM to 5 μM) was equilibrated with 0.5 mg/ml melanin. The binding was saturable with the binding maximum of about 1 μM timolol/g melanin. The binding of 100 nM3H-timolol to melanin increased up to 5 hours and amounted 24 % of the added radioactivity. The best fit of the association constants was obtained by using a two fit model. The association rate constants were 4.92 × 105M−1min−1and 5.95 × 106M−1min−1. The dissociation was rapid in vitro and uniphasic with a dissociation rate constant of 5.08 × 10−3min−1. The pH, ethanol and both enantiomers of propranolol did not appreciably alter the timolol binding, while isoxu

ISSN:8756-3320    

DOI:10.1089/jop.1988.4.29

年代:1988

数据来源: MAL

摘要:

ABSTRACTThe ocular administration of a 50 μL instillation of bunolol hydrochloride, a β1- and β2- adrenoceptor blocking agent, resulted in significantly higher drug levels in the choroid/retina, iris, and ciliary body of pigmented rabbits compared with albino rabbits following topical administration. The concentrations in these tissues also persisted longer in the pigmented rabbits' eyes. However, no statistically significant differences in tissue levels were observed in the cornea or conjunctiva. The results of this study support the previously reported finding with timolol which showed longer retention of the drug in the iris, ciliary, choroid, and retina of pigmented rabbits than albin

ISSN:8756-3320    

DOI:10.1089/jop.1988.4.37

年代:1988

数据来源: MAL

摘要:

ABSTRACTA cryogenic lesion in the rabbit cornea that promotes the formation of arachidonic acid metabolites was used as a model to test the action of two new lipoxygenase inhibitors, TEI-8005 and TEI-8006. The action of these two inhibitors was compared with that of CBS-113A, a new dual inhibitor of cyclooxygenase and lipoxygenase reactions, and with that of nordihydroguaiaretic acid (NDGA), a monooxygenase inhibitor and antioxidant. Injured corneas were incubated for 1 h at 36°C with l-14C-arachidonic acid. Inhibitors at concentrations of 1, 10 and 100 uM were added 10 minutes prior to the addition of arachidonic acid. TEI8006 inhibited 5-hydroxyeicosatetraenoic acid (HETE) at 10 uM, and both 5- and 12-HETE at 100 uM. At 100 uM, CBS-113A also had the same effect, while TEI-8005 at 100 uM induced a more selective inhibition of 5-lipoxygenase. NDGA was the most potent inhibitor of lipoxygenase reactions, but was not selective. Prostaglandins were also affected differentially by the inhibitors. TEI-8006 and NDGA partially inhibited cyclooxygenase products at all concentrations, and CBS-113A produced inhibition at 10 and 100 uM. TEI-8005 did not affect the total cyclooxygenase products, but selectively inhibited thromboxane B2and increased prostacyclin production at 100 uM. The effects of these inhibitors may be of value in understanding the mechanisms involved in corneal inflammation

ISSN:8756-3320    

DOI:10.1089/jop.1988.4.43

年代:1988

数据来源: MAL

摘要:

ABSTRACTAn indirect immunoperoxidase technique was used to demonstrate progesterone binding in rabbit cornea as a measure of steroid absorption into corneal tissues. Tissue preparation prior to immune staining was prepared by both a pre-fixed, paraffin-embedding method and a post-fixed, cryostat sectioning method. Rabbit antiprogesterone antiserum and peroxidase conjugated goat antirabbit antiserum were used as a primary and secondary antibody respectively. The immune staining of the antibody-treated sections was then developed in a solution of 3-3′ diaminobenzidine-hydrogen peroxide system. The resulting, brown colored, end-products at the site of reaction indicate the location of bound steroid in the sections. Paraffin-embedded sections showed negative staining in both steroid treated and untreated control corneas while fixed frozen sections showed only positive staining for the treated corneas. The results suggest the preservation of the immunogenicity in the treated frozen sections. The negative result observed in the paraffin-embedded sections may be attributed to the loss of steroid from the tissues during the dehydration and paraffin embedding processes. It was found that the immunoreactive progesterone localized mainly in the epithelial cells and the bottom portion of the stroma. Prior application with an excess of triamcinolone acetonide, to the treated corneas gave negative results indicating the reversible and competitive nature of the bindin

ISSN:8756-3320    

DOI:10.1089/jop.1988.4.51

年代:1988

数据来源: MAL

摘要:

ABSTRACTBlood flow in the eye has shown a remarkable ability to autoregulate regardless of intraocular pressure, perfusion pressure or alterations in arterial pressure. This study investigates the possibility that adenosine may play a role in regulating ocular blood flow. Ocular blood flow was measured using radiolabelled85Sr microsphere and laser Doppler techniques. When two adenosine uptake inhibitors, dipyridamole and papaverine were injected intravitreally, the ocular blood flow increased in all ocular tissues tested: iris, iris root-ciliary body, retina and choroid. This increase in blood flow was blocked by the addition of the adenosine antagonist, 8-phenyltheophylline. The increase in flow produced by dipyridamole continued for up to an hour after administration. The increase in blood flow in individual ocular tissues does not appear to be due to shunting (ie. redistribution) of flow because total blood flow to the eye increased but the percent total flow to each individual tissue remained near control values.

ISSN:8756-3320    

DOI:10.1089/jop.1988.4.61

年代:1988

数据来源: MAL

摘要:

ABSTRACTFibronectin is an extracellular structural protein with the unique ability to bind to both cells and collagen. It plays a major role in the development of the cornea. The universal appearance of fibronectin within 8 hours of corneal wounding has promoted major interest in its wound healing properties.The early clinical evidence for fibronectin treatment of recurrent corneal erosion and certain forms of keratitis sicca is strong. The current major problem preventing commercial use is the antigenic nature of fibronectin derived from separate species. Human pooled fibronectin has been suggested as a commercial source of this ubiquitously occurring protein.

ISSN:8756-3320    

DOI:10.1089/jop.1988.4.75

年代:1988

数据来源: MAL