摘要:

ABSTRACTOcular hypertensive patients were enrolled in a 6-week double-masked safety study of 2% MK-927 (27 patients), a topically active carbonic anhydrase inhibitor, administered bilaterally b.i.d.; 9 additional patients received 0.5% timolol as the control agent. Intraocular pressure (IOP) was measured weekly prior to a.m. drug administration; twelve hour diurnal curves were performed prestudy and at 3 and 6 weeks. The mean reduction of IOP prior to a.m. drug administration ranged from 1.2 ± 4.4 mm Hg (SD) to 3.0 ± 4.2 mm Hg with MK-927 and from 4.7 ± 3.9 mm Hg to 8.8 ± 0.6 mm Hg with timolol. Mean outflow facility measured tonographically prestudy and on days 33 to 42 four hours after a.m. drug administration was unchanged in both groups. Corneal sensitivity (Cochet-Bonnet), corneal thickness (ultrasound pachymetry), Schirmer tear testing, and extensive ophthalmologic and medical examinations, and hematologic studies were not substantially altered throughout the study. In this longest chronic administration study to date, MK-927 did not cause adverse ocular or systemic side effe

ISSN:8756-3320    

DOI:10.1089/jop.1992.8.1

年代:1992

数据来源: MAL

摘要:

ABSTRACTA series of ketanserin analogs were studied for their effects on intraocular pressure (IOP) recovery curve of rabbits infused with hypertonic saline. Eight out of 31 compounds tested showed a marked delay in IOP recovery indicating that they are potential antiglaucoma agents. Five out of eight compounds showed equal suppression of the IOP recovery curves of treated and contralateral eyes indicating that these compounds could be absorbed systemically to affect the IOP of the contralateral eye. There were three compounds (GC 679, GC 646, and GC 526) which showed more suppression of the IOP recovery curve of the treated eye than that of the contralateral eye, indicating that these drugs might act primarily at the local site to lower the IOP. Therefore, these three compounds could produce antiglaucoma actions with little systemic side effects, if any.

ISSN:8756-3320    

DOI:10.1089/jop.1992.8.11

年代:1992

数据来源: MAL

摘要:

ABSTRACTThe effect of topical unilateral application of lofexidine, an α2-agonist, on ocular regional blood flow was tested in anesthetized rabbits using radiolabeled microspheres. A significant reduction in blood flow was found only in the ciliary body of the treated eye at 1 hr after lofexidine treatment. However, the IOP of both eyes was decreased significantly at 30 and 60 min post lofexidine treatment. Yohimbine (i.v.) blocked this IOP lowering effect, but only partially prevented the blood flow response. In addition, no significant difference was found in either basal or amphotericin-B stimulated short-circuit current or potential difference of the isolated rabbit iris-ciliary body after 30 minutes of lofexidine treatment. These observations suggest that the IOP lowering effect of lofexidine appears to be mediated by α2-receptors but unrelated to the reduction in the ocular blood flow and net electrogenic ion transpor

ISSN:8756-3320    

DOI:10.1089/jop.1992.8.23

年代:1992

数据来源: MAL

摘要:

ABSTRACTThis paper deals with our findings on the quantities of melanin in the tissues from blue and brown eyes. The amount of melanin in the iris, ciliary body and retinal pigment epithelium-choroid was separately determined. The results are expressed as the amount of melanin in mg tissue as well as the amount of melanin in the whole tissue. The results showed that there was no statistically significant difference between the melanin content of the iris in blue and brown eyes. However the ciliary body and retinal pigment epithelium-choroid from brown eyes had more melanin than the corresponding tissues from blue eyes. Blue and brown eyes with higher colour intensity had more melanin than the corresponding eyes with lesser intensity of colour. It is suggested that the differences between brown and blue eyes in their melanin content may have relevance to the pharmacokinetics of drugs that bind to melanin. This would mean that the larger amounts of melanin would decrease the initial levels of the drugs and would increase the drug levels after prolonged periods.

ISSN:8756-3320    

DOI:10.1089/jop.1992.8.35

年代:1992

数据来源: MAL

摘要:

ABSTRACTThe formation of excess sugar alcohol mediated by aldose reductase (AR) and its intracellular accumulation in lens with resultant hydration is thought to be the initiating mechanism in the pathogenesis of diabetic and galactosemic cataracts. AR is also involved in other diabetic complications including retinopathy and neuropathy. Therefore, there is heightened interest in developing effective AR inhibitors (ARIs) fr possble clnica use in human diabetes. However, the evaluation of these drugs for potential clinical use requires that the compounds be evaluated in appropriate target tissues since AR from different tissues is known to exhibit differential susceptibility to ARIs. The relative efficacy of ARIs in human lens epithelium (HLE) and human retinal pigment epithelium (HRPE) was studied by measuring the degree of inhibition of galactitol formation at various concentrations of ARI following incubation of cells in high galactose media for 72 hrs. Regardless of the structural characteristics of the ARIs investigated, higher doses were required to inhibit polyol synthesis in HRPE as compared to HLE c50s. Based on EDsorbinil. Since some ARIs are known to be bound to plasma proteins, it is conceivable that the observed differences in ED50values could be due to differential binding to serum proteins in the culture medium. This possibility was examined by employing cultures of dog lens epithelium (DLE). These cells, which synthesize much higher levels of galactitol than HLE and HRPE, could e maintaine in serm-free medi for hort peiods (4 hrs) of time. The results, which demonstrate that the extent of polyol inhibition was the same in the presence or absence of serum, suggest that the differences in the potency of the inhibitors may reflect their inherent ativity against AR in HLE and HRPE cells.

ISSN:8756-3320    

DOI:10.1089/jop.1992.8.43

年代:1992

数据来源: MAL

摘要:

ABSTRACTThe cyclooxygenase and lipoxygenase enzyme systems can metabolize a number of C20 polyunsaturated fatty acids. Although arachidonic acid is the usual substrate for these pathways, the eicosanoid precursor pool can be nutritionally manipulated by supplementation with alternative precursors, often generating less active or down-regulatory metabolic products. Prefeeding with gamma-linolenic acid, eicosapentaenoic acid, or a combination of both failed to influence the lagphase, epithelial migration rate, or epithelial wound healing kinetics after either IN or 4N NaOH alkali burning of the rabbit cornea. Initial epithelial wound healing probably does not involve eicosanoid-mediated processes. Essentially linear epithelial healing kinetics continued to closure without a late decrease in wound edge velocity.

ISSN:8756-3320    

DOI:10.1089/jop.1992.8.53

年代:1992

数据来源: MAL

摘要:

ABSTRACTThe effect of mucoadhesive polymeric vehicles on the mydriatic efficacy, and on the systemic and ocular absorption of cyclopentolate from eyedrops was studied in albino rabbits. Combining cyclopentolate base to polygalacturonic (CY-PGA) or hyaluronic (CY-HA) acid resulted in an increased mydriatic effect when compared with cyclopentolate hydrochloride (CY-HCl). During the first half an hour, the systemic absorption of cyclopentolate was lower after CY-PGA than after CY-HCl. The ocular penetration of cyclopentolate, based on drug concentrations in aqueous humor 30 minutes after the eyedrop instillation, was increased 3fold when the polygalacturonate complex was used. CY-PGA, as well as other polymeric salts, might offer a possibility to increase the therapeutic index of cyclopentolate.

ISSN:8756-3320    

DOI:10.1089/jop.1992.8.59

年代:1992

数据来源: MAL

摘要:

ABSTRACTThe effect of a specific 5-lipoxygenase inhibitor, PF5901 (5% in corn oil), on disruption of the blood-aqueous barrier (BAB) in the dog was investigated using a unilateral mild paracentesis model. BAB breakdown was quantitated using anterior chamber fluorophotometry. Fluorescence in the eyes of the PF5901 group was not statistically significantly different (P>0.05) from that in the vehicle group. A tendency towards greater fluorescein concentrations was noted in the PF5901 treated eyes. It was concluded that leukotrienes are not important mediators of BAB disruption in this model and that leukotriene inhibitors may actually exacerbate disruption due to shunting of arachidonate metabolism towards the cyclooxygenase and/or epoxygenase pathways. In a second experiment, the effects of proparacaine and flurbiprofen were evaluated on blood-aqueous barrier disruption and pupil size following a more severe paracentesis. Flurbiprofen dampened both barrier disruption and the miotic response but proparacaine suppressed neither reaction, suggesting that, in the dog, prostaglandins are more important mediators of the ocular irritative response than are sensory neuropeptides.

ISSN:8756-3320    

DOI:10.1089/jop.1992.8.69

年代:1992

数据来源: MAL

摘要:

ABSTRACTIt is well-known that growth factors accelerate wound healing by stimulating mitosis. Growth factors may also directly stimulate the motility of individual cells. We employed two different experimental methods to determine if fibroblast growth factor (FGF) enhances the individual motility of corneal stromal fibroblasts (independent of mitogenlc effects). The effects of FGF on the motility of tissue-cultured rabbit corneal stromal fibroblasts were investigated in a modified Boyden chamber and by the agarose drop motility assay. Both assays showed a significant enhancement of stromal fibroblast motility by FGF at 100 ng/ml. It appears, therefore, that FGF may promote corneal stromal wound healing not only by increased cellular proliferation, but also by increased cellular motility.

ISSN:8756-3320    

DOI:10.1089/jop.1992.8.77

年代:1992

数据来源: MAL

摘要:

ABSTRACTPharmacological agents which modulate the wound healing process by the inhibition of proliferation of fibroblasts may improve the success of glaucoma filtration surgery. Since cell proliferation is essential to the wound healing process, we targeted the surface receptors that are associated with proliferating cells. We present the effects of three such agents--purified mouse anti-human transferrin receptor monoclonal antibody 42/6 (anti-TfR-42/6), anti-transferrin monoclonal antibody bound to a Pseudomonas exotoxin (anti-TfR-PE40) and transforming growth factor-α Pseudomonas exotoxin (TGF-α-PE40)--on human fibroblasts from Tenon's capsule. The inhibition of human subconjunctival fibroblast proliferation by anti-TfR-42/6 (with a concentration up to 25 μg/ml) and by anti-TfR-PE40 and TGF-α-PE40 (both with a concentration range of 5000-0.00001 μg/ml) was determined by colorimetric (OD), and cell counting (CC) assays over a 9-day period. Neither anti-TfR-42/6 nor anti-TfR-PE40 had an antiproliferative effect on the fibroblasts. TGF-α-PE40 demonstrated an antiproliferative effect in a dose response manner. The mean 50% inhibitory dose (ID50) by OD was 32.91 μg/ml, while the ID50by CC was 27.88 μg/ml. EGF was used as a negative control for TGF-α-PE40 toxin. The inhibitory effect of the toxin conjugate was completely blocked by the addition of 1000 μg/ml of EGF. These in vitro studies show that TGF-α-PE40 may be useful in modulating the proliferation of human ocular fibroblasts; they also give some indication of drug dosages for future in vi

ISSN:8756-3320    

DOI:10.1089/jop.1992.8.83

年代:1992

数据来源: MAL