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Biomedical subjects

L Z Bito

Publications and source records attributed to L Z Bito.

At least 19 recordsLinked to original sources
PubMed1992

Intraocular pressure reduction with PhXA34, a new prostaglandin analogue, in patients with ocular hypertension.

In a randomized, double-masked, parallel study, one drop of 0.003% (1 microgram; n = 9) or 0.01% (3 micrograms; n = 10) PhXA34, a new phenyl-substituted prostaglandin F2 alpha analogue (13,14-dihydro-15[R,S]-17-phenyl-18,19,20-trinor-prostaglandin F2 alpha-1-isopropyl ester), or its vehicle (n = 10) was applied topically twice daily for 6 days to one eye in each of 29 patients with ocular hypertension. Compared with either baseline, contralateral, or vehicle control values, PhXA34 caused a significant (P < .001) dose-dependent reduction of intraocular pressure. The reduction lasted at least 12 hours after each drop and 24 to 48 hours after the last drop, with a significant (P < .0001) mean +/- SEM reduction of as much as 10 +/- 1 mm Hg (40%). Conjunctival hyperemia was not produced by 0.003% PhXA34, but was noted in some eyes treated with 0.01% PhXA34, and after repeated tonometry with either concentration. The prostaglandin analogue did not produce clinically obvious miosis, anterior chamber flare or cellular response, or any subjective adverse effects. PhXA34 is a potent, effective, and well-tolerated ocular hypotensive agent based on our results in this small, short-term study. Its potential as a new drug for glaucoma therapy warrants further investigation in long-term, larger studies.

Adult↗
PubMed1992

Steroid glaucoma: corticosteroid-induced ocular hypertension in cats.

This study was undertaken to develop a feline model of corticosteroid-induced ocular hypertension. In the first experiment, eight cats were selected whose intraocular pressure (17 +/- 0.4 mmHg) was consistently below the mean baseline intraocular pressure of our colony (24 +/- 0.5) during the preceding 2 months. Unilateral twice or thrice daily topical application of 10 microliters 1% dexamethasone sodium phosphate caused a gradual intraocular pressure increase that became significant (P less than 0.05) within 2-3 weeks. There was no significant change in body weight, but several eyes developed cataracts. Similar results were obtained with treatment of normotensive cat eyes with dexamethasone, or with 1.0% prednisolone acetate (PredForte) twice a day. Topical application of PGF2 alpha-1-isopropyl ester (0.1 or 0.25 microgram PG equivalent) to such steroid-treated eyes yielded significant intraocular pressure reduction and pupillary miosis, similar in magnitude to those exhibited by normal eyes. When dexamethasone treatment was reduced to once daily, after prolonged twice daily treatment, intraocular pressure decreased only slightly within 10 days. When dexamethasone treatment was stopped, intraocular pressure declined to normal levels within 6-7 days. These findings show that adult cat eyes develop steroid-induced ocular hypertension that is maintained and reversible. As opposed to previous findings on rabbits, steroid-induced feline ocular hypertension appears to be a good model for this clinical condition and may be suitable for the testing of potential glaucoma drugs.

Administration, Topical↗
PubMed1990

In vivo videography of the rhesus monkey accommodative apparatus. Age-related loss of ciliary muscle response to central stimulation.

Fourteen rhesus monkeys, aged 1 to 24 years, underwent permanent implantation of a bipolar stimulating electrode into the Edinger-Westphal nucleus and complete unilateral or bilateral iridectomy. Slit-lamp Scheimpflug videography of the lens and slit-lamp goniovideography of the lens equator, zonule, and ciliary body allowed direct real-time observation and video recording of the movements of these structures during centrally stimulated accommodation and during disaccommodation. Scalloping of the lens capsule at the zonular insertion sites was clearly visible during disaccommodation and even during accommodation when the zonules were folded. During accommodation, the lens became axially thicker, the ciliary ring narrowed, and, at high levels of accommodation, the zonular fibers slackened and even folded and the lens moved downward. With increasing age and concomitantly decreasing accommodative amplitude, these excursions all diminished, so that in the oldest animals, they were very minimal or absent. Maximum centrally stimulated accommodative amplitude declined with age on a time scale similar to that for cholinomimetic drug-induced accommodation in the rhesus monkey and voluntary accommodation in the human.

Accommodation, Ocular↗
PubMed1990

Eicosanoids as a new class of ocular hypotensive agents. 3. Prostaglandin A2-1-isopropyl ester is the most potent reported hypotensive agent on feline eyes.

It has been shown that prostaglandin A2 (PGA2) is a more potent ocular hypotensive agent in cats than other PG free acids. We report here that significant IOP reduction can be achieved in normotensive cat eyes with the use of even lower doses of PGA2-1-isopropyl ester (PGA2-IE) than with PGA2, PGF2 alpha-1-isopropyl ester (PGF2 alpha-IE), or any other known ocular hypotensive agent. Furthermore, single applications of 0.5 microgram of PGA2-IE maintain significant IOP reductions for at least 24 hr. This hypotensive effect is enhanced during the first 3-5 days of daily treatment. Significant IOP reductions were maintained for several months as long as PGA2-IE was applied daily or at least once every 48 hr. None of the cats manifested signs of discomfort in response to treatment with doses ranging from 0.10 to 1.25 micrograms of PGA2-IE. Moreover, the extent of anterior chamber flare was less than that typically observed after the topical application of hypotensive doses of PGE2, PGD2, PGF2 alpha, or the esters or tromethamine salt of PGF2 alpha. Although it is possible that the human eye would respond differently to PGs of the A type, the results of these studies suggests that PGA2-IE or other esters of derived PGs of the A type, and probably the B type, may offer significant therapeutic advantages over the PGF2 alpha tromethamine salt and PGF2 alpha-IE, which have been shown to exert significant hypotensive effects on normal and glaucomatous human eyes.

Administration, Topical↗
PubMed1990

Effects of various anesthetic and autonomic drugs on refraction in monkeys.

Resting refractive correction in ketamine-, pentobarbital-, or halothane-anesthetized rhesus and cynomolgus monkeys was approximately 1-3 diopters myopic, with little difference under the various anesthetic regimens. Topical cyclopentolate or atropine, or systemic hexamethonium eliminated much of the myopia, while epinephrine, phenylephrine and thymoxamine had little effect. Anesthesia-induced myopia in monkeys thus seems comparable to tonic accommodation ("night myopia") in the human. Accommodation induced by electrical stimulation of the Edinger-Westphal nucleus averaged approximately 50% less under halothane than under pentobarbital, possibly due to halothane-induced systemic arterial hypotension.

Accommodation, Ocular↗
PubMed1990

The role of the iris in accommodation of rhesus monkeys.

After unilateral total iridectomy, maximum accommodation inducible by corneal iontophoresis of carbachol in rhesus monkeys was approximately 40% less in the iridectomized than in the contralateral untouched eyes, irrespective of age. Ultrasonographically measured anterior chamber shallowing and lens thickening were also less in the iridectomized eyes. Neither submaximal accommodation induced by intramuscular pilocarpine infusion nor maximum accommodation inducible by midbrain stimulation differed in iridectomized and intact eyes. The authors hypothesize that at maximum cholinomimetic drug-induced contraction, the iris sphincter muscle pulls the ciliary body farther forward and inward than does maximum ciliary muscle contraction alone, allowing additional rounding of the lens and, consequently, additional accommodative power.

Accommodation, Ocular↗
PubMed1990

Effects of prostaglandins F2 alpha, A2, and their esters in glaucomatous monkey eyes.

The effect of prostaglandin (PG) F2 alpha-isopropyl ester (IE), PGA2, or PGA2-IE on intraocular pressure (IOP) was tested in eight cynomolgus monkey eyes with argon laser-induced glaucoma. Dose-response testing and baseline IOP measurements were done. For multiple dose testing, 5 micrograms in 25 microliters (0.02%) of each PG was topically applied twice daily for 5 days. The IOP was measured at 30- or 60-minute intervals for 6 hours after the morning dose each day. A significant (P less than 0.05) reduction of IOP peaked at 5-9 mm Hg below baseline values on the 5th day of treatment for each PG. The ocular hypotensive effect of these PGs progressively became more pronounced during the course of twice-daily dosing, with a significant reduction maintained at least 17 hours after some doses. No more than trace aqueous flare and no cells were observed in any eye during the course of treatment. These findings demonstrate that PGs other than F2 alpha are potent ocular hypotensive agents in primates.

Administration, Topical↗
PubMed1989

Functional morphology of accommodation in the raccoon.

The raccoon (Procyon lotor) is a small carnivore which eats in the upright position, using hand- and finger-like front paws and digits to wash, hold and examine its food at close range. These anatomic and behavioral characteristics prompted structural and functional studies of the accommodative capability of this species. By light and electron microscopy, we observed a prominent ciliary smooth muscle and zonular apparatus. When stimulated by carbachol or pilocarpine, the muscle and zonular apparatus exhibited a shift from longitudinal to reticular or circular orientation of some ciliary muscle bundles, anterior movement of the muscle as a whole, and more oblique crossing of the zonular fiber bundles in the zonular plexus. Maximum carbachol-induced accommodative amplitude measured by coincidence refractometry ranged from 3 to 19 diopters in these 1 to 9 yr old animals, with no definite age-accommodation relationship. A-scan ultrasonographic biometry showed that during accommodation the lens thickened very little, if at all, but moved anteriorly, while the apparent cornea to retina distance increased slightly. The raccoon thus exhibits the greatest accommodative capability of any non-primate terrestrial mammal so far studied.

Accommodation, Ocular↗
PubMed1989

Maintained reduction of intraocular pressure by prostaglandin F2 alpha-1-isopropyl ester applied in multiple doses in ocular hypertensive and glaucoma patients.

In a randomized, double-masked, placebo-controlled study, 0.25 microgram (n = 11) or 0.5 microgram (n = 13) of prostaglandin F2 alpha-1-isopropyl ester (PGF2 alpha-IE) was applied topically twice daily for 8 days to one eye of ocular hypertensive or chronic open-angle glaucoma patients. Compared with contralateral, vehicle-treated eyes, PGF2 alpha-IE significantly (P less than 0.05) reduced intraocular pressure (IOP), beginning 4 hours after the first 0.5-microgram dose and lasting at least 12 hours after the fourteenth dose, with a significant (P less than 0.005) mean reduction of 4 to 6 mmHg maintained throughout the last day of therapy with either dose. A contralateral effect was not observed. Mean tonographic outflow facility was significantly (P less than 0.05) higher in PG-treated compared with vehicle-treated eyes (0.17 +/- 0.02 versus 0.12 +/- 0.01 microliter/minute/mmHg, respectively; +/- standard error of the mean) for the 0.5 microgram dose. Conjunctival hyperemia reached a maximum at 30 to 60 minutes after PGF2 alpha-IE application. Some patients reported mild irritation lasting several minutes after some doses. Visual acuity, accommodative amplitude, pupillary diameter, aqueous humor flare, anterior chamber cellular response, Schirmer's test, pulse rate, and blood pressure were not significantly altered. Our findings show that PGF2 alpha-IE is a potent ocular hypotensive agent and a promising drug for glaucoma therapy.

Aged↗
PubMed1989

The putative and demonstrated miotic effects of prostaglandins in mammals.

The foregoing clearly indicates that there are tremendous differences in the responsiveness of the iris sphincters of different mammalian species to the miotic effects of PGs. The iris sphincter of cats and dogs contracts in response to PGF2 alpha, but not in response to other PGs, at concentrations that can be expected to occur under in vivo physiological conditions. In both of these species, PGF2 alpha, but none of the other PGs tested, yielded a dose-dependent full miosis when applied topically to intact eyes. Although in vivo studies are not available on bovine eyes, in vitro studies show that the isolated bovine iris sphincter exhibits a contractile response in the presence of several PGs, but that the threshold concentration for this response is about hundred-fold higher than the concentration of PGF2 alpha required to cause a similar or an even larger effect on feline or canine iris sphincters. Thus, in contrast to the feline iris, the bovine iris shows low sensitivity and low specificity, exhibiting responses to high concentrations of several PGs. In vivo and in vitro studies also are in full agreement that the iris sphincter of several other species, including rabbits and diurnal primates (rhesus and cynomolgus monkeys, baboons, and humans) do not exhibit similar miotic responses to any of the PGs that had been studied so far. It is difficult to summarize all these findings in a truly quantitative manner because the in vitro studies have used different experimental conditions, especially with respect to the inhibitors or precontracting agents used, while in vivo studies have differed with respect to the form of the PG used and in the mode of its administration. These differences, together with the lack in some instances of adequate descriptions of experimental conditions, must be borne in mind in any effort to compare the effects of PGs on the iris sphincter of different species. Nevertheless, because of the importance of obtaining at least a semi-quantitative picture of the extent of these species differences, the data derived from reports on in vivo studies of miosis have been tabulated in the chapter dealing with the effects of PGs on IOP (see Bito et al., 1989). Results extracted from some of the in vitro studies that have been reviewed in the previous sections are summarized in Table 1. The readers are urged to study the original publications and to bear in mind the problems described in the preceding sections that are encountered when trying to interpret the results presented by van Alphen et al. (1977).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

The ocular effects of eicosanoids and other autacoids: historic background and the need for a broader perspective.

Great progress has been made in describing the synthesis of most known eicosanoids by ocular tissues. This progress has included identification of the spectrum of eicosanoids synthesized by different ocular tissues of different species, as well as comparisons of the relative proportion of individual eicosanoids produced by ocular tissues of different species. In contrast to this wealth of information, the lack of antagonists that are specific to individual eicosanoids has greatly hindered efforts to determine the specific ocular functions of each member of this family of autacoids. Furthermore, the absence of high-affinity ligands that are specific for individual eicosanoid receptors has greatly limited our ability to classify these receptors and to assign specific eicosanoid effects to specific cell types. In the early years of ocular PG research, the lack of recognition of the existence of parallel pathways of arachidonic acid metabolism and the lack of appreciation of the effects of some other autacoids--most notably the recently discovered neuropeptides--led to the premature conclusion that PGs have mediatory roles in a number of ocular pathophysiological responses. More recent studies have demonstrated that some ocular effects, such as chemotaxis, that were first attributed to classical PGs of the E and F type are actually mediated by eicosanoids synthesized by the lipoxygenase pathway, whereas other ocular responses, at least in some species, are mediated by various neuropeptides. These neuropeptides can be released by the same stimuli that cause the release of arachidonic acid. Furthermore, interpretation of the ocular effects of eicosanoids as well as neuropeptides has been complicated by large species differences in the effects of these autacoids on intraocular tissues. Among mammalian species, the rabbit eye and the primate eye may represent opposite extremes with respect to the extent of their responses to irritation and trauma, as well as with respect to their responses to some autacoids, especially eicosanoids and neuropeptides. In spite of these differences, the rabbit remains the animal most widely used in eye research. Consequently, many of the findings reviewed in this volume are also based on studies done only on rabbits. However, in view of the foregoing, we must resist the temptation to extrapolate to primates results obtained only from studies of rabbit eyes.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

A physiological approach to glaucoma management: the use of local hormones and the pharmacokinetics of prostaglandin esters.

It appears that a pragmatic approach, based entirely on the ability of a drug or procedure to reduce IOP, has thus far been used to develop modalities for the management of glaucoma. Barring serendipity, it is unlikely that this approach will produce effective new methods for the management of this ocular disorder, which presents an ever-increasing problem in an increasingly longevous and industrialized world population. Although a better understanding of the biology of aqueous humor dynamics and its pathogenesis, combined with new genetic engineering techniques, may eventually lead to the total elimination of glaucoma, that ultimate solution is unlikely to be achieved within the foreseeable future. Thus, a physiologic approach to glaucoma management must be developed, one that takes into consideration all of our recently acquired knowledge of aqueous humor dynamics and all other relevant physiologic principles. A review of currently available information suggests that from a physiologic point of view the best approach to glaucoma management, at least for the next few decades, will be based on the use of receptor-mediated, naturally occurring ocular hypotensive agents, or at least agents that closely resemble such naturally occurring autacoids. Based on the temporal and spatial limitations of the various classes of receptor-mediated autacoids and on differences in the specificity and the nature of the responses they elicit at different sites, we conclude that a physiologic approach to glaucoma management should focus on the use of topically applied local hormones or their analogs. This approach appears to be feasible in light of demonstrations that several members of one family of local hormones, the eicosanoids that are produced within ocular tissues under physiological conditions are effective ocular hypotensive agents. It has been shown that one member of this family, PGF2 alpha, in its esterified form, is an extremely potent ocular hypotensive agent in its esterified prodrug form in both normotensive and glaucomatous human eyes, yielding significant IOP reduction when topically applied in doses less than one-hundredth that of currently available glaucoma medications. Although no intraocular side effects have been noted in human eyes after topical application of PGF2 alpha-1-isopropylester in submaximal ocular hypotensive doses, such side effects as conjunctival hyperemia and foreign body sensation present a problem and a challenge.4

Administration, Topical↗
PubMed1988

Presbyopia.

Explore the source record for details and available documents.

Aging↗
PubMed1987

The ocular pharmacokinetics of eicosanoids and their derivatives. 1. Comparison of ocular eicosanoid penetration and distribution following the topical application of PGF2 alpha, PGF2 alpha-1-methyl ester, and PGF2 alpha-1-isopropyl ester.

These experiments were undertaken to determine whether the increased ocular hypotensive potency of topically applied prostaglandin (PG) PGF2 alpha esters, as compared with that of PGF2 alpha free acid, can be accounted for by increased penetration of the eicosanoid moiety of the esterified PG into the eye. One hour after the topical application of [3H]PGF2 alpha-1-methyl ester (ME) in peanut oil, the 3H activities in the cornea, aqueous humor, and ciliary body of the rabbit eye were 32-, 22-, and 8-fold higher, respectively, than they were following the topical application of [3H]PGF2 alpha free acid. 3H activity during the first 3 hr declined rapidly in the cornea and more slowly in the aqueous humor, but remained essentially constant in the ciliary body for up to 6 hr, declining rapidly only between 6- and 24 hr. 3H activity in eyes that received [3H]PGF2 alpha ME was also several-fold higher in the anterior sclera and iris than in eyes that were treated with [3H]PGF2 alpha free acid, but this difference was much smaller in the conjunctiva. At 1 hr, most of the 3H activity in the aqueous humor was associated with PGF2 alpha, as determined by chromatography, but at 2- and 3 hr other peaks, presumably reflecting metabolites of PGF2 alpha, became apparent. The penetration and intraocular distribution of 3H activity was similar when [3H]PGF2 alpha ME was applied to the eye in normal saline rather than in peanut oil or when the isopropyl rather than the methyl ester of PGF2 alpha was used. These studies indicate that esterification of the carboxyl group of PGF2 alpha greatly enhances the penetration of the PGF2 alpha moiety into the eye and suggests that effective de-esterification of the PGF2 alpha ester occurs in the cornea, resulting in the delivery of PGF2 alpha free acid into the aqueous humor. It is concluded that topically applied PG esters act as pro-drugs and that the increased ocular penetration of these esters may account for the previously reported increase in their ocular hypotensive potency as compared to that of PG free acid or salts.

Administration, Topical↗
PubMed1987

Slit-lamp studies of the rhesus monkey eye. I. Survey of the anterior segment.

Slit-lamp photographic studies of 144 caged rhesus monkeys, aged 2 months to 35 years, show age-related changes in anterior-chamber depth, lens thickness, anterior and posterior curvatures of the lens, and location of the posterior lens surface relative to the anterior corneal surface. For these parameters, as well as for those measured by other techniques, a difference in slope magnitude and (or) slope sign was found between the growth phase which lasts for 5-6 years, and the adult phase (greater than 5-6 years). Age-related changes in the adult rhesus eye are qualitatively similar in almost all aspects to those observed in the human eye, indicating that the rhesus is a good animal model for the study of human loss of accommodative amplitude.

Aging↗