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Biomedical subjects

J Stjernschantz

Publications and source records attributed to J Stjernschantz.

At least 55 records · Page 3Linked 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

Vascular effects of acetylcholinesterase inhibitors in the rabbit eye: a study with fasciculin and physostigmine.

The vascular effects of fasciculin and physostigmine, two acetylcholinesterase inhibitors, were studied with radioactively labelled microspheres in the rabbit eye. In addition, the effects on the intraocular pressure, pupil size and the aqueous humor protein concentration were determined. Both drugs were injected intracamerally in pentobarbital anesthetized and indomethacin pretreated animals. Fasciculin injected in a dose of 0.5 micrograms (0.7 x 10(-10)M) reduced blood flow in the anterior uvea as determined 30 and 60 min after injection. Higher doses had inconsistent effects. Physostigmine injected in a dose of 3 micrograms (1.1 x 10(-8)M) also reduced blood flow in the anterior uvea. The effect was most pronounced in the iris. Neither drug had any appreciable effect on choroidal or retinal blood flow. Both drugs caused pupillary constriction but the reduction in blood flow was not secondary to miosis. The effects on the intraocular pressure and aqueous humor protein concentration were inconsistent. The reduction in blood flow of the anterior uvea after intracameral injection of acetylcholinesterase inhibitors is consistent with a cholinergic vasoconstriction previously described in the eye during electrical stimulation of the oculomotor nerve.

Animals↗
PubMed1991

Increase in ocular blood flow induced by isobutylmethylxanthine and epinephrine.

Alterations in regional blood flow of the eye were studied in rabbits using the radioactively labelled microsphere technique. The animals were topically treated with 1% IBMX, 0.1% epinephrine in combination with 1% isobutylmethyl-xanthine (IBMX), or with 0.1% epinephrine alone. After IBMX there was a tendency towards an increase in blood flow in the iris, ciliary processes and sclera, whereas the choroidal blood flow tended to decrease. After epinephrine the iridial blood flow increased about 50% at 6 hr. After IBMX combined with epinephrine a biphasic response was obtained: an initial decrease in blood flow of the iris, the ciliary processes and to some extent the choroid was followed by a marked and long lasting increase in blood flow from 2.5 to 7.5 hr in the iris (up to 220%), ciliary processes (123%) and sclera (115%). The choroidal blood flow was not increased. The marked increase in blood flow of the iris and the ciliary processes indicates that the reduction of intraocular pressure seen after topical treatment with a combination of epinephrine and IBMX, is not based on a vascular mechanism. The increase of ocular blood flow after a combination of IBMX and epinephrine is probably based on increased cAMP secondary to inhibition of phosphodiesterases. This may indicate the presence of beta-adrenergic receptors in the ocular vasculature.

1-Methyl-3-isobutylxanthine↗
PubMed1990

Cholinergic vasoconstriction in the eye.

Data is presented to support a physiologic vasoconstrictor function of the parasympathetic nervous system in the anterior uvea of the eye. Studies in rabbits, cats and monkeys demonstrate that stimulation of the parasympathetic nerve fibers running with the oculomotor nerve to the eye induces a reduction in blood flow of the iris and in rabbits in the ciliary processes in addition. Pharmacologic blocking experiments indicate that most of this phenomenon is based on a cholinergic component. Since at least in rabbits mechanical factors such as stretching of the iridial tissue, a steeling phenomenon to nearby tissues of blood as well as secondary effects caused by changes in the intraocular pressure can be excluded, the reduction in blood flow in all likelihood reflects a true vasoconstriction. Experiments in unanesthetized rabbits indicate that there is a continuous physiologic cholinergic vasoconstrictor tone in the iris and ciliary processes normally. Thus, the anterior uvea in mammals may be one of the tissues exhibiting a cholinergic vasoconstriction phenomenon, found more commonly in lower vertebrates.

Animals↗
PubMed1989

Increased uveoscleral outflow as a possible mechanism of ocular hypotension caused by prostaglandin F2 alpha-1-isopropylester in the cynomolgus monkey.

The effects of topical application of a single dose of prostaglandin F2 alpha, administered as the isopropylester, on the intraocular pressure (IOP), aqueous humor flow (AHF), conventional, and uveoscleral outflow were studied in cynomolgus monkeys under pentobarbital anesthesia. 1 microgram PGF2 alpha decreased the IOP by 2.9 +/- 0.6 mmHg (3 hr after the application) as compared with the vehicle-treated control eye. The mean AHF during the whole experiment was slightly higher in the experimental than in the control eye, 1.34 +/- 0.11 microliters min-1 compared with 1.16 +/- 0.09 microliters min-1. The uveoscleral outflow was significantly increased in the PGF2 alpha-treated eye, 0.98 +/- 0.12 microliters min-1 compared with 0.61 +/- 0.10 microliters min-1 for the control eye. The conventional outflow was lower in the experimental eye throughout the experiment. Topical application of 10 micrograms pilocarpine at the time when the fall in IOP was expected prevented the drop in the IOP. Simultaneously the increase in the uveoscleral outflow was abolished. After systemic pretreatment with atropine, 1 mg (kg body weight)-1 i.v., there was no significant difference in IOP, AHF, conventional or uveoscleral outflow between the PGF2 alpha-treated, and the control eye. The results of the present investigation suggest that PGF2 alpha decreases the intraocular pressure by increasing the uveoscleral outflow. The mechanism behind the increase in the uveoscleral outflow remains to be established. Relaxation of the ciliary muscle as well as enlarged intramuscular spaces and loss of extracellular material may contribute to the effect.

Animals↗
PubMed1989

Characterization of the mechanism of acute ocular irritation to YAG laser capsulotomy in rabbits: effects of substance P antagonists, Met-enkephalin, tetracaine and tetrodotoxin.

This study was undertaken to characterize the mechanism of ocular irritation to YAG laser capsulotomy in rabbits. The blocking agents were administered intravitreally. (D-Arg1,D-Pro2,D-Trp7,9)-SP, a substance P antagonist, tended to reduce miosis but had no effect on intraocular pressure (IOP). It had less effect on miosis than (D-Arg1,D-Pro2,D-Trp7,9,Leu11)-SP another SP antagonist. Met-enkephalin and tetracaine had no effect on miosis or the increase in IOP after YAG laser capsulotomy, whereas tetrodotoxin reduced miosis, but had no clear-cut effect on IOP, or the increase in aqueous humor protein concentration. This indicates an involvement of sensory neurons with release of SP or a closely related peptide in the miotic component part while the increase in IOP and the barrier breakdown probably are dependent mainly on a release of prostaglandins.

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

Vasodynamic and angiogenic effects of eicosanoids in the eye.

In the eye, the main vascular response to PGs is vasodilation. Although its effect has not been studied in detail, TxA2 can be expected to cause vasoconstriction in the eye, as it does in other tissues. When applied in high doses, PGs also increase the permeability of the microvasculature in the anterior segment, especially in rabbits. This may contribute to protein leakage associated with disruption of the BAB. The peptidoleukotrienes seem to reduce blood flow in the anterior segment, although more data will be required to substantiate this observation. It has been suggested over the years that PGs have a physiologic role in the autoregulation of the retinal blood flow. It has also been hypothesized that PGs, particularly those of the E series, play an important role in corneal neovascularization. The evidence obtained thus far in support of such hypothesis is not conclusive. It is possible that in the course of corneal vascularization or its induction, PGs are released, together with other mediators such as lipoxygenase products, but the pathophysiologic mechanisms are poorly understood. The role of eicosanoids in CME remains speculative. It is possible that other compounds in the cyclooxygenase pathway such as thromboxane and prostacyclin or some lipoxygenase products play a more important role in CME than the classical PGs, but, there is insufficient data so far to implicate any one eicosanoid or any other autacoids in the initiation of the vascular changes that are associated with CME.

Animals↗
PubMed1988

Effects of calcitonin gene-related peptide in the eye. A study in rabbits and cats.

Calcitonin gene-related peptide (CGRP) has recently been demonstrated in sensory neurons of the eye. The purpose of the present study was to determine the effects of exogenous CGRP in the rabbit and cat eye. CGRP was injected intracamerally and the intraocular pressure was measured in cannulated eyes. The pupil diameter and the aqueous humor protein concentration were also measured. Indomethacin was used to prevent prostaglandin synthesis and tetrodotoxin (TTX) to block nerve conductance. In the rabbit eye, CGRP caused iridial hyperemia, a breakdown of the blood-aqueous barrier and increased intraocular pressure. These responses were dose-related. The increase in IOP as well as the breakdown of the blood-aqueous barrier could not be blocked with TTX or indomethacin. In cats CGRP caused a decrease in IOP and had only slight effect on the aqueous humor protein concentration. Neither in rabbits nor in cats had CGRP any detectable effect on the pupil size. Intracameral injection of 0.1 microgram (7.4 x 10(-11) moles) substance P together with 0.1 microgram (2.6 x 10(-11) moles) CGRP in rabbits caused maximal miosis but did not potentiate the intraocular effects of CGRP only. These results indicate that CGRP has marked vascular effects in the rabbit eye, causing a breakdown of the blood-aqueous barrier and increased IOP. The mechanism of this phenomenon does not involve prostaglandins neither nerve conduction, implying most likely a direct effect on the vascular smooth muscle. The mechanism of the decrease of IOP in cats remains unknown.

Animals↗
PubMed1986

Calcitonin gene-related peptide in the eye: release by sensory nerve stimulation and effects associated with neurogenic inflammation.

Calcitonin gene-related peptide (CGRP) in the anterior uvea coexists with tachykinins (substance P and neurokinin A) in sensory nerve fibers deriving from the trigeminal ganglion. Mechanical or electrical stimulation of the intracranial part of the trigeminal nerve/ganglion in rabbits produced a marked hyperemia in the anterior segment of the eye, increased intraocular pressure, breakdown of the blood-aqueous barrier and miosis. Simultaneously, CGRP-like immunoreactivity was released into the aqueous humor. This suggests that the highly vasoactive CGRP can be released from sensory nerve fibers to participate in vascular responses. Unlike the tachykinins, CGRP per se was without effect on the pupillary diameter while disrupting the blood-aqueous barrier (resulting in aqueous flare) upon intravitreal injection. In addition, CGRP enhanced the aqueous flare evoked by a minimal eye trauma (infrared irradiation of the iris). The miosis evoked by the intravitreal injection of substance P was more pronounced when CGRP was injected simultaneously, and finally, substance P induced aqueous flare much more effectively when given together with a threshold dose of CGRP.

Animals↗
PubMed1986

A study of the mechanism of ocular irritation following YAG laser capsulotomy in rabbits.

The irritative response to Nd:YAG laser capsulotomy was studied in unanaesthetized rabbits. Posterior lens capsulotomy with a total energy of 100 mJ had no effect on the pupil size but increased the intraocular pressure by 5-10 mmHg and caused a breakdown of the blood-aqueous barrier. Anterior lens capsulotomy with a total energy of 20, 60 or 100 mJ caused constriction of the pupil, and an increase in intraocular pressure in a dose-dependent manner, and a breakdown of the blood-aqueous barrier. Indomethacin attenuated all the component parts of the irritative response and (D-arg1, D-pro2, D-trp7,9, leu11)-SP attenuated the miotic response. A combination of indomethacin and the substance P antagonist almost completely abolished the irritative response. This indicates that the acute YAG-laser-induced irritation in the rabbit eye is dependent both on a release of prostaglandins and on substance P, the former probably releasing the latter from sensory nerves.

Animals↗
PubMed1985

Effects of somatostatin, a somatostatin analog, neurotensin and met-enkephalin in the eye with special reference to the irritative response.

The effects of somatostatin, cyclo(D-Trp-Lys-Thr-Phe-Pro-Phe) acetate, a somatostatin analog, neurotensin, and met-enkephalin were studied in the rabbit eye by measuring the intraocular pressure (IOP), aqueous humor protein concentration, ocular blood flow and the pupil diameter. Somatostatin or the analog injected intracamerally (10 micrograms/eye) and infused intra-arterially (0.6-4 micrograms/min) had no significant effect on the parameters studied in normal eyes. However, somatostatin and, particularly, the analog attenuated the miotic response to a standard nociceptive stimulus consisting of topical application of 1% neutral formaldehyde. The other component parts of the irritative response were not attenuated. Intracameral injection of 1-2 micrograms neurotensin caused vasodilation in the anterior segment of the eye, a slight increase in aqueous humor protein concentration, and some decrease in IOP. Intracameral injection of 1-50 micrograms met-enkephalin had no effect on the blood-aqueous barrier, IOP or the pupil diameter. Neither did this dose of met-enkephalin attenuate the miotic response to exogenous substance P. It seems likely that somatostatin and the somatostatin analog attenuate the miotic response to nociceptive stimuli by preventing the release of a substance, presumably substance P, from sensory nerves.

Animals↗
PubMed1985

A study of the efficacy of two commercial preparations of timolol maleate with special reference to side effects.

The intraocular pressure lowering effect of 2 commercial preparations of timolol maleate was studied in 57 adult outpatients suffering from open angle glaucoma or ocular hypertension. Special attention was paid to side effects of topical treatment with timolol, while comparing the efficacy of the 2 preparations. The intraocular pressure lowering effect with each strength (0.25% and 0.5%) of both preparations (Blocanol and Oftan-Timolol) was identical. No clearcut effect on lacrimal gland function, accommodation, or pupil size was seen. The adverse effects of timolol maleate during 6 months of treatment were of transient nature and generally mild. The only serious adverse effect was respiratory distress which occurred with 0.25% timolol in one patient. The respiratory distress developed slowly and the trial had to be discontinued for this patient after 2 months of treatment. There was a tendency toward a decrease in blood pressure and heart rate with both commercial preparations.

Clinical Trials as Topic↗
PubMed1985

Serum antibody level to S-antigen in children with chronic uveitis.

Bovine S-antigen was purified by gel filtration and ion exchange chromatography according to previously described techniques. An enzyme linked immunosorbent assay (ELISA) using antiserum to bovine S-antigen raised in guinea-pigs was employed to detect S-antigen in the chromatographic fractions. The purity of the S-antigen was determined by SDS-PAGE electrophoresis, where a single band was found. The purified S-antigen in microgram quantities together with Freund's complete adjuvant induced uveitis in rats two weeks after injection into the foot pad. Serum samples from children suffering from chronic uveitis and healthy children were tested for antibodies to S-antigen by the ELISA. A statistically significant difference in the level of specific antibodies between patients and controls was found. There was no clear-cut correlation between the severity of uveitis and antibody titre, but cases with retinal involvement and aggressive uveitis all showed definite elevations of antibodies to S-antigen.

Antibodies↗
PubMed1984

Substance P-like immunoreactivity in the trigeminal ganglion. A fluorescence, light and electron microscope study.

The trigeminal ganglion of rat and guinea pig was studied for the presence of immunoreactive substance-P using fluorescence, light and electronmicroscopy. In untreated animals substance P containing cells, with a diameter of 15 to 50 micron, were distributed throughout the ganglion and comprised 10-30% of all ganglion cells. Colchicine, injected intraventricularly to inhibit intra-axonal transport, had no effect on the number of substance P cells; but when the drug was injected directly into the posterior root of the ganglion, the proportion of these cells increased to as much as 50%. In the electron microscope, immunoreactive substance-P was confined to ganglion cells classified as B type according to the arrangement of subcellular organelles, and to unmyelinated nerve fibers. Subcellularly the immunoreactivity appeared in cytoplasmic vesicles, as well as dispersed in the nerve fibers and the perikarya of neurons. The great number of substance P immunoreactive ganglion cells suggests that they do not comprise a well defined subpopulation of the B-cells. However, the immunoreactivity was restricted to a distinct ultrastructural type of neurons with unmyelinated nerve fibers, suggesting that they also may share some distinct functions.

Animals↗