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Biomedical subjects

J Stjernschantz

Publications and source records attributed to J Stjernschantz.

At least 73 records · Page 4Linked to original sources

Ocular responses to leukotriene C4 and D4 in the cat.

The effects of leukotriene C4 (LTC4) and D4 (LTD4) on the iridial smooth muscles, intraocular pressure, blood-aqueous barrier and regional blood flow in the eye have been studied in cats. The test compounds were injected into the anterior chamber. Both LTC4 and LTD4 caused a dose-dependent constriction of the pupil, the agents being about equipotent. The effect on the iridial sphincter muscle was not dependent on nerve conduction, cyclo-oxygenase products or muscarinic receptors. Maximal constriction was achieved with 0.1-1 microgram of the test compounds. The smallest dose to induce a decrease in pupil diameter was 0.01 microgram. After intracameral injection of 4 micrograms the miotic response was markedly delayed. This indicates that in high concentrations LTC4 and LTD4 probably also stimulate the iridial dilator muscle. The blood flow in the anterior uvea decreased after intracameral injection of 4 micrograms LTC4/LTD4. Smaller doses had no clear effect. There was no effect on the blood-aqueous barrier as judged from the aqueous humor protein concentration. The intraocular pressure decreased slightly after injection of the test compounds.

Animals↗

Regional spinal cord blood flow in the rabbit, cat and monkey.

Regional blood flow in the spinal cord was measured in rabbits, cats and monkeys with radioactively labelled microspheres. The reproducibility of the method was tested in rabbits by 3 consecutive determinations with differently labelled microspheres within the different cord regions, and was found to be good. In all 3 species, the blood flow was higher in the lumbar part of the cord than in the thoracic part, and in rabbits and monkeys it was also higher in the cervical than in the thoracic part. The flow values for the cervical, lower thoracic and lumbar parts of the cord in rabbits were 33.3, 24.7, and 27.3 ml X min-1 X 100 g-1, respectively, and in monkeys the respective figures were 14.9, 10.5 and 19.7 ml X min-1 X 100 g-1. Corresponding values for cats were only obtained during moderate hyperventilation, and were 12.2, 10.6, and 15.4 ml X min-1 X 100 g-1, respectively. The results are in good accordance with those of previous studies of the blood flow in the spinal cord in which other techniques have been employed.

Animals↗

Intraocular effects of lipoxygenase pathway products in arachidonic acid metabolism.

Arachidonic acid is metabolized through the lipoxygenase pathways to hydroperoxy acids (HPETEs), hydroxy acids (HETEs), and leukotrienes, derivatives of 5-HPETE. 5-HETE, 12-HETE, 15-HETE, and 15-HPETE were injected intracamerally in rabbits and leukotriene B4 (LTB4), leukotriene C4 (LTC4 and leukotriene D4 (LTD4) were injected intracamerally in guinea pigs, rabbits and cats. The effects on the intraocular pressure, aqueous humour protein and leukocyte concentration as well as pupil diameter were assessed. 5-HETE, 12-HETE, 15-HETE and 15-HPETE did not cause any change in the parameters studied. LTB4 caused a marked accumulation of leukocytes in the aqueous humour of cats and rabbits, and to some extent in guinea pigs. LTC4 and LTD4 were ineffective in guinea pigs and rabbits, but caused an intense long-lasting non-muscarinic miosis in cats. Thus, most of the lipoxygenase products tested showed little activity in the anterior segment of the eye, except LTB4, that caused leukocyte infiltration, and LTC4 and LTD4 that caused miosis in cats.

Animals↗

[Leukotrienes].

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Humans↗

The leukotrienes.

This paper reviews the leukotrienes, a new group of biologically active compounds in the metabolism of eicosapolyenoic acids. The leukotrienes are acyclic eicosanoids that arise through the 5-lipoxygenase pathway from eicosatrienoic, eicosatetraenoic, and eicosapentaenoic acid. Of these eicosatetraenoic acid, arachidonic acid, is the most important source of leukotrienes. Leukotriene B4 (LTB4), a dihydroxy metabolite, has been shown to exert marked chemotactic effect in many different animal species. LTB4 probably plays a role in inflammatory responses, and has been detected in several pathologic conditions. Reaction of LTA4, another lipoxygenase metabolite of arachidonic acid, with glutathione yields peptidolipid leukotrienes, LTC4, LTD4, and LTE4; these are components of slow reacting substance (SRS and SRS-A). The peptidolipid leukotrienes are potent bronchoconstrictors and enhance mucus production in the lungs. Furthermore, they constrict coronary arteries and have a negative inotropic effect. They probably play an important role in asthma and anaphylaxis. LTB4 and the peptidolipid leukotrienes may be important in several other organs, too, e.g., the skin and the eye. They may exert effects on a variety of smooth muscles and have neuronal and immunological effects.

Animals↗

Enzyme-linked immunosorbent assay of substance P: a study in the eye.

A solid phase enzyme-linked immunosorbent assay for quantitation of substance P is presented. The assay measures the capacity of soluble substance P to compete with the solid phase antigen for a limited quantity of specific substance P antibody. The solid-phase antigen consists of a synthetic substance P.poly-D-glutamic acid conjugate coated to polystyrene micro-ELISA plate wells. Soluble substance P and antibodies to substance P are first preincubated together and then added to the wells containing solid-phase antigen. Subsequently the wells are incubated with anti-antibodies conjugated to alkaline phosphatase. The wells are finally incubated with p-nitrophenyl phosphate an the absorbance is read in a spectrophotometer 16--24 hr after the start of the assay. The threshold for detection of substance P was 5--10 pg per well (0.25 ml). Substance P was extracted from rabbit eyes and the values obtained with the present method are compared with previously reported values based on radioimmunoassay.

Animals↗

The miotic effect of substance P on the isolated rabbit iris.

The effect of substance P on the rabbit iris was investigated by continuously monitoring the pupil size in vitro. Continuous perfusion with substance P caused a concentration-dependent contraction of the iridial sphincter muscle. The threshold was 2 x 10(-10) M. A concentration-response curve was made for 60 sec exposures of the iris to substance P. Blockade of muscarinic, nicotinic, alpha-, and beta-adrenergic receptors as well as blockade with the putative presynaptic substance P-blocking agent baclofen did not affect the constrictor response to substance P. Pretreatment of the rabbits with indomethacin was also without effect. No effect of substance P was seen on the isolated iridial dilator muscle. Although the miotic response to substance P was observed in a calcium-free perfusion fluid, EGTA added to calcium-free perfusate diminished the effect of substance P. The response of the iris to substance P and the time course of the response make it likely that substance P is involved in the miosis of the nerve-mediated irritative response of the eye.

Adrenergic alpha-Antagonists↗

Intraocular effects of substance P in the rabbit.

The intraocular effects of substance P (SP) were studied in rabbits by measuring the pupil diameter, intraocular pressure (IOP), and aqueous humor protein concentration. Most of the animals were pretreated with indomethacin to avoid any interaction with prostaglandins. Intracameral injection of 1 to 150 ng of SP caused strong and persistent miosis without appreciably affecting the aqueous humor protein concentration or IOP. Intracameral injection of 0.8 to 11 micrograms of SP also induced an increase in IOP (7 to 8 mm Hg) without any apparent concomitant disruption in the blood-aqueous barrier. Outflow facility of aqueous humor decreased by a mean value of 50% after intracameral injection of 0.8 to 1.5 microgram of SP. Since the increase in IOP could be prevented by iridectomy, it was probably caused by a pupillary block from the intense miosis induced by SP. No disruption in the blood-aqueous barrier could be detected after intra-arterial infusion of 10 micrograms of SP or intravitreal injection of 100 ng of SP, indicating that the ciliary epithelium was practically insensitive to exogenous SP. Topical as well as subconjunctival administration of up to 1 mg of SP did not cause any irritative response in the eye. The results show that with concentrations of SP causing intense miosis, the eye does not exhibit visible hyperemia and disruption of the blood-aqueous barrier. This finding is consistent with the hypothesis that after certain irritative stimuli, miosis is mediated by a pathway separate from the hyperemia and disruption of the blood-aqueous barrier.

Administration, Topical↗

Cholinergic vasoconstrictor effects in the rabbit eye: vasomotor effects of pentobarbital anesthesia.

Oculomotor nerve stimulation causes vasoconstriction in the anterior uvea, which is due partly to a muscarinic mechanism and partly to a non-sympathetic aminergic mechanism. The labelled microsphere method was used to analyze the effect of pentobarbital anesthesia on the resting cholinergic vasomotor tone in the anterior uvea and to determine the relationship between stimulation frequency and vasomotor response. An attempt was made also to ascertain whether the aminergic part of the vasoconstriction is caused by release of 5-hydroxytryptamine or norepinephrine. Induction of pentobarbital anesthesia caused a marked vasodilation in the iris and the ciliary processes and a subsequent muscarinic blockade had no effect on the blood flow. A similar result was obtained in the optic nerve. In the choroid plexus, heart muscle, pineal body and coecum, pentobarbital anesthesia caused vasodilation and a subsequent muscarinic blockade caused vasoconstriction. In the brain pentobarbital anesthesia caused a marked reduction in the blood flow of the grey matter and a moderate reduction in the white matter. After a muscarinic blockade there was some increase in the blood flow of the grey matter. Stimulation of the oculomotor nerve caused near maximum vasomotor responses at 10-20 Hz; maximum effect on the pupil size was obtained at 40-50 Hz. Depletion of 5-hydroxytryptamine with fenfluramine did not prevent the aminergic part of the vasoconstriction and a marked vasoconstriction was also observed after pretreatment with reserpine. The results indicate the pentobarbital anesthesia abolishes most of the spontaneous cholinergic vasoconstrictor tone of the anterior uvea and that the aminergic part of the oculomotor nerve induced vasoconstriction is caused by the stimulation of phentolamine-sensitive receptors by a mechanism probably not involving release of norepinephrine or 5-hydroxytryptamine.

Animals↗

Vasomotor effects of facial nerve stimulation: noncholinergic vasodilation in the eye.

The effect of facial nerve stimulation on ocular blood flow was studied in rabbits. The intracranial part of the facial nerve was stimulated electrically and the regional blood flow was measured with labelled microspheres. Effects on the intraocular pressure were determined in a separate series of experiments. Stimulation increased choroidal blood flow by about 200%. The blood flow of the iris and the ciliary processes also increased. The blood flow of the eyelids and the nictitating membrane increased by approximately 1000%, and the blood flow of Harder's gland increased by about 200%. The blood flow of the tongue and the submandibular gland also increased. The increase in the uveal blood flow could not be abolished by a cholinergic or ganglionic blockade. Ganglionic blockade abolished most of the increase in the blood flow of the eyelids, nictitating membrane and Harder's gland; the cholinergic blockade seemed less effective. The intraocular pressure increased with a mean value of 6 mmHg during optimal (20-30 Hz) stimulation. The increase could not be prevented by cholinergic blockade. Much of the increase in uveal blood flow seemed to be caused by stimulation of unconventional nerves. It is suggested that these nerves may be peptidergic using VIP as a transmitter and lacking a hexamethonium sensitive synapse between the site of stimulation and the eye. Their nature--afferent or efferent--remains unknown. A great part of the increase in blood flow of the eyelids, nictitating membrane and Harder's gland seemed to be due to other mechanisms involving nerves with a peripheral synapse.

Animals↗

Heterophoria--its influence on stereopsis and the importance of cycloplegia in refraction testing of pilot applicants.

Heterophoria, its influence on stereopsis, and the importance of cycloplegia in refraction testing of pilot applicants were studied. Distant heterophoria was found in 94.5-100% while near heterophoria was found in 86.9-98.1% of the cases, depending on the test used. Hyperphoria of over 1 prism diopter was extremely rare. No statistically significant correlation between distant heterophoria and the degree of stereopsis could be demonstrated at a range of up to at least 6 prism diopters. Cycloplegia induced a mean difference of +0.75 diopter in refraction before and during cycloplegia. Eight percent of the applicants failed because of refractive errors (spherical extremes, -0.75 diopter and +4.50 diopters; cylindrical extreme, 1.25 diopters). It is concluded that stereopsis does not seem to be affected much by heterophoria within moderate limits, and that cycloplegia in refraction testing of young pilot applicants must be considered relatively important.

Accommodation, Ocular↗