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M Astin

Publications and source records attributed to M Astin.

15 recordsLinked to original sources
PubMed2005

Altered neuroendocrine response and gastric dysmotility in the Flinders Sensitive Line rat.

In the search for animal models that can replicate some features of functional dyspepsia (FD) patients, we turned our interest to the Flinders Sensitive Line (FSL) rat. Gastric motility disturbances prevalent in FD patients as well as urine corticosterone and plasma prolactin were measured following buspirone challenge. Flinders Resistant Line (FRL) rat was used as control. The results show that the FSL rats have a disturbed gastric motility, reflected as both an increased gastric accommodation rate and gastric volume during gastric distension as well as a delayed gastric emptying, the latter possibly as a consequence of the former. Lipid administration resulted in a significant increase in maximal gastric volume only in the FRL rats. Both the corticosterone response to buspirone and the 24-h urinary output of corticosterone were normal in FSL rats. Similar to FD patients, the FSL rat showed supersensitivity to buspirone in the increase in prolactin release. Although FSL rats show some features similar to a subset of FD patients, the increased gastric accommodation contrasts to the reduced accommodation often seen in FD patients. Further studies are warranted to determine the relevance of this rat strain as a model for FD.

Animals↗
PubMed2000

Microvascular effects of selective prostaglandin analogues in the eye with special reference to latanoprost and glaucoma treatment.

Prostaglandin F(2alpha) analogues have recently been introduced on the market for glaucoma treatment. While these drugs have a well-documented intraocular pressure reducing effect only a limited number of studies have been published regarding their effects on the microvasculature in the eye. Since many naturally occurring prostaglandins have marked effects on the cardiovascular system it is conceivable that synthetic prostaglandins used as glaucoma drugs may exert microvascular effects in the eye, even if they exhibit receptor selectivity. Latanoprost, the active principle of Xalatan((R)) eye drops, is a selective FP prostanoid receptor agonist, and much of the paper is focused on the microvascular effects of latanoprost and some closely related prostaglandin analogues. The purpose of the paper is to review the literature on the microvascular effects of prostaglandins in the eye, and to present some unpublished data on the effects of selective prostaglandin analogues. Most of the prostaglandin analogues studied exhibit selectivity for the FP prostanoid receptor. Results from studies with the following prostaglandin analogues are presented in the paper: PGF(2alpha)-isopropyl ester (PGF(2alpha)-IE), 17-phenyl-18,19,20-trinor-PGF(2alpha)-isopropyl ester (17-phenyl-PGF(2a)-IE), 15-keto-17-phenyl-18,19, 20-trinor-PGF(2alpha)-isopropyl ester (15-keto-17-phenyl-PGF(2a)-IE), 13,14-dihydro-17-phenyl-18,19,20-trinor-PGF(2alpha)-isopropy l ester (latanoprost), 13,14-dihydro-15R,S-17-phenyl-18,19, 20-trinor-PGF(2alpha)-isopropyl ester (PhXA34), 17-phenyl-18,19, 20-trinor-PGE(2)-isopropyl ester (17-phenyl-PGE(2)-IE), and 19R-hydroxy-PGE(2) (19R-OH-PGE(2)). The regional blood flow has been determined with radioactively labelled microspheres, the blood volume with (51)Cr labelled erythrocytes and the capillary permeability to albumin with (125)I and (131)I labelled albumin. PGF(2alpha)-IE has been shown to exert marked microvascular effects in the rabbit anterior segment including vasodilatation, increased capillary permeability, and a breakdown of the blood-aqueous barrier. 17-phenyl-PGF(2alpha)-IE, 15-keto-17-phenyl-PGF(2alpha)-IE, and PhXA34/latanoprost exerted significantly less vasodilatory effect, and little effect on capillary permeability was seen with the FP receptor agonists when studied with Evans blue. Intravenous administration of PhXA34 at a dose range of 1-100 microg/kg b.w. had no consistent effect on the regional blood flow in the eye indicating that FP receptors in the ocular blood vessels are not expressed in the rabbit, or alternatively are not functionally coupled to regulation of vascular tone. In cats topical application of PGF(2alpha)-IE had no significant effect the on the regional blood flow in cannulated eyes. No blood flow experiments were performed in intact eyes with PGF(2alpha)-IE. 17-phenyl-PGF(2alpha)-IE and latanoprost caused some vasodilation in the anterior segment. None of the analogues had any significant effect on the blood volume in the ocular tissues, but an increase in capillary permeability to albumin was seen in several tissues of the eye. However, in the eyelid, nictitating membrane and conjunctiva exposed to high concentrations of the prostaglandins no or only little leakage of albumin was detected. It appears that the intraocular microvasculature in the cat exhibits some sensitivity to FP prostanoid receptor agonists. (ABSTRACT TRUNCATED)

Animals↗
PubMed1999

Effect of latanoprost on regional blood flow and capillary permeability in the monkey eye.

OBJECTIVE: To evaluate the effects of latanoprost on regional blood flow and capillary permeability in the monkey eye. METHODS: Anesthetized cynomolgus monkeys were unilaterally treated with a single dose containing 6 pg of latanoprost; or 10 microg of PhXA34 (13,14-dihydro-15R, S-17-phenyl-18,19,20-trinor-prostaglandin F2alpha [PGF2alpha]-isopropyl ester), which contains about 50% latanoprost. Regional blood flow in the eye was measured with radioactively labeled microspheres; capillary permeability was measured by determining the extravascular plasma-equivalent albumin space using 125I-albumin, 131I-albumin, and 51Cr-labeled erythrocytes. RESULTS: Latanoprost or PhXA34 had no or only a slight effect on the regional blood flow when measured 1, 2 1/2, 3, 4 1/2, and 6 hours after dose administration, with the exception of the anterior sclera, in which a moderate increase in blood flow was detected. No effect on capillary permeability to albumin was detected when studied 30 minutes to 2 1/2 hours and 5 to 6 hours after dose administration. CONCLUSION: Latanoprost, a selective prostaglandin F receptor agonist, exerted no or only slight vascular effects for up to 6 hours after dose administration in the monkey eye, with the exception of the anterior sclera, in which a moderate increase in blood flow was detected. CLINICAL RELEVANCE: Naturally occurring prostaglandins may cause marked microcirculatory changes in the eye that could be of clinical concern. Latanoprost, a selective prostaglandin F receptor agonist, seems to be devoid of such effects.

Administration, Topical↗
PubMed1998

Effects of prostaglandin E2, F2alpha, and latanoprost acid on isolated ocular blood vessels in vitro.

The vascular effects of PGE2, PGF2alpha and latanoprost acid on isolated bovine long posterior ciliary arteries and episcleral veins have been investigated using a small vessel myograph. PGE2 caused vasorelaxation both in the ciliary artery and episcleral vein (EC50: 7.9x10(-9) M and 2.1x10(-8) M respectively). Blockade of thromboxane receptors with GR 32191B, a TP receptor antagonist, shifted the concentration-response curves to the left in both preparations, probably indicating a slight co-stimulation of TP receptors in these vessels. Blockade of tachykinin NK-1 receptors had no effect on the PGE2 concentration-response curve. PGF2alpha caused a concentration dependent contraction in half of the ciliary arteries examined and relaxation in the other half. In the presence of the thromboxane receptor antagonist (GR 3211B) PGF2alpha always induced relaxation of the ciliary artery (EC50:1.3x10[-5] M). At higher concentrations PGF2alpha tended to slightly constrict the episcleral veins, but in the presence of the TP receptor antagonist (GR 32191B) only relaxation was observed. Latanoprost acid contracted the ciliary artery at concentrations above 10(-6) M. This effect was completely abolished by the TP receptor antagonist (GR 32191B). In the episcleral vein latanoprost acid induced a slight relaxation but in the presence of the TP receptor antagonist (GR 32191B) no effect was observed. These results indicate that PGE2 invariably induces vasorelaxation of bovine ciliary arteries and episcleral veins, whereas both PGF2alpha and latanoprost acid at high concentrations can cause vasoconstriction probably by stimulating TP receptors. PGF2alpha causes marked relaxation of both ciliary arteries and episcleral veins in the presence of the TP blocker which seems unlikely to be mediated by FP receptors.

Animals↗
PubMed1997

Mechanism of prostaglandin E2-, F2alpha- and latanoprost acid-induced relaxation of submental veins.

The mechanism of prostaglandin E2-, prostaglandin F2alpha- and latanoprost acid (13,14-dihydro-17-phenyl-18,19,20-trinor-prostaglandin F2alpha)-induced relaxation of the rabbit submental vein was studied. Prostaglandin E2 caused maximum relaxation of endothelin-1 precontracted vessels (EC50: 1.8 x 10(-8) M). Much of the relaxation could be abolished by denuding the endothelium with the nitric oxide synthase inhibitor, L-NAME (N(G)-Nitro-L-arginine methylester). CGRP-(8-37) (calcitonin gene-related peptide fragment (8-37)), a calcitonin gene-related peptide receptor antagonist, exhibited a partial blocking effect, whereas the tachykinin NK1 receptor blocker, GR 82334 ([D-Pro9[Spiro-gamma-Lactam]Leu10,Trp11]physalaemin (1-11)), markedly attenuated the response. Both prostaglandin F2alpha and the relatively selective FP receptor agonist, latanoprost acid, caused relaxation of the veins to about 50% of the precontracted state in the presence of GR 32191B ([1R-[1alpha(Z),2beta,3beta,5alpha]]-(+)-7-[5-([1,1'-b iphenyl]-4-ylmethoxy)-3-hydroxy-2-(1-piperidinyl)cyclopentyl]-4-he ptenoic acid), a thromboxane receptor antagonist (EC50: for prostaglandin F2alpha 7.9 x 10(-9) M, and for latanoprost acid 4.9 x 10(-9) M). L-NAME, as well as denuding the endothelium, completely abolished the effect. In addition, most or at least a large part of the relaxation was also blocked by CGRP-(8-37) as well as GR 82334. These results indicate that the FP receptor-mediated relaxation of veins is based on release of nitric oxide in addition to involvement of calcitonin gene-related peptide and substance P, or some other tachykinin, probably released from perivascular sensory nerves. The more pronounced relaxation induced by prostaglandin E2 could be due to vasodilator EP receptors in the smooth muscle layer of the veins.

Animals↗
PubMed1997

Analysis of variance of microspheres blood flow measurements in rabbits.

As part of a larger study on the interpretation of angiographically derived hemodynamic parameters, blood flow in several ocular tissues was measured using the radioactively labelled microspheres technique. As an unexpected secondary results, it was found that the microspheres data gave quantitative information on hyperaemic effects in the eye. This is the subject of the present paper. The measurements were made in 13 anaesthetized pigmented rabbits. In each animal, three blood flow measurements were performed at three different ocular perfusion pressures (60-15 mmHg). The perfusion pressures of the experimental eye were varied by changing the intra-ocular pressure. The contra-lateral eye served as a control. Labelled microspheres were used as a non-recirculating blood flow indicator, enabling the estimation of regional blood flows, in this case for the iris, ciliary body, peripheral choroid and peripapillary choroid separately. Using analysis of variance with perfusion pressure as covariate and taking into account the blood flow of the control eye, hyperaemia could be quantified in the experimental eye. Apart from a difference amongst animals, hyperaemia depended on tissue type. The amount of hyperaemia proved to be more pronounced in the anterior part of the eye, iris and ciliary body, and to decrease towards the posterior pole. With regard to the causes of this hyperaemia one could speculate about the invasive handling (anterior eye needles) topical administration of tropicamide, in combination with the general anaesthesia.

Analysis of Variance↗
PubMed1997

Fluorescein angiographic evaluation of the effect of latanoprost treatment on blood-retinal barrier integrity: a review of studies conducted on pseudophakic glaucoma patients and on phakic and aphakic monkeys.

Endogenous prostaglandins (PGs) have been claimed to play a role in the development of cystoid macular edema (CME). Two fluorescein angiographic studies evaluating the effect of latanoprost, a new ocular hypotensive PG analogue, on blood-retinal barrier integrity are, therefore, reviewed here. In the first study, six of eight unilaterally aphakic cynomolgus monkeys were treated bilaterally once daily for six months with 0.035% latanoprost (seven times the clinically used oculohypotensive concentration). Two of the animals served as controls. Fluorescein angiography of the fundus after one, three and six months of treatment revealed no leakage of fluorescein in any of the 16 eyes. In another study, pseudophakic eyes of 16 glaucoma patients who received twice-daily treatment with 0.006% latanoprost for four weeks were compared to eight patients treated with placebo. Biomicroscopic examination did not reveal any signs of CME and only one placebo-treated eye revealed a slight perifoveal leakage of fluorescein. These studies suggest that topically-applied latanoprost does not have a fluorescein angiographically detectable direct effect on the integrity of the blood-retinal barrier system in phakic or aphakic monkey eyes or in pseudophakic human eyes. This does not rule out the occurrence of CME in eyes more susceptible to CME, due to vitreous loss, posterior capsulotomy, or other postoperative situations. Especially in those eyes a study with latanoprost is proposed. Since, fluorescein angiography is a rather crude method of detecting abnormalities of the blood-retinal barriers, vitreous fluorometry in addition is suggested.

Animals↗
PubMed1997

Mediation of prostaglandin f2 alpha-induced ocular surface hyperemia by sensory nerves in rabbits.

PURPOSE: Prostaglandin F2 alpha (PGF2 alpha) and several other prostaglandins cause surface hyperemia of the eye when applied topically. The purpose of the present study was to investigate the role of sensory nerves in prostaglandin-induced ocular hyperemia. METHODS: The ophthalmic branch of the trigeminal nerve was unilaterally electrocoagulated in rabbits using a stereotaxic technique. Two weeks later the animals received bilaterally one drop of PGF2 alpha-isopropyl ester (PGF2 alpha-IE) at a dose of 1 microgram/ eye. The blood flow to the different parts of the eye was measured with the radioactively labeled microsphere technique before, 30 and 60 min after treatment with PGF2 alpha-IE. RESULTS: In the control eyes with intact sensory innervation, PGF2 alpha-IE caused a marked increase in blood flow to the surface structures of the eye (conjunctiva, anterior sclera, eyelids and nictitating membrane) and the iris, and a moderate increase in the blood flow to the ciliary processes, but no increase in the choroidal blood flow. In the denervated eyes the increase in blood flow to the surface structures was almost completely abolished, and there was also a tendency toward less increase in blood flow in the anterior uvea. CONCLUSIONS: These results indicate that PGF2 alpha-induced ocular surface hyperemia, at least at the early stage, is mediated to a large extent by sensory nerves.

Animals↗
PubMed1996

Study of choroidal blood flow by comparison of SLO fluorescein angiography and microspheres.

Choroidal hemodynamics estimated with parameters describing the dye build-up curves obtained with video fluorescein angiography, were compared with a classical regional blood flow measurement: radioactively labelled microspheres. Video fluorescein angiograms (Rodenstock's SLO 101) and microspheres blood flow measurements were made in 13 anaesthetized pigmented rabbits. Ocular perfusion pressures were varied from 60 to 15 mmHg by changing the intraocular pressure. The angiographically derived dye build-up curves were described by means of an exponential model. One of the model parameters is the time constant tau theoretically reflecting local blood refreshment time. Labelled microspheres act as a non-recirculating blood flow indicator, enabling the estimation of regional blood flows. The relation between choroidal blood flow and perfusion pressure is nearly linear, suggesting the passive nature of choroidal vasculature. There is a significant correlation between tau and microspheres flow (R = 0.67, P < 0.01). According to the rheological model the product of blood flow and tau corresponds to the relevant blood volume. Hence, a function for the volume of the choriocapillaris as a function of perfusion pressure was established. The model parameter tau can be interpreted as the local blood refreshment time. Since the parameter tau, unlike microspheres, can be used clinically, tau may be used to retrieve information on choroidal hemodynamics in clinical practice. Information on the spatial distribution of choroidal hemodynamics is also obtained.

Animals↗
PubMed1996

The prevalence of pain in a disabled population.

An estimated 1.7 million disabled adults (95% CI +/- 74,000), living in private households in Great Britain, reported pain symptoms which severely affected their daily activities. That is, the pain they experienced is so severe, unrelieved and recurring as to limit or prevent their ability to perform ordinary, everyday, activities. They represent 30% of disabled adults suggesting that pain is a substantial cause of disability and a major public health problem. The prevalence of severely limiting pain increased with age declining beyond age 55 though younger disabled adults, and women generally, reported more severe pain symptoms. Pain was associated with disabilities which commonly have a physical origin and directly affect bodily movement, compounding the problems of daily living for this population. Three-quarters of those whose lives were limited by pain said the worst bouts of pain occurred at least once a week; half took analgesic medicine every day. More than nine out of ten disabled people suffering pain had recent contact with primary and community health or hospital services.

Activities of Daily Living↗
PubMed1994

Role of nitric oxide in PGF2 alpha-induced ocular hyperemia.

The effect of nitric oxide synthase inhibition on prostaglandin F2 alpha (PGF2 alpha)-induced ocular hyperemia in the rabbit has been studied. PGF2 alpha was administered topically as the isopropyl ester (PGF2 alpha-IE) unilaterally, with the other eye serving as a control. The regional blood flow in the eye was determined with radioactively-labelled microspheres in conscious animals. Synthesis of nitric oxide (NO) was blocked by L-NMMA (200 mg kg-1 b.w., i.v.). PGF2 alpha-IE induced marked hyperemia of the surface structures of the eye (conjunctiva, eye lids, nictitating membrane, anterior sclera), as well as increased blood flow of the anterior uvea. L-NMMA blocked the hyperemia of the surface structures but not completely the increase in blood flow of the anterior uvea. PhXA41 (13,14-dihydro-17-phenyl-18,19,20-trinor-PGF2 alpha-isopropyl ester), a selective prostaglandin FP-receptor agonist, had no significant effect on the ocular blood flow. These results indicate that PGF2 alpha causes surface hyperemia of the eye by activating nitric oxide synthase, but this mechanism seems to be only partly involved in the increase in blood flow of the ciliary processes and the iris. The PGF2 alpha-induced ocular hyperemia is unlikely to be mediated by FP receptors.

Amino Acid Oxidoreductases↗
PubMed1993

Phenyl-substituted prostaglandins: potent and selective antiglaucoma agents.

A series of phenyl-substituted analogues of prostaglandin F2 alpha (PGF2 alpha) were prepared and evaluated for ocular hypotensive effect and side effects in different animal models. In addition, the activity of the analogues on FP receptors was studied in vitro. The results were compared with those of PGF2 alpha and its isopropyl ester. The phenyl-substituted PGF2 alpha analogues exhibited good intraocular pressure reducing effect, were more selective, and exhibited a much higher therapeutic index in the eye than PGF2 alpha or its isopropyl ester. The analogues exhibited high activity on FP receptors in a stereoselective manner for the 15 alpha-hydroxyl group.

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↗
PubMed1987

Argon laser therapy of endometriosis: a review of 92 consecutive patients.

The conception rate, relief of pain, and safety of argon laser photocoagulation of endometriosis were evaluated in 92 patients. All patients were treated at the time of diagnosis with the argon laser delivered through a flexible quartz fiber passed through the operating channel of a standard and unmodified laparoscope. The uncorrected pregnancy rate was 34% (19 of 56), with 64% of the pregnancies occurring within 6 months of therapy. The conception rate was slightly greater in women with infertility of 24 months or less and in women without other fertility factors. Ninety-two percent of 50 women with pelvic pain reported a reduction of their pain after treatment. The argon laser is an effective, simple, and safe alternative for the treatment of mild or moderate endometriosis.

Actuarial Analysis↗