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W S Wilson

Publications and source records attributed to W S Wilson.

At least 19 recordsLinked to original sources
PubMed2005

Minimally invasive, direct, real time measurement of drug concentration in the anterior eye.

AIMS: To evaluate a corneal contact lens which effectively turns the anterior chamber of the eye into a cuvette, enabling the concentration of a drug to be measured using absorption spectroscopy. METHODS: A hand held contact lens incorporating optical fibres connected to a spectrograph enabled a beam of light to be directed in, across, and out of the anterior chamber. The device was used to follow the time course of drug concentration in the anterior chamber of rabbit (sedated) and humans, using topical brimonidine or fluorescein (with or without local anaesthesia). Absorbance measurements were taken for a 5-25 second period, repeated every 30 minutes. Drug concentrations were compared using absorbance peak height. RESULTS: Corneal absorption starts to rise rapidly at wavelengths shorter than 315 nm. The light path within the anterior chamber is 6.9 mm (rabbit) and 5.8 mm (human), the absorbance measured also includes a corneal component. Application of fluorescein (three drops of 2% solution) in rabbit allowed detection, 60 minutes later, of a large absorbance peak at 490 nm. In the human eye, the device could not measure fluorescein (applied as in rabbit), but clearly detected brimonidine for 3 hours following topical application of 0.6 mg. Modification of the device to measure fluorescence resulted in the detection of 5.3 nM fluorescein in the ex vivo rabbit eye, an increase in sensitivity of two orders of magnitude over the absorption measurements. CONCLUSION: This device has the potential to allow repeated measurements of drug concentrations in the anterior eye provided the drug has suitable absorption or fluorescence characteristics.

Absorption↗
PubMed2001

Dominant role of an endothelium-derived hyperpolarizing factor (EDHF)-like vasodilator in the ciliary vascular bed of the bovine isolated perfused eye.

1. The roles of the endothelium-derived nitric oxide, prostacyclin and endothelium-derived hyperpolarizing factor (EDHF) in mediating vasodilator responses to acetylcholine and bradykinin were assessed in the ciliary vascular bed of the bovine isolated perfused eye preparation. 2. Vasodilatation to acetylcholine or bradykinin was unaffected by the nitric oxide synthase inhibitor, L-NAME (100 microM), or the cyclo-oxygenase inhibitor, flurbiprofen (30 microM), but was virtually abolished following treatment with a high concentration of KCl (30 mM), or by damaging the endothelium with the detergent, CHAPS (0.3%, 2 min). 3. Acetylcholine-induced vasodilatation was unaffected by glibenclamide (10 microM), an inhibitor of ATP-sensitive K(+) channels (K(+)(ATP)), but was significantly attenuated by TEA (10 mM), a non-selective inhibitor of K(+) channels. 4. The small conductance calcium-sensitive K(+) channel (SK(+)(Ca)) inhibitor, apamin (100 nM), and the large conductance calcium-sensitive K(+) channel (BK(+)(Ca)) inhibitor, iberiotoxin (50 nM), had no significant effect on acetylcholine-induced vasodilatation. In contrast, the intermediate (IK(+)(Ca))/large conductance calcium-sensitive K(+) channel inhibitor, charybdotoxin (50 nM), powerfully blocked these vasodilator responses, and uncovered a vasoconstrictor response. 5. The combination of apamin (100 nM) with a sub-threshold concentration of charybdotoxin (10 nM) significantly attenuated acetylcholine-induced vasodilatation, but the combination of apamin (100 nM) with iberiotoxin (50 nM) had no effect. 6. In conclusion, blockade by a high concentration of KCl, by charybdotoxin, or by the combination of apamin with a sub-threshold concentration of charybdotoxin, strongly suggests that vasodilatation in the bovine isolated perfused eye is mediated by an EDHF.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2001

Intraocular pressure and vascular effects of sodium azide in bovine perfused eye.

The effects of the nitrovasodilator, sodium azide, on intraocular pressure (IOP) and ciliary vascular tone were compared. IOP was measured in the bovine isolated eye that was perfused via the ciliary artery. Separately, vasodilator effects were assessed after raising the vascular tone using noradrenaline (10 microM). Aqueous humor formation (AHF) rate was estimated by a fluorescein dilution method. Cyclic GMP in the ciliary processes was measured by radioimmunoassay. When compared with controls, sodium azide (10 nmole bolus dose) was found to lower IOP (2.2 +/- 0.3 mm Hg; P < 0.01) via a reduction in AHF (12.19 +/- 0.26 microl/min to 6.36 +/- 0.53 microl/min; P < 0.001). Azide (1 micromole) also reduced ciliary vascular resistance (81.0 +/- 5.5%; P < 0.01). However, the drug was 20x more potent as an ocular hypotensive than as a vasodilator (ED50 0.28 nmole on IOP, 5.55 nmole on vascular effect). Azide (10 nmole) also increased levels of ciliary cyclic GMP (127 +/- 17 fmol/mg protein to 233 +/- 27 fmol/mg protein; P < 0.01). The IOP-lowering effect of azide does not appear to depend on its ability to activate guanylyl cyclase (GC) in vascular smooth muscle, but rather is likely a consequence of direct activation of ciliary epithelial GC.

Animals↗
PubMed1999

Atriopeptin, sodium azide and cyclic GMP reduce secretion of aqueous humour and inhibit intracellular calcium release in bovine cultured ciliary epithelium.

This study examined the involvement of cyclic GMP, protein kinase G and intracellular Ca2+ movements in the modulation of aqueous humour formation. Using the bovine arterially-perfused eye preparation, drug effects on intraocular pressure and aqueous humour formation rate were measured by manometry and fluorescein dilution, respectively. Drug effects on intracellular [Ca2+] were determined by fura-2 fluorescence ratio technique in nontransformed, cultured ciliary epithelium. Intra-arterial injection of atriopeptin (50 pmol) or sodium azide (10 nmol) produced significant reduction in aqueous humour formation (>38%). This was blocked by selective inhibition (KT-5823) of protein kinase G, but not by selective inhibition (KT-5720) of protein kinase A. Reductions of intraocular pressure produced by atriopeptin or azide were almost completely blocked by KT-5823. ATP (100 microM) caused rapid, transient increase in intracellular Ca2+ followed by a slow decline and prolonged plateau. This response showed concentration-dependent inhibition by atriopeptin, azide or 8-bromo cyclic GMP, and this inhibition of the rapid (peak) Ca2+ increase was enhanced by zaprinast (100 microM; phosphodiesterase inhibitor). KT-5823 blocked the suppression of the peak Ca2+ response but not suppression of the plateau. Arterial perfusion of ATP (0.1-100 microM) produced a concentration-dependent decrease in aqueous humour formation. Aqueous humour formation in the bovine eye can be manipulated through cyclic GMP, operating via protein kinase G. Close parallels appear when Ca2+ movements are modified by similar manipulations of cyclic GMP, suggesting that Ca2+ transients may play an important role in aqueous humour formation and that interplay occurs between cyclic GMP and Ca2+.

Adenosine Triphosphate↗
PubMed1999

Effect of oral administration of vitamin C on human aqueous humor ascorbate concentration.

AIM: To study oral administration of vitamin C on human aqueous humour ascorbate concentration. METHODS: High performance liquid chromatography (HPLC) coupled with electrochemical detector (ECD) was used. The effect of oral administration of various doses of ascorbic acid, 0 (control), 1.0, 1.5, 2.0, 3.0, and 5.0 g, on its concentration in aqueous humour, obtained from volunteer cataract patients was studied. RESULTS: The concentration of ascorbic acid in aqueous humour of control group (without administration of vitamin-C tablet or drug containing ascorbic acid was (254 +/- 119) mg.L-1. This study revealed that the administration of 2.0 g of ascorbic acid saturate the aqueous humour and further increase in the dose (3.0 g and 5.0 g) did not increase its concentration in aqueous humour, although its concentration was increased in plasma. CONCLUSION: Oral administration of 2.0 g of Vc is sufficient to saturate the aqueous humour where it may be helpful in controlling the intra-ocular pressure.

Aged↗
PubMed1997

Mobilisation of intracellular calcium by P2Y2 receptors in cultured, non-transformed bovine ciliary epithelial cells.

PURPOSE: To examine extracellular ATP for its ability to mobilise intracellular calcium in bovine ciliary epithelial cells; to establish and characterise P2Y2 receptor-mediated signal transduction in this tissue. METHODS: Bovine ciliary epithelial cells were isolated and cultured until confluence. The cells were reseeded on sterile coverslips and grown to obtain monolayers, then loaded with fura-2. Fluorescence was measured by a computer-controlled spectrofluorimeter and values calculated for intracellular calcium concentration. ATP, its analogues and other drugs were tested for their ability to mobilise intracellular calcium by adding them to the bathing solution. RESULTS: Basal cytosolic calcium in bovine ciliary epithelium was 138.4 +/- 0.8 nM (n = 274). In the presence of extracellular Ca2+, ATP, UTP or ADP induced a transient dose-dependent increase in intracellular calcium (maximum approx. 400%), which declined rapidly. The agonist potency order was UTP = ATP > ADP > AMP. Adenosine, alpha, beta-methylene-ATP and 2-methylthio-ATP were ineffective in mobilising intracellular calcium, as were adrenaline, noradrenaline, acetylcholine and carbachol. The response to ATP and UTP remained, in the absence of extracellular calcium or the presence of nickel. Desensitisation of the calcium response by repeated exposure to ATP was augmented by phorbol-myristate-acetate and abolished by staurosporine. The ATP response was abolished by preincubation with pertussis toxin. Microfluorimetric measurements on single cells established that both pigmented and non-pigmented epithelia responded to ATP or UTP similarly. CONCLUSIONS: In the bovine ciliary epithelium, ATP stimulates P2Y2 receptors coupled to a pertussis toxin-sensitive G protein. The results also suggest that this receptor activates phospholipase C, leading to mobilisation of calcium from intracellular stores.

Adenosine Diphosphate↗
PubMed1997

Atriopeptin lowers aqueous humor formation and intraocular pressure and elevates ciliary cyclic GMP but lacks uveal vascular effects in the bovine perfused eye.

The effects of atriopeptin (AP) on intraocular pressure (IOP), aqueous humor formation (AHF) and ciliary cyclic GMP in bovine eyes perfused in vitro through a ciliary artery were investigated. AHF was monitored fluorophotometrically by perfusing the anterior chamber with Bárány's mock aqueous humor containing fluorescein. To study the effect of AP on cyclic GMP synthesis, eyes were injected with an intra-arterial bolus of AP prior to dissection of the ciliary processes. For comparison, individual ciliary processes, or isolated ciliary epithelial cells were incubated with AP. Cyclic GMP was extracted by homogenization, aqueous partition and column chromatography, and measured by radioimmunoassay (RIA). Decreases in IOP or AHF were seen approximately 15 min after the injection of AP and persisted throughout a 60-80 min perfusion. Arterial perfusion pressure was not significantly altered by AP, even when vascular tone was raised by adding noradrenaline to the perfusate. In whole eyes, ciliary cyclic GMP increased in response to AP. Cyclic GMP in isolated ciliary processes, or cultured ciliary epithelial cells incubated with AP also increased. We conclude that the decrease in IOP in the bovine eye by AP is due to a reduction in AHF, which is independent of any vascular effect. Ciliary cyclic GMP may be the intracellular mediator involved.

Adrenergic alpha-Agonists↗
PubMed1995

The effects of antidepressant drugs on salivary flow and content of sodium and potassium ions in human parotid saliva.

Stimulated parotid saliva was collected, using the Carlson-Crittenden cup, from normal controls and patients on antidepressant drugs. The saliva from patients using amitriptyline, dothiepin (tricyclics), fluoxetine and paroxetine (selective serotonin re-uptake inhibitors; SSRI) was analysed for flow rate, [Na+] and [K+], and was compared with that from unmedicated, non-depressed volunteers for all variables. The tricyclic antidepressants produced a significant reduction in flow (amitriptyline, p < 0.01; dothiepin, p < 0.05), and consequent decrease in [Na+] and increase in [K+]. These effects were presumably due to muscarinic receptor blockade. The SSRIs produced no significant change in these variables. A prospective study of dothiepin in non-depressed patients confirmed that it decreases stimulated parotid flow. This finding also suggested that depression itself contributed little to the oral dryness observed in and reported by the depressed patients. The patients' subjective rating of oral dryness related well to a reduction in stimulated flow. This applied to those taking either tricyclics or SSRI, both showing a reduced flow rate relative to control (p < 0.001 and p < 0.05, respectively). This amounted to a 58% reduction in flow rate in the tricyclic group. The data suggest that measurement of stimulated parotid salivary flow is a reliable indicator of drug-induced oral dryness.

Adult↗
PubMed1995

Drug effects on intraocular pressure and vascular flow in the bovine perfused eye using radiolabelled microspheres.

A novel technique is described in which the effect of the beta-adrenoceptor antagonists timolol and carteolol, and the vasodilators sodium nitroprusside (SNP) and verapamil on intraocular pressure (IOP) and the distribution of ocular flow in the bovine arterially perfused eye is investigated using radiolabelled microspheres. At maximum IOP-reducing dose timolol was found to significantly reduce perfusion in the choroid and, at higher dose, it was found to significantly reduce perfusion in the iris. By contrast, a maximal IOP-reducing dose of carteolol markedly reduced perfusion in the iris, ciliary body and choroid. Vasoconstriction induced by carteolol was not inhibited by the alpha-antagonist phentolamine. Against a background of vascular tone induced by noradrenaline, SNP and verapamil were found to significantly increase perfusion in the iris, ciliary body and choroid. The effects of these drugs upon the vasculature of the bovine perfused eye are varied and complex and may not bear a direct relationship to their ocular hypotensive effect.

Adrenergic beta-Antagonists↗
PubMed1995

Effects of timolol, terbutaline and forskolin on IOP, aqueous humour formation and ciliary cyclic AMP levels in the bovine eye.

We have studied the effects of terbutaline, timolol, forskolin and 8-bromo cyclic AMP on aqueous humour formation, intraocular pressure and on ciliary epithelial cyclic AMP levels, either in presence or in absence of IBMX, using the bovine isolated arterially perfused eye, excised ciliary processes and cultured ciliary epithelium. Both terbutaline, a beta-adrenoceptor agonist, and timolol, a beta-adrenoceptor antagonist, caused significant reduction in aqueous humour formation and intraocular pressure but produced no effect on ciliary epithelial cyclic AMP content in the absence of IBMX. Even a three times higher dose of terbutaline was entirely ineffective in producing any effect on ciliary cyclic AMP in the perfused eye. On the other hand, terbutaline at the IOP-reducing dose, produced a significant increase in cyclic AMP when injected after 30 min perfusion with IBMX. Incubation of excised ciliary processes or cultured ciliary epithelial cells with terbutaline (10(-6) to 10(-4) M) produced concentration-dependent increases in cyclic AMP, in both tissues, even in the absence of IBMX. Forskolin, which stimulates cyclic AMP synthesis without interacting with cell surface receptors, was found to produce highly significant increases in ciliary cyclic AMP content both in presence and in absence of IBMX but had no effect on aqueous humour formation in the isolated eye. IBMX perfused at concentrations of 1 mM or 10 microM had no effect on basal levels of ciliary cyclic AMP but the 1 mM concentration produced a marked and significant reduction in IOP. Direct application of 8-bromo cyclic AMP, a cell permeable analogue, more resistant to hydrolysis by phosphodiesterases, had also no effect on aqueous humour formation in the perfused eye. It is concluded that in the bovine arterially perfused eye, the correlation between the aqueous humour formation rate and ciliary epithelial cyclic AMP content is unclear.

1-Methyl-3-isobutylxanthine↗
PubMed1994

Late results of percutaneous transluminal coronary angioplasty of two or more major native coronary arteries.

Of 613 consecutive patients with multivessel coronary artery disease (CAD) undergoing revascularization, 521 patients (85%) underwent primary management with percutaneous transluminal coronary angioplasty (PTCA). To examine long-term outcome in a series of patients often referred for coronary artery bypass graft (CABG) surgery, all patients undergoing multivessel dilations were identified for late follow-up analysis (n = 161). Mean age was 65 years; 54 patients (34%) were women. Four hundred fifty-five of 502 lesions (90.6%) were successfully dilated. Major in-hospital procedural complications occurred in 6 patients (3.7%), including death in 3 (1.9%), nonfatal Q-wave myocardial infarction in 2 (1.2%), and CABG in 1 (0.6%). Final follow-up data were available in 159 patients (99%) at a mean of 39 +/- 18 months. Including in-hospital events, actuarial 3-year survival was 93%, and 3-year infarct-free survival was 90%. At final follow-up, 143 of 146 patients alive (98%) were angina free. Crossover to CABG was required in 25 patients (16%). Repeat PTCA was performed in 67 patients (42%) (mean 1.7 PTCAs/patient, range 1 to 7). PTCA is an effective therapeutic alternative in the management of most patients with multivessel CAD requiring revascularization. A strategy using multiple repeated PTCA procedures when necessary results in prolonged infarct-free survival, with long-term freedom from angina and limited crossover to CABG.

Aged↗
PubMed1993

The bovine arterially-perfused eye: an in vitro method for the study of drug mechanisms on IOP, aqueous humour formation and uveal vasculature.

A method is reported in which the isolated bovine eye is perfused through a long posterior ciliary artery with buffered physiological saline, to provide simultaneous monitoring of drug effects on intraocular pressure (IOP), vascular resistance and the condition of the blood-aqueous barrier. With perfusion under constant pressure of 45 mm Hg, perfusate flows at 1.64 +/- 0.12 ml.min-1 (mean +/- SEM) and IOP is 7.26 +/- 0.16 mm Hg. Applying a constant flow rate of 2.25 ml.min-1, IOP averages 10.19 +/- 0.32 mm Hg and in both cases this can be maintained for around 2h. Increasing the perfusion flow rate from 1.5 to 3.5 ml.min-1 produces a 76% rise in perfusion pressure but IOP increases only insignificantly (< 10%). The inclusion in the perfusion fluid of dextran and albumin to maintain oncotic pressure similar to that of plasma makes no difference to the IOP achieved and does not affect the leakiness of the barrier. The preparation shows a net consumption of oxygen, supporting the hypothesis that the aqueous humour formed is secreted by active transport processes. Timolol (in bolus doses of 1-300 nmol) injected into the perfusing fluid is shown to induce a dose-dependent fall in IOP within 5 min, reaching a steady state within 40 min. Timolol, however, causes no significant change in vascular resistance, whether this is measured as perfusion flow rate under constant pressure or as perfusion pressure at constant flow rate, nor does it alter the permeability of the barrier. Other beta-blockers such as oxprenolol and betaxolol also induce dose-dependent decreases in IOP. By applying a fluorescein dilution technique, it is found that the aqueous formation rate (K(out) = 0.0046 min-1, or 12.9 microliters.min-1) is also reduced by timolol and, in a dose-dependent manner, by the new carbonic anhydrase inhibitor, MK-927. The bovine perfused eye offers a useful method for studying the mechanisms of action of drugs on IOP and aqueous humour formation, in isolation from the complicating influences of the CNS and the cardiovascular system and without the necessity to kill animals for experimental purposes.

Adrenergic beta-Antagonists↗
PubMed1990

Inhibition by indomethacin of the increased facility of outflow induced by adrenaline.

Topical adrenaline lowers intraocular pressure (IOP) in the rabbit largely due to an increase in facility of outflow of aqueous humour. This paper studies the inhibition by indomethacin or piroxicam of the adrenaline-induced rise in facility of outflow. Topical indomethacin is shown to reduce the acute IOP changes induced by adrenaline in conscious rabbits; both the early rise and the prolonged fall in pressure were inhibited. In anaesthetized rabbits, indomethacin pretreatment prevented the large rise in facility of outflow which normally follows topical adrenaline. Indomethacin did not block the mydriasis induced by adrenaline, nor did it significantly alter aqueous humour protein levels. Piroxicam, a cyclo-oxygenase inhibitor which, unlike indomethacin, does not block Ca2+ movements in some tissues, also blocked the adrenaline-induced rise in facility of outflow, suggesting that this increased facility depends on cyclo-oxygenase and not on Ca2+ movements. Verapamil, a drug which blocks Ca2+ channels, was shown to inhibit the brief ocular hypertensive effect of adrenaline in the conscious rabbit, but to leave the hypotensive phase unchanged. It is concluded that the hypotensive mechanism of adrenaline may depend on synthesis of a prostaglandin, since inhibition of the adrenaline-induced rise in facility is achieved by inhibitors of cyclooxygenase. Despite previous reports that a prostaglandin may be responsible for the brief hypertensive phase, the present evidence suggests that Ca2+ movements may be involved, perhaps in activation of the extraocular muscles.

Animals↗
PubMed1986

Regional distribution of acetylcholine and associated enzymes and their regeneration in corneal epithelium.

Acetylcholine and choline acetyltransferase are found in high concentrations in the corneal epithelium of most species, although their function is unknown. We have measured the levels of each in different regions of the rabbit cornea and found that both are much more abundant in central than in peripheral cornea or conjunctival epithelium. Following abrasion of the cornea, epithelial cells from the surrounding cornea or conjunctiva move over rapidly and regenerate. We have assayed choline acetyltransferase and total protein after complete or incomplete abrasion of the corneal epithelium. Acetylcholine-synthesizing activity was not detectable in the regenerating cells until 14-21 days later (depending on the degree of abrasion). Like glycogen and oxidative enzymes, which are also much more abundant in corneal than conjunctival epithelium, choline acetyltransferase regeneration is complete about 28 days after abrasion. In contrast with acetylcholine and choline acetyltransferase, cholinesterase activity is low and its distribution relatively uniform over cornea and conjunctiva. The high ratio of acetylcholine synthesis to cholinesterase activity suggests that acetylcholine released from the corneal epithelium would be able to diffuse to more distant structures within the eye.

Acetylcholine↗
PubMed1983

Iris delay, a neglected factor in aqueous humour dynamics. A study in the cynomolgus monkey (Macaca fascicularis).

A method is described, intended for measuring the rate--over a short period of time--of aqueous humour outflow in non-anaesthetized primates. [125I] and [131I]-o-iodohippurates were infused s.c. at an interval into the conscious Cynomolgus monkey so as to give two time-displaced plasma curves. The isotope concentrations were measured in plasma by frequent sampling over the first 1-2 hr and in aqueous humour at the end of the experiment under brief anaesthesia. The coefficient of diffusion (kdiff) between plasma and aqueous, and the coefficient of loss (kout) out of the anterior chamber were calculated by making the usual assumptions about aqueous dynamics. Topical treatment of one eye with timolol consistently reduced kout, as expected, but many control values for kout were lower than expected or (impossibly) negative. Examination of the data reveals a likely source of error emanating from the commonly made assumption that diffusion of marker substance (in our case iodohippurate) from plasma to aqueous humour is proportional to the instantaneous concentration difference between plasma and aqueous. In fact, there may be a delay of several minutes during which the substance negotiates the stroma and anterior boundary layer of the iris. Evidence is presented that variation between and within individual monkeys may stem from the highly variable anatomy of the iris and from changes in sympathetic tone operating on the blood vessels and perhaps the anterior boundary layer.

Animals↗