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Biomedical subjects

C A Paterson

Publications and source records attributed to C A Paterson.

At least 91 records · Page 5Linked to original sources
PubMed1986

A protective role for ascorbic acid during inflammatory episodes in the eye.

During an experimentally induced inflammatory response in the rabbit eye, the decrease in the ascorbic acid concentration within the aqueous humor corresponded, in large part, to the infiltration of leukocytes into this ocular fluid. Additional in vitro studies demonstrated that activated leukocytes reacted with ascorbic acid, diminishing the concentration of this vitamin in the surrounding medium. We suggest that the very high concentrations of ascorbic acid found in the aqueous humor of a number of species affords extracellular protection for the ocular tissues against oxygen radicals and metabolites released by infiltrating leukocytes during ocular inflammation.

Animals↗
PubMed1986

Modulation of corneal lipoxygenase by ascorbic acid.

We have examined the influence of ascorbic acid on the generation of lipoxygenase products by the rabbit cornea, an avascular tissue which is continuously bathed by high concentrations of ascorbic acid present within the aqueous humor of the eye. Corneal homogenates were incubated with [14C]arachidonic acid and the resulting metabolites separated by thin-layer chromatography. The metabolites were then quantified by liquid scintillation counting techniques. The biosynthesis of the major lipoxygenase product formed by the cornea, 12-HETE, was significantly inhibited by physiological concentrations of ascorbic acid; PGE2 formation by the cornea was not altered in the presence of ascorbic acid. Furthermore, ascorbic acid inhibited the formation of 12-HETE in the presence of catalase, indicating that hydrogen peroxide generated by ascorbate was not responsible for diminishing the lipoxygenase activity of the cornea. However, high concentrations of hydrogen peroxide (10(-4) M) did inhibit the formation of 12-HETE by the corneal homogenates. Another antioxidant, 2,6-dichlorophenol-indophenol (10 micrograms ml-1), also inhibited the formation of 12-HETE by the cornea. Therefore, it appears that the inhibition of corneal lipoxygenase by ascorbic acid could be related to the antioxidant properties of this vitamin. These studies suggest that ascorbic acid within the aqueous humor might modulate lipoxygenase activity within the cornea.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1985

Ocular blood flow after experimental alkali burns and prostaglandin administration.

Ocular blood flow was determined using radioactive strontium 85 microspheres after an alkali (sodium hydroxide [NaOH]) burn to the eye. With 20 microL of NaOH, blood flow was significantly increased in the iris, ciliary processes, and choroid from two through four hours. This correlated well with the sustained increase in intraocular pressure (IOP) seen after a 20-microL burn. A 50-microL burn increased blood flow at one hour, but it returned toward normal levels beyond two hours. In general terms, there appeared to be a meaningful correlation between IOP changes and altered blood flow following ocular alkali burns. The blood flow changes paralleled those occurring after the topical application of prostaglandins and supported the concept that ocular blood flow dynamics are mediated by prostaglandins.

Alkalies↗
PubMed1985

Characteristics of 45Ca uptake by the rabbit lens.

Lens 45Ca uptake was shown to increase when the external calcium concentration was less than 1 mM, suggesting that calcium ions themselves are able to interact with lens membranes in a way that influences the mechanism of calcium permeability. Strontium ions, added to a calcium-deficient bathing solution, were shown to attenuate the increased 45Ca uptake by the lens. There was no evidence for extracellular binding of calcium. Lens membrane permeability to calcium appeared not to be voltage-dependent since 45Ca uptake was not affected when the lens was depolarized by high potassium solutions. Calcium channel blockers were shown not to reduce the increased calcium leak resulting from exposure of the lens to a calcium-deficient medium.

Animals↗
PubMed1985

Generation of lipoxygenase products in the avascular tissues of the eye.

We have examined the ability of the avascular cornea and lens to generate lipoxygenase products from arachidonic acid. The cornea and lens were obtained from rabbit and frog eyes, and their ability to metabolize exogenous [14C]-arachidonic acid determined in vitro. The cornea of rabbits and frogs formed lipoxygenase products from arachidonic acid. Both rabbit and frog corneas were found to generate considerable quantities of 12-HETE, although other lipoxygenase products were also produced. In contrast, no lipoxygenase products were detected following incubations of rabbit or frog lens with arachidonic acid. Thus, the cornea and lens, the two avascular tissues in the eye, exhibit marked differences in their ability to metabolize arachidonic acid via lipoxygenase enzymes.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1985

Interaction between ophthalmic drugs and intraocular lenses.

We evaluated the in vitro interaction between commonly used ophthalmic drugs and a series of intraocular lenses to determine if the lenses could act as a drug reservoir in the eye. Lenses examined included anterior and posterior chamber lenses as well as iris plane lenses. Assessment of lens uptake was made by immersing the lens for nine days in a radioactive drug solution with a concentration equal to that found in the anterior chamber one hour after drug administration. No evidence of drug uptake was found for any lens immersed in epinephrine, norepinephrine, dexamethasone, or chloramphenicol.

Absorption↗
PubMed1985

Examination of lens calcium balance using 45Ca uptake studies.

The utility of 45Ca efflux studies to examine lens calcium balance is limited because of the dominant contribution of efflux from the extracellular space of the lens. On the other hand, examination of lens 45Ca uptake characteristics can generate valuable information regarding the mechanism by which calcium is largely restricted from the intracellular compartment. Such studies have enabled us to demonstrate that the access of calcium to the intracellular compartment is dependent to some extent upon the concentration of calcium in the extracellular environment. Additionally, experimental evidence speaks against extracellular binding of calcium. Finally, lens membrane permeability to calcium appears to be independent of membrane voltage.

Animals↗
PubMed1985

The effect of sodium citrate on the stimulation of polymorphonuclear leukocytes.

Topical administration of sodium citrate reduces the incidence of corneal ulceration and perforation following an alkali burn to the eye. The specific mechanism by which sodium citrate prevents the ulceration is not understood, although citrate does inhibit the infiltration of polymorphonuclear leukocytes (PMNs) into the cornea following an alkali burn. In the present study, the effects of sodium citrate and another calcium chelator, ethylene glycol bis (beta-aminoethylether)-N,N'tetraacetic acid (EGTA), upon PMN oxygen consumption and lysosomal enzyme release were determined. Oxygen consumption was measured polarographically using a Clark-type oxygen electrode, and lysosomal enzyme release was determined by intra- and extra-cellular measurements of myeloperoxidase activity. Opsonized zymosan and N-formylmethionylleucylphenylalanine (FMLP) were used to stimulate neutrophil oxygen consumption and lysosomal release. Both sodium citrate and EGTA inhibited PMN oxygen consumption and lysosomal enzyme release in response to opsonized zymosan. In contrast, neither sodium citrate nor EGTA reduced PMN oxygen consumption or lysosomal enzyme release in response to FMLP. Therefore, the ability of sodium citrate (and EGTA) to inhibit PMN stimulation is dependent upon the choice of stimulus. Until the inflammatory mediators involved in the ulcerative process following an alkali burn to the eye are delineated, the impact of sodium citrate upon PMN stimulation in vivo cannot be resolved.

Burns, Chemical↗
PubMed1984

Anomalous effects of anti-inflammatory corticosteroids in endotoxin-induced ocular inflammation.

The effect of anti-inflammatory corticosteroids upon leukocyte infiltration was investigated in vivo, using the eye as an experimental model. The inflammatory response was induced by injecting bacterial endotoxin into the vitreous body of the albino rabbit eye. Polymorphonuclear leukocyte (PMN) infiltration into the aqueous humor was quantified by counting cells directly, whereas accumulation of leukocytes in the ocular tissues was determined by measuring myeloperoxidase (MPO) activity. Systemically administered corticosteroids inhibited plasma protein leakage and PMN infiltration into the aqueous humor, but, anomalously, increased MPO activity and hence the number of PMNs in the ciliary body. These findings were confirmed qualitatively by histology. However, the clinical manifestations of the inflammatory responses were almost totally suppressed by the corticosteroids. We suggest that the inhibitory effect of corticosteroids on PMN infiltration into the aqueous humor, and possibly inflammatory exudates in general, represents the suppression of inflammatory cell activity in a manner which is unrelated to a direct effect on leukocyte movement.

Adrenal Cortex Hormones↗
PubMed1984

Ascorbic acid inhibits the activity of polymorphonuclear leukocytes in inflamed ocular tissues.

Myeloperoxidase (MPO) is present at high levels in polymorphonuclear leukocytes (PMNs) and has been used as a marker to quantify the accumulation of PMNs in inflamed tissues. MPO activity in inflamed ocular tissues was inhibited by aspirates of aqueous humor. This inhibition could be duplicated by the addition of ascorbic acid at concentrations equivalent to those present in the aliquots of aqueous humor. Similarly, aqueous humor and ascorbic acid inhibited MPO from isolated rabbit leukocytes. Therefore, ascorbic acid appears to inhibit the functional activity of the peroxidase in PMNs, thus preventing potential tissue damage by this enzyme when released during leukocyte degranulation in inflammation. Ascorbic acid might fulfill a role as an endogenous anti-inflammatory agent in the eye.

Animals↗
PubMed1984

Characteristics of polymorphonuclear leukocyte infiltration into the alkali burned eye and the influence of sodium citrate.

Polymorphonuclear leukocytes (PMNs) are considered to play a central role in the corneal ulceration process subsequent to an alkali burn. We have described the time course of PMN infiltration into the ocular tissues following an alkali burn. In addition, we examined the effect of sodium citrate upon the accumulation of PMNs in the alkali burned cornea. The accumulation of PMNs into the cornea and iris-ciliary body was quantified by measuring myeloperoxidase (MPO), an enzyme marker for these inflammatory cells. Leukocytes in aqueous humor aspirates and corneal washes were counted directly under a microscope. In the alkali burned cornea, we found an initial transient, yet substantial, infiltration of PMNs, peaking at about 12-24 hr and limited to the peripheral cornea; this subsided by about 72 hr. By 14 days, the MPO activity, and hence the number of leukocytes, had risen again, and by 21 days the level had increased by several fold. Qualitatively similar biphasic patterns of leukocyte infiltration were observed in the iris-ciliary body and aqueous humor. Leukocyte numbers in corneal washes only increased between 4-24 hr following the alkali burn. The exceptionally high degree of leukocyte infiltration into the cornea at 21 days corresponded with the presence of ulceration. Topical administration of sodium citrate (10%) inhibited the early and late phase of PMN accumulation in the alkali burned cornea, i.e. at 24 hr (-63%) and 21 days (-92%). The inhibition of PMN infiltration by sodium citrate correlates with the reduced corneal ulceration observed following treatment with this compound.

Animals↗
PubMed1984

PMN accumulation in aqueous humor and iris-ciliary body during intraocular inflammation.

The accumulation of polymorphonuclear leukocytes (PMNs) was determined in the aqueous humor and iris-ciliary body following an intravitreal injection of endotoxin in the albino rabbit. PMN accumulation in the iris-ciliary body was quantified by measuring myeloperoxidase (MPO) activity in homogenates of this tissue. Leukocyte appearance in the aqueous humor was determined by counting the number of PMNs in diluted aspirates of aqueous humor and also by measuring MPO activity in the same aspirates. Twenty-four hours following an intravitreal injection of endotoxin, there was marked vasodilatation in the iris, breakdown of the blood-aqueous barrier, and infiltration of PMNs into the aqueous humor. There was, however, no correlation between MPO activity in the iris-ciliary body and the number of PMNs or the MPO activity in the aqueous humor. Furthermore, the number of PMNs in the aqueous humor did not increase with increasing amounts of intravitreally injected endotoxin, whereas MPO activity in the iris-ciliary body increased in a dose-dependent manner. The results of this study suggest that quantification of leukocytes in the aqueous humor does not represent a meaningful index of intraocular inflammation.

Animals↗
PubMed1983

Chlorpromazine effects upon rabbit lens water and electrolyte balance.

Chlorpromazine (CPZ) concentrations of 5 x 10(-5)M or greater were found to disrupt lens electrolyte and water balance significantly. Lens sodium and calcium levels increased while potassium decreased. These changes were accompanied by water accumulation. Such effects of CPZ were not dependent upon exposure to ultraviolet light. Electrical measurements revealed that CPZ induced depolarization of the lens potential but little change of overall lens conductance. 86Rb efflux from the lens was unaltered by a 1 hr exposure to CPZ. The active sodium pump in the lens was inhibited by CPZ, as evidenced by a reduction in Na- K-ATPase activity.

Animals↗
PubMed1983

Lens cation transport and permeability changes following exposure to hydrogen peroxide.

Exposure of the rabbit lens, in vitro, to 10(-3) M-hydrogen peroxide resulted in an increase of the lens sodium, calcium and water content together with a decrease of the lens potassium content. No such changes were observed in the presence of 10(-4) or 10(-5) M-hydrogen peroxide. 10(-3) M-hydrogen peroxide was observed to diminish 86Rb uptake by 32% and to reduce the lens Na+-, K+-ATPase activity by 37%. The lens potential remained ouabain-sensitive after peroxide treatment. These findings suggest that only partial inhibition of the lens sodium pump takes place in the presence of 10(-3) M-hydrogen peroxide. Lens depolarization, increased lens conductance and an increase rate of 86Rb efflux were also observed upon exposure of the lens to 10(-3) M-hydrogen peroxide. Such alterations of 86Rb efflux and electrophysiological parameters indicate that hydrogen peroxide changes the passive permeability of lens membranes.

Animals↗
PubMed1983

Na,K-ATPase in simulated eye bank and cryoextracted rabbit lenses, and human eye bank lenses and cataracts.

In the rabbit, cryoextraction of the lens and subsequent storage in Tyrode's solution did not alter the Na,K-ATPase activity from that determined in immediately excised rabbit lenses. Similarly, the procedures employed with the rabbit eye to simulate collection and storage of normal human eyes (eye banking) had no effect upon the Na,K-ATPase activity of the lens. These results permitted the investigation of human lenses with the knowledge that measured Na,K-ATPase activity had not been altered grossly by any manipulation procedures. Analysis of Na,K-ATPase activity in 44 eye bank lenses, 14 primary nuclear cataracts, 11 primary cortical cataracts, 18 primary posterior subcapsular cataracts, and 31 mixed cataracts revealed no significant difference in the enzyme activity between these groups. Similarly, there was no correlation between electrolyte levels and Na,K-ATPase in a further 18 mixed cataracts. It is concluded that, despite an often pronounced electrolyte imbalance, human cataract can develop without significant alteration in Na,K-ATPase activity.

Adenosine Triphosphatases↗
PubMed1982

Studies on calcium regulation in relation to sodium-potassium balance in the rabbit lens.

Net changes in the levels of lens calcium, magnesium, sodium, potassium, and water content were determined following exposure in vitro to iodoacetate, ouabain, lanthanum, cyanide, quercetin and cold temperature. The lens calcium content rose following inhibition of lens metabolism but did not change following specific inhibition of the sodium pump. The data revealed that regulation of the lens calcium balance is largely independent of lens sodium and potassium content. A greater increase in lens sodium content upon iodoacetate treatment vs. ouabain treatment is discussed in relation to the elevation of lens calcium.

Animals↗