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Biomedical subjects

K Green

Publications and source records attributed to K Green.

At least 253 records · Page 14Linked to original sources

Penetration of topical indomethacin into phakic and aphakic rabbit eyes.

The penetration of indomethacin labeled with radioactive carbon (14C) into all ocular tissues and fluids was determined at various intervals in both phakic and aphakic rabbit eyes after either single or multiple (every 12 hours for three days) topical application (50 microL) regimens. More indomethacin was found in the vitreous of aphakic eyes compared with phakic eyes after single- or multiple-drop administration. Retinal and choroidal indomethacin concentrations were equal in both phakic and aphakic eyes after either drug regimen and are much greater than those of the vitreous. A pathway other than diffusion through the vitreous exists for the drug to reach these tissues. The concentration of indomethacin reaching the retina and choroid is not sufficient to inhibit prostaglandin formation locally. The concentrations of indomethacin are high enough to inhibit the biotransformation of prostaglandin precursor only in the anterior segment.

Administration, Topical↗

Radial keratotomy. Effect on cornea and aqueous humor physiology in the rabbit.

Radial keratotomy may cause anatomical damage to the rabbit corneal endothelium. To determine if physiological and functional alterations occur, radial keratotomy was performed on rabbit corneas using eight incisions with sparing of a 3.5-mm central pupillary area. Cornea endothelial membrane permeabilities were determined at various times up to ten weeks following the procedure using simultaneous flux determinations of tritiated inulin and dextran labeled with radioactive carbon on isolated corneas. At all times after radial keratotomy, there was no probable physiologically important change in corneal endothelial permeability to either of the labeled compounds. Fluorophotometry performed in a second group of animals at varying intervals following radial keratotomy showed no probable physiologically important change in endothelial fluorescein permeability. Aqueous humor turnover rate was reduced 16% and 29% at one week and nine to ten weeks, respectively, following radial keratotomy.

Animals↗

Multiple-drop study of topically applied 1% delta 9-tetrahydrocannabinol in human eyes.

Twenty-eight male volunteers were given either 1% delta 9-tetrahydrocannabinol (delta 9-THC) or vehicle alone (light mineral oil). They used the medication four times per day for one week. Five volunteers, four of which used vehicle alone, discontinued the study because of burning sensation and lid swelling. In the 23 volunteers who completed the study, there was no difference in intraocular pressure between eyes treated with 1% delta 9-THC and controls.

Administration, Topical↗

Characteristics of bicarbonate, sodium, and chloride fluxes in the rabbit corneal endothelium.

Unidirectional fluxes of bicarbonate, sodium and chloride were measured across the isolated rabbit corneal endothelium. Bicarbonate and sodium fluxes were measured between 13 and 37 degrees C and were found to be temperature-sensitive. Ouabain (10(-6)M), which inhibits endothelial fluid transport, reduced the net bicarbonate flux by 32% but had no significant effect on sodium fluxes. Amiloride (10(-4)M) did not alter sodium transport, but slightly increased the unidirectional bicarbonate fluxes. Sodium fluxes were unchanged in chloride-free and potassium-free Ringer solutions, and net sodium transport was unaffected in the presence of carbonic anhydrase, acetazolamide, or low (5 mM) bicarbonate Ringer, but was reduced by 45% in bicarbonate-free Ringer. A net chloride flux was found in the same direction (stroma to aqueous) as bicarbonate and sodium. This chloride flux (2.18 muEq/cm2/hr) was of the same magnitude as bicarbonate but was sodium-independent. These findings suggest that: (1) like bicarbonate and fluid transport, sodium transport is bicarbonate-dependent, temperature-sensitive, and chloride-independent; (2) sodium transport is not stoichiometrically coupled to bicarbonate; and (3) neither sodium nor bicarbonate transport are coupled to that of chloride.

Acetazolamide↗

Conversion of arachidonic acid in human maternal and neonatal mononuclear leukocytes.

The metabolism of exogenous [1-14C]arachidonic acid in neonatal and maternal peripheral mononuclear leukocytes was studied. Both neonatal and maternal leukocytes converted arachidonic acid to hydroxy acids and to prostaglandin E2, but small amounts of PGF2 alpha and thromboxane B2 were also found. In addition a polar arachidonic acid metabolite with conjugated double bonds was identified in the supernatant from both maternal and neonatal leukocytes. This might be a leukotriene, but further attempts at biochemical characterization are necessary in order to confirm this.

Arachidonic Acid↗

Bullous pemphigoid and multiple autoimmune diseases. Alopecia universalis, bullous pemphigoid, hypothyroidism, rheumatoid arthritis, and neutropenia in one patient.

A 57-year-old white man developed Hashimoto's thyroiditis, bullous pemphigoid, and autoimmune neutropenia during the last year of his life. In addition, he had alopecia universalis since the age of 21 and rheumatoid arthritis since the age of 38. This unique constellation of autoimmune diseases has not been reported previously. Its significance is discussed in relation to the polyglandular failure syndrome and thymoma-related autoimmune disease.

Alopecia↗

Radial keratotomy and corneal permeability in Owl Monkey.

Radial keratotomy was performed on Owl Monkey corneas using 8 incisions with sparing of a 3.5mm central pupillary area. Cornea endothelial membrane permeabilities were determined at 2 days, and 4 weeks, following the procedure using simultaneous flux determinations of 3H-labeled inulin and 14C-labelled dextran. Inulin permeability was increased 27% two days following the procedure, and had returned to levels comparable to the unoperated eye 4 weeks following the procedure. Dextran permeability was unaltered at both 2 days, and 4 weeks, following the procedure. This study has shown that radial keratotomy causes a transient reduction in endothelial barrier function with the production of physiologically significant 'holes' in the membrane in the immediate post-operative period. The relationship of this physiological alteration to ultimate endothelial cell function is, at the present time, unknown.

Animals↗

Intracellular pH and glutathione levels in rabbit corneal endothelium following storage in moist chamber and MK medium.

Rabbit corneas were stored for up to 14 days at 4 C either as the whole eye in a moist chamber or as the isolated cornea in MK medium with HEPES buffer. The intracellular pH, the glutathione content, and its oxidation state were determined in the endothelial cells of fresh and stored tissue. The endothelial pH was found to be unchanged following storage of up to 7 days by either method, but after 14 days the pH rose slightly but statistically significantly in corneas stored by both techniques. The intracellular pH was similar in endothelia of those corneas stored in MK medium and of those stored as the whole eye in a moist chamber, for all time periods studied. The intracellular total and percent oxidized glutathione of the endothelium were increased by 50 and 180%, respectively, following 7 days of moist chamber storage. Over this time period there was a 50-fold increase in total glutathione content of the aqueous humor in the stored eyes. In contrast, corneas stored in MK medium for 7 days maintained intracellular total glutathione at levels similar to those of fresh corneas. A gradual but constant decrease in percent oxidized glutathione was observed with increasing length of storage. In terms of pH and glutathione content, the MK medium provided a much more stable environment for the stored cornea than did the aqueous humor in the stored eye.

Animals↗

Ocular effects of topical administration of delta 9-tetrahydrocannabinol in man.

delta 9-Tetrahydrocannabinol (THC) or vehicle alone was applied topically to one eye of normal paid volunteers. Ocular and systemic toxic effects and intraocular responses were measured in different series. Toxicity was limited to minor conjunctival injection that was of short (less than 60 minutes) duration and occurred with both drug and vehicle alone. Subjective responses indicated a sensation of minor burning and/or tearing. No fall in intraocular pressure was found. A small (1 mm) but significant mydriasis occurred in both the treated eye and untreated eye and was not drug related. Single-drop administration of delta 9-THC did not, therefore, cause any significant ocular irritation or reduce IOP.

Administration, Topical↗

Corneal endothelial glutathione after photodynamic change.

Rabbit corneal endothelial cells perfused with 5 X 10(-6)M rose bengal and exposed to incandescent light demonstrated no alteration of either total of or percent oxidized glutathione after 1 hr. Addition of 5400 U/ml catalase to the perfusing solution had no effect on total glutathione levels but caused a marked reduction in percent oxidized glutathione in corneas exposed to light as well as in those not exposed to light. Substitution of sucrose for glucose in the perfusing solution had no effect on total or percent oxidized glutathione. Perfusion of rabbit corneal endothelium with 0.5 mM chlorpromazine and exposure to ultraviolet (UV) light resulted in no change in total glutathione content. A marked reduction in percent oxidized glutathione occurred, however, in corneas perfused with 0.5 mM chlorpromazine both in the presence and absence of UV light. It is concluded that photodynamically induced swelling of corneas is not the result of a failure of the glutathione redox system.

Animals↗

Chlorpromazine-induced corneal endothelial phototoxicity.

Chlorpromazine, which has been used extensively for the treatment of psychiatric disorders, is known to accumulate in the posterior corneal stroma, lens, and uveal tract. Because it is a phototoxic compound, the potential exists for it to cause cellular damage after light exposure. Specular microscopic perfusion of corneal endothelial cells in darkness with 0.5 mM chlorpromazine HCl resulted in a swelling rate of 18 +/- 2 micrometer/hr, whereas corneas exposed to long-wavelength ultraviolet light for 3 min in the presence of 0.5 mM chlorpromazine swelled at 37 +/- 9 micrometer/hr (p less than 0.01). Preirradiation of 0.5 mM chlorpromazine solution with ultraviolet light for 30 min and subsequent corneal perfusion with the solution resulted in a corneal swelling rate of 45 +/- 19 micrometer/hr. Cornea endothelial cells perfused with 0.5 mM chlorpromazine that was preirradiated with ultraviolet light showed marked swelling on scanning electron microscopic examination, whereas those perfused with nonirradiated chlorpromazine were flat and showed a normal mosaic pattern. Combining either 500 U/ml catalase or 290 U/ml superoxide dismutase with chlorpromazine did not alter photoinduction of corneal swelling. The data suggest that corneal endothelial chlorpromazine phototoxicity is secondary to cytotoxic products resulting from the photodynamically induced decomposition of chlorpromazine and is not caused by hydrogen peroxide or superoxide anion generated during the phototoxic reaction.

Animals↗

Photodynamic alteration of cornea endothelium. Relation to bicarbonate fluxes and oxygen concentration.

Corneas were mounted in flux chambers and endothelial bicarbonate fluxes were determined following sensitization of endothelial cells with 5 . 10(-6) M rose bengal and exposure to light. Corneas exposed to light demonstrated an increased passive bicarbonate flux compared to corneas not photosensitized. Active bicarbonate flux was reduced after 5 min of light exposure, but not after 1 min of light exposure. The increase in passive bicarbonate flux was prevented by the addition of 200 microgram/ml catalase to the bathing solution; however, catalase had no effect on the photodynamic alteration of active flux. Neither 10 mM ascorbic acid nor 1.012 gram/l glutathione prevented the photodynamically induced increase in passive flux. Perfusion of corneas with 5 . 10(-6) M rose bengal dissolved in a sucrose-substituted Krebs-Ringer bicarbonate solution with a PO2 of 124 +/- 4.0 mmHg and exposed to light swelled at rates more rapid than corneas treated in a similar fashion but perfused with a solution with a PO2 of 20 +/- 4.6 mmHg. This study demonstrated that photodynamically induced corneal endothelial cell alteration results in increased passive bicarbonate flux, a time-dependent decrease in active bicarbonate flux, is oxygen dependent, and is at least in part secondary to H2O2 produced by the dismutation reaction of the superoxide free radical.

Animals↗

Hydrogen peroxide and corneal endothelium.

Because of recent evidence of low levels of hydrogen peroxide in the aqueous humor, studies were performed to determine levels of corneal endothelial toxicity as well as factors modifying toxicity. Perfusion of cornea endothelial cells for 3 h with varying concentrations of hydrogen peroxide demonstrated a threshold of toxicity at a concentration between 0.3 and 0.5 mM H2O2. The toxic effect resulted in rapid corneal swelling as well as disruption of endothelial cell cytoplasm and organelles. Both the physiologic and anatomic toxic effects of 0.5 mM H2O2 could be blocked with 5400 U/ml catalase. Exposure of corneas to 20 mM H2O2 for 10 min in the presence of EDTA - Fe+3 resulted in an enhancement of corneal swelling rate more rapid than that which resulted from a 10 min exposure to 20 mM H2O2 alone. Neither the presence of ascorbic acid nor the absence of glutathione and adenosine had and effect on the cornea swelling rate which occurred during a 3 h perfusion of endothelium with 0.3 mM H2O2. Chelated iron had no effect on the corneal swelling induced by phototactivation of rose bengal presensitized cornea endothelial cells.

Animals↗