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Biomedical subjects

J C Le Douarec

Publications and source records attributed to J C Le Douarec.

At least 19 recordsLinked to original sources
PubMed1981

Penetration of five beta-adrenergic antagonists into the rabbit eye after ocular instillation.

Aqueous humor and serum levels of five beta-adrenergic blockers were measured using gas chromatographic techniques following ocular instillation of 1% solutions to rabbits. Octanol/buffer partition ratios were also determined. No apparent relationship was found between the peak levels of the agents in aqueous humor and their octanol/buffer partition ratios. However, peak aqueous humor levels of timolol (461 ng/100 mg) and practolol (919 ng/100 mg), whose partition ratios were less than unity, occurred somewhat later (1 h) than the peaks of propranolol (859 ng/100 mg at 30 min), oxprenolol (1,771 ng/100 mg at 30 min) or alprenolol (1,004 ng/100 mg at 10 min) whose partition ratios exceeded unity. Peak levels in serum of timolol (8.0 ng/100 microliter), propranolol (4.2 ng/100 microliter), oxprenolol (11.5 ng/100 microliter), and alprenolol (4.5 ng/100 microliter) were achieved within 10 min and reduced to less than 15% within 4 h. Peak serum levels of practolol (9.9 ng/100 microliter) occurred somewhat later (2 h) and remained high (41%) 6 h later.

Administration, Topical↗
PubMed1979

Tear film breakup time prolonged with unmedicated cellulose polymer inserts.

Unmedicated cellulose polymer (UCP) inserts exhibited marked superiority over six commercial artificial tear substitutes in enhancing and maintaining precorneal tear film stability as measured by tear film breakup time (BUT) in rabbits. The application of UCP inserts into one eye also resulted in an appreciable elevation of the BUT in the contralateral untreated eye. Sham inserts (polyethylene pieces) equal in size to our larger than UCP inserts lacked similar effects, which suggests that the latter actions of UCP inserts are most likely due to a slow release of polymer into the tear film rather than to induction of reflex responses associated with insertion of an inert foreign body into the cul-de-sac. The results indicate that UCP inserts, by virtue of their ability to maintain the integrity of the precorneal tear film over extended periods of time, may represent an important advance in the treatment of dry-eye diseases.

Animals↗
PubMed1979

[Experimental alpha-chymotrypsin model of glaucoma in the rabbit: histopathological studies (author's transl)].

The injection of alpha-chymotrypsin into the posterior chamber of the eye is known to produce an experimental ocular hypertension of long duration in animals. The present study reports the pathological changes which occur in the eye during the first nine months after the ocular injection of alpha-chymotrypsin in rabbits. Six weeks after treatment most of the eyes showed a buphthalmia and an intraocular pressure elevation which varied greatly from animal to animal. The anterior chamber angle of the treated eyes showed a progressive enlargement. Several days after the enzyme injection a transient increase in thickness of the cornea and Descemet membrane was noted. Cupping of the optic disc, characterized by a total disappearance of the optic nerve head fibers and an excavation beginning at margins of the retina appeared after four months and in most cases were present seven months after the treatment. More or less prominent retinal degeneration was also evidenced three months after enzyme injection. The results indicate alpha-chymotrypsin-induced occular hypertension in the rabbit leads after several months to pathological change in the eye analogous to that observed in human glaucoma.

Animals↗
PubMed1978

[Experimental studies with timolol: a new ocular hypotensive agent (author's transl)].

The present report reviews the animal pharmacology supporting the clinical use of timolol maleate ophthalmic solution in the therapy of glaucoma and elevated intraocular pressure (IOP). The studies have included the effects of timolol upon normal IOP of rabbits and upon elevated IOP in two models of experimental ocular hypertension. Comparisons are made between the latter actions of timolol and those of the reference adrenergic antiglaucoma agent, epinephrine. The interaction of timolol and the beta-adrenergic stimulant, isoproterenol, was also studied to assess the ability of timolol to block beta-adrenergic receptors in the eye. Additionally, the penetration and distribution of timolol in ocular and extraocular tissues and fluids following local application to the eyes of rabbits is described and a resume of the toxicological studies with timolol are presented.

Animals↗
PubMed1977

Comparison of the effects of timolol and other adrenergic agents on intraocular pressure in the rabbit.

The effect of timolol, propranolol, epinephrine, and isoproterenol on intraocular pressure (IOP) (measured by tonometry) were compared after topical administration in conscious rabbits. Epinephrine and isoproterenol decreased IOP in normotensive rabbits, whereas propranolol had no effect. Timolol produced only a slight and inconsistent lowering of IOP in normotensive rabbits. All four agents reduced IOP elevated by an oral water load; the adrenergic agonists were substantially more active than the two beta-adrenergic blocking agents. In alpha-chymotrypsin-induced ocular hypertension, epinephrine, isoproterenol, and timolol were essentially equally effective, whereas propranolol exhibited only weak activity. In this latter model, timolol did not lose its effectiveness after multiple instillations (three/day) over an 8-day period. The concentration of timolol in the acqueous humor after topical application of effective hypotensive doses was relatively high as compared to that found in plasma. In addition, topical doses of timolol required to lower IOP were considerably greater than those needed to reduce or block the ocular hypotensive activity of isoproterenol. The mode of action and therapeutic implications of beta-adrenergic blocking agents in glaucoma are discussed.

Adrenergic beta-Antagonists↗
PubMed1976

Standardization of an experimental immune uveitis in the rabbit for topical testing of drugs.

An egg albumin uveitis of the Arthus active type was developed in the rabbit. The experimental conditions were investigated in detail with regard to the following factors: influence of the number of sensitizing injections on serum antibody production, length of the recovery period which elapsed between sensitization and challenge, and influence of the size of the challenging dose on the severity of the inflammatory response. To develop the procedure optimally, emphasis was given to criteria of evaluation. Refractive index, protein and immunoglobulin assays in the aqueous humor of inflamed eyes were significantly correlated. These objective measures were considered more reliable than arbitrary grading systems. In addition, supportive histopathologic observations have been made in rabbit eyes. The above studies led to a reproducible model of uveitis in which drugs were tested topically. Dexamethasone phosphate in solution and indomethacin in suspension were effective in a dose-related manner. 6-Mercaptopurine did not demonstrate a useful anti-inflammatory effect.

Administration, Topical↗
PubMed1975

Arachidonic acid-induced elevation of intraocular pressure and anti-inflammatory agents.

Arachidonic acid, a precursor of prostaglandin E2 subconjunctivally injected into rabbit eyes in concentrations of 0.8 to 5 per cent, produced a dose-related rise of intraocular pressure (IOP) similar to the one observed after topical administration of PGE2 in concentrations of 0.001 to 0.1 per cent. Indomethacin, a nonsteroidal anti-inflammatory agent, had an inhibitory effect when administered systemically or topically prior to arachidonic acid. Dose-response relationships were demonstrated by topical and oral administration of Indomethacin which, as expected, had no effect on PGE2. Dexamethasone did not exert any inhibitory effect on the increased IOP following arachidonic acid administration. Indomethacin applied topically readily penetrated into the aqueous humor in concentrations considerably above those appearing in the plasma, which justifies the use of this route of administration. Since prostaglandin (PG) appeared to be implicated in ocular inflammation, these findings underline the specificity of action of Indomethacin and suggest its use in the topical treatment of ocular inflammation.

Administration, Oral↗