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Biomedical subjects

A Schroeder

Publications and source records attributed to A Schroeder.

At least 19 recordsLinked to original sources

The effect of intracameral ethacrynic acid on the intraocular pressure of living monkeys.

Previous studies have shown that the sulfhydryl-reactive ethacrynic acid increases outflow facility in living monkeys when perfused via the anterior chamber. To study its potential clinical use further, living monkeys were intracamerally injected with 10 microliters of ethacrynic acid, with concentrations ranging from 0.5 to 7.5 mmol/l. The fellow control eye was injected with 10 microliters of diluent. The status of the anterior segment was monitored by slit-lamp biomicroscopy and the intraocular pressure was measured by pneumatonometry with the monkeys anesthetized with ketamine. The anterior segment of living monkeys tolerated injections up to 3.0-mmol/l ethacrynic acid without marked adverse effects. One of 13 monkey eyes injected with 3.0-mmol/l ethacrynic acid demonstrated mild reversible segmental corneal edema. The greatest mean intraocular pressure reduction in the 3.0- to 3.75-mmol/l group occurred at six hours, with the experimental intraocular pressure decreasing 2.9 mm Hg compared to a mean intraocular pressure increase of 0.1 mm Hg in the control group (n = 19). Concentrations of ethacrynic acid less than 3.0 mmol/l did not provide reliable reduction of intraocular pressure, whereas concentrations greater than 3.75 mmol/l caused a greater incidence and severity of corneal edema. We believe that the intracameral injection of ethacrynic acid can reliably and safely reduce intraocular pressure in living monkey eyes, and that this drug deserves further investigation as a potential antiglaucomatous agent.

Animals

The axonally secreted cell adhesion molecule, axonin-1. Primary structure, immunoglobulin-like and fibronectin-type-III-like domains and glycosyl-phosphatidylinositol anchorage.

Axonin-1 is an axon-associated cell adhesion molecule (AxCAM) of the chicken, which promotes neurite outgrowth by interaction with the AxCAM L1(G4) of the neuritic membrane. Here we report the cloning and sequence determination of a cDNA encoding axonin-1. Peptides generated by enzymatic cleavage showed similarity to the AxCAM F11. Degenerated polymerase chain reaction (PCR) primers were designed and an axonin-1 fragment was amplified from mRNA of embryonic retina. Screening of a cDNA library from embryonic brain resulted in the isolation of a 4.0-kb cDNA insert with an open reading frame of 3108 nucleotides. The deduced polypeptide of 1036 amino acids includes a putative hydrophobic N-terminal signal sequence of 23 or 25 amino acids and a C-terminal hydrophobic sequence of 29 amino acids which is suggestive of sequences serving as signal for the attachment of a glycosyl-phosphatidylinositol (glycosyl-PtdIns) anchor. The putative mature form of axonin-1 comprises six immunoglobulin-like repeats, followed by four fibronectin-type III repeats. Axonin-1 exhibits 75% amino acid identity with the AxCAM TAG-1 of the rat, suggesting that it is the chicken homologue of TAG-1. Like TAG-1, axonin-1 is glycosyl-PtdIns-anchored to the neuronal membrane; in contrast to TAG-1, it does not exhibit an Arg-Gly-Asp sequence.

Amino Acid Sequence

Effects of topical ethacrynic acid adducts on intraocular pressure in rabbits and monkeys.

We evaluated the effect of topical ethacrynic acid on rabbit and monkey intraocular pressure. In a preliminary experiment, 100-mmol/L ethacrynic acid applied topically to Dutch-Belted rabbit eyes was associated with an 8-mm Hg lowering of intraocular pressure. However, corneal edema was severe, and the corneal epithelium sloughed off. To try to maintain the pressure-lowering effect but reduce the corneal side effects, we attempted to create an adduct of ethacrynic acid by utilizing ethacrynic acid's sulfhydryl reactivity. Ethacrynic acid was mixed with equimolar cysteine to bind the sulfhydryl-reactive sites on ethacrynic acid. The goal was to expose the cornea to adducted ethacrynic acid, which might then dissociate in the anterior chamber via a retro-Michael reaction. Intraocular pressure decreased 8.9 mm Hg (n = 40) with this treatment, and corneal edema was lessened (32 of 40 eyes had mild to no edema). However, we observed that when the eye was treated before ethacrynic acid-cysteine administration with topical acetylcysteine, the corneal side effects were reduced further and the intraocular pressure effect remained. In living cynomolgus monkeys receiving a single pretreatment drop of 75-mmol/L acetylcysteine followed by two drops of 130-mmol/L ethacrynic acid and 130-mmol/L cysteine, an intraocular pressure lowering of 9.9 mm Hg was observed (n = 7). However, in three of seven eyes corneal edema developed. Pretreatment with two drops of acetylcysteine eliminated the pressure-lowering effect but did not confer any added corneal protection. Our results indicate that topical ethacrynic acid-cysteine is effective in lowering the intraocular pressure of rabbits and cynomolgus monkeys and, when combined with acetylcysteine pretreatment, may offer the potential for a new topical therapeutic regimen for use in glaucoma.

Acetylcysteine

Indications for angled implants.

The development of dental implants has led to an expansion of indications and to perfection of implantation methods and implant systems. Angulation problems due to anatomic limitations, however, still remain. The indications for the use of angled Bonefit I.T.I. implants are described.

Alveolar Process

Ethacrynic acid induces reversible shape and cytoskeletal changes in cultured cells.

Cell cultures derived from trabecular meshworks of human and bovine eyes and from bovine vascular endothelia were incubated at 37 degrees C for 1 hr with ethacrynic acid (ECA, 0.1-0.5 mmol/l) dissolved in culture medium. At 2 hr after the initial exposure, ECA at concentrations up to 0.4 mmol/l induced a reversible alteration in cell shape in all three cell types that was coincident with a change in the staining pattern of major cytoskeletal components including actin, alpha-actinin, vinculin, and vimentin. Distinct progressive alterations in beta-tubulin also occurred, with initial changes observed 10 min after ECA exposure. The ECA-induced changes in tubulin were blocked in part by preincubation with taxol (which stabilizes the microtubule structure), but they appeared to differ from those occurring with nocodazole (which interferes with tubulin assembly). These results suggest the possibility that ECA-induced increases in outflow facility may be mediated by alterations in the cytoskeletons of outflow pathway cells.

Adolescent

Explantation procedure in the F-type and Bonefit ITI implant system.

The explantation technique for the ITI F-type and Bonefit implant system is described. Although implant survival rates are high, the risk of failure must be considered. In some cases implants will have to be removed for reasons other than failure of the implant itself.

Dental Implantation, Endosseous

Dissociation between the effect of aceclidine on outflow facility and accommodation.

The dose/effect relationships for intracameral doses of aceclidine HCl and pilocarpine HCl on total facility of outflow and accommodative amplitude were compared in the cynomolgus monkey eye in vivo. The largest dose of aceclidine tested (20 micrograms), resulted in an average increase of 270% in outflow facility, whereas accommodation was limited to an average of 5 diopters. In contrast, 20 micrograms of intracameral pilocarpine (which is submaximal in increasing facility) resulted in an average of 19 diopters of accommodation. These results provide further evidence for a dissociation between the accommodative and outflow facility functions of the ciliary muscle.

Accommodation, Ocular

[The accumulation of osteocementum around a dental implant under physical loading].

Hollow cylinder implants of titanium with a titanium spray surface were implanted in macaca speciosa, as previously described (Schweiz.Mschr.Zahnheilk.86: 713, 1976). This time, however, the implants were submitted to masticatory forces. Histologically it can be shown that the ankylotic contact between implant and bone, which is initially obtained, remains after 6-16 months. In one case the substance encasing the implant at its deepest part was identified as genuine osteocementum.

Animals