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Biomedical subjects

C S Cook

Publications and source records attributed to C S Cook.

48 records · Page 3Linked to original sources

Copper concentration in cornea, iris, normal, and cataractous lenses and intraocular fluids of vertebrates.

A method using electrothermal atomic absorption spectroscopy was developed for the determination of copper (Cu) concentration in the cornea, iris, and lens of a variety of species, including dog, cat, rabbit, horse, and toad. Previously described methods were used to determine Cu in aqueous and vitreous humor. There was little difference between copper levels in the same tissue or fluid across the species. However, there were age and pathology-related changes in Cu concentration of the aqueous humor, cornea, and lens. In the groups of older dogs, the Cu concentration of the aqueous humor and cornea is significantly lower than the two younger groups. In both the dog and rabbit, lenses from young animals have the lowest copper concentration which increases and then finally decreases with age. Canine hypermature cataracts have a significantly higher copper concentration than control dogs of all age groups. There was no correlation between Cu concentration in the intraocular fluids and the cataractous lenses taken from the same eye. The role such an increase in lenticular Cu concentration may play in cataractogenesis needs to be explored.

Age Factors↗

Experimental hypercupremia does not result in increases in copper in lens, iris, or ocular fluids.

Rabbits were continuously administered copper sulfate via subcutaneously implanted osmotic pumps. After one month, plasma, liver, ocular tissues and fluids were analyzed for copper by atomic absorption spectrophotometry. No elevation in copper content of the ocular fluids, lens or iris was noted although, dose-related increases were seen in the plasma and liver indicating that the copper was absorbed and disseminated systemically. It is likely that excess copper, like that which is normally ingested and absorbed, is largely protein-bound in the circulation, preventing crossing of the blood-ocular barrier.

Animals↗

Sequential scanning electron microscopic analyses of normal and spontaneously occurring abnormal ocular development in C57B1/6J mice.

Embryos of C57B1/6J mice were examined grossly, and by light and scanning electron microscopy on days 8 through 19 of gestation. Adult eyes were examined by slit lamp biomicroscopy and light microscopy. A spontaneous incidence of eye malformations including microphthalmia, microphakia, corneal opacity and anterior segment dysgenesis was observed at a rate of 13.2% in the adults and 10.8% in the day 14 embryos. Scanning electron microscopy demonstrates the complex series of coordinated changes in shape and tissue interrelationships observed in normal ocular development. Possible routes of abnormal ocular morphogenesis beginning as early as the time of optic vesicle formation are discussed.

Animals↗

Response of the canine corneal endothelium to intraocular irrigation with saline solution, balanced salt solution, and balanced salt solution with glutathione.

The right or left anterior chamber of 12 dogs (ie, 24 eyes) was irrigated with 100 ml of 0.9% saline solution, balanced salt solution, or balanced salt solution with glutathione (8 eyes/solution) for 22 minutes. Changes in endothelial cell density and corneal thickness from pretreatment values were evaluated immediately after, and at 2 and 7 days after irrigation. Using specular microscopy and scanning and transmission electron microscopy, corneas were examined immediately after and at 2, 7, and 14 days after irrigation. Changes were not seen in endothelial cell density after irrigation with any of the solutions evaluated. Corneal thickness increased 4% immediately after irrigation with 0.9% saline solution and returned to normal by 1 week after irrigation; treatment with 0.9% saline solution was not associated with visible corneal edema. Ultrastructural changes attributable to differences in irrigating solution composition were not observed. The difference between the endothelium's response to limited irrigation with saline solution, balanced salt solution, and balanced salt solution with glutathione was small and irrigation with these solutions was not associated with permanent endothelial damage.

Acetates↗

Idiopathic hyperaldosteronism in a dog.

Idiopathic hyperaldosteronism was diagnosed in an 8-year-old castrated male Yorkshire Terrier, based on increased concentration of plasma aldosterone, hypertension, hypernatremia, decreased natriuresis, hypokalemia, and hyperkaluria. Unilateral adrenalectomy was performed after visualization of a nodule on the right adrenal gland. Hyperplasia of the zona glomerulosa and increased postoperative aldosterone concentrations supported the diagnosis of idiopathic hyperaldosteronism.

Adrenal Glands↗

Malignant melanoma of the conjunctiva in a cat.

A conjunctival melanoma was diagnosed in an adult domestic cat. The neoplasm was excised without further complications. It is important to differentiate conjunctival melanoma from other types of pigmented ocular neoplasia. In man, conjunctival melanomas are often malignant tumors with potential for metastatic behavior. Although this neoplasm had histologic features of malignancy, no evidence of local recurrence or metastasis has been apparent during the 11-month follow-up period.

Animals↗

Metastatic ocular squamous cell carcinoma in a cat.

Bilateral ocular metastatic squamous cell carcinoma was diagnosed in a cat. Ophthalmic signs included bilaterally swollen optic discs, choroidal pallor, and retinal vascular engorgement. A retinal detachment was apparent in the left eye and retinal edema and hemorrhage in the right eye. Systemic signs of progressive visual impairment, ataxia, and weakness were noted. The patient's condition continued to deteriorate despite therapy with systemic antibiotics and corticosteroids, and euthanasia was performed. The diagnosis was made upon histologic examination that revealed metastasis of malignant squamous cells to both globes, the brain, and lungs.

Animals↗

Metabolism of actisomide in the dog, monkey and man: a novel rearrangement of N-dealkylated metabolites.

The metabolism of actisomide, a novel antiarrhythmic agent, was studied in the dog, monkey and man and was found to be more extensive in the monkey than in the dog or man. The major metabolites identified were a piperidinyl hydroxylated metabolite, the mono-N-dealkylated, cyclized and piperidine hydroxylated metabolite, and the cyclized and mono-N-dealkylated metabolite. Excretion of the parent drug was higher in urine than in feces in the dog, but in the monkey and man, urinary and fecal excretion of actisomide was similar. In all species the metabolites were primarily excreted in feces.

Adult↗

Keratolenticular dysgenesis (Peters' anomaly) as a result of acute embryonic insult during gastrulation.

Keratolenticular dysgenesis (Peters' anomaly) was induced in mice by exposure to the human teratogens, ethanol or 13-cis retinoic acid (isotretinoin, Accutane). Acute teratogen exposure on the seventh day of gestation (corresponding to the third week of human gestation) resulted in an eye malformation incidence of 46% to 100% in day 14 fetuses. Of the abnormal eyes, 10% to 29% demonstrated failure of detachment of the lens from the surface ectoderm. Delayed lens detachment was seen as anterior lenticonus in 33% to 35% of the abnormal eyes. Abnormal lens detachment appeared to result in mechanical interference with neural crest migration to form the corneal stroma and endothelium, and iris stroma. This secondary effect on neural crest derivatives is exhibited in the adult animals as corneal opacities associated with defects in Descemet's membrane and endothelium, and anterior polar cataracts.

Animals↗

Pharmacokinetics of disopyramide in the dog. Importance of mono-N-dealkylated metabolite kinetics in assessing pharmacokinetic modeling of the parent drug.

The antiarrhythmic drug disopyramide (DP) is metabolized to the mono-N-dealkylated compound (MND) and to the pyrrolidone derivative (PYR). This study examines the detailed pharmacokinetic characteristics of DP and MND when given simultaneously or separately to dogs. DP and MND were both relatively well absorbed and showed similar pharmacokinetic characteristics. However, the amount of PYR relative to MND as judged by the area under the plasma concentration-time curves (AUC) following oral or iv administration was much greater with DP than with MND. These findings were also supported by the urinary excretion values where the PYR/MND ratio with DP was much greater than with the MND administration. For an explanation of this phenomenon, plasma concentration-time curves for DP, MND, and PYR were simultaneously analyzed assuming various pharmacokinetic models. The plasma levels of these compounds were best described when nonlinear kinetics were assumed for conversion of MND to PYR.

Absorption↗

Stereoselectivity in the metabolism of disopyramide enantiomers in rat and dog.

The metabolism and pharmacokinetics of (S)-(+)- and (R)-(-)-disopyramide (DP) were compared in laboratory animals. In rats, after oral administration of (S)-(+)-DP phosphate salt at a dose of 38.8 mg of DP free base per kg, the mean maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) were 1.43 micrograms/ml and 4.47 micrograms . hr/ml, respectively, and after (R)-(-)-DP administration, the values were 4.93 micrograms/ml and 17.05 micrograms . hr/ml, respectively. Similar recoveries (approximately 55% of the dose) of DP and its metabolites in the urine and bile of rats were obtained after administration of the individual (S)-(+)- and (R)-(-)-enantiomers of DP. These results indicate similar oral absorption of the two enantiomers, but greater metabolism with (S)-(+)-DP in rats. In dogs, the AUC of DP after iv administration of (R)-(-)-DP phosphate salt at a dose of 15 mg of DP free base per kg was 1.6 times greater than that after (S)-(+)-DP phosphate salt. Inasmuch as volumes of distribution of the two enantiomers were similar, this difference can be attributed to a difference in the elimination rates of the enantiomers. After an oral dose, the difference in AUC of the two enantiomers was greater than that after an iv dose. The mean values of Cmax and AUC after a 15-mg/kg oral dose of (S)-(+)-DP were 1.32 micrograms/ml and 4.07 micrograms . hr/ml, respectively, and with (R)-(-)-DP the values were 2.88 micrograms/ml and 9.21 micrograms . hr/ml, respectively. The Cmax and AUC of the total drug-related materials (drug plus its metabolites) were similar. These results, together with the similarity in the urinary excretion of total drug related compounds, indicated that after equivalent doses of the two enantiomers, oral absorptions were similar, but the first-pass metabolism was greater with (S)-(+)-DP. The present study also demonstrated that N-dealkylation in dogs and arylhydroxylation in rats are stereoselective metabolic pathways, thus illustrating species differences in the stereoselective metabolism of DP.

Administration, Oral↗