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Biomedical subjects

J Friend

Publications and source records attributed to J Friend.

At least 37 records · Page 2Linked to original sources

5-Fluorouracil toxicity to the ocular surface epithelium.

The antimetabolite, 5-fluorouracil (5-FU), has been used to control proliferation of retinal pigment epithelial cells and fibrocytes, and is currently the subject of a multicenter clinical trial of its value in the control of scarring after glaucoma operations. To evaluate possible ocular surface toxicity, the effect of 5-FU on the mitotic rate and differentiation of the ocular surface epithelium in rabbits was measured. 5-FU was instilled into eyes with 10-mm diameter central epithelial wounds and into nonwounded eyes at a dose of 9 mg per day for 4 days. Saline treated control wounded eyes healed within 4 days (n = 5) while 40% (4 of 10) of the 5-FU treated wounded eyes had defects at 4 days. The normal mitotic rate of the corneal epithelium was 1.0 +/- 0.3 (n = 4) tritiated thymidine labeled cells per 100 basal corneal epithelial cells after 2.5 hr incubation. Saline treated control wounded eyes had an increased mitotic rate, 7.1 +/- 1.3 (n = 5) labeled cells per 100 basal corneal epithelial cells after 2.5 hr incubation. Topical 5-FU decreased both of those rates to about 1% of normal. The normal conjunctival epithelial mitotic rate was 1.8 +/- 0.4 (n = 4) labeled cells per 60 basal cells after per 2.5 hr incubation. This rate was the same in wounded eyes, but was decreased in eyes treated with 5-FU. Thus, 5-FU (9 mg/day topically) has serious toxic effects to ocular surface epithelium which must be carefully considered if this drug is to be used clinically.

Animals

Ocular surface epithelium and corneal vascularization in rabbits. I. The role of wounding.

A new model for rabbit corneal vascularization, created by making a penetrating wound in corneas with epithelium of conjunctival origin, is described. Obligate resurfacing of the cornea from conjunctival epithelium usually leads to a small, but consistent peripheral superficial corneal vascularization. Subsequent penetrating wounds elicit, in 75% of cases, a marked vascular ingrowth. Normal eyes and eyes resurfaced by peripheral corneal epithelial cells do not vascularize after such wounds. The vessels are located in the anterior corneal stroma, and the regenerated epithelium has a conjunctival appearance. Although increased hydration plays a role in this vascularization, the extent of vascularization was much greater in the presence of regenerated epithelium of conjunctival origin than in the presence of regenerated epithelium of corneal origin.

Animals

Functional competence of regenerating ocular surface epithelium.

Several aspects of the ocular surface epithelium, including its clinical appearance, its effect on the strength of underlying stromal wounds, and its healing rates, have been compared between regenerating epithelium of conjunctival and that of corneal origin in rabbits. The results showed that conjunctival epithelium could not transform completely into functionally competent corneal epithelium within 6 weeks.

Animals

Effects of ultraviolet radiation on corneal epithelial metabolism.

Acute exposure to ultraviolet light to 257 nm wavelength produced a photokeratitis associated with characteristic metabolic alterations of corneal epithelial metabolism in rabbits. Significant increases in corneal hydration occurred simultaneously with decreased corneal epithelial glycogen content, but adenosine triphosphate content and enzyme activity of epithelial extracts were not affected despite clinical and histological damage to the corneal epithelium. The pattern and time course of ultraviolet damage to the cornea are distinctly different from those of other forms of trauma.

Animals

Biochemical transformation of regenerating ocular surface epithelium.

Several biochemical parameters, including glycogen levels, and the activities of hexokinase, phosphorylase, and lactate dehydrogenase have been compared in regenerating epithelium of conjunctival and corneal origin in rabbits. The study was designed to determine the extent of biochemical transformation of conjunctival into corneal epithelium completed within 6 weeks. Although histological transformation, especially in the case of the chemically damaged eyes, is not. Glycogen and lactate dehydrogenase levels remained well below normal corneal epithelial levels for the period of observation.

Animals

Spironolactone stimulation of gonadotropin secretion in boys with delayed adolescence.

Spironolactone (Aldactone) acts as an antiandrogen by blocking testosterone synthesis and competing with testosterone for the androgen receptor. These properties of the mineralcorticoid antagonist were used in an attempt to interrupt the gonadal-pituitary-hypothalamic negative feedback axis and thereby stimulate LH and FSH in 7 boys with delayed puberty. Following administration of aldactone (5 mg/kg) daily for one week, there was a significant (P less than .01) mean increase in serum LH of 60%. In all 7 boys an absolute rise in LH was observed, but these changes were statistically significant in only 5 individuals. While mean FSH levels increased by 60% in this group of boys, the individual responses were variable. No rise in gonadotropin levels occurred in 2 patients with Kallmann's syndrome, who also received 5 mg/kg of spironolactone daily for 1 week. Large doses of the drug appeared necessary to stimulate gonadotropin secretion since a dose of 3 mg/kg per day did not cause LH or FSH increments in 2 additional patients with delayed puberty. Progesterone and 17alpha-hydeoxyprogesterone levels increased to a greater extent than LH and FSH in response to spironolactone, reflecting either adrenal or testicular enzyme inhibition. Spiornolactone is the first drug shown to be capable of stimulating gonadotropin secretion by interrupting negative feedback inhibition in boys with delayed puberty.

Adolescent

Corneal epithelial changes during midterm storage.

The increased use of donor epithelium in keratoplasty for severe corneal disease has prompted an investigation of epithelial viability during midterm storage. Glycogen, ATP, and ADP have been used as indicators of the metabolic state of epithelial cells. These substances have been measured after conventional moist-chamber storage at 4 degrees C. for 1, 2, and 12 days and after immersion at 4 degrees C. in McCarey-Kaufman medium for 1, 2, and 12 days. In addition, recovery of glycogen and ATP stores has been evaluated after warming of the tissue in the storage solution to 37 degrees C. The evidence indicates that the corneal epithelium may recover these biologically important substances, despite depletion secondary to delayed cooling of donor eyes.

Adenosine Diphosphate

Corneal epithelial preservation.

While clinical experience has demonstrated that current storage techniques are adequate for the preservation of human endothelial cells, increased use of donor epithelium in cases of severe disturbance to epithelial and stromal integrity requires a reexamination of storage effects on the epithelial layer. Measurement of human and rabbit metabolite levels in stored corneas indicates that the epithelium is maintained in a normal state only if the eye is cooled promptly. If cold storage is delayed for as little as one hour after death, glucose levels in the stroma and aqueous fall below levels known to be required for preservation of epithelial integrity. The fundamental time of interest in preservation of donor corneal tissue is in the interval between death and cooling of the eye. If prompt enucleation is not possible, ice should be applied to maintain viability of the epithelium.

Animals

Biochmical aspects of contact lens wear.

Glycogen, adenosine triphosphate, and hydration were measured in rabbit corneal epithelium to determine whether the corneal epithelium glycogen decrease, increase in epithelial hydration, and decrease in epithelial adenosine triphosphate stores, seen as a result of contact lens wear, were secondary only to anoxia or may also have resulted from mild trauma, with no interference to oxygenation. Conventional contact lens wear, trauma, and oxygen-permeable contact lens wear caused metabolic changes, showing trauma as well as anoxia may play an important role in the corneal epithelial response to contact lens wear.

Adenosine Diphosphate