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Diabetic rats were produced by intravenous injection of streptozotocin. Of these, eleven rats were treated with topical instillation of 0.5% aldose reductase inhibitor (ARI), while ten received vehicle alone. The corneal endothelium of these diabetic rats was examined by specular microscopy and compared to age-matched nondiabetic rats (ten rats). Computerized morphometric analysis of individual cells demonstrated that the endothelium of the untreated diabetic rats had marked polymegathism (increased coefficient of variation in cell area) and pleomorphism (decreased percentage of hexagonal cells), as previously observed in diabetic patients. Similar endothelial changes were also noted in the ARI-treated diabetic rats, but to a significantly lesser extent. These results suggest that topically applied ARI can be effective in reducing morphologic changes of the diabetic endothelium, and that activation of the sorbitol pathway may be implicated in the etiology of such endothelial changes.

To assess the effects of metabolic control upon beta cell function in diabetes, pro-insulin and insulin were determined following gel-filtration of plasma at two time points in each three diabetic patients, once when the metabolic state was severely deranged and again after the metabolic state had improved after therapy. Before therapy, proinsulin concentration were 30 pM (as IRI), both fasting and at 2 hours after an oral glucose load. These values did not change with treatment. Insulin concentrations were 22 pM at both time points before therapy. With treatment, plasma insulin increased 2-fold at fasting and 7-fold at 2 hours after oral glucose. These results suggest an exhaustion of the insulin pool in beta cells during severe metabolic decompensation of diabetes, a condition which may be reversed by correction of the metabolic states of the patients with proper therapy.

To determine the effect of long-term topical application of commercial beta-blockers on the corneal endothelium, normal rats were randomly assigned to receive a drop of 0.5% timolol, 1% befunolol, or 2% carteolol four times daily for 8 months. Specular microscopy showed marked pleomorphism in the endothelium after three months of treatment with 1% befunolol. In contrast, the eyes treated with either 0.5% timolol or 2% carteolol demonstrated no significant change in endothelial morphology. Scanning and transmission electron microscopy at eight months after treatment revealed marked degeneration of the endothelium of the eyes treated with 1% befunolol. Similar endothelial changes were also noted in the 0.5% timolol-treated group, but to a significantly lesser extent. The eyes treated with 2% carteolol, however, showed only mild alteration of the endothelial ultrastructure. These results indicate that the corneal endothelium can be affected by long-term topical administration of commercial beta-blockers.

An experiment was conducted in 76 mice (3 to 9 weeks of age) to investigate the characteristics in growth of major skeletal bones and their sexual differences. The length of ulna, radius, femur and tibia attained their maximum growth rate at earlier age, and showed no sexual difference in their growth patterns. Scapula length and width, humerus length and os coxae width reached the maximum growth rate at a later age than the forearm and shank, and showed no sexual difference in their growth, although those bones presented larger adult sizes for male than female. The length of vertebrae showed significant sexual differences in their growth patterns and adult sizes, except for lumber vertebrae. A significant sex difference in body weight caused the sexual differences in relative growth of bones to body weight. According to their relative growth to the length of humerus, the skeletal bones could be well grouped into three categories. A significant sexual difference was seen in the relative growth of scapula length. In general, it seemed that the bones growing in a vertical direction grew earlier than the bones growing in a horizontal direction, especially those of the forearm and shank. The results obtained in mice were in good agreement with the findings in pigs.

A study was made of inhibitory effects of an aldose reductase inhibitor, CT-112 (5-(3-ethoxy-4-pentyloxyphenyl)-2,4-thiazolidinedione) ophthalmic solution, on the accumulation of sugar alcohol (dulcitol) in the corneal epithelium of rats fed on a 50% galactose diet. The effects were correlated with the concentrations of the drug solution. The rats were divided into 6 groups. One group was fed on a regular laboratory chow and was untreated. The other 5 groups were fed on a 50% galactose diet, and 0.1, 0.25, 0.5 or 1.0% CT-112 ophthalmic solution or its vehicle was instilled in both eyes 4 times a day in each of the 5 treated groups. After 2 weeks, the corneal epithelium was scraped off in all rats and its dulcitol content was determined by gas chromatography. CT-112 ophthalmic solution was found to inhibit the accumulation of dulcitol in a dose-dependent manner, except for the 1.0% solution which had an activity comparable to the 0.25% solution.

In situ hybridization with DNA probes labeled with biotin and detected by the avidin-alkaline phosphatase/5-bromo-chloroindoxyl phosphate-nitro blue tetrazolium system has been used to localize DNA sequences in chromosomes. To observe the hybridization signals, a phase contrast microscope has often been used because of the good visibility it provides. Use of a 595 nm band pass filter with the phase contrast microscope enhances signal contrast after in situ hybridization without reducing resolution.