Tolerance of ocular iontophoresis in healthy volunteers.

To evaluate ocular tolerance, healthy volunteers were iontophoresed transclerally using novel OcuPhor trade mark hydrogel drug delivery applicators filled with balanced salt solution. In this three-period crossover study in 24 male and female subjects, 16 subjects received 0 mA and two of the following DC currents: 0.1, 0.5., 1.0, 2.0, 3.0, or 4.0 mA for 20 min; 6 subjects received 3 mA for 20 min and 1.5 mA for 40 min (both equivalent to 60 mAmin total charge). Safety and tolerance were determined by subjective VAS and objective ophthalmic assessments. Subjects were evaluated before and up to 22 hr after dosing. The applicators were well-tolerated and no clinically significant changes in symptomology or in ophthalmic assessments were seen following exposure to 0-3.0 mA for 20 min or 1.5 mA for 40 min. At 4.0 mA 2 of 4 subjects reported a burning sensation under the applicator during dosing which resolved by 22 hr post-dose; superficial changes in fluorescein staining were observed at 1 hr, but not at 22 hr. The OcuPhor trade mark system has promise for noninvasive drug delivery to the eye.     

Movements of cultured corneal epithelial cells and stromal fibroblasts in electric fields

The effects of an externally applied direct-current electric field on the movement of cultured rabbit corneal epithelial cells and stromal fibroblasts were studied. After a latency of approximately 20 minutes in an electric field, both epithelial cells and stromal fibroblasts became spindle shaped and underwent galvanotropism by aligning their long axes perpendicular to the applied electric field. The electric field stimulus thresholds for galvanotropic movements in epithelial cells and stromal fibroblasts were 4V/cm and 6 V/cm, respectively. After an additional latency of 30 minutes, both cell types manifested galvanotaxic movements: epithelial cells commenced migration in the cathodal (downfield) direction and stromal fibroblasts in the anodal (upfield) direction. For both types of cells, ruffled membranes and lamellipodia were abundant at the leading edges of migrating cells and cell processes underwent retraction at the trailing edges. At field strengths of above 10 V/cm, evidence of cellular damage (manifested by cellular rounding and detachment), attributable to the electric field treatment, was observed after 4 hours. These preliminary results suggest that galvanotaxic responses could be exploited clinically in the enhancement of corneal wound healing.     

Atropine effects on delayed discrimination performance of rats

The effects of atropine sulfate (ATS) and atropine methyl nitrate (ATM) on the conditional discrimination behavior of rats were investigated in eight-hour experimental sessions. Responding of rats was reinforced on either a lighted or a darkened lever depending on whether lights over both levers had been on during the preceding sample portion of the trial. Zero-delay and four-second-delay trials were randomly interspersed. Quality of performance was analyzed using the A' sensitivity measure of signal detection theory. Both drugs reduced both sensitivity and the percentage of trials on which responding occurred (percent response) below saline treatment levels. The two drugs did not reliably differ from each other in their effects on sensitivity during the zero-delay condition, but reliable differences between the two drugs emerged during the four-second-delay condition at doses above 0.8 mg/kg. Percent response recovered more rapidly for animals treated with ATS than responding occurred (percent response) below saline treatment levels. The two drugs did not reliably differ from each other in their effects on sensitivity during the zero-delay condition, but reliable differences between the two drugs emerged during the four-second-delay condition at doses above 0.8 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of age on binding of MK-801 in the cat visual cortex.

We have examined the effect of age on the binding of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine maleate (MK-801) in the cat visual cortex. We hypothesized that this binding might change with age because: (1) MK-801 binds to a site associated with the N-methyl-D-aspartate (NMDA) receptor; (2) the NMDA receptor complex has been implicated in neural plasticity; (3) plasticity in the cat visual cortex is age dependent. We used standard receptor binding techniques to measure MK-801 binding in membrane homogenates in cats aged 7 days (d), 21 d, 43 d, 83 d, 7-8 months (mo) and over 2 years. Glutamate (100 microM), glycine (30 microM) and spermidine (20 microM) were used to enhance binding. We found that MK-801 binding is maximal at about 6 weeks of age, decreases slightly by 83 days and then decreases more dramatically in adults. Saturation analysis showed that the of binding with age resulted from variation in number of binding sites and not from variation in affinity. The ability of Mg2+ to inhibit MK-801 binding did not change with age. Dark rearing did not alter the development of MK-801 binding sites.     

Learning and memory function in men with untreated blood pressure elevation

Learning and memory processes were compared in 20 men with untreated blood pressure elevation and 20 normotensive control subjects matched for age, education, and average alcohol consumption. Subjects were identified from a larger sample of 469 factory workers who had participated in an epidemiologic investigation. Three measures (e.g., Symbol-Digit Learning Test [Ryan & Butters, 1980] and Visual Reproductions-Immediate and Delayed Recall [Wechsler, 1945] ) from a previously administered test battery were chosen for comparison on the basis of statistical power calculations. Results indicate that relative to normotensive control subjects, men with elevated blood pressure performed more poorly on all three tests. These results are independent of other known influences on neuropsychological performance and are likely a consequence of elevated blood pressure.     

Simple staining for heat-fixed brain sections after topographical pH analysis or autoradiographic studies

Powerful topographic techniques are now available, among which autoradiographic and fluorescent mapping are the most prevalent. These techniques produce images that usually do not correlate with brain anatomy; subsequent staining is required to allow a precise association between the parameter(s) investigated and brain structures. A simple staining procedure is described, compatible with heat-fixed brain sections, and that was found particularly valuable in association with topographical tissue pH studies using the fluorescent pH indicator umbelliferone.