rich nuclear RNA was formed in the rats which increased their performance linearly with time during learning. Some animals showed a nonlinear performance curve. The nuclear RNA formed in the neurons of these rats had a ribosomal type of base composition.

Inflammation surrounding implantable glucose sensors may be controlled through local release of dexamethasone at the site of implantation. In the present study, we evaluated the distribution of dexamethasone in rat subcutaneous tissue during the first 2.5 days after local release. Osmotic pumps containing [3H]dexamethasone were implanted into the subcutaneous tissue of rats. Digital autoradiography was used to measure the distribution of the [3H]dexamethasone within the subcutaneous tissue at 6, 24, and 60 h after implantation. Measured concentration profiles, near the catheter tip through which the agent was released, were compared to mathematical models of drug diffusion and elimination. The results demonstrate that the majority of the [3H]dexamethasone delivered into the subcutaneous tissue was found within a 3 mm region surrounding the catheter tip. There was good agreement between the experimental data and the mathematical model. The diffusion coefficient for dexamethasone in subcutaneous tissue was found to be D = 4.11 +/- 1.77 x 10(-10) m2/s, and the elimination rate constant was found to be k = 3.65 +/- 2.24 x 10(-5) s(-1). The diffusion coefficient and elimination rate constants for dexamethasone in subcutaneous tissue have not been previously reported. The use of a mathematical model may be useful in predicting the effectiveness of local delivery of dexamethasone around implantable glucose sensors.

A relatively simple method for the determination of the diffusion coefficient of a substance that has been injected into tissue is described. We illustrate this method using [3]dexamethasone injected into the subcutaneous tissue of rats. Digital autoradiography was used to measure the distribution of the [3H] dexamethasone within the subcutaneous tissue at 2.5 and 20 min after injection. Measured concentration profiles of the injection were compared to a mathematical model of drug diffusion from an injection. There was good agreement between the experimental data and the mathematical model. The diffusion coefficient found using this simple injection method was (4.01 +/- 2.01) x 10(-10) m2/s. This D value was very close to the value of D = (4.11 +/- 1.77) x 10(-10) m2/s found previously using different mathematical and experimental techniques with osmotic pumps implanted for 6, 24, and 60 h in rats (1). The simple method given here for the determination of the diffusion coefficient is general enough to be applied to other substances and tissues as well.

A relatively simple method for the determination of the diffusion coefficient of a substance that has been injected into tissue is described. We illustrate this method using [3]dexamethasone injected into the subcutaneous tissue of rats. Digital autoradiography was used to measure the distribution of the [3H] dexamethasone within the subcutaneous tissue at 2.5 and 20 min after injection. Measured concentration profiles of the injection were compared to a mathematical model of drug diffusion from an injection. There was good agreement between the experimental data and the mathematical model. The diffusion coefficient found using this simple injection method was (4.01 +/- 2.01) x 10(-10) m2/s. This D value was very close to the value of D = (4.11 +/- 1.77) x 10(-10) m2/s found previously using different mathematical and experimental techniques with osmotic pumps implanted for 6, 24, and 60 h in rats (1). The simple method given here for the determination of the diffusion coefficient is general enough to be applied to other substances and tissues as well.

Several recent reports suggest that controlled local release of dexamethasone may be useful for preventing inflammation around an implantable glucose sensor [1,2]. This decrease in inflammation is expected to increase glucose sensor function and lifetime. Local delivery of dexamethasone would permit high interstitial drug concentrations at the site of glucose sensor implantation without producing high systemic drug levels. Although dexamethasone is a commonly used anti-inflammatory agent, its local concentration, diffusion coefficient and rate of elimination have not been reported following subcutaneous release. The ability of dexamethasone to penetrate subcutaneous tissue can be measured and quantified by comparison to mathematical models [3]. This method allows a reliable estimate of the drug concentration in the tissue near the implanted glucose sensor.