TNF alpha affects the expression of GFAP and S100B: implications for Alzheimer's disease.

Neurodegenerative disorders such as Alzheimer's disease are characterized by increased intracellular and extracellular concentrations of the astrocytic proteins glial fibrillary acidic protein (GFAP) and S100B. The present study examined the potential contribution of tumor necrosis factor alpha (TNFalpha) to these changes by measuring astrocyte viability along with the intracellular and extracellular expression of GFAP and S100B following exposure to this cytokine. Although TNFalpha did not affect astrocyte viability, the extracellular levels of both proteins were increased three-fold with associated reductions in immunocytochemical labeling.

Comparative bioavailability study of three sustained release quinidine formulations.

The absorption characteristics of 3 sustained release quinidine formulations were assessed in 12 healthy male volunteers in a randomised 3-way crossover trial. Each formulation ('Quinidex' 300mg, 'Biquin Durules' 250mg and 'Quinaglute Dura-Tabs' 324mg) was administered as a single tablet every 12 hours for 5 days. Peak quinidine serum concentrations of 2.7 +/- 0.8 mg/L occurred 2.5 +/- 1.1 hour after 'Quinaglute' administration, significantly higher (p less than 0.01) than concentrations of 1.6 +/- 0.4 mg/L achieved 4.2 +/- 1.1 hours following 'Biquin' dosing and 1.7 +/- 0.6 mg/L attained 3.9 +/- 2.7 hours after 'Quinidex' ingestion. The extent of absorption based on AUC infinity and normalised for the anhydrous quinidine content was similar for the 3 products. Following multiple dosing, the mean steady-state trough concentration of quinidine was 2.06 +/- 0.56 mg/L for 'Quinidex', significantly greater (p less than 0.05) than that of 'Biquin' (1.18 +/- 0.67 mg/L) or 'Quinaglute' (1.58 +/- 0.58 mg/L). The rate of absorption was found to be much slower for 'Quinidex' than for the other 2 sustained release quinidine formulations. Comparison of the residual sums of squares from simple linear regression of Wagner-Nelson plots did not demonstrate a preference for a zero- or first-order absorption model. Nevertheless, the absorption of 'Quinidex' was twice as prolonged as that of 'Biquin' and 'Quinaglute' regardless of model; first-order absorption half-lives were 2.83 +/- 1.02 hours, 1.25 +/- 0.6 hours and 1.43 +/- 0.88 hours, respectively. The data also suggest that 'Quinidex' absorption may continue beyond 12 hours in some subjects.(ABSTRACT TRUNCATED AT 250 WORDS)