In a 6-month, double-blind, placebo-controlled study, 100 to 150 mg/d indomethacin appeared to protect mild to moderately impaired Alzheimer's disease patients from the degree of cognitive decline exhibited by a well-matched, placebo-treated group. Over a battery of cognitive tests, indomethacin patients improved 1.3% (+/- 1.8%), whereas placebo patients declined 8.4% (+/- 2.3%)--a significant difference (p < 0.003). Caveats include adverse reactions to indomethacin and the limited scale of the trial.

No abstract

Methamphetamine in large doses decreases striatal tyrosine hydroxylase activity. This effect is prevented by neuroleptic agents such as chlorpromazine and haloperidol which would suggest that released dopamine may be involved in the response. To test this hypothesis, we have altered dopamine synthesis with alpha-methyl-p-tyrosine and L-Dopa and found that dopamine synthesis is necessary for the observed depression of striatal TH activity by methamphetamine. In the adrenal gland, however, the increase in TH activity by methamphetamine is not prevented by inhibition of catecholamine synthesis. It is possible that released dopamine may be inhibiting TH activity by activation of pre- or postsynaptic dopamine receptors in the neostriatum resulting in activation of the neuronal feedback pathway or released dopamine may act on dendrodendritic autoreceptors in the substantia nigra.

The effect of ranitidine in preventing mucosal damage caused by nonsteroidal antiinflammatory drugs (NSAIDs) was evaluated for eight weeks in a prospective study of 144 patients requiring NSAIDs. Patients with normal endoscopic findings were randomly assigned to receive either ranitidine 150 mg twice daily or placebo for eight weeks, along with either ibuprofen, indomethacin, naproxen, sulindac, or piroxicam. Duodenal damage was significantly less in the ranitidine group compared with the placebo group by weeks 4 and 8 (P less than or equal to 0.01). Duodenal ulcers did not develop in any patients on ranitidine (0/57) compared with 4/49 patients (8%) on placebo (P = 0.02). No significant difference was found between treatment groups with respect to gastric damage; 6/60 (10%) in the ranitidine group compared with 6/50 (12%) in the placebo group developed gastric ulcers. These findings suggest that acid suppression is of greater importance for mucosal protection in the duodenum than in the stomach, where other defense mechanisms may be operative. While ranitidine is an effective prophylaxis for NSAID-induced damage in the duodenum, further studies are needed to define specific risk groups and to assess the potential usefulness of more complete acid suppression in preventing gastric mucosal damage.