Taurine analogues as modifiers of the accumulation of 45calcium ions in a rat retinal membrane preparation

The effects of a series of taurine analogues on the accumulation of 45calcium ions in a crude rat retinal membrane preparation are reported. 45Calcium ion accumulation was measured at high (1.4 mM) calcium ion concentration in the presence and absence of ATP. In the absence of ATP, taurine and alpha-sulfo-beta-alanine both inhibit 45calcium ion accumulation. alpha-Sulfo-beta-alanine is the more potent of the two compounds (50% vs. 30% inhibition at 20 mM). The trans aminocycloalkanesulfonic acid analogues of taurine [(+/-) trans-2-aminocyclopentanesulfonic acid and (+/-) trans-2-aminocyclohexanesulfonic acid] are stimulators (3- to 4-fold) of 45calcium ion accumulation. In the presence of ATP (1.2 mM), taurine and the analogues of taurine had no effect. Structure-activity-relationships of these compounds pertinent to their effects on 45calcium ion accumulation at a high calcium ion concentration and in the absence of ATP are discussed. In addition, the inhibitory effects of taurine on 45calcium accumulation in subfractions of the retina (rod outer segments, synaptosomes, and mitochondria) and the effects of the divalent ionophore A23187 on 45calcium accumulation were also investigated.     

Effects of chronic fluoxetine treatment on behavioral and neuroendocrine responses to meta-chlorophenylpiperazine in obsessive-compulsive disorder

To investigate the effect of fluoxetine on serotonergic sensitivity in obsessive-compulsive disorder (OCD), the partial serotonin agonist metachlorophenylpiperazine (mCPP) was compared to placebo under double-blind conditions in six patients with OCD before and during treatment with fluoxetine. Readministration of oral mCPP (0.5 mg/kg) after at least 12 weeks of fluoxetine treatment did not increase obsessive-compulsive (OC) symptoms, in contrast to exacerbation of OC symptoms produced by mCPP before treatment. Chronic fluoxetine treatment resulted in a significant increase in prolactin and cortisol response to mCPP. This may be accounted for, however, by substantially increased plasma mCPP levels during fluoxetine treatment. Chronic fluoxetine treatment diminished the behavioral sensitivity to mCPP and did not diminish, but may have partially normalized, the neuroendocrine response to mCPP in patients with OCD. These adaptive homeostatic effects may reflect fluoxetine's antiobsessional mechanism.     

Open trial of intravenous clomipramine in five treatment-refractory patients with obsessive-compulsive disorder.

In a preliminary trial, five oral-clomipramine-refractory patients with obsessive-compulsive disorder (OCD) were treated openly with 14 intravenous clomipramine infusions each. Using standardized assessments, three patients were rated as much improved, one as unchanged, and one as minimally improved. Statistically significant improvements were noted on both the Yale-Brown Obsessive Compulsive Scale and the NIMH Global OCD scores. No patient discontinued treatment because of side effects. Although the results are provocative in that three of five patients were much improved at the end of the protocol, conclusions about preferential efficacy for the intravenous route must await a placebo-controlled trial.     

NSAID-induced mucosal injury

Nonsalicylate, nonsteroidal anti-inflammatory drug (NSAID)-induced injury to the gastroduodenal mucosa may be responsible for significant ulceration and bleeding. The pathophysiology of gastroduodenal injury is reviewed and risk factors predisposing to NSAID injury are discussed. Finally, data are presented on the concurrent use of prostaglandin analogues and sucralfate in preventing mucosal injury.