Metallothionein expression by NG2 glial cells following CNS injury.

Metallothionein (MT) expression is rapidly up-regulated following CNS injury, and there is a strong correlation between the presence or absence of MTand improved or impaired (respectively) recovery from such trauma.We now report that a distinct subset of NG2-positive, GFAP-negative glial cells bordering the injury tract express MT following focal injury to the adult rat neocortex. To confirm the ability of these NG2 glial cells to express MT, we have isolated and cultured them and identified that they can express MT following stimulation with zinc. To investigate the functional importance of MT expression by NG2 glial cells, we plated cortical neurons onto these cells and found that expression of MT enhanced the permissivity of NG2 glial cells to neurite outgrowth. Our data suggest that expression of MT by NG2 glial cells may contribute to the overall permissiveness of these cells to axon regeneration.

Neurochemical diversity of dystrophic neurites in the early and late stages of Alzheimer's disease.

We examined the neurochemical and morphological diversity of abnormal neurites associated with beta-amyloid plaque formation in the early and late stages of Alzheimer's disease. Preclinical Alzheimer's disease was characterised by the presence of abnormal neurites containing either neurofilament or chromogranin A immunoreactivity. All clustered dystrophic neurites in these cases were associated with beta-amyloid plaques. Neurofilament immunoreactive dystrophic neurites in preclinical Alzheimer's disease could be further subclassified into bulb- and ring-like structures, and these abnormal neurites contained both phosphorylated and dephosphorylated neurofilament epitopes. Dystrophic neurites in Alzheimer's disease could be subdivided into predominantly neurofilament, tau, or chromogranin A immunolabeled forms. Some neurofilament immunoreactive neurites had a core region labeled for tau. The neurofilaments of the dystrophic neurites in Alzheimer's disease had the same complement of phosphorylation- and dephosphorylation-dependent epitopes as observed in preclinical cases. Therefore, an abnormal accumulation of variably phosphorylated neurofilaments represent the earliest cytoskeletal alteration associated with dystrophic neurite formation. Furthermore, these data indicate that dystrophic neurites may "mature" through neurofilament-abundant forms to the neurites containing the profoundly altered filaments labeled for tau. The precise morphological and neurochemical changes associated with dystrophic neurite formation suggests that beta-amyloid plaques are causing physical damage to surrounding axons. The resultant axonal sprouting and profound cytoskeletal alterations would follow the chronic stimulation of the stereotypical reaction to such physical trauma.

Endoscopic evaluation of rioprostil in the management of non-steroidal anti-inflammatory drug-induced gastritis: an interim analysis.

The effects of the synthetic prostaglandin E1 analogue, rioprostil, on non-steroidal anti-inflammatory drug-induced (NSAID) gastritis are investigated. The study is of randomized, double-blind design. Patients are included who had classical or definite rheumatoid arthritis or osteoarthritis, had been taking a stable dose of NSAID or aspirin for at least one month and had endoscopically proven gastric lesion. Endoscopy is performed prior to, and at 4, 8 and 12 weeks of the treatment period. Patients receive either rioprostil, 300 micrograms or 100 micrograms q.d.s., or placebo q.d.s. The results of the endoscopies show greater healing of the mucosa in patients taking rioprostil compared with those taking placebo. It is therefore concluded that rioprostil is an effective compound for the management of patients with NSAID-induced gastritis.

The antigastrolesive activity of rioprostil, a 16-methyl prostaglandin-E1 analogue in healthy volunteers.

The antigastrolesive activity of rioprostil, an orally effective synthetic 16-methyl analogue of prostaglandin-E1, with potent antisecretory and antigastrolesive properties in animals, is evaluated in a series of studies involving 166 healthy male volunteers. Three double-blind, randomized, parallel, placebo-controlled studies are conducted independently at three study centres. In two studies the protective effect of rioprostil against endoscopically-demonstrated mucosal changes caused by concurrent administration of aspirin is examined. The third study evaluates the inhibitory effect of rioprostil on faecal blood loss produced by co-administration of aspirin. Oral doses of rioprostil give significant dose-dependent protection against aspirin-induced mucosal changes. The total mucosal scores at day 3 and day 11 are significantly lower in each of the rioprostil + aspirin groups compared with the aspirin treated group. The total mucosal scores generally decrease with increasing rioprostil dose. Daily faecal blood loss is significantly lower in each of the groups of subjects treated with rioprostil + aspirin, compared with those treated with aspirin + placebo. This study shows that rioprostil provides significant protection against mucosal damage caused by high doses of concomitantly administered aspirin.

Effect of rioprostil on aspirin-induced gastrointestinal mucosal changes in normal volunteers.

Rioprostil, a 15-deoxy-16-methyl prostaglandin E1, was evaluated for its effect on aspirin-induced gastrointestinal mucosal changes in normal volunteers. Fifty-six normal male volunteers were evaluated by endoscopy in a double-blind, placebo-controlled study. Aspirin was given at a dose of 975 mg four times per day. Rioprostil was given at doses of 60, 120, and 300 micrograms four times per day. Rioprostil, at both antisecretory and subantisecretory doses, prevented or reduced aspirin-induced injury. Increased stool frequency was the most common side effect and appeared to be a dose-related effect of rioprostil occurring at only antisecretory doses.