Safety and efficacy of a non-steroidal anti-androgen, based on results of a post marketing surveillance of nilutamide.

The use, tolerability and efficacy of the non-steroidal anti-androgen nilutamide (Anandron(R)) in daily clinical practice was investigated in this 5-y project. In total 725 patients were recruited from 27 Dutch centres. The investigated population was very heterogeneous and different therapeutic options were reported. We may conclude that in general good results have been obtained, especially in first line combination therapy combined with luteinising hormone releasing hormone (LHRH) agonists. Patients with a good performance status at inclusion seem to benefit more from nilutamide combination therapy.Prostate Cancer and Prostatic Diseases (2001) 4, 112-117

Effects of stress and exercise on rat hippocampus and striatum extracellular lactate.

Extracellular lactate was continuously monitored (lactography) to determine the effect of various stressors to assess glucose metabolism in the rat hippocampus and striatum. It appeared that immobilization, emotional stress, and exercise (physiological stress) all resulted in an increase in hippocampal extracellular lactate. Exercise had the most pronounced effect. These increases were different for rats raised in different laboratories. Only during exercise a transient increase in lactate was seen in striatum. Peripheral infusions of epinephrine and/or corticosterone did not affect the basal levels of hippocampal lactate. Adrenodemedullated rats showed an attenuated lactate increase compared with control rats during and shortly after exercise. Administration of ipsapirone, an anxiolytic drug, attenuated the stress-induced formation of the hippocampal lactate. The present study demonstrates the usefulness of lactography to monitor regional brain metabolism in freely moving animals, exposed to various stressors, breeding conditions, or drugs. The observed different responsiveness of the two brain-region studies emphasizes the different involvement of the striatum and hippocampus in motor and emotional behavior, respectively. Lactate formation is stimulated by excitatory neuronal activity, presumably originating in the cerebral cortex, although adrenal hormones appear to contribute.

Mild stress stimulates rat hippocampal glucose utilization transiently via NMDA receptors, as assessed by lactography.

Lactography is a novel technique that allows the continuous on-line registration of brain extracellular lactate in the freely behaving animal and that is based on a fluorimetric enzymatic assay of brain dialysates. Electroconvulsive shock, activation of the glutamate receptor (NMDA-type) and mild stress (immobilization, cold stress or handling) result in transient increases in the efflux of lactate from the rat hippocampus. The increase following immobilization stress was attenuated by the NMDA-receptor antagonist 2-amino-5-phosphopentanoic acid and after several pre-exposures to this stressor. These experiments suggest that mild stress activates glutamatergic neurons, which may be less after habituation to stress.