Automated classification of short echo time in in vivo 1H brain tumor spectra: a multicenter study.

Automated pattern recognition techniques are needed to help radiologists categorize MRS data of brain tumors according to histological type and grade. A major question is whether a computer program "trained" on spectra from one hospital will be able to classify those from another, particularly if the acquisition protocol is different. A subset of 144 histopathologically validated brain tumor spectra in the INTERPRET database, obtained from three of the collaborating centers, was grouped into meningiomas, low-grade astrocytomas, and "aggressive tumors" (glioblastomas and metastases). Spectra from two centers formed the training set (94 spectra) while the third acted as the test set (50 spectra). Linear discriminant analysis successfully classified 48/50 in the test set; the remaining two were atypical cases. When the training and test sets were combined, 133 of the 144 spectra were correctly classified using the leave-one-out procedure. These spectra had been obtained using different sequences (STEAM and PRESS), different echo times (20, 30, 31, and 32 ms), different repetition times (1600 and 2000 ms), and different manufacturers' instruments (GE and Philips). Pattern recognition algorithms are less sensitive to acquisition parameters than had been expected.     

Effect of repeated treatment with tianeptine and fluoxetine on the central alpha(1)-adrenergic system

Tianeptine (TIA) is an antidepressant drug which enhances the reuptake of serotonin but, in contrast to tricyclics, shows no affinity for neurotransmitter receptors. The present study was aimed at determining whether repeated TIA treatment induced adaptive changes in the alpha(1)-adrenergic system, similar to those reported by us earlier for tricyclic antidepressants. The experiments were carried out on male mice and rats. TIA was administered at a dose of 5 or 10mg/kg once or repeatedly (twice daily for 14 days) and fluoxetine (FLU), used as a reference compound, at a dose of 10mg/kg. The obtained results showed that TIA administered repeatedly potentiated the methoxamine- and phenylephrine (PHEN)-induced exploratory hyperactivity in rats and clonidine-induced aggressiveness in mice, the effects mediated by alpha(1)-adrenoceptors. TIA given repeatedly (but not acutely) increased the binding (B(max)) of alpha(1)-adrenergic receptors in cerebral cortex for [(3)H]prazosin. However, the ability of the alpha(1)-adrenoceptor agonist PHEN to compete for these sites was not significantly changed. The above results indicate that repeated TIA administration increases the responsiveness of the alpha(1)-adrenergic system (behavioural and biochemical changes). On the other hand, FLU did not affect any behavioural and biochemical changes in this system.     

Pharmacological profile of milnacipran, a new antidepressant, given acutely.

Pharmacological effects of acute treatment with milnacipran (MIL), a clinically active antidepressant (a noradrenaline [NA] and 5-hydroxytryptamine [5-HT] reuptake inhibitor without any affinity for neurotransmitter receptors) were studied in mice and rats. MIL inhibited the reserpine- or apomorphine-induced hypothermia in mice and enhanced the L-5-hydroxytryptophan-induced head twitches in rats. It reduced the immobility time in Porsolt's test in mice and rats, but either did not change the locomotor activity (mice) or decreased it (rats). MIL changed neither the clonidine-induced aggressiveness in mice nor the behavioral syndrome induced by oxotremorine in rats. The obtained results indicate that MIL, given acutely, shows a pharmacological profile similar to that of tricyclic NA and 5-HT reuptake inhibitors. In contrast to the antidepressants mentioned above, MIL does not exhibit an alpha1-adrenolytic or cholinolytic activity (in vivo tests).     

Effect of repeated treatment with milnacipran on the central dopaminergic system

Milnacipran (MIL) is a representative of a new class of antidepressants (SNRIs) which inhibit the reuptake of serotonin and noradrenaline, but, in contrast to tricyclics, show no affinity for neurotransmitters receptors. The present study was aimed at determining whether repeated MIL administration (given at doses of 10 or 30 mg/kg, twice daily for 14 days) induced the adaptive changes in the dopaminergic system similar to those reported by us earlier for tricyclic antidepressants. The obtained results showed that MIL administered repeatedly did not change the responsiveness of dopamine D1 receptors since it did not change the SKF 38393-induced grooming. Repeated MIL treatment increased the hyperlocomotion induced by D-amphetamine and 7-OH-DPAT, but did not affect the D-amphetamine and apomorphine stereotypies. The binding parameters (Bmax and Kd) to dopamine D1 and D2 receptors in the limbic forebrain were not affected by repeated MIL treatment when [3H]SCH 23390 and [3H]spiperone, respectively, were used as ligands. On the other hand, the increased density of dopamine D2 receptors (Bmax) was observed in the striatum after repeated treatment with MIL. MIL administered acutely or repeatedly did not change the binding of [3H]7-OH-DPAT to dopamine D3 receptors in the islands of Calleja and the shell region of the nucleus accumbens septi. The above results indicate that repeated MIL administration induces the adaptive changes in the dopaminergic system, especially it enhances the functional responsiveness of dopamine D2 and D3 receptors. However, the question whether this increased functional responsiveness is important for the clinical antidepressant efficacy, remains open.     

Pneumocystis carinii pneumonia in a Yorkshire terrier dog.

A 14-month-old male Yorkshire terrier was presented to the Autonomous University of Barcelona Veterinary Teaching Hospital because of a history of chronic non-productive cough and acute dyspnea. A follow-up radiograph revealed a diffuse, bilaterally interstitial-alveolar lung disease with presence of air bronchograms. The dog died 5 h after admission with severe dyspnea. Histological sections of the necropsy specimens revealed the presence of characteristic Pneumocystis carinii cysts within alveolar spaces. A diagnosis of P. carinii pneumonia (PCP) was made on the basis of these results. To our knowledge, PCP has not been described in a Yorkshire terrier dog.     

Antidepressant drugs given repeatedly increase the behavioural effects of methoxamine

In this study we investigated the effect of imipramine, citalopram and mianserin on behavioural effects of methoxamine, an α₁-adrenoceptor agonist, in the rat. Methoxamine (25 and 50 m?g) given into the brain lateral ventricle, increases the exploratory activity assessed in the open field test (time of walking, ambulatory activity, rearing ⁺ peeping). The studied antidepressants, administered repeatedly (10 mg/kg p.o., twice daily, 14 days) but not in single doses, enhance the above effects of methoxamine. The results provide further arguments for the hypothesis that antidepressant drugs administered repeatedly induce a functional α₁-adrenoceptor up-regulation.