Repeated trimipramine induces dopamine D2/D3 and alpha1-adrenergic up-regulation

Trimipramine (TRI), which shows a clinical antidepressant activity, is chemically related to imipramine but does not inhibit the reuptake of noradrenaline and 5-hydroxytryptamine, nor does it induce beta-adrenergic down-regulation. The mechanism of its antidepressant activity is still unknown. The aim of the present study was to find out whether TRI given repeatedly was able to induce adaptive changes in the dopaminergic and alpha1-adrenergic systems, demonstrated by us previously for various antidepressants. TRI was given to male Wistar rats and male Albino Swiss mice perorally twice daily for 14 days. In the acute experiment TRI (given i.p.) does not antagonize the reserpine hypothermia in mice and does not potentiate the 5-hydroxytryptophan head twitches in rats. TRI given repeatedly to rats increases the locomotor hyperactivity induced by d-amphetamine, quinpirole and (+)-7-hydroxy-dipropyloaminotetralin (dopamine D2 and D3 effects). The stereotypies induced by d-amphetamine or apomorphine are not potentiated by TRI. It increases the behaviour stimulation evoked by phenylephrine (given intraventricularly) in rats, evaluated in the open field test as well as the aggressiveness evoked by clonidine in mice, both these effects being mediated by an alpha1-adrenergic receptor. It may be concluded that, like other tricyclic antidepressants studied previously, TRI given repeatedly increases the responsiveness of brain dopamine D2 and D3 (locomotor activity but not stereotypy) as well as alpha1-adrenergic receptors to their agonists. A question arises whether the reuptake inhibition is of any importance to the adaptive changes induced by repeated antidepressants, suggested to be responsible for the antidepressant activity.     

A Comparative Study of Mechanical Properties,Thermal Conductivity,Residual Stresses,and Wear Resistance of Aluminum-Alumina Composites Obtained by Squeeze Casting and Powder Metallurgy

Squeeze casting and powder metallurgy techniques were employed to fabricate AlSi12/Al₂O₃ composites, which are lightweight structural materials with potential applications in the automotive industry. The impact of the processing route on the material properties was studied. Comparative analyses were conducted for the Vickers hardness, flexural strength, fracture toughness, thermal conductivity, thermal residual stresses, and frictional wear. Our results show that the squeeze cast composite exhibits superior properties to those obtained using powder metallurgy.

     

Effect of MoO3, Nd2O3, and RuO2 on the crystallization of soda–lime aluminoborosilicate glasses

The effect of adding Nd₂O₃, MoO₃, and RuO₂ separately or simultaneously on the crystallization of a soda–lime aluminoborosilicate glass during cooling from the melt or glass heating was studied by DTA, XRD (at room and high temperature), SEM, Raman, and optical absorption. Nd₂O₃ addition strongly reduces liquid–liquid phase separation and crystallization of calcium and sodium molybdates (CaMoO₄ (powellite) and Na₂MoO₄) in Mo-rich compositions as long as Nd³⁺ ions remain solubilized in the glassy network. This suggests that (MoO₄)^2? entities and Nd³⁺ ions are close to each other in the glass structure (Nd³⁺ ions would prevent the clustering of molybdate entities). The effect of MoO₃ addition in Nd-rich compositions is more complex since an increase of the solubility of Nd₂O₃ is observed, whereas the nucleation rate of an Nd-rich silicate apatite (Ca₂Nd₈(SiO₄)₆O₂) in the bulk of the glass increases as soon as molybdates crystallized. The addition of RuO₂ has a nucleating effect on apatite crystallization in the bulk but not on molybdates crystallization.     

A digital X-ray imaging system based on silicon strip detectors working in edge-on configuration

We present the energy resolution and imaging performance of a digital X-ray imaging system based on a 512-strip silicon strip detector (SSD) working in the edge-on configuration. The SSDs tested in the system are 300 μm thick with 1 or 2-cm-long strips and 100 μm pitch. To ensure a very small dead area of the SSD working in edge-on configuration, the detector is cut perpendicular to the strips at a distance of only 20 μm from the end of the strips. The 512-strip silicon detector is read out by eight 64-channel integrated circuits called DEDIX [Grybos et al., IEEE Trans. Nucl. Sci. NS-54 (2007) 1207]. The DEDIX IC operates in a single photon counting mode with two independent amplitude discriminators per channel. The readout electronic channel connected to a detector with effective input capacitance of about 2 pF has an average equivalent noise charge (ENC) of about 163 el. rms and is able to count 1 Mcps of average rate of input pulses. The system consisting of 512 channels has an excellent channel-to-channel uniformity—the effective threshold spread calculated to the charge-sensitive amplifier inputs is 12 el. rms (at one sigma level). With this system a few test images of a phantom have been taken in the 10–30 keV energy range.     

Assignment of the 2.03 ppm resonance in in vivo <Superscript>1</Superscript>H MRS of human brain tumour cystic fluid: contribution of macromolecules

MRI and MRS are established techniques for the evaluation of intracranial mass lesions and cysts. The 2.03 ppm signal recorded in their ¹H-MRS spectra is often assigned to NAA from outer volume contamination, although it has also been detected in non-infiltrating tumours and large cysts. We have investigated the molecular origin of this resonance in ten samples of cystic fluids from human brain tumours. The NMR detected content of the 2.03 ppm resonance in 136 ms echo time spectra, assuming an N- CH₃ origin, was 3.19 ± 1.01 mM. Only one third (34 ± 12%) of the N-acetyl containing compound (NAC) signal could be extracted by perchloric acid (PCA) indicating that most of it originated in a macromolecular PCA-insoluble component. Chemical analysis of the cyst fluids showed that sialic acid bound to macromolecules would account for 64.3% and hexuronic containing compounds for 29.2% of the NMR-detectable ex vivo signal, 93.4% of the signal at TE 136 ms. Lactate content measured by NMR (6.4 ± 4.4 mM) and the predominance of NAC originating in sialic acid point to a major origin from tumour rather than from plasma for this 2.03 ppm resonance.     

Some behavioral effects of 1,3-di-o-tolylguanidine, opipramol and sertraline, the sigma site ligands

1,3-Di-o-tolylguanidine (DTG), opipramol (OPI) and sertraline (SER), sigma site ligands, were studied in Wistar rats and Albino Swiss mice, mainly with regard to their interaction with dopamine drugs. DTG and SER (at the highest doses only) decreased the spontaneous locomotor activity. DTG did not change the amphetamine locomotor hyperactivity, while OPI and SER decreased it. The amphetamine stereotypy was slightly increased (prolonged) by all the three drugs. OPI antagonized the locomotor hyperactivity, stereotypy, aggression and climbing, all those being induced by apomorphine; DTG inhibited only the aggression, while SER-the aggression and climbing (the latter was also inhibited by paroxetine, which showed no affinity for sigma sites). DTG and SER (but not paroxetine) were able to increase the locomotor hyperactivity induced by quinpirole. That effect was antagonized by OPI which-when given alone-did not affect the quinpirole hyperlocomotion. The reserpine-induced akinesia was not affected by DTG, OPI or SER; the L-DOPA hyperactivity in reserpinized rats was changed (increased) by DTG only. DTG and SER (also paroxetine and citalopram), but not OPI, increased the cocaine locomotor hyperactivity. All the three sigma ligands given alone did not evoke catalepsy; the haloperidol- and spiperone-induced catalepsy was attenuated by DTG and OPI, but increased by SER. The MK-801-induced hyperactivity was decreased by DTG, but increased by OPI and SER. In the forced swimming test, only DTG slightly reduced the immobility time; the reduction of the immobility time induced by MK-801 was not changed by DTG, but increased by OPI and SER. Only DTG evoked a dose-dependent decrease in the body temperature, which was not changed by rimcazole. The above results indicate that the sigma site ligands studied differ in their pharmacological profile; however, it is still difficult to determine unequivocally whether they show agonistic or antagonistic properties.     

Neuropsychological slowness in obsessive-compulsive patients. Is it confined to tests involving the fronto-subcortical systems?

BACKGROUND: Although it is acknowledged that obsessive-compulsive (OC) patients may be slower than healthy controls in performing neuropsychological tests, speed has usually been treated as a confounding variable. It is possible, however, that the slower performance of OC patients is itself the result of a dysfunction of specific neural circuits (in particular of fronto-subcortical systems). METHOD: A neuropsychological battery including tests sensitive to fronto- and temporo-subcortical dysfunction was administered to a group of OC patients and a group of healthy controls. Each test provided independent indices of accuracy and speed. RESULTS: OC patients were significantly slower than controls only when performing tasks involving the fronto-subcortical systems, whereas they did not differ from controls with respect to accuracy indices. CONCLUSION: It may be that neuropsychological slowness of OC patients is not merely an epiphenomenon of meticulous concern for correct test execution or intrusion of obsessive thoughts, but reflects the dysfunction of fronto-subcortical systems.     

Plasma prolactin response to D-fenfluramine is blunted in bulimic patients with frequent binge episodes

BACKGROUND: Abnormalities of brain serotonin (5-HT) transmission have been implicated in the pathophysiology of bulimia nervosa (BN), but no conclusive data have yet been provided. The purpose of this study was to assess 5-HT transmission via the measurement of the prolactin (PRL) response to the specific 5-HT releasing agent D-fenfluramine (D-FEN) in both patients with BN and comparison subjects. METHODS: According to a double-blind placebo-controlled design, plasma PRL response to D-FEN was measured in 14 drug-free bulimics and 14 matched healthy controls. In both patients and controls, eating-related psychopathology, depressive and obsessive-compulsive symptoms, and aggressiveness were measured by rating scales. RESULTS: Baseline plasma levels of PRL and 17 beta-oestradiol were significantly reduced in bulimic patients, whereas basal plasma levels of cortisol did not significantly differ from healthy controls. PRL response to D-FEN was not different between patients and controls as groups, but it was significantly blunted in bulimics with high frequency bingeing (> or = 2 binge episodes per day; N = 7) as compared to both those with low frequency bingeing (< or = 1 binge episode per day; N = 7) and matched controls. A significant negative correlation emerged between the frequency of binge episodes and the hormone response to D-FEN. Moreover, although patients scored higher than healthy subjects on rating scales assessing depressive and obsessive-compulsive symptoms and aggressiveness, no significant correlation was found between these measures and the PRL response to D-FEN. CONCLUSIONS: These results support the idea that serotonin transmission is impaired in bulimic patients with frequent binge episodes.     

Social and clinical factors influencing the choice of coping strategies in relatives of patients with schizophrenia: results of the BIOMED I study

The impact of social and clinical factors on the choice of coping strategies of a sample of 236 relatives of patients with schizophrenia, living in five European countries, was explored using well-validated questionnaires. The adoption of problem-focused coping strategies was more frequent among young relatives and among relatives of younger patients, and was associated with higher levels of practical and emotional social support and of professional help. In contrast, emotion-focused strategies were more frequently adopted by relatives who had been living longer with the patient and who had poorer social support. It is suggested that supportive and educational interventions should be provided as early as possible to relatives of patients with schizophrenia, which, in addition to having a practical focus, should also have a social focus, aiming at extending the family's social network.     

Correction to: A Comparative Study of Mechanical Properties,Thermal Conductivity,Residual Stresses,and Wear Resistance of Aluminum-Alumina Composites Obtained by Squeeze Casting and Powder Metallurgy

Metallurgical and Materials Transactions A -