Effectiveness of clozapine and olanzapine: a comparison in severe, psychotically ill patients

The aim of our study was to evaluate the effectivenessof clozapine and olanzapine in the treatment of schizophrenicpatients. Either clozapine or olanzapine signifcantly ameliorated positive symptoms, but only clozapine was effective in reducinganxiety and hallucinations, while olanzapine was more effective in reducing negative symptoms, such as mannerism and posturing, blunted affect and emotional withdrawal. Olanzapine-treated patients obtained significantly higher GAF scores than clozapine-treated patients and more frequently participated in rehabilitative programmes. In conclusio, olanzapine therapy has surprisingly been shown to be more effective than clozapine in improving social and working skills

In vitro effects of cocaine on tunneling nanotube formation and extracellular vesicle release in glioblastoma cell cultures

The effects of cocaine (150 nM, 300 nM, and 150 μM) on human glioblastoma cell cultures were studied on tunneling nanotube formation (1-h cocaine treatment) and extracellular vesicle release (1-, 3-, and 8-h cocaine treatment). Cocaine significantly increased the number of tunneling nanotubes only at the lowest concentration used. The release of extracellular vesicles (mainly exosomes) into the medium was stimulated by cocaine at each concentration used with a maximum effect at the highest concentration tested (150 μM). Moreover, cocaine (150 nM) significantly increased the number of vesicles with 61-80 nm diameter while at concentrations of 300 nM and 150 μM, and the smaller vesicles (30-40 nm diameter) were significantly increased with a reduction of the larger vesicles (41-60 nm diameter). A time dependence in the release of extracellular vesicles was observed. In view of the proposed role of these novel intercellular communication modes in the glial-neuronal plasticity, it seems possible that they can participate in the processes leading to cocaine addiction. The molecular target/s involved in these cocaine effects could be specific molecular components of plasma membrane lipid rafts and/or cocaine-induced modifications in cytoplasmic lipid composition

Bioinformatics and mathematical modelling in the study of receptor-receptor interactions and receptor oligomerization: focus on adenosine receptors.

none8sìThe concept of intra-membrane receptor-receptor interactions (RRIs) between different types of G protein-coupled receptors (GPCRs) and evidence for their existence was introduced by Agnati and Fuxe in 1980/81 through the biochemical analysis of the effects of neuropeptides on the binding characteristics of monoamine receptors in membrane preparations from discrete brain regions and functional studies of the interactions between neuropeptides and monoamines in the control of specific functions such as motor control and arterial blood pressure control in animal models. Whether GPCRs can form high-order structures is still a topic of an intense debate. Increasing evidence, however, suggests that the hypothesis of the existence of high-order receptor oligomers is correct. A fundamental consequence of the view describing GPCRs as interacting structures, with the likely formation at the plasma membrane of receptor aggregates of multiple receptors (Receptor Mosaics) is that it is no longer possible to describe signal transduction simply as the result of the binding of the chemical signal to its receptor, but rather as the result of a filtering/integration of chemical signals by the Receptor Mosaics (RMs) and membrane-associated proteins. Thus, in parallel with experimental research, significant efforts were spent in bioinformatics and mathematical modelling. We review here the main approaches that have been used to assess the interaction interfaces allowing the assembly of GPCRs and to shed some light on the integrative functions emerging from the complex behaviour of these RMs. Particular attention was paid to the RMs generated by adenosine A(2A), dopamine D-2, cannabinoid CB1, and metabotropic glutamate mGlu(5) receptors (A(2A). D-2, CB1, and mGlu(5), respectively), and a possible approach to model the interplay between the D-2-A(2A)-CB1 and D-2-A(2A)-mGlu(5) trimers is proposed. This article is part of a Special Issue entitled: "Adenosine Receptors". (C) 2010 Elsevier B.V. All rights reserved.openD. GUIDOLIN; F. CIRUELA; S. GENEDANI; M. GUESCINI; C. TORTORELLA; G. ALBERTIN; K. FUXE; L.F. AGNATID., Guidolin; F., Ciruela; S., Genedani; Guescini, Michele; C., Tortorella; G., Albertin; K., Fuxe; L. F., Agnat

Neural damage biomarkers during open carotid surgery versus endovascular approach

BACKGROUND: Carotid endarterectomy (CEA) is the gold standard for treating severe carotid artery stenosis, whereas carotid artery stenting (CAS) represents an endovascular alternative. The objective of this study was to assess the potential neural damage following open or endovascular carotid surgery measured by peripheral blood concentration of 3 biomarkers: S100β, matrix metalloproteinase-9 (MMP-9), and d-dimer. METHODS: Data for this prospective investigation were obtained from the Carotid Markers study (January 2010-2011), which sought to measure the levels of specific biomarkers of neuronal damage and thrombosis on candidates to CEA or CAS presenting at the Department of Vascular Surgery of the Nuovo Ospedale S. Agostino Estense of Modena (Italy) at baseline and at 24 hr after surgery. Relevant medical comorbidities were noted. RESULTS: A total of 113 consecutive patients were enrolled in the study, 41 in the endarterectomy group and 72 in the endovascular group. The baseline levels of the studied biomarkers did not show any statistically significant difference between the groups with the exception of MMP-9, which showed higher concentrations in the endovascular group (median 731 vs. 401, P = 0.0007), while 24 hr after surgery the endarterectomy group featured significantly higher peripheral blood concentrations of MMP-9, S100β, and d-dimer. Conversely, no significant difference was detected in the endovascular group except the d-dimer level. CONCLUSIONS: Neural damage biomarkers demonstrated a substantial difference between open and endovascular carotid surgery, which, if performed in selected patients, may become a less invasive alternative to CEA

Neuropeptides of the stress response and monocyte motility

Monocyte locomotion is influenced by neuropeptides of the stress response. In particular, ACTH1-24 and CRF behave as chemokinetic agents while ACTH1-39 and Alpha-MSH have no effect on the migration of monocytes. The present data suggest that these neuropeptides may play a physiological role in the immune responseand that in stressful situations they may modify the functional activity of the immune system

ACTH and its role in immune-neuroendocrine functions. A comparative study

Adrenocorticotropic hormone (ACTH) belongs to the melanocortine group of related peptides which share a common precursor, the pro-opiomelanocortin (POMC). Melanocortin expresses its functional effects by the stimulation of specific G-protein coupled receptors, To date, five receptor subtypes have been cloned. The POMC gene has been highly conserved during evolution, and ACTH has been found in different cells from invertebrates to vertebrates to vertebrates, including man. With regards the immune system, the presence of melanocortin receptors and the production of ACTH have been reported in invertebrate and vertebrate immune-competent cells. Among its various physiological effects, ATCH has been shown to play a central role in immmune responses, such as chemotaxis and phagocytosis, in lower and higher forms of life. Moreover, ACTH is a key actor in stress response, and the complex cascade of events observed in vertebrates is reproduced and concentrated in intvertebrate immunocytes. On the basis of the present findings, ACTH should be considered an important immunoregulator, forming part of the complex mosaic of relationships between the immune and neuroendocrine system which appears to have been substantially maintained over the course of evolution

Development and behavioral outcomes of perinatal inhibition of ornithine decarboxylase.

Rats were treated with alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC), at a dose of 200 mg/kg/day SC, either prenatally (to the mothers, on days 16 to 20 of gestation) or neonatally (to the pups, on days 1 to 10 after birth). At this dose level neither maternal reproductive performance (prenatal treatment) nor gain in body weight on the part of offspring were affected. Earlier developmental alterations were rapidly overcome. Prenatally-treated rats proved less active than controls in the open field, performed better in passive avoidance retention (both preweaning and postweaning), and had a shorter post-ejaculatory interval in the male copulatory test. Postnatally-treated rats performed better than controls in two-way active avoidance conditioning, and in passive avoidance retention (as adults). Reproductive performance of the treated female offspring was similar to that of controls. ODC activity in brains of DFMO-exposed offspring was substantially inhibited throughout treatment (-72 to -41%, compared with respective controls), but showed a strong rebound after termination of treatment (up to +400%, compared with respective controls). These results show that partial inhibition of ODC activity during a limited period of the perinatal life has no adverse effect on the overall behavioral development of rats: indeed, some performances are actually improved. This being the most likely due to a rebound ODC hyperactivity after termination of treatment, when brain maturation is still in progress