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  • 11
    In: Current Neuropharmacology, February 2018, Vol.16(2), pp.117-117
    ISSN: 1570-159X
    Source: Bentham Science (IngentaConnect)
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  • 12
    Language: English
    In: International Journal of Molecular Medicine, September 2011, Vol.28(3), pp.437-442
    Description: Preclinical studies have shown that the anti-glucocorticoid drug mifepristone effectively inhibits HIV replication both in vitro and in vivo. However, the drug did not demonstrate anti-HIV activity in a previous phase I/II study when administered at the daily dose of 75-225 mg. The aim of this study was to assess whether mifepristone may exert antiretroviral activity or influence immunological parameters when administered orally at daily doses of 150 or 300 mg in highly active antiretroviral therapy (HAART)-naïve HIV-infected patients. We performed an open label non-randomized phase II study that included 26 patients who underwent 28 days of once daily oral administration of 150 (12 subjects) or 300 mg (14 subjects) of mifepristone. A total of 3 patients dropped out of the study, respectively 1 in the 150 mg dose group and 2 in the 300 mg dose group. The main hemato­chemical alterations reported were hypokalemia and increase in the blood levels of cortisol, especially in those patients that received mifepristone at the dose of 300 mg/day. Although we observed a trend of reduced viral load along the study in both groups, statistical significance was not achieved for either the primary nor the secondary endpoints. In summary, mifepristone treatment was well-tolerated but it failed to significantly influence viro-immunological parameters in HAART-naïve HIV-infected patients.
    Keywords: Surgical Stapler;
    ISSN: 1107-3756
    E-ISSN: 1791244X
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  • 13
    Language: English
    In: Current Neuropharmacology, 2011, Vol.9(5), p.1-81
    ISSN: 1570-159X
    E-ISSN: 1875-6190
    Source: Bentham Science Publishers
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  • 14
    Language: English
    In: Current Neuropharmacology, 2018, Vol.16(2), p.117-117
    Keywords: Article;
    ISSN: 1570-159X
    E-ISSN: 1875-6190
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  • 15
    Language: English
    In: Psychopharmacology, 2011, Vol.217(3), pp.301-313
    Description: Byline: Sara Morley-Fletcher (1), Jerome Mairesse (1), Amelie Soumier (2), Mounira Banasr (2), Francesca Fagioli (3), Cecilia Gabriel (4), Elisabeth Mocaer (4), Annie Daszuta (2), Bruce McEwen (5), Ferdinando Nicoletti (1,6,7), Stefania Maccari (1) Keywords: Agomelatine; Prenatal stress; Adult neurogenesis; Ventral hippocampus; Fluoxetine; Phospho-CREB; Metabotropic glutamate receptors Abstract: Rationale and objectives The rat model of prenatal restraint stress (PRS) replicates factors that are implicated in the etiology of anxious/depressive disorders. We used this model to test the therapeutic efficacy of agomelatine, a novel antidepressant that behaves as a mixed MT1/MT2 melatonin receptor agonist/5-HT.sub.2c serotonin receptor antagonist. Results Adult PRS rats showed behavioral, cellular, and biochemical abnormalities that were consistent with an anxious/depressive phenotype. These included an increased immobility in the forced swim test, an anxiety-like behavior in the elevated plus maze, reduced hippocampal levels of phosphorylated cAMP-responsive element binding protein (p-CREB), reduced hippocampal levels of mGlu2/3 and mGlu5 metabotropic glutamate receptors, and reduced neurogenesis in the ventral hippocampus, the specific portion of the hippocampus that encodes memories related to stress and emotions. All of these changes were reversed by a 3- or 6-week treatment with agomelatine (40--50 mg/kg, i.p., once a day). Remarkably, agomelatine had no effect in age-matched control rats, thereby behaving as a "disease-dependent" drug. Conclusions These data indicate that agomelatine did not act on individual symptoms but corrected all aspects of the pathological epigenetic programming triggered by PRS. Our findings strongly support the antidepressant activity of agomelatine and suggest that the drug impacts mechanisms that lie at the core of anxious/depressive disorders. Author Affiliation: (1) Neuroplasticity Team, UMR 8576 CNRS Structural and Functional Glycobiology Unit, University Lille North of France (USTL), 59655, Villeneuve d'Ascq, France (2) IC2N, IBDLM, UMR6216, CNRS, Marseille, France (3) Azienda Sanitaria Locale, RM.E. Unita Operativa Complessa Adolescent, Rome, Italy (4) Institut de Recherches Internationales Servier, Courbevoie, France (5) Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, New York, USA (6) Department of Human Physiology and Pharmacology, Sapienza University, Rome, Italy (7) I.N.M. Neuromed, Pozzilli, Italy Article History: Registration Date: 24/03/2011 Received Date: 10/01/2011 Accepted Date: 23/03/2011 Online Date: 19/04/2011 Article note: S. Morley-Fletcher and J. Mairesse contributed equally to this work.
    Keywords: Agomelatine ; Prenatal stress ; Adult neurogenesis ; Ventral hippocampus ; Fluoxetine ; Phospho-CREB ; Metabotropic glutamate receptors
    ISSN: 0033-3158
    E-ISSN: 1432-2072
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  • 16
    In: International Journal of Geriatric Psychiatry, April 2014, Vol.29(4), pp.439-440
    Description: Byline: Martina Curto, Antonio Martocchia, Fabrizia Comite, Sergio Scaccianoce, Dionysios Xenos, Carla Nasca, Stefano Ferracuti, Paolo Girardi, Ferdinando Nicoletti, Paolo Falaschi ***** No abstract is available for this article. *****
    Keywords: Elderly Patients ; Depression (Mood disorder) ; Alzheimer's Disease ; Comorbidity ; Brain;
    ISSN: 0885-6230
    E-ISSN: 1099-1166
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  • 17
    In: Epilepsia, July 2015, Vol.56(7), pp.1141-1151
    Description: To purchase or authenticate to the full-text of this article, please visit this link: http://onlinelibrary.wiley.com/doi/10.1111/epi.13024/abstract Byline: Valerio D'Amore, Constanze Randow, Ferdinando Nicoletti, Richard Teke Ngomba, Gilles Luijtelaar Keywords: Glutamate; GABA ; Absence epilepsy; WAG/Rij rats; mGlu PAM Summary Objective Glutamate and [gamma]-aminobutyric acid (GABA) are the key neurotransmitter systems in the cortical-thalamocortical network, involved in normal and pathologic oscillations such as spike-wave discharges (SWDs), which characterize different forms of absence epilepsy. Metabotropic glutamate (mGlu) and GABA receptors are widely expressed within this network. Herein, we examined the effects of two selective positive allosteric modulators (PAMs) of mGlu1 and mGlu5 receptors, the GABA reuptake inhibitor, tiagabine, and their interaction in the somatosensory cortex and thalamus on SWDs in WAG/Rij rats. Methods Male WAG/Rij rats were equipped with bilateral cannulas in the somatosensory cortex (S1po) or the ventrobasal (VB) thalamic nuclei, and with cortical electroencephalography (EEG) electrodes. Rats received a single dose of the mGlu1 receptor PAM, RO0711401, or the mGlu5 receptor PAM, VU0360172, various doses of tiagabine, or VU0360172 combined with tiagabine. Results Both PAMs suppressed SWDs regardless of the site of injection. Tiagabine enhanced SWDs when injected into the thalamus, but, unexpectedly, suppressed SWDs in a dose-dependent manner when injected into the cortex. Intracortical co-injection of VU0360172 and tiagabine produced slightly larger effects as compared to either VU0360172 or tiagabine alone. Intrathalamic co-injections of VU0360172 and subthreshold doses of tiagabine caused an antiabsence effect similar to that exhibited by VU0360172 alone in the first 10 min. At 30 min, however, the antiabsence effect of VU0360172 was prevented by subthreshold doses of tiagabine, and the combination produced a paradoxical proabsence effect at 40 and 50 min. Significance These data (1) show that mGlu1 and mGlu5 receptor PAMs reduce absence seizures acting at both thalamic and cortical levels; (2) demonstrate for the first time that tiagabine, despite its established absence-enhancing effect, reduces SWDs when injected into the somatosensory cortex; and (3) indicate that the efficacy of VU0360172 in the thalamus may be critically affected by the availability of (extra)synaptic GABA. CAPTION(S): Data S1. Surgery and EEG Recordings.
    Keywords: Glutamate ; Gaba ; Absence Epilepsy ; Wag /Rij Rats ; Mg Lu Pam
    ISSN: 0013-9580
    E-ISSN: 1528-1167
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  • 18
    In: International Journal of Cancer, 15 April 2017, Vol.140(8), pp.1713-1726
    Description: The possible use of HIV protease inhibitors (HIV‐PI) as new therapeutic option for the treatment of cancer primarily originated from their success in treating HIV‐related Kaposi's sarcoma (KS). While these findings were initially attributed to immune reconstitution and better control of oncogenic viral infections, the number of reports on solid tumors, KS, lymphoma, fibrosarcoma, multiple myeloma and prostate cancer suggest other mechanisms for the anti‐neoplastic activity of PIs. However, a major drawback for the possible adoption of HIV‐PIs in the therapy of cancer relies on their relatively weak anticancer potency and important side effects. This has propelled several groups to generate derivatives of HIV‐PIs for anticancer use, through modifications such as attachment of different moieties, ligands and transporters, including saquinavir‐loaded folic acid conjugated nanoparticles and nitric oxide (NO) derivatives of HIV‐PIs. In this article, we discuss the current preclinical and clinical evidences for the potential use of HIV‐PIs, and of novel derivatives, such as saquinavir‐NO in the treatment of cancer.
    Keywords: Hiv Protease Inhibitors ; Saquinavir‐No ; Cancer Therapeutics
    ISSN: 0020-7136
    E-ISSN: 1097-0215
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  • 19
    Language: English
    In: Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 05 January 2014, Vol.369(1633), pp.20130162
    Description: Approximately half of all patients with multiple sclerosis (MS) experience cognitive dysfunction, including learning and memory impairment. Recent studies suggest that hippocampal pathology is involved, although the mechanisms underlying these deficits remain poorly understood. Evidence obtained from a mouse model of MS, the experimental autoimmune encephalomyelitis (EAE), suggests that in the hippocampus of EAE mice long-term potentiation (LTP) is favoured over long-term depression in response to repetitive synaptic activation, through a mechanism dependent on enhanced IL-1β released from infiltrating lymphocytes or activated microglia. Facilitated LTP during an immune-mediated attack might underlie functional recovery, but also cognitive deficits and excitotoxic neurodegeneration. Having identified that pro-inflammatory cytokines such as IL-1β can influence synaptic function and integrity in early MS, it is hoped that new treatments targeted towards preventing synaptic pathology can be developed.
    Keywords: Experimental Autoimmune Encephalomyelitis ; Hippocampus ; Interleukin-1β ; Long-Term Potentiation ; Multiple Sclerosis ; Synaptic Plasticity ; Models, Neurological ; Cytokines -- Metabolism ; Encephalomyelitis, Autoimmune, Experimental -- Physiopathology ; Hippocampus -- Pathology ; Long-Term Potentiation -- Physiology ; Multiple Sclerosis -- Physiopathology ; Synapses -- Physiology
    ISSN: 09628436
    E-ISSN: 1471-2970
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  • 20
    Language: English
    In: European Journal of Pharmacology, 05 September 2018, Vol.834, pp.92-102
    Description: Gasotransmitters are a group of gaseous molecules, with pleiotropic biological functions. These molecules include nitric oxide (NO), hydrogen sulfide (H S), and carbon monoxide (CO). Abnormal production and metabolism of these molecules have been observed in several pathological conditions. The understanding of the role of gasotransmitters in the immune system has grown significantly in the past years, and independent studies have shed light on the effect of exogenous and endogenous gasotransmitters on immune responses. Moreover, encouraging results come from the efficacy of NO-, CO- and H S -donors in preclinical animal models of autoimmune, acute and chronic inflammatory diseases. To date, data on the influence of gasotransmitters in immunity and immunopathology are often scattered and partial, and the scarcity of clinical trials using NO-, CO- and H S -donors, reveals that more effort is warranted. This review focuses on the role of gasotransmitters in the immune system and covers the evidences on the possible use of gasotransmitters for the treatment of inflammatory conditions.
    Keywords: Gasotransmitter ; Nitric Oxide ; Hydrogen Sulfide ; Carbon Monoxide ; Immune System ; Eae ; Neuroinflammation ; Multiple Sclerosis ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0014-2999
    E-ISSN: 1879-0712
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