1,2,4-triazol-3-yl-thiopropyl-tetrahydrobenzazepines: a series of potent and selective dopamine D(3) receptor antagonists

The discovery of new highly potent and selective dopamine D3 receptor antagonists has recently permitted characterization of the role of the dopamine D3 receptor in a wide range of preclinical animal models. A novel series of 1,2,4-triazol-3-yl-thiopropyl-tetrahydrobenzazepines demonstrating a high level of D3 affinity and selectivity with an excellent pharmacokinetic profile is reported here. In particular, the pyrazolyl derivative 35 showed good oral bioavailability and brain penetration associated with high potency and selectivity in vitro. In vivo characterization of 35 confirmed that this compound blocks the expression of nicotine- and cocaine-conditioned place preference in the rat, prevents nicotine-triggered reinstatement of nicotine-seeking behavior in the rat, reduces oral operant alcohol self-administration in the mouse, increases extracellular levels of acetylcholine in the rat medial prefrontal cortex, and potentiates the amplitude of the relative cerebral blood volume response to d-amphetamine in a regionally specific manner in the rat brain.     

Acute effect of whole body vibration on postural control in congenitally blind subjects: a preliminary evidence

Abstract

Purpose: The purpose of this study was to investigate the acute effects of whole body vibration at optimal frequency, on postural control in blind subjects.

Method: Twenty-four participants, 12 congenital blind males (Experimental Group), and 12 non-disabled males with no visual impairment (Control Groups) were recruited. The area of the ellipse and the total distance of the center of pressure displacements, as postural control parameters, were evaluated at baseline (T0), immediately after the vibration (T1), after 10?min (T10) and after 20?min (T20). Whole body vibration protocol consisted into 5 sets of 1?min for each vibration, with 1?min rest between each set on a vibrating platform.

Results: The total distance of center of pressure showed a significant difference (p?<?0.05) amongst groups, while the area remained constant. No significant differences were detected among times of assessments, or in the interaction group?×?time.

Conclusion: No impairments in static balance were found after an acute bout of whole body vibration at optimal frequency in blind subjects and, consequently, whole body vibration may be considered as a safe application in individuals who are blind.     

Consolidation treatment with rituximab induces complete and persistent remission of mixed type Evans syndrome.

We describe a 58-year-old woman affected by immune thrombocytopenic purpura (ITP) since 1999, well controlled by low doses of steroid for 4 years, who experienced a relapse with severe mixed type Evans syndrome in March 2006. After an initial response to high doses of steroid, severe anaemia recurred 2 months later, this time resistant to second-line therapy with intravenous immunoglobulins (IVIG) and cyclophosphamide. So in May, we started the treatment with anti-CD20 monoclonal antibody rituximab with the dose of 375 mg/m2 once weekly for a total of four doses. We obtained a full normalization of haemoglobin concentration, but the disease haemolytic parameters persisted. Therefore, we decided to treat the patient with two monthly courses of rituximab, and a gradual normalization of haptoglobin and lactate dehydrogenase (LDH) plasma levels was finally achieved, with a sustained response up to date, lasting more than 12 months. We conclude that rituximab treatment is effective in refractory patients with mixed type Evans syndrome, and consolidation therapy should be considered to prolong beneficial effects achieved during the induction.