Anxiolytic- and antidepressant-like effects of the non-peptide vasopressin V1b receptor antagonist, SSR149415, suggest an innovative approach for the treatment of stress-related disorders

The limbic localization of the arginine vasopressin V(1b) receptor has prompted speculation as to a potential role of this receptor in the control of emotional processes. To investigate this possibility, we have studied the behavioral effects of SSR149415, the first selective and orally active non-peptide antagonist of vasopressin V(1b) receptors, in a variety of classical (punished drinking, elevated plus-maze, and light/dark tests) and atypical (fear/anxiety defense test battery and social defeat-induced anxiety) rodent models of anxiety, and in two models of depression [forced swimming and chronic mild stress (CMS)]. When tested in classical tests of anxiety, SSR149415 produced anxiolytic-like activity at doses that ranged from 1 to 30 mg/kg (i.p. or p.o.), but the magnitude of these effects was overall less than that of the benzodiazepine anxiolytic diazepam, which was used as a positive control. In contrast, SSR149415 produced clear-cut anxiolytic-like activity in models involving traumatic stress exposure, such as the social defeat paradigm and the defense test battery (1-30 mg/kg, p.o.). In the forced swimming test, SSR149415 (10-30 mg/kg, p.o.) produced antidepressant-like effects in both normal and hypophysectomized rats. Moreover, in the CMS model in mice, repeated administration of SSR149415 (10 and 30 mg/kg, i.p.) for 39 days improved the degradation of the physical state, anxiety, despair, and the loss of coping behavior produced by stress. These findings point to a role for vasopressin in the modulation of emotional processes via the V(1b) receptor, and suggest that its blockade may represent a novel avenue for the treatment of affective disorders.     

The Expanding Spectrum of Human coronin 1A deficiency

The skin is the largest organ of our body; it consists of the epidermis, dermis, hair follicles, sweat glands, blood vessels, and connective tissue matrix. Its main function is to act as a barrier to the outside world and protect us from infections. Any component of the skin is subject to insults from the environment and/or from within the body. Primary immune deficiency patients present with recurrent or prolonged infections not frequently seen in healthy individuals. Oftentimes, these infections involve the skin. Primary immune deficiency may also present with noninfectious cutaneous signs, such as eczema; erythroderma; granulomas; dysplasia of the skin, hair, nails, or teeth; pigmentary changes; angioedema; urticaria; vasculitis; or autoimmune skin disease due to immune dysregulation. Prompt recognition of the underlying diagnosis and initiation of treatment decrease morbidity. This review provides the reader with an up-to-date summary of the common dermatologic manifestations of primary immune deficiency diseases.     

Dehydroepiandrosterone (DHEA) improves pulmonary hypertension in chronic obstructive pulmonary disease (COPD): a pilot study

ObjectivesIt was previously shown that dehydroepiandrosterone (DHEA) reverses chronic hypoxia-induced pulmonary hypertension (PH) in rats, but whether DHEA can improve the clinical and hemodynamic status of patients with PH associated to chronic obstructive pulmonary disease (PH-COPD) has not been studied whereas it is a very severe poorly treated disease.Patients and methodsEight patients with PH-COPD were treated with DHEA (200 mg daily orally) for 3 months. The primary end-point was the change in the 6-minute walk test (6-MWT) distance. Secondary end-points included pulmonary hemodynamics, lung function tests and tolerance of treatment.ResultsThe 6-MWT increased in all cases, from 333 m (median [IQR]) (257; 378) to 390 m (362; 440) (P < 0.05). Mean pulmonary artery pressure decreased from 26 mmHg (25; 27) to 21.5 mmHg (20; 25) (P < 0.05) and pulmonary vascular resistance from 4.2 UI (3.5; 4.4) to 2.6 UI (2.5; 3.8) (P < 0.05). The carbon monoxide diffusing capacity of the lung (DLCO % predicted) increased significantly from 27.4% (20.1; 29.3) to 36.4% (14.6; 39.6) (P < 0.05). DHEA treatment did not change respiratory parameters of gas exchange and the 200 mg per day of DHEA used was perfectly tolerated with no side effect reported.ConclusionDHEA treatment significantly improves 6-MWT distance, pulmonary hemodynamics and DLCO of patients with PH-COPD, without worsening gas exchange, as do other pharmacological treatments of PH (trial registration NCT00581087).     

N(o)-cadherin role for HSCs

In this issue of Blood, Bromberg et al and Greenbaum et al delete the gene encoding the cell adhesion molecule N-cadherin in osteoblastic cells forming the hematopoietic stem cell (HSC) niche to demonstrate that N-cadherin has no role in regulating hematopoiesis.